Randall Merchant - Academia.edu (original) (raw)
Papers by Randall Merchant
Journal of Neuroscience Nursing, 2014
A major goal in the care of patients with neurological problems is to prevent or minimize episode... more A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP.
Neurosurgery, Dec 1, 1989
Earlier, we conducted Phase I clinical trials to determine any acute toxicity of adoptive immunot... more Earlier, we conducted Phase I clinical trials to determine any acute toxicity of adoptive immunotherapy with intralesional injections of autologous lymphocytes expressing lymphokine-activated killer (LAK) activity and recombinant interleukin-2 (rIL-2) in patients with malignant glioma. Within six weeks of craniotomy and intralesional injection of autologous LAK cells plus rIL-2, 3 of 29 patients demonstrated a decline in clinical status and evidence on computed tomographic and magnetic resonance imaging scans of edema and mass of unknown character at the site of previous surgery and immunotherapy. Craniotomy was performed to remove the tissue and reduce intracranial pressure. Microscopic examination of the excised material indicated no new tumor growth within the resected mass, but rather that the tissue had the histological characteristics of a chronic sterile abscess including necrosis, fibrosis, and influx of inflammatory cells. Factors that may have contributed to this reaction in the 3 patients were age, Karnofsky score, the extent of tumor excision, and immune status. All 3 had also been treated with greater than average numbers of rIL-2 activated lymphocytes that demonstrated significant in vitro LAK activity. The results suggest that in patients whose clinical status is good and who are not immunosuppressed by corticosteroids, the dose-limiting toxicity of intraparenchymal immunotherapy with LAK cells plus rIL-2 for glioma may be related to the total, absolute number of activated cells injected, and this toxicity develops over time and is manifested by development of a sterile abscess.
Phytother Res, 1990
Page 1. Dietary Chlorella pyrenoidosa for Patients with Malignant Glioma: Effects on Immunocompet... more Page 1. Dietary Chlorella pyrenoidosa for Patients with Malignant Glioma: Effects on Immunocompetence, Quality of Life, and Survival? Randall E. Merchant,* Charles D. Rice, and Harold F. Young Department of Anatomy and ...
Indian Pediatr 35 883 887, Sep 1, 1998
Neurosurgery, 1992
It is well documented that drug delivery into experimental and human brain tumors is limited by t... more It is well documented that drug delivery into experimental and human brain tumors is limited by the variably intact blood-brain barrier (BBB) at the growing edge. The aim of the present investigation was to examine the histopathological changes that occur after a single intralesional injection of human recombinant interleukin-2 (rIL-2) into a growing glioma and determine whether the injection improved delivery of cytotoxic drug into the neuropil surrounding the site of lymphokine injection. Because an intracerebral injection of rIL-2 causes a temporary breakdown in the BBB, we hoped to enhance drug penetration into peritumoral areas of brain with an intact BBB by using the novel biomodulating effect of rIL-2 on the cerebral endothelial cells. The results demonstrated that an intralesional injection of 7.2 x 10(4) National Units rIL-2 on Day 7 after tumor inoculation did not accentuate the already increased cerebrovascular permeability produced by the glioma nor did rIL-2 trigger additional or aggravate neurological deficits in glioma-bearing rats. Before the administration of chemotherapy in vivo, the RT-2 glioma cells were tested for in vitro sensitivity by colorimetric assay. At 24 hours after exposure to either methotrexate (MTX), vincristine (VIN), or doxorubicin (DOX), no significant inhibition of metabolic activity was observed. In contrast, a timed pulsed of any drug for 5 minutes caused significant dose-dependent inhibition of RT-2 glioma cells at 48 hours to 5 days after drug administration. Animal models receiving an intralesional injection of rIL-2 followed 3 days later by an intravenous dose of 30 mg/kg MTX, 0.23 mg/kg VIN, or 10 mg/kg DOX demonstrated that only MTX combined with intralesional rIL-2 significantly inhibited intracranial proliferation of RT-2 glioma cells. Use of intralesional rIL-2 and intravenous chemotherapy, however, did not significantly increase survival in this animal model of glioma. These results show that the combination of cytotoxic drugs with intralesional rIL-2 can be safely applied in the management of glioma and may form a rational basis for additional pharmacological investigations of a wider assortment of chemotherapies in combination with rIL-2 for intracranial malignancies.
Drug and Alcohol Dependence, 2015
Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microst... more Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microstructural organization of white matter (WM), and the most consistent DTI finding regarding cocaine-related WM alterations is in the corpus callosum (CC). WM injury has also been observed in subjects with traumatic brain injury (TBI), including in the CC. We used DTI to test if the WM microstructure is relatively more impaired in cocaine-dependent subjects who had suffered a mild TBI (mTBI). Fractional anisotropy (FA), which reflects the degree of alignment of cellular structures within fiber tracts and their structural integrity, was compared across cocaine-dependent subjects with mTBI (COCTBI group, n=9), matched cocaine-dependent subjects without TBI (COC group, n=12), and matched healthy controls (CTL group, n=12). The COCTBI group had significantly lower FA in the genu, body, and splenium of CC, than the CTL group whenever the education was controlled or not. The COC group had significantly lower FA in the left and right anterior corona radiata than the CTL group only when the education was controlled. There was no significant difference in FA between the COC and COCTBI groups. Cocaine dependence (or mTBI) related WM impairments in the CC were not detectable in this small subject sample. The significant finding in the CC suggests that the concurrence of cocaine dependence and mTBI might result in more severe damage to the CC, which could even be detected in small sample size.
Journal of neuro-oncology, 1999
We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell li... more We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell line, with a retroviral expression vector containing the human IL-6 cDNA and investigated the effects of IL-6 secretion on glioma formation in the syngeneic Fischer rat. Two subclones producing high and low levels (35 and 3.5 ng/10(6) cells/48 h) of IL-6 were identified and were termed T9.F/IL6/hi and T9.F/IL6/lo, respectively. Subcutaneous (SC) injection of 1 x 10(6) parental T9.F cells resulted in 100% tumor formation and progression. When 1 x 10(6) IL-6 secreting T9.F cells were injected SC, a small palpable tumor formed which sometimes regressed. In this regard, no tumors were detected after 30 days in 76% (13/17) of animals injected with T9.F/IL6/hi cells, whereas only 10% (1/10) of the rats injected with T9.F/IL6/lo cells completely rejected their tumors within this time frame. The addition of an IL-6 neutralizing antibody to the T9.F/IL6/hi SC inoculum followed by an intratumoral in...
Journal of neuro-oncology, 1997
It has been shown that adoptive immunotherapy can be curative for established malignant tumors. T... more It has been shown that adoptive immunotherapy can be curative for established malignant tumors. The key to this treatment lies in obtaining sufficient numbers of lymphocytes which are sensitized to recognize tumor antigens and carry out immunological reactions to destroy tumor cells. Reported here are the results of experiments to: 1) sensitize lymphocytes to the antigens of rat glioma cells and expand them ex vivo for use in adoptive immunotherapy, 2) characterize the cells of the expanded population, and 3) evaluate antitumor activity in a cohort of rats with well-established intracranial gliomas. Viable RT-2 glioma cells were injected into the hind foot pads of syngeneic Fischer 344 rats. After 10 days, the tumor draining lymph nodes (DLN) were harvested from the injected limbs and mechanically dissociated. The cells of the DLN were then suspended in culture medium supplemented with low dose interleukin-2 (IL-2) and incubated for 18 hours with Bryostatin-1 and ionomycin (Bryo/Io)...
Cancer research, 1987
Immunotherapy with the lymphokine interleukin-2 (IL-2), with or without lymphokine activated kill... more Immunotherapy with the lymphokine interleukin-2 (IL-2), with or without lymphokine activated killer (LAK) cells, offers a new approach to the treatment of solid tumors. Unfortunately, most patients receiving IL-2 and LAK cells develop a "third space syndrome" from a presumed generalized increase of vascular permeability. We have investigated the role of IL-2 on lung fluid balance, by measuring changes in lung water and albumin intake. Rats were injected with IL-2 500,000 U i.p. three times a day for 1 to 4 days. At the completion of the injections, lungs were isolated and perfused, and total lung water (TLW) and 125I-albumin uptake were measured. After 1 day of injections, TLW increased from 4.90 +/- 0.14 to 5.57 +/- 0.34 ml/g dry lung and albumin uptake nearly doubled from 0.47 +/- 0.08 to 0.91 +/- 0.28 cm3/s/g dry lung X 10(-3). Longer injection periods increased both TLW and albumin uptake further. After 2 days, TLW and albumin uptake were also significantly increased b...
Cancer research, Jan 15, 1990
The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstr... more The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstrictor effect of hypocapnia and the endothelium-dependent vasodilator effect of acetylcholine (Ach) were examined in anesthetized rats equipped with cranial windows. Prior to the functional studies, each of six animals received an i.v. infusion of rIL-2 (6 x 10(5) IU/kg) every 8 h for 3 days. At the same time, six control animals received infusions of equivalent volumes of sterile water. Eight h after the final infusion, each animal was anesthetized and equipped with a cranial window for the observation of pial arterioles overlying the left frontoparietal cortex. Pial arteriolar diameters were measured before and after the topical application of Ach which in normal cerebral arterioles elicits the release of endothelium-dependent relaxing factor, causing vasodilation. When arteriolar diameters returned to base line, they were measured again both before and during hyperventilation-induced h...
European Journal of Cancer and Clinical Oncology, 1985
We examined the fine structure and enzymatic activity of cells composing colonies grown from bloo... more We examined the fine structure and enzymatic activity of cells composing colonies grown from blood and/or spleen of eight patients with hairy cell leukemia. Mononuclear cells (MNC) were plated over an agar layer in a medium containing methylcellulose and leukocyte-conditioned medium. After 7-10 days incubation colonies were harvested for cytologic study. Colony cells possessed a euchromatic nucleus with an occasional nucleolus. Their cytoplasm contained a prominent Golgi region, numerous mitochondria and small vesicles, many short strands of rough endoplasmic reticulum (RER) and an infrequent phagosome. Well-developed ribosome-lamella complexes and what may have been their intermediate forms appeared in colony cells from three patients. Strong activity for tartrate-resistant acid phosphatase, localized in the RER, nuclear envelope and some Golgi vesicles, was evident in 50-95% of all colony cells. Our results indicate that a high proportion of MNC forming colonies in this culture system maintain the characteristic morphology and cytochemical activity of hairy cells.
Journal of Neuroscience Nursing, 2014
A major goal in the care of patients with neurological problems is to prevent or minimize episode... more A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP.
Toxicology, 1995
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent environmental immunomodulati... more 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent environmental immunomodulating agents identified so far. Historically, mice have been used to model mammalian immunobiology and most of the data gathered on the immunotoxicity of TCDD has been obtained from studies with mice. However, rats have been used more extensively in toxicological research to establish human risk assessment criteria. A need exists, therefore, to develop a database using the rat model in immunotoxicology so that complete animal toxicity studies can be conducted. We have treated female Fischer 344 rats with a single i.p. dose of 0.3, 3.0, or 30.0 micrograms/kg TCDD or corn oil vehicle and examined cytotoxic T-cell (CTL) activities 24 days following treatment. Syngeneic in vivo tumor-specific CTLs were generated that model cell-mediated immune reactions against neoplastically transformed self antigens. RT2, a virally-induced Fischer 344 rat glioma, and D74, a ethylnitrosurea-induced Fischer 344 rat glioma were used as targets. This immunological parameter was compared to body, thymic, and liver weights as well as liver ethoxyresorufin deethylase (EROD) activity on day 24 post-TCDD treatment. The results indicate that Fischer 344 rats are very sensitive to TCDD as indicated by severe thymic atrophy and EROD induction at all three doses. In contrast, CTL activity was only marginally affected by these same doses of TCDD with only a modest suppression noted at the highest dose. These results indicate that the CTL response in rats may not be useful in characterizing the effects of this xenobiotic on immunocompetence in the rat.
Phytotherapy Research, 2000
Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While a... more Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While available therapy is often disappointing, most patients can be helped with a combination of medication, exercise and maintenance of a regular sleep schedule. The objective of the present study was to determine if adding nutritional supplements derived from the unicellular green alga, Chlorella pyrenoidosa, produced any improvements in the clinical and functional status in patients with moderately severe symptoms of fibromyalgia syndrome. Eligible patients had 2+ palpable tenderness at 11 or more of 18 defined tender points and had a tender point index (TPI) of at least 22. Each day for 2 months, participants consumed two commercially available Chlorella-based products, 10 g of 'Sun Chlorella' tablets and 100 mL of liquid 'Wakasa Gold'. Any amelioration of symptoms was validated and quantified using semi-objective and subjective outcome measures systematically administered at clinic visits on days 0, 30 and 60 of the diet therapy. Eighteen of the 20 patients enrolled completed the 2 month trial. The average TPI for the group which at onset was 32, decreased to a mean of 25 after 2 months. This decrease was statistically significant (p = 0.01), representing a 22% decrease in pain intensity. Blood samples taken on each occasion indicated no significant alterations in serum chemistries, formed elements, and circulating lymphocyte subsets. Compilations of the results of patient interviews and self-assessment questionnaires revealed that seven patients felt that the dietary supplement had improved their fibromyalgia symptoms, while six thought they had experienced no change, and five believed the symptoms had worsened over the time of the trial. The results of this pilot study suggest that dietary Chlorella supplementation may help relieve the symptoms of fibromyalgia in some patients and that a larger, more comprehensive double-blind, placebo-controlled clinical trial in these patients is warranted.
Neurosurgical FOCUS, 2002
reviewed and formulated opinions based on the evidence on protocol design and the outcome measure... more reviewed and formulated opinions based on the evidence on protocol design and the outcome measures used for clinical trials in patients with a severe or moderate traumatic brain injury (TBI). First, in view of the heterogeneity of the population under study, the authors suggest that block randomization and stratification should always be used in the design of neurotrauma trials. Second, although the Glasgow Outcome Scale (GOS) remains the most widely used and accepted instrument for TBI trials, the authors believe the eight-point expanded scale that has recently been designed will ultimately provide greater discrimination, and narrower categories and will ultimately prove superior for detecting more subtle changes in outcome. Furthermore, the authors recommend, in view of the profound cognitive impairment in survivors of TBI, that neuropsychological tests be explored further as an adjunct to the GOS. Future research should focus on the development of more sensitive and specific surrogate outcome measures such as magnetic resonance imaging, neurochemical, neuropsychological, and quality of life measures in order to detect a neuroprotective effect in patients with TBI.
Neurosurgery, 1994
Nervous system-specific transcription factors that bind to the octameric deoxyribonucleic acid se... more Nervous system-specific transcription factors that bind to the octameric deoxyribonucleic acid sequence motif ATGCAAAT (or ATTTGCAT) are known as N-Oct proteins. Neurons and glia contain the ubiquitous Oct-1 protein and four polypeptide complexes termed N-Oct-2, N-Oct-3, N-Oct-4, and N-Oct-5. Previously, we showed that N-Oct proteins are differentially expressed by human neuroblastoma and glioblastoma cell lines in vitro. We have now extended this work to freshly isolated human primary and metastatic brain tumors. Contrary to brain tumor cell lines, of the five astrocytomas and three glioblastomas analyzed, all but two tumors displayed the complete N-Oct protein profile, irrespective of histopathological tumor grade. Two astrocytomas were negative for N-Oct-4. Ten of 13 ependymomas exhibited N-Oct-2, N-Oct-3, and N-Oct-4 but lacked the N-Oct-5 complex. In contrast, brain metastases of two patients with extracerebral carcinomas contained only Oct-1, and cerebral metastases from two cases of B cell lymphomas showed Oct-1 and Oct-2 complexes, the characteristic Oct protein pattern of B lymphocytes. Thus, metastatic carcinoma and lymphoma expressed a non-nervous system phenotype of Oct proteins.
Journal of Neurotrauma, 2009
Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone... more Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.
Journal of Neurosurgery, 1992
Patients harboring a malignant brain tumor have been described as being highly immunosuppressed, ... more Patients harboring a malignant brain tumor have been described as being highly immunosuppressed, as evidenced by reduced numbers of T cells and the decreased ability of their lymphocytes to produce interleukin-2 (IL-2). In order to determine whether an intrinsic abnormality exists in the T lymphocytes of glioma patients and to evaluate what role corticosteroids may play in glioma-associated immunosuppression, in vitro T cell proliferative function in the presence of recombinant IL-2 (rIL-2) was examined in age-matched groups of normal control subjects, steroid-free patients with glial tumors, steroid-dependent patients with glial tumors, and steroid-dependent patients with nonglial cerebral tumors. The results demonstrated that, when enriched T cell populations of all brain-tumor patients were stimulated with rIL-2 and phytohemagglutinin (PHA), there were no statistically significant differences between any groups. In contrast, when T cell populations were stimulated with mitogenic combinations of phorbol ester, calcium ionophore, and rIL-2, those from steroid-dependent patients with glial tumors had a significantly lower response than those from normal control subjects, suggesting that a population of T cells capable of responding to phorbol ester/ionomycin and not PHA stimulation is inhibited by corticosteroid therapy in glioma patients. In addition, T cells of four brain-tumor patient/age-matched control subject pairs were stimulated with either phorbol ester/ionomycin or PHA for 24 hours; three of the four patients expressed low-affinity IL-2 receptor levels as high or higher than their respective control subjects, suggesting that IL-2 receptor expression in these patients may be quantitatively normal once the T cell number is corrected. Taken together, these results show that the decreased PHA responsiveness that has been previously reported in lymphocytes of glioma patients is not due to a cellular abnormality within the potentially responsive cells, but rather reflects the reduced proportion of T cells within their peripheral blood which, as a consequence, reduces the level of IL-2 production attained upon activation.
Journal of Neuro-oncology, 2003
One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostl... more One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostly confined to the T cell lineage. A deficiency in the production of naive T cells from the thymus could contribute to the lymphopenia seen in GBM patients. In this study we asked whether thymic function and the production of recent thymic emigrant (RTE) T cells from the thymus was influenced by intracranial (i.c.) glioma progression. We found significant thymic involution in animals with progressive i.c. gliomas. Involuted thymi from animals with progressive i.c. T9.F gliomas showed dramatic losses of CD4+CD8 + (DP) thymocytes. Microscopic analysis complemented those findings by demonstrating a reversal of the typical cortico-medullary structure. Significant increases in apoptosis accompanied the rapid loss of viable thymocytes, which was prevented in part by adrenalectomy, suggesting a dominant role for endogenous glucocorticoids. This thymic involution was also associated with a significant decrease in peripheral RTE T cells, reflecting the diminished thymic function. Finally, we found that CD8 + RTE T cells were enriched in progressively growing T9 gliomas, which points to an immunological role for RTE's in anti-glioma immunity. Our findings may shed light on the significance of thymic function for anti-glioma immunity and the response to immunotherapeutic treatment paradigms.
Journal of Neuro-Oncology, 2005
We have recently reported that activation of tumor-specific T cells by subcutaneous vaccination w... more We have recently reported that activation of tumor-specific T cells by subcutaneous vaccination with irradiated T9 glioma cells of syngeneic rats with a pre-existing, intracranial (i.c.) T9 glioma (T9+vaccination) promotes the mobilization of myeloid suppressor cells (MSC) which inhibit T cell function resulting in unregulated tumor progression. The current study investigated if this immunological paradigm could be recapitulated in T cell deficient rats, in other rat glioma models or using a dendritic cell (DC) vaccine. When nude rats were used in the T9+vaccination model, the level of MSC tumor infiltration remained low in vaccinated and control groups and there was no significant difference in tumor size between the groups. Increased tumor infiltration by MSC after vaccination with respective irradiated tumor cells was observed in the 9L, F98 and D74 gliomas. RT-2 tumors were markedly infiltrated with MSC regardless of vaccination. Enhanced tumor progression in response to immunization and T cell activation was observed in rats bearing F98 and D74 gliomas, although less pronounced than in the T9 model, and there was a trend for increased tumor size in the 9L glioma model. Increased MSC infiltrate and augmented T9 glioma growth were observed when DC pulsed with T9 cell lysate was used as a vaccine. These results suggest that MSC infiltration and unregulated tumor growth in response to vaccination is T cell-dependent; is not unique to the T9 glioma; and can be recapitulated with an alternate immunization approach.
Journal of Neuroscience Nursing, 2014
A major goal in the care of patients with neurological problems is to prevent or minimize episode... more A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP.
Neurosurgery, Dec 1, 1989
Earlier, we conducted Phase I clinical trials to determine any acute toxicity of adoptive immunot... more Earlier, we conducted Phase I clinical trials to determine any acute toxicity of adoptive immunotherapy with intralesional injections of autologous lymphocytes expressing lymphokine-activated killer (LAK) activity and recombinant interleukin-2 (rIL-2) in patients with malignant glioma. Within six weeks of craniotomy and intralesional injection of autologous LAK cells plus rIL-2, 3 of 29 patients demonstrated a decline in clinical status and evidence on computed tomographic and magnetic resonance imaging scans of edema and mass of unknown character at the site of previous surgery and immunotherapy. Craniotomy was performed to remove the tissue and reduce intracranial pressure. Microscopic examination of the excised material indicated no new tumor growth within the resected mass, but rather that the tissue had the histological characteristics of a chronic sterile abscess including necrosis, fibrosis, and influx of inflammatory cells. Factors that may have contributed to this reaction in the 3 patients were age, Karnofsky score, the extent of tumor excision, and immune status. All 3 had also been treated with greater than average numbers of rIL-2 activated lymphocytes that demonstrated significant in vitro LAK activity. The results suggest that in patients whose clinical status is good and who are not immunosuppressed by corticosteroids, the dose-limiting toxicity of intraparenchymal immunotherapy with LAK cells plus rIL-2 for glioma may be related to the total, absolute number of activated cells injected, and this toxicity develops over time and is manifested by development of a sterile abscess.
Phytother Res, 1990
Page 1. Dietary Chlorella pyrenoidosa for Patients with Malignant Glioma: Effects on Immunocompet... more Page 1. Dietary Chlorella pyrenoidosa for Patients with Malignant Glioma: Effects on Immunocompetence, Quality of Life, and Survival? Randall E. Merchant,* Charles D. Rice, and Harold F. Young Department of Anatomy and ...
Indian Pediatr 35 883 887, Sep 1, 1998
Neurosurgery, 1992
It is well documented that drug delivery into experimental and human brain tumors is limited by t... more It is well documented that drug delivery into experimental and human brain tumors is limited by the variably intact blood-brain barrier (BBB) at the growing edge. The aim of the present investigation was to examine the histopathological changes that occur after a single intralesional injection of human recombinant interleukin-2 (rIL-2) into a growing glioma and determine whether the injection improved delivery of cytotoxic drug into the neuropil surrounding the site of lymphokine injection. Because an intracerebral injection of rIL-2 causes a temporary breakdown in the BBB, we hoped to enhance drug penetration into peritumoral areas of brain with an intact BBB by using the novel biomodulating effect of rIL-2 on the cerebral endothelial cells. The results demonstrated that an intralesional injection of 7.2 x 10(4) National Units rIL-2 on Day 7 after tumor inoculation did not accentuate the already increased cerebrovascular permeability produced by the glioma nor did rIL-2 trigger additional or aggravate neurological deficits in glioma-bearing rats. Before the administration of chemotherapy in vivo, the RT-2 glioma cells were tested for in vitro sensitivity by colorimetric assay. At 24 hours after exposure to either methotrexate (MTX), vincristine (VIN), or doxorubicin (DOX), no significant inhibition of metabolic activity was observed. In contrast, a timed pulsed of any drug for 5 minutes caused significant dose-dependent inhibition of RT-2 glioma cells at 48 hours to 5 days after drug administration. Animal models receiving an intralesional injection of rIL-2 followed 3 days later by an intravenous dose of 30 mg/kg MTX, 0.23 mg/kg VIN, or 10 mg/kg DOX demonstrated that only MTX combined with intralesional rIL-2 significantly inhibited intracranial proliferation of RT-2 glioma cells. Use of intralesional rIL-2 and intravenous chemotherapy, however, did not significantly increase survival in this animal model of glioma. These results show that the combination of cytotoxic drugs with intralesional rIL-2 can be safely applied in the management of glioma and may form a rational basis for additional pharmacological investigations of a wider assortment of chemotherapies in combination with rIL-2 for intracranial malignancies.
Drug and Alcohol Dependence, 2015
Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microst... more Diffusion tensor imaging (DTI) is a useful technique for non-invasively investigating the microstructural organization of white matter (WM), and the most consistent DTI finding regarding cocaine-related WM alterations is in the corpus callosum (CC). WM injury has also been observed in subjects with traumatic brain injury (TBI), including in the CC. We used DTI to test if the WM microstructure is relatively more impaired in cocaine-dependent subjects who had suffered a mild TBI (mTBI). Fractional anisotropy (FA), which reflects the degree of alignment of cellular structures within fiber tracts and their structural integrity, was compared across cocaine-dependent subjects with mTBI (COCTBI group, n=9), matched cocaine-dependent subjects without TBI (COC group, n=12), and matched healthy controls (CTL group, n=12). The COCTBI group had significantly lower FA in the genu, body, and splenium of CC, than the CTL group whenever the education was controlled or not. The COC group had significantly lower FA in the left and right anterior corona radiata than the CTL group only when the education was controlled. There was no significant difference in FA between the COC and COCTBI groups. Cocaine dependence (or mTBI) related WM impairments in the CC were not detectable in this small subject sample. The significant finding in the CC suggests that the concurrence of cocaine dependence and mTBI might result in more severe damage to the CC, which could even be detected in small sample size.
Journal of neuro-oncology, 1999
We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell li... more We transduced a highly tumorigenic T9 clone (T9.F), isolated from the rat T9 glioblastoma cell line, with a retroviral expression vector containing the human IL-6 cDNA and investigated the effects of IL-6 secretion on glioma formation in the syngeneic Fischer rat. Two subclones producing high and low levels (35 and 3.5 ng/10(6) cells/48 h) of IL-6 were identified and were termed T9.F/IL6/hi and T9.F/IL6/lo, respectively. Subcutaneous (SC) injection of 1 x 10(6) parental T9.F cells resulted in 100% tumor formation and progression. When 1 x 10(6) IL-6 secreting T9.F cells were injected SC, a small palpable tumor formed which sometimes regressed. In this regard, no tumors were detected after 30 days in 76% (13/17) of animals injected with T9.F/IL6/hi cells, whereas only 10% (1/10) of the rats injected with T9.F/IL6/lo cells completely rejected their tumors within this time frame. The addition of an IL-6 neutralizing antibody to the T9.F/IL6/hi SC inoculum followed by an intratumoral in...
Journal of neuro-oncology, 1997
It has been shown that adoptive immunotherapy can be curative for established malignant tumors. T... more It has been shown that adoptive immunotherapy can be curative for established malignant tumors. The key to this treatment lies in obtaining sufficient numbers of lymphocytes which are sensitized to recognize tumor antigens and carry out immunological reactions to destroy tumor cells. Reported here are the results of experiments to: 1) sensitize lymphocytes to the antigens of rat glioma cells and expand them ex vivo for use in adoptive immunotherapy, 2) characterize the cells of the expanded population, and 3) evaluate antitumor activity in a cohort of rats with well-established intracranial gliomas. Viable RT-2 glioma cells were injected into the hind foot pads of syngeneic Fischer 344 rats. After 10 days, the tumor draining lymph nodes (DLN) were harvested from the injected limbs and mechanically dissociated. The cells of the DLN were then suspended in culture medium supplemented with low dose interleukin-2 (IL-2) and incubated for 18 hours with Bryostatin-1 and ionomycin (Bryo/Io)...
Cancer research, 1987
Immunotherapy with the lymphokine interleukin-2 (IL-2), with or without lymphokine activated kill... more Immunotherapy with the lymphokine interleukin-2 (IL-2), with or without lymphokine activated killer (LAK) cells, offers a new approach to the treatment of solid tumors. Unfortunately, most patients receiving IL-2 and LAK cells develop a "third space syndrome" from a presumed generalized increase of vascular permeability. We have investigated the role of IL-2 on lung fluid balance, by measuring changes in lung water and albumin intake. Rats were injected with IL-2 500,000 U i.p. three times a day for 1 to 4 days. At the completion of the injections, lungs were isolated and perfused, and total lung water (TLW) and 125I-albumin uptake were measured. After 1 day of injections, TLW increased from 4.90 +/- 0.14 to 5.57 +/- 0.34 ml/g dry lung and albumin uptake nearly doubled from 0.47 +/- 0.08 to 0.91 +/- 0.28 cm3/s/g dry lung X 10(-3). Longer injection periods increased both TLW and albumin uptake further. After 2 days, TLW and albumin uptake were also significantly increased b...
Cancer research, Jan 15, 1990
The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstr... more The effects of systemic human recombinant interleukin 2 (rIL-2) infusion upon both the vasoconstrictor effect of hypocapnia and the endothelium-dependent vasodilator effect of acetylcholine (Ach) were examined in anesthetized rats equipped with cranial windows. Prior to the functional studies, each of six animals received an i.v. infusion of rIL-2 (6 x 10(5) IU/kg) every 8 h for 3 days. At the same time, six control animals received infusions of equivalent volumes of sterile water. Eight h after the final infusion, each animal was anesthetized and equipped with a cranial window for the observation of pial arterioles overlying the left frontoparietal cortex. Pial arteriolar diameters were measured before and after the topical application of Ach which in normal cerebral arterioles elicits the release of endothelium-dependent relaxing factor, causing vasodilation. When arteriolar diameters returned to base line, they were measured again both before and during hyperventilation-induced h...
European Journal of Cancer and Clinical Oncology, 1985
We examined the fine structure and enzymatic activity of cells composing colonies grown from bloo... more We examined the fine structure and enzymatic activity of cells composing colonies grown from blood and/or spleen of eight patients with hairy cell leukemia. Mononuclear cells (MNC) were plated over an agar layer in a medium containing methylcellulose and leukocyte-conditioned medium. After 7-10 days incubation colonies were harvested for cytologic study. Colony cells possessed a euchromatic nucleus with an occasional nucleolus. Their cytoplasm contained a prominent Golgi region, numerous mitochondria and small vesicles, many short strands of rough endoplasmic reticulum (RER) and an infrequent phagosome. Well-developed ribosome-lamella complexes and what may have been their intermediate forms appeared in colony cells from three patients. Strong activity for tartrate-resistant acid phosphatase, localized in the RER, nuclear envelope and some Golgi vesicles, was evident in 50-95% of all colony cells. Our results indicate that a high proportion of MNC forming colonies in this culture system maintain the characteristic morphology and cytochemical activity of hairy cells.
Journal of Neuroscience Nursing, 2014
A major goal in the care of patients with neurological problems is to prevent or minimize episode... more A major goal in the care of patients with neurological problems is to prevent or minimize episodes of increased intracranial pressure (ICP). Elevations in ICP in response to nursing interventions have been acknowledged since the 1960s when ICP monitoring was first introduced in the clinical setting. Until recently, few studies have specifically examined the effect of oral care on ICP, and oral care and other hygiene measures were combined or not specified, prohibiting a direct interpretation of the influence of oral care alone on ICP. The purpose of this study was to describe the relationship between routine oral care interventions and the changes in ICP specifically focusing on the effect of intensity and duration of this intervention. Twenty-three patients with a clinical condition requiring ICP monitoring were enrolled over a 12-month period. Oral care provided by neuroscience intensive care nurses was observed and videotaped. Characteristics of the intervention were documented including products used, patient positioning, and duration of the intervention. A 1-5 subjective scale was used to score intensity of oral care. Wrist actigraphy data were collected from the nurses to provide an objective measure of intensity. Patient physiologic data were collected at 12-second epochs 5 minutes before, during, and 5 minutes after oral care. The mixed-effect repeated measures analysis of variance model indicated that there was a statistically significant increase in ICP in response to oral care (p = .0031). There was, however, no clinically significant effect on ICP. This study provides evidence that oral care is safe to perform in patients in the absence of preexisting elevated ICP.
Toxicology, 1995
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent environmental immunomodulati... more 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is one of the most potent environmental immunomodulating agents identified so far. Historically, mice have been used to model mammalian immunobiology and most of the data gathered on the immunotoxicity of TCDD has been obtained from studies with mice. However, rats have been used more extensively in toxicological research to establish human risk assessment criteria. A need exists, therefore, to develop a database using the rat model in immunotoxicology so that complete animal toxicity studies can be conducted. We have treated female Fischer 344 rats with a single i.p. dose of 0.3, 3.0, or 30.0 micrograms/kg TCDD or corn oil vehicle and examined cytotoxic T-cell (CTL) activities 24 days following treatment. Syngeneic in vivo tumor-specific CTLs were generated that model cell-mediated immune reactions against neoplastically transformed self antigens. RT2, a virally-induced Fischer 344 rat glioma, and D74, a ethylnitrosurea-induced Fischer 344 rat glioma were used as targets. This immunological parameter was compared to body, thymic, and liver weights as well as liver ethoxyresorufin deethylase (EROD) activity on day 24 post-TCDD treatment. The results indicate that Fischer 344 rats are very sensitive to TCDD as indicated by severe thymic atrophy and EROD induction at all three doses. In contrast, CTL activity was only marginally affected by these same doses of TCDD with only a modest suppression noted at the highest dose. These results indicate that the CTL response in rats may not be useful in characterizing the effects of this xenobiotic on immunocompetence in the rat.
Phytotherapy Research, 2000
Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While a... more Fibromyalgia syndrome is a common, chronic musculoskeletal disorder of unknown aetiology. While available therapy is often disappointing, most patients can be helped with a combination of medication, exercise and maintenance of a regular sleep schedule. The objective of the present study was to determine if adding nutritional supplements derived from the unicellular green alga, Chlorella pyrenoidosa, produced any improvements in the clinical and functional status in patients with moderately severe symptoms of fibromyalgia syndrome. Eligible patients had 2+ palpable tenderness at 11 or more of 18 defined tender points and had a tender point index (TPI) of at least 22. Each day for 2 months, participants consumed two commercially available Chlorella-based products, 10 g of 'Sun Chlorella' tablets and 100 mL of liquid 'Wakasa Gold'. Any amelioration of symptoms was validated and quantified using semi-objective and subjective outcome measures systematically administered at clinic visits on days 0, 30 and 60 of the diet therapy. Eighteen of the 20 patients enrolled completed the 2 month trial. The average TPI for the group which at onset was 32, decreased to a mean of 25 after 2 months. This decrease was statistically significant (p = 0.01), representing a 22% decrease in pain intensity. Blood samples taken on each occasion indicated no significant alterations in serum chemistries, formed elements, and circulating lymphocyte subsets. Compilations of the results of patient interviews and self-assessment questionnaires revealed that seven patients felt that the dietary supplement had improved their fibromyalgia symptoms, while six thought they had experienced no change, and five believed the symptoms had worsened over the time of the trial. The results of this pilot study suggest that dietary Chlorella supplementation may help relieve the symptoms of fibromyalgia in some patients and that a larger, more comprehensive double-blind, placebo-controlled clinical trial in these patients is warranted.
Neurosurgical FOCUS, 2002
reviewed and formulated opinions based on the evidence on protocol design and the outcome measure... more reviewed and formulated opinions based on the evidence on protocol design and the outcome measures used for clinical trials in patients with a severe or moderate traumatic brain injury (TBI). First, in view of the heterogeneity of the population under study, the authors suggest that block randomization and stratification should always be used in the design of neurotrauma trials. Second, although the Glasgow Outcome Scale (GOS) remains the most widely used and accepted instrument for TBI trials, the authors believe the eight-point expanded scale that has recently been designed will ultimately provide greater discrimination, and narrower categories and will ultimately prove superior for detecting more subtle changes in outcome. Furthermore, the authors recommend, in view of the profound cognitive impairment in survivors of TBI, that neuropsychological tests be explored further as an adjunct to the GOS. Future research should focus on the development of more sensitive and specific surrogate outcome measures such as magnetic resonance imaging, neurochemical, neuropsychological, and quality of life measures in order to detect a neuroprotective effect in patients with TBI.
Neurosurgery, 1994
Nervous system-specific transcription factors that bind to the octameric deoxyribonucleic acid se... more Nervous system-specific transcription factors that bind to the octameric deoxyribonucleic acid sequence motif ATGCAAAT (or ATTTGCAT) are known as N-Oct proteins. Neurons and glia contain the ubiquitous Oct-1 protein and four polypeptide complexes termed N-Oct-2, N-Oct-3, N-Oct-4, and N-Oct-5. Previously, we showed that N-Oct proteins are differentially expressed by human neuroblastoma and glioblastoma cell lines in vitro. We have now extended this work to freshly isolated human primary and metastatic brain tumors. Contrary to brain tumor cell lines, of the five astrocytomas and three glioblastomas analyzed, all but two tumors displayed the complete N-Oct protein profile, irrespective of histopathological tumor grade. Two astrocytomas were negative for N-Oct-4. Ten of 13 ependymomas exhibited N-Oct-2, N-Oct-3, and N-Oct-4 but lacked the N-Oct-5 complex. In contrast, brain metastases of two patients with extracerebral carcinomas contained only Oct-1, and cerebral metastases from two cases of B cell lymphomas showed Oct-1 and Oct-2 complexes, the characteristic Oct protein pattern of B lymphocytes. Thus, metastatic carcinoma and lymphoma expressed a non-nervous system phenotype of Oct proteins.
Journal of Neurotrauma, 2009
Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone... more Traumatic brain injury (TBI) is a major cause of death and disability. In the United States alone approximately 1.4 million sustain a TBI each year, of which 50,000 people die, and over 200,000 are hospitalized. Despite numerous prior clinical trials no standard pharmacotherapy for the treatment of TBI has been established. Citicoline, a naturally occurring endogenous compound, offers the potential of neuroprotection, neurorecovery, and neurofacilitation to enhance recovery after TBI. Citicoline has a favorable side-effect profile in humans and several meta-analyses suggest a benefit of citicoline treatment in stroke and dementia. COBRIT is a randomized, double-blind, placebo-controlled, multi-center trial of the effects of 90 days of citicoline on functional outcome in patients with complicated mild, moderate, and severe TBI. In all, 1292 patients will be recruited over an estimated 32 months from eight clinical sites with random assignment to citicoline (1000 mg twice a day) or placebo (twice a day), administered enterally or orally. Functional outcomes are assessed at 30, 90, and 180 days after the day of randomization. The primary outcome consists of a set of measures that will be analyzed as a composite measure using a global test procedure at 90 days. The measures comprise the following core battery: the California Verbal Learning Test II; the Controlled Oral Word Association Test; Digit Span; Extended Glasgow Outcome Scale; the Processing Speed Index; Stroop Test part 1 and Stroop Test part 2; and Trail Making Test parts A and B. Secondary outcomes include survival, toxicity, and rate of recovery.
Journal of Neurosurgery, 1992
Patients harboring a malignant brain tumor have been described as being highly immunosuppressed, ... more Patients harboring a malignant brain tumor have been described as being highly immunosuppressed, as evidenced by reduced numbers of T cells and the decreased ability of their lymphocytes to produce interleukin-2 (IL-2). In order to determine whether an intrinsic abnormality exists in the T lymphocytes of glioma patients and to evaluate what role corticosteroids may play in glioma-associated immunosuppression, in vitro T cell proliferative function in the presence of recombinant IL-2 (rIL-2) was examined in age-matched groups of normal control subjects, steroid-free patients with glial tumors, steroid-dependent patients with glial tumors, and steroid-dependent patients with nonglial cerebral tumors. The results demonstrated that, when enriched T cell populations of all brain-tumor patients were stimulated with rIL-2 and phytohemagglutinin (PHA), there were no statistically significant differences between any groups. In contrast, when T cell populations were stimulated with mitogenic combinations of phorbol ester, calcium ionophore, and rIL-2, those from steroid-dependent patients with glial tumors had a significantly lower response than those from normal control subjects, suggesting that a population of T cells capable of responding to phorbol ester/ionomycin and not PHA stimulation is inhibited by corticosteroid therapy in glioma patients. In addition, T cells of four brain-tumor patient/age-matched control subject pairs were stimulated with either phorbol ester/ionomycin or PHA for 24 hours; three of the four patients expressed low-affinity IL-2 receptor levels as high or higher than their respective control subjects, suggesting that IL-2 receptor expression in these patients may be quantitatively normal once the T cell number is corrected. Taken together, these results show that the decreased PHA responsiveness that has been previously reported in lymphocytes of glioma patients is not due to a cellular abnormality within the potentially responsive cells, but rather reflects the reduced proportion of T cells within their peripheral blood which, as a consequence, reduces the level of IL-2 production attained upon activation.
Journal of Neuro-oncology, 2003
One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostl... more One of the hallmarks of patients with glioblastoma multiforme (GBM) is profound lymphopenia mostly confined to the T cell lineage. A deficiency in the production of naive T cells from the thymus could contribute to the lymphopenia seen in GBM patients. In this study we asked whether thymic function and the production of recent thymic emigrant (RTE) T cells from the thymus was influenced by intracranial (i.c.) glioma progression. We found significant thymic involution in animals with progressive i.c. gliomas. Involuted thymi from animals with progressive i.c. T9.F gliomas showed dramatic losses of CD4+CD8 + (DP) thymocytes. Microscopic analysis complemented those findings by demonstrating a reversal of the typical cortico-medullary structure. Significant increases in apoptosis accompanied the rapid loss of viable thymocytes, which was prevented in part by adrenalectomy, suggesting a dominant role for endogenous glucocorticoids. This thymic involution was also associated with a significant decrease in peripheral RTE T cells, reflecting the diminished thymic function. Finally, we found that CD8 + RTE T cells were enriched in progressively growing T9 gliomas, which points to an immunological role for RTE's in anti-glioma immunity. Our findings may shed light on the significance of thymic function for anti-glioma immunity and the response to immunotherapeutic treatment paradigms.
Journal of Neuro-Oncology, 2005
We have recently reported that activation of tumor-specific T cells by subcutaneous vaccination w... more We have recently reported that activation of tumor-specific T cells by subcutaneous vaccination with irradiated T9 glioma cells of syngeneic rats with a pre-existing, intracranial (i.c.) T9 glioma (T9+vaccination) promotes the mobilization of myeloid suppressor cells (MSC) which inhibit T cell function resulting in unregulated tumor progression. The current study investigated if this immunological paradigm could be recapitulated in T cell deficient rats, in other rat glioma models or using a dendritic cell (DC) vaccine. When nude rats were used in the T9+vaccination model, the level of MSC tumor infiltration remained low in vaccinated and control groups and there was no significant difference in tumor size between the groups. Increased tumor infiltration by MSC after vaccination with respective irradiated tumor cells was observed in the 9L, F98 and D74 gliomas. RT-2 tumors were markedly infiltrated with MSC regardless of vaccination. Enhanced tumor progression in response to immunization and T cell activation was observed in rats bearing F98 and D74 gliomas, although less pronounced than in the T9 model, and there was a trend for increased tumor size in the 9L glioma model. Increased MSC infiltrate and augmented T9 glioma growth were observed when DC pulsed with T9 cell lysate was used as a vaccine. These results suggest that MSC infiltration and unregulated tumor growth in response to vaccination is T cell-dependent; is not unique to the T9 glioma; and can be recapitulated with an alternate immunization approach.