G. ten Velde - Academia.edu (original) (raw)
Papers by G. ten Velde
European Respiratory Journal, 1994
A solitary pulmonary nodule due to eosinophilic granuloma. G.P.M. ten Velde, F.B.J.M. Thunnissen,... more A solitary pulmonary nodule due to eosinophilic granuloma. G.P.M. ten Velde, F.B.J.M. Thunnissen, J.M.A. van Engelshoven, E.F.M. Wouters. ERS Journals Ltd 1994. ABSTRACT: A symptomless 42 year old man with a smoking history of 40 packyears presented with a solitary pulmonary nodule highly suggestive of lung cancer.
CHEST Journal, 1991
A 67-year-old woman had a large mediastinal mass with calcification. On roentgenogram of 30 years... more A 67-year-old woman had a large mediastinal mass with calcification. On roentgenogram of 30 years ago, the same mass without calcification was seen. The mediastinal mass was removed by surgery and proved to be a non-Hodgkin's lymphoma (NHL), most probably as a transition from a giant lymph node hyperplasia (Castleman's disease).
Acta Cytologica, 1989
The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of ... more The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of the lung are described. Histologic material was available for comparison in three of the four cases. FNA of these lesions usually yielded moderately to poorly cellular smears. The smears showed a mixture of chronic inflammatory cells and tissue fragments, without a predominance of plasma cells. Characteristic cytologic findings were not observed. The cytologic findings can be distinguished from those of other circumscribed benign and malignant lesions, however. The diagnosis of an inflammatory pseudotumor of the lung may be suggested by a combination of roentgenographic (a localized density) and FNA findings, which may justify a more conservative surgical approach.
The Netherlands journal of medicine, 1986
Nederlands tijdschrift voor geneeskunde, Jan 29, 1989
Snoring is an epiphenomenon of obstructive respiration during sleep, which may be caused by highe... more Snoring is an epiphenomenon of obstructive respiration during sleep, which may be caused by higher airway abnormalities and may result in impaired quality of nocturnal sleep, complaints of fatigue and daytime sleepiness, decreased performance level, psychic complaints and cardiovascular problems. The test results of seven patients complaining of excessive snoring and daytime sleepiness are discussed. The importance of multidisciplinary management of the underlying pathology is stressed.
Lung cancer (Amsterdam, Netherlands), 2003
Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurolo... more Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurol...
Nederlands tijdschrift voor geneeskunde, Jan 3, 2002
Journal of neuro-oncology, 2000
In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain me... more In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. One-hundred and twenty-five patients with SCLC were investigated with MR-imaging. In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. This study showed that at presentation an unexpectedly high percentage of SCLC patients had asymptomatic BM on MR-imaging. We propose th...
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 1998
This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) i... more This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) is a risk factor for massive haemoptysis in patients primarily treated by a combination of EBB and external irradiation (XRT) for NSCLC. The records of 938 patients with inoperable NSCLC who were treated with XRT and/or EBB were reviewed. The patients were divided into five groups as follows: group XRT, treated by XRT alone (n = 421); group XRTelig, treated by XRT but eligible for EBB (n = 419); group XRTEBB, primarily treated with EBB+XRT (n = 62); group EBBrec, treated by EBB for recurrence after XRT (n = 23); and group EBB, treated by EBB alone (n = 13). EBB was delivered using HDR. Patients with bronchoscopy-proven endobronchial tumour in the proximal airways, i.e. the trachea, the main bronchus or lobar bronchus were considered eligible for EBB. One hundred one out of 938 patients (10.8%) died from massive haemoptysis. The incidence was 4.3% in group XRT, 13.1% in group XRTelig and 2...
Neuroradiology, 1996
We prospectively investigated 40 patients with small-cell carcinoma of the lung (SCLC) for signs ... more We prospectively investigated 40 patients with small-cell carcinoma of the lung (SCLC) for signs of brain metastasis by neurological examination and MRI of the brain, to determine the significance of MRI for staging. MRI could not be completed in one patient, who was excluded from the study. The MRI studies of the remaining patients showed no abnormalities in 12, cerebral infarcts in 2 and brain metastases in 11 patients, of whom 3 no relevant symptoms. Nonenhancing white matter lesions were found in 14 patients. In 3 of the 4 patients with an abnormal neurological examination at diagnosis, nonenhancing white matter lesions later developed into contrast enhancing lesions compatible with brain metastases; in 2, this occurred during the course of the chemotherapy. MRI did not change the clinical staging in patients with asymptomatic brain metastases.
CLINICAL NUCLEAR MEDICINE, 1997
Small cell lung cancer (SCLC) tumors have neuroendocrine features. In vitro and in vivo studies h... more Small cell lung cancer (SCLC) tumors have neuroendocrine features. In vitro and in vivo studies have demonstrated that 50%-75% of SCLC tumors express receptors for somatostatin. This might enable in vivo localization of the primary tumor and its metastases by using scintigraphy with a radiolabeled somatostatin analogue, such as octreotide. The efficacy of scanning with In-111 labeled octreotide (octreotide scan) was studied in the staging of SCLC patients and compared with the results of conventional staging (liver ECHO, bone scintigraphy, MRI of the brain, spine, and pelvis). Imaging was performed in 29 patients with histologically confirmed SCLC at 4, 24, and 48 hours after intravenous injection of 185 MBq In-111 octreotide. In 24 of 29 patients, the primary tumor was visualized. In these 24 patients, 26 metastases were demonstrated with conventional staging, of which only nine were visualized with octreotide scan. Octreotide scans showed two metastases in the brain that were not visualized by MRI. In the other five patients, five metastases were demonstrated with conventional staging. Only two of these were detected with octreotide scan. However, octreotide scan did show a further metastasis in the brain that was not visualized by MR imaging. Octreotide imaging has a limited use in the detection of SCLC metastases compared to conventional staging. It might have some specific value in the detection of brain involvement in patients with limited disease.
Circulation Research, 1995
Myocytes are electrically coupled by gap junctions, which are composed of low-resistance intercel... more Myocytes are electrically coupled by gap junctions, which are composed of low-resistance intercellular channels. The major cardiac gap junction protein is connexin43 (Cx43). The distribution of Cx43 has been studied by immunofluorescence to visualize the electrical coupling between atrial tissue and sinoatrial node. From modeling studies, this coupling was inferred to be gradual in order to shield the sinoatrial node from the atrial hyperpolarizing influence. The actual Cx43 labeling pattern did not show the expected gradient but instead a rather black and white staining in a striking pattern of strands of cells. We used an immunohistochemical marker (anti-alpha-smooth muscle actin [alpha SMA]) that specifically cross-reacts with guinea pig sinoatrial node cells together with Cx43 antibody to stain previously electrophysiologically mapped sinoatrial nodes. We found that in the guinea pig sinoatrial node the impulse originates in an alpha SMA-positive, virtually Cx43-negative, region (primary pacemaker region). The impulse then travels obliquely upward to the crista terminalis through a region where layers of alpha SMA-positive cells alternate with layers of Cx43-positive SMA-negative cells. The layers of Cx43-positive cells appear to become broader and thicker in the direction of the crista terminalis, whereas the layers of alpha SMA-positive cells become thinner and narrower. Lateral contacts between Cx43- and alpha SMA-positive cells were very sparse and only detected where the Cx43-positive strands ended (the region where alpha SMA-positive cells fill the whole space between endocardium and epicardium, ie, the putative primary pacemaker region). From these results, we conclude that the primary pacemaker is shielded from the hyperpolarizing influence of the atrium by a gradient in coupling brought about by tissue geometric factors rather than by a gradient of gap junction density.
Circulation Research, 1994
Connexin40 (Cx40) is a member of the connexin family of gap junction proteins. Its mRNA, abundant... more Connexin40 (Cx40) is a member of the connexin family of gap junction proteins. Its mRNA, abundant in lung, is also present in mammalian heart, although in lower amount. Rabbit antipeptide antibodies directed to the COOH terminus (residues 335 to 356) of rat Cx40 were characterized to investigate the distribution of Cx40 in rat and guinea pig cardiac tissues. The affinity-purified antibodies detect specifically a major protein (Mr, 40000) in immunoblots of total extracts from rat lung and rat and guinea pig heart. In sections of guinea pig atrial tissue treated for immunofluorescence, a strong labeling associated with myocytes was seen with a distribution consistent with that of intercalated disks. The results of immunoelectron microscopy carried out with guinea pig atrial tissue showed that epitopes recognized by these antibodies were exclusively associated with gap junctions. These results, added to those of control experiments, demonstrate that antibodies 335-356 are specific for Cx40. Doublelabeling experiments carried out with lung sections using anti-factor VIII and anti-Cx40 antibodies suggest that Cx40 is expressed in blood vessel endothelial cells. In guinea pig and rat heart sections, investigated using both immunofluorescence and immunoperoxidase techniques, a signal was also found to be associated with vascular walls. In guinea pig heart, only atrial myocytes are Cx4O-positive. No labeling was detected in ventricular myocytes, including those of the His bundle and the bundle branches, which otherwise do express connexin43 (Cx43). In rat heart Cx4O -expressing myocytes are localized in the conduction system, ie, the His bundle, the bundle branches, and the Purkinje fibers. Cx43 is not detected either in the His bundle or in the proximal parts of the bundle branches, and consequently, Cx4O is the first connexin demonstrated in this region of the rat conduction system. Cx40 was not detected in the working ventricular myocytes. Doublelabeling experiments carried out with hen anti-Cx43 antibodies and rabbit anti-Cx4O antibodies demonstrated that, in tissues expressing both Cx43 and Cx4O, these two connexins were localized in the same immunoreactive sites. A few sites, however, appear to contain only one or the other of these two connexins. (Circ Res. 1994;74:839-851.)
American Journal of Respiratory and Critical Care Medicine, 1996
Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premali... more Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.
British Journal of Cancer, Feb 1, 1997
A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced restin... more A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced resting energy expenditure (REE) and a decreased energy intake contribute to weight loss. Enhanced systemic levels of inflammatory mediators were found to be related to the enhanced REE in lung cancer. The aim of the present study was to investigate energy metabolism and systemic levels of inflammatory mediators in small-cell lung carcinoma (SCLC) patients before and after treatment with chemotherapy. Hypermetabolism and an enhanced inflammatory response have already been demonstrated in SCLC by our group before. Twelve newly diagnosed SCLC patients were consecutively included in the study. REE was measured by indirect calorimetry and body composition was determined by bioelectrical impedance (BIA) before and 1 month after treatment. To assess the inflammatory state the acute-phase proteins, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), both soluble tumour necrosis factor (TNF) receptors, (sTNF-R)-55 and sTNF-R75, and soluble intercellular adhesion molecule (slCAM)-1 were measured in plasma before and 1 month after treatment. CRP was assessed by turbidemetry, whereas the other inflammatory parameters were measured by enzyme-linked immunosorbent assay (ELISA). A significant reduction in REE was found irrespective of therapeutic outcome, whereas body weight and body composition remained stable. The acute-phase proteins CRP and LBP were reduced significantly after treatment with chemotherapy, whereas both sTNF receptors and sICAM-1 remained enhanced. No correlation, however, existed between the decrease in REE and the decrease in the acute-phase proteins. In conclusion, chemotherapeutic treatment attenuates the tumour-related metabolic derangements and acute-phase response. Serum levels of soluble intercellular adhesion molecule 1 are increased in chronic lymphocytic leukemia and correlate with clinical stage and prognostic markers. Blood 84: 3010-3016 Chumlea WC and Baumgartner RN (1989) Status of anthropometry and body composition data in elderly subjects. Am J Clin Nutrition 50: 1158-1166 Collichio FA, Woolf PD and Brower M (1994) Management of patients with small cell carcinoma and the syndrome of ectopic corticotropin secretion.
Eur J Cancer, 1998
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Cancer Research, Dec 1, 1994
Previous studies have shown that an elevated resting energy expendi tare (REE) frequently occurs ... more Previous studies have shown that an elevated resting energy expendi tare (REE) frequently occurs in lung cancer patlent& The aim of the presentstudywasto assessthe balancebetweenREEand dietaryintake and to analyze the contributing factors of elevated REE in newly detected lung cancer patients. One hundred newly detected lung cancer patients were evaluated. Measured values of REE were adjusted for the values predicted by the Harris-Benedict formula and for fat-free mass assessed by the bioelectrical impedance method. Dietary intake was measured using a dietary history. A substantial number of patients (30%) had a weight loss of 10% or more from their preillness stable weight. An elevated REE was found In 74% of the patients Stratificationby tumor localizationrevealedthat patients with a central tumor had a significantly higher REE [121 ±13% (SD) versus 110 ±10% of predicted, P < 0.001] and significantly higher level of C-reactive protein (35 ±35 mg/liter versus 16 ±26 mg/liter, P = 0.006) compared with patients with a peripheral tumOr. Dietary Intake was significantly lower in the weight-losing group (1872 ±542 kcal/day versus 2169 ±782 kcal/day, P < 0.05) compared with the weight stable group. We conclude that both elevated REE and decreased dietary Intake contribute to weight loss in lung cancer patients. Tumor localiza tion and inflammation were found to be contributing factors to the elevated REE. Received 5/3/94; accepted 10/17/94.
European Respiratory Journal, 1994
A solitary pulmonary nodule due to eosinophilic granuloma. G.P.M. ten Velde, F.B.J.M. Thunnissen,... more A solitary pulmonary nodule due to eosinophilic granuloma. G.P.M. ten Velde, F.B.J.M. Thunnissen, J.M.A. van Engelshoven, E.F.M. Wouters. ERS Journals Ltd 1994. ABSTRACT: A symptomless 42 year old man with a smoking history of 40 packyears presented with a solitary pulmonary nodule highly suggestive of lung cancer.
CHEST Journal, 1991
A 67-year-old woman had a large mediastinal mass with calcification. On roentgenogram of 30 years... more A 67-year-old woman had a large mediastinal mass with calcification. On roentgenogram of 30 years ago, the same mass without calcification was seen. The mediastinal mass was removed by surgery and proved to be a non-Hodgkin&amp;amp;amp;#39;s lymphoma (NHL), most probably as a transition from a giant lymph node hyperplasia (Castleman&amp;amp;amp;#39;s disease).
Acta Cytologica, 1989
The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of ... more The fine needle aspiration (FNA) cytologic findings in four cases of inflammatory pseudotumor of the lung are described. Histologic material was available for comparison in three of the four cases. FNA of these lesions usually yielded moderately to poorly cellular smears. The smears showed a mixture of chronic inflammatory cells and tissue fragments, without a predominance of plasma cells. Characteristic cytologic findings were not observed. The cytologic findings can be distinguished from those of other circumscribed benign and malignant lesions, however. The diagnosis of an inflammatory pseudotumor of the lung may be suggested by a combination of roentgenographic (a localized density) and FNA findings, which may justify a more conservative surgical approach.
The Netherlands journal of medicine, 1986
Nederlands tijdschrift voor geneeskunde, Jan 29, 1989
Snoring is an epiphenomenon of obstructive respiration during sleep, which may be caused by highe... more Snoring is an epiphenomenon of obstructive respiration during sleep, which may be caused by higher airway abnormalities and may result in impaired quality of nocturnal sleep, complaints of fatigue and daytime sleepiness, decreased performance level, psychic complaints and cardiovascular problems. The test results of seven patients complaining of excessive snoring and daytime sleepiness are discussed. The importance of multidisciplinary management of the underlying pathology is stressed.
Lung cancer (Amsterdam, Netherlands), 2003
Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurolo... more Magnetic resonance imaging (MRI) of the brain and extensive neurological examination by a neurologist was performed as part of initial staging evaluation of 91 neurologic asymptomatic patients with large cell carcinoma or adenocarcinoma of the lung. Patients were followed up for at least 6 months. Evidence of metastatic brain disease was documented in 13 (14%) patients. Two of these patients were found suspective of brain metastases (BM) by the neurologist. The detection of BM resulted in upstaging of 1 (3%) patient in stage I/II, 4 (21%) patients in stage IIIA and 2 (11%) patients in IIIB. Especially for patients in stage III this upstaging is of importance as aggressive locoregional treatment can be abandoned. Evaluation of the brain with MRI is a sensitive method of detecting BM in neurologic asymptomatic patients and is recommended as part of the initial staging of patients with large cell carcinoma or adenocarcinoma of the lung in stage III. Additional examination by the neurol...
Nederlands tijdschrift voor geneeskunde, Jan 3, 2002
Journal of neuro-oncology, 2000
In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain me... more In this study we evaluated the usefulness of MR-imaging in the detection of asymptomatic brain metastases (BM) at the initial diagnosis in patients with small cell lung cancer (SCLC) and studied the follow-up of these patients. One-hundred and twenty-five patients with SCLC were investigated with MR-imaging. In 112 patients with normal neurological findings, MR-imaging of the brain demonstrated BM in 17 patients (15%). Six of these 17 patients were therefore upgraded to extensive disease (ED). Two of these 17 patients died during chemotherapy because of progressive disease and 3 patients became neurologic symptomatic with progressive disease on MR-imaging of the brain. After completion of chemotherapy a repeated MR-imaging of the brain in the remaining 12 patients showed 1 complete remission, 4 partial remission and 7 progressive disease of the BM. This study showed that at presentation an unexpectedly high percentage of SCLC patients had asymptomatic BM on MR-imaging. We propose th...
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 1998
This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) i... more This retrospective study was conducted to investigate whether endobronchial brachytherapy (EBB) is a risk factor for massive haemoptysis in patients primarily treated by a combination of EBB and external irradiation (XRT) for NSCLC. The records of 938 patients with inoperable NSCLC who were treated with XRT and/or EBB were reviewed. The patients were divided into five groups as follows: group XRT, treated by XRT alone (n = 421); group XRTelig, treated by XRT but eligible for EBB (n = 419); group XRTEBB, primarily treated with EBB+XRT (n = 62); group EBBrec, treated by EBB for recurrence after XRT (n = 23); and group EBB, treated by EBB alone (n = 13). EBB was delivered using HDR. Patients with bronchoscopy-proven endobronchial tumour in the proximal airways, i.e. the trachea, the main bronchus or lobar bronchus were considered eligible for EBB. One hundred one out of 938 patients (10.8%) died from massive haemoptysis. The incidence was 4.3% in group XRT, 13.1% in group XRTelig and 2...
Neuroradiology, 1996
We prospectively investigated 40 patients with small-cell carcinoma of the lung (SCLC) for signs ... more We prospectively investigated 40 patients with small-cell carcinoma of the lung (SCLC) for signs of brain metastasis by neurological examination and MRI of the brain, to determine the significance of MRI for staging. MRI could not be completed in one patient, who was excluded from the study. The MRI studies of the remaining patients showed no abnormalities in 12, cerebral infarcts in 2 and brain metastases in 11 patients, of whom 3 no relevant symptoms. Nonenhancing white matter lesions were found in 14 patients. In 3 of the 4 patients with an abnormal neurological examination at diagnosis, nonenhancing white matter lesions later developed into contrast enhancing lesions compatible with brain metastases; in 2, this occurred during the course of the chemotherapy. MRI did not change the clinical staging in patients with asymptomatic brain metastases.
CLINICAL NUCLEAR MEDICINE, 1997
Small cell lung cancer (SCLC) tumors have neuroendocrine features. In vitro and in vivo studies h... more Small cell lung cancer (SCLC) tumors have neuroendocrine features. In vitro and in vivo studies have demonstrated that 50%-75% of SCLC tumors express receptors for somatostatin. This might enable in vivo localization of the primary tumor and its metastases by using scintigraphy with a radiolabeled somatostatin analogue, such as octreotide. The efficacy of scanning with In-111 labeled octreotide (octreotide scan) was studied in the staging of SCLC patients and compared with the results of conventional staging (liver ECHO, bone scintigraphy, MRI of the brain, spine, and pelvis). Imaging was performed in 29 patients with histologically confirmed SCLC at 4, 24, and 48 hours after intravenous injection of 185 MBq In-111 octreotide. In 24 of 29 patients, the primary tumor was visualized. In these 24 patients, 26 metastases were demonstrated with conventional staging, of which only nine were visualized with octreotide scan. Octreotide scans showed two metastases in the brain that were not visualized by MRI. In the other five patients, five metastases were demonstrated with conventional staging. Only two of these were detected with octreotide scan. However, octreotide scan did show a further metastasis in the brain that was not visualized by MR imaging. Octreotide imaging has a limited use in the detection of SCLC metastases compared to conventional staging. It might have some specific value in the detection of brain involvement in patients with limited disease.
Circulation Research, 1995
Myocytes are electrically coupled by gap junctions, which are composed of low-resistance intercel... more Myocytes are electrically coupled by gap junctions, which are composed of low-resistance intercellular channels. The major cardiac gap junction protein is connexin43 (Cx43). The distribution of Cx43 has been studied by immunofluorescence to visualize the electrical coupling between atrial tissue and sinoatrial node. From modeling studies, this coupling was inferred to be gradual in order to shield the sinoatrial node from the atrial hyperpolarizing influence. The actual Cx43 labeling pattern did not show the expected gradient but instead a rather black and white staining in a striking pattern of strands of cells. We used an immunohistochemical marker (anti-alpha-smooth muscle actin [alpha SMA]) that specifically cross-reacts with guinea pig sinoatrial node cells together with Cx43 antibody to stain previously electrophysiologically mapped sinoatrial nodes. We found that in the guinea pig sinoatrial node the impulse originates in an alpha SMA-positive, virtually Cx43-negative, region (primary pacemaker region). The impulse then travels obliquely upward to the crista terminalis through a region where layers of alpha SMA-positive cells alternate with layers of Cx43-positive SMA-negative cells. The layers of Cx43-positive cells appear to become broader and thicker in the direction of the crista terminalis, whereas the layers of alpha SMA-positive cells become thinner and narrower. Lateral contacts between Cx43- and alpha SMA-positive cells were very sparse and only detected where the Cx43-positive strands ended (the region where alpha SMA-positive cells fill the whole space between endocardium and epicardium, ie, the putative primary pacemaker region). From these results, we conclude that the primary pacemaker is shielded from the hyperpolarizing influence of the atrium by a gradient in coupling brought about by tissue geometric factors rather than by a gradient of gap junction density.
Circulation Research, 1994
Connexin40 (Cx40) is a member of the connexin family of gap junction proteins. Its mRNA, abundant... more Connexin40 (Cx40) is a member of the connexin family of gap junction proteins. Its mRNA, abundant in lung, is also present in mammalian heart, although in lower amount. Rabbit antipeptide antibodies directed to the COOH terminus (residues 335 to 356) of rat Cx40 were characterized to investigate the distribution of Cx40 in rat and guinea pig cardiac tissues. The affinity-purified antibodies detect specifically a major protein (Mr, 40000) in immunoblots of total extracts from rat lung and rat and guinea pig heart. In sections of guinea pig atrial tissue treated for immunofluorescence, a strong labeling associated with myocytes was seen with a distribution consistent with that of intercalated disks. The results of immunoelectron microscopy carried out with guinea pig atrial tissue showed that epitopes recognized by these antibodies were exclusively associated with gap junctions. These results, added to those of control experiments, demonstrate that antibodies 335-356 are specific for Cx40. Doublelabeling experiments carried out with lung sections using anti-factor VIII and anti-Cx40 antibodies suggest that Cx40 is expressed in blood vessel endothelial cells. In guinea pig and rat heart sections, investigated using both immunofluorescence and immunoperoxidase techniques, a signal was also found to be associated with vascular walls. In guinea pig heart, only atrial myocytes are Cx4O-positive. No labeling was detected in ventricular myocytes, including those of the His bundle and the bundle branches, which otherwise do express connexin43 (Cx43). In rat heart Cx4O -expressing myocytes are localized in the conduction system, ie, the His bundle, the bundle branches, and the Purkinje fibers. Cx43 is not detected either in the His bundle or in the proximal parts of the bundle branches, and consequently, Cx4O is the first connexin demonstrated in this region of the rat conduction system. Cx40 was not detected in the working ventricular myocytes. Doublelabeling experiments carried out with hen anti-Cx43 antibodies and rabbit anti-Cx4O antibodies demonstrated that, in tissues expressing both Cx43 and Cx4O, these two connexins were localized in the same immunoreactive sites. A few sites, however, appear to contain only one or the other of these two connexins. (Circ Res. 1994;74:839-851.)
American Journal of Respiratory and Critical Care Medicine, 1996
Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premali... more Dysplasia in squamous metaplasia of the respiratory tract was believed to be a reversible premalignant lesion. Recently, presumably irreversible genetic alterations have been demonstrated in squamous metaplasia with dysplasia in lung-resection specimens. The genetic alterations were closely similar to those in adjacent bronchial carcinoma. There remains the question of which changes in squamous metaplastic lesions are premalignant, and which of these changes predict the occurrence of carcinoma of the respiratory tract. The purpose of this study was to determine the positive predictive value for respiratory-tract malignancy of the grade of dysplasia, p53 immunoreactivity, proliferative activity, and Bcl-2 in bronchial biopsy specimens exhibiting squamous metaplasia. Bronchial biopsies of 51 patients with squamous metaplasia diagnosed between 1982 and 1993 were used. Immunohistochemistry was done after microwave pretreatment of the biopsy specimens. Only unequivocally stained nuclei were counted. Normal bronchial epithelium obtained from autopsies was used as a control. In 31 patients, a synchronous or metachronous carcinoma was present (61%). Positive p53 immunoreactivity was found in 22 of the 51 patients (43%). The positive predictive values of p53 and of a high grade of dysplasia for carcinoma of the respiratory tract were 91% and 80%, respectively. Although the hyperproliferative state of squamous metaplastic lesions was clearly established, neither the percentage of MIB-1 labelling nor the mitotic index distinguished patient groups with and without carcinoma. No increased Bcl-2 immunostaining was found in squamous metaplasia. In conclusion, p53 immunoreactivity in squamous metaplastic lesions in bronchial biopsies is a marker of carcinoma of the respiratory tract.
British Journal of Cancer, Feb 1, 1997
A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced restin... more A disturbed energy balance has been demonstrated in lung cancer patients. Both an enhanced resting energy expenditure (REE) and a decreased energy intake contribute to weight loss. Enhanced systemic levels of inflammatory mediators were found to be related to the enhanced REE in lung cancer. The aim of the present study was to investigate energy metabolism and systemic levels of inflammatory mediators in small-cell lung carcinoma (SCLC) patients before and after treatment with chemotherapy. Hypermetabolism and an enhanced inflammatory response have already been demonstrated in SCLC by our group before. Twelve newly diagnosed SCLC patients were consecutively included in the study. REE was measured by indirect calorimetry and body composition was determined by bioelectrical impedance (BIA) before and 1 month after treatment. To assess the inflammatory state the acute-phase proteins, C-reactive protein (CRP) and lipopolysaccharide-binding protein (LBP), both soluble tumour necrosis factor (TNF) receptors, (sTNF-R)-55 and sTNF-R75, and soluble intercellular adhesion molecule (slCAM)-1 were measured in plasma before and 1 month after treatment. CRP was assessed by turbidemetry, whereas the other inflammatory parameters were measured by enzyme-linked immunosorbent assay (ELISA). A significant reduction in REE was found irrespective of therapeutic outcome, whereas body weight and body composition remained stable. The acute-phase proteins CRP and LBP were reduced significantly after treatment with chemotherapy, whereas both sTNF receptors and sICAM-1 remained enhanced. No correlation, however, existed between the decrease in REE and the decrease in the acute-phase proteins. In conclusion, chemotherapeutic treatment attenuates the tumour-related metabolic derangements and acute-phase response. Serum levels of soluble intercellular adhesion molecule 1 are increased in chronic lymphocytic leukemia and correlate with clinical stage and prognostic markers. Blood 84: 3010-3016 Chumlea WC and Baumgartner RN (1989) Status of anthropometry and body composition data in elderly subjects. Am J Clin Nutrition 50: 1158-1166 Collichio FA, Woolf PD and Brower M (1994) Management of patients with small cell carcinoma and the syndrome of ectopic corticotropin secretion.
Eur J Cancer, 1998
RefDoc Bienvenue - Welcome. Refdoc est un service / is powered by. ...
Cancer Research, Dec 1, 1994
Previous studies have shown that an elevated resting energy expendi tare (REE) frequently occurs ... more Previous studies have shown that an elevated resting energy expendi tare (REE) frequently occurs in lung cancer patlent& The aim of the presentstudywasto assessthe balancebetweenREEand dietaryintake and to analyze the contributing factors of elevated REE in newly detected lung cancer patients. One hundred newly detected lung cancer patients were evaluated. Measured values of REE were adjusted for the values predicted by the Harris-Benedict formula and for fat-free mass assessed by the bioelectrical impedance method. Dietary intake was measured using a dietary history. A substantial number of patients (30%) had a weight loss of 10% or more from their preillness stable weight. An elevated REE was found In 74% of the patients Stratificationby tumor localizationrevealedthat patients with a central tumor had a significantly higher REE [121 ±13% (SD) versus 110 ±10% of predicted, P < 0.001] and significantly higher level of C-reactive protein (35 ±35 mg/liter versus 16 ±26 mg/liter, P = 0.006) compared with patients with a peripheral tumOr. Dietary Intake was significantly lower in the weight-losing group (1872 ±542 kcal/day versus 2169 ±782 kcal/day, P < 0.05) compared with the weight stable group. We conclude that both elevated REE and decreased dietary Intake contribute to weight loss in lung cancer patients. Tumor localiza tion and inflammation were found to be contributing factors to the elevated REE. Received 5/3/94; accepted 10/17/94.