Laurence Demers | Penn State University (original) (raw)

Papers by Laurence Demers

Cancer Research

Recent evidence indicates that hormone-responsive but not -resistant human breast cancer cells in... more Recent evidence indicates that hormone-responsive but not -resistant human breast cancer cells in culture are sensitive to the antiproliferative effect of the polyamine (PA) biosynthetic inhibitor alpha-difluoromethylornithine (DFMO). The present experiments were designed to investigate the potential differential involvement of the PA pathway in the growth of these different biological subtypes of human breast cancer. Thus, we evaluated the effect of DFMO on proliferation, ornithine decarboxylase (ODC) activity, and PA levels of the hormone-dependent MCF-7 and -independent MDA-MB-231 breast cancer cell lines. When tested at comparable cell density, the two cell lines had similar levels of ODC activity and PA. Administration of DFMO (0.01, 0.1, 1, 4 mM) for 6 days caused a similar dose-dependent inhibition of proliferation (up to approximately 15% of control) associated with suppression of ODC activity to undetectable levels at the highest dose. In both cell lines, putrescine and spermidine levels were maximally suppressed by doses of DFMO greater than 0.1 mM. Higher doses of DFMO (1 and 4 mM) also suppressed spermine levels to approximately 60% of control. In detailed time-course studies, DFMO administration (0.1 mM) similarly suppressed by 80% the rise in ODC observed in both cell lines following a medium change. At all time points, putrescine and spermidine levels were likewise suppressed to a similar extent. Addition of putrescine (0.1-2.5 mM) to DFMO-treated cells repleted cellular PA levels and restored growth to approximately 80% of control in both cell lines. We conclude that, under these experimental conditions, PA are similarly involved in the growth of the hormone-responsive MCF-7 and -resistant MDA-MB-231 human breast cancer cell lines.

Extended exposure to weightlessness results in bone loss. How- ever, little information exists as... more Extended exposure to weightlessness results in bone loss. How- ever, little information exists as to the precise nature or time course of this bone loss. Bone resorption results in the release of collagen breakdown products, including N-telopeptide and the pyridinium (PYD) cross-links, pyridinoline and deoxypyridinoline. Urinary pyr- idinoline and deoxypyridinoline are known to increase during bed rest. We assessed excretion

Advances in prostaglandin and thromboxane research

1. Adv Prostaglandin Thromboxane Res. 1980;8:1633-5. Mechanism of action of castor oil: a biochem... more 1. Adv Prostaglandin Thromboxane Res. 1980;8:1633-5. Mechanism of action of castor oil: a biochemical link to the prostaglandins. Luderer JR, Demers LM, Nomides CT, Hayes AH Jr. PMID: 7377011 [PubMed - indexed for MEDLINE]. MeSH Terms. ...

Research communications in chemical pathology and pharmacology

The effects of hydralazine on arachidonic acid metabolism were studied in isolated washed human p... more The effects of hydralazine on arachidonic acid metabolism were studied in isolated washed human platelets. The washed platelets (10(9)/ml) were exposed to 14C-arachidonic acid and incubated for 15 minutes in a platelet aggregometer (37 degrees C). The media was then extracted and the reaction products separated by means of reversed phase high pressure liquid chromatography. In this system, hydralazine inhibited the production of TXB2 (the stable metabolite of TXA2) and enhanced the production of PGF2 alpha and PGE2 in a dose dependent fashion. Indomethacin, blocked the production of all prostaglandin compounds normally synthesized by platelets. These results suggest that hydralazine is a specific thromboxane synthetase inhibitor and that its vasodilatory effects might be related to its ability to block the production of an endogenous vasoconstrictor (i.e. TXA2).

Gastroenterology

Although parenteral neurotensin (NT) inhibits stimulated gastric acid secretion, published report... more Although parenteral neurotensin (NT) inhibits stimulated gastric acid secretion, published reports on the effect of centrally administered NT on gastric acid secretion are conflicting. This study provides evidence suggesting that, in chronic gastric fistula rats, intracerebroventricularly administered NT (15-60 micrograms) significantly reduces both basal and pentagastrin-, 2-deoxy-D-glucose-, and carbachol-but not histamine-stimulated gastric acid secretion. Using radioimmunoassay, the concentration of plasma immunoreactive NT increased from 30 to 200 pg/ml at 30 and 60 min, respectively after a single intracerebroventricular (i.c.v.) administration of NT at a dose of 60 micrograms. These serum NT concentrations can be reproduced by a constant NT i.v. infusion at 2 micrograms/kg.h. This parenteral infusion dose does not inhibit acid secretion as does i.c.v. NT. Pretreatment with the i.c.v. dopamine-2 receptor antagonists haloperidol or domperidone totally abolishes the inhibitory e...

The American journal of clinical nutrition, 2008

Whole-grain foods are associated in observational studies with a lower body mass index and lower ... more Whole-grain foods are associated in observational studies with a lower body mass index and lower cardiovascular disease (CVD) risk. However, few clinical trials have tested whether incorporating whole grains into a hypocaloric diet increases weight loss and improves CVD risk factors. The aim of this study was to determine whether including whole-grain foods in a hypocaloric (reduced by 500 kcal/d) diet enhances weight loss and improves CVD risk factors. Obese adults (25 M, 25 F) with metabolic syndrome were randomly assigned to receive dietary advice either to avoid whole-grain foods or to obtain all of their grain servings from whole grains for 12 wk. All participants were given the same dietary advice in other respects for weight loss. Body weight, waist circumference, and percentage body fat decreased significantly (P<0.001) in both groups over the study period, but there was a significantly (P=0.03) greater decrease in percentage body fat in the abdominal region in the whole-...

Clinical chemistry, 2002

Purchase of automated systems in today's clinical laboratory needs justification based on dem... more Purchase of automated systems in today's clinical laboratory needs justification based on demonstrable improvements in efficiency and a sound payback model. Few studies provide information on laboratory automation that focuses on the preanalytical portion of specimen processing. We recently evaluated an automated preanalytical processing unit (GENESIS FE500) at two academic health centers. This preanalytical unit processes blood specimens through automated specimen sorting, centrifugation, decapping, labeling, aliquoting, and placement of the processed specimen in the analytical rack. We quantified the output of the FE500 by processing >3000 barcode-labeled specimens according to a protocol designed to test all of the features of this automated specimen-processing unit. Depending on the batch size, aliquot number requested, and percentage of tubes that required centrifugation, the mean system output performance varied between 93 and 502 total tubes/h. Throughput increased whe...

Cancer research, 1998

The high concentrations of estradiol (E2) found in breast tumors of postmenopausal women could be... more The high concentrations of estradiol (E2) found in breast tumors of postmenopausal women could be the result of enhanced uptake from plasma or in situ aromatization of androgens to estrogens. To test the relative importance of these two mechanisms, a model system allowing precise distinction between each is required. Such a model was established using aromatase (A+)- and sham (A-)-transfected MCF-7 cells inoculated into ovariectomized (OVX) nude mice. To validate the model, the confounding effect of peripheral aromatization was first excluded experimentally. A- cells were inoculated into OVX mice as homoimplants (A- cells on both flanks) or heteroimplants (A- cells on one flank and A+ cells on the other), and growth of A- cells in response to exogenous aromatase substrate, androstenedione (delta4A), was evaluated. A- cells did not grow in either group during the 8 weeks of observation, indicating the lack of peripheral aromatization in OVX mice. The biological effects of in situ aro...

Clinical chemistry, 1993

Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, wer... more Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects. Both cross-links were increased in cancer patients with and without clinically detectable bone metastases, although patients with bone and liver involvement had higher mean concentrations. The mean concentrations of both cross-links were also significantly higher in the urine samples of inpatients than in an outpatient ambulatory population. These findings suggest that the measurement of PYD and DPD in urine may be useful in assessing bone metastases and bone resorption in cancer patients.

Clinical chemistry, 1995

Several biochemical markers of bone formation and bone resorption have recently been developed. T... more Several biochemical markers of bone formation and bone resorption have recently been developed. These markers have been evaluated for clinical utility in patients with metabolic bone disease, including Paget disease and osteoporosis, and for their potential use in cancer patients whose disease has metastasized to bone. We have evaluated seven markers of bone turnover in the plasma and urine of 94 patients with newly diagnosed or progressive malignancy with and without clinical evidence of bone metastases. As determined by a positive bone scan and (or) bone survey, 30 patients had metastases to bone; 51 patients had metastatic cancer without overt bony involvement; and 13 patients had local disease without bone metastases. To evaluate the predictive value of these markers in the metastatic population, we utilized a "Z-score" and logistic regression analysis to distinguish patients with documented bone metastatic disease from those patients without clinical evidence of bone ...

Journal of chromatography, Jan 8, 1983

Clinical pharmacology and therapeutics, 1982

The humoral and hemodynamic effects of converting enzyme inhibition captopril are presented in tw... more The humoral and hemodynamic effects of converting enzyme inhibition captopril are presented in two patients with primary hyperaldosteronism (PHA). In all, 20 patients with resistant hypertension were treated with the angiotensin converting enzyme inhibitor captopril. In 18 patients with essential or renovascular hypertension mean (+/- SEM) plasma renin activity (PRA) rose from 5.0 +/- 1.4 to 35.3 +/- 5.3 ng/ml/hr (P less than 0.01) and mean (+/- SEM) plasma aldosterone (PA) declined from 25.8 +/- 2.9 to 15.1 +/- 1.9 ng/ml (P less than 0.01) after captopril. In two patients with PHA the PRA was not stimulated by converting enzyme inhibition, although there was modest decline in PA and a temporary reduction in blood pressure. After surgical removal of aldosterone-producing adenomas, PRA responsed appropriately to captopril. These cases illustrate that a disease process can modify the response to a drug and demonstrate that, in patients with PHA, captopril does not stimulate PRA, induc...

The Journal of clinical endocrinology and metabolism, 1988

Serum 3 alpha-androstanediol glucuronide (3 alpha-Adiol-G) is considered to be an indicator of pe... more Serum 3 alpha-androstanediol glucuronide (3 alpha-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3 alpha-Adiol-G and secreted from the cell. Elevated serum 3 alpha-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3 alpha-Adiol-G concentrations. Although there was considerable overlap of serum 3 alpha-Adiol-G values among the groups defined by hair density or acne scores, we found statistically significant correlations between serum 3 alpha-Adiol-G and chest hairiness (P = 0.0034), acne (P = 0.0005), and a combined chest hairiness and acne score (P = 0.0018). There was no significa...

The American journal of physiology, 1990

We compared gastric myoelectrical activity and endogenous neuroendocrine responses in subjects wi... more We compared gastric myoelectrical activity and endogenous neuroendocrine responses in subjects with and without motion sickness elicited by illusory self-motion or vection. Rotating a drum with black and white vertical stripes around seated stationary subjects (n = 22) produced vection. Gastric myoelectrical activity was recorded with cutaneous electrodes. Thirteen subjects developed gastric dysrhythmias [4- to 9-cycles/min (cpm) signals] and motion sickness during vection, whereas nine subjects maintained normal 3-cpm gastric rhythms and remained symptom free. Base-line plasma cortisol and beta-endorphin levels were significantly greater (P less than 0.01) in the subjects who would develop gastric dysrhythmias and nausea compared with the subjects who would not develop motion sickness. Norepinephrine levels increased in the nauseated group immediately after vection ceased (354.6 +/- 41.1 pg/ml) compared with the symptom-free subjects (223.1 +/- 22.8 pg/ml, P less than 0.05). Epinep...

Prostaglandins, Leukotrienes and Medicine, 1983

Proceedings of the National Academy of Sciences, 1992

Previous work showed that production of transforming growth factor 13 (TGF-I) by osteoblast-like ... more Previous work showed that production of transforming growth factor 13 (TGF-I) by osteoblast-like rat UMR 106 cells was increased by 17l-estradiol at physiological concentrations. To determine whether ovariectomy alters the concentration of TGF-IJ in rat long bones, female Sprague-Dawley rats were either sham-operated (a = 19) or ovariectomized (a = 19), pair-fed a semisynthetic diet for 6 weeks, and sacrificed. Tibial and femoral diaphyses were removed and extracted by demineralization. Ovariectomy lowered serum estrogen; did not alter body weight, serum magnesium, or serum 1,25-dihydroxyvitamin D; and produced only modest differences in serum calcium and phosphate concentrations. Hydroxyproline was higher and extractable protein was lower in bones from ovariectomized rats than in bones from shamoperated rats; calcium content did not differ between the two groups of animals. Ovariectomy lowered the concentration of

Background: Whole-grain foods are associated in observational studies with a lower body mass inde... more Background: Whole-grain foods are associated in observational studies with a lower body mass index and lower cardiovascular disease(CVD)risk.However,fewclinicaltrialshavetestedwhether incorporating whole grains into a hypocaloric diet increases weight loss and improves CVD risk factors. Objective:Theaimofthisstudywastodeterminewhetherincluding whole-grain foods in a hypocaloric (reduced by 500 kcal/d) diet enhances weight loss and improves CVD risk factors. Design: Obese adults (25 M, 25 F) with