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Biomedical subjects

B Feldman

Publications and source records attributed to B Feldman.

At least 37 records · Page 2Linked to original sources
PubMed1995

Glyburide crosses the placenta in vivo in pregnant rats.

Non-insulin-dependent diabetes mellitus (NIDDM) is normally treated by oral hypoglycaemic agents, but their use is excluded during pregnancy because of their potential teratogenic and hypoglycaemic effects on the fetus. This caveat was recently questioned as glyburide was shown to cross an isolated cotyledon in vitro in insignificant amounts. In the present study, placental transport of glyburide in vivo was examined as an indispensable step towards clinical trials. Tritiated glyburide, C14 albumin or C14-labelled diazepam were injected into 13, 9 and 11 pregnant rats, respectively and the radioactivity was measured thereafter in maternal blood and in whole fetal extracts. The ratios between radioactivity in fetal tissue to that in maternal blood for glyburide (0.535 +/- 0.068) were similar to those of diazepam (0.641 +/- 0.057) which readily crosses the placenta. However, they differed significantly from those for albumin (0.048 +/- 0.0004) which does not cross. Moreover, glyburide in fetal tissue consistently reflected its concentration in maternal blood when measured at consecutive intervals after intravenous injection in the mother. In contrast, albumin in fetal tissue was low at all time points regardless of its levels in maternal blood when measured at different times after injection. These data suggest that glyburide crosses the placenta of pregnant rats and should therefore be considered with caution as a hypoglycaemic agent in the treatment of gestational diabetes.

Animals↗
PubMed1995

Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene.

The antiproliferative properties of lycopene, the major tomato carotenoid, were compared with those of alpha- and beta-carotene. Lycopene, delivered in cell culture medium from stock solutions in tetrahydrofuran, strongly inhibited proliferation of endometrial (Ishikawa), mammary (MCF-7), and lung (NCI-H226) human cancer cells with half-maximal inhibitory concentration of 1-2 microM; alpha- and beta-carotene were far less effective inhibitors. For example, in Ishikawa cells, a 4-fold higher concentration of alpha-carotene or a 10-fold higher concentration of beta-carotene was needed for the same order of growth suppression. The inhibitory effect of lycopene was detected after 24 hours of incubation, and it was maintained for at least three days. In contrast to cancer cells, human fibroblasts were less sensitive to lycopene, and the cells gradually escaped growth inhibition over time. In addition to its inhibitory effect on basal endometrial cancer cell proliferation, lycopene also suppressed insulin-like growth factor-I-stimulated growth. Insulin-like growth factors are major autocrine/paracrine regulators of mammary and endometrial cancer cell growth. Therefore, lycopene interference in this major autocrine/paracrine system may open new avenues for research on the role of lycopene in the regulation of endometrial cancer and other tumors.

Anticarcinogenic Agents↗
PubMed1994

Serum levels of soluble interleukin-2 receptor. A marker of disease activity in localized scleroderma.

OBJECTIVE: To determine whether circulating serum levels of soluble interleukin-2 receptor (sIL-2R) are elevated in patients with localized scleroderma, and if levels of sIL-2R can differentiate between active and inactive disease. METHODS: Seventeen patients with localized scleroderma were categorized by overall physician assessment into active, inactive, and indeterminate groups, according to disease activity. Serum sIL-2R levels were analyzed and correlated with disease activity. RESULTS: The mean sIL-2R level was significantly higher (P = 0.005) in those with active disease (1,675 +/- 823 units/ml) than in those with inactive disease (722 +/- 218 units/ml). CONCLUSION: Serum sIL-2R levels are elevated in patients with localized scleroderma. When present, elevated sIL-2R levels appear to be able to differentiate active from inactive disease. This fact also suggests cell-mediated immune activation in this condition. Further serial studies are required to assess the value and sensitivity of sIL-2R levels in measuring changes in disease activity.

Adolescent↗
PubMed1994

Is hypersomnolence a feature of seasonal affective disorder?

We examined hypersomnolence as experienced among individuals meeting standardized diagnostic criteria for Seasonal Affective Disorder (SAD). Data were available from 115 individuals attending a mood disorders clinic specializing in treatment of this disorder. Three modes of assessment were employed: retrospective self-reports (Seasonal Patterns Assessment Questionnaire), cross-sectional interviews (Standardized Interview Guide for the Hamilton Depression Scale, SAD Version), and prospective sleep diaries. Results indicated that self-reported total hours of sleep varied significantly across the seasons, with longest sleep occurring in winter and shortest sleep in summer. Seasonal sleep changes, as indicated by the SPAQ did not correlate significantly, however, with severity of depressive symptoms as indicated by the Hamilton scale. Multiple regression analyses indicated that only social activity levels (one of seven SPAQ items) was significantly and uniquely related to the severity of depression. When data obtained by the three instruments were compared, self-reported hours of sleep (whether measured by SPAQ or Hamilton interview) were significantly higher than indicated by prospective sleep diaries. We conclude that hypersomnolence may not be a central feature of SAD and that the validity of the SPAQ as an index of this disorder requires further investigation.

Adult↗
PubMed1994

A panel of monoclonal antibodies to rat plectin: distinction by epitope mapping and immunoreactivity with different tissues and cell lines.

A panel of twelve monoclonal antibodies (mAbs) to plectin was analyzed to localize molecular epitopes and assess their utility for various immunotechniques. Based on staining patterns obtained by immunoblotting of proteolytic plectin fragments five groups of mAbs with spatially closely linked epitopes were distinguished. In combination with previous results obtained with recombinant mutant proteins, the epitopes of all mAbs could be shown to reside within three separated domains of plectin's rod domain. Immunoblot analyses of several different rat tissues and a number of cultured cell lines derived from various species, including rat, hamster, cow, mouse and man, revealed considerable variations in immunoreactivity of antibodies. Differences in mAb immunoreactivities were also revealed by immunofluorescence microscopy of different tissues and cultured cell lines. One third of the mAbs examined produced staining patterns that were indistinguishable from those generated by conventional rabbit antisera, confirming the widespread and highly divers cellular localization of plectin previously reported. Microinjection of several monoclonal antibodies into Rat 1 cells had no detectable effects on the structure and organization of plectin arrays or of other cytoskeletal filaments. This new collection of mAbs provides a more reliable tool for histological studies than previously available antisera and should be useful for studies of tissue and cell type specific functions of plectin domains in vivo and in vitro.

Animals↗
PubMed1994

Post-acute rehabilitation outcome: relationship to case-management techniques and strategy.

Successful outcome for the traumatically brain-injured (TBI) patient is dependent on both a productive clinical therapy program and an effective case-management strategy by the carrier. This retrospective study focuses on identifying those case-management techniques which contributed to improvement in the disability, living, and occupational status of patients in a post-acute rehabilitation program. Statistical analysis indicated a positive relationship between two case-management factors and improved patient outcome. Additional analysis demonstrated predictive qualities of specific admission data for patient program cost. A review of these case-management techniques and their impact on discharge disability, living, and occupational status will be discussed.

Adult↗
PubMed1994

Intraperitoneal cisplatin chemotherapy versus abdominopelvic irradiation in ovarian carcinoma patients after second look laparotomy. A reassessment based on mature data.

In a previously published study we compared the outcome probability within 3 years after diagnosis in two groups of advanced ovarian carcinoma patients in complete clinical remission with minimal or no residual disease at second look laparotomy, performed after completion of cisplatin based combination chemotherapy. One group (n = 18) received after reexploration, abdominopelvic irradiation (RT group), the other diagnosed during a later period (n = 19), received after reexploration three courses of introperitoneal cisplatin chemotherapy with systemic thiosulfate protection (IP) group). In the present study the outcome of the same patients is compared after they have all been followed for at least 5 years or till death. A clear trend towards a more favorable, through statistically not significant, 5 year survival was observed (68%), in the IP group, vs 39% in the RT group (p = 0.07). In patients with a negative second-look laparotomy, the respective 5 year survival rates were 92% and 60% (p = 0.08). While the duration of the progression-free interval was similar in both treatment groups the survival after diagnosis of recurrence was significantly better in the IP group (41% vs 0%, p = 0.03).

Abdomen↗
PubMed1993

Estrogen and progesterone receptors in the uterine artery of rats during and after pregnancy.

Changes in the level of estrogen and progesterone receptors in the uterine artery of the rat were studied during pregnancy in order to evaluate the estrogen dependency of this artery. The weight of the uterine artery and its content of estrogen and progesterone receptors were measured. The steroid receptor content was also measured in the uterus and aorta as the tissues of these organs are estrogen-responsive and non-responsive, respectively. The uterine artery weight increased more than fourfold up to the middle of pregnancy and towards the end of pregnancy increased even further. The increase in weight was parallel to the increase in the level of plasma 17 beta-estradiol. During pregnancy a dramatic increase was detected in the number of uterine artery estrogen receptors. The estrogen receptor level was highest at term pregnancy, and following birth decreased to a low value. The level of progesterone receptors in the uterine artery increased modestly, though significantly, during pregnancy, and rose steeply at puerperium. No meaningful changes were seen in the aorta. The changes in estrogen and progesterone receptor levels in the rat uterine artery wall during and after pregnancy may suggest estrogen dependency of this tissue.

Animals↗
PubMed1993

Muscarinic receptor subtypes in human nasal mucosa: characterization, autoradiographic localization, and function in vitro.

Muscarinic receptors play important roles in the regulation of glandular secretion and vasomotor tone in human nasal mucosa. M1, M2, and M3 muscarinic receptor subtypes were pharmacologically characterized in human inferior turbinates by receptor-binding assays using [3H](-)quinuclidinyl benzilate (QNB, identifies total muscarinic receptors) and [3H]-pirenzepine (PZ). Receptors were localized by autoradiography, and their function examined in vitro by assaying mucus secretion from cultured nasal mucosal explants. In competition assays, PZ was employed as a selective muscarinic antagonist for M1 receptors, gallamine and AF-DX 116 for M2 receptors, and 4-DAMP for M3 receptors. These ligands are selective at low nanomolar concentrations, but can interact with other muscarinic receptors at higher concentrations. It is not known if they can interact with putative M4 and M5 muscarinic receptor subtypes. Using [3H](-)QNB, total muscarinic receptor binding was 688.4 +/- 49.6 fmol/mg protein (Bmax), with a Kd of 1.47 +/- 0.13 nM. [3H]-PZ bound to 45% of the total QNB binding sites. In competition experiments, 4-DAMP displaced [3H](-)QNB with the lowest IC50, followed by PZ and AF-DX 116. Autoradiograms demonstrated that [3H](-)QNB binding was completely displaced by 4-DAMP, partially displaced by PZ, but not displaced by gallamine or AF-DX 116, and suggested that M1 and M3 subtypes coexist in submucosal glands. The localization of M1 receptors on submucosal glands was confirmed by direct labeling with [3H]-PZ. [3H]-PZ also labeled vessels, but with a low silver grain density. Autoradiographic [3H]-QNB binding was displaced by 4-DAMP and atropine, but not by PZ, gallamine, or AF-DX 116. In studies of mucus secretion in vitro, 4-DAMP significantly inhibited methacholine-induced secretion. Although less effective, PZ also had significant inhibitory effects. Neither gallamine nor AF-DX 116 had any inhibitory effect. M1 receptors (PZ binding sites) may regulate glandular secretion while M3 receptors (4-DAMP binding sites) may regulate glandular secretion and vasomotor tone in human nasal mucosa.

Autoradiography↗
PubMed1992

Frequency of late potentials on signal-averaged electrocardiograms during thallium stress testing in coronary artery disease.

Late potentials detected by signal-averaged electrocardiography (SAECG) are an important noninvasive indicator identifying patients with previous myocardial infarction at risk for developing ventricular tachycardia. The role of myocardial ischemia in the development of late potentials is undefined. This study attempts to determine if late potentials on SAECG can be produced during scintigraphically proven ischemia. A signal-averaged electrocardiogram was obtained before and immediately after single-photon emission computed tomography thallium exercise testing in 51 patients. Reversible ischemia was documented in 25 cases with no significant changes in the parameters of SAECG; patients with previous myocardial infarction (n = 10) also had no significant changes from baseline. Multivariate analysis with respect to reversible ischemia and previous myocardial infarction was unrevealing. Patients with late potentials at baseline (n = 10) who developed reversible ischemia (n = 5) had a shorter QRS duration than those with late potentials at baseline and no reversible ischemia. The data indicate that exercise-induced scintigraphically proven ischemia does not alter SAECG even in the presence of previous myocardial infarction. Patients with late potentials at baseline may actually have a shortened QRS duration during reversible ischemia as opposed to the expected lengthening of the QRS.

Coronary Disease↗
PubMed1991

Monoclonal antibody mapping of structural and functional plectin epitopes.

To map structural and functional epitopes of the cytomatrix protein plectin, a set of mAbs was prepared by immunization of mice. Using immunoblot analysis of plectin fragments obtained after limited digestion with various proteases, two groups of mAbs were distinguished. The epitopes of one group (1) were located on a 130-kD terminal segment of the plectin 300-kD polypeptide chain, whereas those of the other group (2) bound within a 40kD segment confined to a central domain of the polypeptide chain. Domains containing the epitopes of group 2 mAbs were shown to include in vitro phosphorylation sites for kinase A, whereas kinase C phosphorylation sites were found on the same terminal segment that contained group 1 mAb epitopes. Rotary shadowing EM of mAb (Fab fragment) -decorated plectin molecules at various states of aggregation, ranging from characteristic dumbbell-shaped single molecules to highly complex multimeric structures, revealed that the epitopes of group 1 as well as those of group 2 mAbs were located on plectin's roughly 200-nm long rod domain interlinking its two globular end domains. Epitopes of group 1 mAbs were localized within a region near the center of the rod, those of group 2 in more peripheral sections near the globular end domains. Solid-phase binding assays carried out in the presence of Fab fragments of mAbs demonstrated an interference of certain group 1 mAbs in the interactions of plectin with vimentin and lamin B. On the other hand, plectin's self-interaction was inhibited mainly by Fab fragments with epitopes in the peripheral rod domain (group 2 mAbs). Together, these results suggested that the molecular binding sites of plectin for vimentin and lamin B, as well as the phosphorylation sites for kinase C, were confined to a defined central section of plectin's rod domain. In addition, they suggest an involvement of peripheral rod sections in plectin self-association.

Animals↗
PubMed1991

Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome.

To determine if outcomes of low birth weight neonates with respiratory distress syndrome can be improved by the administration of multiple doses of bovine surfactant, we conducted two identical multicenter, controlled trials, and the results were combined for analysis. Seven hundred and ninety-eight neonates weighing 600 to 1750 g at birth who had developed respiratory distress syndrome within 6 hours of birth were assigned randomly to receive either 100 mg of phospholipid/kg of Survanta, a modified bovine surfactant (n = 402), or a sham dosing procedure (n = 396). Neonates whose respiratory distress persisted could be given up to three more doses, with all doses to be given in the first 48 hours after birth. Dosing was performed by investigators not involved in the clinical care of the neonates; nursery staff were kept blinded as to the treatment assignment. Fewer Survanta-treated neonates died of any cause (18.4% vs 27.3%, P = .002), died of respiratory distress syndrome (9.0% vs 20.3%, P less than .001), and either died or developed bronchopulmonary dysplasia due to respiratory distress syndrome (51.2% vs 64.6%, P less than .001). Neonates who received Survanta also had greater improvement in their oxygenation and ventilatory status from baseline to 72 hours than did control neonates. Survanta-treated neonates were at lowered risk for developing pulmonary interstitial emphysema (18.6% vs 39.3%, P less than .001) and other pulmonary air leaks (11.5% vs 25.9%, P less than .001). We conclude that multiple doses of Survanta given after diagnosis of respiratory distress syndrome reduce mortality and morbidity.

Administration, Inhalation↗
PubMed1989

The Utah anesthesia workstation.

A prototype anesthesia workstation has been developed to demonstrate the feasibility of a computer-assisted anesthesia workplace. The workstation provides a central display of information and aids the user in controlling and monitoring the anesthesia delivery system. The anesthesiologist interacts with the workstation through a Macintosh computer, which is easy for the clinician to understand and to use. Seventeen sensors and monitors transmit information from the anesthesia delivery system to the computer. The computer monitors this information using a set of rules, evaluated once each breath, to detect changes in the delivery system. If an event is detected, the computer alerts the anesthesiologist with a diagram, a text message, and an audible warning. A laboratory test of the monitoring system was performed to see if it properly identified 26 different critical events during simulated low flow and closed circuit anesthesia. Five hundred and eight-three of 660 simulated critical events (88%) were identified with the unique and correct message. On 35 occasions, multiple messages were displayed, including the correct one. Critical events were misidentified or not detected 42 times. Eight false positive alarms occurred during the 20 h of testing; all occurred as a result of baseline drift in a single transducer. These results demonstrate that a sophisticated monitoring system can reliably diagnose specific anesthesia machine failures.

Anesthesiology↗
PubMed1989

Anti-tumor immunity in breast cancer evaluated by a computerized tube leukocyte adherence inhibition (LAI) assay.

Seventy-four women admitted for breast biopsy were monitored before surgery for anti-tumor cell-mediated immunity using a computerized tube leukocyte adherence inhibition (LAI) assay. Spent medium from breast, lung and colon adenocarcinoma cell lines was used as the source of organ-specific neoantigens for standardization of the assay. Peripheral blood leukocytes from 25/40 (62.5%) patients diagnosed after surgery as breast cancer responded to spent medium with a positive non-adherence index (NAI). A positive NAI was inversely related to tumor mass because only 7/18 (38.8%) of those with Stage III or IV had a positive NAI; while 18/22 (81.8%) of those with Stage I or II were positive. Cross-reactive antigenicity was not observed when spent medium from breast cancer was incubated with leukocytes from patients with several other solid tumors nor when leukocytes from breast cancer patients were incubated with spent medium from lung or colon carcinoma cell lines. The antigenic material in the spent medium appears to be an organ-specific neoantigen because only 1/34 patients with benign breast disease had a positive NAI and all normal healthy control individuals were negative. The results of this study show that spent medium of a breast carcinoma cell line is more reliable than crude cancer extracts for use in LAI to detect specific anti-tumor cellular immune responses. The improved method presented in this report can be a useful tool in the early diagnosis of breast cancer and for monitoring of patients with this disease.

Adult↗