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Biomedical subjects

S Epstein

Publications and source records attributed to S Epstein.

At least 37 records · Page 2Linked to original sources
PubMed2000

Use of fluorescent microspheres to localize in vivo gene transfer injection sites.

The potential for using gene therapy to treat a variety of disease states is growing rapidly. Many vector types and delivery systems have been developed that allow the optimization of protein production levels and kinetics for a given therapeutic gene product. In cases in which a transient, localized delivery of gene product is desired, any determination of the locale of transfected tissue by non-marker genes is problematic. We describe a technique by which the use of fluorescent microspheres can help in identifying potentially transfected tissue. Adenovirus containing the gene for beta-galactosidase (beta-gal) was mixed with fluorescent microspheres and injected into rat skeletal muscle and porcine myocardium. The injection sites could be visualized under ultraviolet light and correlated with beta-gal enzyme expression. This method is simple, inexpensive and generally useful for in vivo gene transfer experiments.

Adenoviridae↗
PubMed1999

CD38/ADP-ribosyl cyclase: A new role in the regulation of osteoclastic bone resorption.

The multifunctional ADP-ribosyl cyclase, CD38, catalyzes the cyclization of NAD(+) to cyclic ADP-ribose (cADPr). The latter gates Ca(2+) release through microsomal membrane-resident ryanodine receptors (RyRs). We first cloned and sequenced full-length CD38 cDNA from a rabbit osteoclast cDNA library. The predicted amino acid sequence displayed 59, 59, and 50% similarity, respectively, to the mouse, rat, and human CD38. In situ RT-PCR revealed intense cytoplasmic staining of osteoclasts, confirming CD38 mRNA expression. Both confocal microscopy and Western blotting confirmed the plasma membrane localization of the CD38 protein. The ADP-ribosyl cyclase activity of osteoclastic CD38 was next demonstrated by its ability to cyclize the NAD(+) surrogate, NGD(+), to its fluorescent derivative cGDP-ribose. We then examined the effects of CD38 on osteoclast function. CD38 activation by an agonist antibody (A10) in the presence of substrate (NAD(+)) triggered a cytosolic Ca(2+) signal. Both ryanodine receptor modulators, ryanodine, and caffeine, markedly attenuated this cytosolic Ca(2+) change. Furthermore, the anti-CD38 agonist antibody expectedly inhibited bone resorption in the pit assay and elevated interleukin-6 (IL-6) secretion. IL-6, in turn, enhanced CD38 mRNA expression. Taken together, the results provide compelling evidence for a new role for CD38/ADP-ribosyl cyclase in the control of bone resorption, most likely exerted via cADPr.

ADP-ribosyl Cyclase↗
PubMed1999

Network oscillations generated by balancing graded asymmetric reciprocal inhibition in passive neurons.

We describe a novel mechanism by which network oscillations can arise from reciprocal inhibitory connections between two entirely passive neurons. The model was inspired by the activation of the gastric mill rhythm in the crab stomatogastric ganglion by the modulatory commissural ganglion neuron 1 (MCN1), but it is studied here in general terms. One model neuron has a linear current-voltage (I-V) curve with a low (L) resting potential, and the second model neuron has a linear current-voltage curve with a high (H) resting potential. The inhibitory connections between them are graded. There is an extrinsic modulatory excitatory input to the L neuron, and the L neuron presynaptically inhibits the modulatory neuron. Activation of the extrinsic modulatory neuron elicits stable network oscillations in which the L and H neurons are active in alternation. The oscillations arise because the graded reciprocal synapses create the equivalent of a negative-slope conductance region in the I-V curves for the cells. Geometrical methods are used to analyze the properties of and the mechanism underlying these network oscillations.

Animals↗
PubMed1999

Molecular and functional evidence for calcineurin-A alpha and beta isoforms in the osteoclast: novel insights into cyclosporin A action on bone resorption.

We provide the first molecular evidence for the presence of a functional serine/threonine phosphatase, calcineurin-A (CN-A), in the osteoclast. Polymerase chain reaction (PCR) of an osteoclast cDNA library, together with restriction mapping, revealed two isoform sequences, alpha and beta. We then examined the functionality of the detected CN-A by assessing the effect of a classical antagonist, cyclosporin A (CsA), in the osteoclast resorption (pit) assay. CsA (0.1 and 1 microg ml-1) potently inhibited bone resorption. The presence of lymphocytes, with or without prior exposure to CsA in vivo, failed to reverse the CsA-induced resorption-inhibition. Expectedly, CsA had no direct effect on cytosolic Ca2+ levels in fura-2-loaded osteoclasts. These studies are a prelude to further investigations into the possible role of CN-A in osteoclast regulation. Finally, mechanistic studies on the bone effects of CsA, a widely used immunosupressant, should proceed from these observations.

Animals↗
PubMed1999

Organization resources for families of children with deafness or hearing loss.

National health and education mandates emphasize the value of and need for early identification and intervention for children who are deaf and hard of hearing. Pediatricians in collaboration with other professionals in a multidisciplinary approach play a vital role in linking families to appropriate care. Understanding the concept of choices in communication and education resources and the process of parental and caregiver grieving enables the pediatrician to assist the family in finding needed services, agencies, and resources.

Child↗
PubMed1999

Interferon-alpha, unlike interferon-gamma, does not cause bone loss in the rat.

Interferons (IFN) are a group of related glycoproteins. IFN-gamma, in vitro, has been shown to inhibit resorption; however, an in vivo experiment showed that it had the opposite effect, resulting in bone loss that was comparable to that caused by cyclosporine A. IFN-alpha has numerous clinical applications but is used most extensively in the treatment of chronic hepatitis B and chronic hepatitis C. Research into the effects of IFN-alpha on bone mineral metabolism has been very sparse, and the majority of studies reflect in vitro models. Like IFN-gamma, there exists discordance between in vitro and in vivo studies on IFN-alpha. Both in vivo and in vitro studies demonstrate that IFN-alpha decreases bone resorption, whereas osteoblasts may or may not be affected in vivo. This study was designed to provide information on the in vivo effects of IFN-alpha in the rat model, because we feel that, given its widespread clinical use, this is an extremely important issue. Rats were given low dose IFN-alpha (1.6 x 10(6) IU/m2), intermediate dose IFN-alpha (5.35 x 10(6) IU/m2), and high dose IFN-alpha (30 x 10(6) IU/m2) three times per week for 28 days. Serum osteocalcin (bone gla protein, or BGP) and parathyroid hormone (PTH) were measured serially and, after double labeling, the bones were examined histomorphometrically. IFN-alpha did not alter any of the histomorphometric parameters measured and did not affect PTH. However, it produced a disparate BGP response. Low dose IFN-alpha resulted in a statistically significant increase in serum BGP on days 14 and 28, whereas intermediate and high doses of IFN-alpha did not. Overall, these results provide no evidence of a deleterious effect of IFN-alpha on bone metabolism and confirm the limited clinical study.

Animals↗
PubMed1999

The relation of rational and experiential information processing styles to personality, basic beliefs, and the ratio-bias phenomenon.

A new version of the Rational-Experiential Inventory (REI), which measures rational and experiential thinking styles and includes subscales of self-reported ability and engagement, was examined in two studies. In Study 1, the two main scales were independent, and they and their subscales exhibited discriminant validity and contributed to the prediction of a variety of measures beyond the contribution of the Big Five scales. A rational thinking style was most strongly and directly related to Ego Strength, Openness, Conscientiousness, and favorable basic beliefs about the self and the world, and it was most strongly inversely related to Neuroticism and Conservatism. An experiential thinking style was most strongly directly related to Extraversion, Agreeableness, Favorable Relationships Beliefs, and Emotional Expressivity, and it was most strongly inversely related to Categorical Thinking, Distrust of Others, and Intolerance. In Study 2, a rational thinking style was inversely related and an experiential thinking style was unrelated to nonoptimal responses in a game of chance. It was concluded that the new REI is a significant improvement over the previous version and measures unique aspects of personality.

Adult↗
PubMed1999

A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis.

Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm. We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose. The latter activates ryanodine receptors of the inner nuclear membrane to trigger nucleoplasmic Ca2+ release.

3T3 Cells↗
PubMed1999

Improved strategies for diagnosis and treatment of osteoporosis.

OBJECTIVE: Osteoporosis is a silent epidemic that afflicts millions of postmenopausal women around the world. Osteoporosis places an enormous economic burden on society, including significant morbidity and mortality. Because of the increasing numbers of patients with osteoporosis, primary care physicians have become the front line for the diagnosis and treatment of this condition. Thus, the primary care provider should be able to diagnose osteoporosis in both asymptomatic and symptomatic women, perform a thorough workup to exclude secondary causes of osteoporosis, and optimally prevent and treat osteoporosis using the various forms of pharmacologic and nonpharmacologic therapies. DESIGN: Review of current literature and articles dealing with pathophysiology, diagnosis, and treatment of osteoporosis. RESULTS: Diagnostic and therapeutic modalities can reduce the incidence of fractures. CONCLUSIONS: The diagnosis and treatment of osteoporosis has greatly improved but needs further efforts to prevent the disease.

Age Distribution↗
PubMed1999

[Laparoscopy in abdominal trauma].

Laparoscopy is very useful in penetrating abdominal trauma, in particular to exclude intraabdominal lesions in stab wounds. In blunt abdominal trauma laparoscopy is not the first choice of diagnostic means though it warrants comparable good results to CTscan and ultrasound. Invasiveness, high costs, and time consuming procedure require a critical and specific application making it suitable especially in unclear clinical situations and equivocal diagnostic findings. Without doubt laparoscopy is only useful in hemodynamically stable patients and is of secondary value in polytraumatized patients. In the future it has to be thought about laparoscopy in local anesthesia and in bedside procedure e.g. on the intensive care unit. Laparoscopy should be regarded as an integral part of diagnostic spectrum in blunt abdominal trauma.

Abdominal Injuries↗
PubMed1999

Drug testing in elite athletes--the Israeli perspective.

BACKGROUND: The use of performance-enhancing drugs by athletes, in particular anabolic steroids, is probably one of the major problems in sports today. During the early 1990s the Israeli Sports Federation and Olympic Committee established the Israeli Sports Anti-Doping Committee. OBJECTIVES: To present a follow-up on tests for use of performance-enhancing drugs among elite Israeli athletes from 1993 until the present. METHODS: Since 1993, 273 drug tests (urine samples) were performed in elite Israeli athletes. These tests were done during major competitions, and at random during the regular training season without prior notice to the athletes. The urine samples were sent for analysis to an official drug laboratory of the Olympic Committee in Cologne, Germany. RESULTS: Since 1993, seven (2.7%) male Israeli elite athletes (5 weight lifters, a javelin thrower, and a sprinter) tested positive for performance-enhancing drugs--all of them for anabolic steroids, and two for diuretics as well. DISCUSSION: These findings suggest that the phenomenon of performance-enhancing drug use by elite athletes has also entered Israeli sports, and probably represent the tip of the iceberg among Israeli sportsmen. Therefore, more drug tests should be performed, especially at random without prior notice and during the regular season. Athletes in the most popular sports such as soccer and basketball should also be tested. The concern over the use of these agents is both medical and ethical.

Anabolic Agents↗
PubMed1998

Effect of benazepril on complex ventricular arrhythmias in older patients with congestive heart failure, prior myocardial infarction, and normal left ventricular ejection fraction.

Sixty patients, mean age 82 +/- 8 years, with congestive heart failure, prior myocardial infarction, normal left ventricular ejection fraction, and > or = 30 ventricular premature complexes per hour detected by 24-hour ambulatory electrocardiograms, and who were treated with diuretics, were randomized to treatment with benazepril 20 to 40 mg/day (30 patients) or to no benazepril (30 patients). At a median of 6 months after treatment, follow-up 24-hour ambulatory electrocardiograms showed that compared with no benazepril, benazepril caused no significant reduction in the number of ventricular premature complexes per hour or in the number of runs of ventricular tachycardia per 24 hours.

Aged↗
PubMed1998

Mycophenolate mofetil: a promising new immunosuppressant that does not cause bone loss in the rat.

BACKGROUND: Posttransplantation bone disease is a well-described phenomenon; among its etiology is immunosuppressant-induced bone disease. Mycophenolate mofetil (MMF) has emerged as a promising new immunosuppressant. Our study was designed to investigate the effect of MMF on in vivo bone mineral metabolism. METHODS: Twenty-four 6-month-old male Sprague-Dawley rats were randomized into two groups to receive either MMF vehicle daily for 28 days or 30 mg/kg MMF daily for 28 days. The serum was assayed for osteocalcin and 1,25-dihydroxy vitamin D3. Subsequent to double-labeling, the right tibiae were removed on day 28 for histomorphometry. RESULTS: MMF suppressed bone gla protein (osteocalcin) levels on days 14 and 28 (P < 0.05). Except for percentage osteoid perimeter, there was no difference in bone histomorphometry between the two groups. CONCLUSION: In this relatively short-term study, MMF did not cause osteopenia in the rat model, but the suppressed bone gla protein merits further study.

Animals↗
PubMed1998

Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture.

p52 is a subunit of nuclear factor (NF)-kappa B transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the I kappa B family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further suggest that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors.

Adoptive Transfer↗
PubMed1998

Depressive realism from the perspective of cognitive-experiential self-theory.

To explain why the depressive realism effect has been found in trivial, artificial laboratory but not in more realistic or emotionally engaging situations, the authors hypothesized that depressed people overcompensate for a tendency toward maladaptive experiential (intuitive) processing by exercising excessive rational control in trivial situations. In more consequential situations, they are unable to control their maladaptive experiential processing because it is excessive, or their rational control is insufficient, or both. As predicted, a subclinically depressed group (n = 39) made more optimal decisions than a nondepressed control group (n = 36) under trivial conditions, and the groups converged under more consequential conditions, with the depressed group responding less and the control group more optimally. Also, the depressed group reported engaging in less rational processing and in more maladaptive experiential processing in everyday life than did the control group.

Analysis of Variance↗
PubMed1998

The fate of bone after renal transplantation.

Post-renal-transplantation bone disease is a well known entity. Immunosuppressive agents and persistence of hyperparathyroidism have primarily been implicated in its etiology. Renal transplantation patients are unique in that the bone changes occur on a background of pre-existing renal osteodystrophy. This review focuses on post-renal-transplantation bone disease. Unfortunately, the existing data in the review period, besides being scanty, provide conflicting information. This is due to the diversity of immunosuppressive regimens employed, the patient populations studied, diagnostic tools and criteria used by different centers, and the lack of formal trials.

Animals↗
PubMed1998

Immunosuppressant drugs and bone disease: a clinician's perspective.

Immunosuppressant agents are used widely for a variety of diseases, and their usage will increase as organ transplantation becomes more frequent. One of the consequences of their administration is the occurrence of rapid bone loss with fractures. Generally, glucocorticoids (GC) are the main culprit, but calmodulin-calcineurin phosphatase inhibitors, e.g., cyclosporine and tacrolimus, seem to play a role as does the underlying disease, which necessitates treatment or organ transplantation. The mechanisms for the bone disease are multifactorial and actively being researched. The management at present is largely empirical and consists of calcium, vitamin D, and antiresorbers, especially bisphosphonates. In order to achieve an optimum treatment strategy, bone density measurements are essential to define the severity of the bone loss, help decide therapy and monitor progress of the patient.

Journal Article↗