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Biomedical subjects

M Rosenbaum

Publications and source records attributed to M Rosenbaum.

At least 55 records · Page 3Linked to original sources

Effects of gender, body composition, and menopause on plasma concentrations of leptin.

Circulating concentrations of leptin ([leptin]) vary directly with body mass index and percentage body fat, and may thus constitute an afferent limb of a system regulating body fatness. We tested the hypotheses that: 1) Plasma [leptin] vary more directly with absolute fat mass than with fractional body fatness per se: and 2). The relationship between fat mass and [leptin] is significantly affected by gender and by menopausal status. [Leptin] in the post-absorptive state was examined in 67 subjects (26 male, 20 premenopausal female, 21 postmenopausal females; 43 never-obese, 24 obese) at usual body weight. Body composition was determined by hydrodensitometry, and [leptin] was determined by a double antibody ELISA assay. In male and pre-menopausal female subjects, subcutaneous adipose tissue aspirations were performed for determination of adipocyte volume by the osmium fixation method, and a 3 hour oral glucose tolerance tests was performed. At usual body weight, ([leptin]) was better correlated with absolute fat mass than with body mass index (BMI) or percentage body fat. BMI and % body fat did not account for any of the variance in [leptin] beyond that attributable to FM, per se. The regression equations relating FM to [leptin] did not differ significantly between obese and never-obese subjects. [Leptin] and fasting serum insulin concentrations were significantly correlated in males only. [Leptin] was significantly higher in pre- and post-menopausal females compared to males, even when [leptin] was corrected for differences in body composition (pre-menopausal females > post-menopausal females > males). While plasma [leptin], corrected for FM, declines significantly in women post-menopause, this decline is not sufficient to account for the striking sexual dimorphism in the relationship of leptin to fat mass. This sexual dimorphism is apparently also due, in part, to a suppressive effect of circulating androgens on [leptin].

Adipose Tissue↗

Molecular mimicry between the immunodominant ribosomal protein P0 of Trypanosoma cruzi and a functional epitope on the human beta 1-adrenergic receptor.

Sera from chagasic patients possess antibodies recognizing the carboxy-terminal part of the ribosomal P0 protein of Trypanosoma cruzi and the second extracellular loop of the human beta 1-adrenergic receptor. Comparison of both peptides showed that they contain a pentapeptide with very high homology (AESEE in P0 and AESDE in the human beta 1-adrenergic receptor). Using a competitive immunoenzyme assay, recognition of the peptide corresponding to the second extracellular loop (H26R) was inhibited by both P0-14i (AAAESEEEDDDDDF) and P0-beta (AESEE). Concomitantly, recognition of P0-beta was inhibited with the H26R peptide. Recognition of P0 in Western blots was inhibited by P0-14i, P0-beta, and H26R, but not by a peptide corresponding to the second extracellular loop of the human beta 2-adrenergic receptor or by an unrelated peptide. Autoantibodies affinity purified with the immobilized H26R peptide were shown to exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats. This effect was blocked by both the specific beta 1 blocker bisoprolol and the peptide P0-beta. These results unambiguously prove that T. cruzi is able to induce a functional autoimmune response against the cardiovascular human beta 1-adrenergic receptor through a molecular mimicry mechanism.

Amino Acid Sequence↗

Changes in energy expenditure resulting from altered body weight.

BACKGROUND: No current treatment for obesity reliably sustains weight loss, perhaps because compensatory metabolic processes resist the maintenance of the altered body weight. We examined the effects of experimental perturbations of body weight on energy expenditure to determine whether they lead to metabolic changes and whether obese subjects and those who have never been obese respond similarly. METHODS: We repeatedly measured 24-hour total energy expenditure, resting and nonresting energy expenditure, and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese. The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding. RESULTS: Maintenance of a body weight at a level 10 percent or more below the initial weight was associated with a mean (+/- SD) reduction in total energy expenditure of 6 +/- 3 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 5 kcal per kilogram per day in the obese subjects (P < 0.001). Resting energy expenditure and nonresting energy expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in both groups of subjects. Maintenance of body weight at a level 10 percent above the usual weight was associated with an increase in total energy expenditure of 9 +/- 7 kcal per kilogram of fat-free mass per day in the subjects who had never been obese (P < 0.001) and 8 +/- 4 kcal per kilogram per day in the obese subjects (P < 0.001). The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day, respectively, after weight gain. These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects. CONCLUSIONS: Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure, which oppose the maintenance of a body weight that is different from the usual weight. These compensatory changes may account for the poor long-term efficacy of treatments for obesity.

Adult↗

Autonomic nervous system activity in weight gain and weight loss.

Studies in both animals and humans indicate that the autonomic nervous system (ANS) responds to changes in systemic energy balance. In the present study, ANS response to weight change was examined by sequential blockade of cardiac autonomic innervation with parasympathetic (atropine) and sympathetic (esmolol) blockers. Change in heart period (interbeat interval) from baseline after atropine defined the amount of parasympathetic control (PC), and the subsequent change after esmolol defined the amount of sympathetic control (SC). In nonobese subjects, weight gain to 10% above initial body weight resulted in a decrease in PC and an increase in SC, and conversely, weight loss to 10% below initial weight resulted in an increase in PC and a decrease in SC. In obese subjects, weight loss resulted in the same pattern of changes in PC and SC. The major changes were in the parasympathetic arm of the ANS. These findings support the hypothesis that the ANS acts to oppose weight change.

Adrenergic beta-Antagonists↗

Contactless semi-implantable electromagnetic middle ear device for the treatment of sensorineural hearing loss. Short-term and long-term animal experiments.

A contactless electromagnetic hearing device has been designed following basic science experiments, improvement of electronics, and precision micromechanics. Different prototypes have been developed and tested in the laboratory, fresh human temporal bones, and acute and chronic animal experimentation. A conductive hearing loss model was first developed in the cat using samarium cobalt as the target magnet. Later, a highly efficient electromagnetic air-core coil was selected to vibrate a neodymium iron boron magnet cemented to the body of the incus and tested in acute and chronic experiments using the cat as the model. In this group of animals, the ossicular chain was left intact. There was no failure of the target magnet, driving coil, or implanted electronics. The only problem encountered in this evaluation was a malfunction of the receiving antenna that had to be redesigned and retrofitted into the implanted units. This system would be suitable for the treatment of moderate to severe sensorineural hearing loss. Planning to begin human clinical trials is ongoing.

Animals↗

Embolism interruptus.

Explore the source record for details and available documents.

Echocardiography, Transesophageal↗

Cancer-associated fasciitis panniculitis.

BACKGROUND: Eosinophilic fasciitis and the related fasciitis panniculitis syndrome (FPS) are the clinical and morphologic expression of a variety of disorders, of which chronic inflammation and fibrous thickening of the subcutaneous septa, fascia, and perimysium are common. FPS in patients with cancer has been reported sporadically. METHODS: In the course of our studies of FPS we have encountered three patients who had an associated neoplasia. Nine reports of patients have been taken from the literature. The clinical and histologic data of FPS in the 12 patients were analyzed in the search of distinctive features from FPS in patients with no evidence of malignancy. RESULTS: Among patients with cancer-associated FPS there was a female predominance (8 patients), predilection for hematolymphatic malignancies (9 patients), precedence of the FPS to cancer diagnosis (10 patients) by a median lag time of 1 year, and unresponsiveness to prednisone therapy in most patients (7 of 8 patients). CONCLUSIONS: Cancer-associated FPS has several characteristics of a paraneoplastic syndrome: it occurs at a distance from the tumor, certain types of tumors are overrepresented among patients with FPS, it evolves in concert with the neoplasia, and it sometimes remits after successful cancer surgery. In contrast to idiopathic FPS, cancer-associated FPS shows a female predominance, and it usually fails to respond to corticotherapy.

Adenocarcinoma↗

Mothering on crack cocaine: a grounded theory analysis.

Mothers who use crack cocaine are commonly believed to be selfish, uncaring, and neglectful of their children. For this paper, the grounded theory method was used to analyze 68 semi-structured depth interviews with cocaine-using mothers. These women's views of motherhood, the strategies they used to manage mothering on cocaine, and the contextual influences on mothering outcomes were explored. Contrary to popular assumptions, the women highly valued motherhood and held firm standards for childrearing. Mothers were concerned about the possible risks to their children and used a process of defensive compensation to protect both their children and their maternal identities from the negative influences of crack cocaine. When unable to fulfil their maternal responsibilities by other means, some mothers placed their children with family members, and others lost custody involuntarily. When children were forcibly removed, mothers often increased their drug use to cope with the loss. Social and economic conditions influenced the outcomes of mothering on crack.

Adult↗

Similarities of psychiatric disorders of AIDS and syphilis: history repeats itself.

There are marked similarities in the psychiatric disorders associated with autoimmune deficiency syndrome (AIDS) and syphilis (paresis). Although depression is most common, the psychiatric disorders in both conditions include the entire range of clinical syndromes that can simulate any type of mental disorder, functional or organic. The underlying neuropathology and methods of transmission are also similar. The author also notes that the social and moral attitudes toward patients with AIDS and syphilis are alike, including moral and religious prohibitions against the use of condoms.

AIDS Dementia Complex↗

A contactless electromagnetic implantable middle ear device for sensorineural hearing loss.

Following basic science experiments, improvement of precision micromechanics and electronics design, and development of different prototypes, a contactless electromagnetic hearing device has been successfully implanted in cats (acute experiments). Chronic animal experiments using the cat as well as the rabbit are ongoing to test the components of the device. A highly efficient air core coil is used to vibrate a neodymium-iron-boron magnet cemented to the body of the incus. The parts of the system, including implanted electronics (hybrid circuit, solid state), are laser welded and hermetically sealed. The system allows for the generation of enough force which vibrates the magnet implanted on the incus. It would be suitable for the treatment of moderate to severe sensorineural hearing loss.

Animals↗

Lack of beta 3-adrenergic effect on lipolysis in human subcutaneous adipose tissue.

Human adipocytes are responsive to both alpha- (antilipolytic) and beta-(lipolytic) actions of catecholamine agonists. These effects are mediated by G proteins which interact with adenylcyclase beta 1- and beta 2-adrenoreceptor (AR) subtypes are identified in human adipose tissue. The existence of a third beta-adrenergic (beta 3) receptor has been recently proposed. The beta 3-AR has been reported to mediate catecholamine-induced cAMP accumulation and to be more responsive in this regard than either the beta 1- or the beta 2-AR. To examine the possibility that a beta 3-AR plays a significant role in the control of catecholamine-stimulated lipolysis in human adipose tissue, we used a sensitive in vitro measure of lipolysis. Abdominal and gluteal sc adipose tissue samples from 14 adults were incubated with isoproterenol, a nonspecific beta-AR agonist which activates adenylyl cyclase via all three beta-AR subtypes, in the presence of varying concentrations of a beta-AR antagonist, alprenolol, which blocks the beta 1- and beta 2-AR, but not the beta 3-AR. In tissue from both abdominal and gluteal sites, alprenolol (10(-3) M) completely abolished the lipolytic response to isoproterenol (10(-6) M). Alprenolol (10(-3) M) alone reduced basal lipolysis by 10.2 +/- 2.2% (SEM) in abdominal tissue (P < 0.01), and 7.1 +/- 2.7% in gluteal tissue (P < 0.05). In the presence of alprenolol (10(-3) M), isoproterenol (10(-6) M) had no demonstrable lipolytic effect. The probability of incorrect acceptance of the null hypothesis that isoproterenol had no effect on lipolysis in alprenolol-blocked tissue is P beta < 0.05 for both depots. As an additional control, pooled inguinal adipose tissue from adult male Sprague-Dawley rats was incubated with the same concentrations of alprenolol. Rat adipose tissue has been previously shown to express the beta 3-adrenoreceptor and lipolysis was increased in rat adipose tissue in the presence of alprenolol 10(-4) M and 10(-5) M. We conclude that beta 3-ARs, if present in human adipocyte plasma membranes, do not significantly affect rates of lipolysis.

Abdomen↗

Proarrhythmic effects of procainamide and tocainide in a canine infarction model.

A canine model of myocardial infarction (MI) was used to study the type and frequency of ventricular antiarrhythmic and proarrhythmic effects due to procainamide and tocainide and the risk factors associated with development of proarrhythmia. An anterior MI was created by a 2-h occlusion of the left anterior descending artery (LAD) with complete reperfusion. Programmed ventricular stimulation was performed on two occasions after MI, on days 4-6 and on days 8-10, before drug and during antiarrhythmic drug infusion at three dose levels. The antiarrhythmic drugs were given in a randomized cross-over design. Only procainamide caused a dose-dependent increase in QRS, JTc, and right ventricular effective refractory period (ERP). Neither procainamide nor tocainide made sustained ventricular tachycardia (VT) noninducible, but procainamide slowed the tachycardia rate. Both drugs successfully made ventricular fibrillation (VF) noninducible: procainamide in 78% of trials and tocainide in 50% of trials. Proarrhythmia (development of inducible VT during drug when not present before drug or inability to terminate VT during drug administration) developed in 29% of dogs that received procainamide and 25% of dogs that received tocainide. There was no apparent correlation of QRS, JTc, and right ventricular ERP after drugs and proarrhythmia due to procainamide or tocainide. There was no significant difference in the size of MI between dogs with one or more proarrhythmic response to either drug and dogs that had no proarrhythmia. In this model, procainamide and tocainide had no antiarrhythmic efficacy for VT, but had moderate proarrhythmia potential that was unpredictable.

Animals↗