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Biomedical subjects

S Levin

Publications and source records attributed to S Levin.

At least 109 records · Page 6Linked to original sources

Effects of two weeks of feed restriction on some common toxicologic parameters in Sprague-Dawley rats.

This study was intended to identify changes caused by short-term reduced feed intake in rats such as may occur with unpalatable feed or other forms of anorexia. For 2 wk, groups of rats (10/sex/group) were fed ad libitum (control group) or given 75% (mildly restricted group), 50% (moderately restricted group), or 25% (severely restricted group) of the amount of feed eaten the day before by controls. The control group and mildly restricted group grew steadily, but the terminal body weights of the mildly restricted group (both males and females) were only about 80% of controls. The moderately restricted group did not grow during the first week but grew slightly during the second week (terminal body weights about 65% of control). The severely restricted group lost weight throughout the study (terminal weight about 40% of control). Restricted groups exhibited hemoconcentration directly related to the degree of feed restriction. White blood cell counts were reduced (principally due to lymphopenia) in severely restricted rats. Platelet counts were decreased in all restricted groups. Total serum protein concentration was reduced (decreased globulins) in all female restricted groups and in the severely restricted males. The severely restricted rats had increased serum bilirubin, electrolyte derangements, and (in females only) decreased cholesterol. Thymus and liver weights (absolute and relative) were decreased in the moderately and severely restricted groups. All the feed-restricted groups had an increased incidence of superficial gastric erosions. The mildly and moderately restricted groups had slightly decreased hematopoietic tissue in sternal bone marrow, while the severely restricted group had bone marrow necrosis, thymic atrophy, and mild testicular degeneration. Findings in the severely restricted group were distinct from those in the other groups on the basis of their severity and were considered adverse. Changes in the mildly and moderately restricted groups were considered adaptive and innocuous since feed restriction of this degree has historically been associated with increased longevity and decreased disease incidence in chronic studies.

Alanine Transaminase↗

Home parenteral antibiotic therapy for patients with cystic fibrosis.

Cystic fibrosis is a genetic disease that affects multiple organ systems. Pulmonary complications associated with it frequently require intense intravenous antibiotic therapy. Home care allows patients to be treated at home, reducing the disruption of family life. New drug administration devices allow the patient increased mobility and independence. With adequate family and nursing support, patients may be able to attend work or school. Reduced hospital stays are good for the patient and cost effective for the hospital. The success of home antibiotic therapy depends on careful selection of the candidate, antibiotic regimen, nursing agency, and home care company. Many patients and families, though motivated, cannot manage the additional stress and time commitment required for home intravenous antibiotic and chest physical therapy. This time commitment may be reduced somewhat by limiting the number of antibiotics and the frequency of their administration.

Anti-Bacterial Agents↗

Transient erythroblastopenia of childhood. Evidence for cell-mediated suppression of erythropoiesis.

PURPOSE: T cell-mediated red cell aplasia in a 4 1/2-year-old child with transient erythroblastopenia of childhood (TEC) is described. PATIENTS AND METHODS: Erythropoiesis was studied by assessing the colony growth of marrow erythroid progenitors at the time of diagnosis and during recovery. RESULTS: The colony-forming unit-erythroid (CFU-E) growth of whole marrow at diagnosis was only 28% that of the control. T-cell depletion of the patient's marrow was followed by a more than fivefold increase in CFU-E growth, as compared with 20% inhibition of CFU-E and 40% inhibition of burst-forming unit-erythroid (BFU-E) growth in control marrow. The number of colony-forming unit-granulocyte-macrophage (CFU-GM) in both control and patient's marrow was not significantly altered by all of these manipulations. During early and late recovery, CFU-E and BFU-E growth improved substantially, and the effect of T-cell depletion diminished. Increased numbers of peripheral T-suppressor lymphocytes, as well as activation of natural killer (NK) cells and high levels of interferon, all consistent with viral infection, were found at presentation. Clinical recovery was associated with normalization of T-suppressor lymphocyte number. CONCLUSIONS: The results suggest that in this child with TEC, a preceding viral infection may have caused activation of suppressor T-cells and interferon secretion leading to cell-mediated suppression of erythropoiesis.

Anemia↗

Hezekiah's boil.

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Bible↗

Characterization of de novo duplications in eight patients by using fluorescence in situ hybridization with chromosome-specific DNA libraries.

Fluorescence in situ hybridization (FISH) with chromosome-specific DNA libraries was performed on samples from eight patients with de novo chromosomal duplications. In five cases, the clinical phenotype and/or cytogenetic evaluations suggested a likely origin of the duplicated material. In the remaining three cases, careful examination of the GTG-banding pattern indicated multiple possible origins; hybridization with more than one chromosome-specific library was performed on two of these cases. In all cases, FISH conclusively identified the chromosomal origin of the duplicated material. In addition, the hybridization pattern was useful in quantitatively delineating the duplication in two cases.

Aneuploidy↗

Atrial natriuretic peptide: direct effects on human red blood cell dynamics.

The ability to deform is an important feature of red blood cells (RBCs) for performing their function of oxygen delivery. Little is known about the hormonal regulation of RBC deformability. Here we report that human atrial natriuretic peptide (ANP) acts directly on human RBCs leading to the elevation of local bending fluctuations of the cell membrane. These changes are accompanied by an increase in the filterability of RBCs. These ANP effects were mimicked by cyclic GMP analogues, suggesting modulation of local membrane bending fluctuations and RBC filterability via a cyclic GMP-dependent pathway. The effect of ANP on the mechanical properties of RBCs suggests that ANP may increase the passage red blood cells through capillaries resulting in an improved oxygen delivery to the tissues.

Atrial Natriuretic Factor↗

Correlation between local cell membrane displacements and filterability of human red blood cells.

Local mechanical fluctuations of the cell membrane of human erythrocytes were shown to involve MgATP- and Mg(2+)-driven fast membrane displacements. We propose that these local bending deformations of the cell membrane are important for cell passage through capillaries. In order to verify this hypothesis, we examined cell membrane fluctuations and filterability of erythrocytes over a wide range of medium osmolalities (180-675 mosmol/kg H2O). The results indicate the existence of a positive correlation between the amplitude of local cell membrane displacements and cell filterability. We suggest that the occurrence of metabolically driven membrane displacements on the side surface of the red blood cell diminishes its bending stiffness and enables it to fold more efficiently upon entrance into blood capillaries. Thus, local cell membrane displacements seem to play an important role in microcirculation.

Culture Media↗

Promotional activities of the non-genotoxic carcinogen bemitradine (SC-33643).

Bemitradine (SC-33643), a diuretic antihypertensive agent, was studied for its carcinogenicity in a 2-year bioassay in Charles River CD rats via dietary admix at dosages of 50, 150 and 450 mg kg-1 for up to 97 weeks (after which they were followed for eight additional weeks without treatment). Body weights were decreased compared to controls: 5-15% in the female and 10-12% in the male dosage groups by week 105 of the study. Prolactin values were significantly increased in 150 and 450 mg kg-1 females. The compound caused significant increased incidences of liver, thyroid (both sexes) and mammary (females only) neoplasms. The metabolism of bemitradine was studied in both rats and man. Bemitradine and its primary metabolite (SC-36741; desethylbemitradine) were tested and found to be non-genotoxic in Ames, rat primary hepatocyte UDS, CHO/HGPRT, CHO cytogenetics, in vivo mouse micronucleus and mouse lymphoma TK+/- (bemitradine only) assays. Finally, in an altered hepatic foci (Y-glutamyl transpeptidase positive) promotion assay in female Charles River CD rats, bemitradine was found to be a promotor, though not as potent as phenobarbital. We concluded that bemitradine (which has been dropped from development) is a non-genotoxic carcinogen which appears to act by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands. Tumors seen in the thyroid were probably secondary to the effects of bemitradine on metabolism.

Animals↗

Induction of colitis in rats by 2-2'-azobis(2-amidinopropane) dihydrochloride.

Reactive oxygen metabolites (ROM) may play a role in the pathophysiology of inflammatory bowel disease (IBD) and ischemia-reperfusion-induced intestinal injury. Although there are many reports of intestinal mucosal injury associated with neutrophil-derived ROM, free radicals themselves have not been reported to induce intestinal mucosal injury. We administered intrarectally 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) to rats, an azo compound that generates free radicals in vitro. Acute mucosal injury was assessed histologically by light microscopy and biochemically by myeloperoxidase (MPO) activity. Intrarectal administration of AAPH (60, 90, 150 mg/kg) caused erythema, edema, and histologically verifiable mucosal inflammation. MPO activity was increased 9- to 18-fold above the control level. The levels of thiobarbituric acid (TBA) reactants and sulfhydryls (SH) were significantly (P less than 0.01) increased and decreased, respectively, by 90 mg/kg AAPH. Sulfasalazine, 5-aminosalicylic acid, the LTB4 receptor antagonist SC-41930, and the antioxidant glutathione prevented the inflammation. This model of mucosal inflammation may be useful in evaluating new therapeutic agents for the treatment of IBD.

Amidines↗

Mucosal protective activity of prostaglandin analogs in rodent colonic inflammation.

The mucosal protective prostaglandin analogs misoprostol, enisoprost, and SC-46275 (the 17E-18-cyclopentenyl analog of enisoprost) were tested in mouse and rat colitis induced by the intrarectal instillation of dilute acetic acid. Colitis was assessed by histology and colonic levels of myeloperoxidase (a neutrophil marker enzyme). When given as enemas 30 min ahead of colitis induction, 15(R)-15-methyl-PGE2 (arbaprostil) and 15(S)-15-methyl-PGE1 were inactive; however, misoprostol, enisoprost, and SC-46275 protected against colonic inflammation with ED50 values of 24, 12 and 1.3 micrograms/kg, respectively, in rats and 11, 5, and 1 micrograms/kg, respectively, in mice. These compounds may have utility in the medical management of human inflammatory bowel disease.

Acetates↗

Abnormalities of smooth pursuit and saccadic control in schizophrenia and affective disorders.

Smooth pursuit abnormalities have been reported in patients with schizophrenia and their first-degree relatives, suggesting that abnormal tracking may serve as a biological marker for schizophrenia. Recent studies in schizophrenic patients have found reduced pursuit gain, low initial acceleration and abnormal gain-corrective saccade interactions. Impaired saccadic initiation has been noted in anti-saccade tasks and in predictive saccade generation, as has saccadic hypometria. While abnormalities have been found in affective disorder patients, studies of their first-degree relatives suggest that abnormalities during pursuit are more closely associated with schizophrenia. Identification of specific defects allows informed speculation about their neural substrates and suggests possible relationships between the ocular motor defects and other cognitive and perceptual abnormalities associated with the major psychiatric disorders.

Humans↗

Oxygenation-deoxygenation cycle of erythrocytes modulates submicron cell membrane fluctuations.

Low frequency submicron fluctuations of the cell membrane were recently shown to be characteristic for different cell types, nevertheless their physiological role is yet unknown. Point dark-field microscopy based recordings of these local displacements of cell membrane in human erythrocytes, subjected to cyclic oxygenation and deoxygenation, reveals a reversible decrease of displacement amplitudes from 290 +/- 49 to 160 +/- 32 nm, respectively. A higher rate of RBC adhesion to a glass substratum is observed upon deoxygenation, probably due to a low level of fluctuation amplitudes. The variation in the amplitude of these displacements were reconstituted in open RBC ghosts by perfusing them with composite solutions of 2,3 diphosphoglycerate, Mg+2, and MgATP, which mimic the intracellular metabolite concentrations in oxygenated and deoxygenated erythrocytes. The mere change in intracellular Mg+2 during oxygenation-deoxygenation cycle is sufficient to explain these findings. The results imply that the magnitude of fluctuations amplitude is directly connected with cell deformability. This study suggests that the physiological cycle of oxygenation-deoxygenation provides a dynamic control of the bending deformability and adhesiveness characteristics of the RBC via a Mg+2-dependent reversible assembly of membrane-skeleton proteins. The existing coupling between oxygenation-deoxygenation of the RBC and its mechanical properties is expected to play a key role in blood microcirculation and may constitute an example of a general situation for other circulating blood cells, where the metabolic control of cytoskeleton dynamics may modulate their dynamic mechanical properties.

2,3-Diphosphoglycerate↗

Correlates of a residential pesticide contamination in a self-selected sample.

We evaluated the behavioral, health perception, and physical health correlates of a residential pesticide misapplication on 54 individuals and identified factors differentially related to various levels of distress. Study participants were mainly concerned with health issues and exhibited somatic symptoms. Behavioral actions designed to obtain information regarding exposure levels and to reduce exposure were adopted. We found that factors such as a higher contamination level, involvement in a lawsuit, and belonging to a consumer action group, were strongly related to higher levels of psychological distress and, to a lesser extent, to behaviors, somatic symptoms, and health perceptions.

Adolescent↗

The interferon system in patients with malignant disease.

Since the interferon (IFN) system involves both IFN producing and IFN responding cells, it is possible to study separately these phenomena, relating them to disease entities as well as to response to therapy. Numerous studies in animals and man suggest effectiveness of IFN and IFN inducer therapy in cancer. However, the competency of the various components of the endogenous IFN system in malignancy has received little attention. These studies show that in malignancy there may be (1) a high incidence of elevated blood levels of IFN; (2) a deficient response of peripheral blood mononuclear cells to endogenous and exogenous IFN; and (3) increased uninduced in vitro IFN production by these cells. These findings indicate that cancer patients are equipped with the ability to produce IFN and suggest that it may be the deficient response of their cells to IFN that plays a role in the development and progression of the disease. Furthermore, the finding of increased spontaneous "uninduced" production of IFN by cells from cancer patients suggests the possibility of an intracellular inducer such as found in persistently virus-infected cells.

Humans↗

Cost-effectiveness analysis of extended conservative therapy versus surgical intervention in the management of herniated lumbar intervertebral disc.

The management of herniated lumbar intervertebral disc for patients not responding to an initial trial of conservative therapy is generally surgical. Little is known about the effect of continued conservative therapy on patients who have not improved or have deteriorated within the first 3 months. This study assessed which form of treatment, surgical or continued conservative therapy, is more cost-effective once an adequate trial of conservative therapy has failed. The study is a retrospective chart review of 55 white male truck drivers who presented with acutely herniated nucleus pulposus between 1985 and 1989. Twenty-five patients underwent surgery, and 30 underwent continued conservative therapy after initial rehabilitation. No significant difference was found in outcome (80% good or fair in both the surgical and conservative groups) or costs ($55,000 +/- $1,000/case during a 5-year period), hence no difference in the cost-effectiveness between the two treatment modalities (each $63,000 +/- $2,000/adjusted outcome). Conservatively treated patients, however, missed significantly more work. It was concluded that, for a patient not responding to the initial trial of conservative therapy, the option to undergo continued conservative treatment should be made available.

Adult↗