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Biomedical subjects

B Schwartz

Publications and source records attributed to B Schwartz.

At least 55 records · Page 3Linked to original sources

Serum leptin levels in the elderly: relationship with gender and nutritional status.

PURPOSE: Assessment of whether, there is a positive correlation between serum leptin levels, and BMI or/ nutritional status in the elderly as reported for the younger population. METHODS: A cross-sectional study, conducted in 62 elderly residents of a nursing home in Israel, and the subjects were divided into three different categories according to BMI. Serum leptin and other biochemical parameters were assessed. Correlation was calculated by the Pearson's correlation coefficients and statistical analysis by paired Student's t test. The relationship of BMI, leptin levels and nutritional status was determined. RESULTS: Significant differences between men and women were obtained for weight, total energy intake, carbohydrates, cholesterol and leptin. Serum leptin levels in women were three times higher than in men and higher compared with to their respective parallel BMI categories in men. A positive correlated scattering between BMI and leptin levels (r=0.65, p< 0.0001) was shown only for the different BMI categories in women. CONCLUSIONS: In the elderly, as in the young population, a positive correlation was obtained for BMI and leptin. In addition, significantly higher differences in circulating leptin were found in the women compared with the consistently low levels found in the men. The results suggest that female hormones do not play a significant role in determining serum leptin levels.

Aged↗

Diagnosis and management of febrile children using the WHO/UNICEF guidelines for IMCI in Dhaka, Bangladesh.

OBJECTIVE: To determine whether the fever module in the WHO/UNICEF guidelines for the integrated management of childhood illness (IMCI) identifies children with bacterial infections in an area of low malaria prevalence. METHODS: Physicians assessed a systematic sample of 669 sick children aged 2-59 months who presented to the outpatient department of Dhaka Shishu Hospital, Bangladesh. FINDINGS: Had IMCI guidelines been used to evaluate the children, 78% of those with bacterial infections would have received antibiotics: the majority of children with meningitis (100%), pneumonia (95%), otitis media (95%) and urinary tract infection (83%); and 50% or less of children with bacteraemia (50%), dysentery (48%), and skin infections (30%). The current fever module identified only one additional case of meningitis. Children with bacteraemia were more likely to be febrile, feel hot, and have a history of fever than those with dysentery and skin infections. Fever combined with parental perception of fast breathing provided a more sensitive fever module for the detection of bacteraemia than the current IMCI module. CONCLUSIONS: In an area of low malaria prevalence, the IMCI guidelines provide antibiotics to the majority of children with bacterial infections, but improvements in the fever module are possible.

Bacterial Infections↗

Crystal structure at 2.5 A resolution of zinc-substituted copper amine oxidase of Hansenula polymorpha expressed in Escherichia coli.

Copper amine oxidases (CAOs) catalyze the two-electron oxidation of primary amines to aldehydes, utilizing molecular oxygen as a terminal electron acceptor. To accomplish this transformation, CAOs utilize two cofactors: a mononuclear copper, and a unique redox cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ or TOPA quinone). TPQ is derived via posttranslational modification of a specific tyrosine residue within the protein itself. In this study, the structure of an amine oxidase from Hansenula polymorpha has been solved to 2.5 A resolution, in which the precursor tyrosine is unprocessed to TPQ, and the copper site is occupied by zinc. Significantly, the precursor tyrosine directly ligands the metal, thus providing the closest analogue to date of an intermediate in TPQ production. Besides this result, the rearrangement of other active site residues (relative to the mature enzyme) proposed to be involved in the binding of molecular oxygen may shed light on how CAOs efficiently use their active site to carry out both cofactor formation and catalysis.

Amine Oxidase (Copper-Containing)↗

Preparing for elimination of congenital Rubella syndrome (CRS): summary of a workshop on CRS elimination in the United States.

The goal of eliminating indigenous rubella and congenital rubella syndrome (CRS) in the United States in the near future is now within reach, because rubella incidence has been sustained at record-low levels since the mid-1990s. Effective prevention strategies to eliminate CRS and rubella require improvement in the surveillance of CRS and congenital rubella infection (CRI). The purpose of the workshop was to review rubella and CRS epidemiology, as well as current clinical, diagnostic, and laboratory practices, to determine whether new strategies are needed to achieve and document CRS elimination. Workshop participants agreed that surveillance for CRS must be strengthened, particularly through augmented laboratory capabilities, and the case definition for CRS must be revised to reflect the current scientific information available. Further studies of methods are needed to identify high-risk populations and geographic areas for rubella and CRS and to enhance identification of infants with CRS.

Humans↗

Severe pneumococcal pneumonia in previously healthy children: the role of preceding influenza infection.

An outbreak of severe pneumococcal pneumonia among children occurred in Iowa from November 1995 through January 1996. An associated outbreak of influenza disease was predominantly caused by influenza A (H1N1) for the first time since 1989. We conducted a case-control study to determine whether preceding influenza infection was directly associated with pneumococcal illness. We identified 13 children with severe pneumococcal pneumonia. Patients were more likely than control subjects to report experiencing an influenza-like illness in the 7-28 days preceding admission (matched odds ratio [OR], 12.4; 95% confidence interval [CI], 1.7-306). Likewise, family members of patients were more likely than those of control subjects to report experiencing an influenza-like illness in the 28 days preceding their admission date (OR, 2.6; 95% CI, 1.0-6. 3). Patients were more likely than control subjects to have a positive influenza A (H1N1) convalescent serology (matched OR, 3.7; 95% CI, 1.0-18.1). This study provides direct and indirect evidence that influenza infection led to severe pneumococcal pneumonia among these children. Prevention of pneumococcal disease should be included among the potential benefits of influenza vaccination.

Adolescent↗

Increased carriage of trimethoprim/sulfamethoxazole-resistant Streptococcus pneumoniae in Malawian children after treatment for malaria with sulfadoxine/pyrimethamine.

Treatment of malaria with sulfadoxine/pyrimethamine and of presumed bacterial infections with trimethoprim/sulfamethoxazole (cotrimoxazole) was assessed to see if either increases the carriage of cotrimoxazole-resistant Streptococcus pneumoniae in Malawian children. Children <5 years old treated with sulfadoxine/pyrimethamine, cotrimoxazole, or no antimicrobial agent were enrolled in a prospective observational study. Nasopharyngeal swabs were taken before treatment and 1 and 4 weeks later. Pneumococci were tested for antibiotic susceptibility by broth microdilution. In sulfadoxine/pyrimethamine-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 38.1% at the initial visit to 44.1% at the 4-week follow-up visit (P=.048). For cotrimoxazole-treated children, the proportion colonized with cotrimoxazole-nonsusceptible pneumococci increased from 41.5% at the initial visit to 52% at the 1-week follow-up visit (P=.0017) and returned to 41.7% at the 4-week follow-up. Expanding use of sulfadoxine/pyrimethamine to treat chloroquine-resistant malaria may have implications for national pneumonia programs in developing countries where cotrimoxazole is widely used.

Anti-Bacterial Agents↗

Kinetic analysis of oxygen utilization during cofactor biogenesis in a copper-containing amine oxidase from yeast.

A detailed kinetic analysis of oxygen consumption during TPQ biogenesis has been carried out on a yeast copper amine oxidase. O(2) is consumed in a single, exponential phase, the rate of which responds linearly to dissolved oxygen concentration. This behavior is observed up to conditions of maximally obtainable oxygen concentrations. In contrast, no viscosity effect is observed on rate, implicating a high K(m) for O(2). Binding of oxygen appears to occur faster than its consumption and to result in displacement of the precursor tyrosine onto copper to form a charge-transfer species, described in the the preceding paper of this issue [Dove, J. E., Schwartz, B., Williams, N. K., and Klinman, J. P. (2000) Biochemistry 39, 3690-3698). Reaction between this intermediate and O(2) is proposed to occur in a rate-limiting step, and to proceed more rapidly when the tyrosine is deprotonated. This rate-limiting step in cofactor biogenesis does not display a solvent isotope effect and is, thus, uncoupled from proton transfer. Comparisons are drawn between the proposed biogenesis mechanism and that for the oxidation of reduced cofactor during catalytic turnover in the mature enzyme.

Amine Oxidase (Copper-Containing)↗

Investigation of spectroscopic intermediates during copper-binding and TPQ formation in wild-type and active-site mutants of a copper-containing amine oxidase from yeast.

Copper amine oxidases possess the unusual ability to generate autocatalytically their organic cofactor, which is subsequently utilized in turnover. This cofactor, 2,4,5-trihydroxyphenylalanine quinone (TPQ), is formed within the active site of these enzymes by the oxidation of a single tyrosine residue. In vitro, copper(II) and oxygen are both necessary and sufficient for the conversion of tyrosine to TPQ. In this study, the biogenesis of TPQ has been characterized in an amine oxidase from Hansenula polymorpha expressed as the apo-enzyme in Escherichia coli. With the WT enzyme, optical absorbances which are copper or oxygen dependent are observed and characterized. Active-site mutants are used to investigate further the nature of these spectral species. Evidence is presented which suggests that tyrosine is activated for reaction with oxygen by liganding to Cu(II). In the following paper in this issue [Schwartz, B., Dove, J. E., and Klinman, J. P. (2000) Biochemistry 39, 3699-3707], the initial reaction of precursor protein with oxygen is characterized kinetically. Taken together, the available data suggest a mechanism for the oxidation of tyrosine to TPQ where the role of the copper is to activate substrate.

Amine Oxidase (Copper-Containing)↗

Dietary regulation and localization of apoptosis cascade proteins in the colonic crypt.

This study was designed primarily to assess the localization of apoptosis cascade proteins along the rat colonic crypt and secondarily to test whether the activity and/or localization of these proteins are affected by the enrichment of the diet with the soluble fiber pectin. Expression of apoptosis cascade proteins was assessed in isolated colonocytes harvested from the luminal and basal crypt colonocyte populations. Two different dietary regimens were tested: a standard diet (diet A), and a diet enriched in pectin (diet B), a soluble fiber that undergoes fermentation in the cecum and produces high concentrations of intracolonic short-chain fatty acids. Caspase-1 expression was maximal in luminal colonocytes of rats fed diet B, as evidenced by Western blot and immunohistological analyses. Expression of the cleaved poly(ADP-ribose) polymerase product was elevated in both the luminal and basal colonocytes of the pectin-fed group, whereas in rats fed diet A, the expression was lower, especially in basal crypt colonocytes. The highest expression of the antiapoptotic protein Bcl-2 was observed in the lower compartments of the colonic crypt tissue and was maximal in the rat group fed a standard diet. The apoptotic index in colonocytes of rats fed diet B was higher than that measured in rats fed diet A. Cumulatively, our results indicate that apoptosis cascade proteins are differentially localized along the lumen-crypt axis, and their expression and activity may be controlled by dietary components. These results may, at least partially, account for the documented protective effect of butyrogenic fibers on colorectal cancer.

Animals↗

Estrogen controls expression and bioresponse of 1,25-dihydroxyvitamin D receptors in the rat colon.

Estrogen receptors are extensively expressed in the gastrointestinal tract, however their physiological role is not clear yet. Estrogen and 1,25-dihydroxyvitamin D [1,25(OH)2D3] apparently share common activities in the intestine such as growth-suppressing effects on the colonic mucosa and positively influence intestinal calcium absorption. In view of our previous studies showing up-regulation of vitamin D receptors (VDR) in the duodenal mucosa and in osteoblasts, the present study was designed to address a possible interaction between estrogen and the vitamin D endocrine system in the colonic mucosa. Three groups of female rats were studied: sham operated ('Sham'), ovariectomized ('OVX'), and ovariectomized estrogen-treated ('OVX+E'). VDR gene expression was assessed by Northern blot analysis, VDR protein expression was assessed by ligand-binding assays, and Western-blotting. Endogenous 1,25(OH)2D3 bioactivity in colonic mucosal extracts was assessed by alkaline phosphatase activity and calbindin-9kD mRNA expression. Northern blots revealed marked increase in band intensity corresponding with the VDR mRNA product in 'Sham' or 'OVX+E' vs. 'OVX'. In ligand-binding experiments, 1,25(OH)2D3 was shown to bind specifically to a single class of receptors in extracts obtained from each of the groups (Kd--0.03 nM). The maximal VDR binding capacity of colonic mucosal extracts was 203 +/- 23 fmol/mg protein in 'Sham', 362 +/- 41 in 'OVX+E' and 102 +/- 15 in 'OVX' ('Sham' or 'OVX+E' vs. 'OVX', p < 0.001). Western-blot analysis also revealed higher VDR protein expression in the estrogen-exposed animals. Alkaline phosphatase activity and calbindin-9kD mRNA expression were significantly higher in colonic mucosal extracts from estrogen-exposed rats. Estrogen increases VDR gene transcript level, protein expression and endogenous 1,25(OH)2D3 bioactivity in colonic mucosa, which may suggest that some of the estrogen activities in the colonic mucosa, such as its growth-suppressing effect, could be mediated, at least in part, by an increase in colonic mucosa responsiveness to endogenous 1,25(OH)2D3.

Animals↗

Regional differences in optic disc and retinal circulation.

PURPOSE: To determine regional differences in the circulation of the optic disc, the peripapillary choroid and the retinal vessels using the techniques of computerized image analysis and fluorescein angiography. METHODS: Ten young normal subjects were studied. Fluorescein angiography was performed with a scanning laser ophthalmoscope. The rate of filling of fluorescein or slope was measured in the four quadrants of the optic disc, the peripapillary choroid and the major retinal arteries and veins. A total of 125 points was measured from each image of the fluorescein angiograms for a total of 20 to 30 images. Retinal vessel width was measured using computerized image analysis. RESULTS: Comparison of the rates of filling of fluorescein or slopes showed significant differences from zero among the four quadrants of the optic disc (p= 0.01 to <0.02), of the peripapillary choroid (p=0.01 to <0.05) and among the major retinal arteries (p=0.01 to <0.02) and retinal veins (p=0.02 to <0.05). No significant differences were noted between the quadrants for retinal arterial width with the retinal veins only showing a significant difference between the inferior nasal and inferior temporal vein (p=0.02 to <0.05). CONCLUSION: Evaluation of the circulation of the optic disc, retina, and peripapillary choroid should take into account regional differences among these structures.

Adult↗

Self-determination. The tyranny of freedom.

Americans now live in a time and a place in which freedom and autonomy are valued above all else and in which expanded opportunities for self-determination are regarded as a sign of the psychological well-being of individuals and the moral well-being of the culture. This article argues that freedom, autonomy, and self-determination can become excessive, and that when that happens, freedom can be experienced as a kind of tyranny. The article further argues that unduly influenced by the ideology of economics and rational-choice theory, modern American society has created an excess of freedom, with resulting increases in people's dissatisfaction with their lives and in clinical depression. One significant task for a future psychology of optimal functioning is to deemphasize individual freedom and to determine which cultural constraints are necessary for people to live meaningful and satisfying lives.

Depressive Disorder↗

Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells.

Cell-to-cell adhesion, an important event in differentiation, is impaired during advanced stages of tumorigenesis. In this study, we examined the possible regulation of cell-adhesion proteins by the differentiation agent butyrate in LS174T and HM7 cells, two types of human colon cancer cells that differ in their ability to produce mucin and colonize the liver of experimental animals. The more aggressive, high-mucin-producing cell line (HM7), a clone selected from LS174T cells, showed a scattered and undifferentiated ultramorphological appearance and low basal alkaline phosphatase activity; the proteins beta-catenin and E-cadherin, as detected by immunostaining, were expressed in the cells' nuclei. All of these properties were significantly less pronounced in the less aggressive, low-mucin-producing LS174T cells. In both cell lines, butyrate treatment enhanced cell-to-cell interaction, alkaline phosphate activity, translocation of beta-catenin and E-cadherin from the nuclei to the membrane junctions, and transcription and translation of the 120-kDa E-cadherin isoform, but not of its 100-kDa isoform. Analysis of possible mechanisms of E-cadherin up-regulation revealed that butyrate induces the release of nuclear proteins from the E-cadherin promoter sequence, reducing transcription repression. We suggest that butyrate activates E-cadherin transcription through translocation of nuclear transcription factors bearing specific repressor activity. We surmise that abrogation of nuclear 100-kDa E-cadherin and beta-catenin expression following butyrate treatment is related to the control of E-cadherin gene transcription.

Alkaline Phosphatase↗

Association of ocular pressure and optic disc cup volume with red blood cell sodium-potassium ATPase inhibition.

PURPOSE: To determine if there were significant differences between the number of red blood cell ouabain binding sites in normals and untreated ocular hypertensives plus one open-angle glaucoma patient. METHODS: We measured the binding of (3)H ouabain to erythrocyte membranes of 23 normals, 25 ocular hypertensives and one open-angle glaucoma. We also measured the levels of plasma cortisol and digoxin in these subjects. Characteristics of cupping of the optic disc and thickness of the retinal nerve fiber layer, as well as area of optic disc pallor of these subjects were measured by stereophotogrammetry and by computerized image analysis from single and stereo photographs. RESULTS: The number of (3)H ouabain binding sites was observed to be significantly less in the ocular hypertensives and one glaucoma compared to the normals (p = 0.0009). In multi-variate analyses, to determine what other factors affected this difference, there was a significant negative association with mean intraocular pressure (p = 0.003) (average of both eyes) and total cup volume (average of both eyes) (p = 0.005), diagnosis of ocular hypertension and glaucoma (p = 0.0005) and male gender (p = 0.019). There was a significant positive association with plasma cortisol levels (p = 0.048), and diastolic blood pressure (p = 0.037). CONCLUSIONS: The number of (3)H ouabain binding sites in red blood cells decreases significantly with increasing ocular pressure and increasing cup volume indicating the possible presence of an increased systemic endogenous digoxin-like inhibitor and/or difference in the isozymes of Na(+), K(+)-ATPase which may be associated with increased levels of plasma cortisol in ocular hypertensives and glaucomas.

Binding Sites↗

Fungal keratitis after laser in situ keratomileusis: a case report.

PURPOSE: To report a case of fungal keratitis resulting after laser in situ keratomileusis (LASIK). METHODS: A 38-year-old white man in good health developed a corneal infiltrate with laboratory confirmation of fungal keratitis after LASIK. Corneal scrapings were taken. Silver stain was positive for hyphae. Culture was positive for Curvularia sp. The patient was started on intensive natamycin 5% and amphotericin 0.15% topical therapy. RESULTS: The patient's keratitis was successfully treated with intensive antifungal therapy. CONCLUSIONS: Infectious keratitis is a rare but a serious potential complication after LASIK. To our knowledge, no previous case of fungal keratitis after LASIK has been reported. This case emphasizes the importance of surveillance for infection after LASIK.

Adult↗