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Biomedical subjects

J Bernstein

Publications and source records attributed to J Bernstein.

At least 145 records · Page 8Linked to original sources

Tryptophanyl-tRNA synthetase from Bacillus subtilis. Characterization and role of hydrophobicity in substrate recognition.

The tryptophanyl-tRNA synthetase from Bacillus subtilis was purified to homogeneity and characterized. It has an alpha 2 subunit structure and a molecular weight of 77,000. Tryptophanyl-tRNA synthetase does not catalyze any significant proofreading. It activates tryptophan as well as the three fluorinated analogues, DL-4-fluoro-, DL-5-fluoro-, or DL-6-fluorotryptophan (4F-, 5F-, and 6F-Trp), in the ATP-pyrophosphate exchange reaction. In the aminoacylation reaction, the fluorotryptophans act as competitive inhibitors of Trp. Their relative activities follow the same order in both reactions: Trp greater than 4F-Trp greater than 6F-Trp greater than 5F-Trp. This order is the inverse of the order of relative hydrophobicities of these compounds, pointing to the importance of hydrophobic interactions in the selective recognition by tryptophanyl-tRNA synthetase among this group of substrates. To define the physical basis of the relative hydrophobicities, the crystallographic structure of 4F-Trp was determined and compared to that of trptophan. Charge distributions calculated for tryptophan and its different fluoroanalogues on the basis of molecular structures were supported by their carbon-13 NMR spectra. Correlations between charge distributions and relative hydrophobicities suggest that the polarity of the C-F bond represents an underlying factor determining the hydrophobicities of 4F-, 5F-, and 6F-Trp, thus relating tryptophanyl-tRNA synthetase selectivity toward tryptophan and its fluoroanalogues directly to their electronic configurations.

Adenosine Monophosphate↗

Prospective study of respiratory effects of formaldehyde among healthy and asthmatic medical students.

We conducted a prospective evaluation of pulmonary function and respiratory symptoms among 103 medical students exposed to formaldehyde over a 7-month period to determine the incidence of bronchoconstriction and respiratory symptoms in response to exposure. Time-weighted average formaldehyde exposures were generally less than 1 part per million (ppm) and peak exposures were less than 5 ppm. Acute symptoms of eye and upper respiratory irritation were significantly associated with exposure. There was no pattern of bronchoconstriction in response to exposure after either 2 weeks or 7 months. Twelve subjects had a history of asthma; they were no more likely to have symptoms of respiratory irritation or changes in pulmonary function than those without such a history. These findings are consistent with previous case reports that indicate exposure to formaldehyde vapor at levels that are commonly encountered in occupational and residential settings do not commonly cause significant bronchoconstriction, even among subjects with preexisting asthma.

Adult↗

Renal tubular dysgenesis: delayed onset of oligohydramnios.

Two premature sibs had Potter sequence and died of respiratory failure within the first day. Ultrasonography at 26 weeks during the earlier of the two pregnancies showed complete absence of amniotic fluid, and the urinary bladder was not visualized. Ultrasound examinations during the second pregnancy showed adequate amniotic fluid at 16 and 20 weeks, with a subsequent reduction in fluid volume. Two older sibs had also died of respiratory failure shortly after birth. Postmortem histopathologic studies showed all four sibs to have severely deficient renal tubular development. However, the presence of numerous glomeruli indicated prolific nephrogenesis. Most of the tubules in sections of cortex had the lectin-binding and immunohistochemical characteristics of collecting ducts; proximal tubules were not identified by lectin-binding. Electron-microscopic examination showed a general absence of differentiated characteristics in cortical tubular epithelium, except that rare tubules contained rudimentary proximal tubular brush borders. Three of the sibs were boys, one a girl. The three children that were studied had normal chromosomes. Two unaffected sibs are alive and well. Neither parent has any clinical evidence of renal disease. These studies support the interpretation that renal tubular dysgenesis is autosomal recessive with pleiotropy. However, the relatively late appearance of oligohydramnios makes early diagnosis difficult, even when the condition is suspected.

Amniotic Fluid↗

Renal tubular differentiation in mouse and mouse metanephric culture. I. Ultrastructural studies.

We studied the morphologic features of renal tubular differentiation in transfilter metanephric culture. Differentiation of portions of the S-shaped loop into proximal convoluted tubule was detected shortly after 72 h of culture by the appearance of microvilli, coated membrane invaginations, and an apical vacuolar-microtubular network. These features developed synchronously, and the microvilli became progressively more numerous and more compact to form a brush border. Computer-assisted morphometric analysis showed only minor differences between proximal tubular cells from 18-day embryos and tubular cells from 7-day cultures of blastema taken from 11-day embryos. Segments of tubule corresponding to distal convoluted tubules were lined with relatively simple cells that contained few differentiating characteristics. Morphometric modeling of the tubular cells indicated a simple shape consistent with an inherent transport function.

Animals↗

Renal tubular differentiation in mouse and mouse metanephric culture. II. Na-K-ATPase activity.

Sodium-potassium adenosine triphosphatase (Na-K-ATPase) activity was measured by microassay, and the surface density of basolateral membranes was measured morphometrically in postglomerular segments of single tubules isolated from normally developing, intact mouse kidneys and from transfilter metanephric cultures. Proximal tubule Na-K-ATPase activity was 1092 +/- 480 pmol/mm per hour in newborn mice, increasing to 2462 +/- 258 in 1-week-old and 3470 +/- 578 pmol/mm per hour in adult mice. The Na-K-ATPase activity in newborn mice was approximately one-third of the activity in adult mice. Tubular Na-K-ATPase in transfilter metanephric culture was 972 +/- 536 pmol/mm per hour, a mean value almost identical to that in newborn mice. The surface density of basolateral cell membranes was 1.36 +/- 0.60 microns2/microns3 in newborn mice and 1.34 +/- 0.45 microns2/microns3 in 1-week-old mice, increasing to 2.70 +/- 0.98 microns2/microns3 in 4-week-old mice and 2.89 +/- 0.51 microns2/microns3 in adult mice. The surface density of tubular basolateral cell membranes in transfilter metanephric culture was 1.13 +/- 0.51 microns2/microns3, not significantly different from the surface density in newborn mice. The calculated mean surface area of basolateral membranes per unit tubular length was greater in cultures than in newborns, however, because total epithelial volume per unit length was significantly larger in the cultured tubules. Membrane surface area in intact mice increased with age, the surface area per unit length of tubule in adults being 4.6 times the area in newborn animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Impaired clearance of Escherichia coli bacteremia in early biliary obstruction.

Adult male rats underwent common bile duct ligation or sham celiotomy. At intervals of 7 and 14 days postoperatively, bacteremia was induced by intravenous injection of 10(9) Escherichia coli or intraperitoneal injection of 10(6) E. coli. Serial quantitative blood cultures and quantitative whole organ cultures were obtained. One week after surgery, clearance of bacteremia was impaired in all of the animals. Clearance of intraperitoneally injected E. coli was less efficient in the duct ligation rats. Fourteen days postoperatively, clearance of bacteremia induced by intravenous or intraperitoneal injection had improved in the sham celiotomy rats but was still significantly impaired in the duct ligation rats. An increased number of viable E. coli were recovered from the lungs of duct ligation rats after intravenous administration. We found that rats with obstructive jaundice do not respond normally to a bacteremia challenge. This impairment in reticuloendothelial function can be noted as early as 1 week after common duct ligation.

Animals↗

Predictive value of renal pathology in diffuse proliferative lupus glomerulonephritis. Lupus Nephritis Collaborative Study Group.

We tested the value of the activity (AI) and chronicity (CI) indices devised by Austin et al as predictors of outcome in lupus patients with diffuse proliferative glomerulonephritis (DPGN). Four renal pathologists independently scored the AI and CI on 84 renal biopsy specimens from patients with lupus DPGN followed for 109 +/- 74 weeks (mean +/- SD), and the mean score was compared to the development of renal failure and to adverse outcome (combined data for renal failure, death and predefined clinical stop points). Receiver operator characteristic curves were derived from a series of 2 x 2 tables in which one variable was renal failure or adverse outcome and the other variable was AI or CI dichotomized by a cut-off point. Over the entire range (0 to 10) of the CI there was no value that separated patients who developed renal failure from those who did not. The ROC curve analysis indicated that the sensitivity and specificity of the CI were too low to allow it to function as a good test. Once patients entering renal failure were identified, the mean CI approached but did not reach a significant difference when compared to the mean CI of those who did not go into renal failure (4.38 +/- 0.42, mean +/- SE vs. 3.19 +/- 0.23, P = 0.0620). The CI did not predict the adverse clinical outcomes. There was no cut-off value of the CI which separated patients who had an adverse outcome from those who did not, and this result was confirmed by ROC analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Otitis media in children. I. The systemic immune response to nontypable Hemophilus influenzae.

Twenty-one infants experienced 29 episodes of otitis media with effusion caused by nontypable Hemophilus influenzae (NTHI) during 2 y of observation. Bactericidal antibody was detected in acute serum of 26% of the subjects at a mean titer of 0.8 +/- 0.3 (log2) and was observed in convalescent serum of all of the individuals at a mean titer of 4.0 +/- 0.3 (log2, P less than .001). The serum bactericidal antibody response was not age-dependent (r = .08, P greater than .05). Serum concentrations of bactericidal antibody remained stable for the entire observation period in 90% of the children. The presence of serum bactericidal antibody correlated significantly with a reduction in the number of bacteria present in the middle ear fluid (P less than .025). Eight children experienced a second episode of otitis media with effusion caused by a different serotype of NTHI. All those who lacked bactericidal antibody against the organism causing the second episode possessed bactericidal antibody against the first strain at the time of the second episode. These data suggest that the immune response to NTHI in otitis media with effusion is type-specific. The occurrence of second episodes of otitis media with effusion due to different strains of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of cross-protection.

Antibodies, Bacterial↗

Otitis media in children: local immune response to nontypeable Haemophilus influenzae.

Twenty children experienced 30 episodes of otitis media with effusion due to nontypeable (NT) Haemophilus influenzae in the first 2 years of life. The local and systemic immune responses to homologous strains of NT H. influenzae were determined by an immunodot assay. Strain-specific immunoglobulin G (IgG) antibody predominated in the middle ear fluid (MEF). It was detected in 91% of the children, compared with IgM in 48% (P less than 0.005), IgA in 52% (P less than 0.005), and secretory IgA in 18% (P less than 0.005). The titer (log2) of NT H. influenzae-specific IgG antibody (mean +/- standard error, 8.2 +/- 0.1) exceeded the titers of IgM (3.4 +/- 0.1), IgA (3.7 +/- 0.1), and secretory IgA (1.2 +/- 0.3). NT H. influenzae-specific antibody was detected exclusively in MEFs of individuals who possessed homologous serum antibody. Although antibody titers in MEF declined over time, serum antibody titers remained stable. These data suggest that immunity to NT H. influenzae in the middle ear, in part, reflects systemic immunity. Whereas local antibody disappears after resolution of the infection, systemic antibody persists.

Antibodies, Bacterial↗

Trait-anxiety and sense of coherence: a longitudinal study.

A study of trait-anxiety and sense of coherence on a group of medical students over 18 mo. shows that, although both characteristics are rather stable over time, the measure of sense of coherence is more sensitive to stressors than A-trait and is better predicted by A-trait than the opposite.

Adolescent↗

Isolation and characterization of an utero-active compound from Agave americana.

Crude extracts of Agave americana contain two utero-active compounds. One of these, tentatively named "Fraction B", has been purified to chromatographic homogeneity. Its pharmacological actions are similar to those of acetylcholine. However its chromatographic and electrophoretic mobilities are different. Some chemical properties of fraction B are compatible with the structure of an acyl derivative of choline different from acetylcholine.

Animals↗

Polymorph IV of 4-amino-N-2-pyridinylbenzenesulfonamide (sulfapyridine).

C11H11N3O2S, Mr = 249.3, monoclinic, P2(1)/c, a = 13.56 (4), b = 6.48 (1), c = 14.12 (3) A, beta = 113.7 (1) degrees, V = 1136.4 (44) A3, Z = 4, D chi = 1.457 g cm-3, lambda(Mo K alpha) = 0.70926 A, mu = 2.29 cm-1, F(000) = 520, T = 291 K, final R = 0.085 for 1287 independent observed reflections. Sulfapyridine is a sulfonamide drug with antibacterial, antithyroid and antidiabetic properties. The molecule exhibits the same conformation as in all except one of the polymorphs previously studied, despite a hydrogen-bonded packing mode which differs from that observed in the three earlier reported polymorphs. Form IV exhibits three hydrogen bonds of the type N...N = 2.91 (1) A and N...O = 3.007 (7) and 3.076 (7) A.

Hydrogen Bonding↗

Glomerular basement membrane thickness in recurrent and persistent hematuria and nephrotic syndrome: correlation with sex and age.

The glomerular basement membranes (GBM) were measured in 264 patients with recurrent and persistent hematuria (152 males, 112 females), 47 patients with minimal change nephrotic syndrome (26 males, 21 females), and 91 patients with focal segmental glomerular sclerosis and nephrotic syndrome (55 males, 36 females). The average number of glomeruli measured was 2.5 per case. Analysis of the data showed GBM thickness to be significantly greater in males (n = 233) than in females (n = 169) (Student's t-test, P less than 0.01). There was no difference in GBM thickness between the two groups of nephrotics; the data were subsequently combined and the group referred to as idiopathic nephrotic syndrome. There was also no difference in GBM thickness among the immunofluorescence-defined subcategories of recurrent hematuria, and these groups were combined. GBM thickness was significantly greater in the idiopathic nephrotic syndrome than in recurrent hematuria (Kruskal-Wallis H test, Po = less than 0.001). Analysis of the data showed, in both conditions, a gradual increase with age throughout the span of the study (1-69 years). Regression analysis of GBM thickness and age in recurrent hematuria showed Ro = 0.43 and Po = less than 0.001, in idiopathic nephrotic syndrome Ro = 0.61 and Po = less than 0.001. The differences between nephrotic syndrome and recurrent hematuria may be based on the inclusion in the recurrent hematuria group of patients with genetically thin GBM; they may also be based on the inclusion in the idiopathic nephrotic syndrome group of patients with subendothelial thickening, a relatively frequent occurrence.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗