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Biomedical subjects

M Hirsch

Publications and source records attributed to M Hirsch.

At least 37 records · Page 2Linked to original sources
PubMed1996

Amino acid sequence determinants of beta-lactamase structure and activity.

TEM-1 beta-lactamase catalyzes the hydrolysis of beta-lactam antibiotics such as the penicillins and cephalosporins, thus providing for bacterial resistance to these compounds. To determine the amino acid residues critical for the structure and function of TEM-1 beta-lactamase, the codons for each of the 263 amino acid residues that constitute the mature form of the enzyme were randomized using a site-directed mutagenesis procedure. Functional random mutants were selected based on their ability to confer ampicillin resistance to Escherichia coli. The DNA sequence of several functional mutants was determined for each set of random mutants. It was found that 43 out of the 263 amino acid residues do not tolerate substitutions and therefore are critical for the structure and activity of the enzyme. In addition, a comparison of conserved residue positions among functional beta-lactamase mutants with conserved residues in the beta-lactamase gene family identified many positions which did not tolerate substitutions in the mutagenesis studies but are freely substituted among members of the gene family. This observation may be due to the accumulation of compensating mutations among members of the gene family. Finally, the sequence variability at residue positions among functional mutants was quantitated by calculating the effective number of substitutions at each position using information-theoretical entropy. These values were used to obtain a quantitative estimate of the correlation between the sequence variability at a position and the fractional accessible surface area of the residue. The correlation is found to be statistically significant in that buried residues tend to exhibit low variability and invariant residues tend to exhibit low solvent exposure. However, the correlation is weak because most residues are neither completely buried nor invariant.

Amino Acid Sequence↗
PubMed1996

Selective second trimester fetal reduction due to 46XY, 10q+ fetus.

Second-trimester amniocentesis of a twin gestation revealed one normal karyotype, whereas the other had a 46XY, 10q+, indicating an excess of genetic material on chromosome number 10. A selective reduction of the affected twin was carried out on the 20th week of gestation; the outcome of pregnancy and delivery at term of the normal twin were both uneventful.

Adult↗
PubMed1995

A randomized trial of the activity and safety of Ro 24-7429 (Tat antagonist) versus nucleoside for human immunodeficiency virus infection. The AIDS Clinical Trials Group 213 Team.

Ro 24-7429, a Tat antagonist, dosed at 75, 150, or 300 mg/day, was compared with nucleoside analogue (zidovudine or didanosine) for 12 weeks in 96 human immunodeficiency virus (HIV)-infected patients to assess safety and activity. The primary adverse effect of Ro 24-7429 was rash, which necessitated treatment discontinuation in 6 of 71 patients. Nucleoside analogue treatment produced an average increase in CD4 cell count of 28 cells/mm3 at week 8 versus a decrease of 27 cells/mm3 in recipients of Ro 24-7429 (P < .001). Serum HIV p24 antigen levels decreased by an average of 111 pg/mL in nucleoside recipients at week 8 compared with an increase of 41 pg/mL in recipients of Ro 24-7429 (P = .007). Nucleoside-treated patients had a mean 0.66 log10 reduction in infectious peripheral blood mononuclear cells, while Ro 24-7429 recipients had a mean 0.02 log10 reduction (P = .02). No dose-response relationships were observed in the Ro 24-7429 groups. In this study, Ro 24-7429 treatment showed no evidence of antiviral activity.

Adult↗
PubMed1995

Dibutyryl cyclic adenosine monophosphate and forskolin alter the paracellular pathway in cultured corneal endothelial cells.

PURPOSE: This study describes the effects of the cyclic adenosine monophosphate (cAMP) pathway on the tight junctional barrier of the corneal endothelium, which plays a critical role in maintaining the corneal stroma in an underhydrated, transparent state. METHODS: Subcultured bovine corneal endothelial cells grown on filters were used to study the effects of dibutyryl-cAMP and forskolin on transendothelial electrical resistance and [3H]inulin flux. The tight junction-associated protein ZO-1 (zonula occludens protein-1) and F-actin were visualized by indirect immunofluorescence, and the ultrastructural organization of junctional complexes was studied by freeze-fracture electron microscopy. RESULTS: Cells formed a continuous monolayer of closely apposed hexagonal-type cells separated by a discontinuous belt of tight junctions with a transendothelial electrical resistance of 20.8 +/- 0.6 omega.cm2. Dibutyryl-cAMP (10(-4) M) and forskolin (10(-5) M) increased cell cAMP, significantly decreased the transendothelial resistance by 54% and 43%, respectively, and increased the flux of [3H]inulin from the apical to the basal side of the cells by 56% and 40%, respectively. Both agents also induced condensation of F-actin at the cell borders without any marked changes in the immunostaining of ZO-1 that delineated cell peripheries. However, freeze-fracture studies showed that dibutyryl-cAMP and forskolin induced dispersion of the tight junction network. CONCLUSIONS: These data suggest that activation of the cAMP-dependent pathway, leading to structural changes of the tight junctional network, may modulate the passive fluxes mediated by the paracellular pathway of the corneal endothelial barrier.

Actins↗
PubMed1995

Incomplete belts of tight junctions in cultured non-pigmented human ciliary epithelial cells.

Tight junctions of cultured human non-pigmented ciliary epithelial cells were studied with the freeze-fracture technique and related to the transepithelial electrical resistance of these monolayers. Isolated tight junctional fibrils or small groups and networks of tight junctions sometimes associated with gap junctions were revealed in freeze-fracture images of the lateral plasma membrane. The tight junctions always formed incomplete belts, so that the apical and basolateral plasma membrane domains often were in continuity without morphological evidence of interposed intercellular junctions. The monolayers revealed a transepithelial resistance of 19.7 +/- 2.1 omega.cm2. Protamine induced a reversible increase of the transepithelial resistance of the cultures by 91 +/- 12%, but still the tight junctions formed incomplete belts. We conclude that contrary to complete networks of tight junctions in native non-pigmented ciliary epithelium, cultured monolayers only express incomplete belts of tight junctions which may be the morphological correlate of the relatively low transepithelial resistance of these monolayers. Interpretations on transepithelial transport and permeability characteristics of these cultures have to take into account the differences in junctional morphology from their native epithelium.

Cells, Cultured↗
PubMed1995

Allergy as a risk factor for nursing care problems in the elderly cancer patient.

The purpose of this secondary analysis was to determine (a) the nursing diagnoses in elderly patients with cancer and (b) whether elderly cancer patients with a current or past history of allergy were at risk for selected nursing problems. A retrospective clinical data base from 59 patients (32 male, 27 female) with a diagnosis of cancer and an age range of 55-85 years with a mean age of 65.6 years was examined. The most frequently occurring priority nursing diagnoses identified by Clinical Nurse Specialists (CNS) were Pain, Risk for Infection, and Impairment of Skin Integrity. When examining the comprehensive list of priority and nonpriority nursing diagnoses, identified for these patients with cancer, it was found that those with a history of allergy were significantly more likely to have a high risk for infection than those without a history of allergy. Two other diagnoses (knowledge deficit and potential fluid volume deficit) occurred in a significant number in the allergy group, but there was no occurrence of these two diagnoses in the nonallergy group. The limitations of assessing immunologic status as a part of regular nursing assessments were discussed. Recommendations were provided for future research in the area of immunology, aging, and nursing diagnoses.

Aged↗
PubMed1995

Intrapartum management of the low-birth-weight breech fetus.

Breech presentation is prevalent among preterm deliveries and contributes to neonatal mortality far beyond its prevalence. The management of a preterm breech delivery is controversial. We present our retrospective experience with 185 consecutive preterm breech deliveries, part delivered by cesarean section and part delivered vaginally as assisted breech delivery or total breech extraction), and compare the perinatal outcome between these two groups in terms of perinatal mortality (PPD) and perinatal morbidity (neonatal asphyxia). No statistically significant difference was found for either variable in the two examined groups. We therefore conclude that the method of delivery of low birth weight (1000-2500) breeches has no effect on perinatal outcome.

Asphyxia Neonatorum↗
PubMed1994

Objective and subjective sleep disturbances in patients with rheumatoid arthritis. A reappraisal.

OBJECTIVE: To assess objective and subjective evidence of sleep disturbances in patients with rheumatoid arthritis (RA) and to examine correlations between parameters of inflammatory activity and sleep pathology. METHODS: Nineteen RA patients and 19 age-matched healthy control subjects underwent all-night polysomnography on 2 consecutive nights. RA patients were also evaluated for daytime sleepiness by mean sleep latency test and responded to a self-report questionnaire on their first night. RESULTS: Whereas normal sleep architecture is conserved in RA, we confirmed former findings of severe sleep fragmentation and an enhanced presence of primary sleep disorders. No correlation exists between RA activity and the sleep disorders. Subjective assessment was not consistent with the objective evidence of sleep disruption, unlike the findings in patients with fibrositis. CONCLUSION: Sleep is severely disturbed in patients with RA, regardless of the inflammatory disease activity. The specificity of the sleep disorders assessed needs confirmation, as does specific sleep therapy for these patients.

Adult↗
PubMed1994

Tight junctions of the human ciliary epithelium: regional morphology and implications on transepithelial resistance.

The tight junctions of the human ciliary epithelium have been studied using the freeze-fracture technique with particular regard to regional differences in the tight junction networks and implications on the transepithelial resistance. The tight junctions of the non-pigmented epithelium always form continuous networks and consist of from two to more than 20 superimposed strands (mean 3 to 4), suggesting that relatively tight and leaky sites of the paracellular pathway coexist within the same cell perimeter. The tight junction morphology is more complex in the anterior pars plicata than in the posterior pars plicata, but its complexity increases again towards the pars plana. The application of an electrical circuit analysis to morphometric freeze-fracture data suggests that the transepithelial resistance decreases from the anterior pars plicata (32 omega cm2) towards the posterior plicata (26 omega cm2) and becomes lowest in the pars plana (19 omega cm2) and that the transepithelial resistance of the native epithelium is lower than most reported calculations based on electrophysiological measurements. We conclude that human ciliary epithelium is a leaky layer, but that the anterior ciliary processes are less leaky than the posterior processes and the pars plana despite the occurrence of the breakdown of the blood-aqueous barrier predominantly in the anterior pars plicata.

Ciliary Body↗
PubMed1994

Tight junctions and paracellular permeability in cultured bovine corneal endothelial cells.

Intramembrane specializations of cultured bovine corneal endothelial cells were studied with thin section and freeze-fracture electron microscopy and related to the paracellular permeability and the transendothelial resistance (Rt) of the monolayers. The following intercellular junctions were found: single and discontinuous networks of tight junctions (TJ) which girdle the apico-lateral cell perimeter incompletely, gap junctions, and membrane undulations suggesting intermediate junctions. The macromolecular tracer ruthenium red penetrated into the lateral intercellular space beyond the level of the incomplete belt of TJ. Rt of these monolayers was 20.9 +/- 1.0 omega.cm2. Protamine induced a reversible increase of Rt to 118 +/- 5% of its control value. We conclude that incomplete belts of TJ may be the morphological counterpart of the high paracellular permeability of this monolayer and functionally and morphologically resemble those of their native endothelium. Cultured corneal endothelial cells are an excellent model for studying the influence of incomplete belts of TJ on paracellular permeability of cells.

Animals↗