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Biomedical subjects

E Weiss

Publications and source records attributed to E Weiss.

At least 199 records · Page 11Linked to original sources

The DNA sequence of the H-2kb gene: evidence for gene conversion as a mechanism for the generation of polymorphism in histocompatibilty antigens.

We have determined the DNA sequence of the H-2Kb gene of the C57B1/10 mouse. Comparison of this sequence with that of the allelic H-2Kd shows surprisingly that the exons have accumulated more mutations than their introns. Moreover, many of these changes in the exons are clustered in short regions or hot spots. Additional comparison of these sequences with the H-2Ld and H-2Db sequences shows that, in several cases, the altered sequence generated at the hot spot is identical to the corresponding region of a non-allelic H-2 gene. The clustered changes are responsible for 60% of the amino acid differences between the H-2Kb and H-2Kd genes and suggest that micro-gene conversion events occurring within the exons and involving only tens of nucleotides are an important mechanism for the generation of polymorphic differences between natural H-2 alleles.

5' Flanking Region↗

Verapamil improves exercise capacity in chronic atrial fibrillation: double-blind crossover study.

Oral verapamil has previously been shown to reduce heart rate at rest and during mild exercise in chronic atrial fibrillation. Its efficacy in improving cardiovascular performance at higher levels of exercise and its safety were investigated in a prospective, randomized, placebo controlled double-blind study preceded by an open label titration phase in 20 digitalized patients with chronic atrial fibrillation. Maximal exercise capacity was improved (from 522 +/- 257 to 806 +/- 348 work units, p less than 0.0005) when tested by a standardized multistage ergometry exercise test. Heart rate was also reduced at rest, at the end of 3 minutes of 300 KPM exercise, and at the point of maximal exercise. Blood pressure and double product were also reduced. Its efficacy and safety may make verapamil the treatment of choice in chronic atrial fibrillation.

Adult↗

Visualization of anti-histone antibodies on SV40 minichromosomes by scanning transmission electron microscopy (STEM).

The unique capabilities of the scanning transmission electron microscope (STEM) have been used for a high resolution study of antibody binding to individual SV40 minichromosomes. A method of sample preparation has been developed which allows direct visualization of the antibody molecules in a clearly recognizable form. Using this technique, we have studied the binding of anti-H2B and anti-H3 immunoglobulins to SV40 minichromosomes. The results indicate that histones H2B and H3 are located only in the nucleosomes and are absent in the linker regions.

Animals↗

The role of calcium ion in luteal function in the rat.

The regulatory role of calcium ion was investigated in isolated 10-day-old corpora lutea incubated in vitro. The corpora lutea were induced in immature rats by a single injection of PMSG (15 i.u.) on day 30. We examined the effect of various incubation conditions on the increase (about 7-fold) in cyclic AMP (cAMP) concentration by LH (5 micrograms/ml) and its reversal by PGF2 alpha (10 microM). In calcium-free medium (+0.5 mM EGTA) the stimulation by LH was only slightly impaired, and PGF2 alpha was fully effective in suppressing it. Similarly, both LH and PGF2 alpha acted normally in the presence of 100 microM verapamil, a blocker of calcium uptake. Trifluoperazine (TFP, 3-300 microM) a potent inactivator of calmodulin, did not interfere with the action of PGF2 alpha. The effect of LH was increased by TFP (30 and 300 microM); this was probably due to inhibition of calmodulin-dependent phosphodiesterase, since the increase of the response to LH by IBMX (0.5 mM) plus TFP (30 microM) was similar to that by IBMX alone. Finally, the uptake of radioactive calcium was not increased by PGF2 alpha in the absence or presence of LH. These results do not support the suggestion that calcium ion mediates the hormonal regulation of cAMP in the rat corpus luteum.

Animals↗

Biphasic culture system for rapid Campylobacter cultivation.

We developed a biphasic culture system consisting of 4 ml of brucella agar (BA) and 6 ml of brucella broth (BB) in 25-cm2 tissue culture flasks, which were incubated in air (BB/BAa) or in a gas mixture of 5% O2, 10% CO2, and 85% N2 (BB/BAg). These media were also used with a supplement consisting of ferrous sulfate, sodium metabisulfite, and sodium pyruvate and incubated as above (FB/FAa and FB/FAg, respectively). Highly satisfactory growth of Campylobacter jejuni 301 was obtained with all medium-gas phase combinations provided that the number of viable cells in the inoculum was large (greater than or equal to 10(6)/ml). The use of FB/FAa permitted the inoculum to be reduced to 100 cells per ml. With an adjusted gas phase (BB/BAg and FB/FAg), near-optimal growth was obtained from an inoculum of 1 to 10 cells per ml. Under most of these conditions the generation time was approximately 90 min. During the logarithmic growth phase, the cells retained their typical spiral morphology and high motility. These media also proved to be highly satisfactory for the cultivation of fresh isolates as well as other stock strains of Campylobacter. When the broth phase of the cultures, after addition of 15% glycerol, was quickly frozen and maintained at -70 degrees C, all strains thus far examined were readily recoverable and satisfactorily cultivated without additional passage.

Agar↗

Cell surface hydrophobicity of dental plaque microorganisms in situ.

The cell surface hydrophobicity of bacteria obtained directly from human tooth surfaces was assayed by measuring their adherence to liquid hydrocarbons. Fresh samples of supragingival dental plaque were washed and dispersed in buffer. Adherence of the plaque microorganisms to hexadecane, octane, and xylene was tested turbidimetrically and by direct microscopic observation. The results clearly show that the vast majority of bacteria comprising dental plaque exhibit pronounced cell surface hydrophobicity. These data support the hypothesis that hydrophobic interactions play a major role in mediating bacterial adherence on tooth surfaces.

Bacteria↗

Superiority of oral verapamil therapy to digoxin in treatment of chronic atrial fibrillation.

The efficacy and safety of oral verapamil, 240 mg, with or without digoxin were studied in 52 patients with chronic atrial fibrillation at rest, and during mild and maximal exercise. Twenty-four patients were studied during the following therapeutic modalities: no therapy; digoxin, 0.25 mg and 0.5 mg daily; digoxin, 0.25 mg and verapamil; and verapamil alone. Heart rate at rest and during all levels of exercise was decreased significantly (p less than 0.005), either by combining digoxin with verapamil or by verapamil therapy alone. In contrast, the excessive heart rate response to exercise was not prevented by digoxin even with good serum concentrations. The improved control of heart rate with verapamil was associated with a significantly improved exercise capacity. Verapamil is an important and safe modality of treatment, with or without digoxin, in the long-term control of heart rate in chronic atrial fibrillation. It is superior to digoxin in controlling the ventricular rate and in improving exercise capacity.

Administration, Oral↗

Expression of murine H-2Kb histocompatibility antigen in cells transformed with cloned H-2 genes.

Cosmids containing H-2 histocompatibility antigen genes of the H-2b haplotype have been isolated. One of these genes expresses a 45,000 molecular weight protein, indistinguishable from H-2Kb when introduced into mouse L cells. These H-2Kb transformed L cells can be killed by allospecific anti-H-2Kb cytotoxic T cells. Moreover, when infected with influenza virus, they can be killed by an H-2Kb-restricted, influenza virus-specific cytotoxic T cell line. These results show that expression of the H-2Kb gene product on the L-cell surface is sufficient to make it a target for specific T-cell killing.

Animals↗

Monozygotic twins discordant for Ullrich-Turner syndrome.

Ullrich-Turner syndrome occurred in one of a pair of female twins. The chromosome constitution of the affected twin was 45,X/46,XX and that of the normal twin 46,XX. Investigation of banded chromosomes, red cell antigens, HLA types, red cell enzymes, and serum proteins indicates monozygosity. The twins are discordant for height, pterygium colli, ovarian function, strabismus, dental eruption, external ear formation, hearing loss, and performance scores on the Wechsler Intelligence Test. All of these differences can be attributed to X monosomy in one cell line in the affected twin, presumably resulting from mitotic nondisjunction or anaphase lag early during embryonic development. Ten other pairs of apparently monozygotic twins discordant for the Ullrich-Turner syndrome have been reported previously, and the findings in these cases are reviewed.

Adolescent↗

Ornithine metabolism in the genus Rochalimaea.

Ornithine metabolism was studied in two strains of the trench fever rickettsia Rochalimaea quintana, Fuller and Guadalupe, and in the vole agent, a strain of Rochalimaea but not necessarily of Rochalimaea quintana. The metabolic activity of intact cells and cell-free extracts was measured by monitoring the evolution of 14CO2 from [1-14C]ornithine. Low levels of activity were obtained with all three strains, but requirements for the demonstration of this activity differed. With the cells of the Fuller and Guadalupe strains, the decarboxylation of ornithine was almost completely dependent on added pyruvate or succinate, presumably as sources of energy for transport. This enhancement was not prevented by the presence of chloramphenicol. The activity of the vole agent, on the other hand, required the complete medium. This activity was prevented by chloramphenicol added at the same time as the medium but not by chloramphenicol added after 1 h of incubation. In cell-free extracts, the demonstration of ornithine decarboxylase activity in the vole agent required prior induction with medium containing ornithine, whereas in the other two strains, the activity was constitutive. The activities of the extracts of the Fuller strain and the vole agent differed also in pH optimum, which was somewhat lower for the vole agent, and in the added pyridoxal phosphate requirement, which was greater for the Fuller strain. Comparable experiments with Rickettsia typhi and Rickettsia prowazekii failed to reveal evidence of ornithine metabolism.

Bacterial Proteins↗

The influence of verapamil on serum digoxin concentration.

The effect of verapamil on the pharmacokinetics of digoxin was studied in 49 patients with chronic atrial fibrillation. A dose of 240 mg/day of verapamil was given to the patients who were receiving a stable dose of digoxin. Serum digoxin levels rose from 0.76 +/- 0.54 ng/ml (mean +/- SD) to 1.31 +/- 0.54 ng/ml during verapamil treatment (p less than 0.0005). This effect was dose-dependent, as shown in seven subjects who received 160 mg and then, 240 mg of verapamil: There was a stepwise rise in serum digoxin concentration from a control value of 0.60 +/- 0.11 ng/ml to 0.84 +/- 0.18 ng/ml and 1.24 +/- 0.40 ng/ml, respectively (p less than 0.01 for both steps). The effect of verapamil developed gradually within the first few days in seven subjects in whom serum digoxin concentration reached, within 7 days, 90% of the increase observed 14 days after onset of verapamil. Renal digoxin clearance decreased significantly (26.1 +/- 0.7 vs 55.1 +/- 12.3 ml/min, p less than 0.005) in six patients in whom serum digoxin concentration increased. It did not change in one patient in whom serum digoxin concentration was not influenced by verapamil. Creatine clearance did not change in any of these seven. The same effects on digoxin clearance were observed in three normal subjects. Among the 49 patients, verapamil resulted in the development of signs and symptoms that suggested digitalis toxicity in seven. Verapamil significantly increased serum digoxin concentration. The process is dose-dependent and gradual, and it is at least partially explained by reduced renal excretion without reduction in glomerular filtration. The dose of digoxin may need readjustment in patients who are concomitantly receiving verapamil.

Adult↗