Search PubMed⌕ Search

Biomedical subjects

J Weber

Publications and source records attributed to J Weber.

At least 325 records · Page 18Linked to original sources
PubMed1993

Specific placement of tryptophan in the catalytic sites of Escherichia coli F1-ATPase provides a direct probe of nucleotide binding: maximal ATP hydrolysis occurs with three sites occupied.

Residue beta Y331 of Escherichia coli F1-ATPase is known from previous affinity labeling, mutagenesis, and lin-benzo-ADP binding experiments to interact directly with the adenine moiety of substrates bound in catalytic sites. Here we mutagenized beta Y331 to tryptophan. Mutant cells grew well on succinate or limiting glucose; purified mutant F1 had kappa cat/Km and lin-benzo-ADP binding characteristics similar to wild type. Fluorescence from beta W331 residues exhibited a maximum at 349 nm, indicating a polar environment in unoccupied sites. ATP, ADP, or AMPPNP caused virtually complete quenching of beta W331 fluorescence, so that the fluorescence of mutant F1 with occupied catalytic sites resembled that of wild-type enzyme. Therefore the beta W331 fluorescence provided a direct probe of nucleotide binding to catalytic sites under true equilibrium conditions. We measured ATP binding and hydrolysis in parallel experiments and found that occupancy of one or two catalytic sites per F1 molecule did not yield significant rates of hydrolysis while occupancy of all three sites yielded Vmax rates. Km(ATP) was similar to Kd3, the Kd for ATP binding to the third catalytic site. We also measured AMPPNP and ADP binding parameters. For ADP, the "on" rate at the first catalytic site was much faster (> or = 5 x 10(5) M-1 s-1) than seen previously by centrifuge column procedures, although the Kd was not much changed. For AMPPNP, the "on" rate at the first site was 2 orders of magnitude less than for ADP or ATP, and the Kd was similar to that for ADP.

Adenosine Diphosphate↗
PubMed1993

Combined application of site-directed mutagenesis, 2-azido-ATP labeling, and lin-benzo-ATP binding to study the noncatalytic sites of Escherichia coli F1-ATPase.

Noncatalytic nucleotide sites of Escherichia coli F1-ATPase were studied by site-directed mutagenesis, covalent photolabeling with 2-azido-ATP, and lin-benzo-ATP binding. In wild-type, 89% of 2-azido-ATP label was bound to beta-subunit, whereas in the beta Y354F mutant, 95% of the label was bound to alpha-subunit. In the alpha R365Y mutant, label was seen on both alpha (38%) and beta (62%); whereas in the alpha R365F mutant, 93% was on beta. The fluorescence of noncatalytic site-bound lin-benzo-ATP was quenched markedly in F1 from wild-type (76% quench), alpha R365F (85%), alpha R365Y (90%), and alpha R365Y, beta Y354F (83%), but only by 28% in beta Y354F. These results together demonstrate that residues alpha R365 and beta Y354 lie close to the base moiety of adenine nucleotide bound in F1 noncatalytic sites. From comparison of sequences of alpha- and beta-subunits, it appears that residue alpha R365 in noncatalytic sites is equivalent to residue beta Y331 of the catalytic sites. Two unintended mutants were obtained in which alpha-subunit was increased in length by 17 amino acids due to repeat of residues alpha 361 to alpha 377, with either F or Y in the repeated alpha 365 position. Soluble F1 was obtained from both mutants, with novel properties.

Adenosine Triphosphate↗
PubMed1993

[Lethal Salmonella enteritidis meningoencephalitis in an adult with a carcinoma of an unknown primary site].

A 71-year-old man with an aortobifemoral bypass graft had experienced several episodes of severe pain in the thoracic and lumbar spine, followed by severe abdominal pain, during the preceding two weeks. Physical examination, chest X-ray, ultrasonography and computed tomography of the abdomen provided no specific pointers to a diagnosis. He was anaemic (haemoglobin 95 g/l), but had a normal WBC count with neutrophilia (up to 91%) and thrombocytopenia (up to 24,000/microliters). The transaminase and lactate dehydrogenase activities were raised, as were the bilirubin level and the retention values. There was a metabolic acidosis (pH 7.20). Because of suspected septicaemia ciprofloxacin (twice daily 200 mg) was administered intravenously. But the patient gradually lost consciousness, required mechanical ventilation and died 24 hours after admission in circulatory failure. Autopsy revealed a meningoencephalitis, carcinoma of unknown primary with bone marrow carcinomatosis as well as widespread carcinomatosis of blood and lymph vessels. The findings of blood, urine and sputum cultures, available only postmortally, revealed growth of tetracycline-resistant Salmonellae enteritidis.

Aged↗
PubMed1993

Quantification of congruence between the right and left visual fields.

In the past, congruence between the right and left visual fields could only be evaluated subjectively. This study presents a congruence index to assess the similarity of the two visual fields objectively and quantitatively based on probability calculations. In 18 patients with suprachiasmal lesions of the visual pathways (cerebrovascular accident or tumor), the index found a homonymous congruence in all cases (100%). Of 26 persons with pituitary adenoma, in 22 cases (85%) the index found heteronymous congruence. The validity of the method may be even higher, because all cases with atypical indices also had atypical congruence by subjective evaluation. Using this new method in 41 patients with primary open-angle glaucoma, heteronymous congruence was detected in 73% and homonymous congruence was found in 17%. This new index may be useful for the development of computerized parametric methods of differential diagnosis.

Adult↗
PubMed1993

Comparison of spatial thresholds and intensity thresholds in glaucoma.

Spatial resolution perimetry and conventional perimetry measure different qualities of the functional performance of the eye. Theoretically, spatial resolution is directly related to the density of intact sensory units, but the relation of intensity to the density of intact sensory units is unknown. Previous studies indicated an almost linear relationship of global indices of spatial thresholds and intensity thresholds. The purpose of our study is to look at any difference in the behaviour of local threshold values and their precise relation. We examined 41 eyes of 23 patients with open angle glaucoma. Perimetry was carried out using the Humphrey Field Analyzer, and program 30-S or program 30-2 and the ring perimeter and standard program. Because test point patterns of the two examinations were different, the best matching points were calculated. If the distance between next points in both examinations was more than 5 degrees, the location was excluded. The Humphrey program 30-2 provided 47 matching points, the Humphrey program 30-S furnished 49 matching points for 50 locations. For the range of 20..36 dB in conventional perimetry, linearity could be verified in relation to the local thresholds in ring perimetry. The spatial threshold units used in the ring perimeter are the logarithm of spatial extend. Vice versa, spatial resolution is a power function of spatial thresholds. Based on the linear relationship of both thresholds, spatial resolution is a power function of intensity thresholds. In other words, if the intensity threshold is reduced from 36 to 30 dB, the spatial resolution is nearly half.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

ESWL and oral dissolution therapy. What factors influence results?

With the aim of identifying the criteria that have a decisive influence on the success of treatment of gallstones with ESWL and oral dissolution therapy, we investigated, in 117 patients, the stone-free rate as a function of sex, age, weight quotient, number of stones, total stone volume, and gallbladder function. The following inclusion criteria were applied: (1) the Munich criteria, (2) a follow-up period of at least 12 months, or (3) freedom from stones irrespective of the duration of the period of follow-up. Although, owing to the small number of cases involved, no significantly differing results were seen in the parameters investigated, clear tendencies were indeed observed. While age, sex, and weight quotient appear to have no influence on the stone-free rate, the number of stones, total stone volume, and gallbladder function do appear to have an effect on the results of treatment. Patients with solitary stones not more than 20 mm in diameter, and patients with a small total stone volume and good gallbladder function would appear to have the best chance of becoming stone-free within a short period of time, irrespective of age, sex, or girth.

Administration, Oral↗
PubMed1993

Cerebral potentials evoked by electrical stimulation of the anal canal.

We describe the procedure with which cortical potential responses are evoked by a stimulation of the anal canal to assess the integrity of its sensory pathways. These potentials were recorded in 66 patients. In 44 patients, a cortical evoked response was obtained with a succession of positive and negative peaks, W shaped (35 cases) or V shaped (nine cases). In seven cases, cortical responses were interpreted differently by two independent observers. In these seven patients, such differences could be explained by an insufficient amplification of the recorded electrical waves recorded on paper (< 10 mm). Fifteen patients gave no cortical response. Eight had a neurologic disease that could explain the lack of response. In the seven others, the absence of response was considered as false negative, but six of these stimulations had been carried out during the first part of the study. There is some evidence that cortical evoked potentials may be obtained after an electrical stimulation of the anal canal, but a training period seems necessary to master the technique and obtain reproducible and recognizable responses.

Adult↗
PubMed1993

The effect of a biphasic desogestrel-containing oral contraceptive on carbohydrate metabolism and various hormonal parameters.

During 6 cycles of treatment of 19 women, the effect of a low-dose biphasic oral contraceptive containing 40 micrograms ethinylestradiol + 25 micrograms desogestrel (7 tablets) and 30 micrograms ethinylestradiol + 125 micrograms desogestrel (15 tablets) on various hormonal parameters and glucose metabolism was compared with the values of the pre- and post-treatment cycle. There was a profound reduction in gonadotropin secretion and ovarian steroid synthesis. The serum levels of testosterone were reduced by 35%, free testosterone by 55%, and DHEA-S by 30%. Cortisol increased by 100%, SHBG by 250%, and TBG by 60%, while FT3 and FT4 were only marginally influenced. Fasting levels of glucose and insulin did not change significantly, but the glucose load revealed a slight impairment of glucose tolerance. Three weeks after termination of pill intake, the various parameters returned to pretreatment levels, except for SHBG and TBG which were still elevated by 20 to 30%. The results demonstrate a marked preponderance of the effect of the estrogen component, a reliable inhibition of ovulation and very good cycle control during treatment with the biphasic formulation.

Adult↗
PubMed1993

Effect on lipid metabolism of a biphasic desogestrel-containing oral contraceptive: divergent changes in apolipoprotein B and E and transitory decrease in Lp(a) levels.

The effect of a low dose biphasic oral contraceptive containing 40 micrograms ethinylestradiol + 25 micrograms desogestrel (7 tablets) and 30 micrograms ethinylestradiol + 125 micrograms desogestrel (15 tablets) on lipid metabolism was investigated in 19 women during 6 cycles of treatment and compared to the values of the pre- and post-treatment cycle. During treatment, all components of HDL increased reversibly by 10 to 30%. The levels of total cholesterol (CH), LDL-CH and IDL-CH rose only slightly, while those of total triglycerides (TG), VLDL-TG and LDL-TG rose continuously by more than 100% until the 6th cycle. At the same time, plasma levels of VLDL-CH increased by 60% and of apolipoprotein B by 20%. Contrary to this, apolipoprotein E decreased by 25% during treatment, and Lp(a) was transitorily reduced during the 3rd cycle. After termination of intake, total CH, LDL-CH, IDL-CH and apolipoprotein B remained elevated, while total TG, VLDL-TG, VLDL-CH and LDL-TG decreased significantly, but were still elevated during the post-treatment cycle. The levels of apolipoprotein E returned to pre-treatment values. The results indicate a marked preponderance of the effect of the estrogen component. The rise in TG and VLDL synthesis seems to be outweighed by an enhanced removal of apolipoprotein E-containing remnants which might offer protection from the development of atherosclerosis.

Adult↗