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J Horvath

Publications and source records attributed to J Horvath.

69 records · Page 4Linked to original sources

Isolation and amino acid sequence of corticotropin-releasing factor from pig hypothalami.

A polypeptide was isolated from acid extracts of porcine hypothalami on the basis of its high ability to stimulate the release of corticotropin from superfused rat pituitary cells. After an initial separation by gel filtration on Sephadex G-25, further purification was carried out by reversed-phase HPLC. The isolated material was homogeneous chromatographically and by N-terminal sequencing. Based on automated gas-phase sequencing of the intact and CNBr-cleaved peptide and on carboxypeptidase Y digestion, the primary structure of this 41-residue polypeptide was determined to be Ser-Glu-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val -Leu-Glu-Met-Ala-Arg-Ala-Glu-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys -Leu-Met-Glu-Asn-Phe-NH2. Porcine corticotropin-releasing factor (CRF) shares a common amino acid sequence (residues 1-39) with rat and human CRF and differs from these only in positions 40 and 41. However, isoleucine was also present at position 40 in porcine CRF, but in a smaller percentage than asparagine. The sequence of porcine CRF shows 83% homology with ovine CRF. Porcine CRF markedly stimulated the release of corticotropin from superfused rat and pig pituitary cells. The biological activity and close structural relationship to CRFs of other species indicate that the peptide isolated represents porcine CRF.

Amino Acid Sequence↗

Radioimmunoassay for 6-D-tryptophan analog of luteinizing hormone-releasing hormone: measurement of serum levels after administration of long-acting microcapsule formulations.

A sensitive and specific radioimmunoassay for [6-D-tryptophan]luteinizing hormone-releasing hormone [( D-Trp6]LH-RH) was developed and used for following the rate of liberation of [D-Trp6]LH-RH from a long-acting delivery system based on a microcapsule formulation. Rabbit antibodies were generated against [D-Trp6]LH-RH conjugated to bovine serum albumin with glutaraldehyde. Crossreactivity with LH-RH was less than 1%; there was no significant crossreactivity with other peptides. The minimal detectable dose of [D-Trp6]LH-RH was 2 pg per tube. Intra- and interassay coefficients of variation were 8% and 10%, respectively. The radioimmunoassay was suitable for direct determination of [D-Trp6]LH-RH in serum, permitting the study of blood levels of the analog after single injections into normal men and after once-a-month administration of microcapsules to rats. In men, 90 min after subcutaneous injection of 250 micrograms of the peptide, serum [D-Trp6]LH-RH rose to 6-12 ng/ml. Luteinizing hormone was increased 90 min and 24 hr after the administration of the analog. Several batches of microcapsules were tested in rats and the rate of release of [D-Trp6]LH-RH was followed. The improved batch of microcapsules of [D-Trp6]LH-RH increased serum concentrations of the analog for 30 days or longer after intramuscular injection. This was accompanied by suppression of testosterone levels for more than 30 days. This radioimmunoassay should be of value for monitoring [D-Trp6]LH-RH during long-term therapy.

Animals↗

The structure of adenovirus chromatin in infected cells.

The structure of adenovirus chromatin in infected cells was studied by micrococcal nuclease digestion and hybridization with virus-specific probes. In the early phase of infection (5 h) a significant proportion of viral molecules was organized like actively transcribed cellular chromatin. As expected for a transcriptionally active population of molecules, even at high multiplicity of infection the nucleosomal repeating pattern was less distinct than in a transformed cell which contained the corresponding but less active genomic region. The observed repeating pattern in infected cells was unlikely to be due to integrated molecules since less than 0.07% of input genomes became associated with cellular DNA. After the onset of viral DNA replication, the pool of viral chromatin organized like cellular chromatin rapidly increased. In addition, newly replicated molecules also maintained the cellular chromatin-like organization as measured by [3H]thymidine incorporation after the cessation of cellular DNA synthesis. These data suggest that newly replicated viral molecules are organized by histones into cell-like chromatin throughout the infection cycle. Coincident with the peak of viral DNA and core protein synthesis, and the decline of histone synthesis, the late, core-like non-repeating viral chromatin became dominant, increasingly obscuring the underlying repeating pattern. Experiments suggest that this late chromatin is destined for encapsidation, that the early chromatin persists and that viral core proteins do not displace histones on viral DNA. A model is proposed suggesting that transcription and type I replication occur on histone-condensed templates, while type II replication products late in infection are condensed by core proteins and are destined for encapsidation.

Adenoviruses, Human↗

Hepatocellular carcinoma associated with hepatitis B in a renal graft recipient.

Hepatitis B virus (HBV) infection, which is common in renal dialysis and transplant units, has been shown to be associated with the development of hepatocellular carcinoma. We report the case of a patient in whom HBV infection was detected after renal transplantation, and who developed a hepatocellular carcinoma 12 years later. The availability of effective preventive and surveillance techniques offers a potential means of reducing the development of hepatocellular carcinoma in these patients.

Adult↗

Effect of age on angiotensin II receptors from rat brain.

1. Angiotensin II receptor binding was studied in specific regions of rat brain at different ages from birth to 14 weeks. 2. The number of specific angiotensin II receptors increased in all regions during the first 2 weeks of life and then decreased to adult levels. Peak numbers of receptors were up to 10 times the adult numbers. 3. The midbrain and thalamus-hypothalamus had maximum numbers of angiotensin II receptors at 2 weeks of age, whereas the rest of the brain regions had maximum number at 1 week. 4. Saralasin-infusion experiments suggested that circulating angiotensin-related peptides could reach brain angiotensin II receptors in 2 week old rats, but not in 6 week old rats. 5. It is postulated that the centrally mediated actions of circulating angiotensin II may be particularly important in the newborn.

Aging↗

Aspirin, protein transacetylation and inhibition of prostaglandin synthetase in the kidney.

1 The effect of aspirin on the kidney has been investigated in mice and rabbits. [Acetyl-(14)C]-aspirin was administered intraperitoneally in doses ranging from subtherapeutic to toxic. The degree of acetylation of protein was determined by the radioactivity remaining on protein precipitates of renal cortex and medulla after sequential washing designed to remove non-covalently bound material. Controls were established, by the use of [carboxyl-(14)C]-aspirin.2 The acetyl-(14)C residue was bound to renal proteins in a linear manner in increasing amounts with increasing dosage up to 100 mg/kg. The [carboxyl-(14)C]-aspirin was not bound and thus the salicylate portion of the molecule was not bound covalently to the renal protein. The time course of the acetylation was rapid, consistent with the rate of aspirin absorption. The disappearance of acetylated protein was slow, with a T(1/2) of 112.5 h in the renal cortex, and 129.5 h in the renal medulla.3 Differential centrifugation, Sephadex chromatography and gel electrophoresis were carried out on tissue homogenates to determine the site of acetylation. The acetylation was greatest in the microsomal fraction, although all protein fractions showed some degree of acetylation.4 The prostaglandin synthetase activity of a particulate preparation from rabbit kidney was determined by a spectrophotometric assay of malondialdehyde formation. Aspirin (10 mg/kg, i.v.) significantly inhibited prostaglandin synthetase in the renal cortex and medulla.5 Aspirin and renal proteins undergo a transacetylation reaction resulting in stable acetylated protein, with acetylation being greatest in the microsomal fraction. Aspirin has been shown to inhibit prostaglandin synthetase and this could lead to functional impairment of the tissue.

Acetylation↗

Effects of timolol and hydrochlorothiazide on blood-pressure and plasma renin activity. Double-blind factorial trial.

The effects of timolol (10 mg thrice daily) and hydrochlorothiazide (50 mg/day) have been compared in a double-blind factorial trial in 20 patients with essential hypertension. There were four randomised test phases of 8 weeks each during which patients received timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and no treatment (placebo). Blood-pressure was measured weekly, alternately at the outpatient clinic and at the patient's home. Supine mean arterial pressure fell from 119 mm Hg in the placebo phase to 110 mm Hg in the hydrochlorothiazide phase, 106 mm Hg in the timolol phase, and 101 mm Hg in the combined timolol plus hydrochlorothiazide phase. Factorial analysis revealed that these effects of the two drugs were additive without any potentiation or antagonism. Mean plasma-renin activity (P.R.A.) was 5-02 ng/ml/3 h in the placebo phase falling to 1-79 in the timolol phase and rising to 9-54 in the diuretic phase, but remaining unchanged in the combined treatment phase (5-40 ng/ml/3 h). The data suggest that the hypotensive action of timolol is not dependent on the concomitant fall in P.R.A. The methods described provide a valuable tool for quantitating the effects of a given drug, and hence a valid basis for objective comparison.

Adrenergic beta-Antagonists↗

Health helpers.

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Attitude to Health↗

Reversal of renal failure and control of hypertension in patients with occlusion of the renal artery.

Results of arteriographic investigation of patients with deteriorating renal function or poorly controlled hypertension have revealed that thrombosis of the renal artery is not an uncommon exacerbating factor. Seventeen patients with one or more occluded renal arteries had an operation to improve renal function or to control hypertension. Stenosis of the contralateral renal artery was present in addition to the occlusion in four patients. Reconstructive arterial procedures were performed in 15 patients and nephrectomy was performed in two. Eight patients with renal failure had marked improvement in renal function after revascularization of the occluded renal arteries. The group had a mean preoperative serum creatinine value of 7.95+/-1.81 (S.E.) milligrams per cent which fell postoperatively to 3.91+/-1.21 (S.E.) milligrams per cent at a mean follow-up period 20 months. Preoperative control of hypertension was difficult in 16 of the 17 patients. Postoperatively, the blood pressure fell to normal levels in six patients, and in an additional eight patients, it did so with the administration of antihypertension therapy. The hypertension was unchanged in two patients. Plasma renin activity was measured in 14 of the patients with hypertension. It was elevated in 13 patients and normal in one patient. Postoperatively, the blood pressure was unchanged in the patient with normal plasma renin activity, but in 12 of the 13 patients with elevated plasma renin activity, the blood pressure returned to normal levels. It is concluded that patients with occluded renal arteries should be treated surgically. The major benefits of an aggressive approach to this condition are reversal of renal failure and control of hypertension.

Acute Kidney Injury↗

Placental endothelial nitric oxide synthase localization and expression in normal human pregnancy and pre-eclampsia.

1. The aim of the present study was to investigate whether pre-eclampisa, a state of placental hypoxia, is associated with placental abnormalities in the amount, distribution and expression of endothelial nitric oxide synthase (eNOS). 2. Localization and intensity of eNOS was determined by immunohistochemistry using an antibody specific for eNOS. The amount of eNOS mRNA expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and the densitometry of gel bands was expressed as a ratio of the band density of the housekeeping gene beta2-microglobulin. 3. Endothelial NOS staining was localized to syncytiotrophoblast cells within the villi and decidual trophoblast cells. It was not present in the endothelium of terminal villous vessels. There was no significant difference in eNOS villous or decidual staining intensity between normal pregnancy (NP; n = 12), pre-eclampsia (n = 14), or gestational hypertension (GH; n = 4). Staining for eNOS was not significantly different in the decidua compared with the villi in NP, GH or pre-eclampsia. Within the decidua, the depth of eNOS staining was similar in NP, pre-eclampisa and GH. 4. There was no significant difference in eNOS mRNA expression between NP (0.70 +/- 0.11), pre-eclampsia (0.5 +/- 0.07) or GH (0.69 +/- 0.26). 5. These findings suggest that the amount of eNOS in the placenta is not deficient in pre-eclampsia, excluding a possible pathogenic role for eNOS in this disease. Furthermore, placental hypoxia, which is associated with pre-eclampsia, did not induce an upregulation of eNOS

Adolescent↗

Obstetrical ultrasound in remote communities: an approach to health program evaluation.

This paper illustrates one approach to evaluating the impact of an obstetrical ultrasound outreach program in remote Indian communities. The pregnancy characteristics and obstetrical outcomes of 240 deliveries in 2 groups of communities with and without the program are compared. After controlling for maternal age, parity, obstetrical risk score and presence of diabetes and hypertension during pregnancy, Program Area women are found to differ significantly from Control Area women in several medical care measures. There are more health care contacts, fewer medical referrals out of the community and a lower proportion of non-hospital births. There are however more inductions of labour and longer hospital stays. The small sample size was not sufficient to detect differences in rare events such as perinatal deaths. Despite its shortcomings, the quasi-experimental design provides health planners with important information regarding medical technologies and interventions, particularly when randomized controlled trials are deemed not to be feasible and the only alternative is unsubstantiated opinions.

Adult↗

Failure of patent aorto-renal grafts to cure hypertension in renin positive patients.

Correction of renal artery stenosis in a hypertensive patient does not always result in cure of the hypertension. In a follow-up on 127 patients operated on for renovascular hypertension over a 24-year period 32 patients with favourable preoperative factors, unilateral disease, normal renal parenchyma and a positive renal vein renin ratio were studied. 20/32 were regarded as cured with a BP of less than 140/90 and 12/32 were regarded as unsuccessful with a BP, although lessened, higher than 140/90. Hypotensive medication was required in 10/12 in the latter group and was still required in 8/20 of the former. The cure rate of less than 2/3rd is lower than most reports in the literature. The possible causes of the discrepancy are discussed.

Adult↗