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Biomedical subjects

K D Bhoola

Publications and source records attributed to K D Bhoola.

At least 91 records · Page 5Linked to original sources
PubMed1988

Localisation of immunoreactive kininogen and tissue kallikrein in the human nephron.

The cellular localisation of kininogen and its relationships with tissue kallikrein containing cells was studied in the human kidney by the peroxidase-antiperoxidase method using antisera to human LMW kininogen and to human tissue kallikrein. Immunoreactive kininogen was localised in the principal cells of collecting ducts. Immunoreactive tissue kallikrein was detected in the connecting tubule cells, segment of the nephron preceding the cortical collecting ducts. The co-existence of tissue kallikrein and kininogen in the same transitional tubule, but in different cells, was established by the use of serial sections and double immunostaining. This anatomical relationship is in accordance with known studies that describe intermingling of principal cells and connecting tubule cells where connecting tubules merge into cortical collecting ducts in the human nephron. The close relationship between cells that contain tissue kallikrein and its substrate, kininogen, suggests that kinins could be generated in the lumen of distal cortical segments of the human nephron.

Humans↗
PubMed1988

Urinary guanosine 3':5'-cyclic monophosphate but not tissue kallikrein follows the plasma atrial natriuretic factor response to acute volume expansion with saline.

1. The relationship between plasma immunoreactive atrial natriuretic factor (Ir-ANF) and the urinary excretion of sodium, guanosine 3':5'-cyclic monophosphate (cyclic GMP) and of tissue kallikrein was examined in seven healthy female volunteers. 2. Each volunteer attended on two occasions, a control and a saline infusion day. On the infusion day saline (2 litres, 0.9% NaCl) was administered over 60 min. Measurements of plasma Ir-ANF and urinary excretion of sodium, cyclic GMP and of tissue kallikrein were made at 30 min intervals during the infusion and for 3 h after the infusion. 3. Mean (+/- SEM) urinary sodium excretion increased from a basal value (time 0) of 102 +/- 15 mumo/min to 222 +/- 47 mumol/min 60-90 min from the start of the infusion and thereafter remained significantly elevated (P less than 0.01) above sodium excretion on the control day. 4. In response to saline infusion there was a transient rise in mean (+/- SEM) plasma Ir-ANF from 6.7 +/- 0.8 pmol/l to a peak of 22.5 +/- 3.7 pmol/l at 75 min, falling to 12.7 +/- 1.9 pmol/l at 135 min. The peak plasma Ir-ANF level on the infusion day was significantly elevated (P less than 0.05) above the time-matched measurement on the control day. 5. Similarly, there was a transient rise in mean (+/- SEM) urinary cyclic GMP excretion on the infusion day from 30.9 +/- 4.4 fmol/min to 64.6 +/- 11.4 fmol/min during the 60-90 min collection period, returning to 43.7 +/- 14.5 fmol/min at 210-240 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Comparison of the action of cholecystokinin, carbachol and vasoactive intestinal peptide on receptor-activated formation of cyclic GMP and cyclic AMP in the striatum and the pancreas.

Sulphated cholecystokinin octapeptide (CCK-8S) and sodium nitroprusside (SNP) increased the formation of cyclic GMP in rat striatal slices with no effect on cyclic AMP. CCK-8S, SNP and carbachol increased the formation of cyclic GMP in guinea-pig pancreatic lobules, but had no effect on levels of cyclic AMP. Vasoactive intestinal peptide (VIP) significantly stimulated the formation of cyclic AMP in both striatal and pancreatic tissue without effect on levels of cyclic GMP in these tissues. In rat striatal slices carbachol significantly inhibited the VIP-stimulated increase in cyclic AMP.

Animals↗
PubMed1986

Studies on renal and urinary kallikrein in spontaneously hypertensive rats.

Urinary kallikrein excretion, active (A) and total (T), was significantly reduced in the Okamato spontaneously hypertensive rat (SHR). The renal content of A and T soluble tissue kallikrein was clearly greater in this strain. Arginine vasopressin stimulated the release of both A and T kallikrein from renal cortical slices of the normotensive (N) Wistar strain, this response was not observed in the SHR. PGE2 stimulated release of A kallikrein in the N strain and both A and T enzyme in the SHR. It is suggested that urinary kallikrein excretion values may not necessarily reflect the endogenous levels of the enzyme in the kidney. Both the level and release of renal tissue kallikrein may become altered either in response to or as a result of chronically elevated blood pressure.

Angiotensin II↗
PubMed1986

Opioid inhibition of adenylate cyclase in the striatum and vas deferens of the rat.

The activity of adenylate cyclase in striatal membrane-enriched fractions (25,000 g) was inhibited by morphine, beta-endorphin, [D-Ala2-D-Leu5] enkephalin (DADLenk), fentanyl and bremazocine. Whereas guanosine triphosphate (GTP) appeared essential for the expression of this effect, sodium chloride seemed to enhance the degree of inhibition. Dopamine stimulation and sodium fluoride activation of the enzyme was also suppressed by morphine, beta-endorphin and DADLenk. beta-Endorphin and DADLenk inhibited adenylate cyclase activity in vasa deferentia membrane-enriched fractions (25,000 g); both opioids required GTP and NaCl and were inhibited by a delta-opioid receptor antagonist and by naloxone. Morphine, bremazocine and tifluadom did not significantly alter the activity of the vas deferens enzyme. Basal cyclic AMP values of striatal slices were not significantly altered by morphine, beta-endorphin or DADLenk. However, dopamine-induced elevation of cyclic AMP was reduced by morphine and this effect of the opiate was suppressed by naloxone. Only beta-endorphin lowered the basal cyclic AMP values in the vas deferens. The physiological relevance of adenylate cyclase coupling to opioid receptor subtypes is considered.

Adenylyl Cyclase Inhibitors↗
PubMed1985

Salivary secretion and connective tissue disease in man.

Parotid and submandibular gland secretions collected from patients with rheumatoid arthritis or systemic sclerosis have been analysed and the results compared with those obtained from a matched group of healthy individuals. Flow rates were measured and the saliva samples assayed for amylase, kallikrein, protein, and salivary IgA concentration. The results showed that only patients with rheumatoid arthritis had a reduced salivary flow, especially parotid flow, with a significantly increased concentration of salivary IgA in both parotid and submandibular saliva. Patients with systemic sclerosis did not show significantly altered salivary flow rates, but there was a marked depletion of salivary IgA content in both parotid and submandibular saliva. Neither disease states appeared to alter the kallikrein or amylase content of saliva. The possible clinical value of these findings is discussed.

Adult↗
PubMed1984

Schistosomiasis and bladder carcinoma in Natal.

In a retrospective study 184 biopsy reports of primary malignant bladder tumours in males which had been received from the Department of Pathology, University of Natal, during 1971-1982 were analysed. The age and race of the patients, the histological type of the tumours and the presence or absence of concomitant schistosomal infection were noted. There were 103 squamous and 62 transitional cell carcinomas, and 19 adenocarcinomas or undifferentiated types of malignant tumour. Of the patients 153 were Blacks and 31 Indians, 61,4% of the Blacks had squamous cell carcinoma, as against 29% of the Indians (P less than 0,01). Bladder carcinoma among Blacks occurred at a younger age (5th decade) than that among Indians (6th decade). The prevalence of schistosomiasis in the whole group was 40,8%. The prevalence was highest in the Blacks (44,4%); in the Indians it was 22,6%. Schistosomal infection was most commonly associated with squamous cell carcinoma (61%) (P less than 0,0001).

Adenocarcinoma↗
PubMed1984

Development and characterization of a radioimmunoassay to measure human tissue kallikrein in biological fluids.

A direct radioimmunoassay has been developed to measure tissue kallikrein in human biological fluids. These fluids include serum, plasma, urine, pancreatic juice and saliva. Purified kallikreins from human urine and human saliva were used to raise rabbit antibody and each was labelled with Na125I for use in the radioimmunoassay. A comparison of the different antigen-antibody systems was then made. Bound and free enzyme were separated by a double-antibody technique. The usable range of the standard curve was from 2.5 to 100 micrograms kallikrein/l. The intra-assay coefficient of variation was 4.7%, the interassay coefficient of variation 8.9% and the recoveries of purified kallikrein added to the samples were 99.3, 96.0, 110.8 and 81.2% for urine, saliva, serum and plasma respectively. Parallel dilution curves were obtained for serum and plasma, as well as for urine, saliva and pancreatic juice. However, plasma anticoagulated with EDTA or heparin gave consistently lower values than serum, when measured in the radioimmunoassay. From eight different subjects plasma (EDTA) values were on average 50% lower than those of serum. Experiments designed to determine the cause of this difference revealed that treatment of blood with some anticoagulants, in particular heparin and EDTA, resulted in a marked reduction in the amount of measurable tissue kallikrein.

Body Fluids↗
PubMed1983

Purification and properties of guinea-pig submandibular-gland kallikrein.

Guinea-pig submandibular kallikrein has been purified from the glands to electrophoretic homogeneity by conventional procedures. The enzyme is active as a kininogenase, releasing kallidin at a rate of 462 micrograms/min per mg of protein from bovine kininogen, and proved potently hypotensive in the guinea pig and in the dog, properties which indicate its tissue kallikrein nature. The specific activity determined on the substrate N-alpha-benzoyl-L-arginine ethyl ester (11.1 mumol/min per mg of protein) is much lower than that measured with N-acetyl-L-phenylalanyl-L-arginine ethyl ester (483 mumol/min per mg of protein). The latter value is of an order of magnitude comparable with the specific activities of other tissue kallikreins determined with this sensitive kallikrein substrate. The enzyme is a glycoprotein consisting of 237 amino acid residues and containing three to four glucosamine molecules. Its amino acid composition is not identical with that reported for guinea-pig coagulating-gland kallikrein, but is remarkably similar to that of the porcine tissue kallikreins. Apparent Mr values are 29000 (sodium dodecyl sulphate/polyacrylamide-gel electrophoresis) or 34000 (gel filtration). The amino acid sequence of the first 31 N-terminal residues was determined and was found to be closely homologous with that of other tissue kallikreins.

Amino Acid Sequence↗
PubMed1980

Vasoactive intestinal polypeptide (VIP)-sensitive adenylate cyclase in rat brain: regional distribution and localization on hypothalamic neurons.

The regional distribution of the vasoactive intestinal polypeptide (VIP)-sensitive stimulation of adenylate cyclase activity was studied in homogenates or rat brain. The order of sensitivity of this peptide on enzyme activity was: olfactory bulb > hippocampus > thalamus > occipital cortex congruent to frontal cortex congruent to midbrain congruent to hypothalamus > striatum > cerebellum congruent to brain stem > spinal cord. With neurotoxin-induced lesions the possible location of VIP-sensitive adenylate cyclase within the anterior hypothalamus was investigated. Intrahypothalamic 6-hydroxydopamine blocked the stimulatory effect of VIP on hypothalmic adenylate cyclase, but neither kainic acid nor 5,7-dihydroxytryptamine lesions had any effect. Similarly, there was a 71% reduction in the sensitivity of VIP-sensitive adenylate cyclase activity in animals whose hypothalamic noradrenergic innervation had been interrupted by transection of the ascending dorsal and ventral bundles. Biochemical analyses of the lesions suggested that loss of VIP action on adenylate cyclase was associated with loss of hypothalamic noradrenaline-containing neurons. These results may give insight into those regions of rat brain where VIP may have a neurotransmitter role, and point to a possible noradrenergic localization of the VIP-sensitive adenylate cyclase within the hypothalamus.

5,7-Dihydroxytryptamine↗
PubMed1980

Modulation of cyclic AMP in isolated rat uterine tissue slices by porcine relaxin.

Porcine relaxin produced a rapid, dose-related rise of cyclic AMP values in rat uterine tissue incubated in vitro. In time-course experiments, peak cyclic AMP concentrations were observed in the uterine slices at 5 min; subsequently the values fell, at first rapidly and then more slowly with the tissue concentration remaining significantly raised at 15 min. Levels of cyclic GMP in the same tissue slices were not significantly altered by relaxin. Furthermore, no increase in basal cyclic AMP values was measured in control slices prepared from the rat heart or jejunum. An increase in cyclic AMP concentration comparable to that found in the rat uterus was observed in slices of porcine uterus and cervix but not of vagina when they were stimulated with porcine relaxin. Our results suggest that the hormonal action of relaxin on the uterus and cervix is mediated through receptors linked to the enzyme, adenylate cyclase.

Animals↗
PubMed1979

The clinical syndrome of Impila (Callilepis laureola) poisoning in children.

The administration of herbal medicines made from Callilepis laureola is common among the Black population in Natal. This practice can and does cause poisoning, which has only been diagnosed with any confidence at postmortem examination, where the characteristic hepatic and renal tubular necrosis is obvious. Necropsy records of 50 children in whom these typical histological changes were noted were analysed retrospectively in order to determine the clinical picture. Results show that the disease can be recognized in young Black children when there is hypoglycaemia and an alteration in the level of consciousness, together with evidence of hepatic and renal dysfunction. This syndrome can easily be distinguished from viral hepatitis and fulminant hepatic failure, but less readily from Reye's syndrome.

Child↗
PubMed1979

Eosinophilic fasciitis. A case report.

We describe a patient with a scleroderma-like illness which involved the arms and legs but not the face and hands. Clinical, laboratory and histological features were those of the recently described syndrome, eosinophilic fasciitis. This rare condition is worthy of note because it appears to have a much better prognosis than conventional scleroderma, and because it responds very well to corticosteroid therapy.

Adult↗
PubMed1979

Immunogenicity of guinea-pig submandibular and coagulating gland kininogenases.

The antigenic relationship between submandibular and coagulating gland kininogenases of the guinea-pig has been examined using Ouchterlony double diffusion, crossed and rocket immunoelectrophoresis and immunofluorescent techniques. The evidence suggests a partial immunological identity between submandibular and coagulating gland kininogenases of the guinea-pig. In this respect these enzymes seem to differ from the glandular kallikreins of other species (porcine, human and rat) which apparently share a complete immunological identity.

Animals↗
PubMed1978

A survey of salivary kallikrein and amylase in a population of schoolgirls, throughout the menstrual cycle.

1. The values for kallikrein, amylase and protein were determined in samples of saliva obtained from 220 girls aged 14--18 years. 2. The concentrations of protein and amylase and kallikrein activities (per ml of saliva) were considerably more variable in samples taken in the morning than those in the afternnon. 3. The median amylase activity was about two and a half times greater in the morning than that in the afternoon. No such differences were seen in the median values for protein or kallikrein. 4. Examination of the vlues for salivary kallikrein during the menstrual cycle showed that there was significantly greater activity during days 29--32 and 1--4 than during the rest of the cycle. This pattern was most marked in the morning values of kallikrein but not apparent either in the morning or in the afternoon values of protein or amylase.

Adolescent↗