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Biomedical subjects

K D Bhoola

Publications and source records attributed to K D Bhoola.

At least 73 records · Page 4Linked to original sources

An ontogenic study of renal tissue kallikrein in Okamoto spontaneously hypertensive rats: comparisons with human hypertensive nephropathy.

Urinary excretion of tissue kallikrein is reduced in essential hypertension. Although a similar finding has been reported in spontaneously hypertensive rats (SHR), only a few studies have been concerned with the amount of enzyme within the kidney both at the time of onset and during progression of the hypertension. We have performed an ontogenic study on the renal parenchymal values and immunoreactivity of tissue kallikrein in Okamoto SHR aged 4-78 weeks. Additionally, these two parameters were analysed in human biopsies taken from patients with hypertensive nephropathy. The enzymatic activity of renal tissue kallikrein (active and total; specifically antagonized by anti-tissue kallikrein antibodies), increased from 4 to 52 weeks in SHR when compared to normotensive Wistar Kyoto (WKY) rats; this increase was associated with a significant increase in blood pressure. In contrast, 78 weeks SHR and human biopsy tissue showed a substantial reduction in tissue kallikrein values. Also, both renal tissues showed a reduction in immunoreactivity in the cells of the connecting tubules that specifically store the enzyme. In advanced hypertension the observed reduction in tissue kallikrein was probably secondary to a loss of distal tubular mass, as a result of tubular atrophy and fibrosis. The greater values for renal tissue kallikrein in the kidney and reported reduced urinary excretion during the early phases of spontaneous hypertension may be explained by a primary defect in the mechanisms that regulate release of tissue kallikrein from the connecting tubule cells.

Animals↗

Tissue kallikrein and the effect of bromocriptine in human prolactin and growth hormone-secreting pituitary adenomas.

Tissue kallikrein (TK) is present and co-localises with prolactin producing cells in human prolactinoma and mixed growth hormone (GH) and prolactin-secreting pituitary adenomas. TK immunoreactivity was reduced or absent in these types of adenomas from patients who had received the dopamine agonist, bromocriptine before surgery. Pure GH secreting adenomas had no TK immunoreactivity.

Adenoma↗

Evidence that nitric oxide or a related substance is a neurovasodilator in the submandibular gland of the cat.

Close-arterial injection of L-NG-nitro arginine methyl ester, a compound that inhibits the synthesis of nitric oxide (NO), caused a dose-dependent reduction in both the parasympathetic and sympathetic (rebound) nerve-induced vasodilatation within the submandibular gland of the cat. At the same time, salivary secretion produced by each nerve was relatively unaffected, and the sympathetic vasoconstriction was enhanced. These results suggest that NO or a related compound may be either a neurotransmitter or neuromodulator contributing to the autonomic nerve-induced vasodilatation in the submandibular gland of the cat.

Animals↗

Determination of tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis.

An enzyme-linked immunosorbant assay was developed to determine tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complexes in pooled synovial fluid of patients with rheumatoid, osteo and psoriatic arthritis. Even though basal values could be determined, the addition of synovial fluid shifted the standard curves for both tissue kallikrein and alpha 1-antitrypsin-tissue kallikrein complex to the right, because of the presence of a novel inhibitor.

Arthritis, Psoriatic↗

Comparison of plasma prekallikrein levels in human skin blister and chamber fluids from volunteer subjects and psoriatic patients.

Suction blisters were successfully raised on lesional, perilesional and non-lesional skin of psoriatic patients. Similar blisters were created on the skin of volunteer subjects. A specific method has been established for the measurement of plasma prekallikrein, and validated for blister fluid, skin chamber fluid, plasma and synovial fluid. Combined levels of plasma prekallikrein and its active form were compared in blister fluids obtained from psoriatic patients and the volunteers. Significantly higher values for plasma prekallikrein were found in the non-lesional blister fluids of psoriatic patients when compared to the volunteer subjects.

Blister↗

Tissue kallikrein and kininogen in human sweat glands and psoriatic skin.

The cellular localization of immunoreactive tissue kallikrein and kininogen was studied in normal and psoriatic human skin. Immunoreactivity to both enzyme and substrate was observed in secretory granules of the dark cells in the secretory fundus (acinus) of the sweat glands. Double immunostaining revealed a segmental distribution of the two antigens. Each acinar section contained either tissue kallikrein or kininogen. However, there appeared to be a junctional zone in which both were present, but in separate dark cells. Immunoreactivity for both antigens was also observed in close apposition to the luminal microvilli of the duct cells. No specific immunostaining was seen in sebaceous glands, hair follicles, keratinocytes and other cells of the secretory unit such as myoepithelial or clear cells. In psoriatic skin there were in addition many neutrophils immunoreactive for tissue kallikrein in the epidermis and psoriatic scales. Mitogenic action of kinins may account to some extent for the characteristic accelerated turnover of epidermal cells in psoriasis and locally applied kinin antagonists may prove of value in the treatment of this disease.

Humans↗

Cellular localisation of atrial natriuretic factor in the human kidney.

We have localised atrial natriuretic factor (ANF) in the human kidney by immunocytochemistry and radioimmunoassay. ANF is specifically visualised in the distal convoluted tubule cells and the intercalated cells of the connecting tubules and collecting ducts of the human nephron. The number of immunoreactive cells and tissue values for the peptide were compared between samples from normal kidneys and biopsies obtained from hypertensive patients, in whom the tissue ANF immunoreactivity was found to be reduced. Specific experiments are necessary to establish whether renal ANF is synthesised de novo or captured through endocytosis by the renal tubular cells. The possible functional roles of renal ANF are discussed.

Aged↗

Electrolyte and humoral responses of renal transplant patients to head-out water immersion.

Eighteen renal transplant recipients and sixteen volunteers were subjected to the physiological manoeuvre of head-out water immersion, in order to compare changes in electrolyte and humoral responses known to occur in healthy individuals with those arising as a result of renal denervation in the transplant recipients. Although the tubular sodium response to water immersion was normal, tubular potassium excretion was markedly different in the transplant patients. Plasma values of atrial natriuretic factor increased in both groups and showed a close temporal relationship to urinary excretion of cyclic GMP. The attenuation in transplant recipients of the well-documented suppression of plasma renin activity during water immersion was probably due to a combination of factors, namely lack of renal innervation and an increase in circulating ANF. The small but significant increase in the excretion of enzymically active urinary kallikrein observed only in the transplant recipients during immersion still requires explanation.

Adult↗

Characterization of a tissue kallikrein in human prolactin-secreting adenomas.

Immunoreactive tissue kallikrein was co-localized with prolactin in all the eleven prolactin-secreting adenomas of the human anterior pituitary gland examined in this study. The intracellular distribution of immunoreactivity in the prolactin-secreting cells suggests that tissue kallikrein is located within the Golgi complex of these cells. Both the intracellular hormone-processing action and the kininogenase activity of tissue kallikrein may be of functional importance in human prolactinomas.

Adolescent↗

Relationship between ANP, cyclic GMP and tissue kallikrein following saline infusion in healthy volunteers.

Infusion of saline in healthy volunteers produced a significant rise in plasma atrial natriuretic peptide, which was accompanied by the urinary excretion of cyclic GMP and sodium. Although the time-course of cyclic GMP excretion almost mirrored that of plasma ANP, that of sodium showed sustained phase, indicating involvement of additional humoral regulators. ANP did not stimulate the excretion of enzymic or immunoreactive tissue kallikrein.

Adult↗

Kinin receptors on epithelial cells and smooth muscle of the trachea.

Kallidin and bradykinin produce a biphasic response, contraction followed by relaxation on the isolated guinea-pig tracheal muscle. Two population of receptors appear to regulate the action of kinins on the trachea. Receptors on the epithelium seem to release chemical mediators that control the relaxation response. The question whether similar or different receptors modulate contraction of the smooth muscle may be answered by the use of appropriate antagonists. The occurrence of kinins in bronchial lavage of patients with asthma raises the question of the source of tissue kallikrein involved in the formation of kallidin. We have identified immunoreactive tissue kallikrein in the submucous glands of the trachea.

Acetylcholine↗

Presence of immunoreactive tissue kallikrein in human polymorphonuclear (PMN) leucocytes.

The presence of tissue kallikrein in polymorphonuclear (PMN) leucocytes from normal human blood and from patients with rheumatoid arthritis and pyelonephritis was investigated. Immunoreactive tissue kallikrein was specifically detected in neutrophil leucocytes. PMN leucocytes displayed a granular staining. In the synovial membrane and kidney, the cells were aggregated into pockets as part of an inflammatory infiltrate. The presence of immunoreactive tissue kallikrein in human PMN leucocytes may provide a new insight into the importance of this enzyme in inflammation.

Arthritis, Rheumatoid↗

Identification of a tissue kallikrein in human polymorphonuclear leucocytes.

We have identified a tissue kallikrein in polymorphonuclear (PMN) leucocytes of normal human blood and bone marrow by immunocytochemistry, radioimmunoassay and enzymology. Immunoreactive tissue kallikrein was visualized in the mature neutrophil leucocytes and in immature forms such as metamyelocytes and myelocytes. No tissue kallikrein was detected in eosinophil leucocytes, lymphocytes, macrophages, megakaryocytes and platelets. So far, we have failed to observe immunoreactivity to tissue kallikrein in basophils. The presence of tissue kallikrein in extracts prepared from PMN leucocytes isolated from peripheral blood was demonstrated by immunodiffusion, dot-blotting and by radioimmunoassay. The kininogenase and amidase activity of the extracts resembled that of tissue kallikrein in being resistant to soya bean trypsin inhibitor and sensitive to trasylol. The amidase activity attributable to tissue kallikrein was completely inhibited by specific antisera.

Amidohydrolases↗

A tissue kallikrein in the synovial fluid of patients with rheumatoid arthritis.

Tissue kallikrein is an enzyme that forms the vasoactive peptide kallidin from an endogenous substrate L-kininogen. Tissue kallikrein has been identified in joint fluids and in inflammatory infiltrates within synovial membranes. It is suggested that tissue kallikrein and kinins have an important role in synovitis and joint damage. Immunoreactive tissue kallikrein and amidase activity were both measured in the synovial fluid of 24 patients with rheumatoid arthritis (RA) and 12 with osteoarthritis (OA). Active enzyme concentrations were higher in RA than in OA and correlated well with the lysosomal enzymes beta-glucuronidase and lactate dehydrogenase. Both total immunoreactive tissue kallikrein and the proenzyme values were similar in RA and OA. Tissue kallikrein was localised by immunocytochemistry to the polymorphonuclear leucocytes present in the synovial fluid and membranes of patients with RA.

Adult↗

Anionic salivary proteins associated with connective tissue disorders: sialated tissue kallikreins.

Parotid saliva was collected from 32 patients with rheumatoid arthritis, 10 with systemic lupus erythematosus, three with mixed connective tissue disease, 12 with progressive systemic sclerosis, two with primary Sjögren's syndrome, and four with Raynaud's syndrome. Tissue kallikreins were measured by radioimmunoassay, and saliva samples were subjected to isoelectric focusing followed by immunoblotting or silver staining. The results showed that the saliva of patients with connective tissue diseases contained increased amounts of immunoreactive tissue kallikrein. In addition, there was an increase in the multiple forms of anionic tissue kallikreins, resulting mainly from a shift in their distribution towards that of higher sialic acid content and lower isoelectric point. These changes were most obvious in patients with systemic lupus erythematosus. Novel or unusual glycosylation may explain the occurrence of increased amounts of anionic salivary proteins in connective tissue diseases.

Adolescent↗

Modulation of guinea-pig lung adenylate cyclase by ovalbumin sensitization.

1. The regulation of lung adenylate cyclase was investigated in guinea pigs sensitized with high dose (300-500 micrograms kg-1) ovalbumin to raise IgG(I) and low dose (2.8-4.0 micrograms kg-1) to raise to IgG/IgE (II) antibodies. 2. Basal activity of sensitized II (IgG/IgE antibodies) lung adenylate cyclase was approximately double that of the control values. 3. Guanosine 5'-triphosphate (GTP) was a potent activator of adenylate cyclase from the sensitized II (IgG/IgE) lung membranes. 4. The sensitivity of lung membrane adenylate cyclase to stimulation by beta-adrenoceptor agonists or VIP was reduced whereas no significant difference was observed with histamine or bradykinin on the sensitized II membranes. 5. Possible mechanisms involved in the increase in basal activity and in the decreased sensitivity to beta-adrenoceptor- and VIP-mediated stimulation of adenylate cyclase by ovalbumin sensitization of guinea-pig lung membranes are discussed.

Adenylyl Cyclases↗