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Biomedical subjects

M M Khan

Publications and source records attributed to M M Khan.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effects of glucose transport on the incorporation of 32P-inorganic phosphate into phospholipids in Hymenolepis diminuta (Cestoda).

1. The absorption of glucose and alpha-methyl-D-glucoside by Hymenolepis diminuta was concentration dependent. 2. alpha-Methyl-D-glucoside competitively inhibited glucose absorption and was not metabolised by the parasite. 3. alpha-Methyl-D-glucoside significantly lowered (P less than 0.05) the incorporation of 32Pi into all phospholipid classes. 4. Glucose inhibited (P less than 0.01) 32Pi incorporation into phosphatidylcholine only. 5. Phlorizin did not affect 32Pi labelling of phospholipids. 6. Serotonin and histamine stimulated (P less than 0.01) 32Pi labelling of all phospholipid classes. 7. Radioactivities in water soluble fractions were increased (P less than 0.01) in the presence of glucose, serotonin and histamine.

Animals↗
PubMed1987

Congener derivatives and conjugates of histamine: synthesis and tissue and receptor selectivity of the derivatives.

A series of 19 congener derivatives and conjugates of histamine was synthesized and tested to determine whether the ligands would alter the conventional histamine activity in various tissues. The derivatives, which contained either branched or unbranched aliphatic groups, aromatic amide groups, or dipeptides, exhibited affinities for histamine type 1 and/or type 2 receptors that were widely different from the progenitor. The p-trifluoromethyl derivative of histamine with an intermediate chain length of four methylenes (compound 13) was the most potent lymphocytes H2 receptor agonist but was inactive on guinea pig myocardium H2 receptors. The deletion of a single methylene chain (compound 12) from this compound resulted in total loss of its H2 activity on lymphocytes and its H1 activity on aorta. Compound 12 became an exclusive H1 agonist on lymphocytes H1 receptors. The dipeptide conjugate (compound 17) and the aliphatic congener derivative (compound 18), both with four methylenes, retained some of the activity on guinea pig myocardium H2 receptors, but lost their activity on lymphocytes H2 receptors. Therefore, histamine can be modified at sites that are at a distance from the imidazole moiety, resulting in tissue selective histamine receptor agonists.

Animals↗
PubMed1987

Conjugates of catecholamines. VII. Synthesis and beta-adrenergic activity of peptide catecholamine conjugates.

A series of novel catecholamine derivatives has been prepared in which one of the N-methyl substituents of isoproterenol has been extended by a spacer consisting of a chain of four methylenes which terminates with an amide linkage to a peptide, the point of attachment being via the aromatic amino group of p-aminophenylalanine. In one of the derivatives, two catecholamines are attached to the same peptide in this manner. The peptides, which range in size from three to eight amino acid residues and contain phenylalanine, glycine, and L-alpha-amino-delta-hydroxyvaleric acid, were synthesized via stepwise and fragment condensation techniques. The beta-adrenergic agonist activities of the derivatives were evaluated in vitro by measuring the intracellular accumulation of cyclic AMP in S49 mouse lymphoma cells.

Adrenergic beta-Agonists↗
PubMed1986

High potency congeners of isoproterenol. Binding to beta-adrenergic receptors, activation of adenylate cyclase and stimulation of intracellular cyclic AMP synthesis.

The potency of a p-toluide derivative and a p-trifluoromethyl derivative of isoproterenol on the beta1 receptor of turkey erythrocytes and on the beta2 receptor of S49 lymphoma cells was measured in comparison with isoproterenol. Binding assays showed that the p-trifluoromethyl derivative possessed an affinity for the receptor, which was two hundred times higher than that of isoproterenol, in the case of turkey erythrocytes, and sixty times higher in the case of the S49 cells. By measuring the Kact of adenylate cyclase, the activity of the p-trifluoromethyl derivative was thirty to forty times higher than that of isoproterenol for the turkey erythrocyte membrane as well as for the S49 lysed cells. In stimulation of intracellular cyclic AMP accumulation, the Kact showed that the p-trifluoromethyl derivative was forty and twenty times more active than isoproterenol in turkey erythrocytes and in S49 cells, respectively. The p-toluide derivative gave similar results. The superior affinity of the above isoproterenol congeners for both beta 1 and beta 2 adrenergic receptors makes these compounds excellent candidates for use as labeled agonist ligands in studies of beta receptors. The possibility is discussed that the relatively large substituent on the amino group of the catecholamine congeners might perhaps bind to lipids associated with the receptor.

Adenylyl Cyclases↗
PubMed1986

The effects of derivatives of histamine on natural suppressor cells.

Histamine is an impressive modulator of immune functions at least via its effects on lymphoid cells. Its in vivo effects will not be used practically as long as they produce the profound cardiovascular and pulmonary effects for which the drug is known. A series of 13 congener derivatives and conjugates of histamine was constructed and was tested to investigate whether chemical alterations would result in pharmacologic actions on leukocytes that were more potent and effect specific than histamine. The new compounds, which contained spacer groups of varying lengths between ligand and carrier and with various aromatic modifying groups, showed potencies widely different from histamine when tested in natural suppressor cells. Some compounds showed selective effects on natural suppressor cells in that they were inactive on myocardial tissue, whereas other compounds were selectively active on the myocardium. Some compounds augmented the suppressive capacity of natural suppressor cells in mixed leukocyte reactions via H1 receptors. Our scheme might be more widely extrapolated to other low m.w. immune modulators in an attempt to make them lymphocyte specific. The data also encourage the in vivo testing of selected histamine analogues as selective modulators of immunity. Some of these modulators might be experimentally useful in vivo because they may lack actions in other tissues.

Adenylyl Cyclases↗
PubMed1986

Beta-adrenergic receptors on human suppressor, helper, and cytolytic lymphocytes.

Using the radioligand beta-adrenergic blocker [125I]cyanopindolol (ICYP), we have characterized the beta-adrenergic receptors on Leu 3+ (T helper [TH]), Leu 2+, 9.3- (T suppressor [Ts]) and Leu 2+, 9.3+ (T cytolytic [Tc]) subsets of human lymphocytes. Peripheral blood T cells were isolated by rosetting, and then subsets were purified by their affinities to monoclonal antibodies against their Leu 3 and 9.3 markers. ICYP binding to the subsets was saturable with time and with concentration; the binding was stereoselective and reversible by beta-adrenergic antagonists. A biological response produced by beta agonists increased intracellular concentrations of cAMP and corresponded to the number of binding sites. Each subset of cells had a number of binding sites, which was characteristic for the given subset. The data indicate that the density of distribution of beta-adrenergic receptors was not homogeneous on the precursors of phenotypically and functionally distinct T cells (Ts approximately 2900, Tc approximately 1800 and TH approximately 750 binding sites). The displacement studies using beta-adrenergic agonists were performed on the cytolytic and suppressor T cell subsets, suggesting that the receptors were mainly of the beta-2 type. The immunobiological significance of such selective distribution of numbers and subtypes of beta-adrenergic receptors on distinct T cell subsets is under investigation.

Epinephrine↗
PubMed1986

Regulatory effects of mast cells on lymphoid cells: the role of histamine type 1 receptors in the interaction between mast cells, helper T cells and natural suppressor cells.

We have investigated the role of mast cells as modulators of lymphocyte function because the mast cells are concentrated in the areas of lymphoid storage; they are dependent upon T-cell growth factor for their proliferation; and they appear to be the principle if not sole storage site for histamine. We have tested the influence of mast cells on the proliferation of alloreactive cloned helper T cells, mixed leukocyte reactions, and the suppressive capacity of natural suppressor cells. We used an IL-3-dependent mast cell line that at high numbers (greater than 10(5)) suppressed and at low numbers (10(3) to 6 X 10(4)) augmented the proliferation of TH cells. Addition of histamine to cocultures enhanced the mast cell mediated proliferation of TH cells without directly affecting the helper cells. The action of histamine appeared to be mediated with H1 type receptors on these mast cells. Pretreatment of natural suppressor cells with supernatants from mast cell enhanced their suppressive capability. Here too, histamines enhanced suppression by the NS cell via histamine type 1 receptors on the natural suppressor cells. Our data suggest that mast cells may be a major modulator of the lymphoid cell immune function and demonstrate a role of histamine type 1 receptors in the interaction between mast cells, helper T cells, and natural suppressor cells.

Animals↗
PubMed1986

Heart failure associated with infective endocarditis. A review of 40 cases.

Thirty one (78%) of 40 consecutive patients (aged 13-79, mean 44 years) with infective endocarditis had congestive heart failure at presentation. Twenty six (65%) had had rheumatic heart disease and 17 (43%) patients had prosthetic valves. Eight (20%) patients had undergone dental procedures within three months of presentation. Blood cultures were positive in only 22 (55%) of the patients. In nine (41%) of them streptococci of the viridans group were isolated and in seven (32%) patients endocarditis was due to Staphylococcus aureus. Eight patients had Q fever endocarditis. Sixteen patients required operation because of haemodynamic deterioration while they were in hospital; 11 patients had native valves and five had prosthetic valves. Seven had emergency operations and were pyrexial at that time. Four of the seven died in hospital. Of the 12 who were alive and well after surgery only two required further surgery two and three years after the initial operation. Twelve (30%) of the 40 patients died in hospital; in 10 death was mainly due to left ventricular failure or congestive heart failure. All patients died who had renal failure (four cases), myocardial infarction (two cases), complete heart block (one case), or ventricular fibrillation (two cases) before operation. Six (33%) of the 18 patients with culture negative endocarditis died. Two of the four patients seen and treated more than 12 weeks after the onset of symptoms died, as did three of the five patients with prosthetic valves who required surgery while in hospital. Three patients with neurological complications survived and only two (29%) of the seven patients with blood cultures that were positive for Staphylococcus aureus died. Of these 40 high risk patients optimal antibiotic treatment and early surgery for haemodynamic difficulty ensured that 28 (70%) were discharged from hospital alive and well.

Adolescent↗
PubMed1986

High dose intravenous streptokinase in acute myocardial infarction--short and long term prognosis.

Streptokinase (1 million international units) was given intravenously over 30 or 60 minutes to 50 patients four hours or less after the onset of acute myocardial infarction. All were aged less than or equal to 70 years and had 4 mm or greater ST segment elevation in anterior or inferior leads. Rapid (mean 95 min) ST segment resolution, which was taken to indicate reperfusion of the myocardium, occurred in 36 (72%) patients. In these 36 the average time from onset of symptoms to peak creatine kinase, creatine kinase MB, and myoglobin was 9.45 hours, whereas it was 17 hours in the 14 patients in whom indirect criteria did not indicate reperfusion. Reperfusion arrhythmias were invariably present and ventricular tachycardia developed in five patients and ventricular fibrillation in two. The infarct related artery was seen to be open in 28 (70%) of the 40 patients who had delayed coronary arteriography. The frequency of patency in the infarct related artery was no different in patients given streptokinase less than 2 hours or between 2-4 hours from onset of symptoms nor did it differ when streptokinase was infused over 30 or 60 minutes. Mean left ventricular ejection fraction was 57% in those with a patient infarct related artery and 48% in those with an occluded vessel. Eight patients subsequently underwent elective percutaneous transluminal coronary angioplasty after successful thrombolysis and six had coronary artery bypass grafting. There were nine in-hospital reocclusions of the infarct related coronary arteries. Two bleeding episodes occurred; one required transfusion. Five of the 50 patients died in hospital. All of them had had an anterior myocardial infarction; four had bifascicular block and one had right bundle branch block. During follow up, four patients died, two suddenly and two from reinfarction. During follow up (mean 15 months) the frequency of reinfarction, dyspnoea, and angina was low and there was no difference in the proportions of patients returning to work between those with an open infarct related artery and those with a closed infarct related artery. Intravenous administration of high dose streptokinase to selected patients during the acute phase of myocardial infarction is a safe, effective, and practical method of thrombolysis. It must, however, be followed by coronary arteriography to select those patients in whom percutaneous transluminal coronary angioplasty or coronary artery bypass grafting will be helpful.

Adult↗
PubMed1985

Immunoregulatory T cells in man. Histamine-induced suppressor T cells are derived from a Leu 2+ (T8+) subpopulation distinct from that which gives rise to cytotoxic T cells.

One mechanism of histamine-mediated inhibition of the immune response in man is to activate T suppressor cells that bear the Leu 2 (OKT8) marker. The current study was undertaken to characterize the histamine-induced suppressor cell using a monoclonal antibody (9.3) shown previously to distinguish cytotoxic T cells from antigen-specific suppressor T cells. Leu 2+ cells isolated from peripheral blood were further separated with antibody 9.3 into Leu 2+, 9.3+, and Leu 2+, 9.3- subsets and each subset was incubated with different concentrations of histamine before determining their ability to suppress immune responses in vitro. The results indicate that the Leu 2+, 9.3- subpopulation includes all histamine-induced suppressor cells, that 10(-4) M histamine is the optimal concentration for suppressor cell induction, and that exposure of Leu 2+, 9.3- cells to histamine for 30 s is sufficient to initiate the induction process. After treatment with histamine these cells inhibit both phytohemagglutinin-induced T cell proliferation and pokeweed mitogen-induced B cell differentiation. The suppression of phytohemagglutinin-induced proliferation was resistant to x-irradiation with 1,200 rad, either before or after histamine exposure, suggesting that Leu 2+, 9.3- cells need not proliferate to become suppressor cells or exert suppression. Moreover, suppression by these cells was not due to altered kinetics of the response. Finally, a histamine type 2 receptor antagonist (cimetidine) but not a type 1 receptor antagonist (mepyramine) blocked the induction of suppressor cells. On the basis of these results and our previous studies of antigen specific suppressor cells, we conclude that Leu 2+ suppressor cells in man are derived from a precursor pool that is phenotypically distinct from cells that can differentiate into cytotoxic T cells.

Antibodies, Monoclonal↗
PubMed1985

Pharmacologic effects of autacoids on subsets of T cells. Regulation of expression/function of histamine-2 receptors by a subset of suppressor cells.

Autacoids (principally histamine, beta adrenergic catecholamines, and prostaglandins E and A) have only recently been recognized as substantive moderators of a number of immune functions. If autacoids are to be considered as potential therapeutic immunomodulators, it is necessary to understand their effects on subsets of T cells while they are and are not in contact with each other. This report demonstrates that autacoid receptors are nonrandomly distributed on phenotypically and functionally distinct subsets of human T cells. Each human T cell subset responded to both histamine and isoproterenol, but the dose response curve and maximal efficacy varied widely between the subsets. The suppressor T cells were more responsive to both histamine and isoproterenol than helper/inducer T cells (TH) or cytotoxic T cells (Tc). We found that after mitogenic stimulation the response to histamine, but not isoproterenol, was greatly increased only in TH (Leu 3+) and Tc (Leu 2+, 9.3+) subsets, and that this effect may be regulated by suppressor T cells (Leu 2+, 9.3-). The dramatic rise in cAMP accumulation in response to histamine in mitogen-treated TH and Tc was totally blocked by an H2 antagonist (cimetidine), but not by an H1 antagonist (mepyramine). These findings indicate interdependence of (a) immunologically uncommitted subsets in their response to selected drugs, and (b) control of basal- and autacoid-induced cAMP production, as well as (c) increased qualitative and quantitative selectivity, which is caused by mitogen. If we had performed these experiments only on unseparated cells we would not have observed the remarkable selectivity of autacoid effects on subsets of T cells.

Autacoids↗
PubMed1985

The effects of autacoids on cloned murine lymphoid cells: modulation of IL 2 secretion and the activity of natural suppressor cells.

The pharmacologic effects of histamine and isoproterenol (autacoids) were studied on clones of murine T helper (TH) and natural suppressor (NS) cells. The data are consistent with receptors for the autacoids being nonrandomly distributed on phenotypically and functionally distinct clones. The effects of histamine on IL 2 secretion by TH cells could be either inhibitory or stimulatory, depending on the conditions of incubation with the autacoid. When TH cells were pretreated with histamine, their secretion of IL 2 was augmented; conversely, if histamine was added to the TH cells in the presence of antigen, IL 2 secretion was inhibited. The suppressor function of NS cells was enhanced by preincubation with histamine (10(-4) M) for 4 hr before the washed NS cells were added to responder and stimulator cells in mixed lymphocyte cultures. Two H1 receptor antagonists, mepyramine (10(-6) M) and pyrobutamine (10(-7) M), each competitively blocked the histamine activation of the NS cells, but an H2 receptor antagonist cimetidine (10(-5) M) did not alter the suppressor-enhancing function of histamine. Activation of NS cells did not occur if histamine was added with responder, stimulator, and co-cultured cells in MLR. The effects of each autacoid were additive in cytolytic T cells alone. The adenylate cyclase pools that can be stimulated by isoproterenol and histamine in cytolytic T cells may be independent of each other, but further work will be needed to prove this point.

Animals↗