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Biomedical subjects

L H Block

Publications and source records attributed to L H Block.

At least 91 records · Page 5Linked to original sources
PubMed1982

[Immunopharmacology of corticosteroids].

Immunopharmacological effects of corticosteroids are primarily dependent upon their capacity to modify inflammatory reactions at various levels. Their molecular effects are related to the vascular system and to lymphocytes, phagocytes and mast cells, all cell types being involved in inflammation. They modulate the physiology, molecular biology and membrane dynamics of these cells thereby influencing cellular and humoral immune functions. The complexity of these effects may at least partially explain the usefulness of corticosteroids in cases of immunoproliferative, autoimmune and allergic disorders.

Adrenal Cortex Hormones↗
PubMed1982

Polymedicine: known and unknown drug interactions.

Despite more than 15 years of extensive scrutiny, adverse drug interactions, especially in the elderly, remain a problem for the clinician. A two-pronged approach is suggested to contend with drug interactions: detection or avoidance of known drug interactions; and predictions and characterization of hitherto unknown interactions. The former approach is aided by critical reference sources on the subject and the use of drug interaction screening aids such as drug interactions alert lists or rotating drug discs. Computers are becoming increasingly important not only for the detection of potential drug interactions but also for the delineation of drug therapy options. Ultimately, computers can be used to predict interactions on the basis of physiochemical, pharmacokinetic, and pharmacodynamic data. For the present, extensive epidemiologic research programs can serve to ferret out interactions. Limited accessibility to such program data bases mandates a high index of suspicion in prepared and well-informed observers if the drug interaction problem is to be dealt with.

Documentation↗
PubMed1981

Changes in tissue sensitivity to vasopressin in hereditary hypothalamic diabetes insipidus.

Specific binding of (125I) arg8-vasopressin to mononuclear phagocytes of the circulating blood was studied in 3 patients (one male, two females) with hereditary hypothalamic diabetes insipidus before, during and after therapy with 1-desamino-8-D-arginine vasopressin and compared with values of 15 normal donors (7 males, 8 females). Before therapy specific radioligand binding activity was considerably increased (0.3 +/- 0.08 fmoles/2.2 X 10(5) cells/ml) versus controls (0.23 +/- 0.04 fmoles/2.2 X 10(5) cells/ml). Increased binding was due to increase in receptor concentration per cell. In contrast, during treatment and after withdrawal of therapy the receptor binding activity was 0.1 +/- 0.05 fmoles/2.2 X 10(5) cells/ml. The dissociation constant (KD) for hormone binding before therapy (25 +/- 0.2 pM) was roughly identical with that of normal donors (24 +/- 0.8 pM), indicating insignificant changes in receptor affinity. During treatment and 48 h after withdrawal of therapy, however, the KD value was 11 +/- 0.45 pM, which amy be accounted for by an elevation in the binding affinity. We conclude that untreated patients with hereditary hypothalamic diabetes insipidus have increased tissue sensitivity to vasopressin, but have decreased binding capacity during and even two days after discontinuation of therapy, possibly as the result of 1-desamino-8-D arginine vasopressin-induced desensitization phenomena.

Adolescent↗
PubMed1981

Receptor dysfunctions in human disease.

The characterization of binding parameters of hormones and drugs to specific receptors at various human cell types have introduced an interesting approach for the evaluation of pathogenic mechanisms involved in endocrine and metabolic disorders. The dysregulation of cellular receptors in those disease include changes in receptor number, changes in binding affinity and production of antibodies against receptor molecules. It can be concluded from these observations that altered receptor physiology may be of important value for abnormalities in cellular recognition and control mechanisms which can be observed in neoplastic, inflammatory, immune and developmental diseases.

Adenylyl Cyclases↗
PubMed1981

125I-8-L-arginine vasopressin binding to human mononuclear phagocytes.

The binding of vasopressin to human circulating blood cells was examined. Direct binding studies with preparations of single cell types indicated that the mononuclear phagocyte system is almost entirely responsible for binding of the hormone. Binding of 125I-8-L-arginine vasopressin (AVP) (40 pM) in the presence of excess unlabeled hormone was saturable (2.8 +/- 0.4 fmol/2 x 10(6) cells per ml), was linear with cell number, was dependent upon the concentration of the radioligand used, and was reversible. Binding equilibrium was achieved in 30--40 min at 22 degrees C. Scatchard analysis of binding at this time showed an apparent dissociation constant of 25 +/- 0.21 pM, providing an estimate of 640 +/- 80 sites/cell. Pretreatment of the cells with cytochalasin B, an agent that can block phagocytosis, did not modify radioligand binding, which indicates that 125I-AVP uptake by the cells is due to binding and not to endocytosis. Specificity of vasopressin-sensitive sites on mononuclear phagocytes was demonstrated with a series of vasopressin analogues with various degrees of antidiuretic potency, and with peptide hormones that bind to specific receptors on circulating blood cells but that lack antidiuretic activity. AVP (40 pM) elevated the intracellular level of cyclic AMP from 137 +/- 8.6 to 350 +/- 20.5 pmol/mg cell protein. The binding affinities of the various analogues were correlated with their ability to stimulate intracellular cyclic AMP synthesis (Lys8-vasopressin less than deamino(8-D-Arg)-vasopressin less than oxytocin).

Arginine Vasopressin↗
PubMed1980

[Oxidative metabolism of phagocytes: physicochemical events and clinical relevance (author's transl)].

The microbicidal activity of phagocytes is primarily dependent upon two intracellular processes: degranulation and respiratory burst. The latter one is associated with a partial reduction of molecular oxygen leading to the production of highly reactive oxydizing agents with microbicidal activity. Since an efficiant intracellular antimicrobial function of phagocytes is mainly based on the intracellular process of fusion of lysosomes with the phagocytic vesicles and the production of highly reactive oxygen radicales, disturbances of both these events will cause increased susceptibility against microorganisms and in most of the cases severe infections.

Chemical Phenomena↗
PubMed1980

Release of endogenous pyrogen-activating factor from concanavalin A-stimulated human lymphocytes.

Evidence is presented that the mitogen concanavalin A stimulates human lymphocytes to produce a nonpyrogenic lymphokine (LK) that is capable of activating human monocytes but not granulocytes to produce endogenous pyrogen (EP) in vitro. The potency of this preparation should facilitate further studies to purify and characterize this agent and determine its relation to other know LK. It seems likely that this factor, which we have called EP-activating factor (EPAF), plays a significant role in the development of fever in states of delayed hypersensitivity in man.

Concanavalin A↗
PubMed1980

Inhibition of mitogen-induced lymphokine production by cyclosporin A.

The new antilymphocytic agent Cyclosporin A was found to inhibit the production and/or secretion of migration inhibitory factor (MIF) in human lymphocytes stimulated by Concanavalin A. Preincubation for one hour with the compound, followed by 8 hr restoration period of the cells in absence of the drug, resulted in moderate decrease in MIF synthesis and/or release. Cell viability was not affected. The agent was shown not to interfere with MIF action on the macrophage. We conclude that the molecular mechanism of action of Cyclosporin A is based, at least partially, on a blockade of synthesis and/or secretion of lymphokines from immunocompetent cells.

Concanavalin A↗
PubMed1980

[Status febrilis: humoral and cellular factors].

Clinical fever seems clearly associated with those diseases in which inflammation, in one form or other, plays a dominant role. The actual contribution of the various listed factors to the febrile response associated with any specific disease may, of course, be complex. For instance in a gram-positive infection, inflammatory cells may be activated to produce endogenous pyrogen at the site of bacterial multiplication by any or all of the following mechanisms, most of which have been demonstrated experimentally: phagocytosis of bacteria, chemotactic factors produced by bacteria or released from injured tissue of complement activation, immune reactions (either cellular or antibody-mediated) in a previously sensitized host, and toxins, e.g. endotoxins which may activate phagocytic cells directly.

Chemotaxis↗
PubMed1980

Effects of aspirin on platelet aggregation as a function of dosage and time.

There are reports on the effects of high doses of aspirin on the alteration of platelet aggregation. In our study single doses of aspirin ranging from 81 to 325 mg were given orally to 7 normal subjects. In vitro measurement of platelet aggregation was carried out as a function of time. Based on our data we conclude that low-dose aspirin (81 mg) inhibits platelet aggregation. Both the rate and extent of platelet aggregation are impaired with low-dose aspirin, but neither the rate nor extent of platelet aggregation depends on the size of the dose. Platelet aggregation inhibition by a single dose of aspirin orally (greater than or equal to 81 mg) may be expected to persist for the life of the platelets affected.

Adult↗
PubMed1979

Biological and clinical relevance of human macrophage migration inhibitory factor (MIF).

The first isolation and characterization of a lymphokine, the human MIF (MSF), and the availability of a specific MIF (MSF)-antibody provide an opportunity to establish a new parameter for detection of cellular immune mechanisms in various clinical situations. The precise estimation of quantitative amounts of MIF by sensitive immunochemical techniques could gain new insights into the pathogenesis of a number of clinical disorders. In addition, the exact detection of quantitative amounts of MIF in body fluids could have prognostic value.

Antibodies↗
PubMed1979

Neutrophil function and host resistance.

The part played by the phagocytic cells against invading pathogens has been known since the work of Metchnikoff nearly a century ago. This review deals primarily with the role of the neutrophilic polymorphonuclear leukocyte in host defense against microbial infections. The overall function of these cells in protection from infection is dependent on a number of steps. First, an adequate number of functionally mature neutrophils have to be produced and released into the circulation by the bone marrow. Cells must circulate normally and be capable of adhering to capillary and venule walls overlying inflammatory sites. The next step involves the exit of phagocytes from the blood stream through the capillary wall and emigration into the tissues to establish contact with the invading pathogens. This process is accomplished by the locomotive characteristics of these cells and chemotaxis. Most organisms must then be phagocytized to be killed. Two discrete phases are involved in phagocytosis; the "recognition" and attachment phase followed by the ingestion phase. After phagocytosis a series of coordinated morphologic and biochemical events are set into motion which leads to eventual death and lysis of the ingested microbes. A variety of antimicrobial mechanisms are involved in this final step and indicate that these cells have an appreciable reserve capacity if one mechanism is impaired. Recent evidence which clarifies mechanisms involved in all these stages is discussed.

Animals↗
PubMed1979

Fever: pathogenesis, pathophysiology, and purpose.

Fever appears to have evolved in vertebrate hosts as an adaptive mechanism for controlling infection. This phenomenon is produced by certain exogenous (largely microbial) stimuli that activated bone-marrow-derived phagocytes to release a fever-inducing hormone (endogenous pyrogen). Endogenous pyrogen, in turn, circulates to the thermoregulatory center of the brain (preoptic area of the anterior hypothalamus) where it causes an elevation in the "set-point" for normal body temperature. Warm blooded animals produced fever by increasing heat production (through shivering) or reducing heat loss (by peripheral vasoconstriction), whereas cold blooded animals do so only by behavioral mechanisms (seeking a warmer environment). This paper discusses current concepts that involve the mechanism of endogenous pyrogen production, the role of central transmittors, and the probable function of fever in combating disease.

Animals↗
PubMed1978

Nonspecific resistance to bacterial infections. Enhancement by ubiquinone-8.

A lipid fraction from Escherichia coli was extracted with apolar solvents and was found to protect mice from a number of experimental bacterial infections. The benzoquinone, ubiquinone-8, was isolated from this extract by high pressure liquid chromatography and identified as such by nuclear magnetic resonance and mass spectrometry. At a dose of 25 mg/kg this substance was found to provide complete protection against otherwise lethal infections with gram-negative and gram-positive bacteria in mice. Treatment was most effective when given intravenously 24 h before infection. In comparative studies, ubiquinone-8 had a clearly higher activity than ubiquinones-4, Q6, and Q10. A highly significant increase in the clearance rate of bacteria from the blood by the spleen and the liver of treated animals, correlated well with the protective effect of ubiquinone-8. The compound stimulated the ability of mouse macrophages to incorporate sheep erythrocytes and significantly increased the number of antibody-producing cells in spleens of mice.

Animals↗
PubMed1978

Human migration inhibitory factor: purification and immunochemical characterization.

Using gel filtration and preparative isotachophoresis, the migration inhibitory factor (MIF) was highly purified from human lymphocytes activated with concanavalin A. MIF is an acidic protein with a mol wt of approximately equal to 25,000 daltons as determined by gel filtration and analytical polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. The protein inhibits migration of macrophages in the capillary test and in addition, has a slowing effect on the electrophoretic mobility of guinea pig peritoneal macrophages. Rabbit antibodies specific for this protein, as determined by immunochemical techniques, neutralized the biological effect of MIF on migration and on the electrophoretic mobility of macrophages.

Antigen-Antibody Reactions↗