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Biomedical subjects

L H Block

Publications and source records attributed to L H Block.

10 recordsLinked to original sources

Atherosclerosis, cell motility, calcium, and calcium-channel blockers.

Three key players in the humoral-cellular interactions that occur during the early development of atherosclerosis are presented as they activate platelets and vascular smooth muscle cells but eventually can be corrected by calcium-channel blockers. Platelet-activating factors via phospholipase C and phosphoinositides increase cytosolic calcium and phosphorylate contractile proteins, thereby inducing a change--aggregation and the secretory response of platelets. Low-density lipoprotein (LDL) has a similar hormone-like action and activates the signal transfer cascade that eventually leads to platelet aggregation as well as vascular smooth muscle cell proliferation. These effects can be greatly reduced by high-density lipoproteins. Platelet-derived growth factor stimulates the transcription of the LDL-receptor gene as well as the HMG-CoA reductase gene. The latter is inhibited by calcium-channel antagonists while the former is further enhanced. Thus, calcium-channel antagonists interfere with the stimulus-response coupling not only via slow calcium-channel influx inhibition but also by an additional membrane action and interference with gene activation.

Arteriosclerosis

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

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

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

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

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

Aqueous solubility of 14C-triamcinolone acetonide.

The blue tetrazolium colorimetric assay has often been employed in the analysis of corticosteroids. However, the reaction between blue tetrazolium and corticosteroids partly depends on the apparent pH of the system. In an earlier study of the temperature dependence of the solubility and dissolution of triamcinolone acetonide in aqueous dissolution media (distilled water and 0.2-1.0 M potassium chloride solutions), pH was not considered. To determine the reliability of the data previously reported, the solubility of 14C-triamcinolone acetonide was determined by a radioisotopic method. The results of the analyses, using a liquid scintillation counting system, indicate that the steroid solubility is generally about 20% lower than that reported previously.

Carbon Radioisotopes