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Biomedical subjects

W R Beisel

Publications and source records attributed to W R Beisel.

32 records · Page 2Linked to original sources

Sequential changes in the concentration of specific serum proteins during typhoid fever infection in man.

An automated immunoprecipitin system has been utilized to quantitate the concentration of 10 specific proteins in the plasma of man. Values obtained by this technique are in agreement with the published concentrations for these specific plasma proteins. This technique was utilized to determine the sequential change s in 10 individual plasma proteins of volunteers exposed to Salmonella typhi. In those volunteers who developed typical typhoid fever, plasma concentrations of the acute phase proteins, alpha1-acid glycoprotein, alpha1-antitrypsin, and haptoglobin, as well as C3 complement were significantly increased with the onset of febrile illness. In contrast, the concentration of plasma albumin and tranferrin were depressed while plasma IgM became elevated during early convalescence from this infection. No significant changes were observed in the plasma concentrations of alpha2-macroglobulin, IgG, or IgA. In the exposed volunteers who did not become ill, the only significant change was a brief depression of alpha1-antitrypsin. During typhoid fever the patterns of change for individual plasma acute-phase globulins were different from those reported for patients with hepatitis, myocaridal infarction, or surgery.

Adult

Marylanders defeat Philadelphia: yellow fever updated.

Those strategic points which influence this amateur historian to declare a victory for Baltimore and Maryland over Philadelphia are: I. Based upon clinical and epidemiological data, two Marylanders, Potter and Davidge, were among the first to contest Rush and his contagion theory; they told him so and published their views. To prove this point, Potter went to the extreme of inoculating himself with presumedly infected material. Stubbins Ffirth, a young University of Pennsylvania medical student, did the same four years later. To Rush's credit was ultimate abandonment of his originally held views. II. John Crawford, of Baltimore, although not the originator of the insect concept of transmission of infectious agents, published his concepts in 1811. III. Henry Rose Carter, a Maryland graduate, clearly delineated, in 1898, that after identification of an index case of yellow fever an extrinsic incubation period was necessary before the evolution of secondary cases. IV. James Carroll, another University of Maryland graduate, who worked as Deputy under Walter Reed with Lazear and Agramonte, helped prove Finlay's original concept that the Aedes aegypti mosquito was the natural vector of yellow fever. Carroll himself was the first experimentally induced case. V. Studies in primates provide new approaches for management of yellow fever. Nutritional support and treatment with specific anti-viral agents may be useful for therapy of human yellow fever. Maryland members of the Climatological are mindful of Philadelphia's rich medical heritage and of the many battles won in the City of Brotherly Love. Physicians in colonial and early America experienced The best and worst of times, theirs was an age of foolishness and belief, of incredulity and light, of darkness, despair and hope. This tale of two cities ends in peace.

Animals

Changes in blood pH in rats after infection with Streptococcus pneumoniae.

Acid-base alterations in Streptococcus pneumoniae infection were studied in 80 male albino rats. Hematocrit and concentrations of plasma electrolytes, glucose, and total protein were also measured. At 3-h intervals throughout a 27-h study, four control and four infected rats were anesthetized with ether, and blood samples were taken. Arterial blood pH, Po2, and hematocrit increased in the infected group, whereas arterial Pco2, HCO3-, and venous Po2 decreased. Plasma K+ concentration increased slightly and glucose levels decreased in the infected rats as the sepsis progressed. No significant changes were observed in venous blood pH, HCO3-, and Pco2. Plasma Na+, Cl-, and total protein remained unchanged. The increase in arterial blood pH and decrease in arterial Pco2 and HCO3- indicated respiratory alkalosis, which was present in rats infected with S. pneumoniae.

Acid-Base Equilibrium

Detection of a leukocytic endogenous mediator-like mediator of serum amino acid and zinc depression during various infectious illnesses.

Serum samples from patients with many different kinds of infection were shown to contain a substance characteristic of leukocytic endogenous mediator. Generalized bacterial infections produced more leukocytic endogenous mediator than did localized ones; viral infections produced very little. In typhoid fever, mediator concentrations increased before the onset of illness.

Abscess

Metabolic response to infection.

A generalized infectious process leads to a broad and complex array of metabolic responses within the host. Certain of these responses have a direct causal relationship to the interactions of body cells with invading microorganisms or their products, or to specific host defensive mechanisms. Other host metabolic responses have less clearly defined roles although they involve many tissues and seem to be initiated and regulated by certain hormones-like endogenous mediators. These latter responses contribute to the maintenance of body homeostasis, the provision of metabolizable energy to meet increased body needs, and the synthesis of the acute phase reactant serum proteins.

Amino Acids

A protein from polymorphonuclear leukocytes (LEM) which affects the rate of hepatic amino acid transport and synthesis of acute-phase globulins.

A proteinaceous secretion from phagocytizing polymorphonuclear leukocytes, termed "leukocytic endogenous mediator" (LEM), has been shown to have marked effects on hepatic amino acid transport and RNA and protein synthesis. A single injection of LEM results in a marked accumulation of labeled nonmetabolizable model amino acids in the liver of normal rats. The LEM-stimulated uptake of amino acids by liver was observed in adrenalectomized, hypophysectomized, thyroidectomized, or diabetic rats and could not be duplicated by pharmacological doses of a large variety of hormones. In addition, LEM stimulated an increased uptake of alpha-aminoisobutyric acid by isolated livers during their perfusion in vitro. LEM also stimulated an increased incorporation of orotic acid into hepatic RNA of intact rats, especially into the bound ribosomal fraction. This increased synthesis of RNA preceded an enhanced hepatic production of a number of the acute-phase plasma globulins. LEM did not stimulate the adenylate cyclase-cAMP system in liver and was not found to utilize this system as a second messenger. Thus, the effects of LEM in stimulating hepatic amino acid transport appear to be direct, without mediation by other hormones, and to be independent of cAMP. On the other hand, the ability of LEM to stimulate RNA and acute phase globulin synthesis in liver may require the presence of physiological quantities of hormones such as adrenal corticoids.

Adenylyl Cyclases

Relationship between serum chromium concentrations and glucose utilization in normal and infected subjects.

Studies in healthy individuals demonstrate that serum chromium concentrations fall precipitiously following the intravenous administration of a 30-gm. glucose load. Significant decreases from baseline control fasting serum Cr concentrations were also observed when intravenous glucose was given during sandfly fever. Glucose disappearance rates also decreased significantly to approximately one half of pre-illness control values while serum Cr values declined still further. In addition, serum Cr disappearance rates could be calculated. When individual preexposure and postexposure serum glucose and Cr disappearance rates were compared, significant linear correlation was found (P smaller than 0.05). Acute infection appears to reduce the availability of circulating Cr, which may contribute to the altered glucose metabolism characteristic of acute infections even in the presence of elevated insulin levels and other hormonal changes.

Acute Disease

Mechanisms of oral staphylococcal enterotoxin B-induced emesis in the monkey (38553).

Vomition is the most consistent response to oral SEB challenge in the monkey. The technique of cross-circulation clearly differentiates local neural phenomenon from humoral mechanisms. Our results support the theory that SED-induced vomition follows stimulation of local neural receptors in the gut. The evidence indicates no significant amount of enterotoxin absorption or stimulation of vomition by any centrally acting humoral mechanism.

Administration, Oral

Serum zinc, iron, and copper concentrations during typhoid fever in man: effect of chloramphenicol therapy.

In volunteers experimentally infected with Salmonella typhi, serum iron and zinc concentrations became significantly depressed and there was a concomitant rise in serum copper before the onset of overt clinical illness. However, after several days of fever and the initiation of chloramphenicol therapy, serum iron and zinc concentrations significantly increased. Additional studies--in volunteers with typhoid fever treated with chloramphenicol, in a volunteer with typhoid fever receiving cefazolin and gentamicin, and in untreated rhesus monkeys infected with Salmonella typhimurium--provided evidence that the increase in serum iron concentration during the febrile phase was the result of chloramphenicol therapy, whereas the increase in serum zinc concentrations was a disease-related phenomenon. The importance of trace-metal monitoring during infectious disease and chemotherapy is discussed.

Adult

Tryptophan metabolism in relation to amino acid alterations during typhoid fever.

With the onset of fever in volunteers exposed to virulent Salmonella typhii as part of a vaccine evaluation study, urinary excretion of kynurenine, acetyl-kynurenine and o-amino-hippurate significantly increased by N-methylnicotinamide decreased. Serum tryptophan concentration at that time was 116% of control in contrast to total serum amino acid values at 83% of control. A 3 gram oral tryptophan load given during illness further increased serum tryptophan concentration to 186% of control and enhanced excretion of the aforementioned catabolites. In addition, urinary anthranilate glucuronide, kynurenate and xanthurenate rose significantly; 3-hydroxykynurenine increased only slightly and N-methyl-nicotinamide was unaltered. Thus, though a tryptophan load aids in detection of alterations in tryptophan catabolism via the kynurenine pathway as a whole, it also distorts the pattern of metabolites detected, seemingly by causing more kynurenine to be shunted to the mitochondria to be acted upon by kynurenine 3-hydroxylase and kynurenine aminotransferase. In unloaded patients the increased urinary excretion of tryptophan metabolites during typhoid fever merely reflect the enhanced flux of amino acids from muscle to liver, akin to that noted in other infections, in excess of that needed for the synthesis of serum proteins or for other metabolic pathways.

Amino Acids