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A W Shafer

Publications and source records attributed to A W Shafer.

16 recordsLinked to original sources

Conversion of bovine growth hormone cysteine residues to serine affects secretion by cultured cells and growth rates in transgenic mice.

GHs have been found to possess two disulfide bonds. We set out to determine the importance of bovine (b) GH's disulfide bonds relative to the ability of the hormone to be secreted by cultured cells in vitro and to promote growth in transgenic mice. We have generated six mutated bGH genes that encode serine (Ser) substitutions for cysteines (Cys). These mutated genes were used to generate bGH analogs in which either one or both disulfide bonds are destroyed. When the small loop of bGH was destroyed (Cys181-Ser or Cys189-Ser), the bGH analogs were found to be secreted by mouse L-cells at levels comparable to those of wild-type bGH. However, secretion was drastically reduced when the large loop was abolished (Cys53-Ser or Cys164-Ser). An immunofluorescence study of these bGH analogs revealed two distinct patterns of subcellular localization. Bovine GH analogs with mutations in the small loop demonstrated a perinuclear distribution similar to that of wild-type bGH, but analogs containing a disrupted large loop revealed a uniform cytoplasmic distribution pattern. When these mutated bGH genes were individually introduced into transgenic mice, only those animals that expressed bGH analogs with the large loop intact demonstrated a growth-enhanced phenotype. Transgenic mice that expressed bGH analogs lacking the large loop showed growth rates similar to those of nontransgenic mice. These results suggest that the integrity of the large loop, but not that of the small loop, is essential for the growth-enhancing activity of bGH in transgenic mice.

Amino Acid Sequence

Hazardous donors.

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Blood Donors

Use of blood and blood components.

The indications for transfusions are anemia compromising delivery of oxygen, acute blood loss, cardiopulmonary bypass, exchange transfusion, maintenance of hemostasis, and sepsis associated with granulocytopenia. When transfusion therapy is indicated, only that component of whole blood which is needed for correction of the problem should be given. The options for use each component have been discussed.

Acute Disease

Acute changes in oxyhemoglobin affinity. Effects on oxygen transport and utilization.

It has been postulated that 2,3-diphosphoglycerate (DPG)-mediated changes in oxyhemoglobin affinity play an important role in oxygen delivery; however, the effect of an acute increase in affinity without changing red cell mass has not been systematically evaluated. This study was designed to measure changes in oxygen transport and oxygen consumption produced by an acute increase in oxyhemoglobin affinity caused by an autologous exchange transfusion using DPG-depleted stored blood. From each of 10 5-kg rhesus monkeys, 100 ml of blood was taken on the 1st and 3rd wk of the study and each stored in 25 ml of acid-citrate-dextrose storage solution. On the 5th wk, each animal underwent an exchange transfusion with 200 ml of its stored blood. Hemodynamic data were obtained before and 30 min after transfusion. The oxyhemoglobin dissociation curve shifted to the left (P(50) changed from 33.9 to 27.2 mm Hg), as mean red cell DPG decreased from 28.6 to 12.7 mumol/g of hemoglobin. No significant change was noted in pH, P(CO2), base deficit, arterial or venous percent saturation of hemoglobin, cardiac output, or oxygen consumption. However, a fall in mixed venous P(O2) from 35.3 to 27.9 mm Hg occurred.Thus, an acute shift of the oxyhemoglobin curve to the left was accompanied by a significant decrease in the mixed venous P(O2) without evidence of acidosis, decreased oxygen consumption, or a compensatory increase in cardiac output.

Acid-Base Equilibrium

Metabolic and morphological observations on the effect of surface-active agents of leukocytes.

Morphological and metabolic observations have been made on the effects of endotoxin, deoxycholate, and digitonin (at less than 50 microg/ml) on polymorphonuclear leukocytes and mononuclear cells. The agents stimulate the respiration and glucose oxidation of these cells in a manner similar to that seen during phagocytosis. Electron microscopy revealed no morphological changes with the first two agents, but dramatic membrane changes were seen in the case of digitonin. Here tubular projections of characteristic size and shape formed on and split off the membrane. All the agents stimulated uptake of inulin, but efforts to demonstrate increased pinocytosis by electron microscopy have not so far succeeded, probably due to limitations in present experimental techniques.

Animals

Etiology of leukemia. A review.

A variety of factors probably are etiologically involved in leukemia, not only in different cases but also within individual cases. Abnormalities of chromosomes have been found in various types of leukemia. Whether these chromosomal alterations are primary or secondary is undetermined, but it is likely that they are at least contributory in the development of leukemia. There is an increasing body of evidence incriminating viruses in leukemogenesis in man, and they may be a factor in all cases. Certain chemicals may be important etiologic factors in a few cases. Many different studies have established that ionizing radiation in large doses may be leukemogenic. Whether small doses of irradiation are dangerous has not been demonstrated.

Chromosome Aberrations

Priapism during filtration leukapheresis.

Priapism has been observed during two out of 3,680 filtration leukapheresis procedures in male donors and has been reported during hemodialysis. Both procedures are associated with enhanced granulocyte adhesion and aggregation presumably due to C5a. During both procedures, heparin is administered and this drug has been shown to cause heparin-dependent anti-platelet antibodies. It is suggested that complement mediated venous leukostasis or immune-induced platelet aggregates might impair the normal blood flow from the penis and result in a state of priapism.

Adult

Broadening the base of a rare donor program by targeting minority populations.

Some red cell phenotypes are found exclusively in one race and may be of low frequency. Finding compatible blood for patients needing one of these rare types has been extremely difficult. A program was implemented to screen large numbers of donors for blood types found solely in their racial group. Implementation steps included obtaining broad community endorsement of the concept, educating blood service personnel, developing educational materials, enlisting the support of a knowledgeable physician from a minority group, developing a computer program to facilitate selection of donors to be tested, beginning the program and making the necessary adjustments, doing the laboratory testing to identify rare bloods, notifying the rare donors, and maintaining the enthusiasm of the entire blood service for the rare donor screening program. After 7706 black donors were typed, 1 Cr-, 5 Hy-, 24 U-, and 20 Js(b-) persons were found; one U- donor was also Js(b-).

Black People