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Biomedical subjects

J S Thompson

Publications and source records attributed to J S Thompson.

At least 343 records · Page 19Linked to original sources

Structural and electronic mimics of the active site of cobalt(II)-substituted zinc metalloenzymes.

Complexes of cobalt(II) and zinc(II) which involve monodentate coordination of two alkyl carboxylate and two imidazole ligands in a slightly distorted tetrahedral fashion have visible and magnetic circular dichroism spectra remarkably similar to the cobalt(II)-substituted proteolytic enzymes thermolysin and carboxypeptidase A. Single crystal x-ray structure determinations on [Co(C2H5COO)2Im2], Im = imidazole, and its zinc counterpart reveal only minor structural differences between the cobalt and zinc species. Electron paramagnetic resonance spectra of cobalt(II) doped into zinc(II) complexes with known structures demonstrate the extreme sensitivity of the g-values to minor structural differences.

Binding Sites↗

Structure and function of carboxypeptidase A alpha in supercooled water.

The spectral and enzymatic characteristics of chromophoric derivatives of carboxypeptidase A alpha (EC 3.4.17.1) have been examined at subzero temperatures in supercooled water-in-oil emulsions. Substrate and temperature dependencies of enzyme kinetics indicated the existence of a solution-like enzyme phase that greatly extends the temperature range (greater than 60 degrees C) over which the activity of this enzyme can be measured. The emulsion spectra were virtually identical to those of solutions over a wide range of temperatures. Subzero temperatures (less than -10 degrees C) may induce changes of enzyme conformation but not of geometry at the site of the metal atom, nor do they adversely affect activity at any of the temperatures studied. Both structure and function of carboxypeptidase A alpha can be examined in supercooled water under identical reaction conditions.

Carboxypeptidases↗

The evolution of abdominal stab wound management.

The results of the selective management of 300 abdominal stab wound victims have been reviewed for a 5-year period. Initially the need for laparotomy was evaluated by sinography, later physical examination, and most recently by local wound exploration combined with peritoneal lavage. The use of sinography resulted in an unnecessary laparotomy rate of 38%. Exploration based upon physical findings eventuated in 36% unnecessary laparotomies, of which 79% were negative, 17% morbidity, and no mortality. Local wound exploration followed by peritoneal lavage when peritoneal violation was suspected resulted in 8% unnecessary laparotomies of which half were negative, 9% morbidity, and no mortality. Based on this experience we have adopted the following approach to abdominal stab wounds. Patients with unexplained blood loss or overt signs of visceral injury undergo prompt exploration. In all other cass with intact peritoneum are discharged from the Emergency Department. If peritoneal violation is evident peri toneal lavage is performed. If the lavage is positive laparotomy is undertaken, and if negative the patient is hospitalized for an additional 24 hours of observation.

Abdominal Injuries↗

Effect of intermittent-flow centrifugation leukapheresis on donor leukocyte counts.

Effects of intermittent-flow centrifugation leukapheresis (IFCL) on leukocyte counts in donor blood have not been reported. Accordingly, total and differential white blood cell counts were preformed serially during IFCL. A significant decrease (p less than 0.05) in all types of leukocytes occurred in donor blood early in pheresis and was probably the consequence of hemodilution. Concentrations of most leukocyte types remained decreased throughout the procedure, and a rebound leukocytosis was not detected. Thus, leukocyte kinetics in donor blood during IFCL differ from those reported for filtration leukapheresis in which the pattern of selective neutropenia followed by rebound neutrophilia has been ascribed to complement activation.

Centrifugation↗

New granulocyte antigens demonstrated by microgranulocytotoxicity assay.

Although granulocyte transfusions and bone marrow transplantation are becoming common clinical modalities, our knowledge of surface nonerythroid, nonlymphoid, non-HLA hematopoetic antigens remains very incomplete. Accordingly, we have systematically screened sera from recipients of multiple granulocyte and whole blood transfusions, and immunoneutropenic patients for antibodies directed primarily at granulocytes. The initial screens demonstrated that >50% of the sera from the above sources contained non-HLA cytotoxic and/or agglutinating antibodies. Preliminary clustering indicated seven possible new specificities detected by microgranulocytotoxicity. Calculations for Hardy-Weinberg goodness of fit based on a study of 98 unrelated donors plus informative families established that 5 of these were alleles of a single new locus termed Human Granulocyte Antigen (HGA)-3a, b, c, d, and e. Absorptions indicated that these antigens were present on mature granulocytes but absent from platelets, lymphocytes, monocytes, and myeloid precursors. A single antigen of another separate locus, HGA-1, was also identified. Absorptions revealed a quite different distribution for HGA-1 than HGA-3, this antigen being detected on monocytes and myeloblasts as well as on mature granulocytes. Independent segregation of the three loci from HLA, from the NA-NB and the 5a-5b antigens, and from themselves was confirmed in informative families.Finally, it seems likely that other antigens will be identified because several other sera that react with both monocytes and granulocytes have been detected.

Alleles↗

The wandering spleen in infancy and childhood.

The wandering spleen is an unusual entity, which has been described rarely in infants and children. Although patients may be asymptomatic, some may present with torsion of the spleen with associated vovulus and vascular infarcation. Two asymptomatic patients with wandering spleen are described. Radiographic signs and isotopic scan findings of wandering spleen are discussed and the literature is reviewed.

Child↗

Studies on levamisole--induced agranulocytosis.

Widespread clinical trials of leavo-tetramisole (levamisole) as an immunopotentiating agent in rheumatoid arthritis, metastatic carcinoma, and immunodeficiency states have been complicated by agranulocytosis (AGC) in 2.5%-13% of patients. Other than a relationship with prolonged high dosage, very little is known regarding the pathogenesis of levamisole-induced AGC. Whereas leukoagglutination was negative, fluorochromatic microgranulocytotoxicity (GCY) tests were positive with serum from 10 of 10 acutely neutropenic patients. The antibody was IgM, reacted with 100% of unrelated granulocytes, but not with T or B lymphocytes. Some sera also reacted with monocytes and the myeloid cell line, K-562. Tests for antigen-antibody complexes or cold autoantibodies were negative. Although clinical evidence strongly suggests a haptene (drug) mechanism, in vitro mixing experiments were also negative. An alternative choice parallels the model of aldomet-induced Coombs'-positive hemolytic anemia. Finally, GCY first became positive 2-3 mo prior to the onset of AGC on two patients, suggesting the possibility of identifying those at risk well before the onset of neutropenia.

Agranulocytosis↗

HLA antigens and schizophrenia.

We typed 45 schizophrenic patients for 35 HLA antigens and compared their frequencies with 1,263 population controls. No significant differences between schizophrenics and controls were found. When the schizophrenics were subtyped, a significant (P less than .05) excess of Aw26 was found among the hebephrenics, compared with the population controls. When the published literature on schizophrenia-HLA associations was surveyed, none of the reported associations were found to be consistent across studies. Some possible explanations for the heterogeneity among studies are discussed and it is concluded that an association between schizophrenia and any of the HLA antigens has not yet been demonstrated.

Adult↗

Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody.

Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.

Adult↗

The subtrapezial space.

The subtrapezial space as it is depicted on computed tomography scans of patients positioned with their arms above their heads is described and illustrated. Knowledge of the outline and contents of this area is useful in the recognition of enlarged lymph nodes.

Adipose Tissue↗

Free hypothenar full-thickness grafts for distal digital defects.

The application of free full-thickness grafts of palmar skin from the hypothenar area is advocated for full thickness digital tip defects too large for open treatment. The traditional objection to this site as a donor for full-thickness skin on the basis of sensitivity and pain has not been confirmed. Strict, meticulous attention to detail is required for success in utilizing this technique. Other methods of treatment are reviewed and indications, advantages, and disadvantages of the free full-thickness graft of hypothenar skin are discussed.

Adult↗

Effect of blood transfusions on survival of cadaver and living related renal transplants.

The effect of blood transfusion was analyzed in 194 first cadaver renal transplants and 86 living related renal transplants. The association of blood transfusion with HLA genotyping and poor risk recipients was analyzed. Exclusion of poor risk recipients improved graft survival among the transfused group of patients but not in the small subgroup of nontransfused recipients. No effect of blood transfusion was observed in the living related group. Improved graft survival was observed in both the haplotype-matched and nonhaplotype-matched transfused cadaver recipients. The haplotype-transfused recipients had grafts survival rates of 69 and 66% at 1 and 2 years, respectively. The greatest beneficial effect was seen in the double haplotype-transfused cadaver recipients with graft survival rates of 80 and 71% for the same period. The lack of beneficial effect of transfusion in the living related patients is felt to be a result of the fact that the maximum effect had already been achieved by a far superior donor-recipient histocompatibility than is able to be achieved in a large group of cadaver recipients.

Blood Transfusion↗