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Biomedical subjects

D R Schultz

Publications and source records attributed to D R Schultz.

At least 55 records · Page 3Linked to original sources

The first component of human complement: on the mechanism of activation by some carbohydrates.

Four synthetic saccharides (mono-, di-, tri-, tetra-) linked to the carrier 8-methoxycarbonyloctanol were used in the presence or absence of a polysaccharide (PS) purified from ant venom to study the activation of C1 and the consumption of C4 in normal serum. The carrier was essential for the recorded activities of the saccharides. The alpha D mannose-O-carrier did not cause C1 activation and C4 consumption by itself, but it enhanced these activities when combined with the venom PS. The alpha L fuc(1 leads to 4)beta D glc-NAc-O-carrier caused C1 activation but no C4 consumption by itself at a high concentration (1.4 mg/ml), and enhanced C1 activation and C4 consumption in combination with the venom PS. The beta D gal(1 leads to 3)alpha L fuc(1 leads to 4)beta D glc-NAc-O-carrier caused both C1 activation and C4 consumption in normal human serum by itself. The alpha L fuc(1 leads to 2)beta D gal[alpha L fuc(1 leads to 4)]beta D glc-NAc-O-carrier neither caused C1 activation and C4 consumption by itself, nor did it enhance these activities when combined with the venom PS. Neither EAC1hu nor EAC1hu bound 3H-PS or 3H-beta D gal(1 leads to 3)alpha L fuc(1 leads to 4)beta D glc-NAc-O-carrier. Also, the precursor human C1 on EA (EAC1) was not activated by the venom PS. Thus, the overall evidence shows that human precursor C1 is activated by these carbohydrates solely by an interaction with C1q subunit of macromolecular C1.

Animals↗

Endothelial cells of bovine pulmonary artery lack receptors for C3b and for the Fc portion of immunoglobulin G.

Bovine pulmonary endothelial cells do not possess receptors for the 3b component of complement (C3b) or for the Fc portion of immunoglobulin G. The lack of these receptors may help explain the nonthrombogenic function of endothelial cells. Our findings rule out the possibility that endothelial cells participate in pulmonary immune complex disease through the binding of C3b or Fc fragments.

Animals↗

Synthesis of renin substrate by rat liver.

The present study attempts to determine if the isolated rat liver is capable of synthesizing renin substrate from 14C-labelled amino acids added in the perfusate. The renin substrate is characterized via reaction with renin, forming a substance that is subsequently identified as proangiotensin. Extensive evaluation of the reaction product is carried out by using molecular-sieve chromatography, countercurrent distribution, reactivity with converting enzyme, radioimmunological technique and bioassay. The results demonstrate that isolated rat liver perfused with artificial salt solution is capable of synthesizing a protein that reacts with renin to form a radioactive substance indistinguishable from proangiotensin.

Angiotensinogen↗

Western equine encephalitis with rapid onset of parkinsonism.

A patient with confirmed western equine encephalitis had the rapid onset of postencephalitic parkinsonian sequelae. This observation corroborates similar previous but rare reports. Response to therapy with levodopa, dopa decarboxylase inhibitor, and trihexyphenidyl was dramatic. However, remission maintained for 12 months without medication suggests that the parkinsonism would have remitted spontaneously. In either case, this has not previously been reported with the western equine togavirus.

Adult↗

Localization of angiotensin converting enzyme (kininase II). I. Preparation of antibody-hemeoctapeptide conjugates.

Antibodies to pig lung angiotensin converting enzyme (kininase II) were conjugated to a heme-octapeptide (8-microperoxidase, 8-MP) derived from cytochrome c. 8-MP, which has only one reactive amine, was coupled to antibody in a two-step procedure using a bifunctional active ester, bis-succinyl succinate. In the first-step, 8-MP-succinyl succinate, a stable compound which can be stored. In a second step, the remaining active ester was used for coupling to reactive amines of the antibody. The conjugate consists of 1.6-2.3 8-MP moieties per antibody. Using these procedures, the formation of complex polymers is avoided. Each molecule of conjugate possesses both immunoreactivity and peroxidatic activity. The conjugate has been used to localize angiotensin converting enzyme along the plasma membrane and associated caveolae of pig aortic endothelial cells in culture.

Antibodies↗

Evidence that C1s participates in the alternative complement pathway.

Purified C1s, subcomponent of C1, induced electrophoretic conversion of factor B and consumption of hemolytic C3 and C5 in sera genetically deficient in C2 or C4. Blocking of the hemolytic activity of C1s in C2-deficient serum by F(ab')2 anti-C1s resulted in inhibition of the alternative pathway, as indicated by the failure of zymosan or cobra venom factor to induce comsumption of C3 and C6. Zymosan also failed to activate the alternative pathway when C1s was absorbed from C1r-deficient serum using a solid immunoabsorbent. These data, showing that C1s participates in the alternative pathway under certain experimental conditions, suggest the interesing possibility that C1s is important in the activation sequence of both the classical and the alternative pathway more generally.

Animals↗

Immunoblastic lymphadenopathy with mixed cryoglobulinemia. A detailed case study.

The premise that chronic antigenic stimulation may be involved in lymphoproliferative disorders was considered in a patient with immunoblastic lymphadenopathy who had received liver extract by injection and by mouth for many years. The salient features were lymphadenopathy and hepatosplenomegaly, a predominance of lymphocytes and plasmacytoid cells with mitotic figures in lymph-node imprints, a cryoglobulin containing IgG, IgA, IgM and bound complement components, depressed serum complement levels, and Coombs-test-positive erythrocytes. Immunoglobulin concentrations per 100 ml of serum were IgG, 5900 mg, IgA, 1480 mg, and IgM, 5640 mg, with normal ranges of 710 to 1540, 60 to 490, and 37 to 204 mg, respectively. Serum precipitins to an antigen (or antigens) in the liver extract resided in the IgA and IgM classes. Complete remission followed one course of cyclophosphamide, vincristine, and prednisone. We propose that the syndrome was caused by chronic antigenic stimulation with liver extract.

Complement System Proteins↗

Immunologically-mediated renal disease in Waldenström's macroglobulinemia.

A patient with Walderström macroglobulinemia associated with nephrotic syndrome is described. Serum cryoglobulin and rheumatoid factor were absent. Intramembranous electron-dense deposits were demonstrated in kidney biopsy material by electron microscopy. Deposits of immunoglobulin G (IgG), M (IgM) and the third component of complement (C3) were identified in kidney biopsy tissue by immunofluorescent staining methods. The serum immunoglobulins were characterized by chromatographic and immunochemical methods and showed a monocional IgM-K, IgG-K and gamma-chain piece of undefined structure. Free K- and gamma-chains were found in the urine. The IgM was not complexed to the IgG or vice versa, but the IgG was in an affregated form. Although it is not known which immunoglobulin initiated the tissue injury, IgG, IgM and complement deposits probably contributed to the renal dysfunction. The nephrotic syndrome diminished after treatemnt with chlorambucin and corticosteroids.

Animals↗

Hemolytic anemia associated with multiple autoantibodies and low serum complement.

A 37 year old woman with extravascular hemolytic anemia had a positive Monospot test associated with positive antiglobulin and anticomplement Coombs' tests, cold agglutinins and warm autoantibodies. IgG-kappa (k) antibodies, which reacted with all panel red cells at 37 degrees C, were eluted from her circulating red cells. However, neither immunoglobulins nor C3 was detected after her serum was adsorbed with heterologous red cell stroma at 37 degrees C and eluted at the same temperature in glycine buffer. In contrast, IgM-kappa and IgM-lambda (lambda), IgG-3-kappa, IgG4-lambda, IgA-lambda and C3 were eluted at 37 degrees C from heterologous red cell stroma after adsorption with her serum at 0 degrees C. Thus, antibodies of several types, which were present in the patient's serum, reacted optimally with red cell antigens at low temperature. Cold-reactive IgG3-kappa antibodies, which also capable of interacting with red cells at 37 degrees C, probably accounted for the IgG-kappa antibodies eluted from the patient's circulating red cells. The patient's serum C4 titers were decreased, with low normal to moderately depressed C3 and low normal C5, indicating that the anti-red cell IgM and/or IgG3-kappa antibodies probably fixed complement. A localized cold stress test resulted in a transient increase in plasma hemoglobin and a decrease in serum C3 titer. These findings, and the beneficial clinical response obtained with small doses of prednisone, suggest that both the cold-reactive antibodies and the IgG-kappa on circulating red cells were pathophysiologically significant. This is the first report of a patient with multiple red cell autoantibodies in whom serum complement component titers were determined in conjunction with characterization of the anti-red cell immunoglobulins. Subclinical infectious mononucleosis may have preceded the prolonged hemolytic episode. Clinical evidence of systemic lupus erythematosus has not appeared.

Adsorption↗