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Biomedical subjects

D Schultz

Publications and source records attributed to D Schultz.

32 records · Page 2Linked to original sources

Secretion of rabbit C-reactive protein by transfected human cell lines is more rapid than by cultured rabbit hepatocytes.

C-reactive protein (CRP) is a major acute phase protein in humans and rabbits. Its synthesis by the liver varies over a 1000-fold range depending on the presence and severity of inflammatory stimuli. In previous studies of synthesis and secretion of rabbit CRP, we showed that secretion becomes more efficient over the course of the acute phase response as CRP synthesis rates increase (Macintyre, S.S., Kushner, I., and Samols, D. (1985) J. Biol. Chem. 260, 4169-4173). The current studies were undertaken to help distinguish between two alternative explanations for this finding: 1) that secretion efficiency may simply be a property of the rate of synthesis and intracellular concentration of CRP or 2) that secretion may be regulated by separate intracellular mechanisms. A fusion gene containing the mouse metallothionein I promoter linked to the protein coding region of the rabbit CRP gene was introduced into the human hepatoma cell line, NPLC, and the nonliver cell line, HeLa. In this system a graded response of the mouse metallothionein I promoter following exposure to increasing zinc concentrations results in increasing CRP synthesis. Unlike hepatocytes from rabbits undergoing the acute phase response, we found that rabbit CRP was secreted by these transfected cell lines with a very high degree of efficiency which was independent of the rate of CRP synthesis. This finding implies that normal rabbit hepatocytes retard the secretion of CRP and that this inhibition is diminished as the acute phase response progresses. It further indicates that the relationship between changes in synthetic rate and efficiency of secretion of rabbit CRP is not a causal one and that synthesis and secretion of CRP by rabbit hepatocytes are regulated by independent intracellular mechanisms during the acute phase response.

Animals

A comparison of local recurrence and resection margins for stage I primary cutaneous malignant melanomas.

A retrospective review of 552 patients with clinical stage I primary cutaneous malignant melanomas was undertaken comparing margins of resection and local recurrence between 1966 and 1981. The overall local recurrence rate was 8 per 552 (1.45 percent). We observed no instances of local recurrence in lesions less than 1.40 mm thick with resection margins of at least 1 cm. A comparison of resection margins greater than 2 cm versus less than 2 cm for lesions less than 1.00 mm thick showed no difference at the 0.05 level of significance for local recurrence (0 per 228 versus 2 per 154; 1.3 percent) or survival. While narrower margins of resection for thinner, low-risk stage I malignant melanomas appear safe, the exact minimum margin of resection needed to satisfy both oncologic and cosmetic considerations, whether 1 or 2 cm, will need to be determined by a large prospective, randomized study.

Adolescent

Effects of in vitro and in vivo anticanine T lymphocyte and anticanine class II-specific monoclonal antibodies in the beagle.

Two murine anticanine lymphocyte monoclonal antibodies, designated T83 and B1F6, were assessed for (1) in vitro antiepitope activity to circulating lymphocyte subsets, their functional effects on lymphoproliferative assays and binding specificities to diverse cell suspensions and tissue sections; (2) in vivo effects after administration on cells expressing the target epitopes, lymphoproliferation, and allograft survival; and (3) the host immune response to the injected murine immunoglobulins. The monoclonal antibody T83 (IgG3) appeared to be specific for a T cell subset with an up-regulating function on lymphoproliferation. It caused a profound depletion of cells with the appropriate epitope after intravenous administration but it bound to lymphocyte membrane epitopes on some cells in peripheral blood that did not become depleted and putatively caused other modulating effects on lymphocyte function. The monoclonal antibody B1F6 (IgG2a, previously described) was immunologically specific in vitro for cells expressing class II major histocompatibility complex antigens. In the dog, this also consisted of 50% of T lymphocytes. After intravenous administration, there were functional effects similar to those of T83. A modest prolongation of survival of renal allografts was observed when both mAbs were used as the sole immunosuppressive agent. These studies also demonstrated the occurrence of natural canine antimurine IgG antibodies. Administration of either monoclonal antibody was followed by a rapid increase in the concentration of the antimouse antibody(s). We postulate that the presence of canine natural antimouse IgG markedly influenced the biologic effects of in vivo administered monoclonals.

Animals

Monokines regulate glycosylation of acute-phase proteins.

The acute-phase response to inflammatory stimuli, characterized by increased synthesis of acute-phase proteins (APP), is often accompanied by changes in the glycosylation patterns of some of these proteins. While expression of APP genes in hepatocytes is regulated by monokines, mechanisms governing changes in glycosylation are not known. Exposure of human hepatoma cell line Hep 3B to conditioned medium from LPS-activated human monocytes and to medium from the keratocarcinoma cell line COLO-16 led to increased synthesis of alpha 1 proteinase-inhibitor and ceruloplasmin and to alterations of their glycosylation patterns similar to those seen in human serum in various inflammatory states. IL-1, tumor necrosis factor, and hepatocyte stimulating factor I increased synthesis of ceruloplasmin without alterations in the pattern of its glycosylation. These findings demonstrate that altered glycosylation seen in plasma in some inflammatory states can be explained by the effects of monokines on glycosylation in hepatocytes and that gene expression and glycosylation of some APP during the acute-phase response may be regulated by different mechanisms.

Acute-Phase Proteins

Complement activation and corticosteroid therapy in the development of the adult respiratory distress syndrome.

Fifty-nine patients in septic shock were observed for the development of the adult respiratory distress syndrome (ARDS) prior to and after receiving either 30 mg/kg methylprednisolone sodium succinate, 6 mg/kg dexamethasone sodium phosphate or no steroid. Serum levels of C3, C4 and Factor B allowed classification of 42 patients by activation of complement pathways. Despite a trend toward patients with severe septic shock who activate the alternative pathway being protected from the development of ARDS, complement pathway determination did not allow prediction of the development of ARDS and steroid pretreatment did not influence complement levels or prevent ARDS.

Complement Activation

Diet, blood pressure, and hematologic variables of nulliparous women attending a prenatal clinic.

Diet, hematology, and blood pressures of 1800 black and white nulliparous women were surveyed at a prenatal clinic. Although black women had higher blood pressure and lower hemoglobin and hematocrit means that white women, no racial differences were found for prevalence of anemia or hypertension. White women reported less adequate intakes of protein/iron and vitamins B and C compared with black women. No associations between dietary intake and anemia or hypertension were found in univariate analysis. Failure to find racial differences in prevalence of hypertension and anemia may reflect improvements in the dietary supplementation and health care available to lower socioeconomic, black women in the last decade.

Adolescent

[Diagnostic value of muscle biopsy findings in myotonic dystrophy (Curschmann-Steinert) (author's transl)].

By histological, enzyme histochemical, histometrical and ultrastructural studies of 15 muscle biopsies from patients with myotonic dystrophy the typical morphological picture of a myopathy with multiple internal nuclei, sarcoplasmic masses and ring fibers can be shown only in 7 cases with very severe or prolonged clinical course. There is fiber degeneration under the sarcolemma which corresponds to findings in myopathies caused by hypothyroidism. Type-I-fiber-atrophy, which is thought to be an early morphological sign of the disease. can be demonstrated in our material only in proximal muscle groups, especially biceps muscle, whereas tibialis anterior muscle shows a slight focal atrophy of both mean fiber types, which is not helpful for differential diagnosis. Therefore in early cases of myotonic dystrophy which are not clarified by clinical and electromyographic investigation, a biopsy of biceps muscle should be done. Advanced cases as a rule can be confirmed by EMG without muscle biopsy. The morphological differential diagnosis of type-I-fiber-atrophy and the similarities of fiber degeneration under the sarcolemma in myotonic dystrophy as well as in myopathy caused by hypothyroidism are discussed.

Biopsy

[Sequential hepato-splenic scintigraphy for measurement of hepatic blood flow (author's transl)].

The arterial and portal components of total liver blood flow were determined quantitatively in 31 patients by means of a new, non-invasive method. Sequential hepato-splenic scintigraphy has been employed, using a scintillation camera linked to a computer system. In normals, the proportion of portal flow was 71%, whereas in patients with portal hypertension it averaged 21%. Our experience indicates that the procedure can be of considerable value in the pre-operative diagnosis and postoperative follow-up of portal hypertension.

Adolescent

Effect of guanidine, germine, and steroids in a case of botulism.

A patient with severe type A botulism demonstrated several interesting features. Characteristic electrophysiologic findings are not necessary for the diagnosis. Guanidine hydrochloride provided mild improvement. High doses of steroids and low dose of germine-monoacetate had no effect.

Action Potentials