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Biomedical subjects

C Schmid

Publications and source records attributed to C Schmid.

At least 307 records · Page 17Linked to original sources
PubMed1990

Synthesis of tetrahydrobiopterin in Friend erythroleukemia cells and its modulator effect on cell proliferation.

The induction of the enzymes in the tetrahydrobiopterin pathway by dimethyl sulfoxide (DMSO) was investigated in subclones F4N and B8/3 of the proerythroblastoid Friend erythroleukemia cell line (MEL). GTP-cyclohydrolase, the initial enzyme in the biosynthetic pathway, is virtually absent in both clones, but expression increases during 3 days of DMSO treatment. The final enzyme levels show 12-fold (subclone B8/3) and 40-fold (subclone F4N) increases compared to initial values. Enhancement of 6-pyruvoyl tetrahydropterin synthase activity is detectable 6 h after exposure to DMSO and continues to increase in the 3-day time period to 2.4-fold and 1.8-fold levels in subclones B8/3 and F4N, respectively. Sepiapterin reductase is present in unstimulated F4N cells and absent in B8/3 cells. The enzyme activity is not affected by DMSO treatment in either cell line. This explains why DMSO treatment causes accumulation of tetrahydrobiopterin in the MEL subclone F4N, but not in subclone B8/3. MEL cells are devoid of phenylalanine hydroxylase for which tetrahydrobiopterin serves as cofactor. In F4N, but not in B8/3, tetrahydrobiopterin modulates the rate of [3H]thymidine incorporation, thus being functionally linked with cell proliferation rather than with differentiation. In contrast to T lymphocytes, periods of tetrahydrobiopterin synthesis and of modulator function are uncoupled in MEL cells.

Alcohol Oxidoreductases↗
PubMed1990

Pretreatment of prosthetic valve sewing-ring with the antibiotic/fibrin sealant compound as a prophylactic tool against prosthetic valve endocarditis.

Prosthetic valve endocarditis (PVE) remains a dreaded complication following heart valve replacement despite perioperative antibiotic (AB) prophylaxis. In order to increase the AB concentration in the sewing ring, an experimental study including topical application of the gentamicin derivative EMD 46/217 and fibrin sealant (F) as AB-carrier was initiated. In vitro pretreatment of Dacron with the gentamicin derivative and F was followed by constant AB release for 3 weeks. In a subsequent animal study, four Dacron rings with different pretreatment were implanted in the descending aorta of 10 pigs after direct contamination with 10(8) Staphylococcus aureus solution. One ring was pretreated with the AB/F compound, a second ring with the AB alone. Ring 3 (no pretreatment) and ring 4 (F alone) served as controls. After 1 week, the sewing rings and their corresponding implantation sites were assayed for measurement of AB-content and for culture. The AB content of AB/F-rings was 24.99 +/- 7.16 micrograms/g wet weight, while rings pretreated with the AB alone contained no measurable drug amounts with the exception of one specimen (0.5 microgram/g) (AB/F vs. AB-rings: P less than 0.0005). The corresponding implantation sites to AB/F rings contained 1.07 +/- 0.54 micrograms/g AB, whereas in only 2 of 10 implantation sites of AB rings, low AB levels were found (0.05 and 0.2 micrograms/g) (AB/F vs. AB ring implantation sites: P less than 0.0005). While all control rings and 9 of 10 AB rings were infected, 5 of 10 AB/F rings remained sterile after culture (AB/F vs. AB rings: P = 0.05). This finding correlated with the AB content in the suture rings.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗
PubMed1990

Heart transplantation: intraoperative management, postoperative therapy and complications.

Currently, heart transplantation (HTX) is performed as an orthotopic cardiac replacement according to the technique of Lower and Shumway in over 95% of the cases with good results. Survival after heterotopic HTX, by contrast, remain poor (one year survival: 50%). Postoperative therapy compiles primarily prophylactic measures to prevent complications, especially organ rejection and infections. Immunosuppressive prophylaxis generally includes a triple drug therapy consisting of cyclosporin, prednisolone, and azathioprine for maintenance therapy. Initially there is often an additional application of poly- or monoclonal antibodies. The prime measure to prevent infection during the initial hospital stay will be reversed isolation of the recipient. Initial antibiotic prophylaxis resembles that of conservative cardiac surgery, but in addition antiviral and antifungal prophylaxis is applied. The most common postoperative complication following HTX is cardiac rejection, which is detected by routine endomyocardial biopsies. At our institution the incidence of rejection decreases from 3.07 episodes per patient in the first 3 months to 1.97 episodes during the last 6 months of the first year after HTX. In general, acute rejection is treated by methylprednisolone (3 x 500 mg/day) or anti-T-cell-antibodies. Infections often occur following intervals of increased immunosuppression, usually early postoperatively and following therapy of acute rejections. Often, invasive diagnostic measures have to be taken rapidly in order to allow for specific therapy (antibiotics, antimycotic treatment, virostatic agents). Close follow-up of the heart transplant recipient and rapid therapy of possible postoperative complications enable the current one-year survival rates of 80% or more.

Anesthesia↗
PubMed1990

Comparison of bone marrow histology in early chronic granulocytic leukemia and in leukemoid reaction.

A retrospective study was performed on bone marrow biopsies of 50 untreated patients with leukemoid reactions (LR) and 50 untreated patients with early chronic granulocytic leukemia (CGL). A comparison was made between hematopoietic and adipose tissues, bone and its cells, as well as other stromal components in these two disorders. Histologic and histomorphometric analyses revealed significant differences in trabecular structure, in localization of fat cells, in numbers of sinusoids, capillaries and various stromal elements. No significant differences between LR and CGL were detected in the quantity of erythro- and granulocytopoiesis and of megakaryocytes, but these were smaller in CGL than in LR. This histologic and histomorphometric evaluation demonstrates that certain histologic features may serve as valuable aids in distinguishing LR from CGL.

Adipose Tissue↗
PubMed1990

Effects of insulin-like growth factor I in man.

A 6-day period of subcutaneous infusion with recombinant human insulin-like growth factor I in three healthy male volunteers resulted in an increase in the ratio of insulin to C-peptide levels and significant decreases in triglyceride levels and the ratio of total to high density lipoprotein-cholesterol in serum. Increased renal plasma flow and glomerular filtration rates were also observed.

Adult↗
PubMed1990

Regulation of binding proteins for insulin-like growth factors (IGF) in humans. Increased expression of IGF binding protein 2 during IGF I treatment of healthy adults and in patients with extrapancreatic tumor hypoglycemia.

UNLABELLED: Insulin-like growth factors (IGFs) in blood form two complexes with specific binding proteins (BPs): a large, growth hormone (GH)-dependent complex with restricted capillary permeability, and a smaller complex, inversely related to GH, with high turnover of its IGF pool and free capillary permeability. The distribution of BPs and of IGFs I and II between these complexes was studied in sera from healthy adults treated with IGF I or/and GH and from patients with extrapancreatic tumor hypoglycemia. Like GH, IGF I administration raises IGF I and two glycosylation variants of IGFBP-3 in the large complex, but unlike GH drastically reduces IGF II. During IGF I infusion, IGFBP-3 appears in the small complex whose IGFBP-2 and IGF I increase three- to fivefold and fivefold, respectively. GH treatment, associated with elevated insulin levels, suppresses IGFBP-2 and inhibits its increase owing to infused IGF I. The small complex of tumor sera contains increased amounts of IGFBP-2 and -3, and two- to threefold elevated IGF II. CONCLUSIONS: low GH and/or insulin during IGF I infusion and in extrapancreatic tumor hypoglycemia enhance expression of IGFBP-2 and favor partition of IGFBP-3 into the small complex. Free capillary passage and high turnover of its increased IGF I or II pools may contribute to compensate for suppressed insulin secretion during IGF I infusion or to development of tumor hypoglycemia.

Carrier Proteins↗
PubMed1990

Insulin regulates the expression of the insulin-like growth factor binding protein 2 mRNA in rat hepatocytes.

The goal of this study was to find out whether GH or insulin regulate the mRNA expression of the fetal binding protein of insulin-like growth factor (IGFBP-2). Primary hepatocytes from adult rats were used as a test system. IGFBP-2 mRNA was abundant in cells cultured in the absence of hormones and markedly reduced in cultures containing insulin. Addition of GH had no effect on IGFBP-2 mRNA levels although the cells are responsive to GH as demonstrated by a GH mediated elevation of IGF l mRNA levels. Half-maximal down-regulation of IGFBP-2 mRNA levels occurred at an insulin concentration of 1 to 2 x 10(-10) M. The finding that insulin is a potent negative regulator of hepatic IGFBP-2 mRNA levels suggests a physiologically important regulatory link between the two hormones insulin and IGF l.

Animals↗
PubMed1990

[Insulin-like growth factors (IGF I and IGF II) and diabetes].

IGF I and IGF II are insulin-like peptide hormones circulating in blood bound to specific carrier proteins. IGF I mediates many actions of growth hormone--hence its designation as somatomedin C--and it stimulates cell replication, cell differentiation and the synthesis of cellular products (matrix proteins, etc.). Recent investigations in normal human subjects show that pharmacological doses of IGF I increase renal function and have profound metabolic effects that might prove to be useful in the treatment of conditions characterized by relative insulin resistance, such as type 2 diabetes, obesity and hyperlipidemia.

Animals↗
PubMed1990

Busulfan/cyclophosphamide plus bone marrow transplantation is not sufficient to eradicate the malignant clone in juvenile chronic myelogenous leukemia.

Bone marrow transplantation plays an essential role in the successful treatment of both juvenile and adult chronic myelogenous leukemia. Recently, it has been reported that conditioning with high doses of busulfan can successfully replace total body irradiation (TBI), in patients with acute myelogenous leukemia as well as adult chronic myelogenous leukemia. We report here the case of a 29-month-old boy with juvenile chronic myelogenous leukemia (JCML) transplanted with HLA-identical bone marrow after conditioning with busulfan, etoposide and cyclophosphamide. Successful engraftment was followed by early relapse on day 67. A second HLA-identical transplant was performed following myeloablative treatment with TBI. Engraftment was once again successful and the patient remains free of disease more than 24 months after transplantation. We conclude that busulfan is insufficient in eradicating JCML and that TBI is required prior to transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Regulation of hepatic expression of IGF I and fetal IGF binding protein mRNA in streptozotocin-diabetic rats.

Hepatic mRNA levels of insulin-like growth factor I (IGF I) and of the fetal, nonglycosylated 32 kDa IGF-binding protein (BP) were analysed in diabetic, diabetic insulin- and IGF I-treated rats as well as in age-matched, healthy control animals. IGF ImRNA levels are reduced in diabetic rats and increased by insulin treatment. In contrast, the infusion of IGF I does not significantly upregulate IGF I mRNA levels. Fetal IGF BP mRNA expression is very low in healthy control animals, but high levels are found in diabetic rats. Insulin therapy lowers fetal IGF BP mRNA levels, whereas IGF I has no effect. We propose that insulin is a major regulator of the 32 kDa IGF BP levels in adult rats.

Animals↗
PubMed1989

Release of insulin-like growth factor carrier proteins by osteoblasts: stimulation by estradiol and growth hormone.

Osteoblast-like rat calvaria cells release specific insulin-like growth factor (IGF) carrier proteins (CPs). As analyzed by SDS-PAGE under nonreducing conditions, Western blotting and detection by 125I-IGFs, CPs migrating with the IGF-binding subunits of the major CP species of rat serum (42/45/49 kDa) accumulate in cell culture medium. Treatment of the cells with growth hormone and estradiol increases the abundance of this glycosylated CP species. Since the two hormones were previously found to stimulate osteoblast replication via an IGF I-dependent mechanism, the data indicate that hormones may control local IGF action not only by regulating synthesis of IGFs and their receptors but also their presentation by CPs.

Animals↗