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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 667 records · Page 37Linked to original sources

Regulation of the lysine biosynthesis in Pichia guilliermondii.

The regulatory properties of four enzymes (homocitrate synthase, alpha-aminoadipate reductase, saccharopine reductase, saccharopine dehydrogenase) involved in the lysine biosynthesis of Pichia guilliermondii were investigated and compared with the regulatory patterns found in other yeast species. The first enzyme of the pathway, homocitrate synthase, is feedback-inhibited by L-lysine. Some other amino acids (alpha-aminoadipate, glutamate, tryptophan, leucine) and lysine analogues are also inhibitors of one or more enzymes. It is shown that only the synthesis of homocitrate synthase is weakly repressed by L-lysine.

Aldehyde Oxidoreductases↗

X-ray dose-effect relationship on unscheduled DNA synthesis and spontaneous unscheduled DNA synthesis in mouse brain cells studied in vivo.

X-irradiation of the head of adult mice leads to DNA repair synthesis (unscheduled DNA synthesis, UDS) in non-proliferating cells of the brain as shown autoradiographically after injection of 3H-thymidine and subsequent irradiation. The extent of UDS induced by one and the same X-ray dose varies between different cell types and also between different brain areas. Within the range of X-ray doses studied (2 to 100 Gy) a linear dose effect relationship was observed. No evidence of a saturation effect was found. The slopes of the regression lines for the dose effect relationship differ considerably for the different cell types. Two interesting correlations were found, if the present results were compared with other data in the literature: (i) There seems to be a correlation between the extent of UDS and radiosensitivity of the different cell types, the cells with low DNA repair synthetic rates being more radiosensitive. (ii) The extent of UDS of the different cell types correlates well with the extent of protein synthesis of the corresponding cell types. Apart from radiation induced UDS, spontaneous UDS was found to occur in sham-irradiated animals. The extent of spontaneous UDS also differs considerably between different cell types as well as between different brain areas. The increase of spontaneous UDS with increasing duration of immobilization of the animals during sham irradiation suggests a relationship between spontaneous UDS and stress.

Animals↗

Three other types of duodenal polyps: mucosal cysts, focal foveolar hyperplasia, and hyperplastic polyp originating from islands of gastric mucosa.

Seven cases are reported that initially presented on endoscopic examination as duodenal polyps originating from islands of gastric mucosa within the duodenal bulb. Microscopic examination revealed mucosal cysts (MC), focal foveolar hyperplasia (FFH), and hyperplastic polyp (HPP). These lesions must be added to the list of neoplastic and tumorlike lesions of the duodenum that may endoscopically present as polyps.

Aged↗

Competitive action of divalent cations and D600 in frog slow muscle fibers.

Single, slow muscle fibers from Rana temporaria were equilibrated in normal Ringer's. 95 mmol/liter K(+)-solution containing various concentrations of Ca2+, Ni2+, Mn2+ or Mg2+ was applied, and the ensuing contractures were recorded isometrically. While peak tension (Fmax) was little affected, maintained tension (measured 1 min after onset of contracture) strongly depended on the concentration and species of divalent cations. Tension was maintained at its peak value in the presence of all species of divalent cations provided their concentrations were adequately increased. Dose-response curves were hyperbolic; Lineweaver-Burk plots revealed straight lines with different slopes intersecting near 1/Fmax, and indicating the following order of efficiency: Ni2+ greater than Ca2+ greater than Mn2+ much greater than Mg2+. Hill plots for these cations resulted in straight lines with slopes near 1. Qualitatively similar relationships were obtained with contracture solutions containing D600 (3-12 mumol/liter). However, under these conditions higher concentrations of Ca2+ or Ni2+ were required in order to fully maintain tension. After a step concentration change in the medium during contracture, the effects of Ca2+ or D600 were detectable only after a delay of 9 and 18 sec, respectively. It is concluded that divalent cations and D600 compete for the same binding site according to a 1:1 reaction. This site is presumably located inside the transverse tubular system and controls inactivation of the contractile force.

Animals↗

Osteomesopycnosis. A new case.

A 10-year old, mentally and physically normally developed girl complained of back pain following an accident. Radiological findings revealed an inhomogeneous, coarse osteosclerosis along the endplates and posterior parts of the ovoid shaped vertebral bodies, in the proximal and distal femora-, proximal humeri and tibia epiphyses, and along the lateral aspects of the femoral necks. The pelvis presented a mottled appearance of the trabecular pattern at the symphysis pubis and the lateral parts of ischii and sclerosis in the acetabular region. The only laboratory abnormality was a high serum parathormone level. The family history revealed an autosomal dominant inheritance. The name proposed by Maroteaux for this skeletal disorder is osteomesopycnosis, as the lesions were localized to the spine, pelvis and sometimes proximal femur. The skull, ribs, long bones, hands and feet were not involved in the reported 12 cases. Radiographs of this patient showed in addition changes in the hand. This disease must be distinguished from atypical axial osteomalacia.

Child↗

Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6.

Gene cloning and sequencing of the HLA-B locus split antigens B38 (B16.1) and B39 (B16.2) allowed localization of their subtypic as well as their public specificities HLA-Bw4 or -Bw6 to the alpha-helical region of the alpha 1 domain flanked by the amino acid positions 74-83. Comparison of their amino acid sequences with those of other HLA-B-locus alleles established HLA-Bw6 to be distinguished by Ser at residue 77 and Asn at residue 80. In contrast, HLA-Bw4 is characterized by at least seven different patterns of amino acid exchanges at positions 77 and 80-83. Reactivity patterns of Bw4- or Bw6-specific monoclonal antibodies reveal two alloantigenic epitopes contributing to the HLA-Bw4 or -Bw6 specificity residing next to the region of highest diversity of the alpha 1 domain.

Amino Acid Sequence↗

Resistance to methotrexate and multidrug resistance in childhood malignancies.

Resistance to drugs, either primary or acquired, is a main problem in cancer chemotherapy. The paper summarizes our results in regard to resistance to methotrexate and multiple drug resistance in human cell lines of pediatric malignancies and in children with resistant cancer. In cell lines as well as in children we could demonstrate amplification of the gene coding for dihydrofolate reductase as a cause for resistance to MTX. Procedures to overcome drug resistance such as treatment with high dose MTX and leucovorin rescue are discussed. The increased expression of the mdrl gene coding for the P-glycoprotein is related to multidrug resistance. This could be shown in cell lines and in children. The expression decreased when the drug, used for induction of resistance, was omitted for a few weeks from the cell culture medium. Readdition of the drug caused a rapid increase of expression. For the first time data in children are presented which demonstrate the amplification of the gene coding for dihydrofolate reductase or increased expression of the mdrl gene as cause of drug resistance. The clinical implications of these findings are discussed.

Adolescent↗

Adhesiveness and invasiveness of staphylococcal species in a cell culture model.

A model was established for the study of adhesiveness and invasiveness of staphylococcal species. Five collection strains from each of the species Staphylococcus aureus, S. epidermidis, and S. saprophyticus and 26 fresh isolates from patients with urinary tract infections were tested for adhesiveness and invasiveness in HEp-2 cell cultures. All the strains of S. saprophyticus were able to invade the cells and localize intracellularly in the cultures, whereas the invasive potential among the strains of S. aureus and S. epidermidis was lower. The number of adhesive bacteria was also highest among the S. saprophyticus strains, whereas S. epidermidis was the least adhesive. The model may be suitable for further study of urinary tract infection strains.

Bacterial Adhesion↗

Experimental infection of rhesus monkeys with SIV isolated from African green monkeys.

To establish an animal model for AIDS, 6 juvenile rhesus monkeys were infected intravenously with cell-free SIVagmTYO-1, 5, or 7. One animal was infected with SIV of known pathogenicity isolated from a sooty mangabey (SIVsmm). The 2 animals infected with TYO-1, 1 of 2 infected with TYO-7 and the 1 infected with SIVsmm seroconverted within 4-8 weeks after infection and infectious virus could be recovered 8-10 or 44 weeks after infection. Three of the 4 seroconverted monkeys developed a persistent lymphadenopathy 12 weeks after infection. Rhesus monkeys infected with SIVagm could serve as a model to study HIV infection and for vaccine trials.

Acquired Immunodeficiency Syndrome↗

Etiology and incidence of acute pancreatitis: a 20-year study in a single institution.

Reports from various countries raise the question of changes in the incidence and etiology of acute pancreatitis. This study covers patients admitted with acute pancreatitis to a single university department of medicine between 1965 and 1970 and between 1980 and 1985. The absolute number of patients admitted with acute pancreatitis doubled, whereas the percentage of pancreatitic patients in the total population of admitted patients decreased by 38%. No firm conclusion can be made about an increasing incidence of acute pancreatitis from 1970 to 1985. However, the dominating etiological factor was no longer biliary tract disease but significantly shifted to alcoholism, whereas changes in the severity of the disease were not significant. There was a downward trend in mortality with mortality rates of 13 and 8.6% for the first and second period, respectively; however, because of the small number of patients this change did not reach the level of significance.

Acute Disease↗

Decreased essential antioxidants and increased lipid hydroperoxides following high-dose radiochemotherapy.

The blood from 19 patients having bone marrow transplantation was examined for the essential antioxidants alpha-tocopherol and beta-carotene as well as lipid hydroperoxides before, at and after bone marrow transplantation (BMT). Conditioning therapy, preceding BMT in order to achieve marrow ablation and immunosuppression, consists of high-dose chemotherapy which is mostly combined with total body irradiation (TBI). In order to see a possible difference between patients with and without additional TBI, we divided the patients up into two groups; patients receiving TBI (RT+) and patients without TBI (RT-). All patients required total parenteral nutrition beginning one week prior to BMT. After conditioning therapy plasma levels of absolute and lipid-standardized alpha-tocopherol and beta-carotene decreased in both groups, presumably as a result of an enhanced breakdown of these antioxidants. The loss of these lipid-soluble antioxidants has to be considered as a possible cause for early post-transplant toxicity. Lipid hydroperoxides increase significantly in the group of patients with additional TBI, whereas the other group, receiving no additional TBI, showed no significant change. We suggest high-dose supplementation of essential antioxidants for patients undergoing BMT.

Adolescent↗

Isolated pericardial relapse following allogeneic bone marrow transplantation for acute myelogenous leukemia.

A 34-year-old male patient developed an isolated pericardial relapse of an acute myelogenous leukemia (M3) 11 months after marrow grafting from his HLA-identical brother. Alloenzyme pattern analysis revealed recipient type of the myeloblasts obtained from the pericardial effusion. Recurrence of the original leukemia was preceded by a reactivation of latent cytomegalovirus (CMV) infection which, in spite of a systemic humoral immune response to the virus, persisted in the pericardium as shown by dot-blot hybridization using CMV-specific DNA fragments. Activated T cells propagated with IL-2 from the pericardial effusion did not reveal any cytotoxic or restimulation capacity on the original or relapse myeloblasts, nor on other donor, recipient or NK target cells. Local coincidence of virus persistence and leukemic relapse suggested CMV-mediated modulation of the immune response in the pericardium with consequent induction of a proliferation of the original malignant cell clone. After local chemotherapy and one course of systemic treatment the patient is still in complete remission--longer than after the marrow grafting.

Adult↗