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Biomedical subjects

J Schubert

Publications and source records attributed to J Schubert.

At least 217 records · Page 12Linked to original sources
PubMed1991

Does hydrogen peroxide exist "free" in biological systems?

Hydrogen peroxide (H2O2) can diffuse far from the site of production to intracellular locations where biological effects may be greater. The diffusion range is extended by H2O2 carriers formed spontaneously by hydrogen bonding with monomeric and polymeric compounds, including amino and dicarboxylic acids, peptides, proteins, nucleic acid bases, and nucleosides. Hydrogen peroxide adducts (HPAs) are readily synthesized, e.g., crystalline histidine (His)-H2O2 adducts. An equilibrium exists between an adduct-forming compound and H2O2. The detection and relative stabilities of HPAs are measured by the degree of decomposition of H2O2 as influenced by test compounds in buffered solution competing with glucose or fructose for H2O2. The HPAs delay decomposition of H2O2 up to several hundredfold. The overall charge on an HPA, i.e., its ability to penetrate cell membranes, influences the cytotoxic and clastogenic effects of H2O2. Growth inhibition of Salmonella typhimurium LT2 by H2O2 is enhanced by neutral HPAs but decreased by anionic HPAs. Addition of catalase 1, 10, or 30 min after inoculation of S. typhimurium LT2 reduces or nearly eliminates partial growth inhibition by H2O2, but a neutral HPA, especially His-H2O2, transported H2O2 into the cells within 1 min, and in about 10 min completely inhibited growth. The stability of HPAs decreases with increasing pH or increasing temperature, while added Fe(II) in the presence and absence of EDTA accelerates H2O2 and HPA decomposition. Calculations indicate H2O2 hydrogen bonds with nucleic acid-base pairs with no apparent bond strain and energy stabilization comparable to normal hydrogen bonding.

Adenine↗
PubMed1991

Radioprotection of lethally irradiated animals: formulation and correlations.

Disparities in survival of mice and rats after lethal (LD100/30) radiation are resolved using two parameters: 1. total elapsed time (TET), defined as time interval between radioprotector administration to end of irradiation; and 2. area under the curve (AUC) of selected biochemical effects. The AUC from cytochrome oxidase inhibition by KCN, and TET, predict survivals of KCN-treated animals under different experimental conditions.

Animals↗
PubMed1991

Diagnosis of paroxysmal nocturnal haemoglobinuria using immunophenotyping of peripheral blood cells.

Paroxysmal nocturnal haemoglobinuria (PNH) is now generally accepted as a disease in which bone marrow derived cells are deficient in phosphatidylinositolglycan (PIG)-anchored surface molecules. A series of new monoclonal antibodies detecting PIG-anchored surface structures on human leucocytes (CD48, CD55, CD59) has recently been described. In the present study 12 patients with the diagnosis PNH and a positive Ham test were examined for PIG-anchored surface antigen expression on various cell lineages using immunofluorescence. In all patients deficient cells were detected in erythrocyte, granulocyte and monocyte analysis. A deficient lymphocyte subset was also observed in all but one of these patients. Using two-colour analysis, all lymphocyte subpopulations such as T, B and NK cells were found to be affected. In addition, peripheral blood cells of 22 patients with severe aplastic anaemia (SAA) were tested for the PIG-anchoring defect. In five of these patients the defect was detected, and in four of the five the lack of PIG-anchored molecules was confined to the granulocyte and monocyte lineages apparently without affecting the erythrocytes. The results of these studies demonstrate that cytofluorographic testing of peripheral blood cells provides a simple and reliable method for establishing the diagnosis of PNH. Furthermore, especially in the case of aplastic anaemia patients, the sensitivity of immunophenotyping might be superior to conventional laboratory tests.

Anemia, Aplastic↗
PubMed1991

[Systemic lupus erythematosus (SLE) with panniculitis and rhabdomyolysis].

In systemic lupus erythematosus as a multi-system disease the involvement of skeletal muscle has been described as a rather mild polymyositis, myopathy or inclusion-body myositis. Here we present a patient with a severe lupus presenting with a fulminant myositis with rhabdomyolysis and panniculitis.

Adult↗
PubMed1990

[Prevalence of secondary complications in patients with type I diabetes mellitus. Results of a retrospective analysis of 549 type I diabetic patients of the Ulm University clinic].

In a retrospective study, we analyzed the prevalence of diabetes-associated late complications in 549 type 1 (insulin-dependent) diabetic patients who have been treated at the University Hospital of Ulm between 1980 and 1987. Retinopathy, proteinuria and neuropathy depended on the duration of the disease, whereas age was the major determinant of large vessel disease. After 20 years of diabetes, 85% of the patients showed retinopathy, half of them proliferative retinopathy, 52% had persistent proteinuria (greater than 500 mg/day), 20% of them were under dialysis. 74% of the patients showed signs of peripheral and/or autonomic neuropathy, 19% had manifestations of large vessel disease. There was no consistent correlation between the levels of glycosylated hemoglobin and the occurrence of diabetic late complications. However, hypertension was closely associated with both small and large vessel disease.

Adult↗
PubMed1990

The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein.

The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein have been established by Edman degradation. The GM2 activator is composed of 162 amino acids, the first two serine residues being present in only 20% of the material. A single carbohydrate chain is N-glycosidically linked to Asn32. Three hydrophobic alpha-helices may contribute to its lipid-binding site. Three amino acids differ from those found by cDNA sequencing which may be due to a polymorphism. The cerebroside sulfate activator consists of 80 amino acids and carries one N-linked carbohydrate chain at Asn21. The C-terminal valine residue is lacking in about 80% of the material. In spite their similar functions, both activator proteins show no sequence or structural similarities.

Amino Acid Sequence↗
PubMed1990

The PIG-anchoring defect in NK lymphocytes of PNH patients.

Paroxysmal nocturnal hemoglobinuria (PNH) is clinically characterized by intravascular hemolysis, hemoglobinuria, iron deficiency anemia, and venous thrombosis. Pathophysiologically the disease has now been generally accepted as an acquired defect of phosphatidylinositol glycan (PIG)-anchored molecules on the cell surface of bone marrow-derived cells. This defect is functionally characterized by an abnormal susceptibility to complement-mediated lysis and has been described on erythrocytes, granulocytes, monocytes, and platelets. In contrast, contradictory data exist so far on the involvement of lymphocytes and natural killer (NK) cells. Using monoclonal antibodies (MoAbs) against newly defined PIG-linked surface structures such as CD48, CD55, and CD59, which are homogeneously expressed on lymphocytes of normal donors, we analyzed lymphocytes and their subpopulations in nine PNH patients by two color immunofluorescence. Our results showed that CD3+ T cells as well as CD16+ NK cells are at least partially involved in the deficient PIG-molecule surface expression. To more clearly define the defect in PNH, we generated NK clones from a PNH patient. Phenotypic analysis of these NK clones showed that they either were positive (n = 3) for PIG-linked surface structures such as CD48, CD55, and CD59 (eg, NKP1) or were completely negative (n = 7) for all of them (eg, NKP1). In functional tests the PIG-molecule negative clone NKP2 showed increased susceptibility to human complement compared with the PIG molecule positive clone NKP1. When analyzing the mRNA levels of the PIG-linked molecules CD55 and CD59 there was no difference at all between the two clones. We conclude from our data that NK cells as well as other lymphocyte subpopulations are involved in the PIG-linkage defect of PNH. These NK clones with differential expression of PIG-linked surface structures present for the first time ex vivo mutant cell lymphocyte lines that carry the defect leading to PIG deficiency in PNH.

Antibodies, Monoclonal↗
PubMed1990

Further studies on protective effects of vitamins in cyclophosphamide-induced cleft palate.

The effects of vitamins B1, B6, and E administered 1 day before and simultaneously with an embryotoxic dose of cyclophosphamide (CPM) were studied using random-bred mice ICR (VELAZ). A single dose of 20 mg/kg CPM administered i.p. or i.m. on day 12 of pregnancy induced in the foetuses cleft palate and malformations of the upper and lower limbs. Both vitamins B1 and B6 decreased nonsignificantly the overall proportion of malformed foetuses and changed the spectrum of malformations, the decrease in foetuses with malformed upper limbs being statistically significant. In the groups supplemented with vitamins the mean foetal weight was higher in litters without malformed upper limbs than in litters with malformed upper limbs and those of both types in the control group. Similar effects of vitamin E were statistically nonsignificant. It is most likely that vitamins influence the pharmacokinetics of cyclophosphamide or its metabolites. The data provided offer no explanation for the claimed beneficial effects of vitamins for preventing the occurrence of orofacial clefts in patients at risk.

Abnormalities, Drug-Induced↗
PubMed1990

New findings explaining the mode of action in prevention of facial clefting and first clinical experience.

Positive clinical results of nonspecific drug prevention in 63 pregnancies at risk, in families with occurrence of cleft lip, alveolus and palate are demonstrated. The model of cleft palate in mice, induced by dexamethasone, was used for the experimental foundation of the method. A significant decrease in the cleft palate incidence, up to 70%, was shown, when the animals were given vitamin B-complex prophylactically, simultaneously and/or therapeutically. Three main possible modes of action supported by experimental results are discussed. The results may be of interest also in respect of other malformation of multifactorial origin.

Animals↗
PubMed1990

A subset of CD16-natural killer cells without antibody-dependent cellular cytotoxicity function.

The low affinity IgG receptor, CD16 (Fc gamma RIII), is expressed on almost all peripheral blood natural killer (NK) cells. A small subset of CD3- CD16- CD56+ NK cells, representing less than 1% of peripheral blood lymphocytes, expands during in vivo IL-2 treatment. To analyze this CD16- NK cell subset in more detail, NK clones have been generated. One of them (TNK2) has been used to study the function of these cells in more detail. It is demonstrated that TNK2 exerts normal NK activity and displays large granular lymphocyte morphology. Since this clone lacks CD16 expression, antibody-dependent cellular cytotoxicity cannot be exerted. CD16 monoclonal antibodies fail to induce cytotoxic activity against NK-resistant target cells. These studies reveal that the lack of CD16 detection is not due to the modulation or the stage of activation of these NK cells. TNK2 is representative of this small subset of peripheral blood NK cells, expanded during IL-2 treatment, which does not express Fc gamma RIII and therefore cannot perform antibody-dependent cellular cytotoxicity.

Antibodies, Monoclonal↗
PubMed1989

[The effect of plastic corrective measures in penile hypospadias on sex behavior in the fertile age].

There are numerous reports on the morphological results after hypospadia operation whereas only few reports do exist on sexual behaviour after this operative treatment. In our experience every fifth patient (18.5%) had psychogenic disturbances of sexual life. The marriage rate was 20% lower than in an age-related group of the normal population and 24% of the patients have had not any sexual contact as yet. Morphological causes of these disturbances were severe penile deviations (3 out of 16 patients); slight deviation occurred in 13 patients. Therefore, an intraoperative artificial erection has been recommended. In two thirds of the patients with psychogenic inhibitions a morphological cause could be verified. In conclusion, patients with hypospadia operation should controlled up to the sexually active life, if necessary under participation of a psychologist.

Adolescent↗
PubMed1989

[Autologous frozen sperm--an alternative in infertility in the patient with invasively treated testicular tumor?].

Through an optimal treatment of testicular cancer the life expectancy of patients is improved, but more early and late complications were observed after different therapeutic procedures and mainly fertility problems come to the fore. In 70% of the patients (n = 30) an abnormal spermiogram was found prior to treatment. At this time 54% of all patients with testicular cancer (n = 61) were 20 to 30 years old and 43% of these patients wish to have a child. After radical retroperitoneal lymph node dissection in 71% of cases (n = 45) a total or partial loss of ejaculation was found. The cytostatic chemotherapy and radiation treatment are the cause of reversible or irreversible reduction in spermatogenesis and possibly mutagenic alterations. There are several alternatives to treat the infertility problems of cured testicular cancer patients and autologous insemination is favoured by the half of these patients. In our experience with cryopreserved sperm (n = 22) only patients with appropriate sperm quality (greater than 10 Mill. sperms/ml, greater than 30% mobile sperms, greater than 30% thaw motility) are suited to this method. In consideration of these parameters only 25% of testicular cancer patients are suited for long-term sperm preservation. The technical problems of sperm preparation, storage and autologous insemination are described in detail.

Adult↗
PubMed1988

Iron release from ferritin and lipid peroxidation by radiolytically generated reducing radicals.

Iron is involved in the formation of oxidants capable of damaging membranes, protein, and DNA. Using 137Cs gamma radiation, we investigated the release of iron from ferritin and concomitant lipid peroxidation by radiolytically generated reducing radicals, superoxide and the carbon dioxide anion radical. Both radicals released iron from ferritin with similar efficiencies and iron mobilization from ferritin required an iron chelator. Radiolytically generated superoxide anion resulted in peroxidation of phospholipid liposomes as measured by malondialdehyde formation only when ferritin was included as an iron source and the released iron was found to be chelated by the phospholipid liposomes.

Carbon Dioxide↗