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Biomedical subjects

H Schmidt

Publications and source records attributed to H Schmidt.

At least 793 records · Page 44Linked to original sources

Recombinant interferon alpha 2 stimulation of target-binding by natural killer cells.

Even though the enhancement of the lyitc capacity and the kinetics of lysis of natural killer cells (NK) by interferon has been well documented, an increase of the target-effector cell binding percentage is still disputed. We, therefore, modified the Grimm-Bonavida single-cell assay so that 400 to 600 cells per individual determination could be reliably evaluated. Using this assay, which makes possible separate determination of effector-target cell binding and target lysis, we demonstrated that, in addition to lytic capacity, target-effector cell binding is also increased by preincubating NK with 100 to 1,000 IU interferon alpha 2 per 10(6) cells. Our data indicate that interferon alpha 2 induces pre-NK cells to bind target cells and that it activates these pre-NK cells to kill the targets.

Adult↗

[Dyskinetic syndrome following the use of metoclopramide].

The relation to the wide use of metoclopramide side effects are rare. These concern the extrapyramidal-motor system among others in form of dyskinetic syndrome. At the instance of a 15-year-old boy the dramatic course with cramp-like increases of the muscle tonus and compulsive movements in head and shoulder region are described. The knowledge of these medicament-induced symptoms is of differential-diagnostic importance to avoid false diagnose and to act with a definite aim. In easier forms of a dyskinetic syndrome suffices the discontinuation of the metoclopramide medication, in more severe cases proves the use of antiparkinsonian agents.

Adolescent↗

[Oral prophylaxis of herpes infections using acyclovir following bone marrow transplantation: a clinical and clinico-pharmacological study].

Viral infections are one of the major complications after bone marrow transplantation, with high mortality and morbidity. Fourty-six patients between 3 and 48 years old (median 15 years) received orally 400 mg (under age 6, 200 mg) acyclovir 4 times daily from day -12 before to day 84 after BMT. All patients were isolated in laminar-airflow units for at least 23 days with total enteral decontamination. They were concomitantly treated with anti-CMV-hyperimmunoglobulin and cotrimoxazol. During acyclovir prophylaxis seven patients had herpes simplex virus infections, all of them were seropositive before BMT. Acyclovir plasma concentrations were measured by use of a new HPLC method. No acyclovir was present (detection limit 40 ng/ml) in the plasma of five out of six patients with HSV infections. Three of them had non-compliance, and a lack of acyclovir absorption developed in two patients under conditioning regimen. No drug-related side effects were observed. Laboratory tests did not show liver or renal toxicity. Take and hematologic reconstitution were unchanged. In our study, oral acyclovir reduced the incidence of herpes simplex infections after bone marrow transplantation. Herpes infections only occurred in patients with non-compliance or lack of acyclovir absorption.

Acyclovir↗

Antagonistic effects of hexose 1,6-bisphosphates and fructose 2,6-bisphosphate on the activity of 6-phosphofructokinase purified from honey-bee flight muscle.

6-Phosphofructokinase purified from honey-bee flight muscle is inhibited by ATP and, unusually, by glucose 1,6-bisphosphate and fructose 1,6-bisphosphate. The inhibition by either of the bisphosphates is not relieved by AMP, but is relieved by fructose 6-phosphate and especially by fructose 2,6-bisphosphate. Lack of effect by AMP is consistent with a low activity of adenylate kinase in this muscle.

Adenosine Triphosphate↗

[Candida abscesses in the liver and spleen. The sonographic and computed tomographic morphology].

In three patients with acute leukemia candidal abscesses occurred. In spite of ready response to induction chemotherapy, septic fever as well as hepatic and splenic enlargement were observed. Broad-spectrum antibiotics did not improve the patients' condition either. Ultrasonography of liver and spleen revealed multiple, small echolucent foci and target lesions. Computed tomography detected multiple, hypodense foci 1-2 cm in diameter; after contrast medium application there was no enhancement. Candidal septicaemia was demonstrated in all three patients.

Abscess↗

[Bone marrow transplantation in acute leukemia, chronic myeloid leukemia, severe aplastic anemia and stage IV neuroblastoma. Effect of antiviral prevention with anti-CMV-hyperimmunoglobulin and acyclovir].

Bone marrow transplantation was performed between IV/82 and X/85 in 64 patients with acute leukemia (n = 36), chronic myelogenous leukemia (CML; n = 13), severe aplastic anemia (n = 12), and neuroblastoma stage IV (n = 3). Of these patients 57 received allogeneic marrow from HLA-ABCDR identical, MLC-negative sibling donors. Six transplants were performed with syngenic marrow and one with autologous marrow. Of the 64 patients 48 survived 40-1,250 days after transplantation, resulting in a survival rate (SR) of 75% and a survival probability (SP) of 71%. Of the 36 patients suffering from acute leukemia (SR = 64%, SP = 51%), patients with acute myelogenous leukemia (AML) in first complete remission (n = 11; SR = 81%, SP = 76%), as well as patients with acute lymphatic leukemia (ALL) in 1st to 4th complete remission at the time of transplantation (n = 14; SR = 81%, SP = 76%) show a favorable prognosis. A poor survival rate was seen for patients with AML when transplanted in second or partial remission (1/5; SR = 20%), as well as for patients suffering from ALL and transplanted during relapse or partial remission (1/6; SR = 16%). Of 13 patients suffering from CML 12 survived the transplantation free of relapse (SR = 93%, SP = 92%), and one patient died from varicella zoster pneumonia. Of the transplanted patients with severe aplastic anemia, 12 of 13 are surviving with complete hematologic reconstitution; one patient, however, died on day 10 from a sepsis. In our patient group, the SR as well as the SP has been improved through changes in the irradiation protocol concomitant with prophylactic application of anti-CMV hypergammaglobulin, as well as through additional oral medication of Azyklovir. The 41 patients (BMT No. 7-47) with total body irradiation at one time show an SR of 44% and an SP of 41%. The following 46 patients (BMT No. 48-93) have reached an SR of 83% and an SP of 74% under the regimen of fractionated total body irradiation, plus prophylaxis with anti-CMV hypergammaglobulin and Azyklovir. Within this group, no fatal CMV pneumonia was encountered as opposed to six patients lost from CMV pneumonia in the first group.

Acyclovir↗

[Bone marrow transplantation in severe aplastic anemia].

Bone marrow transplantations were performed on 15 patients (aged 5-39 years) with severe aplastic anaemia. Twelve patients are alive 76-1930 days (median 668 d) after transplantation, with complete haematopoetic recovery. Total-body radiation with 3.6 Gy in four patients, cyclosporin A administration to ten patients and buffy-coat transfusion to nine patients entirely prevented early rejection. Two patients died of pneumonia (aspergillus; varicella-zoster virus), one patient died of bleeding from a splenic-artery aneurysm. In patients under the age of 40 years with severe aplastic anaemia bone marrow transplantation as early as possible after diagnosis is the treatment of choice if HLA-identical siblings are available as donors. In patients over 40 years treatment should at first be tried with antithymocyte globulin.

Acute Disease↗

Factors governing the modulation of vinca-alkaloid resistance in doxorubicin-resistant cells by the calmodulin inhibitor trifluoperazine.

Calmodulin inhibitors enhance the cytotoxic effects of doxorubicin (DOX) in DOX-resistant (P388/DOX) P388 mouse leukemia cells by augmenting cellular accumulation and retention of drug. In P388/DOX cells which are cross-resistant to vinblastine (VLB) and vincristine (VCR), cell kill following treatment with VLB and VCR alone was evident only after 12 hr of treatment. Additionally, the 2- to 10-fold increase in cytotoxicity of the vinca alkaloids in the presence of 2 and 4 microM trifluoperazine (TFP) was observed only in P388/DOX cells treated for 12 hr, but not for 3 or 6 hr. However, in DOX-sensitive (P388/S) P388 mouse leukemia cells, cytotoxic effects of VCR but not VLB were apparent after treatment for 3 hr, and cell kill with VLB and VCR was enhanced 2- to 20-fold in the presence of 2 and 4 microM TFP following treatment for 12 hr. Cellular accumulation of [3H]VLB in P388/DOX cells was 12-fold lower than in similarly treated P388/S cells and, in the presence of 2 and 4 microM TFP, cellular VLB levels were enhanced 1.3- to 2.0-fold in P388/S cells and 2- to 8-fold in P388/DOX cells. The effect of TFP in increasing cellular retention of [3H]VLB was more apparent with P388/DOX cells, and retention of [3H]VLB in the presence of 4 microM TFP was enhanced less than 1.5-fold and greater than 4-fold in P388/S and P388/DOX cells respectively. Results from this study and our earlier observations with DOX and TFP in P388/DOX cells demonstrate that: (1) TFP potentiates the cytotoxicity of VLB and VCR in P388/S and P388/DOX cells by augmenting drug accumulation and retention; (2) enhanced cell kill in the presence of TFP with P388/DOX cells is apparent at 1 hr for DOX vs 12 hr for VLB and VCR; and (3) in P388/S cells, TFP has a more striking effect on the cellular accumulation, retention and cytotoxicity of VLB and VCR rather than DOX.

Animals↗

[Lipids and apolipoproteins in relation to the degree of coronary sclerosis].

86 male patients with 0-, 1-, 2- or 3 vascular disease who underwent coronary angiography as well as a control group were examined with regard to their lipoprotein constellation: total (TC-), LDL-, HDL-, beta- and alpha-cholesterol (C); triglycerides; apolipoproteins A, AI and B. Significant differences between the mean values of the control group and the patients with coronary disease were found for the groups with 2- and 3-vascular disease for the following parameters: TC, HDLC, TC/HDLC, LDLC/HDLC, alpha-C, TC/alpha-C, beta-C, alpha-C. The quotients TC/HDLC and TC/alpha-C most closely correlate with the degree of the coronary sclerosis. In the apolipoproteins A, B and the index Apo B/A the patients with coronary disease of the groups 0-3 possess equally lowered or increased serum levels and number values, respectively, in comparison to the control group. The apolipoproteins do not show any relationship to the degree of severity of the coronary sclerosis. By means of the parameters combination (Apo A + TC/alpha-C) with a diagnostic sensitiveness of 0.83 and a specificity of 0.87 a coordination coronary disease--healthy could be performed. The classification according to risks should then be performed by means of a cholesterol quotient (TC/alpha-C or TC/HDLC).

Apolipoproteins↗

[Bone marrow transplantation in chronic myeloid leukemia. Influence of gnotobiotic measures, especially antiviral prophylaxis].

Bone marrow from HLA-identical siblings was transplanted in 14 patients with chronic myeloid leukaemia (CML), including one patient in acceleration phase and one in chronic phase following 2 blast crises. Restoration of the bone-marrow occurred in all cases and Philadelphia chromosome could not be detected in any of the patients after the transplantation. Two patients died due to lung complications. Twelve patients who received antiviral prophylaxis (aciclovir per os, anti-CMV-hyperimmunoglobulin) after the transplantation are in very good condition with 140 to 790 days complete clinical and cytogenetic remission. Bone-marrow transplantation, as a curative measure for patients with CML up to the age of 45 (50), should be included in therapy schemes when an HLA-identical sibling is available.

Acyclovir↗

Natural killer cell activity against a thymoma cell line Thy 121 in bone marrow transplant recipients.

Twenty-one patients with acute and chronic leukemia or severe aplastic anemia were studied for NK activity against a thymoma cell line (Thy 121) before and after allogeneic bone marrow transplantation. The means of the pretransplant and post-transplant levels did not differ from the mean of 134 NK determinations in 67 healthy donors. There was no correlation between pretransplant NK levels and the appearance of graft-versus-host disease. Three weeks following bone marrow transplantation, pretransplant NK levels were observed. The sensitivity of NK cells to interferon was the same as in normal donors both before and after bone marrow transplantation. In contrast to methotrexate, cyclosporin A inhibited NK activity in patients and controls in vitro. In vivo cyclosporin A treatment, however, did not decrease NK levels in bone marrow recipients.

Adolescent↗

Induction of the action potential in innervated slow muscle fibers of the frog. Effects of tetrodotoxin, vincristine and colchicine.

Experiments were made to induce action potentials in innervated slow muscle fibers of Rana temporaria. Drugs were applied to the sciatic nerve or its spinal roots by one of the following methods: implantation of a silastic cuff containing tetrodotoxin (TTX); subepineural injection of TTX combined with subcutaneous injections of vincristine; and epineural application of colchicine or vincristine. Twelve to 50 days later slow fibers responded to direct or indirect stimulation with an action potential. A substantial number of these fibers were innervated by 2 or 3 slow motor axons. It is concluded that these effects of TTX and colchicine (vincristine) are due to inhibition of the axoplasmic transport of an unidentified substance. The results support the hypothesis that the inexcitability of normal slow fibers is due to a 'trophic' effect of their motor axons.

Action Potentials↗

Prenatal diagnosis of "dihydrobiopterin synthetase" deficiency, a variant form of phenylketonuria.

Amniocentesis was performed at 19 weeks gestation in a mother who had previously delivered a boy with "dihydrobiopterin synthetase" (DHBS) deficiency. The amniotic fluid contained neopterin in high (136 nmol/l) and biopterin in very low concentrations (1.8 nmol/l). The activity of the phosphate-eliminating enzyme (PEE, also called 6-pyruvoyl tetrahydropterin synthase, substrate: 7,8-dihydroneopterin triphosphate) which is present in liver and erythrocytes and defective in DHBS deficiency, was measured in the erythrocytes of the family members. The fetal sample showed only 2% of the activity of healthy adult controls and was comparable with that of the affected sibling. Obligate heterozygotes had activities around 20% of the controls. Two fetal control samples showed even higher activities than adult erythrocytes, Sepiapterin reductase activities wer normal in all cases. At autopsy, PEE deficiency was confirmed in the liver of the fetus. We concluded that DHBS deficiency (and most probably also GTP cyclohydrolase I deficiency) can be diagnosed by metabolite measurements in amniotic fluid. PEE activity is measurable in erythrocytes, although the assay needs to be improved. Since maternal tetrahydrobiopterin does not cross the placenta, treatment of a tetrahydrobiopterin-deficient fetus with tetrahydrobiopterin in utero is not possible.

Alcohol Oxidoreductases↗

Histamine augments interleukin-2 production and the activation of cytotoxic T lymphocytes.

Histamine (0.5 g/kg) was found to augment the activation of cytotoxic T lymphocytes in vivo, if injected in the late phase (day 4) of the response. The production of interleukin-2 in concanavalin A-activated spleen cell cultures was also strongly augmented by 1 X 10(-2) M histamine or by a combination of 2 X 10(-3) M histamine and histaminase (diamine oxidase). This suggests the possibility that the augmentation in vivo is mediated by the oxidized histamine derivative imidazolylacetaldehyde, since diamine oxidase occurs in many tissues. The interleukin-2-dependent proliferation of a T cell clone, on the other hand, was not affected by histamine with or without diamine oxidase. The experiments suggest that histamine supports the late phase of the cytotoxic T lymphocyte response by augmenting the interleukin-2 production.

Animals↗

Glutathione augments the activation of cytotoxic T lymphocytes in vivo.

The activation of cytotoxic T lymphocytes (CTL) in vivo was found to be augmented by glutathione if injected i.p. in the late phase but not in the early phase of the response. The effect of glutathione possibly resembles the augmenting effect of 2-mercaptoethanol in lymphocyte cultures.

Animals↗