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Biomedical subjects

M Dietrich

Publications and source records attributed to M Dietrich.

At least 91 records · Page 5Linked to original sources
PubMed1992

Human spumavirus antibodies in sera from African patients.

Serum samples collected from patients with a wide variety of diseases from African and other countries were tested for antibodies to the human spumaretrovirus (HSRV). A spumaviral env-specific ELISA was employed as screening test. Out of 3020 human sera screened, 106 were found to be positive (3.2%). While the majority of patients' sera from Europe (1581) were negative, 26 were positive (1.6%). Sera from healthy adult blood donors (609), from patients with multiple sclerosis (48), Graves' disease (45), and chronic fatigue syndrome (41) were negative or showed a very low prevalence for spumaviral env antibodies. A higher percentage of seropositives (6.3%) were found among 1338 African patients from Tanzania, Kenya, and Gabon. Out of 1180 patients from Tanzania, 708 suffered from tumors, 75 from AIDS, and 128 had gynecological problems; 51 of the Tanzanian patients were HSRV seropositive (4.3%). A particularly high percentage of 16.6% seropositives were identified among nasopharyngeal carcinoma patients (NPC) from Kenya and Tanzania consistent with results reported 10 years ago. However, 20 nasopharyngeal carcinoma patients from Malaysia were HSRV-seronegative. In selected cases, sera from seropositive individuals were reacted with proteins from HSRV-infected cells in vitro. HSRV env- and gag-specific antibodies were specifically detected by these sera in Western blots. The results indicate spumavirus infections in human patients with various diseases at a relatively low prevalence worldwide; in African patients, however, the prevalence of spumavirus infections is markedly higher.

Africa↗
PubMed1992

Soluble tumor necrosis factor receptors correlate with parasitemia and disease severity in human malaria.

Elevated serum or plasma concentration of immunoreactive tumor necrosis factor (TNF) is consistently detected in patients with malaria. TNF levels correlate with high parasitemia and clinical severity but not always with outcome. Since the effects of TNF may be neutralized by soluble TNF receptors, sera of 30 nonimmune patients with malaria were analyzed before and during antimalarial therapy. High concentrations of receptors R1 (55 kDa) and R2 (75 kDa) were detected immunologically in all sera of untreated patients. Levels of immunoreactive TNF correlated closely with levels of soluble TNF R1 and R2 (r = .75 and .59, respectively). In contrast, sera lacked cytotoxic activity against target cells in the TNF bioassays. Soluble TNF receptor levels remained elevated for days after treatment. These results suggest that excessive release of TNF induced by the asexual stage of malaria parasites is controlled by a subsequent shedding of soluble TNF receptors that may bind and deactivate biologically functional TNF.

Adolescent↗
PubMed1992

Urogenital tract infections in pregnancy at King Edward VIII Hospital, Durban, South Africa.

OBJECTIVES: To evaluate the role of detecting asymptomatic bacteriuria and endocervical infections in the black prenatal patients attending King Edward VIII Hospital (KEH), Durban, with the view of justifying a screening programme. Screening for syphilis and human immunodeficiency virus (HIV) infection were also evaluated. SUBJECTS: 181 asymptomatic black prenatal patients attending the antenatal clinic for their first antenatal visit volunteered for the study and gave their written consent. DESIGN: Examination of each prenatal patient included obtaining of endocervical swabs to detect endocervical infections (C trachomatis, N gonorrhoeae), serum for syphilitic and HIV testing, and a midstream specimen of urine for microscopy and culture. RESULTS: Asymptomatic bacteriuria was found in 5.6% of patients in this study. Cervical infections were diagnosed microbiologically in 8.2% of women. These were N gonorrhoeae in 4.1% and C trachomatis in 4.7%. Serological tests for sexually transmitted diseases showed the presence of syphilis in 7.6% and antibody to the HIV in 1.9%. Overall, one or more sexually transmitted diseases were found in 16.5% of the women studied. CONCLUSIONS: This study suggests that all women presenting for routine antenatal care in a setting such as Durban should be screened for lower genital tract infections. Ideally this should include a midstream urine specimen for culture, serum for syphilitic and HIV antibody testing and endocervical swabs for sexually transmitted pathogens. In developing communities, however, more reliable and cheaper methods of endocervical screening need to be available before antenatal screening for cervico-vaginal infections can be justified.

Adolescent↗
PubMed1992

Indirect evidence to suggest that prolactin mediates the adrenal action of haloperidol to stimulate aldosterone and corticosterone secretion in rats.

The effect of dopamine-antagonists on steroid secretion has revealed conflicting results regarding the confirmation of in vivo findings in vitro. In order to discriminate in vivo systemic and local action of the dopamine-antagonist haloperidol (HAL) on aldosterone and corticosterone secretion, microdialysis of the adrenal cortex in conscious, freely moving rats was employed. The effects of 2.5 mg HAL ip or intraadrenal dialysis of 20 micrograms/ml HAL in rats with an intact pituitary gland on PRL, aldosterone, and corticosterone secretion were examined. Systemic HAL application resulted in a 40-fold increase in PRL secretion and stimulated aldosterone and corticosterone production significantly. In contrast, intraadrenal dialysis of HAL had no effect on the secretory pattern of PRL or either steroid hormone, indicating no direct drug action on cells of the rat adrenal cortex. Similarly, ip injection of 2.5 mg HAL in hypophysectomized rats did not alter PRL or steroid hormone levels. We conclude that the dopamine-antagonist HAL stimulates aldosterone and corticosterone secretion in rats through a pituitary factor, probably PRL, but not through direct effects at the adrenal cortex.

Adrenal Cortex↗
PubMed1992

Non-linear finite element analysis of formation and treatment of intervertebral disc herniae.

A biomechanical model of the spine motion segment L2/L3 consisting of the truncated vertebrae, endplates, intervertebral disc and pieces of anterior and posterior longitudinal ligaments has been used for a computer simulation study. A non-linear finite element analysis has shown that small loads compressing the spine, not greater than those occurring in everyday life, cause loss of stability of an intervertebral disc, resulting in lateral dislocation of its nucleus pulposus. This could be a potential cause of discopathy. The model indicates that conservative therapy of herniated disc by the traction method may result in retraction of hernia by about 40 per cent.

Biomechanical Phenomena↗
PubMed1991

[Malaria].

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Animals↗
PubMed1991

Purple acid phosphatase from bovine spleen. Interactions at the active site in relation to the reaction mechanism.

Oxidation of the reduced (pink) phosphate-free bovine spleen acid phosphatase with 1.5 mol H2O2 or sodium peroxodisulfate/mol, in the presence of Mes or Bistris pH 5, leads to a species with an absorption maximum at 558 nm. Addition of acetate or oxidation in the presence of acetate buffer engenders a species with a maximum at 550 nm. Addition of phosphate to both species shifts the maximum immediately to 540 nm; this is the species also found after preparation from the spleen. The assumption that these species represent strongly bidentate-binding hydroxo, acetato and phosphato complexes of the Fe(III)-Fe(III) system is supported by replacement reactions with other ligating oxoanions followed by their typical spectral shifts. These oxoanion complexes cannot be dissociated by gel filtration; this is possible only after reduction to the Fe(II)-Fe(III) system. The oxidized species without EPR signals below g values of 2 still reveals 5% activity which cannot be reduced to zero even in the presence of higher concentrations of peroxodisulfate. The pH optimum of the reaction with alpha-naphthyl phosphate shifts from 5.9 to 5.3 in the oxidized species. The apparent pK values around 4.5 as derived from the pH dependence of activity, of the EPR spectra, and the spectral shifts of the phosphate-saturated reduced and oxidized species are assigned to an aquo/hydroxo equilibrium at the Fe(III) or an equilibrium, where the phosphato ligand is replaced by a hydroxo ligand. A reaction mechanism is proposed in which a hydroxo ligand at the chromophoric Fe(III) attacks the phosphoric acid ester group only when that is monoprotonated and pre-oriented by electrostatic interaction with the nonchromophoric metal ion. Binding and inhibition studies with the oxoanions indicate that they compete with the catalytically active hydroxo group of the reduced and oxidized enzyme with nearly the same inhibition constants. Catalysis is not affected by the oxoanions which replace the additional mu-hydroxo ligand in the 558-nm-absorbing Fe(III)-Fe(III) species. In contrast to hemerythrin and ribonucleotide reductase, a binuclear iron center is proposed for the purple acid phosphatase, which is bridged by a carboxylato and two aquo/hydroxo groups, but without a mu-oxo bridge.

Acid Phosphatase↗
PubMed1991

Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels.

PURPOSE: Hemostatic alterations and elevated tumor necrosis factor/cachectin (TNF alpha) serum levels may contribute to the pathogenesis of organ complications in human Plasmodium falciparum malaria. Therefore, we examined whether altered protein C (PC) and thrombin-antithrombin III (TAT) plasma levels correlated with TNF alpha serum concentrations, parasitemia, and the clinical course of human P. falciparum malaria. PATIENTS AND METHODS: Forty-seven patients with P. falciparum malaria were evaluated prospectively before and during antiparasitic therapy. TNF alpha serum levels were determined by immunoradiometric assay, PC and TAT plasma antigen by enzyme-linked immunosorbent assay, and PC and PC inhibitor-1 (PCI-1) activity levels by functional tests. Cultured endothelial cells were incubated with serum from four patients with malaria and from healthy control subjects and then assayed for procoagulant activity. Northern blot hybridization was used to detect tissue factor mRNA. RESULTS: In vivo, TNF alpha serum concentrations were elevated (median: 38.6 pg/mL; n = 47) while plasma levels of PC (antigen 55.4%; activity 39.0%; n = 47) and PCI-1 (0.56 U/L) were decreased in almost all patients before antiparasitic treatment. At the same time, TAT concentrations were high. These alterations correlated significantly (p less than 0.01) both with the severity of the disease (as defined by organ impairment) and with the number of circulating parasitized erythrocytes. Low PCI-1 activity correlated with low PC activity (p less than 0.001) and antigen (p less than 0.05) levels. The plasma level of coagulation factor IX, another vitamin K-dependent protein, was not significantly changed. In vitro, incubation of endothelial cells with patient serum (severe P. falciparum malaria) increased both endothelial cell procoagulant activity and cytoplasmic tissue factor mRNA levels. CONCLUSION: Elevated levels of TNF alpha and TAT, decreased plasma levels of anticoagulant PC, and the induction of procoagulant activity in endothelial cells by patient serum indicate a shift in the balance of hemostatic activity towards a procoagulant state in P. falciparum malaria. The alterations in TNF alpha, TAT, and PC levels may be a response to infection, since they correlate with parasitemia and are reversed during antiparasitic treatment.

Animals↗
PubMed1991

Immunocytochemical determination of antigen and epitope specificity of HIV-1-specific B cells in lymph-node biopsies from HIV-1-infected individuals.

Knowledge about B-cell dysfunction and HIV-specific antibody production is necessary for the understanding of both HIV-1-related immunopathology and the (vaccine-induced) humoral immunity involved in protection against AIDS. This paper describes the application of recently developed methods to detect epitope specificity of B cells in lymph-node biopsies with antigen-enzyme conjugates. Cryosections of five lymph-node biopsies from HIV-1-infected individuals and four control tissues were stained with a panel of HIV-1 antigen-enzyme conjugates: recombinant HIV-1 proteins (gp 160, gp 120 and p24), labelled with peroxidase, and synthetic peptides representing neutralizing epitopes from gp120 and gp41, labelled with alkaline phosphatase. Antibody-forming cells (AFCs) were detected in all the HIV-1-infected biopsies with gp160, gp120 and/or p24, in numbers up to 350 per section. AFCs producing specific antibodies against peptide 101 (SP 101), representing the neutralizing epitope 586-608 of gp41, were detected in one patient. These techniques allow correlation of in vivo function of B cells with lymph-node pathology, clinical stage of the disease and serological data. Their potential for the elucidation of HIV-related immunopathogenesis and the development of vaccines is discussed.

Amino Acid Sequence↗
PubMed1991

A biomechanical model of the human spinal system.

An experimental study of spinal biomechanics both in vivo and in vitro is difficult and often not reliable enough. The mathematical modelling and computer simulation approach is one that can be successfully applied. Modelling in this case is difficult due to the very complicated, heterogeneous nature of the object under investigation. The paper presents a biomechanical model of the spine system consisting of the spinal column (vertebrae, discs), ligaments, muscles directly and indirectly acting on the spinal column, as well as the rib-cage, abdomen and part of the pelvis. The finite element method combined with the optimization approach has been used for modelling. Typical results of these investigations are presented.

Biomechanical Phenomena↗
PubMed1991

Neither heparin nor acetylsalicylic acid influence the clinical course in human Plasmodium falciparum malaria: a prospective randomized study.

Procoagulant alterations and thrombocytopenia in falciparum malaria correlate with parasitemia, serum levels of tumor necrosis factor alpha (TNF alpha), and clinical severity. Thus, heparin or acetylsalicylic acid (ASA), which are used frequently to prevent thrombosis and (in the case of ASA) to control fever, could be potentially beneficial. We randomized 97 patients with falciparum malaria into three groups: 33 patients received low-dose heparin subcutaneously, 31 received ASA intravenously, and 33 did not receive either drug. All patients received appropriate antiparasitic treatment. Eighteen of 97 patients (seven receiving heparin, five receiving ASA, and 6 in the control group) had complications upon admission. During therapy, elevated TNF alpha and lactate dehydrogenase levels and decreased platelet counts returned to normal values. Except for a minimal partial thromboplastin time prolongation with heparin, heparin or ASA did not affect any laboratory parameter, duration of parasitemia, fever clearance, or the length of hospitalization. Thus, it appears that ASA and heparin do not influence the course of falciparum malaria. Hence, in view of possible side effects, these substances should not be recommended for routine use in the treatment of human malaria.

Aspirin↗
PubMed1990

[Recombinant interferon alpha-2A in the treatment of HIV-associated Kaposi sarcoma. Long-term results].

47 HIV-positive male patients with cutaneous Kaposi's sarcoma (KS) were treated with recombinant interferon alpha-2A (IFN) in an open, prospective study. 45 patients received 18 million I.U. IFN s.c. daily for the first three months. From the fourth month, the patients received 18 million I.U. IFN s.c. three times weekly. Four of the 45 patients withdrew from therapy because of side effects during the first weeks (weeks 2 to 6) of treatment. The remaining 41 patients were treated for a minimum period of two years or until their death. Two further patients received 36 million I.U. IFN daily for three months. After three months of IFN therapy we observed complete remission (CR) in five of the 41 patients (12%), partial remission (PR) in seven patients (17%), stable disease in seven patients (17%) and progressive disease (PD) in 22 patients (54%). The mean survival time from the beginning of IFN therapy to date is 26 months for the 19 responders (patients with CR, PR or SD; six are still alive) and nine months for the 22 non-responders (patients with PD; all died). Recurrence of tumor progression occurred in 15 of the 19 responders after an average of ten months of continuous IFN therapy. The longest time of survival in this group is 54 months up to now. Of the four remaining patients, all in the CR group, two died after 24 and 26 months of IFN therapy, without any recurrence of KS growth (causes of death: Burkitt's lymphoma and unknown). The two other patients, both still alive, have not suffered any recurrence of tumor progression after 40 and 41 months, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

CD34+ hematopoietic progenitor cells are not a major reservoir of the human immunodeficiency virus.

Hematologic abnormalities occur in the majority of patients with acquired immunodeficiency syndrome (AIDS). Infection of the hematopoietic progenitor cells has been proposed as a potential explanation. In this study, different bone marrow cell populations, including the CD34+ hematopoietic progenitor cells, were purified by a fluorescence-activated cell sorter (FACS) and analyzed for the presence of human immunodeficiency virus-1 (HIV-1) proviral DNA using the polymerase chain reaction. A group of 14 patients with AIDS or AIDS-related complex (ARC) was studied (11 with peripheral blood cytopenias). The CD4+ helper cells in the bone marrow were found positive for HIV-1 DNA in all patients. In contrast, CD34+ progenitor cells were positive in only one patient. Two monocyte samples and two samples of CD4-/CD34- lymphocytes/blasts (mainly B and CD8 lymphocytes) were positive. Proviral DNA could not be detected in granulocytes. FACS analysis showed that the percentage of CD34+ hematopoietic progenitor cells was not altered in the bone marrow of AIDS patients in comparison with the HIV-1 seronegative controls. In contrast, the number of CD4+ lymphocytes was markedly reduced in the bone marrow of AIDS patients. These results show that the hematologic abnormalities in AIDS patients are neither explained by direct infection of the hematopoietic progenitor cells with HIV-1 nor by a depletion of progenitor cells.

Antigens, CD34↗
PubMed1990

Inhibition of HIV progression by dithiocarb. German DTC Study Group.

60 patients with HIV-1 infection in Walter Reed stages 2-4 were randomised to treatment with intravenous or oral dithiocarb (diethyldithiocarbamate, DTC) or placebo for 24 weeks in a paired double-blind design. 55 patients were evaluable at the end of the study: no patient who had received DTC but 6 placebo patients had AIDS, a significant difference. Significantly delayed disease progression was observed in the intravenous DTC group compared with its matching placebo. The benefit in the oral DTC group was not statistically significant. During an 18-month follow-up 3 deaths occurred in the original placebo groups, whereas no patient who had initially received DTC died. A significant delay in progression to AIDS was observed in the DTC groups.

Acquired Immunodeficiency Syndrome↗
PubMed1990

[Malaria tropica with activation of blood coagulation and detection of tumor necrosis factor (NF-alpha) in serum].

A 38-year-old patient with cerebral P. falciparum malaria was admitted 12 days after a short trip to Kenya. The serum level of tumor necrosis factor (TNF-alpha) was elevated (251 pg/ml). In contrast, Protein C (plasma activity 36.1%; antigen concentration 31.7%) and protein C inhibitor 1 (activity 0.55 U/ml) levels were decreased. This suggested a state of functional activation of the clotting system which was confirmed by elevated levels (4.8 ng/ml) of circulating thrombin-antithrombin-III-complexes (TAT). Protein S (total and free) and coagulation factor IX levels were within normal range. Under successful antiparasitic therapy, TNF-alpha as well as protein C and protein C inhibitor 1 levels returned to baseline within one week. In the context of other studies that demonstrate procoagulant effects of TNF-alpha, it is remarkable that in the case of complicated P. falciparum malaria, an elevated concentration of TNF-alpha can be paralleled by a decreased plasma level of protein C and an increase in TAT suggesting a procoagulant state.

Adult↗
PubMed1990

A monoclonal antibody directed against the human intercellular adhesion molecule (ICAM-1) modulates the release of tumor necrosis factor-alpha, interferon-gamma and interleukin 1.

ICAM-1 is a cell surface glycoprotein which is one of the ligands for the leukocyte function-associated antigen (LFA-1). It is involved in leukocyte adhesion to endothelial cells as well as in immune functions requiring cell-cell contact. The quantitative expression of ICAM-1 in various cell types can be either induced or enhanced by treatment with cytokines, such as interferon-gamma (IFN-gamma), tumor necrosis factor (TNF)-alpha or interleukin 1 (IL 1), a phenomenon which results in the augmentation of binding to LFA-1-positive cells. In contrast, treatment with anti-ICAM-1 antibodies blocks this binding. A monoclonal antibody (mAb), termed 7F7, which recognizes an epitope on ICAM-1, was used to investigate the role of ICAM-1 in cytokine production by T lymphocytes and monocytes. Production of TNF-alpha. IFN-gamma and IL1 was significantly inhibited (p less than 0.01) by the incubation of mAb 7F7 with phytohemagglutinin-activated blood mononuclear cells (MNC) or isolated E rosette-positive T lymphocytes. The maximal level of inhibition was reached with 1 microgram/ml of purified antibody. A similar inhibition was obtained using saturating concentrations of 400 microliters/ml of mAb 7F7 hybridoma supernatant corresponding to an inhibitory activity of 1 microgram of purified mAb. In contrast, granulocyte/macrophage-colony-stimulating factor release showed a heterogeneous response over five experiments with an increase found in three experiments and a decrease in two experiments. Addition of increasing concentrations of supernatant or purified mAb to unstimulated MNC or T lymphocyte cultures had no effect on cytokine release. The observed inhibition of the production of TNF-alpha. IFN-gamma and IL 1 by antibody-mediated blockade of the ICAM-1 structure probably represents a negative circuit that serves to tune the activation of leukocytes and to avoid an overproduction of cytokines.

Antibodies, Monoclonal↗