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Biomedical subjects

H Wolf

Publications and source records attributed to H Wolf.

At least 847 records · Page 47Linked to original sources

Structural and immunological reactivity of the principal neutralizing determinant V3 of glycoprotein gp120 of HIV-1.

The variable domain V3 in the outer glycoprotein gp120 of HIV-1 is a highly important region with respect to immune response during the course of viral infection. Neutralizing antibodies are produced against this domain: in addition, it has been shown to be a functionally active epitope for T helper and cytotoxic T cells. The high degree of amino acid variability in individual HIV-isolates, however, limits the use of the V3-domain in approaches to vaccine development. In order to characterize the residues important for antibody interaction and binding to MHC class I proteins, we constructed a consensus sequence of the V3-domain with broad reactivity [1] and used synthetic peptides derived from this consensus sequence with individual residues altered to alanine. These peptides were used as antigens in ELISA tests to define the amino acids which are important for binding to human and rabbit/anti-peptide immunoglobulins. In addition, we used these alanine-derived peptides in interaction studies with human HLA-A2.1 and mouse H-2Dd by testing their capacity to stabilize the respective MHC class I protein complexes on the surface of mutant cell lines T2 and RMA-S transfected with Dd gene. The experimental tests allowed us to define individual residues involved in antibody and MHC-protein interaction, respectively. In a further approach, we used those results to design interaction models with HLA-A2.1 and H-2Dd. Therefore, a structural model for H-2Dd was built that exhibits an overall similar conformation to the parental crystal structure of HLA-A2.1. The resulting interaction models show V3-peptide bound in an extended beta-conformation with a bulge in its centre for both H-2Dd and HLA-A2.1 complexes. The N- and C-termini of V3 peptide reside in conserved pockets within both MHC-proteins. Anchoring residues could be determined that are crucial for the binding of the respective MHC class I haplotype. The cross-reactivity of V3-peptide in enhancing the expression of two different MHC class I molecules (H-2Dd and HLA-A2.1) is shown to be based on similar peptide binding that induces an almost identical peptide conformation.

AIDS Vaccines↗

Chest lifting.

The male chest has a female appearance in patients with gynecomastia and those who have experienced a huge weight loss. The disadvantages of reduction mammaplasty for men are the visible scars on the chest wall necessitated because of skin redundancy. The aims of the chest-lifting procedure are to reposition the breast, to create a male appearance by thinning the amount of glandular and fatty tissue, to avoid noticeable scars on the chest wall, and to hide the scar in the middle axillar line.

Adult↗

Fine specificity of the murine antibody response to HIV-1 gp160 determined by synthetic peptides which define selected epitopes.

In this report, we assess the humoral immune response in inbred strains of mice immunized with baculovirus-derived recombinant HIV-1 gp160 (rgp160). Six inbred strains of mice were each immunized with two different concns (5 and 50 micrograms) of rgp160, and the antibody response to rgp160 and synthetic peptides which define distinct gp160 epitopes was examined. Within a given inbred strain of mice, no significant difference in antibody titers to gp160 was observed in those groups receiving either 5 or 50 micrograms of rgp160 per injection. Following three immunizations with rgp160, differences in anti-gp160 titers were observed among the various inbred strains; however, these differences became less apparent after additional injections with rgp160. In addition, each mouse strain exhibited a unique reactivity pattern to seven gp160 epitopes defined by synthetic peptides. Multiple injections with rpg160 were required to induce responses to certain gp160 epitopes. The observed differences in the fine specificity of the humoral immune response to distinct gp160 epitopes among the six inbred strains suggest a genetic basis for regulating the antibody response to these epitopes. This apparent regulation can be overcome by multiple injections with rgp160.

Amino Acid Sequence↗

Hippocampal volume discriminates between normal cognition; questionable and mild dementia in the elderly.

The sensitivity of MRI volumetric measures to detect cognitive dysfunction is examined in 39 participants of an epidemiological field study (age 75-85, MMSE 19-30). According to Clinical dementia rating (CDR), 17 subjects had normal cognition (CDR 0), 12 had questionable (CDR 0.5) and 10 mild dementia (CDR 1). Discriminant analysis based on four hippocampal measures resulted in a correct classification of 76.9% of all subjects. Left-sided and posterior hippocampal measures were more responsible for group discrimination than right-sided and anterior measures. In CDR 0.5, a significant hippocampal volume reduction of 14.3% vs.11.3% (left vs. right) relative to normal was found. The right hippocampus was significantly greater than the left in CDR 0 and CDR 0.5, but not in CDR 1. The magnitude of non-directional hippocampal asymmetry increased with decreasing cognitive state. We conclude that hippocampal atrophy is sensitive to detect cognitive dysfunction and subjects at risk for Alzheimer's disease in the elderly population.

Aged↗

[Zellweger's syndrome (cerebro-hepato-renal syndrome)--its clinical picture, morphology and biochemical diagnosis].

The cerebro-hepato-renal (Zellweger) syndrome is characterised by dysmorphic features, severe muscular hypotonia, hepatic dysfunction and early death in infancy. Recently it has been shown that the disease is an inborn error of metabolism with an unusual variety of metabolic disturbances affecting pipecolic acid, bile acids, plasmalogens and very long chain fatty acids. Ultrastructural and biochemical findings confirming the diagnosis are illustrated. The syndrome is inherited as an autosomal recessive trait, prenatal diagnosis has become possible.

Abnormalities, Multiple↗

Posttraumatic stress disorder following preeclampsia and HELLP syndrome.

Posttraumatic stress disorder (PTSD) in connection with pregnancy was first described in the 1990s--initially in relation to childbirth but later more specifically to the mode of delivery. Instrumental vaginal delivery carries the highest risk of PTSD followed by emergency caesarean section and normal spontaneous delivery. Loss of pregnancy, spontaneous abortion or intrauterine death for example can also lead to PTSD. Little systematic research has been performed regarding the psychological consequences of severe preeclampsia or HELLP syndrome, although it would seem obvious that these conditions may have a great effect The combination of suffering a serious illness combined with an unexpected caesarean section or delivery, often of a premature child, is a heavy burden to bear both physically and psychologically. We describe here three patients who developed PTSD after pregnancies complicated by severe preeclampsia or HELLP syndrome. PTSD can develop after preeclampsia or HELLP syndrome.

Adult↗

Cystosarcoma phyllodes malignum: a case report of a successive triple modality treatment.

This paper reports on a woman with a rapidly growing recurrent cystosarcoma phyllodes malignum after two major attempts of surgery. In this situation, neoadjuvant hyperfractionated radiotherapy, superficial hyperthermia and ifosfamide were administered. Toxicity was mild. Resection of the tumour bed revealed a pathologically complete response with an actual disease free follow-up of 48 months.

Antineoplastic Agents, Alkylating↗

Lack of anti-factor Xa activity in umbilical cord vein samples after subcutaneous administration of heparin or low molecular mass heparin in pregnant women.

Prophylaxis of thromboembolism with low molecular mass (LMM) heparin may offer several advantages over conventional heparin during pregnancy. Heparin-related side effects as osteoporosis, local allergy, thrombocytopenia and increase in liver enzymes may occur less frequently with LMM heparin. However, LMM heparins of different origins have to be considered as individual pharmaceutical compounds. This is of special clinical importance regarding a possible placental passage. We performed a randomized controlled study comparing the anti-factor Xa activities in plasma samples of 60 pregnant women undergoing delivery at term and in the umbilical cord vein of the newborn after subcutaneous administration of 5,000 IU unfractionated (UF) heparin or 1,500 activated partial thromboplastin time units LMM heparin or placebo. Injections were performed about 2 h prior to the delivery. Maternal and fetal blood samples were taken at the same time to assay heparin activity by the heptest coagulation assay and the S2222 chromogenic substrate method. LMM heparin was detected in all maternal plasma samples whereas UF heparin was measurable only in about one third of them. UF heparin as well as LMM heparin were not detectable in samples taken from the umbilical cord vein. The data demonstrate that neither UF nor the LMM heparin used in this study cross the placenta in relevant inhibitory activity towards factor Xa. This finding is in accordance with the previous experiences regarding the safe administration of other LMM heparins for prophylaxis of thromboembolism during pregnancy.

Adult↗

Carbazole antibiotics synthesis in a Streptomyces tendae bald mutant, created by acriflavine treatment.

Acriflavine treatment on Streptomyces tendae generated a bald mutant (bld-1) with an altered antibiotic pattern. The parental strain produced nikkomycins and juglomycins, whereas the mutant bld-1 was only capable of juglomycin synthesis. The existence of a mutant defective in morphogenesis and in nikkomycin biosynthesis suggests a common regulation of these processes. An interesting finding of this study is that mutant bld-1 produced two carbazole derivatives, hitherto never seen in cultures of the parental strain. It seems likely that the DNA intercalating dye acriflavine, by mutagenesis, had activated cryptic genes which are involved in carbazole synthesis. The two carbazole derivatives were identified as the neuronal cell protecting compounds CS-79B and carquinostatin A, recently isolated from a wild-type of S. exfoliatus. We found that both substances showed antibacterial activity.

Acriflavine↗

Predictive relevance of soluble CD44v6 serum levels for the responsiveness to second line hormone- or chemotherapy in patients with metastatic breast cancer.

Concentrations of soluble CD44 standard (sCD44std) and CD44 variant 6 (sCD44v6) isoforms were determined in the sera of 59 patients with distant metastasis from breast cancer receiving second line hormone- or chemotherapy, in comparison to 46 breast cancer patients without detectable recurrent disease and 21 healthy blood donors. The sera of non-metastatic breast cancer, patients contained sCD44std and sCD44v6 concentrations similiar to those of healthy blood donors. In sera of patients with distant metastasis from recurrent breast cancer the median values of sCD44std and sCD44v6 were significantly higher (sCD44std: 502 ng/ml, p=0.03; sCD44v6: 193 ng/ml, p = 0.002) in comparison to healthy blood donors and patients with non-metastatic disease (p<0.001 for both parameters). A significant correlation was observed between sCD44v6 serum concentrations and the number of metastasized organs (p=0.0018), serum LDH concentrations (p<0.0001), tumor grading (p=0.025) and the presence of hepatic metastasis (p=0.028). Furthermore, sCD44v6 expression was associated with the patient's responsiveness to second line hormone- or chemotherapy. Non-responders had significantly higher sCD44v6 levels compared with the responder group (median: 447 ng/ml vs 171 ng/ml; p=0.0007). Logistic regression analysis indicated that sCD44v6 serum levels above 250 ng/ml (p =0.033) and the presence of hepatic metastasis (p=0.009) were independent factors predicting an unfavourable response to therapy.

Adult↗

[Oral hairy leukoplakia in human immunodeficiency virus positive patients: clinical and etiopathogenic aspects].

Clinical and etiopathogenetic features of oral hairy leukoplakia in 5 patients positive for Human Immunodeficiency Virus were studied. Oral hairy leukoplakia were located on the lateral borders of the tongue and showed a corrugated/hairy aspect in all the cases. Histological examination showed hyperparakeratosis, acanthosis, hair like projection (n = 4) koilocyte-like-cells and moderate subepidermal inflammation. Immunohistochemistry revealed positive results for Epstein-Barr virus indicating an active replication of this virus within the epithelial cells of the stratum granulosum and upper stratum spinosum.

Adult↗

[The presence of the Epstein-Barr virus in Waldeyer's lymphatic ring during the acute phase of infectious mononucleosis].

The aim of our research was to detect the existence of virus Epstein-Barr genome in the palatine- and the nasopharyngeal tonsil obtained from six patients during the acute phase of the infectious mononucleosis. The presence of EBV-DNA was demonstrated with the help of nucleic acid hybridization techniques (Southern-Blot and in situ hybridization) in the two components of the lymphoepithelial ring of the throat. The pathogenesis and the therapeutic implications of these findings are discussed.

Acute Disease↗

Simplified radiolabeling and initial experimental studies of the in vivo kinetics of iodine-123 atrial natriuretic peptide.

Conventional methods regarding the iodination of atrial natriuretic factor (ANP) were associated with the use of high performance liquid chromatography in a linear elution technique. This chromatographic system is not standard in most radiochemical laboratories. The present study describes a method that allows labeling of ANP with 123I-iodide by using conventional isocratic HPLC equipment. First, the labeled protein was purified in a cascaded way. Then eight gradients with a ratio of acetonitrile/water of 5/95 up to 60/40 (v/v) and a time range of 5 min were applied. The iodinated ANP eluted at about 25 to 30% of acetonitrile. Centrifugation with a speedvac resulted in an injectable solution. Administration of about 20 MBq/kg [123I]iodo-ANP to a rabbit was performed in a pilot study to evaluate the in vivo kinetics of various organs by dynamic acquisition with a gamma camera. The kidneys showed an increasing uptake from 4.2 to 5.3% of total body activity after 75 min. An increasing tracer uptake was also observed in the skull region from 2.4% after 10 min to 3.6% at 75 min. The time activity curve of the liver showed a decrease from 6.6 to 5.1% and that of the heart from 3.7 to 2.9% at 75 min. Thus, labeling of ANP--and probably other peptides--is possible with a simplified cascade elution procedure without the use of gradient HPLC equipment.

Animals↗

Non-Hodgkin's lymphomas--prognostic analysis and therapeutic recommendations.

The total non-Hodgkin's lymphoma-population between 1960 and 1985 treated by means of radiotherapy or combined radio-chemotherapy in the Medical Academy Dresden was analysed prognostically. 247 patients were classified according to previous scheme, 79 were subdivided on the basis of the recommendations of the Kiel-classification. The remission rates and survival curves achieved bear comparison with international literature (remission rates for the low-malignancy group = 85.3% and for the high-malignancy group = 80.0%; 5-year survival rates for the low-malignancy group = 61.9% and for the high-malignancy group = 41.7%). The influence of histology, clinical stage and involvement of organs is discussed according to our results and information from appropriate reference sources. Our analysis confirms the high importance of a common radiologic-internal outpatient department for coordination of the diagnostic and therapeutic programme. Principles of treatment are presented with special respect to polychemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗