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Biomedical subjects

E Wolpert

Publications and source records attributed to E Wolpert.

At least 19 recordsLinked to original sources

St John's wort: a potential therapy for elderly depressed patients?

St John's wort (Hypericum perforatum) has a 2000-year history of use as a medicinal herb. Its modern application as a plant extract for treating depression has undergone scientific investigation over the last decade, and its effectiveness has been shown in studies comparing it with placebo and reference antidepressants. Our own work supports the contention that LI 160, the best-documented St John's wort medication, is effective at a high dosage even in patients with severe depression. Since the new Berlin Aging Study revealed significant treatment deficiencies among elderly depressive patients, St John's wort extracts may be a useful alternative to benzodiazepines to avoid nontreatment of early depression. Because St John's wort preparations have better tolerability than tricyclic antidepressants, elderly people in particular, can benefit from their use.

Aged↗

HA-1 and the SMCY-derived peptide FIDSYICQV (H-Y) are immunodominant minor histocompatibility antigens after bone marrow transplantation.

BACKGROUND: Allogeneic bone marrow donors can be incompatible at different levels. Even HLA-identical pairs will be still incompatible for numerous minor histocompatibility antigens (mHag). Nevertheless, some incompatibilities are found to be associated with an increased risk of graft-versus-host disease (GVHD), which could be related to the way the immune system recognizes these antigens. METHODS: We determined the specificity of cytotoxic T-cell clones isolated during acute GVHD or during bone marrow graft rejection in patients (n=14) transplanted with marrow from donors who were histoincompatible for different minor and/or major histocompatibility antigens. RESULTS: We found a clear hierarchy among the different types of histoincompatibilities. In three combinations mismatched for a class I allele, all 27 clones isolated during GVHD were specific for the incompatible HLA molecule. In the 11 class I-identical combinations, 14 different mHags were recognized. The mHag HA-1, known to have a significant impact on the development of GVHD, was recognized in the two HA-1-incompatible combinations. In one of these combinations, which was sex mismatched, all 56 clones analyzed were directed against HA-1, demonstrating the dominance of this mHag. In the four HA-1-compatible, sex-mismatched combinations, the anti-H-Y response was directed against one immunodominant epitope rather than against multiple Y-chromosome-encoded epitopes. All male specific cytotoxic T lymphocytes (n=15) recognized the same high-performance liquid chromatography-purified peptide fraction presented by T2 cells. Moreover, all cytotoxic T lymphocytes tested (n=6) were specific for the SMCY-derived peptide FIDSYICQV, originally described as being the H-Y epitope recognized in the context of HLA-A*0201. CONCLUSIONS: Some histocompatibility antigens are recognized in an immunodominant fashion and will therefore be recognized in the majority of mismatched combinations. Only for such antigens, correlations between mismatches and the occurrence of GVHD or graft rejections will be found.

Bone Marrow Transplantation↗

[Group psychotherapy in psychiatry--results of a pilot study and perspectives].

This paper reports about first preliminary results of an investigation by DGPPN regarding group therapeutic work in psychiatric inpatient settings throughout the Federal Republic of Germany. The DGPPN sub-section "Group Therapy in Psychiatry" was set up by starting with this pilot study using a preliminary version of a questionnaire which is currently under revision for future investigations. This paper also deals with a brief historical survey of the origins of group work and group therapy in institutions. In regards to the installation of the new domain of a "Physician for Psychiatry and Psychotherapy" it is intended to theoretically consolidate group therapy in psychiatric facilities. The "Interpersonal Model" of Sullivan is being highlighted as a useful theory towards an integration of various theoretical perspectives such as biological, individual, interpersonal, and sociological ones. This integration is being stressed for education/ training and treatment aspects in psychiatry and psychotherapy as well.

Germany↗

Dominant and cryptic antigens in the MHC class I restricted T cell response across a complex minor histocompatibility barrier: analysis and mapping by elution of cellular peptides.

T cell responses against complex antigens are often directed against a limited set of immunodominant determinants. We have studied this phenomenon at the level of cellularly processed peptides recognized by CTL in the B6 anti-BALB.B minor histocompatibility (H) barrier, comprising at least 29 antigen loci. B6 anti-BALB.B CTL always recognized three reverse phase HPLC fractions in BALB.B eluates, whether the latter were obtained from cell lysates or immunoaffinity purified class I molecules. One of these immunodominant epitopes (termed IDE-1) was H-2Db restricted, and two (termed IDE-2 and IDE-3) were H-2Kb restricted. B6 mice were immunized with spleen cells from B6 congenic mice carrying single minor H loci from BALB.B with the aim to assign IDE to given minor H loci and to investigate whether additional epitopes could be identified in the absence of the immunodominant ones. IDE-3 was found to be associated to the locus H-28; in addition five so called cryptic epitopes were defined. Induction of CTL against these epitopes required immunization with cells of the congenic strain; BALB.B spleen cells failed to immunize. One subgroup of these epitopes (those associated to H-8, H-19 and H-25) were nevertheless found to be processed and loaded in class I molecules of BALB.B cells, while there was no evidence for this for H-35 and H-36. For 10 additional congenic strains, no CTL response was detected. The results are discussed in relation to the genetic and molecular basis of minor H antigens, and mechanisms for epitope dominance operating at the level of the APC or responding T cells.

Animals↗

Transfection of beta 2-microglobulin restores IFN-mediated protection from natural killer cell lysis in YAC-1 lymphoma variants.

A beta 2-microglobulin (beta 2m)-deficient variant of YAC-1, A.H-2-, was transfected with a genomic beta 2m clone. Transfected cells were used to investigate the role of beta 2m in IFN-induced protection from NK cell lysis. IFN-gamma treatment of the NK-sensitive murine YAC-1 lymphoma results in reduced sensitivity to NK cell-mediated lysis in parallel with increased expression of its constitutively low MHC class I expression. It was previously shown that the A.H-2- variant had lost both these capacities, although it retained other responses to IFN-gamma. Here beta 2m transfection restored the YAC-1 phenotype with respect to an inducible expression of MHC class I molecules and a concomitant protection from NK cell lysis after treatment with IFN-gamma. In the absence of IFN-gamma the NK sensitivity of the transfectants did not differ significantly from A.H-2-. A similar protection from NK cell lysis, in parallel with enhanced MHC class I expression, was observed for in vivo-passaged beta 2m transfectants whereas no protection was found for in vivo-passaged A.H-2- cells. The present study provides evidence that the IFN-gamma-mediated protection from NK cell lysis is dependent on beta 2m expression in the YAC-1 lymphoma. Restoration of MHC class I assembly, transport, and concomitantly an IFN-gamma augmentable cell surface expression of MHC class I molecules is a possible explanation for the effect of beta 2m.

Animals↗

Resistance to H-2-restricted but not to allo-H2-specific graft and cytotoxic T lymphocyte responses in lymphoma mutant.

The lymphoma mutant RMA-S escaped graft rejection after transplantation over a minor histocompatibility barrier, whereas it was rejected in H-2 allogeneic mice. The parental control line was rejected in both situations. The mutant, which had been selected against MHC class I molecules retained 5 to 10% of the wild-type H-2Db, Kb, and beta 2-microglobulin expression on the cell surface. It remained sensitive to allo-H-2b CTL in vitro, but was completely resistant to minor histocompatibility antigen-specific, H-2b-restricted CTL. It was equally resistant to other H-2b-restricted responses against internally derived Ag, such as tumor-specific CTL or a CTL clone specific for the influenza virus nucleoprotein. The results indicate a target cell defect that selectively abolishes the sensitivity to H-2-restricted CTL directed against internally processed Ag. This appears sufficient to shift the transplantation response over a minor histocompatibility Ag barrier from rejection to acceptance. There are two possible explanations for the results: 1) a block in the MHC class I-directed pathway for internal Ag processing, and 2) subthreshold H-2/Ag ligand density in relation to triggering requirements of restricted CTL. Regardless of the type of defect, the results demonstrate a difference between allo-H-2-specific and H-2-restricted CTL recognition at the level of the target cell.

Cytotoxicity, Immunologic↗

Effect of diet-induced sodium deficiency on normal and compensatory growth of the lung in young rats.

Sodium deficiency is associated with decreased muscle growth and protein synthesis. We investigated the influence of diet-induced sodium deficiency on the rate and extent of compensatory growth of the right lung after left pneumonectomy in young rats of 83 +/- 1 g body weight. Starting 1 wk before surgery, all rats were fed a diet deficient only in sodium (2-9 mumol Na+/g of food) ad libitum. Sodium-deficient rats were supplied with distilled water, whereas sodium-replete controls were supplied water containing 37 mM NaCl. After 7 d on the experimental diets, both groups were divided and subjected either to sham thoracotomy (Sham) or to left pneumonectomy (PNX). Somatic growth and both normal and compensatory growth of the lungs were assessed 3, 4, and 7 d later. Sodium-deficient animals grew more slowly than control animals. In control PNX rats, right lung weight to body weight ratio (LW/BW) increased to equal that of the combined LW/BW in control Shams by postoperative d 4, and remained at the Sham combined LW/BW value on postoperative d 7. Compensatory lung growth was less rapid in sodium-deficient PNX animals. At postoperative d 4, right LW/BW was low relative to combined LW/BW of sodium-deficient Shams. This ratio approached but did not reach the sodium-deficient Sham combined LW/BW value by d 7. Sodium deficiency thus reduced the rate of compensatory growth of the right lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Low serum testosterone/dihydrotestosterone ratio in patients with pancreatic carcinoma.

Serum testosterone, its metabolite 5 alpha-dihydrotestosterone, and the testosterone/dihydrotestosterone ratio were investigated in 22 male patients with proven pancreatic cancer, and compared with values from male patients with chronic pancreatitis (n = 21) and with nonpancreatic gastrointestinal tumors (n = 19). Testosterone and the testosterone/dihydrotestosterone ratio were significantly lower (p less than 0.001) in the pancreatic cancer group when they were compared with the other two groups. There was no significant difference in the dihydrotestosterone values between cancer groups. A testosterone/dihydrotestosterone ratio of less than 5 clearly distinguished most of the patients (20/22) with cancer of the pancreas from those with other tumors or chronic pancreatitis. The results suggest an alteration in the serum androgen profile in these patients. Therefore, the testosterone/dihydrotestosterone ratio could be a useful marker in the diagnosis of pancreatic carcinoma in male patients.

Dihydrotestosterone↗

Effects of synthetic steroid contraceptives on biliary lipid composition of normal Mexican women.

The effects of two hormonal contraceptives upon the biliary lipid composition of Mexican women were evaluated in a prospective study. Twenty-one healthy volunteers of reproductive age were allocated into three groups (7 subjects each). Group I served as the experimental control (all subjects were bearing a non-medicated IUD), group II received i.m. norethisterone enanthate (NET-e) 200 mg every two months, and group III received an oral combination of 1-norgestrel 150 micrograms and ethinyl estradiol 30 micrograms. The bile lithogenic index as assessed by the relative proportion of cholesterol to bile acids and lecithin was determined in duodenal bile samples obtained before (baseline), during (4 months), and after (12 months) contraceptive administration. The results indicated that NET-e administration resulted in a slight although significant increase of the lithogenic index while the oral formulation did not. The overall data were interpreted as demonstrating that administration of these steroid contraceptives does not constitute a risk factor in terms of gallstone formation in the population studied. The estrogen-like behavior exhibited by NET-e is discussed.

Adult↗

Central nervous side effects following ifosfamide monotherapy of advanced renal carcinoma.

Ten patients with advanced renal carcinoma were treated by ifosfamide (50-60 mg/kd/day x 5 days). The treatment was repeated every 4 weeks and continued until progression appeared. Two patients came into partial remission, two had subjective improvement, and six did not respond. Seven patients developed acute psychopathological symptoms during the first ifosfamide-cycle. Five patients had visual and paranoid hallucinations, four patients were completely confused. Follow-up for up to 10 weeks showed a persisting organic brain syndrome in five patients.

Adult↗

[Treatment of drug-induced dryness of mouth in psychiatric pateints--a controlled comparative study (author's transl)].

The present study examined the effects of various substances on salivary secretion in 25 psychiatric inpatients suffering from depression or schizoprenic disorders. It is well known that tricyclic neuroleptics and anti-depressants lower the rate of salivary excretion and lead to hyposalivation and a dry mouth. The following methods were studied on their effect to compensate hyposalivation: Distigminbromid, sweets, Glandosane, a new synthetic saliva, and water which was gustatory adopted. Salivary flow was measured according to Matzker (7). Subjective feelings of thirst and mouth dryness were recorded by selfconstructed tests. Only Glandosane and Distigminbromid compensated mouth dryness. The recorded amount of salivary flow was within the range of normal controls. There were no significant correlations between the subjective test answers and the objective measurement of salivary rate. Improvement of depression by application of Glandosane could not be observed. Patients treated with Glandosane felt most comfortable whereas in those treated with Distigminbromid side effects as digestive disorders, urinary disorders and changes in perspiration were observed.

Adult↗

[Vigilance and spontaneous nystagmus. An electronystagmographic study (author's transl)].

To clarify the effects of enforced mental alertness upon spontaneous nystagmus (SPN), the ENG curves of 105 patients were studied. During examination for SPN the recordings were done under three test conditions: I: Patients instructed to "just relax" II: Mental activity alerted by silent mental arithmetics III. Recording after finishing the mental tasks Using seven indices of SPN intensity, mental arithmetics caused a significant improvement in six. The Total Amplitude proved to be the most sensible parameter; there was still a significant improvement even after solving the tasks (test cond. III). A significantly higher rate of improvement has been found in patients with a faint SPN while relaxed, i.e. there was a negative correlation between intensity of SPN and the rate of activation. Patients together with directional prepoderance (DP) had a significantly more intensive SPN than patients without DP or a slight DP only, while there was no difference in the rates of activation in both groups. Central or peripheral lesions did not cause a difference in SPN activation rates. The results give further evidence to the considerable influence of mental alertenes upon SPN; the assumption of a fictitious absolute limit between physiologic and pathologic SPN seems questionable. Mental arithmetics proved to be appropriate to maintain vigilance at a high level.

Adolescent↗