[Myelomeningocele--"the next years..."].
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Arnold-Chiari Malformation↗
Biomedical subjects
U Kuhn
Publications and source records attributed to U Kuhn.
Novel mutations in the CHST6 gene causing macular corneal dystrophy.
Macular corneal dystrophy (MCD) is an autosomal recessive disease characterized by corneal opacities and caused by mutations in a carbohydrate sulfotransferase gene, known as CHST6. MCD type I patients show missense mutations in the CHST6-coding region, and MCD type II patients show a large deletion and replacement in the upstream region of CHST6. The objective of this study was to identify the genetic defect in CHST6 gene causing MCD in Italian families. We investigated MCD genotype by using polymerase chain reaction followed by direct sequencing, and results were confirmed by restriction analysis. An enzyme-linked immunosorbent assay was performed to assess the presence of sulfated keratan sulfate in the serum of MCD patients. Biochemical analysis revealed a MCD type I phenotype in two families and a type II phenotype in another family. Two novel missense mutations and a polymorphism in the coding region of CHST6 gene were identified in patients with MCD type I. In one MCD II family, a homozygous deletion in the upstream region of CHST6 gene was found.
Corneal Dystrophies, Hereditary↗
Ventricular outflow obstruction, valve aplasia, bradyarrhythmia, pulmonary hypoplasia and non-immune fetal hydrops because of a large rhabdomyoma in a case of unknown tuberous sclerosis: a prenatal diagnosed cardiac rhabdomyoma with multiple symptoms.
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Adult↗
Indoleamine 2,3-dioxygenase expression in patients with acute graft-versus-host disease after allogeneic stem cell transplantation and in pregnant women: association with the induction of allogeneic immune tolerance?
Indoleamine 2,3-dioxygenase (IDO) is an interferon-gamma (IFN-gamma)-induced enzyme, which is suggested to play an important role in the prevention of allogeneic fetal rejection. IDO effects the suppression of T-cell activity by catabolizing the essential amino acid l-tryptophan. We studied IDO expression by reverse transcription polymerase chain reaction (RT-PCR) in dendritic cells and by real-time RT-PCR in monocytes of patients undergoing allogeneic transplantation for leukaemia, who developed acute graft-versus-host disease (aGvHD), and compared the IDO expression with that of pregnant women and healthy volunteers. A spontaneous IDO expression was detected in the monocytes of 20 pregnant women with an IDO/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) ratio at a median of 1.0%, whereas none of 15 healthy volunteers or patients after allogeneic transplant had any detectable spontaneous IDO expression. The IDO expression increased by in vitro IFN-gamma stimulation in pregnant women (median 116%), healthy volunteers (median 11.7%) and patients with a low-grade aGvHD (grades 0-II) 28 days after transplant (median 433%) but not in patients with a severe aGvHD (grades III-IV) (median 0%), which was highly significant (P < 0.01). IDO expression was also measured in dendritic cells by qualitative RT-PCR, where a spontaneous IDO expression was detected in 16 of 31 (52%) pregnant women versus none of 17 healthy volunteers and none of 62 studied patients after transplant. IFN-gamma-induced IDO expression was detected in all pregnant women, all volunteers and 47 of 49 (96%) patients with a low-grade aGvHD (grades 0-II) after transplant, whereas only in two of 13 (16%) patients with aGvHD grade III-IV was IFN-gamma-induced IDO expression observed. These data suggest that IDO expression might be involved in the development of allogeneic immune tolerance.
Adult↗
Kava-Kava extract LI 150 is as effective as Opipramol and Buspirone in Generalised Anxiety Disorder--an 8-week randomized, double-blind multi-centre clinical trial in 129 out-patients.
OBJECTIVE: An 8-week randomized, reference-controlled, double-blind, multi-centre clinical trial investigated Kava-Kava LI 150 in Generalized Anxiety Disorder (GAD; ICD-10: F41.1). METHOD: 129 out-patients received either 400 mg Kava LI 150, 10 mg Buspirone or 100 mg Opipramol daily for 8 weeks. At week 9, subjects were seen to check for symptoms of withdrawal or relapse. Primary outcome measures comprised the HAMA scale and the proportion of responders at week 8. Secondary measures were the Boerner Anxiety Scale (BOEAS), SAS, CGI, a self-rating scale for well-being (Bf-S), a sleep questionnaire (SF-B), a quality-of-life questionnaire (AL) and global judgements by investigator and patients. RESULTS: In 127 patients (ITT) no significant differences could be observed regarding all efficacy and safety measures. About 75% of patients were classified as responders (50% reduction of HAMA score) in each treatment group, about 60% achieved full remission. CONCLUSION: Kava-Kava LI150 is well tolerated and as effective as Buspirone and Opipramol in the acute treatment of out-patients suffering from GAD.
Adult↗
Cytochrome P450 (P450) isoforms expression, P450 concentration, monooxygenase activities, reactive oxygen species formation, lipid peroxidation, and glutathione content in wild catch carp and tench liver--influence of a two weeks exposure to phenobarbital.
Carps, both sexes, 3 years old, weighing about 1 kg, and tenches of both sexes, 6 years old, weight about 250 g, were caught from a Thuringian lake without industrial pollution in November 1995 (fish without food uptake, water temperature at about 10 degrees C) and kept for 2 weeks in basins with clean water and addition of 0, 0.1, 1.0 or 10.0 mg/l phenobarbital-Na (PB). The concentration of PB was controlled during and at the end of the exposure period. The animals were fed pellets, but no food uptake was observed. After 24-48 h in fresh water the fish were sacrificed and the following hepatic parameters were immediately determined biochemically: monooxygenase functions: cytochrome P450 (P450) content, ethylmorphine N-demethylation (EN), ethoxycoumarin O-deethylation (ECOD), ethoxyresorufin O-deethylation (EROD), 7-benzyloxy-4-methyl-coumarin O-debenzylation (BCDB); oxidase function indicators: microsomal Fe2+/NADPH dependent hydrogen peroxide formation (H2O2), microsomal Fe2+/NADPH dependent luminol and lucigenin amplified chemiluminescence (LMCL, LCCL), microsomal Fe2+/NADPH dependent lipid peroxide formation (LPO); oxidative state: lipid peroxidation products (TBARS) and GSH and GSSG. Additionally, the expression of three P450 isoforms, 1A1, 2B and 3A, was assessed immunohistochemically in tissue samples from brain, gill, heart, spleen, liver, gut and ovary of both fish species and in kidney of tenches. PB did not influence body or liver weights, but increased liver P450 concentration in both species by 50-100%, though not significantly. Carp: PB increased both EN and EROD significantly, but not ECOD and BCDB; H2O2 and TBARS were enhanced significantly. LPO, LMCL and LCCL were not significantly influenced. Tench: PB increased all monooxygenase reactions (EN, ECOD, BCDB and EROD), though only significantly ECOD; H2O2 was elevated only after treatment with 0.1 mg/l PB, whereas LPO was decreased (!) after treatment by all three concentrations, though significantly only after 1.0 mg/l PB. LMCL was depressed (not significantly), but LCCL increased 5fold. TBARS were significantly enhanced. P450 1A1 subtype expression was concentration dependently elevated by PB in gill and liver of both fish and in the heart and kidney of tenches, P450 2B and 3A isoforms expression was induced in brain, gill, heart, liver and gut of both fish and in the kidney of tenches. In summary, the increased activities of the monooxygenase reactions tested and the elevated expression of all three P450 isoforms investigated in certain tissues indicate an induction of the P450 families 1, 2 and 3 by PB in fish.
Animals↗
Capsicum pain plaster in chronic non-specific low back pain.
Topically applied capsaicin (CAS 404-86-4) induces the release of substance P, a neurotransmitter, from sensory C-fibres. In addition, there is a specific blockade of transport and de-novo synthesis of substance P. As a result, repeated applications of capsaicin bring about a long lasting desensitisation to pain (increase of pain threshold). The desensitising effect is fully reversible. The confirmed pharmacodynamic actions and a number of double-blind clinical studies indicate that local capsicum preparations are very suitable for the treatment of neuropathic pain or musculoskeletal disorders, with or without inflammatory components. In a double-blind, randomised parallel-group study a capsicum plaster was compared with a placebo for 3 weeks in 154 patients with non-specific back pain. Inclusion criteria were a history of back pain for a minimum period of 3 months and a degree of pain of 5 or more on an eleven grade visual analogue scale. The principal target variable consisted of the score of 3 combined pain scales. Secondary efficacy measures were tests of mobility, a disability index (in the context of Arhus low back rating scale) and global assessments by physicians and patients. For patients to be rated as responders their total pain score at the final examination after 3 weeks of treatment had to show a reduction by at least 30% of the baseline value. The study unequivocally achieved the target criterion with a rate of responders in the capsicum group of 60.8% against 42.1% in the placebo group (p = 0.0219). The sum of the 3 separate pain scales decreased more markedly in the capsicum group than in the placebo group (38.5% compared to 28.0%; p = 0.002). Relatively slight improvements of the impaired mobility and the functional status are explained by the characteristics of the disorder treated. The efficacy ratings by observers and patients was definitely in favour of capsicum. Adverse effects--mostly harmless and resolving spontaneously--were reported by 15 patients in the capsicum group and by 9 in the placebo group. The tolerance ratings by investigators and patients were superior to the placebo product. This, however, partly is due to the local pharmacological actions of the drug. As in comparably positive randomised studies with capsaicin cream in patients with osteoarthritis or fibromyalgia it was shown that a capsicum plaster preparation can also be used to advantage in chronic non-specific back pain.
Administration, Topical↗
Modulation of extracellular matrix adhesiveness by neurocan and identification of its molecular basis.
Neurocan is one of the major chondroitin sulfate proteoglycans of perinatal rodent brain. HEK-293 cells producing neurocan recombinantly show changes in their behavior. The expression of full-length neurocan led to a detachment of the secreting cells and the formation of floating spheroids. This occurred in the continuous presence of 10% fetal bovine serum in the culture medium. Cells secreting fragments of neurocan-containing chondroitin sulfate chains and the C-terminal domain of the molecule showed a similar behavior, whereas cells expressing fragments of neurocan-containing chondroitin sulfate chains but lacking parts of the C-terminal domain did not show spheroid formation. Cells secreting the hyaluronan-binding N-terminal domain of neurocan showed an enhanced adhesiveness. When untransfected HEK-293 cells were plated on a surface conditioned by spheroid-forming cells, they also formed spheroids. This effect could be abolished by chondroitinase treatment of the conditioned surface. The observations indicate that the ability of the chondroitin sulfate proteoglycan neurocan to modulate the adhesive character of extracellular matrices is dependent on the structural integrity of the C-terminal domain of the core protein.
Cell Adhesion↗
The Saccharomyces cerevisiae RNA-binding protein Rbp29 functions in cytoplasmic mRNA metabolism.
Here we report that the Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encodes a 29-kDa cytoplasmic protein that binds to mRNA in vivo. Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosage- and RNA-dependent manner. In addition, recombinant Rbp29p binds preferentially to poly(A) with nanomolar binding affinity in vitro. Although RBP29 is not essential for cell viability, its deletion exacerbates the slow growth phenotype of yeast strains harboring mutations in the eIF4G genes TIF4631 and TIF4632. Furthermore, overexpression of RBP29 suppresses the temperature-sensitive growth phenotype of specific tif4631, tif4632, and pab1 alleles. These data suggest that Rbp29p is an mRNA-binding protein that plays a role in modulating the expression of cytoplasmic mRNA.
Cytoplasm↗
Comparison of equivalence between the St. John's wort extract LoHyp-57 and fluoxetine.
In a randomised double-blind comparative trial, the antidepressant efficacy of a daily dose of 800 mg of the St. John's wort extract LoHyp-57 (dry extract of St. John's wort, drug extrakt ratio 5-7:1, solvent, ethanol 60% [w/w]) was shown to be equivalent to that of 20 mg fluoxetine (CAS 54910-89-3) in elderly patients with mild or moderate depressive episodes according to ICD 10 (International Statistical Classification of Diseases and Related Health Problems). Treatment was given for six weeks. 149 out-patients (129 females and 20 males) were included in the intention-to-treat analysis. 72 of these patients were assigned to the ICD 10 diagnostic criterion F32.0 (mild depressive episode), while 77 patients were suffering from moderate depressive episodes, corresponding to F32.1. The principal target criterion was the patient's global score on the HAMILTON Depression Scale (items 1-17). During the six-week course of treatment with LoHyp-57, the HAMILTON global score fell from 16.60 points at entry to 7.91 points, and in the fluoxetine sample it fell from 17.18 to 8.11 points. In the group of patients with mild depressive episodes, the score showed a mean fall from 14.21 to 6.21 points on LoHyp-57, and from 15.21 to 7.46 points on fluoxetine. In patients with moderate depressive episodes, the score showed a mean fall from 18.73 to 9.43 points on LoHyp-57 and from 19.10 to 8.75 points on fluoxetine. The efficacy of both medications was found to be equivalent both in mild and moderate depressive episodes. Both treatment groups showed adverse drug reactions (ADRs). Twelve ADRs with a possible relationship to the study medication were reported during treatment with LoHyp-57. Six patients were prematurely withdrawn from treatment with the study medication for this reason. On fluoxetine 17 ADRs occurred with a possible relationship to the study medication. These led to abandonment of treatment and therefore premature withdrawal from the study in 8 cases.
Aged↗
Interferon gamma and interleukin 10 levels in preimplantation embryo culture media.
PURPOSE: The aim of our study is to elucidate whether human oocytes/embryos secrete IFN gamma and/or IL-10 and whether the fertilization process depends on the balance between these cytokines. METHODS: A total of 142 embryo culture media from 24 patients were collected and the cytokine levels were tested with ELISA. RESULTS: IFN gamma and IL-10 were detectable in 40.1% and 29.6% of culture media respectively. The difference of IFN gamma and IL-10 levels in media from fertilized oocytes between day 1 and day 2 are significant (0.46 vs. 1.47 and 34.2 vs. 12.7, respectively). However there was no significant difference between the IFN gamma levels of the media from fertilized and nonfertilized oocytes 0.46 vs. 0.85 at day 1 and 1.47 vs 1.49 at day 2, as well as IL-10 levels 34.2 vs. 30.9 at day 1 and 12.7 vs. 9.58 at day 2 respectively. CONCLUSIONS: Human preimplantation embryos secrete the cytokines IFN gamma and IL-10. No effect of these cytokines on fertilization process could be shown.
Blastocyst↗
Strong association between the responder status of the FC gamma II receptor and recurrent spontaneous abortion.
Several models exist for the aetiology and therapy of recurrent spontaneous abortion (RSA). They are based in part on the assumption that an increased materno-fetal histocompatibility results in an insufficient maternal immunological recognition of the fetus, and thus renders the maternal immune system unable to sustain the pregnancy. The involvement of the FcgammaII receptor (FcgammaIIR) in RSA was suggested, since FcgammaIIR-blocking antibodies, present in normal pregnancies, could not be found in patients suffering from RSA. The FcgammaIIR is known to be functionally and structurally dimorphic, which results in a responder, respectively non-responder pattern. We used an in vitro proliferation assay to distinguish between FcgammaIIR responder and non-responder phenotypes. In 29 RSA couples we found 97% (28/29) of RSA patients and 100% (29/29) of their partners to be responders, whereas 50 fertile couples and a further 100 unrelated controls revealed distributions of responder vs. non-responder of 73% vs. 27% and 70% vs. 30%, respectively. These differences (RSA vs. controls) are highly significant (P less than or equal to 0.0001). Our results suggest further that the FcgammaIIR dimorphism might be involved in the pathogenesis of RSA.
Abortion, Habitual↗
Comparison of the efficacy and tolerance of a garlic preparation vs. bezafibrate.
The efficacy and tolerance of a garlic preparation (Sapec, Kwai) was investigated in a randomized double-blind study vs. bezafibrate. This multi-centre study was conducted in 5 general medical practices and involved 98 patients with primary hyperlipoproteinaemia. The daily doses of the active substances were 900 mg of garlic powder (standardized as to 1.3% alliin) and 600 mg of bezafibrate, respectively. The pre-phase with placebo lasted 6 weeks, the treatment period covered 12 weeks. All patients were advised to observe a low-fat "step-1 diet" for the duration of the study. The 98 case report forms allowed the statistical evaluation of total cholesterol, HDL cholesterol and triglyceride levels for 94 patients, and of LDL cholesterol values for 92 patients. In the course of the treatment both study medications caused a statistically highly significant reduction in total cholesterol, in LDL cholesterol and triglycerides, and an increase in HDL cholesterol. However, there was no significant difference in the efficacies of both medication groups. Side effects were mentioned by 5 patients each in both treatment groups, none of which led to the withdrawal of the patients. Concerning the garlic preparation, there was no correlation between the perception of garlic odour and the influence on the cholesterol level.
Aged↗
Fc receptor blocking antibodies after active immunization for the treatment of recurrent spontaneous abortion.
In a prospective study 140 couples who had at least three spontaneous abortions (RSA) were studied for the presence of Fc receptor blocking antibodies detected by the erythrocyte antibody rosette inhibition (EAI) assay, for anti-paternal cytotoxic antibodies (APCA), and for mixed lymphocyte culture inhibiting (MLCI) antibodies before and after active immunization with paternal lymphocytes. The comparative analysis revealed the EAI assay to possess a higher sensitivity than the APCA and/or MLCI tests in monitoring the specific immune response after active immunization. The success of pregnancy in EAI positive post-immunization patients was not influenced by the presence or absence of APCA or MLCI. In the light of a successful pregnancy outcome of 85.7% (n = 37) in this study we conclude that the monitoring of Fc receptor blocking antibodies is useful in active immunization protocols for RSA patients.
Abortion, Habitual↗
Further characterization of the EAI factor induced by alloimmunization for treatment of recurrent abortion.
In order to remove the EAI "blocking" activity, EA inhibition positive sera from patients with recurrent abortions were absorbed after alloimmunization with paternal lymphocytes by the lymphoblastoid cell line (LCL) of the husband. To avoid non-specific binding via the Fc-receptor, the cells were first fixed with 0.05% glutaraldehyde. Absorption was performed for 3 h at 4 degrees C. For subsequent elution, the cells were incubated with 0.1 M glycine-HCl, pH 2.3, for 30 min at 4 degrees C. After each step, EAI assay was carried out to determine the "blocking" activity in the supernatants. Furthermore, 10% SDS-PAGE and immunoblotting with goat antihuman IgG of the whole serum and the supernatants were performed. The results obtained give evidence that the EAI "blocking" activity can be absorbed by and eluted from the LCL of the immunizing husband, and is due to an IgG antibody directed against an antigen present on the LCL. Further absorption experiments with trophoblast cells will show whether this antigen is also displayed by the trophoblast.
Abortion, Habitual↗
[Immunological aspects of endometriosis].
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Antigens, Tumor-Associated, Carbohydrate↗
[Reproduction immunology].
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Abortion, Habitual↗
[Immunologically-induced abortion--diagnosis and therapy].
As etiological factors responsible for repeated miscarriages disturbances of the maternal-fetal immunoregulation are involved. Diagnostic aspects of the immunobiology of abortion and the clinical management of habitual abortion by immunotherapy are discussed.
Abortion, Habitual↗