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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 199 records · Page 11Linked to original sources

Treatment of chronic palmoplantar eczema with local bath-PUVA therapy.

BACKGROUND: Systemic PUVA therapy may be useful in the treatment of chronic palmoplantar eczema. Topical PUVA-paint avoids some of the unwanted side effects of systemic psoralens and has been used successfully in the treatment of palmoplantar eczema and psoriasis. However, few data are available on the effectiveness of local bath-PUVA therapy in palmoplantar eczema. OBJECTIVE: Our purpose was to assess the effectiveness of local bath-PUVA therapy in 28 patients with chronic palmar or plantar eczema or both who were resistant to conventional topical treatment. METHODS: After fungal or bacterial infection had been excluded in all patients, hands or feet or both were soaked for 15 minutes in warm water containing 1 mg/L 8-methoxypsoralen. Immediately after, the skin was irradiated with increasing doses of UVA, starting with 0.5 J/cm2. PUVA-bath therapy was performed 4 times a week up to a total of 25 treatments. No additional therapy was allowed except emollients. RESULTS: Excellent or good effects were achieved in 93% of the patients with dyshidrotic and in 86% of the patients with hyperkeratotic eczema. In the patients with dyshidrotic eczema, the cumulative doses and the highest single doses of UVA were lower than those in the patients with hyperkeratotic eczema (21.4 vs 27.9 J/cm2 and 2.4 vs 3.0 J/cm2 of UVA), but this was not statistically significant. No phototoxic reactions were observed. CONCLUSION: Local bath-PUVA therapy is of value in the management of chronic palmoplantar eczema resistant to standard modes of topical treatment. Compared with topical PUVA-paint, local bath-PUVA therapy has several advantages, particularly the absence of phototoxic reactions, severe hyperpigmentation, and protracted photosensitivity.

Adolescent↗

In vitro cytokine secretion and maturation phenotype of lymphoma-associated splenic macrophages.

In this study, cytokine secretion capacity and maturation phenotype of human lymphoma-associated splenic macrophages (LASM) were evaluated in a long-term culture. Sixteen spleens from malignant lymphoma patients and five control spleens were investigated. Splenic macrophages (SM) were isolated by teflon adherence and cultured for 6-48 days. Secretion of IL-1 alpha, IL-6 and TNF alpha was measured by ELISA following maximal stimulation with LPS and IFN-gamma, and cytokine mRNA expression was detected by in situ hybridization. Immunohistochemical expression of maturation-associated antigens was evaluated semiquantitatively. Cytokine secretion capacity was significantly altered in LASM which exhibited reduced TNF alpha and IL-6, but elevated IL-1 alpha secretion when compared to control SM. Alterations of cytokine secretion capacity were associated with a modification of LASM maturation phenotype, showing impaired expression of early and chronic/late inflammatory markers. These findings obtained from a long-term culture model suggest that malignant lymphomas induce lasting modifications of cytokine secretion and maturation patterns in LASM.

Adult↗

BRCA1 mutations found in archived early onset breast tumours.

Inherited mutations in the BRCA1 gene are thought to account for approximately 5% of breast cancers in women under the age of 45 years. In order to determine whether mutations could be found at the expected frequency, 60% of the protein coding region of BRCA1 was screened in 75 archived early-onset breast tumours, taken from women under 45 years of age. Two of the 75 tumours (2.7%) had detectable mutations, in close agreement to that predicted. Since BRCA1 mutations found in breast tumours are invariably germline, two immediate consequences are apparent. Firstly, family members of affected patients are likely to carry mutations as well, and should be considered for BRCA1 screening; and secondly, persons harbouring a germline BRCA1 mutation should be examined frequently and indefinitely for new primary tumours in remaining breast tissue.

Adult↗

Escape of HIV-1 is associated with lack of V3 domain-specific antibodies in vivo.

This study was performed to analyse correlates of viral escape in AIDS patients. Peripheral blood mononuclear cells (PBMC) from HIV- donors were inoculated with AIDS patients' serum to detect neutralization-resistant cell-free virus. Infectious virus was detected by polymerase chain reaction (PCR) and analysed by sequencing the V3 region. The escaped virus species was compared with all V3 virus variants found in the patients' PBMC and plasma. In one patient escaped virus was also compared with variants found in CD4+ T cells isolated by FACS from blood, spleen and lymph node. The frequency of the virus variants was determined by cloning and sequence analysis of 20 V3 clones for each PCR amplification. To monitor anti-V3 antibodies by ELISA, each V3 sequence was expressed as fusion with glutathione S-transferase (GST-V3). In our AIDS patients, a V3-directed antibody response against the infectious virus V3 loop was not detectable. In contrast, virus variants unable to infect the donor PBMC in vitro were well recognized by homologous V3-directed antibody. After an interval of 1 year the frequency of these variants clearly decreased, while at the same time the escaped variants grew out and finally represented the predominant viral species both in plasma and PBMC. The infectious variants lacking V3 antibody response were also predominant in CD4+ T cells in spleen and lymph node. Our data indicate that the escape of virus variants is closely related to the lack of V3-directed antibody.

Amino Acid Sequence↗

[Postoperative peridural analgesia. Continuous versus patient-controlled administration of a low-dose mixture of sufentanil, clonidine and bupivacaine].

UNLABELLED: The purpose of our study was to find out whether patient-controlled epidural administration (PCEA) of a mixture containing a low-dose local anaesthetic, opioid and alpha 2-agonist provides as good or better postoperative analgesia as continuous epidural administration of the same analgetic solution. METHODS: 30 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into 2 groups. 90 minutes after induction of general anaesthesia all patients received a continuous epidural infusion of 5 ml/h of the analgetic solution (50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine) until the end of surgery. Immediately postoperatively the patients of group A received a continuous infusion of the study solution (5-8 ml/h), the patients of group B received a baseline continuous epidural infusion (3 ml/h), additionally they could self-administer 5 ml boli via a PCEA device. Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side effects within the first 24 hours postoperatively. A standardised interview on analgesia and side effects was held 2 days after surgery. RESULTS: The PCEA group demanded less epidural analgesics (gr. B: 112 +/- 33 ml vs. gr. A: 135 +/- 20 ml) p < 0.01). Both continuous epidural infusion and patient-controlled administration provided very good analgesia at rest (gr. A: VAS 0.4 +/- 0.4 and gr. B: VAS 0.4 +/- 0.5) (n.s.). On exercise continuous epidural infusion of analgesics resulted in significantly lower pain scores (gr. A: 1.9 +/- 1.1) than patient-controlled application (gr. B: 3.4 +/- 1.1) (p < 0.01). We did not notice severe side effects such as respiratory depression or drop of heart rate or blood pressure. CONCLUSION: In patients at rest both continuous and patient-controlled epidural administration of analgesics provides excellent analgesia after major abdominal surgery. Contrariwise, patients on exercise who could use a PCA-device experienced more pain compared to those with a continuous epidural infusion technique. On the other hand the patients of the PCA-group consumed less epidural analgesics. We did not notice any severe side effects such as respiratory depression or cardiovascular instability during the study.

Aged↗

Elevated frequency of p53-independent apoptosis after irradiation increases levels of DNA breaks in ataxia telangiectasia lymphoblasts.

Ataxia telangiectasia is a recessive generic disease featuring cerebellar degeneration, developmental abnormalities, high cancer risk, immunodeficiency, and radiosensitivity. Increased levels of unrepaired DNA breaks have been observed in irradiated ataxia telangiectasia cells compared to normal cells but no specific DNA break rejoining rate deficiency has been defined. Alterations in radiation-induced p53-dependent apoptosis have been reported for ataxia telangiectasia cells. This study investigated the radiation response of ataxia telangiectasia lymphoblastoid cells using the comet assay and uncovered a new feature of this technique, namely its capacity to preferentially detect living cells. It is shown here that early after exposure to gamma-rays, ataxia telangiectasia lymphoblasts exhibit an elevated frequency of cells committed to die via apoptosis. The observed apoptosis, which is likely to be independent of p53, leads to a higher number of DNA breaks during the first 3 h post irradiation in ataxia telangiectasia cells, relative to controls. Apart from cells undergoing apoptosis, ataxia telangiectasia lymphoblasts have an identical capacity to rejoin radiation-induced DNA breaks as controls. Results suggest that p53-independent apoptosis may contribute to the radiosensitivity and the immune defects of ataxia telangiectasia patients.

Adult↗

Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods.

A human intervention study with vegetable products has been performed in twenty three healthy, non smoking males aged 27-40. It was the aim of the study to assess whether consumption of vegetables containing different carotenoids could protect against DNA damage and oxidative DNA damage. The subjects consumed their normal diets, but abstained from vegetables high in carotenoids throughout the study period. After a 2 week depletion period, they received daily 330 ml tomato juice with 40 mg lycopene (weeks 3 and 4), 330 ml carrot juice with 22.3 mg beta-carotene and 15.7 mg alpha-carotene (weeks 5 and 6), and 10 g dried spinach powder (in water or milk) with 11.3 mg lutein (weeks 7 and 8). Blood was collected weekly and DNA damage was detected in peripheral blood lymphocytes with the 'COMET' assay. Oxidised DNA bases were detected by including an incubation step with endonuclease III. The supplementation of the diet with tomato, carrot or spinach products resulted in a significant decrease in endogenous levels of strand breaks in lymphocyte DNA. Oxidative base damage was significantly reduced during the carrot juice intervention. These findings support the hypothesis that carotenoid containing plant products exert a cancer-protective effect via a decrease in oxidative and other damage to DNA in humans.

Adult↗

Adaptation of ECOSYS-87 to Hong Kong environmental conditions.

This paper describes the adaptation work carried out on the radioecological model ECOSYS for radionuclide transfer in the Hong Kong ecological environment. The adapted model predicts that the ingestion dose due to dry deposition in Hong Kong shows less pronounced seasonal dependence than that in Germany. This is mainly attributed to differences in climate, agricultural and farming practices adopted in the two places. Brief discussions on model sensitivity, uncertainty, and validation are also given.

Agriculture↗

Analysis of hepatitis C virus core protein interaction domains.

Hepatitis C virus (HCV) core protein forms the internal viral coat that encapsidates the genomic RNA and is enveloped in a host cell-derived lipid membrane. As the single capsid protein, core should be capable of multimerization but attempts to produce virus-like particles following expression of HCV structural proteins have not been successful. In this study, we have analysed the interaction capacity of full-length and truncated HCV core using the yeast two-hybrid system. Full-length core containing or lacking the translocation signal for the E1 glycoprotein did not interact with full-length or truncated core proteins. Truncation to the N-terminal 122 aa revealed an interaction domain which was mapped to the tryptophan-rich sequence from aa 82-102 and was termed the main homotypic interaction domain. The C-terminal hydrophobic fragment of core (aa 122-172) was incapable of interacting with itself but interacted with the main homotypic interaction domain in trans (the weak heterotypic interaction domain). Core proteins truncated at their N and C termini (aa 46-102) were trans-activating when fused to the DNA-binding domain of GAL4. Based on our results, we suggest that the C-terminal segment may interact in cis with the main homotypic interaction domain and thereby prevent multimerization. Core-core interaction was also observed for in vitro-translated proteins bound to truncated immobilized core 102. However, interaction was less specific in this system suggesting that protein interaction and possibly conformational alteration of core may be dependent on the experimental system.

Hepacivirus↗

The effect of comonomer composition, silane heating, and filler type on aqueous TEGDMA leachability in model resin composites.

Experimental composites using either bisGMA/TEGDMA or UEDMA/ TEGDMA matrices, quartz or barium glass fillers, and 2 different filler silanization methods were evaluated regarding monomer leachability in distilled water. The leached amount was detected and quantified using gas chromatography. The results showed that twice as much TEGDMA is leached from a bisGMA/TEGDMA based composite than from an UEDMA/ TEGDMA based composite, when both contain 50 wt% TEGDMA. The hypothesis suggested that the higher degree of cure of UEDMA/TEGDMA based composites would be reflected in a lower monomer leaching value, and this hypothesis was supported by the findings. Whether such a correlation exists within groups of UEDMA/TEGDMA based matrices having different degrees of cure was not determined and needs to be investigated in future studies. Variables such as filler composition and silane treatment did not affect the leaching values of TEGDMA in water. That finding suggests that future studies should target differences in matrices, and that the need for considering effects of filler composition and silane treatment methods should not receive the same priority.

Analysis of Variance↗

The V3-directed immune response in natural human immunodeficiency virus type 1 infection is predominantly directed against a variable, discontinuous epitope presented by the gp120 V3 domain.

The specific binding of antibodies to the V3 loop in sera from human immunodeficiency type 1 (HIV-1)-infected individuals was investigated. Different V3 structures were analyzed as full-length loops or by pepscan. Our data show that on full-length V3 loops, both variable regions on either side of the tip of the loop (GPGRAF) contribute to a common epitope for type-specific antibodies. Type-specific antibodies bound strongly and at high titers to native V3 loops but negligibly once the loop was denatured. In contrast to the type-specific, discontinuous epitope, the linear, conserved epitopes presented by the full-length V3 loop, the tip, the amino-terminal base, and the carboxy-terminal base were not accessible to serum antibody. When the V3 sequences were analyzed with linear peptides, antibodies bound preferentially to peptides containing the conserved GPGRAF sequence. Thus, two different specificities of V3-directed antibodies were detected in patient sera. Unlike group-specific antibodies directed against GPGRAF peptides, lack of type-specific antibodies directed against the discontinuous epitope was correlated with viral escape from autologous neutralization. Our data suggest that the full-length conformation of the V3 loop is accessible predominantly to highly type-specific antibodies present in sera from HIV-1-infected individuals. These antibodies are directed against discontinuous V3 epitopes, not against conserved linear V3 targets. The implications of these findings for viral escape and blockade of infection with V3-based vaccines are discussed.

Amino Acid Sequence↗

Induction of S-phase entry by E2F transcription factors depends on their nuclear localization.

The E2F transcription factors are essential for regulating the correct timing of activation of several genes whose products are implicated in cell proliferation and DNA replication. The E2Fs are targets for negative regulation by the retinoblastoma protein family, which includes pRB, p107, and p130, and they are in a pathway that is frequently found altered in human cancers. There are five members of the E2F family, and they can be divided into two functional subgroups. Whereas, upon overexpression, E2F-1, -2, and -3 induce S phase in quiescent fibroblasts and override G1 arrests mediated by the p16INK4A tumor suppressor protein or neutralizing antibodies to cyclin D1, E2F-4 and -5 do not. Using E2F-1 and E2F-4 as representatives of the two subgroups, we showed here, by constructing a set of chimeric proteins, that the amino terminus of E2F-1 is sufficient to confer S-phase-inducing potential as well as the ability to efficiently transactivate an E2F-responsive promoter to E2F-4. We found that the E2F-1 amino terminus directs chimeric proteins to the nucleus. Surprisingly, a short nuclear localization signal derived from simian virus 40 large T antigen could perfectly substitute for the presence of the E2F-1 amino terminus in these assays. Thus, nuclearly localized E2F-4, when overexpressed, displayed biological activities similar to those of E2F-1. Furthermore, we showed that nuclear localization of endogenous E2F-4 is cell cycle regulated, with E2F-4 being nuclear in the G0 and early G1 phases and mainly cytoplasmic after the pRB family members have become phosphorylated. We propose a novel mechanism for the regulation of E2F-dependent transcription in which E2F-4 regulates transcription only from G0 until mid- to late G1 phase whereas E2F-1 is active in late G1 and S phases, until it is inactivated by cyclin A-dependent kinase in late S phase.

Animals↗

Docosahexaenoic and arachidonic acid absorption in preterm infants fed LCP-free or LCP-supplemented formula in comparison to infants fed fortified breast milk.

The absorption of long-chain polyunsaturated fatty acids (LCP) with particular respect to docosahexaenoic (DHA) and arachidonic acid (AA) has been studied in 39 very-low-birth-weight infants appropriate for gestational age after a 10-day feeding period. The infants were fed either a LCP-supplemented formula (n = 11), or a LCP-free formula (n = 11) or breast milk fortified with protein and carbohydrates to have similar protein and energy intakes as in the formula-fed infants (n = 17). Total fat content and fatty acid profile were measured in the human milk, the two formulas, and in the stool samples. After a 10-day feeding period, the fecal excretions of total fat, DHA and AA were measured during a 3-day balance period. The total fat apparent absorption rates were similar in all groups (84.1, 82.1 and 80.6% of intake, respectively). The DHA and AA intakes were significantly (p < 0.01) higher in the group fed the fortified breast milk than in the group fed the LCP-supplemented formula (DHA: 75.5 +/- 12.4 vs. 50.2 +/- 4.2 mg/72 h; AA: 45.5 +/- 5.8 vs. 30.2 +/- 2.7 mg/72 h). There was a tendency for lower apparent absorption rates for both LCPs studied in the group fed fortified breast milk when compared to the group fed LCP-supplemented formula (AA: 70.6 +/- 10.9 vs. 73.0 +/- 8.7% of intake, DHA: 69.0 +/- 10.6 vs. 74.2 +/- 9.5% of intakes, but the differences were not significant. As consequence of the different intakes, the net absorption of the two studied LCP fatty acids were significantly (p < 0.01) higher in the breast milk group than in the group fed the LCP-supplemented formula (DHA: 52.6 +/- 6.1 vs. 36.8 +/- 4.5 mg/72 h; AA: 31.4 +/- 3.1 vs. 22.4 +/- 2.3 mg/72 h). The data demonstrate that DHA and AA are absorbed from the studied LCP-supplemented formula at least as effectively as from human milk. The net absorption of these LCP depend on the amount of dietary intake, and seems to be influenced by the dietary LCP source.

Arachidonic Acid↗

Identification and characterization of a mouse homolog for decidual/trophoblast prolactin-related protein.

Decidual/trophoblast PRL-related protein (d/tPRP) is one member of a large placental PRL gene family composed of at least nine members in the rat and four in the mouse. Only placental lactogen I and II have been characterized in both rat and mouse. The identification of mouse homologs for rat placental PRL family members will facilitate gene manipulation studies aimed at identifying functions for these hormones. In this report, we establish the presence of d/tPRP in the mouse and characterize its complementary DNA, protein, and pattern of expression during mouse gestation. Evaluation of the National Center for Biotechnology Information database of expressed sequence tags resulted in the identification of several mouse complementary DNA clones exhibiting significant homology to rat d/tPRP. One of these clones was obtained from IMAGE Consortium and Research Genetics for further investigation. The full-length mouse clone was found to have an 81% nucleotide homology with rat d/tPRP and to encode a 239-amino acid protein. Like rat d/tPRP, the mouse protein contains two putative N-linked glycosylation sites and six homologously located cysteine residues. Mouse d/tPRP maps to chromosome 13 along with other members of the mouse PRL family. Like the rat, mouse d/tPRP messenger RNA and protein are expressed by antimesometrial decidual cells and spongiotrophoblast and trophoblast giant cells in the junctional zone of the placenta. In summary, we have established the presence of d/tPRP in the mouse and demonstrated its similarity in structure and pattern of expression to rat d/tPRP. This level of conservation between species expands the biological significance of d/tPRP during pregnancy and provides additional opportunities for evaluating its function.

Animals↗

Significance of chromosome arm 14q loss in nonpapillary renal cell carcinomas.

We examined 88 nonpapillary renal cell carcinomas for allelic loss at chromosome arm 14q and correlated the results to size, grade, and stage of these tumors. Fourteen highly polymorphic microsatellite markers on the long arm of chromosome 14 were used for deletion mapping. Loss of heterozygosity (LOH) at the smallest overlapping segment of 14q24.2-qter was seen in 42 of 88 tumors. There was no significant correlation between frequency of 14q LOH and size of tumors (P = 0.11). LOH was frequently seen in grade 2 and 3 tumors (55% and 73%, respectively) and in stage III and IV tumors (53% and 80%, respectively). We found a significant correlation between chromosome arm 14q LOH and nuclear grade (P < 0.001) and stage (P < 0.001) of tumors. These observations indicate the presence of a tumor-suppressor gene at chromosome segment 14q24.2-qter and demonstrate the usefulness of microsatellite analysis for assessing the possible clinical outcome of nonpapillary renal cell carcinomas.

Adult↗

[Primary carcinoma of Bartholin's glands with HPV 18 detection].

A primary carcinoma of the Bartholin's gland is a rarely type of vulva-carcinoma. The patients median age are 55 years and the etiology of the carcinoma are still unknown. Viral influences are discussed. Most frequent types of carcinomas of Bartholin's gland are those of squamous cells and adenocarcinomas. This article reports on a 55 year old patient with a primary carcinoma of Bartholin's gland. The human papillomavirus 18 was detected by a polymerase chain reaction. The correct diagnosis was delayed because of an initial misinterpretation of the carcinoma as a Bartholin cyst, marsupialization and bad healing of the wound. The patient underwent a radical vulvectomy with bilateral inguinofemoral lymphonodectomy in combination with radiation therapy.

Bartholin's Glands↗

[Molecular factors determine primary and secondary therapy of breast carcinoma].

The clinical oncology realizes that the classical approach with systemic adjuvant chemo- and hormonal therapies is not sufficient and will be challenged by cellular and molecular structures which reflect the targets for new therapeutic approaches. These targets are key proteins involved in the signal transduction cascade. In human tumors these proteins have either lost their biological functionality by oncogenic mutations or are constitutively activated. The molecular classification of primary breast cancer was performed by assessing the following factors: estrogen- and progesterone receptors, ERbB-2 mutated p53, uPA, PAI-I, VEGF, DNA-Index and S-Phase. These factors are of prognostic and predictive value.

Antineoplastic Agents, Hormonal↗

[Follow-up during the 1st postoperative year after endovascular exclusion of abdominal aortic aneurysms].

Between January 1995 and December 1996 15 patients, 13 male and 2 female, underwent a transfemoral repair of an infrarenal aortic aneurysm with endovascular stent grafts. In one case the indication was an anastomotic aneurysm after bypass grafting. Stent-systems (MIALHE) were used in 9 cases as a bifurcation graft and in 6 cases as a tube graft. The patients' mean age was 70.2 years. The follow up period ranged from 3 months to one year. The implantation of the stent grafts was primarily successful in all cases. In 6 patients procedure related complications occurred. One postoperative death occurred due to multiple organ failure. In one case a persisting leakage at the proximal end of the stent graft led to a rupture of the aneurysm. Another patient developed gangrene of the colon. Both had to be corrected surgically. There were 3 persisting leakages at the distal end of the stent graft. They were treated with the implantation of covered stents, percutaneously and transfemorally twice and conservatively once. In the follow up, all stent grafts were patent. There were 4 complications in the 6 months follow up: one covered rupture of the common iliac artery at the distal end of the stent graft and one distal leakage at the common iliac artery as well as 2 leakages at the stent graft junction, caused by commencing desintegration were repaired by interventional procedures.

Aged↗