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Biomedical subjects

H Müller

Publications and source records attributed to H Müller.

At least 145 records · Page 8Linked to original sources
PubMed1999

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting.

Dexamethasone (20 mg) or its equivalent in combination with 5-HT3 antagonists appears to be the gold-standard dose for antiemetic prophylaxis. Additional to concerns about the use of corticosteroids with respect to enhanced tumour growth or impaired killing of the tumour cells, there is evidence that high-dosage dexamethasone impairs the control of delayed nausea and emesis, whereas lower doses appear more beneficial. To come closer to the most adequate dose, we started a prospective, single-blind, randomized trial investigating additional dosage of 8 or 20 mg dexamethasone to tropisetron (Navoban), a 5-HT3 receptor antagonist, in cis-platinum-containing chemotherapy. After an interim analysis of 121 courses of chemotherapy in 69 patients, we have been unable to detect major differences between both treatment alternatives. High-dose dexamethasone (20 mg) had no advantage over medium-dose dexamethasone with respect to objective and subjective parameters of acute and delayed nausea and vomiting. In relation to concerns about the use of corticosteroids in non-haematological cancer chemotherapy, we suggest that 8 mg or its equivalent should be used in combination with 5-HT3 antagonists until further research proves otherwise.

Abdominal Neoplasms↗
PubMed1999

Enhancing of anti-viral activity against HIV-1 by stimulation of CD8+ T cells with thymic peptides.

HIV-1 can be neutralized by soluble factors produced and secreted by activated CD8+ T cells. Production of such anti-viral CD8 factors (including chemokines) can be induced with IL-2 or phytohaemagglutinin (PHA). In addition to PHA or IL-2, we have co-stimulated CD8+ T cells with PHA/IL-2 and a mixture of thymic peptides (TP) of molecular weights below 10 kD. For the activation, CD8+ T cells were purified from peripheral blood mononuclear cells of HIV-1- individuals and any resultant anti-viral activity was monitored using an HIV-1 neutralization assay. Using HIV-1 isolates highly resistant to chemokine inhibition we detected significantly higher levels of HIV-1 neutralizing activity in CD8+ T cell culture supernatants which had been co-activated with TP. When the TP-induced anti-viral activity was monitored, neutralization of both non-syncytia-inducing (NSI) and syncytia-inducing (SI) patient isolates was enhanced by 38% (NSI, PHA +/- TP), 66% (SI, PHA +/- TP), 28% (NSI, IL-2 +/- TP), and 57% (SI, IL-2 +/- TP) compared with the anti-viral activity present in supernatants from CD8+ T cell cultures stimulated only with PHA or IL-2. Peptide sequence analysis of purified TP showed that the TP mixture predominantly contains peptides with homology to human histone and collagen sequences. Our data demonstrate that CD8+ T cells are additionally activated by a mixture of TP. In this way, the production of HIV-1 neutralizing CD8 factors can be enhanced.

Adjuvants, Immunologic↗
PubMed1999

Breast reconstruction with latissimus dorsi flap: improved aesthetic results after transection of its humeral insertion.

Does transecting the tendinous insertion of the latissimus dorsi on the humerus improve aesthetic results and avoid the displeasing bulge in the armpit that sometimes occurs when the latissimus dorsi is used for breast reconstruction? In a prospective study, 60 patients who were having breast cancer surgery and simultaneous breast reconstruction using the latissimus dorsi flap were randomized for cutting (n = 29) or leaving intact (n = 31) the tendinous muscle insertion on the humerus. The cosmetic outcome was evaluated by patients and surgeons 6 to 12 months postoperatively. Patients reported good cosmetic results in 29 of 31 cases with the humeral insertion left intact and in 26 of 29 cases when the tendon was cut (p = 0.59), as compared with 21 of 31 cases versus 25 of 29 cases (p = 0.091), according to the surgeon's evaluation. A lateral bulge was more frequently observed by the surgeons in the group with intact insertion (10 of 31 patients), as compared with the group with a transected humeral insertion (2 of 29 patients). Discomfort caused by this bulge was reported by 19 of 31 patients with intact insertion, but only 3 of 29 patients with the tendon cut (p < 0.0001). The additional transection of the tendon was not associated with any complications. The additional transection of the tendinous humeral insertion of the latissimus dorsi muscle improves aesthetic results and avoids a displeasing bulge in the axilla when the latissimus dorsi flap is used for breast reconstruction.

Breast Neoplasms↗
PubMed1999

CDC25A phosphatase is a target of E2F and is required for efficient E2F-induced S phase.

Functional inactivation of the pRB pathway is a very frequent event in human cancer, resulting in deregulated activity of the E2F transcription factors. To understand the functional role of the E2Fs in cell proliferation, we have developed cell lines expressing E2F-1, E2F-2, and E2F-3 fused to the estrogen receptor ligand binding domain (ER). In this study, we demonstrated that activation of all three E2Fs could relieve the mitogen requirement for entry into S phase in Rat1 fibroblasts and that E2F activity leads to a shortening of the G(0)-G(1) phase of the cell cycle by 6 to 7 h. In contrast to the current assumption that E2F-1 is the only E2F capable of inducing apoptosis, we showed that deregulated E2F-2 and E2F-3 activities also result in apoptosis. Using the ERE2F-expressing cell lines, we demonstrated that several genes containing E2F DNA binding sites are efficiently induced by the E2Fs in the absence of protein synthesis. Furthermore, CDC25A is defined as a novel E2F target whose expression can be directly regulated by E2F-1. Data showing that CDC25A is an essential target for E2F-1, since its activity is required for efficient induction of S phase by E2F-1, are provided. Finally, our results show that expression of two E2F target genes, namely CDC25A and cyclin E, is sufficient to induce entry into S phase in quiescent fibroblasts. Taken together, our results provide an important step in defining how E2F activity leads to deregulated proliferation.

Animals↗
PubMed1999

Uterine natural killer cells are targets for a trophoblast cell-specific cytokine, prolactin-like protein A.

PRL-like protein A (PLP-A) is a member of the PRL family expressed in trophoblast cells coincident with establishment of the chorioallantoic placenta. The purpose of this investigation was to identify targets for PLP-A. Using an alkaline phosphatase-tagging strategy, we show that PLP-A specifically interacts with a population of natural killer (NK) lymphocytes within the mesometrial compartment of decidua from pregnant and pseudopregnant rats. These observations are supported by the codistribution of PLP-A targets with cells expressing the rat NK cell surface marker, gp42, the absence of PLP-A binding in conceptuses from NK cell-deficient tg epsilon26 mice, and the specific interaction of PLP-A with a rat NK cell line, RNK-16. We have further demonstrated that PLP-A effectively suppresses RNK-16 cell cytolytic activities. Our results provide evidence for a new paradigm of embryonic-maternal communication involving a PLP-A signaling pathway between trophoblast cells and uterine NK lymphocytes.

Alkaline Phosphatase↗
PubMed1999

Proliferative and apoptotic activity in lobular breast carcinoma.

Apoptotic and proliferative activity was studied in 25 invasive lobular breast carcinomas (ILC), and the relationship with conventional prognostic parameters [tumor size, nodal status, expression of estrogen (ER) and progesterone receptors (PR)] was investigated. Also 12 lobular carcinomata in situ (LCIS), 25 invasive ductal carcinomas (IDC) and 12 normal breast tissue controls were included. MIB-1 growth fraction (GF), mitotic index (MI) and the number of argyrophilic nucleolar organizer regions (AgNOR) served as proliferative parameters. Apoptotic index (AI) was determined after visualization of apoptoses by the TUNEL method. All parameters increased in the following order: control tissue - LCIS - ILC - IDC. Except for a negative correlation between GF and ER expression, no other significant relationship between any of the kinetical parameters and any prognostic parameter could be found in ILC. However, a significant inverse correlation between the GF:AI ratio and both ER and PR expression was registered. We conclude from our results a) that transition from non-invasive to invasive growth in lobular breast cancer is associated with an increased cellular turnover, and b) that proliferative activity is significantly lower in ILC than in IDC. The GF:AI ratio may possibly provide additional prognostic information in lobular breast cancer.

Aged↗
PubMed1999

[Polyomavirus infections in exotic birds in Switzerland].

Polyomavirus infections in budgerigars, in other parrots as well as in passeriformes have been described in many countries, but not in Switzerland so far. This paper reports on cases of polyomavirus infections in three different bird collections in Switzerland. The first outbreak occurred in a mixed collection of passeriformes, the second in a collection of parrotlets (Genus Forpus), and the third in a large groups of parrots (Psittaciformes), of which only one recently acquired Kea (Nestor notabilis) was affected. The clinical symptoms, gross necropsy changes and histopathologic findings are described. The presence of avian polyomavirus was confirmed by the polymerase chain reaction (PCR).

Animals↗
PubMed1999

[Validity of cardiotocography in the detection of umbilical cord complications].

OBJECTIVE: The purpose of this study was to investigate the validity of cardiotocography for the detection of cord complications. MATERIAL AND METHODS: A low-risk population of 4196 cases was selected in which cord complications have been recognized in 34.3%. Cases with cord complications and controls were paired by parity, gestational age, maternal age and mode of delivery. 25 pairs were randomly selected. 50 tracings were presented twice to 4 obstetricians in a double-blind manner. As parameters for the determination of the validity of fetal monitoring the reliability, positive (ppv) and negative predictive value (npv), sensitivity and specificity were used. Inter- and intra-observer variability were also examined. RESULTS: Reliability 52%, ppv 52%, npv 52%, sensitivity 46%, specificity 58%. Interobserver variability: All 4 obstetricians agreed in 47 of 100 evaluations. The level of agreement was higher in the controls (63%) than in the cord complication group (56%). The intraobserver variability was 25%. CONCLUSIONS: Cardiotocography is not useful for the detection of cord complications. The range of possibilities has not been exploited yet, even for the evaluation of the fetal state.

Cardiotocography↗
PubMed1999

[Severe and recent hyponatremia and hypokalemia associated to the use of hydrochlorothiazide, enalapril and citalopram. Clinical case].

We report a 72 years old hypertensive female, treated with enalapril 10 mg/day and hydrochlorothiazide 25 mg/day during three years. She presented a depressive disorder and cytalopram was prescribed in a dose of 10 mg/day. Two weeks before admission, a serum electrolyte analysis disclosed normal results and the cytalopram dose was increased to 20 mg/day. The patient was admitted with a hyponatremic encephalopathy with a plasma sodium of 100 mEq/L and a plasma potassium of 2.0 mEq/L. Cytalopram, enalapril and hydrochlorothiazide were discontinued, hypertonic NaCl and KCl were administered. The patient had a favorable evolution with a remarkable improvement of her symptoms.

Aged↗
PubMed1998

E2F-6: a novel member of the E2F family is an inhibitor of E2F-dependent transcription.

The E2F family of transcription factors are essential for the regulation of genes required for appropriate progression through the cell cycle. Five members of the E2F family have been previously reported, namely E2F1-5. All five are key elements in transcriptional regulation of essential genes, and they can be divided into two functional groups, those that induce S-phase progression when overexpressed in quiescent cells (E2Fs 1-3), and those that do not (E2Fs 4-5). Here, we describe the identification of a novel member of this family, which we refer to as E2F-6. E2F-6 shares significant homology with E2Fs 1-5, especially within the DNA binding, heterodimerization and marked box domains. Unlike E2Fs 1-5, E2F-6 lacks a transactivation and a pocket protein binding domain, hence, forms a unique third group within the E2F family. E2F-6 is a nuclear protein that can form heterodimers with the DP proteins (both DP-I and DP-2) in vitro and in vivo. Our results show that the complex formed between E2F-6 and the DP proteins, possesses high DNA binding activity, displaying a preference for a TTTCCCGC E2F recognition site, which is slightly different to the E2F consensus site derived from the E2 promoter (TTTCGCGC). In contrast to the other members of the E2F family, ectopic expression of E2F-6 inhibits transcription from promoters possessing E2F recognition sites rather than activating transcription. In addition, overexpression of E2F-6 suppresses the transactivational effects of coexpression of E2F-1 and DP-1. The inhibitory effect of E2F-6 is dependent on its DNA binding activity and its ability to form heterodimers with the DPs. Interestingly, ectopic expression of E2F-6 leads to accumulation of cells in S-phase. Our data suggest that E2F-6 expression delays the exit from S-phase rather than inducing S-phase, which further emphasizes the functional difference between E2F-6 and the previously known E2F family members.

Amino Acid Sequence↗
PubMed1998

Infectious bursal disease virus changes the potassium current properties of chicken embryo fibroblasts.

Infectious bursal disease virus (IBDV) is the causative agent of an economically significant poultry disease. IBDV infection leads to apoptosis in chicken embryos and cell cultures. Since changes in cellular ion fluxes during apoptosis have been reported, we investigated the membrane ion currents of chicken embryo fibroblasts (CEFs) inoculated with the Cu-1 strain of IBDV using the patch-clamp recording technique. Incubation of CEFs with IBDV led to marked changes in their K+ outward current properties, with respect to both the kinetics of activation and inactivation and the Ca2+ dependence of the activation. The changes occurred in a time-dependent manner and were complete after 8 h. UV-treated noninfectious virions induced the same K+ current changes as live IBDV. When CEFs were inoculated with IBDV after pretreatment with a neutralizing antibody, about 30% of the cells showed a normal K+ current, whereas the rest exhibited K+ current properties identical to or closely resembling those of IBDV-infected cells. Incubation of CEFs with culture supernatant from IBDV-infected cells from which the virus particles were removed had no influence on the K+ current. Our data strongly suggest that the K+ current changes induced by IBDV are not due to virus replication, but are the result of attachment and/or membrane penetration. Possibly, the altered K+ current may delay the apoptotic process in CEFs after IBDV infection.

Animals↗
PubMed1998

Identification of two new members of the mouse prolactin gene family.

The prolactin (PRL) family consists of a collection of genes expressed in the uterus, placenta, and anterior pituitary. These cytokines/hormones participate in the control of maternal-fetal adaptations to pregnancy. In this report, we establish the presence of two new members of the mouse PRL family. Novel expressed sequence tags (ESTs) with significant homology to PRL were isolated from embryonic, ectoplacental cone, and placental cDNA libraries. The cDNAs were sequenced and compared to other members of the PRL family. The two new cDNAs were assigned to the PRL family based on sequence homology and were referred to as PRL-like protein-F (PLP-F) and PRL-like protein-G (PLP-G). PLP-F cDNA encodes for a predicted 267 amino acid protein containing a 30 amino acid signal peptide and three putative N-linked glycosylation sites. PLP-G cDNA encodes for a predicted 266 amino acid protein containing a 30 amino acid signal peptide and six putative N-linked glycosylation sites. Sequence alignments of these proteins with other members of the PRL family suggest some unique features. Both sequences contain an extra amino acid segment located between exons two and three of the prototypical PRL gene and a nine amino acid carboxy terminal extension. PLP-F contained an additional 15 amino acid region situated between exons four and five of the prototypical PRL gene. Both PLP-F and PLP-G mRNAs were expressed in the placenta but not in other tissues (uterus, brain, thymus, heart, lung, diaphragm, liver, kidney, and ovary). In summary, the two newly identified members share approximately 50% amino acid sequence identity, are specifically expressed in the placenta, and represent a new subfamily within the PRL family.

Amino Acid Sequence↗
PubMed1998

Intracerebral hematomas caused by aneurysm rupture. Experience with 67 cases.

During a six-year (1986-1992) 334 patients with subarachnoid hemorrhage (SAH) were admitted to the Department of Neurosurgery. Medical University of Lübeck, Germany. In 281 patients the SAH was caused by rupture of an intracranial arterial aneurysm, verified by angiography, postmortem examination, or at emergency operation without angiography. In 67 (23.8%) of the 281 aneurysmal SAH patients the initial computerized tomography (CT) demonstrated an intracerebral hematoma (ICH). An ICH localized in the temporal lobe due to the rupture of a middle cerebral artery (MCA) aneurysm was found in 47 patients (70.2%). Forty-three patients were considered for surgery with a surgical mortality of 8 (18.6%). In the group of 19 ICH patients not operated upon, 16 individuals died (84.2%). We therefore advocate active surgical management of ICH patients: hematoma evacuation and aneurysm clipping at the same operation. Emergency surgery in younger patients (grade V) with temporal ICH suggesting the rupture of a MCA or internal carotid artery (ICA) aneurysm can be done without angiography.

Adult↗
PubMed1998

[Effects of electroconvulsive therapy on cognitive functions in therapy-refractory depression].

Within the context of an extensive study of electroconvulsive therapy at the Psychiatric Clinic of the University of Bonn 15 patients suffering from therapy-resistant Major depression (DSM III-R) were examined with a detailed psychometric test battery, containing memory- and nonmemory tests. The test battery had been applied short time before, during and after the treatment with 10 ECT applied unilateral over the nondominant hemisphere. Comparing the test performances before and 1-2 days after the end of the series there were only few remarkable changes: a significant decrease was diagnosed exclusively in 30 min delayed recall of verbal items, while visual short-term memory and visual-constructive performance showed a significant improvement (in spite of unilateral stimulation on the right side). None of the other cognitive functions inclusively speed of performances and reaction time was detracted short time after the end of the ECT-treatment, instead all the measures improved albeit not significantly. Between responders to treatment (50% improvement in HAMD) and non-responders no significant differences neither before nor after the treatment were detected. The non-responders had in nearly all of the tests some better (but not significantly) results despite being older than the group of responders.

Adult↗
PubMed1998

Reliability of interview information in a family study in the elderly.

The aim of the present study was to evaluate the combined test-retest and interrater reliability of different psychiatric lifetime diagnoses yielded in the course of a family study in elderly patients and controls. The following interviews and questionnaires were used in combination: the Composite International Diagnostic Interview (CIDI), the Structured Interview for the Diagnosis of Dementia of the Alzheimer Type, Multi-infarct Dementia and Dementias of Other Aetiology (SI-DAM), the General Health Questionnaire (GHQ-12) and questionnaires for neurasthenia and recurrent brief depression (RBD). Depressive and dementia disorders can be diagnosed with good reliability in a family study setting with the use of these instruments. The diagnoses of phobic disorders, neurasthenia, RBD, subthreshold RBD and psychiatric caseness as indicated by GHQ-12 scores were less reliable in this setting and are therefore less suitable for use in family studies.

Adult↗