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Biomedical subjects

M Klein

Publications and source records attributed to M Klein.

At least 199 records · Page 11Linked to original sources
PubMed1998

Cloning and characterization of promoter and 5'-UTR of the NMDA receptor subunit epsilon 2: evidence for alternative splicing of 5'-non-coding exon.

Using rapid amplification of cDNA ends (RACE), we have cloned the 5'-untranslated region (5'-UTR) of the N-methyl-D-aspartate receptor subunit epsilon 2 from murine forebrain-derived mRNA. We identified two distinct types of cDNA species differing in the presence or absence of one exon sequence. Sequencing of the 5'-non-coding region of the epsilon 2 gene revealed that the epsilon 2 5'-UTR consists of three untranslated exons located at least 20 kb upstream of exon 4 that contains the ATG codon for initiation of translation. This genomic organization shows a close similarity to the epsilon 3 gene. The transcriptional start site was determined by primer extension assays. Expression of the alternative exon sequence was shown by in situ hybridization in the murine brain. Basal transcriptional activity of the epsilon 2 promoter was detected in different neuronal and non-neuronal cell lines with transient reporter gene expression assays. Potential SP1 and CREB binding sites were found in the promoter region. Specific binding of these transcription factors was demonstrated in electrophoretic mobility shift assays.

3T3 Cells↗
PubMed1998

Directly energized uptake of beta-estradiol 17-(beta-D-glucuronide) in plant vacuoles is strongly stimulated by glutathione conjugates.

A directly energized vacuolar pump for glutathione (GS) conjugates has been described for several plant species. Since glucuronate conjugates also occur in plants, we addressed the question whether plant vacuoles take up the abiotic glucuronate conjugate estradiol 17-(beta-glucuronide) (E217G) via a GS conjugate pump, which in some cases has been reported to accept various organic anions as substrates, or via a distinct glucuronate transporter. Uptake studies into vacuoles from rye and barley were performed with E217G and metolachlor-GS (MOC-GS), a substrate of the GS conjugate ATPase, to compare glucuronate conjugate transport into vacuoles containing endogenous flavone glucuronides with those lacking specific glucuronate conjugates, respectively. Our results indicate that E217G and MOC-GS are taken up into vacuoles of both plants via a directly energized mechanism since transport was (i) strictly ATP-dependent; (ii) inhibited by vanadate but not by bafilomycin A1, azide, verapamil, nor by dissipation of the vacuolar DeltapH or DeltaPsi; (iii) E217G uptake into rye vacuoles was partially driven by other nucleotides in the following order of efficiency: ATP > GTP > UTP congruent with CTP, whereas the non-hydrolyzable ATP analogue 5'-adenylyl-beta,gamma-imidodiphosphate, ADP, or PPi did not energize uptake. E217G transport into rye vacuoles was saturable (Km approximately 0.2 mM). The rye-specific luteolin glucuronides decreased uptake rates of E217G and MOC-GS into rye and barley vacuoles to comparable degrees with the mono- and diglucuronidated derivatives (40-60% inhibition) being more effective than the triglucuronide. Inhibition of E217G uptake by luteolin 7-O-diglucuronide was competitive (Ki = 120 microM). Taurocholate had no effect on E217G transport, and uptake of MOC-GS was not inhibited by E217G. Although GS conjugates and oxidized GS decreased MOC-GS transport, E217G uptake into rye and barley vacuoles was stimulated up to 7-fold in a concentration-dependent manner by these substances, with dinitrobenzene-GS being most effective. The stimulation of the GS conjugates was not due to detergent or redox effects and was specific for the E217G pump. GS conjugate stimulation of glucuronate uptake was unique for plants as E217G uptake into yeast microsomal vesicles was not affected. By comparison with a DeltaYCF1 yeast mutant, defective in vacuolar transport of GS conjugates mediated by YCF1, it was shown that E217G was taken up into yeast vesicles via a YCF1-independent directly energized pump. These results indicate that E217G as a glucuronate conjugate is transported across the vacuolar membranes of plants and yeast by a carrier distinct from the GS conjugate ATPase.

Adenosine Triphosphate↗
PubMed1998

[Postoperative management of bone-anchored facial epitheses].

The long-term and successful treatment of facial defects with bone-anchored prostheses requires daily cleaning of the prosthesis, any retention elements and surrounding skin. This keeps a potential problem zone around the implant healthy and free of inflammation. Suitable concepts for care and cleaning aids are discussed.

Craniofacial Abnormalities↗
PubMed1998

[Constant social and spatial environment in aging: memory theory, case examples, practice relevance].

An ecological theory of remembering is formulated which is based on the patterns of meaningfulness in the social and spatial environment. The specific ecological relationship to the environment is affinitive, and also opens access to the resources of the past. In the present study, conditions for this access (in particular with older people) were investigated. It is assumed that older people, especially, when they lose someone with whom they had a fixed relationship seek counselling and that abrupt changes in the spatial environment, such as moving to a home, are rejected by older people. These hypotheses were checked on the basis of material (N = 120) gathered in a counselling service for the aged and they were essentially confirmed. To make matters clear, "typical" and thus every-day experiences of maintenance and loss of competence are cited from the material. Finally, practical conclusions are drawn with regard to work with the aged.

Activities of Daily Living↗
PubMed1998

Enhanced immune responses and resistance against infection in aged mice conferred by Flu-ISCOMs vaccine correlate with up-regulation of costimulatory molecule CD86.

Ageing is associated with a decline in immune function and our primary objective is to 'reverse' age-related decline in protective immune responses to vaccination by formulating vaccines in appropriate delivery systems. In this paper, we demonstrate that influenza vaccine formulated as ISCOMs is highly immunogenic and confers protection in aged mice, when compared to current influenza vaccine. The enhanced protection conferred by Flu-ISCOMs in aged mice correlates with the up-regulation of co-stimulatory molecule, CD86 (B7.2) and to a lesser extent, CD80 (B7.1) expression on antigen presenting cells.

Aging↗
PubMed1998

Treatment of squamous cell carcinomas of the floor of the mouth and tongue by interstitial high-dose-rate irradiation using iridium-192.

The results are presented of afterloading high-dose-rate-radiation with iridium-192 in 34 patients with squamous cell carcinomas of the floor of the mouth and tongue. Some patients were also treated surgically or given percutaneous radio- or chemotherapy. At the time of diagnosis, 28.0% had a T2 tumour, 41.9% a T3 tumour and 30.1% a T4 tumour, 41.2% had positive lymph nodes and 2.9% distant metastases. The response rate was 64.7%, 26.5% of which were complete remissions and 38.2% partial remissions. In 61.8% of cases, the tumour was recurrent and responded with a rate as high as 57.2%, 23.9% of which were complete remissions and 33.3% partial remissions. Survival times were dependent upon therapy results. The mean survival of patients with complete remission was 40.3 months, with partial remission 16.1 months as opposed to 7.2 and 3.5 months respectively in patients showing no change or progressive disease. It can be concluded that afterloading therapy using high-dose-rate-radiation with iridium-192 achieves good palliative results and should be looked at as a supplementary treatment modality for squamous cell carcinomas of the floor of the mouth and tongue.

Adult↗
PubMed1998

A 15-year overview of management and prognosis in primary fallopian tube carcinoma. Austrian Cooperative Study Group for Fallopian Tube Carcinoma.

143 women treated in 28 departments from 1980 to 1995 were retrospectively analysed to study the impact of prognostic factors in primary carcinoma of the fallopian tube. The mean age of the patients was 62.5 years. Sixty (42%) tumours were FIGO stage I, 28 (20%) stage II, 38 (27%) stage III, 17 (12%) stage IV. Complete radical resection was achieved in 102 (71%) patients. In 122 (85%) women, surgery involved removal of the uterus, the adnexa, and/or the omentum or lymph nodes. Postoperative therapy consisted of either irradiation (n = 40; 28%) or chemotherapy (n = 70; 49%); 33 women (23%) did not receive any treatment after surgery. The 5-year survival rate for all cases was 43%. The 5-year survival rate was 59% for stages I and II and 19% for stages III and IV (P < 0.00001). FIGO stage, histological grade and presence of residual tumour had an independent prognostic impact in multivariate analysis. In order to investigate the role of p53 in primary fallopian tube carcinomas, we analysed the immunohistochemical expression of p53 protein regarding survival and FIGO stage in 63 patients (44%). No statistical significance was observed.

Adult↗
PubMed1998

Aprotinin counterbalances an increased risk of peri-operative hemorrhage in CABG patients pre-treated with Aspirin.

OBJECTIVE: As Aspirin (ASA) has proven efficacy in preventing patients with CAD from complications related to cardiovascular diseases, most patients scheduled for CABG are treated with ASA therapy. Consequently, impaired hemostasis is a problem in the management of CABG patients. Clinical studies have shown that Aprotinin can reduce bleeding and the use of blood products by 50% in patients both with and without pre-operative ASA therapy. Concerning the combined effect of peri-operative low-dose ASA therapy and intra-operative high-dose Aprotinin therapy, the gathering of additional and prospective data seemed to be necessary. METHODS: We conducted a double-blind two-centre randomised three-arm study in patients with elective primary CABG surgery. Three groups have been tested, comprising 119 patients in total (group A: ASA + Aprotinin, group B: placebo + Aprotinin, group C: placebo + placebo) to investigate a possible reduction of bleeding in Aprotinin treated patients. For all patients, thromboxane levels were used to identify ASA or placebo treatment. RESULTS: The post-operative blood loss is significantly reduced by 21% after Trasylol administration (B vs. C; P = 0.009). The unexpected result of this study has been that the pre-treatment with ASA led to a further reduction of 18% (A vs. C; P < 0.0001). The difference between the two Aprotinin groups (A and B) is significant (P = 0. 01) in favour of ASA pre-treatment. Myocardial infarction (MI) had been diagnosed at levels of 1.8% in total (2/113), 2.6% (1/38) in group B and 3.2% (1/31 ) in group C. An additional blinded evaluation of ECG, enzyme levels and clinical status revealed 'definite, probable and possible' MIs of 5% in group A, compared to 16% in group B and 13% in group C, thus providing no evidence for a higher risk of infarction by Aprotinin treatment. When comparing the ASA group to non-ASA pre-treatment, a strong trend towards a reduction in MI rate becomes obvious, from 15% to 5% in favour of the ASA pre-treatment (P = 0.08). Concerning other peri-operative complications, no statistical difference between the groups could be detected. CONCLUSIONS: A reduction in post-operative blood loss in primary elective CABG surgery with intra-operative Aprotinin treatment could be confirmed. A low-dose ASA treatment combined with a high-dose aprotinin administration during surgery not only neutralized a potentially higher risk of bleeding, but did in fact reduce the post-operative blood loss. The protective effect of ASA on peri-operative MI has been evident through a reduction of MI rate in ASA treated patients.

Aprotinin↗
PubMed1998

Benefits and costs to community-based physicians teaching primary care to medical students.

The purpose of this study was to determine the benefits and costs to community-based primary care physicians teaching medical students in their offices. Survey data were collected from 185 preceptors between 1990 and 1996. Respondents reported increases in their enjoyment of the practice of medicine (82%), time spent reviewing clinical medicine (66%), desire to keep up with recent developments in medicine (49%), and patients' perception of their stature (44%). However, 61% reported a decrease in the number of patients seen when a student was present. We conclude that despite the costs associated with teaching medical students in their offices, preceptors derived many benefits.

Clinical Clerkship↗
PubMed1998

Centrifugal pumping during routine open heart surgery improves clinical outcome.

Carrying out a 1,000 patient prospective, randomized study comparing a roller pump and the BioMedicus centrifugal pump (CP), hematological parameters, blood loss, renal function, postoperative complications, and lethality data were evaluated. Using a validated preoperative risk stratification method (Cardiac RiskMaster), patients were divided into different risk categories for statistical analysis. This study verified an improved outcome with the use of a CP in routine cardiac surgery, demonstrated by blood handling, blood loss, renal function, and nephrological complication data. There was also a significant reduction in neurological complications. There was no significant difference in postoperative lethality, but high risk patients demonstrated outcomes comparable to those being defined for medium risk patients. Routine cardiac surgical patients as well as multimorbid patients benefit from the use of a CP. Preoperative risk stratification is a valid tool to demonstrate how the employment of new technologies can provide for an improved outcome without increasing overall costs at the same time.

Age Factors↗
PubMed1998

Diagnostic value of procalcitonin: the influence of cardiopulmonary bypass, aprotinin, SIRS, and sepsis.

BACKGROUND: The reasons for a systemic inflammatory response syndrome (SIRS) following ECC are not yet fully understood. Procalcitonin (PCT) blood levels may distinguish between bacterial infections and a non-bacterial systemic inflammation. We investigated the influence of ECC, ECC modified by application of aprotinin, systemic inflammation, and bacterial infection on the PCT values. METHODS: 20 CABG patients were randomized and divided in two groups. Group A served as the control group, while group B perioperatively received a high dose of aprotinin. Blood samples for measurement of PCT were taken 6 times perioperatively. Furthermore, blood samples were taken from 20 preoperatively comparable patients who suffered from bacterial infection (n = 10) (group C) or a SIRS (n = 10) (group D) after ECC; in these groups PCT was determined daily after the onset of inflammation. RESULTS: There was no significant elevation of PCT in group A or B at any time. In sepsis patients a significant elevation of PCT was seen, with the peak level of 18.6+/-6.3 ng/ml on the second day after diagnosis; the PCT level of SIRS patients remained constantly low (<0.9 ng/ml). CONCLUSIONS: In this study it was demonstrated that ECC and the use of aprotinin did not have any influence on the secretion of PCT. A systemic bacterial infection caused a significant increase of PCT, whereas PCT values remained normal in case of a SIRS. So it seems to be possible to distinguish between a primary SIRS and a bacterial sepsis by means of PCT.

Aged↗
PubMed1998

[Energy metabolism in laying hens of different body weight genotypes].

Energy metabolism and some performance parameters were investigated in laying hens of 3 different body weight-genotypes: 6 x 7 (normal-sized, crossbred from normal-sized male and female lines, group 1), 47 x 38 (dwarf-sized, breeding from a dwarf-sized male line and a normal-sized female line, group 2) and 44 x 47 (dwarf-sized, breeding from dwarf-sized male and female lines, group 3). Energy balance was measured by indirect calorimetry through C- and N-balances in 12 animals of each group during 10 consecutive days at production peak, within the period between the 27th and the 37th week of age. Hens were caged individually at 23 degrees C environmental temperature and fed ad libitum on a laying mash. The mean body weight in the dwarf-sized groups 2 and 3 was 32% lower than in the normal-sized group 1 during the energy balance period. The daily gross energy intake in group 2 and 3 was decreased by 33 and 34%, respectively. There were no significant differences in digestibility and metabolizability of gross energy between the groups. The energy requirements for maintenance [kJ ME/kg0.75.d] derived from the energy balances were lower by 4% (P > 0.05) and 14% (P < 0.05) in the dwarf-sized groups 2 and 3 as compared with the normal-sized group 1, when equal coefficients of partial efficiency of metabolizable energy utilization for energy retention in body and eggs are assumed for the 3 body-mass genotypes. There were no relevant differences in body composition at the end of the energy balance periods as well as in egg composition between the 3 experimental groups.

Animals↗
PubMed1998

Heterotypic protection against influenza by immunostimulating complexes is associated with the induction of cross-reactive cytotoxic T lymphocytes.

Influenza immunostimulating complexes (flu-ISCOMs) and a monovalent subvirion vaccine prepared with an H1N1 strain of influenza virus were compared in mice for immunogenicity and protection against challenge with homologous and heterotypic influenza viruses. flu-ISCOMs but not subvirion vaccine fully protected mice against homologous virus challenge after one immunization as assessed by measurement of virus lung titers. The improved protection induced by flu-ISCOMs was associated with a 10-fold higher prechallenge serum hemagglutination inhibition titer. Furthermore, only flu-ISCOMs fully protected mice against mortality and reduced morbidity following challenge with an influenza virus of the serologically distinct H2N2 subtype. This cross-protection correlated with the induction of virus cross-reactive cytotoxic T lymphocytes that recognized a known major histocompatibility class I (H2-Kd)-restricted epitope within the hemagglutinin of influenza virus that is conserved among the H1 and H2 influenza virus subtypes. flu-ISCOMs may offer significant advantages over current commercial formulations as an improved influenza vaccine.

Animals↗
PubMed1998

Procaryotic expression of single-chain variable-fragment (scFv) antibodies: secretion in L-form cells of Proteus mirabilis leads to active product and overcomes the limitations of periplasmic expression in Escherichia coli.

Recently it has been demonstrated that L-form cells of Proteus mirabilis (L VI), which lack a periplasmic compartment, can be efficiently used in the production and secretion of heterologous proteins. In search of novel expression systems for recombinant antibodies, we compared levels of single-chain variable-fragment (scFv) production in Escherichia coli JM109 and P. mirabilis L VI, which express four distinct scFvs of potential clinical interest that show differences in levels of expression and in their tendencies to form aggregates upon periplasmic expression. Production of all analyzed scFvs in E. coli was limited by the severe toxic effect of the heterologous product as indicated by inhibition of culture growth and the formation of insoluble aggregates in the periplasmic space, limiting the yield of active product. In contrast, the L-form cells exhibited nearly unlimited growth under the tested production conditions for all scFvs examined. Moreover, expression experiments with P. mirabilis L VI led to scFv concentrations in the range of 40 to 200 mg per liter of culture medium (corresponding to volume yields 33- to 160-fold higher than those with E. coli JM109), depending on the expressed antibody. In a translocation inhibition experiment the secretion of the scFv constructs was shown to be an active transport coupled to the signal cleavage. We suppose that this direct release of the newly synthesized product into a large volume of the growth medium favors folding into the native active structure. The limited aggregation of scFv observed in the P. mirabilis L VI supernatant (occurring in a first-order-kinetics manner) was found to be due to intrinsic features of the scFv and not related to the expression process of the host cells. The P. mirabilis L VI supernatant was found to be advantageous for scFv purification. A two-step chromatography procedure led to homogeneous scFv with high antigen binding activity as revealed from binding experiments with eukaryotic cells.

Animals↗
PubMed1998

Green tobacco sickness.

OBJECTIVE: To describe the health impact of harvesting tobacco and to suggest prevention and risk reduction strategies to avoid contracting green tobacco sickness (GTS). DATA SOURCES: A literature search of Medline, Toxline, and Toxline65 with the terms "green", "tobacco", and "sickness" covering the years 1966-1998. STUDY SELECTION: All studies, reviews, and commentaries that provided information on the health effects of harvesting green tobacco and disease prevention strategies. DATA SYNTHESIS: GTS occurs when tobacco workers hand-harvest, cut, or load tobacco plants, usually in the early morning or after a rainfall when tobacco plants are covered with moisture. GTS occurs through skin exposure to dissolved nicotine from tobacco leaves. Symptoms of GTS include weakness, headache, nausea, vomiting, dizziness, abdominal cramps, breathing difficulty, abnormal temperature, pallor, diarrhoea, chills, fluctuations in blood pressure or heart rate, and increased perspiration and salivation. The onset of the illness is three to 17 hours after exposure and the duration of illness is one to three days. Initial treatment includes cessation of work, change of clothing, showering, fluid intake, and rest. In more extreme cases, intravenous rehydration, anti-emetics, and dimenhydrinate are administered. Protective, water-resistant clothing; chemical-resistant gloves, boots, and socks; working in dry conditions; and dimenhydrinate can reduce the likelihood of contracting GTS. CONCLUSIONS: It is important to provide education to tobacco workers and employers about GTS. An international public awareness campaign about GTS timed to coincide with the tobacco harvest, along with enforced worker safety regulations, should be undertaken to protect the health of individuals working in tobacco production.

Adolescent↗