Biomedical subjects

E Winter

Publications and source records attributed to E Winter.

At least 37 records · Page 2Linked to original sources

PubMed2000

Dependency of the [18F]fluoromisonidazole uptake on oxygen delivery and tissue oxygenation in the porcine liver.

We have previously shown that the accumulation of fluorine-18-labeled fluoromisonidazole ([(18)F]FMISO) is inversely correlated to tissue oxygenation, allowing the quantification of porcine liver tissue hypoxia in vivo. We determined the activity from administered [(18)F]FMISO in relation to the hepatic oxygen availability and the partial pressure of oxygen in tissue (tPO(2)) to define a critical oxygen delivery on a regional basis. [(18)F]FMISO was injected 2 h after onset of regional liver hypoxia due to arterial occlusion of branches of the hepatic artery in 10 domestic pigs. During the experimental procedure the fractional concentration of inspired oxygen (FiO(2)) was set to 0.67 in group A ( N=5) and to 0.21 in group B ( N=5) animals. Immediately before sacrifice, the tPO(2) was determined in normal flow and flow-impaired liver segments. The standardized uptake values (SUV) for [(18)F]FMISO was calculated from 659 single tissue samples obtained 3 h after injection of approximately 10 MBq/kg body weight [(18)F]FMISO and was compared with the regional total hepatic oxygen delivery (DO(2)) calculated from the regional arterial and portal venous flow (based on (141)Ce- and (99m)Tc-microspheres measurements) and the oxygen content of the arterial and portal venous blood. In 121 tPO(2)-measured liver tissue samples, the mean DO(2) was significantly decreased in occluded liver tissue samples [group A: 0.063 (0.044-0.089); group B: 0.046 (0.032-0.066)] compared to normal flow segments [group A: 0.177 (0.124-0.252); group B: 0.179 (0.128-0.25) mL x min(-1) x g(-1); geometric mean (95% confidence limits); p < 0.01 in group A and p < 0.001 in group B]. The tPO(2) of occluded segments [group A: 5.1 (3.2-8.1); group B: 3.9 (2.4-6.2) mm Hg] was significantly decreased compared to normal flow segments [group A: 20.2 (12.6-32.5); group B: 22.4 (14.3-35.2) mm Hg; p < 0.01 in group A and p < 0.001 in group B]. Three hours after [(18)F]FMISO administration, the mean [(18)F]FMISO SUV determined in tPO(2)-measured occluded segments was significantly higher [group A: 4.08 (3.12-5.34), group B: 5.43 (4.14-7.13)] compared to normal liver tissue [group A: 1.57 (1.2-2.06), group B: 1.5 (1.16-1.93); p < 0.001 for both groups]. The [(18)F]FMISO SUV allowed prediction of the tPO(2) with satisfying accuracy in hypoxic regions using the exponential regression curve [[(18)F]FMISO=1.05+6.7((-0.117 tPO(2))); r(2)=0.75; p < 0.001]. In addition, regardless of ventilation conditions, a significant exponential relationship between the DO(2) and the [(18)F]FMISO SUV was found ( r(2)=0.39, p < 0.001). Our results suggest that the reduction of the oxygen delivery below the critical range of 0.1-0.11 mL x min(-1) x g(-1) regularly causes liver tissue hypoxia. The severity of hypoxia is reflected by the [(18)F]FMISO accumulation and allows the in vivo estimation of the tPO(2) in hypoxic regions.

Animals↗

PubMed2000

cDNA cloning and analysis of tissue-specific expression of mouse peroxisomal straight-chain acyl-CoA oxidase.

Straight-chain acyl-CoA oxidase is the first and rate limiting enzyme in the peroxisomal beta-oxidation pathway catalysing the desaturation of acyl-CoAs to 2-trans-enoyl-CoAs, thereby producing H2O2. To study peroxisomal beta-oxidation we cloned and characterized the cDNA of mouse peroxisomal acyl-CoA oxidase. It consists of 3778 bp, including a 1983-bp ORF encoding a polypeptide of 661 amino-acid residues. Like the rat and human homologue the C-terminus contains an SKL motif, an import signal present in several peroxisomal matrix proteins. Sequence analysis revealed high amino-acid homology with rat (96%) and human (87%) acyl-CoA oxidase in addition to minor homology ( approximately 40%) with other related proteins, such as rabbit trihydroxy-cholestanoyl-CoA oxidase, human branched chain acyl-CoA oxidase and rat trihydroxycoprostanoyl-CoA oxidase. Acyl-CoA oxidase mRNA and protein expression were most abundant in liver followed by kidney, brain and adipose tissue. During mouse brain development acyl-CoA oxidase mRNA expression was highest during the suckling period indicating that peroxisomal beta-oxidation is most critical during this developmental stage. Comparing tissue mRNA levels of peroxisome proliferator-activated receptor alpha and acyl-CoA oxidase, we noticed a constant relationship in all tissues investigated, except heart and adipose tissue in which much more, and respectively, much less, peroxisome proliferator-activated receptor alpha mRNA in proportion to acyl-CoA oxidase mRNA was found. Our data show that acyl-CoA oxidase is an evolutionary highly conserved enzyme with a distinct pattern of expression and indicate an important role in lipid metabolism.

Acyl-CoA Oxidase↗

PubMed2000

Results of an uncemented straight femoral shaft prosthesis after 9 years of follow-up.

The first consecutive 250 implantations of an uncemented, proximally anchored straight femoral shaft prosthesis (BiCONTACT) in 236 patients are included in this prospective follow-up study. Average time of follow-up evaluation was 8.9 years (range, 7.4-10.7 years). At follow-up, 27 patients had died, and 2 could not be located. Seven patients underwent revision-2 for infection, 1 for recurrent dislocation, 2 for component undersizing with rapid subsidence, and 1 for aseptic loosening of a varus-malaligned stem; 1 radiologically well-fixed stem had been revised during acetabular revision. Overall survival was 97.1% after 11 years (confidence limits, 98.7% [upper] and 93.6% [lower]). The average Harris Hip score at time of follow-up was 84.3 points. Radiologically, tiny reactive lines (<2 mm) were present in the distal zones of the femoral shaft, but no radiolucencies could be found in the proximal anchoring zone. The midterm to long-term follow-up results with the evaluated femoral component are encouraging and are comparable to those of modern techniques of cementing in primary total hip arthroplasty.

Adult↗

PubMed1999

Sum1 and Hst1 repress middle sporulation-specific gene expression during mitosis in Saccharomyces cerevisiae.

Meiotic development in yeast is characterized by the sequential induction of temporally distinct classes of genes. Genes that are induced at the middle stages of the pathway share a promoter element, termed the middle sporulation element (MSE), which interacts with the Ndt80 transcriptional activator. We have found that a subclass of MSEs are strong repressor sites during mitosis. SUM1 and HST1, genes previously associated with transcriptional silencing, are required for MSE-mediated repression. Sum1 binds specifically in vitro to MSEs that function as strong repressor sites in vivo. Repression by Sum1 is gene specific and does not extend to neighboring genes. These results suggest that mechanisms used to silence large regions of chromatin may also be used to regulate the expression of specific genes during development. NDT80 is regulated during mitosis by both the Sum1 and Ume6 repressors. These results suggest that progression through sporulation may be controlled by the regulated competition between the Sum1 repressor and Ndt80 activator at key MSEs.

Binding Sites↗

PubMed1999

[Structure quality in outpatient care of chronic pain patients].

BACKGROUND: Outcome quality of medical treatment depends on structure quality of the treatment facility. In the present study we tried evaluate structural parameters of outpatient treatment facilities relating to management of headache, low back pain and cancer pain. METHODS: 109 outpatient treatment facilities (104 offices, 3 outpatient departments of hospitals, 2 pain ambulances of hospitals) in middle franconia, one of the larger Bavarian administrative division (population: 1,6 Mio.), have been evaluated by questionnaires. Questions examined certain structural conditions of the treatment facility as compared to german guidelines for outpatient treatment of pain patients ("Schmerztherapievereinbarung"). RESULTS: Only one treatment facility worked within an interdisciplinary setting. Less than 25% (median) of total patients of an outpatient treatment facility suffered from acute or chronic headache, low back pain or cancer pain. 38% of physicians participated regularly on pain conferences. Established methods for diagnosis and documentation of patients suffering from chronic headache, chronic back pain and cancer pain were regularly used by 16%, 12% and 10% of physicians, respectively. Regular interdisciplinary cooperation in the management of patients with chronic headache, chronic back pain and cancer pain was indicated by 28%, 24% and 41% of physicians, respectively. However, personal discussion of patient related problems took place in less than 5% of physicians. Although a considerable number of different therapies (included as standard therapy for outpatient management of chronic pain in the "Schmerztherapievereinbarung") can be applied in each outpatient treatment facility (median:5), psychological therapy for management of chronic headache, chronic back pain and cancer pain was used regularly by 5%, 2% and 7% of physicians, respectively. Scoring of all examined structural parameters provides a measure for the quality of the parameters of a certain outpatient treatment facility as compared to that of an optimal outpatient facility for pain treatment (quality score=100%). However, 75% of examined outpatient treatment facilities reached quality scores only up to 43%. CONCLUSIONS: There are considerable structural deficits in outpatient treatment facilities involved in management of patients suffering from chronic headache, chronic back pain and cancer pain. Realisation of standards according to the "Schmerztherapievereinbarung" needs organisation of an interdisciplinary network between the different specialties necessary for pain management. Interdisciplinary cooperation should be supported by the official organization of the medical self-government in Germany--the Kassenärztliche Vereinigung--which has to assure optimal conditions for outpatient treatments.

English Abstract↗

PubMed1999

Allogenic bone graft viability after hip revision arthroplasty assessed by dynamic [18F]fluoride ion positron emission tomography.

The biological fate of allogenic bone grafts in the acetabular cavity and their metabolic activity after acetabular augmentation is uncertain but is most important for the stability of hip implants after hip revision arthroplasty. The aim of this study was to quantify regional bone metabolism after hip replacement operations. Dynamic [18F]fluoride ion positron emission tomography (PET) was used to investigate the metabolic activity of acetabular allogenic bone grafts and genuine bone, either 3-6 weeks (short-term group, n = 9) or 5 months to 9 years (long-term group, n = 10) after hip revision arthroplasty. Applying a three-compartment model, the fluoride influx constant was calculated from individually fitted rate constants (Knlf) and by Patlak graphical analysis (Kpat). The results were compared with genuine cancellous and cortical acetabular bone of contralateral hips without surgical trauma (n = 7). In genuine cortical bone, Knlf was significantly increased in short- (+140.9%) and long-term (+100.0%) groups compared with contralateral hips. Allogenic bone grafts were characterised by a significantly increased Knlf in the short-term group (+190.9%) compared with contralateral hips, but decreased almost to the baseline levels of contralateral hips (+45.5%) in the long-term. Values of Knlf cor-related with the rate constant K1 in genuine (r = 0.89, P<0.001) and allogenic bone regions (r = 0.79, P<0.001), indicating a coupling between bone blood flow and bone metabolism in genuine bone as well as allogenic bone grafts. Kpat values were highly correlated with Knlf measurements in all regions. In conclusion, [18F]fluoride ion PET revealed the presence of an increased host bone formation in allogenic bone grafts early after hip revision arthroplasty. In contrast to genuine cortical bone, allogenic bone graft metabolism decreased over time, possibly due to a reduced ability to respond to the same extent as genuine bone to elevated metabolic demands after surgery.

Aged↗

PubMed1999

[Muscle strength after surgical treatment of ruptures of the long biceps tendon by refixation to the short head].

Operative treatment for ruptures of the long biceps tendon still is discussed controversially. In the present literature surgical repair is advised for sporting and high demand patients due to favourable functional results and low loss of strength. Until now only few objective and reproducible results were published. In the present literature the keyhole-technique is recommended due to favourable bio-mechanical conditions. To evaluate postoperative strength 19 patients were investigated after an average follow-up of 6.5 years, by clinical examination and isokinetic measurement. Compared with the non-operated shoulder isokinetic determination of isometric maximal peak torque and strength during concentric stress for elbow-flexion, shoulder-abduction and shoulder-flexion yield to almost identical results for the operated shoulder. According to the criteria of the Constant-Score all patients achieved very good and good results. Refixation to the short head can be advised for treatment of ruptures of the long biceps tendon due to the certain technique with a low complication rate and very good functional outcome.

Adult↗

PubMed1999

Distinct steps in yeast spore morphogenesis require distinct SMK1 MAP kinase thresholds.

The SMK1 mitogen-activated protein kinase is required for spore morphogenesis in Saccharomyces cerevisiae. In contrast to the multiple aberrant spore wall assembly patterns seen even within a single smk1 null ascus, different smk1 missense mutants block in a coordinated fashion at intermediate stages. One smk1 mutant forms asci in which the four spores are surrounded only by prospore wall-like structures, while another smk1 mutant forms asci in which the spores are surrounded by inner but not outer spore wall layers. Stepwise increases in gene dosage of a hypomorphic smk1 allele allow for the completion of progressively later morphological and biochemical events and for the acquisition of distinct spore-resistance phenotypes. Furthermore, smk1 allelic spore phenotypes can be recapitulated by reducing wild-type SMK1 expression. The data demonstrate that SMK1 is required for the execution of multiple steps in spore morphogenesis that require increasing thresholds of SMK1 activity. These results suggest that quantitative changes in mitogen-activated protein kinase signaling play a role in coordinating multiple events of a single cellular differentiation program.

Alleles↗

PubMed1998

Localization and regulation of the cdk-activating kinase (Cak1p) from budding yeast.

Eukaryotic cell cycles are controlled by the activities of cyclin-dependent kinases (cdks). The major cdk in budding yeast, Saccharomyces cerevisiae, is Cdc28p. Activation of Cdc28p requires phosphorylation on threonine 169 and binding to a cyclin. Thr-169 is phosphorylated by the cdk-activating kinase (CAK), Cak1p, which was recently identified as the physiological CAK in budding yeast. Here we present our further characterization of yeast Cak1p. We have found that Cak1p is dispersed throughout the cell as shown by immunofluorescence; biochemical subcellular fractionation confirmed that most of the Cak1p is found in the cytoplasm. Cak1p is a monomeric enzyme in crude yeast lysates. Mutagenesis of potential sites of activating phosphorylation had little effect on the activity of Cak1p in vitro or in vivo. Furthermore, Cak1p contains no posttranslational modifications detectable by two-dimensional isoelectric focusing. We found that Cak1p is a stable protein during exponential growth but that its expression decreases considerably when cells enter stationary phase. In contrast, Cak1p levels oscillate dramatically during meiosis, reflecting regulation at both the transcriptional and post-translational level. The localization and regulation of Cak1p are in contrast to those of the known vertebrate CAK, p40(MO15).

Amino Acid Sequence↗

PubMed1998

[Pain therapy in pediatric oncology].

Malignancy-related pain is of similar frequency in children and adolescents as in adults. In children too evaluation of pain intensity, character and location is the basis for individually adapted pain therapy. The choice of medication is determined by the pathophysiological cause and the intensity of the pain. In addition to non-opioid analgesics, tramadol is used for moderate, and morphine for severe, pain. In the case of neuropathic pain, coanalgesics are employed. If oral treatment with morphine is no longer possible, pain pumps for continuous parenteral treatment must be used in children too. Provided the appropriate medical care is possible, parenteral treatment with potent opioids can also be applied at home. In children, every effort must be made to make painful diagnostic and therapeutic measures as painfree as possible.

Adult↗

PubMed1998

Surgical repair of Achilles tendon rupture. Comparison of surgical with conservative treatment.

Achilles tendon suture combined with a triceps surae tendon tip-over graft was performed in 314 patients with acute rupture of the Achilles tendon between 1980 and 1991. Analysis of these cases showed a low tissue complication rate compared with that reported in the literature. An average of 8.1 years after repair, 223 patients were examined using Holz's scale of clinical assessment after Achilles tendon repair. The results were 'good' in 87.4%, 'fair' in 11.2% and 'poor' in 1.4%. The re-rupture rate was very low (0.4%). These results are better than the re-rupture rate after surgical repair with solely end-to-end suture or after conservative immobilizing or conservative functional treatment. In conclusion, these data show that the fascial reinforcement is a valuable complement to the tendon suture.

Achilles Tendon↗

PubMed1998

Transcriptional regulation of the SMK1 mitogen-activated protein kinase gene during meiotic development in Saccharomyces cerevisiae.

Meiotic development (sporulation) in Saccharomyces cerevisiae is characterized by an ordered pattern of gene expression, with sporulation-specific genes classified as early, middle, mid-late, or late depending on when they are expressed. SMK1 encodes a mitogen-activated protein kinase required for spore morphogenesis that is expressed as a middle sporulation-specific gene. Here, we identify the cis-acting DNA elements that regulate SMK1 transcription and characterize the phenotypes of mutants with altered expression patterns. The SMK1 promoter contains an upstream activating sequence (UASS) that specifically interacts with the transcriptional activator Abf1p. The Abf1p-binding sites from the early HOP1 and the middle SMK1 promoters are functionally interchangeable, demonstrating that these elements do not play a direct role in their differential transcriptional timing. Timing of SMK1 expression is determined by another cis-acting DNA sequence termed MSE (for middle sporulation element). The MSE is required not only for activation of SMK1 transcription during middle sporulation but also for its repression during vegetative growth and early meiosis. In addition, the SMK1 MSE can repress vegetative expression in the context of the HOP1 promoter and convert HOP1 from an early to a middle gene. SMK1 function is not contingent on its tight transcriptional regulation as a middle sporulation-specific gene. However, promoter mutants with different quantitative defects in SMK1 transcript levels during middle sporulation show distinct sporulation phenotypes.

Calcium-Calmodulin-Dependent Protein Kinases↗

PubMed1998

Exogenously acquired Clostridium septicum gas gangrene--a case report.

We report on a 72-year-old woman suffering from gas gangrene of the right leg, which developed 3 days after getting injured while gardening. Due to rapid microbiological diagnosis-direct microscopical examination of muscle biopsies revealed numerous grampositive rods-, immediately performed amputation of the leg and antibiotic treatment with penicillin and metronidazole the patient survived. From the muscle biopsies Clostridium septicum, which is found ubiquitously, was isolated in pure culture.

Aged↗

PubMed1997

The CDK-activating kinase CAK1 can dosage suppress sporulation defects of smk1 MAP kinase mutants and is required for spore wall morphogenesis in Saccharomyces cerevisiae.

Mitogen-activated protein (MAP) kinase pathways are evolutionarily conserved kinase cascades that are required for the response of eukaryotic cells to a wide variety of environmental stimuli. MAP kinase pathways are also required for the execution of developmental and differentiative programs in a variety of cell and tissue types. SMK1 encodes a developmentally regulated MAP kinase in yeast that is required for spore wall morphogenesis. Cyclin-dependent kinase-activating kinases (CAKs) phosphorylate a conserved threonine residue in the activating loop of cyclin-dependent kinases. CAK1 encodes the major CAK activity in yeast and is required for cell cycle progression. The work presented here demonstrates that CAK1 functions positively in the spore wall morphogenesis pathway. First, CAK1 has been isolated as a dosage suppressor of a conditional smk1 mutant that is defective for spore wall morphogenesis. Second, CAK1 mRNA accumulates during spore development contemporaneously with SMK1 mRNA. Third, cak1 mutant strains have been isolated that are able to complete meiosis I and II but are specifically defective in assembly of the spore wall. These results show that cell cycle progression and morphogenetic pathways can be regulated by a single gene product and suggest mechanisms for coordinating these processes during development.

Alleles↗

PubMed1997

Decarboxylation of malonyl-(acyl carrier protein) by 3-oxoacyl-(acyl carrier protein) synthases in plant fatty acid biosynthesis.

In order to identify regulatory steps in fatty acid biosynthesis, the influence of intermediate 3-oxoacyl-(acyl carrier proteins) (3-oxoacyl-ACPs) and end-product acyl-ACPs of the fatty acid synthase reaction on the condensation reaction was investigated in vitro, using total fatty acid synthase preparations and purified 3-oxoacyl-ACP synthases (KASs; EC 2.3.1.41) from Cuphea lanceolata seeds. KAS I and II in the fatty acid synthase preparations were assayed for the elongation of octanoyl- and hexadecanoyl-ACP respectively, and the accumulation of the corresponding condensation product 3-oxoacyl-ACP was studied by modulating the content of the reducing equivalentS NADH and NADPH. Complete omission of reducing equivalents resulted with either KAS in the abnormal synthesis of acetyl-ACP from malonyl-ACP by a decarboxylation reaction. Supplementation with NADPH or NADH, separately or in combination with recombinant 3-oxoacyl-ACP reductase (EC 1.1.1.100), led to a decrease in the amount of acetyl-ACP and a simultaneous increase in elongation products. This demonstrates that the accumulation of 3-oxoacyl-ACP inhibits the condensation reaction on the one hand, and induces the decarboxylation of malonyl-ACP on the other. By carrying out similar experiments with purified enzymes, this decarboxylation was attributed to the action of KAS. Our data point to a regulatory mechanism for the degradation of malonyl-ACP in plants which is activated by the accumulation of the fatty acid synthase intermediate 3-oxoacyl-ACP.

3-Oxoacyl-(Acyl-Carrier-Protein) Synthase↗

PubMed1997

Presence of mycobacterial DNA in sarcoidosis.

In 11 of 35 clinically proven cases of sarcoidosis, we detected DNA sequences coding for the mycobacterial 65-kDa antigen. In four cases, the sequences were homologous to Mycobacterium avium; seven sequences were related to other nontuberculous Mycobacteria. The insertion sequence 1110, characteristic for Mycobacterium avium, was present in three cases. The insertion sequence 6110 of the Mycobacterium tuberculosis complex (M tuberculosis, africanum, bovis, BCG) was not detectable in any of the 11 cases, ruling out the presence of members of the Mycobacterium tuberculosis complex. Therefore, it seems reasonable to speculate about a mycobacterial cause in some cases of sarcoidosis.

DNA, Bacterial↗

PubMed1997

Elderly veterans receiving care at a Veterans Affairs Medical Center while enrolled in Medicare-financed HMOs. Is the taxpayer paying twice?

Elderly veterans who visit our Veterans Affairs (VA) Medical Center primary care clinic often mention they are enrolled in HMOs. Approximately 20% of patients hospitalized at our facility report health insurance coverage. Of 1,000 hospitalizations during a 6-month period in which veterans reported insurance coverage, 337 involved elderly veterans. Of these 337 hospitalizations, 218 (65%) were for 174 veterans who stated they were enrolled in a Medicare-financed HMO. The VA's Medical Care Cost Recovery Program deemed only 46 (21%) of the hospitalizations billable and received reimbursement for 20 (9%). Thus, the VA is providing costly services already paid for by the Health Care Financing Administration under prepaid capitation contracts, and recovers minimal reimbursement from the HMOs.

Aged↗

PubMed1996

Narcolepsy in a 2-year-old boy.

This report describes the prospective follow-up of a 2-year-old child with narcolepsy. The initial clinical diagnosis was confirmed by the onset of cataplexy when the child was 5 years old. He does not have the HLA genotype characteristic of narcolepsy or an identifiable brain lesion, although he has megalencephaly and mild learning difficulties. Treatment with dietary tyrosine supplements who are to young to use stimulants safely. The morbidity of narcolepsy is high and early diagnosis is therefore important, as treatment is effective.

Cataplexy↗