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Biomedical subjects

M Huber

Publications and source records attributed to M Huber.

At least 109 records · Page 6Linked to original sources
PubMed1998

Effective and long-lasting immunity against the parasite Leishmania major in CD8-deficient mice.

The results of earlier investigations that tested whether CD8(+) T cells are required in the defense against Leishmania major have been inconsistent. We used CD8-deficient mice to directly address this issue. After primary infection with L. major, CD8-deficient mice controlled the infection for over 1 year and mounted strong T helper 1 cell responses. Thus, CD8(+) T cells are not required for the long-term control of a primary infection with L. major.

Animals↗
PubMed1998

Significance of Supraventricular Tachyarrhythmias After Coronary Artery Bypass Graft Surgery and Their Prevention by Low-Dose Sotalol: A Prospective Double-Blind Randomized Placebo-Controlled Study.

BACKGROUND: The single most frequent complication after coronary artery bypass graft surgery is the occurrence of supraventricular tachyarrhythmias leading to a prolonged hospital stay. Although several drugs have been used to treat these arrhythmias, effective prevention was only possible with beta-blocking drugs in selected patients. It was, therefore, the aim of the present study to evaluate the significance of supraventricular tachyarrhythmias in presence of today's cardioprotective management in a broad spectrum of patients and to assess the possible preventive effect and safety of low-dose sotalol after coronary artery bypass graft surgery. METHODS AND RESULTS: In a prospective randomized double-blind placebo-controlled trial, 220 consecutive patients referred for elective coronary artery bypass graft surgery were randomized to 80 mg sotalol twice daily (n = 110) or matching placebo (n = 110) for 3 months with the first dose given 2 hours before surgery. There were no significant differences in baseline characteristics between the two groups. Low-dose sotalol reduced the rate of supraventricular arrhythmias from 43% (placebo) to 25% (sotalol, P <.01), which was atrial fibrillation in 83%, flutter in 7%, and other supraventricular arrhythmias in 10%. Only 7% of all arrhythmias were observed after day 9. Hospital stay was 11 +/- 4 days in patients with supraventricular arrhythmias versus 9 +/- 2 days (P <.001) in patients without. On the fourth postoperative day, heart rate was lower in the sotalol group (75 +/- 12 versus 86 +/- 14 beats per min; P <.0001), but QTc was not significantly prolonged (sotalol, 0.44 +/- 0.03; placebo, 0.43 +/- 0.03; P, ns). Study medication had to be discontinued due to side effects in 6.4% of sotalol and 3.6% of placebo patients (P, ns), but relevant side effects occurred only in two sotalol patients late after surgery. CONCLUSIONS: These data show that without antiarrhythmic therapy the incidence of supraventricular arrhythmias after coronary artery bypass graft surgery is high (43%) and that supraventricular arrhythmias were associated with a prolonged hospital stay (+/-2 days). Prophylactic treatment with low-dose sotalol reduced the incidence of supraventricular arrhythmias significantly (by 40%), thereby reducing overall hospital stay in treated patients. Because more than 90% of all supraventricular arrhythmic episodes occurred within 10 days after surgery and considering the small proarrhythmic effect of sotalol late after surgery, prophylactic treatment with sotalol may be recommended for the first 10 postoperative days to safely reduce supraventricular tachyarrhythmias.

Journal Article↗
PubMed1998

[Treatment of portal hypertension by portosystemic shunts].

The use of shunts for the treatment of portal hypertension has been revived after the introduction of the transjugular intrahepatic portosystemic shunt (TIPS) into clinical practice. This interventional procedure has mainly been used as rescue treatment for variceal bleeding resistant to endoscopic therapy and for ascites refractory to diuretic treatment and paracentesis. With respect to variceal bleeding TIPS has a low rate of "operative" mortality of < 1% and variceal rebleeding of 6 to 18%. In patients with refractory ascites the response to treatment is 50 to 92%. The major problems of the TIPS procedure are the increased incidence of hepatic encephalopathy and the high rate of shunt insufficiency of about 50%. Therefore, control of shunt function by duplex-sonography is essential to detect malfunction of the shunt. Radiological revision is then indicated if the clinical symptoms of portal hypertension (varices, ascites) reappear. The TIPS treatment has partially replaced the surgical shunting procedures. This decision is based on the potentially higher mortality of the surgical procedure. However, this has not been proven by randomized studies and, therefore, surgical shunts may also be indicated in selected patients with low operative mortality.

Humans↗
PubMed1998

Visualization of enteroviral replication in myocardial tissue by ultrastructural in situ hybridization: identification of target cells and cytopathic effects.

In humans as well as in various murine models, enteroviruses are capable of inducing a severe acute and chronic myocarditis, which is characterized by myocytotoxic alterations and interstitial mononuclear infiltrates. With regard to the pathogenesis of enteroviral myocarditis, coxsackievirus B3 (CVB3)-infected immunocompetent A.CA/SnJ (H-2f) mice were used as a model to trace viral plus- and minus-strand RNA during acute and chronic organ infection by ultrastructural in situ hybridization techniques. For electron microscopic detection of enteroviral RNA in myocardial tissue, a pre-embedding hybridization technique was developed and optimized for excellent conservation of structural integrity and RNA retention. Herein, we demonstrate how the virus gains access to the myocardium during viremia involving infection of the capillary endothelial cells. In myocytes, viral replication was found to be closely associated with the generation of vesicular regions and lysis of myofibrils, resulting in complete destruction of the internal architecture of the cell. In the course of acute infection, the direct cell-to-cell spread of the virus from one myocyte to the other was found to be related with filaments of the cytoskeleton. The observation of prominent cytopathic alterations in close spatial association with viral replication before the development of the reactive cellular immune response strongly implies that the loss of host cell integrity is a direct consequence of acute viral replication. In addition to myocytes, non-heart muscle cells were found to be infected during acute as well as chronic disease. Viral replication observed in myocardial fibroblasts and immune cells such as B lymphocytes proved to be associated with minor cytopathic effects. The technique of electron microscopic in situ hybridization established for the detection of viral RNA within myocardial tissue provides a powerful tool for the elucidation of molecular and structural interrelationships in organ pathology.

Animals↗
PubMed1997

Consequences of seven novel mutations on the expression and structure of keratinocyte transglutaminase.

We report the molecular characterization of seven new keratinocyte transglutaminase mutations (R315C, S358R, V379L, G473S, R687C, deletion Delta679-696, R127Stop) found in lamellar ichthyosis patients. Arg-315, Ser-358, Val-379, and Gly-473 are highly conserved residues in transglutaminases while Arg-687 and Delta679-696 are not. All mutations strongly decreased transglutaminase activity and protein levels. The mutation R127Stop diminished the amount of mRNA. Structural analysis of these mutations based on the factor XIII A-subunit crystal structure demonstrated that Arg-315, Ser-358, Val-379, and Gly-473 are located in the catalytic core domain, and Arg-687 and the deletion are in the beta-barrel domains. The side chains of amino acids Arg-315, Ser-358, and Gly-473 make ionic and hydrogen bonds important for folding and structural stability of the enzyme but are not directly involved in catalysis. Val-379 is two amino acids away from the active site cysteine, and its change into leucine disturbs the active site structure. The decreased activity and protein level after expression of the R687C and Delta679-696 TGK cDNA in TGK negative keratinocytes excluded that they are polymorphisms. These results identify important amino acids in the central core domain of transglutaminases and show that the C-terminal end influences the structural and functional integrity of TGK.

Arginine↗
PubMed1997

Hydrolysis of a broad spectrum of extracellular matrix proteins by human macrophage elastase.

Macrophage elastase (ME) was originally named when metal-dependent elastolytic activity was detected in conditioned media of murine macrophages. Subsequent cDNA cloning of the mouse and human enzyme demonstrated that ME is a distinct member of the matrix metalloproteinase family. To date, the catalytic parameters that describe the hydrolysis of elastin by ME have not been quantified and its activity against other matrix proteins have not been described. In this report, we have examined the action of purified recombinant human ME (rHME), produced in Escherichia coli, on elastin and other extracellular matrix proteins. On a molar basis, rHME is approximately 30% as active as human leukocyte elastase in solubilizing elastin. rHME also efficiently degrades alpha1-antitrypsin (alpha1-AT), the primary physiological inhibitor of human leukocyte elastase. In addition, rHME efficiently degrades fibronectin, laminin, entactin, type IV collagen, chondroitan sulfate, and heparan sulfate. These results suggest that HME may be required for macrophages to penetrate basement membranes and remodel injured tissue during inflammation. Moreover, abnormal expression of HME may contribute to destructive processes such as pulmonary emphysema and vascular aneurysm formation. To further understand the specificity of HME, the initial cleavage sites in alpha1-AT have been determined. In addition, the hydrolysis of a series of synthetic peptides with different P'1 residues has been determined. rHME can accept large and small amino acids at the P'1 site, but has a preference for leucine.

Amino Acid Sequence↗
PubMed1997

Prenatal diagnosis of lamellar ichthyosis by direct mutational analysis of the keratinocyte transglutaminase gene.

Autosomal recessive lamellar ichthyosis (LI) is a rare inherited disease of cornification of the skin. Recently, the gene responsible for type I LI has been identified and mutations have been described. The identification of mutations in families at risk for LI allows a precise and rapid prenatal diagnosis. A family with a previously unreported mutation is described and a prenatal diagnosis based on a simple polymerase chain reaction (PCR) approach is outlined. The molecular diagnosis was confirmed on post-mortem examination of the skin.

Chorionic Villi Sampling↗
PubMed1997

Prevention of supraventricular tachyarrhythmias after open heart operation by low-dose sotalol: a prospective, double-blind, randomized, placebo-controlled study.

BACKGROUND: The aim of this prospective, double-blind, placebo-controlled trial was to assess the preventive effect and safety of low-dose sotalol after heart operation. METHODS: Two hundred fifty-five consecutive patients referred for elective coronary artery bypass grafting (n = 220) or aortic valve operation (n = 35) were randomized to receive either 80 mg of sotalol twice daily (n = 126) or matching placebo (n = 129) for 3 months, with the first dose given 2 hours before operation. RESULTS: There were no significant baseline differences between the groups. Overall, supraventricular tachyarrhythmias occurred in 36% of patients (82% atrial fibrillation). Hospital stay was 11.6 +/- 5 days in patients with supraventricular arrhythmias, versus 9.5 +/- 2.4 days in patients without it (p < 0.0001). Low-dose sotalol reduced the rate of supraventricular arrhythmias from 46% (placebo) to 26% (sotalol; p = 0.0012), or by 43%. On the fourth postoperative day, heart rate was lower in the sotalol group (74 +/- 12 beats/min versus 85 +/- 15 beats/min; p < 0.0001) but the QT interval corrected for the heart rate was not prolonged (sotalol group, 0.44 +/- 0.03 second; placebo group, 0.43 +/- 0.03 second; p = not significant). Study medication had to be discontinued because of side effects in 5.6% of sotalol and 3.9% of placebo patients (p = not significant), with one possible proarrhythmic event occurring in a patient receiving sotalol. CONCLUSIONS: Because more than 90% of supraventricular arrhythmic episodes occurred within 9 days after operation and 70% of all possibly sotalol related side effects occurred after day 9, the findings in this study imply that prophylactic treatment with sotalol may be limited to the first 9 postoperative days.

Aged↗
PubMed1997

Chinese hamster ovary cells are non-permissive towards infection with coxsackievirus B3 despite functional virus-receptor interactions.

Viral infection is a complex process which includes binding and interaction of the virus with specific cell surface receptors, uptake and uncoating of the virus, and finally replication. Chinese hamster ovary (CHO) cells are non-permissive towards infection with coxsackieviruses of group B (CVB), although they do express a putative CVB-specific receptor protein. In order to localize the block of infection in CHO cells, these cells were tested for binding of radiolabelled CVB3, receptor-mediated transformation of virions into A-particles, and replication of the viral genome. Binding of CVB3 to CHO cells was found to be comparable to the binding of this virus to permissive cell lines. Detergent-solubilized membrane proteins of CHO cells were tested in virus overlay protein-binding assays (VOPBAs) and shown to express a 100 kDa CVB-binding membrane protein similar to the CVB receptor protein which we recently described for permissive HeLa cells. Incubation of CVB3 with intact CHO cells resulted in transformation of cell-bound virions into non-infectious A-particles (deprived of capsid protein VP4), demonstrating the functional activity of the CVB receptor protein on CHO hamster cells. Transfection of recombinant CVB3 cDNA or viral RNA into CHO cells resulted in the production of infectious CVB3 virions, implying that the failure of CVB to infect CHO cells is not caused by a defect in virus replication but results from a block in the uptake of virus particles into the cell after the initial steps of virus-receptor interactions.

Animals↗
PubMed1997

[Determination of cartilage thickness in the ankle joint. an MRT (1.5)-anatomical comparative study].

PURPOSE: The aim of this study was to evaluate the accuracy of MRI in the measurement of cartilage thickness of the ankle joint in comparison to pathologic and histologic specimens. PATIENTS AND METHODS: The ankle joints of four fresh cadaver feet were imaged on a 1.5T MR-unit in the coronal plane. Standard T1-weighted spin echo (SE) and a T1-weighted 3D-GE (FLASH-3D) sequence with fat saturation were applied. Following MR imaging, the talus was explanted and cut parallel to the MR images for macroscopic evaluation and histologic specimens were prepared. MRI measurements of the cartilage thickness of the talus were carried out in two ways: without and with consideration of a transition zone of intermediate signal intensity between hyperintense cartilage and hypointense cortical bone. The data were compared with the anatomic specimens as the gold standard expressing the difference as a percentage value. On histologic specimens thickness of deep calcified cartilage layer was measured. RESULTS: Measurements without the transition zone showed a mean underestimation of talus cartilage thickness of 46.8% (41.3-52.1) for T1-SE and 47.5% (43.1-52.1) for fat saturated FLASH-3D images. Considering the transition zone the mean values were 25.0% (23.1-26.2) and 14.1% (6.7-21.5). The histologic specimens showed a three-fold increase of thickness of deep calcified cartilage layer. CONCLUSIONS: Measurements of the cartilage layer of the ankle joint on MR images are only accurate if the transition zone (calcified cartilage layer) is considered and the optimal pulse sequence (FLASH-3D-fat-sat) is applied.

Aged↗
PubMed1997

Massive and persistent anterograde amnesia in the absence of detectable brain damage: anterograde psychogenic amnesia or gross reduction in sustained effort?

The case of a young patient with severe and persistent anterograde amnesia of no known cause is reported. Anterograde amnesia arose within a 1-month period and has persisted for more than 1 year. Although a wide variety of neurological and neuroradiological assessments were completed (EEG, evoked potential recordings, Doppler sonography, MRI, PET), no evidence of brain damage was detected. Neuropsychologically, the patient was of high intelligence, had average to above-average short-term memory, and normal retrograde memory abilities, but severe and persistent anterograde amnesia in both verbal and nonverbal domains. Furthermore, he demonstrated grossly reduced long-term concentration. It is likely that a complex chain of interacting variables can produce a syndrome that appears phenomenologically as anterograde amnesia without organically measurable correlates.

Adult↗
PubMed1997

Performance of elderly White and African American community residents on the abbreviated CERAD Boston Naming Test.

Differences in the responses of an elderly biracial group of cognitively normal subjects to a 15-item short version of the Boston Naming Test developed for the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) were examined. The subjects consisted of 103 Whites and 136 African Americans who were 70 years of age and older and living in a five-county urban and rural area of North Carolina. They were drawn from the Duke University site of the Established Populations for Epidemiologic Studies of the Elderly (EPESE). All were cognitively normal. With gender, years of education, and age controlled, White subjects performed significantly better than did African American subjects. The items in this test were selected to represent words with a high, medium, and low frequency of occurrence in English. They did not, however, show the expected gradation for either racial group. Medium and low frequency items were of comparable difficulty for the two races. Hierarchical ordering of difficulty would be improved with minor rearrangement of items.

Aged↗
PubMed1997

Mineral oil material in canned foods.

Mineral oil material was determined in canned foods by on-line LC-LC-GC-FID. In the edible oil phase of 90 samples of sea foods, concentrations were mostly around 100 mg/kg, but reached 820 mg/kg. The predominant source of this mineral oil material was lubricating oil used for can manufacturing. Mineral oil contamination of the fish was usually a minor source, but cannot be neglected.

Chromatography, Gel↗
PubMed1997

A novel dinucleotide mutation in keratin 10 in the annular epidermolytic ichthyosis variant of bullous congenital ichthyosiform erythroderma.

Annular epidermolytic ichthyosis has recently been delineated as a distinct clinical phenotype within the spectrum of epidermolytic keratinization disorders. The pattern of inheritance of the disorder is consistent with an autosomal dominant mode of transmission. Here we report a second incidence of this disorder in a family with two affected generations. The proband suffered from bullous ichthyosis and had bouts of disease activity associated with the development of numerous annular and polycyclic erythematous, hyperkeratotic plaques on the trunk and the proximal extremities. Histologic examination showed the typical pathology of epidermolytic hyperkeratosis, and ultrastructural analysis revealed abnormal keratin filament networks and tonofilament clumping with a perinuclear distribution. Molecular analysis revealed a novel tandem CG to GA 2-bp mutation in the same allele of keratin 10 in affected individuals, resulting in an arginine to glutamate substitution at residue 83 (R83E) of the 2B helical segment. We conclude that annular epidermolytic ichthyosis should be considered a variant of bullous congenital ichthyosiform erythroderma.

Adult↗
PubMed1997

Missense mutations in keratin 17 cause either pachyonychia congenita type 2 or a phenotype resembling steatocystoma multiplex.

Pachyonychia congenita (PC) is a group of autosomal dominant ectodermal dysplasias in which the main phenotypic characteristic is hypertrophic nail dystrophy. In the Jackson-Lawler form (PC-2), pachyonychia is accompanied by multiple pilosebaceous cysts, natal teeth, and hair abnormalities. By direct sequencing of genomic PCR products, we report heterozygous K17 missense mutations in the same conserved protein motif in a further five PC-2 families (K17 N92S in one familial and three sporadic cases; K17 Y98D in one familial case) confirming that mutations in this gene are a common cause of PC-2. We also show heterozygous missense mutations in K17 (N92H and R94H) in two families diagnosed as steatocystoma multiplex. Mild nail defects were observed in some but not all of these patients on clinical re-evaluation of these families. All the K17 mutations reported here were shown to co-segregate with the disease in the pedigrees analyzed and were excluded from 100 unaffected, unrelated chromosomes by restriction enzyme analysis of K17 genomic PCR products. We conclude that phenotypic variation is observed with K17 mutations, as is the case with other keratin disorders.

Cysts↗
PubMed1997

Tyrosine phosphorylation events during coxsackievirus B3 replication.

In order to study cellular and viral determinants of pathogenicity, interactions between coxsackievirus B3 (CVB3) replication and cellular protein tyrosine phosphorylation were investigated. During CVB3 infection of HeLa cells, distinct proteins become phosphorylated on tyrosine residues, as detected by the use of antiphosphotyrosine Western blotting. Two proteins of 48 and 200 kDa showed enhanced tyrosine phosphorylation 4 to 5 h postinfection (p.i.), although virus-induced inhibition of cellular protein synthesis had already occurred 3 to 4 h p.i. Subcellular fractionation experiments revealed distinct localization of tyrosine-phosphorylated proteins of 48 and 200 kDa in the cytosol and membrane fractions of infected cells, respectively. In addition, in Vero cells infected with CVB3, echovirus (EV)11, or EV12, increased tyrosine phosphorylation of a 200-kDa protein was detected 6 h p.i. Herbimycin A, a specific inhibitor of Src-like protein tyrosine kinases, was shown to inhibit virus-induced tyrosine phosphorylations and to reduce the production of progeny virions. In contrast, in cells treated with the inhibitors staurosporine and calphostin C, the synthesis of progeny virions was not affected. Immunoprecipitation experiments suggested that the tyrosine-phosphorylated 200-kDa protein in CVB3-infected cells is of cellular origin. In summary, these investigations have begun to unravel the effect of CVB3 as well as EV11 and EV12 replication on cellular tyrosine phosphorylation and support the importance of tyrosine phosphorylation events for effective virus replication. Such cellular phosphorylation events triggered in the course of enterovirus infection may enhance virus replication.

Animals↗