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Biomedical subjects

K Weber

Publications and source records attributed to K Weber.

At least 217 records · Page 12Linked to original sources
PubMed1995

Duplications of mitochondrial DNA in Kearns-Sayre syndrome.

mtDNA duplications were detectable in 10 of 10 patients with mtDNA deletions and Kearns-Sayre syndrome (KSS) and in none of 8 patients with chronic progressive external ophthalmoplegia (CPEO). Thus, duplications of mtDNA seem to be a distinctive feature of KSS, including patients where Pearson's syndrome is the first manifestation. Diabetes mellitus was identified in 4 of 7 patients with high or moderate levels of mtDNA duplications. The balance of mtDNA rearrangements may be central to the pathogenesis of this unique group of disorders.

Adult↗
PubMed1995

Molecular changes of titin in left ventricular dysfunction as a result of chronic hibernation.

Cardiomyocytes of chronic hibernating myocardium are affected by partial to complete loss of sarcomeres, accumulation of glycogen, adaptations in size and shape of mitochondria, reorganisation of nuclear chromatin and depletion of sarcoplasmic reticulum. The nature of these changes, which from a purely morphologic viewpoint are akin to dedifferentiation, needed further clarification at the molecular level. For this purpose we have studied the expression and reorganization of titin, one of the earliest markers of cardiomyocytes differentiation. By use of monoclonal antibodies, recognizing different epitopes distributed over the whole length of the titin molecule, we were able to detect changes in its molecular organization as a result of chronic hibernation. The epitopes of the titin molecule attached to the Z-disc and those present close to the M-line remained detectable at all stages of hibernation, while epitopes at the A-I junction and parts of the myosin anchoring region of the molecule became masked or were lost. A fragmented or punctuated appearance of the titin staining pattern with antibodies to A-I junction related epitopes is found in cells which we consider to represent a more advanced stage of dedifferentiation. Changes in the distribution of the titin molecule or its molecular environment in hibernating myocardium resemble at least in part changes occurring during muscle cell differentiation, although in reversed order.

Animals↗
PubMed1995

The iron-binding protein ferritin is expressed in cells of the osteoblastic lineage in vitro and in vivo.

Ferritin, a metal-binding protein responsible for maintaining the bioavailability of iron, has been demonstrated in cells of the osteoblastic lineage. Messenger RNAs encoding the light and heavy chain subunits of ferritin were detected in ROS 17/2.8, ROS 25/1, and UMR106 rat osteosarcoma cell lines, in fetal rat calvaria, and in primary cultures of rat calvarial osteoblast-like cells. In vivo, the expression of ferritin light-chain mRNA was observed in both active osteoblasts and in osteocytes. A 450-kD iron-binding protein was immunoprecipitated from ROS 17/2.8 cells by an antiferritin antiserum. This protein comigrated with native ferritin, and could be dissociated into subunits comigrating with ferritin light and heavy chains. Addition of extracellular Fe59-transferrin to cultures of ROS 17/2.8 cells resulted in the sequestration of the iron in intracellular ferritin. These observations demonstrate that cells of the osteoblastic lineage possess a functional ferritin-based iron uptake and storage system capable of regulating metal homeostasis in bone.

Animals↗
PubMed1995

Testing a tripartite model: II. Exploring the symptom structure of anxiety and depression in student, adult, and patient samples.

L. A. Clark and D. Watson (1991) proposed a tripartite model of depression and anxiety that divides symptoms into 3 groups: symptoms of general distress that are largely nonspecific, manifestations of anhedonia and low positive affect that are specific to depression, and symptoms of somatic arousal that are relatively unique to anxiety. This model was tested by conducting separate factor analyses of the 90 items in the Mood and Anxiety Symptom Questionnaire (D. Watson & L. A. Clark, 1991) in 5 samples (3 student, 1 adult, 1 patient). The same 3 factors (General Distress, Anhedonia vs. Positive Affect, Somatic Anxiety) emerged in each data set, suggesting that the symptom structure in this domain is highly convergent across diverse samples. Moreover, these factors broadly corresponded to the symptom groups proposed by the tripartite model. Inspection of the individual item loadings suggested some refinements to the model.

Adult↗
PubMed1995

Testing a tripartite model: I. Evaluating the convergent and discriminant validity of anxiety and depression symptom scales.

L.A. Clark and D. Watson (1991) proposed a tripartite model that groups symptoms of depression and anxiety into 3 subtypes: symptoms of general distress that are largely nonspecific, manifestations of somatic tension and arousal that are relatively unique to anxiety, and symptoms of anhedonia and low Positive Affect that are specific to depression. This model was tested in 5 samples (3 student, 1 adult, and 1 patient sample) using the Mood and Anxiety Symptom Questionnaire (MASQ; D. Watson & L. A. Clark, 1991), which was designed to assess the hypothesized symptom groups, together with other symptom and cognition measures. Consistent with the tripartite model, the MASQ Anxious Arousal and Anhedonic Depression scales both differentiated anxiety and depression well and also showed excellent convergent validity. Thus, differentiation of these constructs can be improved by focusing on symptoms that are relatively unique to each.

Adult↗
PubMed1995

Major epiplasmic proteins of ciliates are articulins: cloning, recombinant expression, and structural characterization.

The cytoskeleton of certain protists comprises an extensive membrane skeleton, the epiplasm, which contributes to the cell shape and patterning of the species-specific cortical architecture. The isolated epiplasm of the ciliated protist Pseudomicrothorax dubius consists of two major groups of proteins with molecular masses of 78-80 kD and 11-13 kD, respectively. To characterize the structure of these proteins, peptide sequences of two major polypeptides (78-80 kD) as well as a cDNA representing the entire coding sequence of a minor and hitherto unidentified component (60 kD; p60) of the epiplasm have been determined. All three polypeptides share sequence similarities. They contain repeated valine- and proline-rich motifs of 12 residues with the consensus VPVP--V-V-V-. In p60 the central core domain consists of 24 tandemly repeated VPV motifs. Within the repeat motifs positively and negatively charged residues, when present, show an alternating pattern in register with the V and P positions. Recombinant p60 was purified in 8 M urea and dialyzed against buffer. Infrared spectroscopic measurements indicate 30% beta-sheet. Electron microscopy reveals short filamentous polymers with a rather homogenous diameter (approximately 15-20 nm), but variable lengths. The small polymers form thicker filaments, ribbons, and larger sheets or tubes. A core domain similar to that of P. dubius p60 is also found in the recently described epiplasmic proteins of the flagellate Euglena, the so-called articulins. Our results show that the members of this protein family are not restricted to flagellates, but are also present in the distantly related ciliates where they are major constituents of the epiplasm. Comparison of flagellate and ciliate articulins highlights common features of this novel family of cytoskeletal proteins.

Amino Acid Sequence↗
PubMed1995

Amino acid metabolism in tennis and its possible influence on the neuroendocrine system.

To investigate amino acid metabolism during endurance exercise as well as its influence on plasma prolactin (PRL) we subjected eight nationally ranked tennis players (mean(s.d.) age 25.6(2.8) years, mean(s.d.) weight 83.9(5.7) kg, mean(s.d.) height 184.4(4.6) cm) to 4h of continuous tournament tennis. Venous and capillary blood samples were taken before and after the exercise. Amino acids were measured by HPLC-fluorescence detection as o-phthalaldehyde derivatives; nonesterified fatty acids (NEFA), ammonia, total protein, glucose insulin and PRL by enzymatic methods. Exercise caused a decline of branched-chain amino acids (BCAA) by 28(14)%. Elevation of NEFA resulted in a significant mean(s.d.) increase of free tryptophan (TRP) (9.7(2.6) [pmol/microliter] vs 17.8(6.4) [pmol/microliter]. The mean(s.d.) ratio of free TRP:BCAA increased by 165%(90) which favours entry of free TRP into the brain. However, PRL did not change significantly. We conclude that during long-lasting interval sports BCAA contribute as energy substrates. Alterations in competition of amino acids at the blood-brain barrier favour entry of free TRP into the brain. PRL changes cannot be explained by the increase in plasma level of free TRP or the ratio of free TRP:BCAA.

Adult↗
PubMed1995

Expression of Drosophila lamin C is developmentally regulated: analogies with vertebrate A-type lamins.

Vertebrate nuclear lamins form a multigene family with developmentally controlled expression. In contrast, invertebrates have long been thought to contain only a single lamin, which in Drosophila is the well-characterized lamin Dm0. Recently, however, a Drosophila cDNA clone (pG-IF) has been identified that codes for an intermediate filament protein which harbors a nuclear localization signal but lacks a carboxy-terminal CAAX motif. Based on these data the putative protein encoded by pG-IF was tentatively called Drosophila lamin C. To address whether the pG-IF encoded protein is expressed and whether it encodes a cytoplasmic intermediate filament protein or a nuclear lamin we raised antibodies against the recombinant pG-IF protein. The antibodies decorate the nuclear envelope in Drosophila Kc tissue culture cells as well as in salivary and accessory glands demonstrating that pG-IF encodes a nuclear lamin (lamin C). Antibody decoration, in situ hybridization, western and northern blotting studies show that lamin C is acquired late in embryogenesis. In contrast, lamin Dm0 is constitutively expressed. Lamin C is first detected in late stage 12 embryos in oenocytes, hindgut and posterior spiracles and subsequently also in other differentiated tissues. In third instar larvae lamins C and Dm0 are coexpressed in all tissues tested. Thus, Drosophila has two lamins: lamin Dm0, containing a CaaX motif, is expressed throughout, while lamin C, lacking a CaaX motif, is expressed only later in development. Expression of Drosophila lamin C is similar to that of vertebrate lamin A (plus C), which loses its CaaX motif during incorporation into the lamina.

Animals↗
PubMed1995

Characterisation of neurofilament protein NF70 mRNA from the gastropod Helix aspersa reveals that neuronal and non-neuronal intermediate filament proteins of cerebral ganglia arise from separate lamin-related genes.

The neuronal cytoplasmic intermediate filament (IF) protein HeNF70 of the gastropod Helix aspersa is identified by sequence analysis of the corresponding 4,600 bp cDNA isolated from a cerebral ganglion cDNA library. HeNF70 shares 60% sequence identity with the neuronal LoNF70 protein of the cephalopod Loligo pealei and only 36% identity with the Helix non-neuronal IF-A protein. All three molluscan IF proteins display the lamin-type extended coil 1b subdomain harbouring six additional heptads and all have long C-terminal sequences with substantial homology to the tail domains of nuclear lamins. The lamin-like tail domains of the two neurofilament proteins share a unique motif comprising 13 residues, which is absent from Helix IF-A and all other known non-neuronal IF proteins. HeNF70 is encoded by a 9.5 kb RNA transcript. The very long 7.2 kb 3'-untranslated sequence contains a unique 26 nucleotide repeat extending over 0.5 kb in its 5'-region. The HeNF70 mRNA is expressed at low abundancy in cerebral ganglia but not in any of the 13 non-neuronal tissues tested. In contrast, all tissues express at fairly high levels the same 4.6 and 4.2 kb mRNAs encoding the Helix non-neuronal IF-A/B proteins. Blot hybridisation studies on genomic DNA and ganglion mRNA with subprobes from the cloned HeNF70 cDNA, as well as sequence analysis of an RT-PCR generated partial cDNA encoding a putative HeNF60 protein, indicate at least two different neuronal IF genes in Helix.

Animals↗
PubMed1995

[Increased prevalence of serum IgA Chlamydia antibodies in obesity].

Obesity is metabolically related to diabetes type II. We have previously shown that seroactive (IgG- and IgA-Chlamydia antibody positive) chlamydial infection of asymptomatic patients is more frequent in type II diabetic patients than in nondiabetics, independent from metabolic control. Thus we investigated 119 nondiabetic patients (66 +/- 9 years, HbA1c < 6%) of our department for seroactive chlamydia infection using an immunoperoxidase reaction and compared the results to the anthropometric data. The prevalence of seroactive chlamydial infection was significantly (p < 0.05) higher in the considerably overweight patients with a BMI > 30 kg/m2, both when compared to lean patients (BMI < 24 kg/m2) and when compared to all those with BMI < 30 kg/m2. For slight to moderate obesity the prevalences were slightly (but not significantly) increased. Due to the fact that similar data were obtained for type II diabetic patients, an unknown relation to insulin resistance might be the underlying cause and should be further investigated.

Aged↗
PubMed1995

Characterization of a voltage-activated K-channel gene cluster on human chromosome 12p13.

The Shaker related alpha-subunit subfamily of human voltage-activated KCNA-channels is encoded by several genes in the human genome. We have isolated yeast artificial chromosomes (YACs) spanning approximately 1 Mb of human chromosome 12p13 DNA. Molecular biological characterization of the YAC-insert DNAs revealed that three KCNA genes--KCNA1, KCNA5, KCNA6--are clustered within approximately 300 kb of insert-DNA derived from chromosome 12p13. The KCNA gene cluster has been conserved between mouse and human. The three KCNA genes in the cluster are transcribed from the same DNA strand being arranged in a head-to-tail fashion in the order KCNA6-KCNA1-KCNA5. Northern blot analyses of the KCNA1, KCNA5 and KCNA6 mRNAs in different human brain areas show that the genes are distinctly expressed. Therefore, they may be transcribed independently of each other.

Base Sequence↗
PubMed1994

The expression of different annexins in the fish embryo is developmentally regulated.

The expression of annexins, a family of Ca2+/phospholipid-binding proteins, was analyzed by biochemical and immunological criteria in the fish Misgurnus fossilis (loach), which is a good model system to study embryonic events. Five different annexins (loach annexins A to E) are present as a maternal pool in the unfertilized eggs. Only annexin E is newly synthesized in the early embryo. Its synthesis, already apparent at mid-blastula, decreases in later stages when two additional annexins (F and G) appear. They are present among the newly synthesized polypeptides of mid-gastrula and later embryonic stages and are also found in loach larvae. The developmentally controlled expression of several annexins indicates a specific role of these proteins at certain embryonic stages.

Animals↗
PubMed1994

Eight genes and alternative RNA processing pathways generate an unexpectedly large diversity of cytoplasmic intermediate filament proteins in the nematode Caenorhabditis elegans.

Cytoplasmic intermediate filament (IF) proteins of Caenorhabditis elegans are encoded by a dispersed multigene family comprising at least eight genes which map to three linkage groups. Exon sequences and intron patterns define three distinct subfamilies. While all eight IF genes display the long coil 1b subdomain of nuclear lamins, only six genes (a1-a4, b1 and b2) retain a lamin-like tail domain. Two genes (c1 and c2) have acquired entirely novel tail domains. The overall sequence identity of the rod domains is only 29%. The gene structures show a strong drift in number and positions of introns, none of which are common to all genes. Individual genes share only one to four intron locations with the Helix aspersa IF gene, but all eight nematode genes together account for nine of the 10 introns of the gastropod gene. All C.elegans IF genes are transcribed and all except gene c2 produce trans-spliced mRNAs. Alternatively spliced mRNAs arise from genes a1, b2 and c2 through several mechanisms acting at the transcriptional and posttranscriptional levels. These involve the alternative use of distinct promoters, polyadenylation sequences and both cis and trans RNA splice sites. The resulting sequence variations are restricted to the non-helical end domains. Minimally 12 distinct IF proteins are encoded by the various mRNAs. Different abundances in mixed-stage nematode populations suggest cell type- and/or stage-specific expression of individual mRNAs.

Alternative Splicing↗
PubMed1994

Purification of Golgi adaptor protein 1 from bovine adrenal gland and characterization of its beta 1 (beta') subunit by microsequencing.

A method for the purification of the Golgi adaptor protein 1 from bovine adrenal gland tissue was devised to investigate the relationship of its beta 1 (formerly referred to as beta') subunit to known beta-type sequences. Adrenal gland tissue was chosen for this study because it yielded 2-3 times more adaptor protein 1 than a comparable preparation from bovine brain. Like its neuronal isoform, the beta 1 subunit from adrenal gland adaptor protein 1 is readily cleaved by trypsin into a 63-kDa N-terminal fragment and a 40-kDa C-terminal fragment, while the gamma subunit is largely refractory to digestion. Based on microsequencing of 167 residues from the 63-kDa fragment, we noted 11 differences to the corresponding region of the beta 2 (formerly beta) subunit of the plasma membrane adaptor protein 2, but only one difference to the corresponding region of a beta-type protein encoded by the rat cDNA clone AP105a which is supposed to be a variant of the beta 2 subunit of the plasma membrane adaptor protein 2 [Kirchhausen, T., Nathanson, K. L., Matsui, W., Vaisberg, A., Chow, E. P., Burne, C., Keen, J. H. & Davis, A. E. (1989) Proc. Natl Acad. Sci. USA 84, 8805-8809]. Alignment of 187 residues from the 40-kDa beta 1 C-terminal fragment revealed differences in 77 positions to the corresponding region of the beta 2 subunit and differences in 23 positions compared to the supposed beta 2-like protein. These findings suggest that the protein encoded by the rat cDNA clone AP105a is more closely related to the beta 1 subunit of the bovine adrenal Golgi adaptor protein 1 than to the beta 2 subunit of the rat plasma membrane adaptor protein 2.

Adaptor Protein Complex 1↗