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Biomedical subjects

K Zimmermann

Publications and source records attributed to K Zimmermann.

At least 19 recordsLinked to original sources

Expression of chimeric neo-Rev response element sequences interferes with Rev-dependent HIV-1 Gag expression.

Recombinant plasmids containing reiterated human immunodeficiency virus type 1 (HIV-1) Rev response element (RRE) sequences were constructed to suppress Rev-dependent HIV-1 Gag expression. The mammalian expression vectors pMAMneo containing one, three, or six repeats of the RRE sequence were cotransfected with a HIV-1 HTLV-IIIB proviral DNA into HeLa cells. All three RRE expression plasmids reduced replication of HIV-1 with similar efficacy. Furthermore, the chimeric expression vector pCMV neoRRE6 x ----(containing six copies of the RRE sequence) was used to establish HeLa cell lines constitutively expressing RRE. A plasmid encoding a Rev-dependent HIV-1 p24 Gag protein was cotransfected with the wild-type Rev expression plasmid into three different RRE-expressing HeLa cell lines. p24 Gag protein production in the culture supernatants of the HeLaneoRRE cells was compared with two neo-expressing cell lines. Although all cell lines (HeLaneoRRE, HeLaneo) displayed similar transfection efficiencies, p24 Gag protein synthesis was markedly reduced in the RRE-expressing cell lines in comparison to the control cells.

Base Sequence

Technique for training schizophrenic patients in illness self-management: a controlled trial.

OBJECTIVE: To determine whether schizophrenic outpatients receiving low-dose neuroleptic therapy could learn and retain complex information and skills related to self-management of their illness, a novel technique of teaching, using cognitive and behavioral methods, was designed to compensate for the patients' learning disabilities. METHOD: The subjects were 41 patients with DSM-III-R schizophrenia who were receiving constant maintenance neuroleptic drug therapy. They were randomly assigned to structured, modularized skills training or to supportive group psychotherapy. RESULTS: The patients who received skills training made significant gains in each of the areas taught, while those participating in group therapy did not. The skills learned during training were retained without significant erosion over a 1-year follow-up period. CONCLUSIONS: The effectiveness of modularized teaching of illness self-management skills to schizophrenic patients appears to be largely independent of baseline psychology and symptom improvement. Such an approach is useful for overcoming or compensating for the enduring cognitive and information processing deficits commonly found in schizophrenia.

Activities of Daily Living

Formation of new muscle fibres and tumours after injection of cultured myogenic cells.

We examined the effects of implantation of cultured myogenic cells from a permanent cell line into soleus muscles of histocompatible adult mice. Myogenic cells (10(6) or 10(4)) were implanted into intact muscles, muscles frozen with liquid nitrogen, paralysed with botulinum toxin or reinnervated after long-term (seven months) denervation. Formation of numerous muscle fibres in myogenic cell-injected muscles raised the total number of fibres up to ten times above control by four weeks. Larger effects were found in freeze-damaged than in paralysed muscles. The new fibres had small calibers, considerable length (greater than 1.3 mm, maximum distance over which serial sections were made), were multinucleated and were oriented parallel to the large-diameter fibres of the host muscles. In some experiments beta-galactosidase, introduced into myogenic cells via retroviral transfection, was detected in small and large muscle fibres 4-20 weeks after implantation, indicating survival of the grafted cells and formation of mosaic (host-donor) and new fibres of donor origin. Muscle weight increased significantly and, rather surprisingly, a parallel increase was found in isometric tetanic tension of isolated nerve-muscle preparations; thus tension per mg muscle tissue was not different from normal. By eight weeks reduction of acetylcholine sensitivity and down-regulation of neural cell adhesion molecule to normal were observed, indicating that synaptic transmission at the new fibres was mature. After different periods of time (5-20 weeks, depending on the subclone used) tumours developed in most but not all injected limbs (37 out of 39). The tumours were destructive to the muscles and were classified as rhabdomyosarcomas. Prior to tumour formation, neural cell adhesion molecule positive cells reappeared in the muscles; since the myogenic cells initially produced differentiated muscle fibres, it appears that malignant growth is induced by factors in vivo. Thus, at present the outcome of such implantation is unpredictable.

Acetylcholinesterase

[The categorization of mandibular growth potential by Petrovic, Lavergne and Stutzmann].

The results of the study show whether the classification of mandibular growth potential, as proposed by Petrovic, Lavergne and Stutzmann has any influence on the treatment with a function regulator. X-rays of 140 class II patients were analysed after a treatment time of approximately 2 years. In comparison with 133 class II children without any treatment, a significant increase of mandibular length was observed in almost all children treated. There was no significant difference in the increase of mandibular length between category 2 (low growth potential) and category 5 (high growth potential).

Activator Appliances

trans-activation of the HIV-1 LTR by the HIV-1 Tat and HTLV-I Tax proteins is mediated by different cis-acting sequences.

Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by viral and cellular factors interacting with cis-elements located in the retroviral long terminal repeat (LTR). In this report we analyzed HIV-1 LTR-specific regulatory sequences responsive to the HIV-1 Tat and HTLV-I Tax trans-activator proteins. Our results indicate that the Sp1 binding sites in the HIV-1 LTR are crucially involved in Tat-mediated gene expression in human Jurkat T-cells whereas they are dispensable for HTLV-I Tax-induced activation. In contrast, the NF-kB binding sites within the HIV-1 LTR are essential for Tax-mediated transcription but had only marginal effect on Tat-induced reporter gene expression.

Animals

Transdominant repressors for human T-cell leukemia virus type I rex and human immunodeficiency virus type 1 rev function.

Human T-cell leukemia virus type I (HTLV-I) encodes a 27-kDa trans-acting gene product (Rex) which is involved in the regulated expression of transcripts coding for the viral structural proteins. We used oligonucleotide-directed mutagenesis to generate a series of mutant HTLV-I rex genes. Transient expression experiments demonstrated that 3 of 28 mutant proteins are functionally inactive on the homologous HTLV-I rex response element, whereas an additional 2 mutant proteins are functionally inactive on the heterologous human immunodeficiency virus type 1 rev response element. One of these mutants is able to suppress the function of the wild-type HTLV-I Rex protein in trans on the homologous rex response element sequence. Furthermore, all of these mutants are able to inhibit Rex function on the heterologous rev response element sequence. Intriguingly, only three of these mutants are able to inhibit the human immunodeficiency virus type 1 Rev protein in a dominant-negative manner.

Amino Acid Sequence

Heterogenic mRNAs with an identical protein-coding region of the human embryonic myosin alkali light chain in skeletal muscle cells.

The formation of human myotubes in culture is accompanied by the induction of developmentally regulated, muscle-specific genes. We have studied the expression of human myosin light chain proteins and mRNAs during myogenesis in culture, in particular the skeletal embryonic myosin light chain 1 (MC1emb), which is indistinguishable from MLC1 of adult atrial cardiac muscle (MLC1A) as has been shown for rodent and bovine MLC1emb. We have identified distinct MLC1emb/MLC1A mRNAs in cultured human skeletal muscle cells that differ in their 5' and 3' untranslated regions but contain identical protein-coding regions. The alternative 3' untranslated region is detectable also in RNA of human atria. The different MLC1emb RNAs are likely to be encoded by one gene. It appears that the two MLC1emb 5' untranslated regions of the human gene are specific for man. In the mouse, only one 5' untranslated region of the MLC1emb gene has been detected.

Amino Acid Sequence

[Origin of islets of Langerhans by mitotic division of duct epithelium in the human early fetal period].

The investigations are carried out in 29 human fetal pancreases between the 10th and 19th week of age. Mitosis restricted to the duct epithelium in the 10th to 13th week. In the 14th week start the mitotic activity in the islet parenchyma. The mitotic activity decreased from the 10th to the 13th week, increased to the 15th week and decreased once more to the 19th week.

Cell Division

Nephrogenic adenoma of the bladder: urographic spectrum.

Nephrogenic adenoma is a rare, proliferative response of urothelium to urinary infection or injury of the bladder mucosa. Histologically, the lesion resembles proximal tubules of the nephron. While it can occur throughout the urinary tract, it usually appears in the bladder, with diverse radiographic manifestations. Of 6 patients with nephrogenic adenoma of the bladder, 3 presented with masses in the bladder and 2 with irregularities of the bladder mucosa on urography, while 1 showed no focal urographic abnormalities. There were no distinctive radiographic features of nephrogenic adenoma that would allow it to be differentiated from tumor or other inflammatory lesions. Although it is considered benign, bladder involvement may be extensive and eradication of the tumor may be difficult.

Adenoma

Lymphocyte antigen Leu-19 as a molecular marker of regeneration in human skeletal muscle.

Antigen Leu-19 (Leu19-Ag), a 200- to 220-kDa surface glycoprotein, was originally identified on a subset of human peripheral lymphocytes exhibiting non-major histocompatibility complex-restricted cytotoxicity. Here we report that monoclonal antibody Leu-19 (mAb-Leu19) labels structures in human skeletal muscle: (i) satellite cells, which form the stem cell pool of muscle fiber regeneration, both in normal and diseased muscle; (ii) myotubes and myotube projections in regions of muscle fiber repair; (iii) periodically organized fibrillar structures in areas of regeneration; (iv) the surface of myoblasts and developing myotubes in culture. mAb-Leu19 precipitated a protein of approximately 200 kDa from cultured muscle cells. Our data show that Leu19-Ag is expressed on muscle-specific components of myosegments in repair and thus represents a molecular marker of muscle regeneration. On the basis of this molecular marker and using laser scan microscopy, it is possible to visualize at the light microscopic level hitherto undetectable details of muscle regeneration in routine cryostat sections.

Antigens, Differentiation, T-Lymphocyte

Regulated expression of nuclear protein(s) in myogenic cells that binds to a conserved 3' untranslated region in pro alpha 1 (I) collagen cDNA.

We describe the identification and DNA-binding properties of nuclear proteins from rat L6 myoblasts which recognize an interspecies conserved 3' untranslated segment of pro alpha 1 (I) collagen cDNA. Levels of the two pro alpha 1 (I) collagen RNAs, present in L6 myoblasts, decreased drastically between 54 and 75 h after induction of myotube formation in serum-free medium. Both mRNAs contained a conserved sequence segment of 135 nucleotides (termed tame sequence) in the 3' untranslated region that had 96% homology to the human and murine pro alpha 1 (I) collagen genes. The cDNA of this tame sequence was specifically recognized by nuclear protein(s) from L6 myoblasts, as judged by gel retardation assays and DNase I footprints. The tame-binding protein(s) was able to recognize its target sequence on double-stranded DNA but bound also to the appropriate single-stranded oligonucleotide. Protein that bound to the tame sequence was undetectable in nuclear extracts of L6 myotubes that did not accumulate the two collagen mRNAs. Therefore, the activity of this nuclear protein seems to be linked to accumulation of the sequences that it recognizes in vitro. The collagen RNAs and the nuclear tame-binding proteins reappeared after a change of medium, which further suggests that the RNAs and the protein(s) are coordinately regulated.

Amino Acid Sequence

Localization of the putative precursor of Alzheimer's disease-specific amyloid at nuclear envelopes of adult human muscle.

Cloning and sequence analysis revealed the putative amyloid A4 precursor (pre-A4) of Alzheimer's disease to have characteristics of a membrane-spanning glycoprotein. In addition to brain, pre-A4 mRNA was found in adult human muscle and other tissues. We demonstrate by in situ hybridization that pre-A4 mRNA is present in adult human muscle, in cultured human myoblasts and myotubes. Immunofluorescence with antipeptide antibodies shows the putative pre-A4 protein to be expressed in adult human muscle and associated with some but not all nuclear envelopes. Despite high levels of a single 3.5-kb pre-A4 mRNA species in cultured myoblasts and myotubes, the presence of putative pre-A4 protein could not be detected by immunofluorescence. This suggests that putative pre-A4 protein is stabilized and therefore functioning in the innervated muscle tissue but not in developing, i.e. non-innervated cultured muscle cells. The selective localization of the protein on distinct nuclear envelopes could reflect an interaction with motor endplates.

Adult

[Kidney function and behavior of blood pressure in short-term diabetic patients. A follow-up study 1982-1986].

In 1982 there were increased creatinine values in 24.9 per cent (n = 344) of 1,380 investigated short-term diabetics of a closed territory. The course of disease of these 344 cases was followed in a follow-up-study. None of the patients had come to dialysis treatment. 32.3 per cent had died until 1986. In no case uremia caused the death. Hypertonias had a significant higher creatinine level than normotoniacs. The creatinine rise was on a higher level with the hypertoniacs. In 1982 the frequency of hypertension in the group of the died patients was with 65.8 per cent significant higher than in the group of the 1986 still living patients (32.9 per cent).

Adult