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Biomedical subjects

C Meier

Publications and source records attributed to C Meier.

At least 109 records · Page 6Linked to original sources
PubMed1990

Autonomous growth of lymphoid cells following IL-2 expression from retrovirus vectors containing HIV-1 trans-acting elements.

The human immunodeficiency virus type I (HIV-1) possesses powerful regulatory elements that control the rate of replication of HIV-1 and subsequent processing of HIV-1 genes. We have used this regulatory mechanism to drive expression of foreign genes inserted in retrovirus vectors. This approach was used to express the human IL-2 gene in IL-2-dependent mouse CTLL-2 cells to determine the role of autonomous growth in maintaining proliferation of virus-infected T lymphocytes during HTLV-1-induced adult T-cell leukemia (ATL). Expression of IL-2 sequences in IL-2-dependent mouse CTLL-2 cells resulted in autonomous growth of IL-2-independent CTLL-2 clones. Endogenous expression of IL-2 appeared to interrupt normal constraints of growth in that these IL-2-independent clones showed reduced cell-density-dependent inhibition but not a tumorigenic phenotype. IL-2-independent CTLL-2 clones did not secrete detectable quantities of IL-2 into culture supernatant and exhibited reduced sensitivity to the inhibitory effects of both IL-2 and IL-2 receptor antibody. These results suggest that the IL-2 autocrine loop within these cells involves intracellular IL-2/IL-2 receptor binding. The apparent lack of IL-2 production and poor responsiveness to IL-2 or IL-2 antibodies displayed by cell lines from ATL patients may be explained by an intracellular IL-2/IL-2 receptor autocrine loop.

Animals↗
PubMed1990

Severe neonatal asphyxia due to X-linked centronuclear myopathy.

Severe neonatal centronuclear myopathy is inherited as an X-linked condition characterized by primary asphyxia, extreme muscular hypotonia and absent spontaneous movements. We report seven cases from three families to point out the importance of diagnosis with regard to prognosis, outcome and genetic counselling. In hypotonic diseases, analysis of cerebrospinal fluid, electromyography, nerve conduction velocity creatine kinase and a skin biopsy for fibroblast cultures for metabolic investigations are usually carried out. Needle muscle biopsy is an additional valuable investigation to establish diagnosis. In all our patients we found an increased number of centrally located nuclei with perinuclear halos confirming the diagnosis of centronuclear myopathy. The diagnosis of this disorder will become of greater importance as soon as carrier detection and prenatal diagnosis by DNA-technology are routinely available.

Asphyxia Neonatorum↗
PubMed1990

[Myopathy in the adult form of glycogenosis II. Two case reports and review of the literature].

Clinical, neurophysiological, morphological and biochemical investigations were performed in 2 patients with the adult form of glycogenosis II and related to the findings of 58 well-documented cases published in the literature. According to these findings three types can be distinguished from each other. The first one is characterized by an involvement of the limb-girdle muscles only. The second type shows the same pattern with additional progressive insufficiency of the respiratory muscles. The third type presents with weakness of the respiratory muscles without any other severe muscle involvement. Our case 1 can be related to the first, our case 2 to the second type. EMG-studies in case 1 showed myopathic changes and myotonic discharges without clinical signs of myotonia. A myotonic pattern was described in one third of the published cases. In case 2 neurogenic changes as well as in 4 cases in the literature were found. The muscle biopsy is the diagnostic clue in the differential diagnosis of progressive myopathy in the adult. Patients with glycogenosis II show glycogen storage specially in type I-fibres. The enzyme defect can be confirmed biochemically in muscle tissue or cultured fibroblasts. Various therapeutic concepts have been tried in patients with glycogenosis II but most of them remain disappointing. A diet with a low carbohydrate and a high protein proportion was observed to be of some benefit. In patients with respiratory muscle involvement artificial ventilation support showed a positive effect on the general condition for some time.

Adult↗
PubMed1990

Cloning and characterization of human immunodeficiency virus type 1 variants diminished in the ability to induce syncytium-independent cytolysis.

The phenomenon of interference was exploited to isolate low-abundance noncytopathic human immunodeficiency virus type 1 (HIV-1) variants from a primary HIV-1 isolate from an asymptomatic HIV-1-seropositive hemophiliac. Successive rounds of virus infection of a cytolysis-susceptible CD4+ cell line and isolation of surviving cells resulted in selective amplification of an HIV-1 variant reduced in the ability to induce cytolysis. The presence of a PvuII polymorphism facilitated subsequent amplification and cloning of cytopathic and noncytopathic HIV-1 variants from the primary isolate. Cloned virus stocks from cytopathic and noncytopathic variants exhibited similar replication kinetics, infectivity, and syncytium induction in susceptible host cells. The noncytopathic HIV-1 variant was unable, however, to induce single-cell killing in susceptible host cells. Construction of viral hybrids in which regions of cytopathic and noncytopathic variants were exchanged indicated that determinants for the noncytopathic phenotype map to the envelope glycoprotein. Sequence analysis of the envelope coding regions indicated the absence of two highly conserved N-linked glycosylation sites in the noncytopathic HIV-1 variant, which accompanied differences in processing of precursor gp160 envelope glycoprotein. These results demonstrate that determinants for syncytium-independent single-cell killing are located within the envelope glycoprotein and suggest that single-cell killing is profoundly influenced by alterations in envelope sequence which affect posttranslational processing of HIV-1 envelope glycoprotein within the infected cell.

Amino Acid Sequence↗
PubMed1990

X linked neonatal centronuclear/myotubular myopathy: evidence for linkage to Xq28 DNA marker loci.

We have studied the inheritance of several polymorphic Xq27/28 DNA marker loci in two three generation families with the X linked neonatal lethal form of centronuclear/myotubular myopathy (XL MTM). We found complete linkage of XLMTM to all four informative Xq28 markers analysed, with GCP/RCP (Z = 3.876, theta = 0.00), with DXS15 (Z = 3.737, theta = 0.00), with DXS52 (Z = 2.709, theta = 0.00), and with F8C (Z = 1.020, theta = 0.00). In the absence of any observable recombination, we are unable to sublocalise the XLMTM locus further within the Xq28 region. This evidence for an Xq28 localisation may allow us to carry out useful genetic counselling within such families.

Cell Nucleus↗
PubMed1989

[Neurotoxicity with cytostatic therapy: a review].

Neurotoxicity is of increasing importance in the treatment of cancer patients. Since the dose-limiting hematological toxicity of most cytostatic drugs can now be overcome by modern supportive therapy, high-dose chemotherapy with curative intent can be used more often. Non-hematological toxicities such as neurotoxicity will therefore become dose-limiting with greater frequency, and to avoid disabling neurological side effects of chemotherapy the drug-induced neurological disturbances must be recognized before irreversible damage has occurred. The neurological side effects of the cytostatic drugs are reviewed.

Antineoplastic Agents↗
PubMed1989

Peripheral nerve disorders in Lyme-Borreliosis. Nerve biopsy studies from eight cases.

Clinical, cerebrospinal fluid and nerve biopsy findings from eight patients with peripheral nervous system complications of Lyme-Borreliosis are reported. Five cases showed the typical features of the Garin-Bujadoux-Bannwarth syndrome (meningoradiculoneuritis), one patient had a multiple mononeuritis associated with acrodermatitis chronica atrophicans Herxheimer. Two cases could not be classified under these diagnostic categories. In all patients we observed a prompt relief of signs and symptoms after antibiotic treatment. Nerve biopsy studies showed gross infiltrations of epineurial vasa nervorum and small infiltrations around endoneurial capillaries. The infiltrations consisted of lymphocytes, histiocytes and plasma cells. We did not find necrotizing changes of the vessel walls, but thrombosis and recanalization was observed in some epineurial vessels. Seven biopsies showed a significant loss of myelinated axons due to axonal degeneration. Only in one biopsy did we observe segmental demyelination next to axonal degeneration. We conclude that the PNS complications of Lyme-Borreliosis in early and late stages of the disease are angiopathic due to vasculitis of the vasa nervorum and primarily caused by axonal degeneration.

Acrodermatitis↗
PubMed1989

Human oligodendrocytes in dissociated cell culture.

Human oligodendrocytes have been successfully maintained in cell cultures for 14 weeks using a modification of a method used previously for animal brain cell cultures. Dissociated cell cultures from spinal cords of human foetuses of 10 to 20 weeks gestional age were investigated for up to 98 days. Oligodendrocytes were identified by monoclonal human antiserum specific for myelin-associated glycoprotein, by polyclonal rabbit antiserum against myelin basic protein, and by the mouse monoclonal antibody I6G1. Astrocytes were identified by polyclonal antibodies against glial fibrillary acidic protein. Immunocytochemical cell identification was corroborated by electron microscopy, by which glial cells were investigated both in situ and in culture. Immunocytochemical staining of myelin-associated glycoprotein showed specifically labelled oligodendrocytes on electron microscopy. The present study indicates that human oligodendrocytes, a putative target in demyelinating disease, can be studied in dissociated cell culture of human foetal spinal cord for several weeks in vitro under stable conditions.

Astrocytes↗
PubMed1989

Meningoradiculoneuritis mimicking vertebral disc herniation. A "neurosurgical" complication of Lyme-borreliosis.

We report on 3 patients with meningoradiculoneuritis (MRN) due to Lyme-borreliosis (LB), which presented clinically as vertebral disc herniation. In 2 cases the underlying infection was discovered only after unsuccessful neurosurgical treatment. In the differential diagnosis between MRN and disc herniation the following criteria are suggestive of MRN and should raise suspicion of a non-discogenic aetiology: History of tick bite or erythema chronicum migrans, fever or general malaise, mono- or oligoradiculopathy with absent or insignificant lumbar pain and complaints of a burning character of the radiating pain. In suspicious cases we recommend blood investigations including antibody determination against borrelia burgdorferi and CSF investigations including cell count and cytology, protein and glucose determination, nephelometry and isoelectric focusing to exclude MRN and other conditions that may mimic disc herniation.

Aged↗
PubMed1988

Envelope glycoprotein of HIV induces interference and cytolysis resistance in CD4+ cells: mechanism for persistence in AIDS.

Masking of host cell receptors following retroviral infection is the basis for the phenomenon of virus interference. Amphotropic retrovirus vectors were used to express the HIV envelope glycoprotein in a human CD4+ cell line. Envelope expression is accompanied by a reduction in the level of surface CD4 receptor molecules and correlates with the presence of intracellular envelope-CD4 receptor complexes. Cells expressing the HIV envelope acquire a cytolysis-resistant phenotype such that infection with HIV leads to a non-cytopathic persistent virus infection. Furthermore, phorbol ester-mediated stimulation of viral replication in persistently infected cells results in renewed cytolytic effects which, due to the absence of CD4 in the cell population, are absolutely independent of syncytium formation. This study elucidates the mechanism by which viral persistence is initiated and maintained in the course of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Vasculitic neuropathy in the Garin-Bujadoux-Bannwarth syndrome. A contribution to the understanding of the pathology and pathogenesis of the neurological complications in Lyme borreliosis].

Clinical examinations and nerve biopsies were performed on four patients with meningoradiculoneuritis and positive serology for Borrelia (Garin-Bujadoux-Bannwarth syndrome). Three patients had a painful multiplex mononeuropathy, while one presented with a picture resembling a Guillain-Barré syndrome. Nerve biopsy in two patients revealed marked perivasculitis, in part with thrombosis of the epineural vasa nervorum. In the other two patients there were small pericapillary infiltrates in the endoneurium with strikingly many plasma cells. These findings speak, on the one hand, for angiopathic-ischaemic nerve damage, but on the other for a local immune reaction to the causative microorganism, because of the plasma-rich endoneural infiltrates. The authors suggest that angiopathic-ischaemic tissue lesions and/or local immune reactions may play a role also in the pathogenesis of CNS complications of Lyme disease.

Biopsy↗
PubMed1988

CA-125 serum concentrations during the menstrual cycle.

CA-125 is an antigenic determinant expressed on ovarian cancer cells and serves as serum marker in patients with ovarian cancer. It has also been detected, however, in serum of healthy women and in patients with benign gynecologic diseases. Previous studies in patients with ovarian hyperstimulation syndrome suggested that the production of CA-125 is correlated with proliferative ovarian activity. In this study, we describe the pattern of CA-125 secretion in 13 healthy women during menstrual cycle and during hormonal contraceptive treatment. That pattern is characterized by an increase of CA-125 serum concentrations parallel to the growth of the dominant follicle. It was not observed during hormonal contraceptive treatment. We conclude that CA-125 serum levels during menstrual cycle seem to be dependent upon the cyclic changes in the female genital tract.

Adult↗
PubMed1988

Specific antibody activity against neuroendocrine tissue in a case of POEMS syndrome with IgG gammopathy.

Specific antibody binding activity directed against pituitary tissue was demonstrated in a typical case of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome with paraproteinemia of IgG lambda type. IgG binding against various other tissues could not be detected by immunoelectroblotting and immunocytochemistry. We propose that POEMS syndrome is an antibody-mediated immune disorder, in which the hypophysis is the primary target of the pathologic myeloma antibodies. The immunopathogenetic lesion of the hypophysis could induce secondary disturbances of other organs, thus explaining the multisystemic disorder.

Adult↗
PubMed1987

[Lipid myopathy: a heterogenic familial case].

A case is reported of lipid storage myopathy in a 24-year-old patient and her family. In the patient and an aunt, muscle biopsy disclosed intrafibrillar lipid depositions, and electron microscopy revealed lipid vesicles in the sarcolemma border. In the father, no lipid depositions were observed but electron microscopy showed alterations to mitochondria compatible with a mitochondrial myopathy. In the patient muscular biochemistry revealed a major reduction in NADH oxydase activity and in the aunt a diminished level of carnitin compatible with carnitin deficiency. The heterogeneity of these lipidic myopathies is discussed.

Adult↗