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Biomedical subjects

J Weis

Publications and source records attributed to J Weis.

At least 55 records · Page 3Linked to original sources
PubMed2000

Denervation induces a rapid nuclear accumulation of MRF4 in mature myofibers.

Muscle regulatory factor 4 (MRF4) is a member of the family of myogenic transcription factors, including MyoD, myogenin, and myf-5, that are necessary for the commitment and differentiation of mesoderm to skeletal muscle. Although the function of these transcription factors during embryonic development has been demonstrated, their role in adult muscle has remained elusive. Regulation of the MRF4 gene differs from the genes encoding the other myogenic factors in that its transcripts accumulate in neonatal muscle during maturation and continue to be expressed at relatively high levels in the adult. On the basis of its mRNA expression pattern, MRF4 has been suggested to regulate genes encoding adult contractile proteins and acetylcholine receptor subunits. To test this hypothesis, a specific antiserum was developed to study MRF4 protein expression in adult innervated and denervated muscle, because MRF4 mRNA levels increase by approximately threefold 1 day after nerve resection. By using three different immunohistochemical methods that vary widely in sensitivity, we were unable to detect MRF4 immunoreactivity in adult innervated muscles. The same results were obtained with another MRF4 antiserum generated independently. In contrast, any of these three immunologic techniques readily detected MRF4 immunoreactivity in myofiber and satellite cell nuclei of muscles denervated for 24 hours. The highest proportion of immunopositive nuclei (80%) was found 2-3 days after denervation. Immunoreactivity was no longer detectable by 14 days. There was no differential accumulation of MRF4 protein in the nuclei of satellite cells nor in sole plate (synaptic) nuclei at any time after denervation. No differences were found in the temporal accumulation of MRF4 in nuclei of type I and type II denervated myofibers, consistent with the similar distribution of MRF4 mRNAs in slow- and fast-twitch muscles. Our results are consistent with the lack of phenotype observed in the adult muscles of MRF4-null mutant mice observed by others and suggest that MRF4 may have important roles in the gene programs activated after denervation and during muscle regeneration.

3T3 Cells↗
PubMed2000

Morphological changes following experimental intraventricular haemorrhage and intraventricular fibrinolytic treatment with recombinant tissue plasminogen activator.

Intraventricular haemorrhage (IVH) occurs in up to 50% of patients with primary intracerebral haemorrhage and aneurysmal subarachnoid haemorrhage. It is a significant and independent contributor to mortality and morbidity in these intracranial haemorrhages. Using a model of isolated IVH, we assessed the morphological changes induced by intraventricular bleeding and investigated the effects of intraventricular fibrinolytic treatment following IVH. IVH was induced in 32 pigs by intraventricular infusion of 10 ml autologous blood along with thrombin. The treatment group received an intraventricular injection of 1.5 mg (1 mg/ml) tissue plasminogen activator (tPA) following the injection of blood. The placebo group received the same volume of normal saline. Morphological examinations of the brains were carried out 7 days and 6 weeks following IVH. The ventricles were incompletely filled with blood and significantly enlarged in the placebo group 7 days after the IVH. In contrast, no residual intraventricular clots were visible in the animals treated with tPA, and the diameters of the lateral ventricles had returned to normal within 7 days. Marked losses of the ependymal covering of the ventricular walls were found in the placebo-treated animals, while the ependymal layer was largely intact in the animals treated with tPA. No haemorrhages induced by tPA were observed. The results indicate that intraventricularly administered tPA significantly enhances the lysis of intraventricular blood clots, accelerates the resolution of acute posthaemorrhagic hydrocephalus, and preserves the integrity of the ependymal layer.

Animals↗
PubMed2000

Astrocytic alterations in interleukin-6/Soluble interleukin-6 receptor alpha double-transgenic mice.

Interleukin-6 (IL-6), a major cytokine with diverse effects on cells mainly of the immune and hematopoietic systems, has been linked to several neurological disorders such as acquired immune deficiency syndrome dementia, multiple sclerosis, and Alzheimer's disease. Central nervous system (CNS)-specific expression of IL-6 caused neurodegeneration, massive gliosis, and vascular proliferation in transgenic mice. However, the effects of systemically circulating IL-6 and its receptor IL-6Ralpha on the CNS are unknown. IL-6Ralpha is the specific component of the IL-6 receptor system and hence an important co-factor of IL-6. IL-6Ralpha is bioactive in a membrane-bound and in a soluble (s) form. We investigated the effects of systemically elevated levels of either human IL-6 or human sIL-6Ralpha or both on the CNS of transgenic mice. Although IL-6 and sIL-6Ralpha single transgenic mice were free of neurological disease, IL-6/sIL-6Ralpha double-transgenic mice showed neurological signs, such as tremor, gait abnormalities, and paresis. However, these mice also frequently showed prominent general weakness probably because of the systemic effects of IL-6/IL-6Ralpha such as liver damage and plasmacytomas. IL-6/sIL-6Ralpha transgenic mice exhibited massive reactive gliosis. Lack of signs of neuronal breakdown versus ample astrogliosis suggested that astrocytes were selectively affected in these mice. There was neither vascular proliferation nor inflammatory infiltration. Ultrastructural analysis revealed blood-brain barrier (BBB) changes manifested by hydropic astrocytic end-feet. However, albumin immunohistochemistry did not reveal major BBB leakage. Our results indicate that increased and constitutive systemic expression of IL-6 together with its soluble receptor sIL-6Ralpha is less harmful to the brain than to other organs. The BBB remains primarily intact. IL-6/IL-6Ralpha, however, might be directly responsible for the selective activation of astrocytes.

Animals↗
PubMed2000

Mitochondrial complex I deficiency in a female with multiplex arthrogryposis congenita.

A 10-year-old female with arthrogryposis multiplex congenita is presented. Clinical, neurophysiologic, and histologic findings suggested a mild myopathy. The analysis of enzymatic activity in the homogenate and of mitochondrial function in saponin-permeabilized fibers from the muscle biopsy revealed an approximately twofold-decreased specific activity of the NADH:CoQ oxidoreductase (complex I of the mitochondrial respiratory chain) that was compensated for by an increased number of mitochondria. The complex I deficiency was also detected in cultivated skin fibroblasts of the patient. The observed defect of mitochondrial oxidative phosphorylation in arthrogryposis multiplex congenita may be of pathogenetic relevance.

Arthrogryposis↗
PubMed2000

[Comorbid psychiatric disorders in cancer patients in acute inpatient treatment and medical rehabilitation].

An association between mental disorders, especially affective and anxiety disorders, and cancer has been reported in many clinical studies with inpatients. However, no data exist about the prevalence of mental disorders in patients undergoing acute care or rehabilitation treatment for cancer in Germany. The present study investigated 4-week, 6-month and lifetime prevalence rates of comorbid mental disorders in cancer. 256 patients from 2 rehabilitation clinics and 2 acute care hospitals were examined with standardized screening scales for psychological burden (GHQ-12, HADS) and quality of life (SF-36). Somatic parameters and interventions were assessed through standardized medical records from the attending oncologists. In the second-stage examination a subsample of 120 patients were interviewed with standardized clinical interview (CIDI) in order to obtain DSM-IV diagnoses of mental disorders. 44% (acute care) and 49% (rehabilitation) of the patients have high GHQ scores (cut-off > 4). Furthermore, more than 20% of the cancer patients have elevated scores on the HADS subscales depression and anxiety (cut-off > or = 11). Prevalence rates of mental disorders in the rehabilitation sample are 34% for the 4-week (vs. 24% in the acute care sample), 45% for the 6-month period (vs. 38%), and 79% for lifetime (vs. 49% in the acute care sample). The most frequent current disorders are affective (13% rehabilitation vs. 11% acute care) and anxiety disorders (17% in both samples). The rates of affective and anxiety disorders are much higher than the frequency of these disorders in recent epidemiological studies of the normal population in Germany. The high psychosocial burden expressed by the patients and the frequency of depressive and anxiety disorders emphasize the importance of (1) effective diagnostic strategies to recognize mental disorders, and (2) specialized psychosocial services in oncology, which provide psychological support and effective interventions for cancer patients in acute care and rehabilitation.

Adult↗
PubMed2000

Pleomorphic xanthoastrocytoma derived from glioneuronal malformation in a child with intractable epilepsy.

Malformative lesions as well as neoplasms can cause intractable epilepsy in childhood. Even though the neoplastic nature of a lesion is evident in most cases, the distinction can be difficult in some patients. We present the case of a child with intractable epilepsy caused primarily by a glioneuronal malformation. Years after the first surgical intervention, a pleomorphic xanthoastrocytoma evolved from remnants of this lesion. This case suggests that glioneuronal malformations might be precursor lesions of pleomorphic xanthoastrocytomas.

Astrocytoma↗
PubMed2000

[Not Available].

Epidemiological data show that 40-50% of all cancer patients develop some kind of psychosocial disturbancy during the course of their illness and about 30% will require professional support. Even if there exists a considerable body of knowledge and a differentiated health care System, the vast majority of cancer patients have no chance to receive any proper psychosocial care due to the lack of facilities like psychosocial outpatient Services in the communities and specifically trained psychooncologists on oncology wards, whereas the number of psychooncologists in rehabilitation-clinics seems to be sufficient. Psychooncological societies have established training courses and formulated guidelines relating to some important aspects of psychosocial research and practice, in order to promote good quality in the psychosocial care of cancer patients.

Cancer rehabilitation↗
PubMed1999

[Headache, painful eyes, fever and weight loss].

A 64-year-old patient with herpetic keratouveitis was hospitalized because of fatigue, fever, headache and confusion. Three days before admittance keratouveitis was diagnosed. He reported a recent onset of aversion against meat consumption and weight loss of 11 kg over the last 4 months. Clinical investigation revealed a slightly confused patient with conjunctivitis and reduced vision of the left eye. Laboratory tests showed anemia, hyponatremia, and increased carcinoembryonic antigen (CEA). In the cerebrospinal fluid examination protein concentration was increased, glucose concentration was decreased. CT-scan of the brain revealed multiple, hyperintense, circular lesions. Biopsy showed lymphoplasmacellular infiltration with increased number of glial and oligodendroglial cells with central necrosis. Despite therapy with tuberculostatic and antiviral drugs and corticosteroids the condition of the patient progressively deteriorated. The patient died 42 days after admission. Autopsy revealed a high grade B-cell non-Hodgkin's lymphoma of the jejunum. Septic shock was the cause of death with the lymphoma of the jejunum as a possible nidus of infection. The multiple brain lesions with central necrosis were probably caused by thromboembolization or by a previous viral meningoencephalitis.

Diagnosis, Differential↗
PubMed1999

Interleukin-6 (IL-6) and its soluble receptor support survival of sensory neurons.

The cytokine interleukin-6 (IL-6) has multiple functions in the immune and hematopoietic systems. IL-6 is related to ciliary neurotrophic factor (CNTF), a trophic factor for motoneurons, sensory dorsal root ganglion (DRG) neurons, and other neuronal subpopulations. Both act via related receptor complexes, consisting of one ligand-specific alpha-receptor subunit (IL-6R and CNTFR, respectively) and two signal-transducing receptor components. Even though IL-6 is expressed by neurons and glia, the functions of IL-6 in the nervous system are poorly understood. Here, we report that exogenous human IL-6 promotes the survival of dissociated newborn rat DRG neurons in vitro if supplemented with soluble human IL-6-alpha-receptor. The dosages of human IL-6 and soluble human IL-6R necessary to achieve neurotrophic effects could be reduced markedly by linking ligand and alpha-receptor component in a designer cytokine. Furthermore, we show that newborn rat DRG neurons express and secrete bioactive IL-6. Endogenously secreted IL-6 does not enhance survival of these neurons in vitro, suggesting that DRG neurons do not sufficiently express cell surface IL-6R. Exogenously added soluble rat IL-6R rendered DRG neurons responsive to secreted IL-6. Our results indicate an autocrine function of IL-6 in DRG neuron survival which depends on membrane-bound or soluble IL-6R as a neurotrophic cofactor.

Animals↗
PubMed1999

Trophic effects of cardiotrophin-1 and interleukin-11 on rat dorsal root ganglion neurons in vitro.

Cardiotrophin-1 (CT-1) was originally isolated for its hypertrophy inducing effects on cardiac myocytes whereas interleukin-11 (IL-11) was identified due to its ability to stimulate an interleukin-6 (IL-6) dependent plasmocytoma cell line. Both cytokines are structurally and functionally related to a group of factors called neuropoietic cytokines, which also includes IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), and oncostatin M. These factors have trophic effects on subsets of neurons. In the present study we examined the influence of CT-1 and IL-11 on newborn rat dorsal root ganglion neuron survival in vitro. Mouse CT-1 showed prominent trophic effects that were comparable to those of CNTF and LIF. Mouse IL-11 alone did not enhance neuronal survival, but soluble mouse IL-11 receptor alpha rendered neurons sensitive to IL-11. Surprisingly, soluble IL-11 receptor alpha even had slight neurotrophic effects by itself. These results suggest that CT-1 and IL-11 might also be involved in the physiological regulation of sensory neuron survival. Thus, they might, like CNTF, become tools for the therapeutic intervention in neurodegeneration due to disease, toxicity, and trauma.

Animals↗
PubMed1999

Chemical shift artifact-free microscopy: spectroscopic microimaging of the human skin.

A spectroscopic imaging technique with high spatial resolution was used for the study of human skin in vivo. The measurements were performed using a whole-body magnetic resonance system (1.5 T) with standard gradients and a standard 8-cm diameter circular surface coil. A decisive gain in signal-to-noise ratio was achieved by reducing the receiver bandwidth of the imaging system to values less than +/-5 kHz. The chemical shift misregistration was eliminated by post-detection data processing. The method was tested on different kinds of skin, on the foot sole and head. Water, fat, and chemical shift artifact-free images were obtained with resolution 0.107 x 0.143 mm in plane and slice thickness 1 mm. A major advantage of the spectroscopic imaging procedure is that the pulse sequence can be optimized for the maximum signal-to-noise ratio. There is no need for special modification of the sequence to circumvent the chemical shift artifacts (water, fat suppression, etc.).

Adipose Tissue↗
PubMed1999

Migratory potential of transplantable neural tumor cell lines.

Experimentally induced primitive neuroectodermal tumor (PNET) cell lines were transplanted into neonatal and adult rat brain and examined neuropathologically for their tumorigenic potential. Both cell lines showed a striking migratory behavior in both neonatal and adult brain. Migration of tumor cells was found in host brain parenchyma, along white matter tracts and associated with CSF pathways. These neural tumor cell lines provide a valuable tool for the development of strategies against strongly migrating neural tumors.

Animals↗
PubMed1999

Characterization of human head vasculature by percolation parameters.

A data reduction procedure, originally proposed for characterization of fractals and random percolation clusters, has been used to evaluate the vascular system of the human head. The motivation behind this study arose from the wish to study empirically transport properties of vascular systems and to find a suitable formalism for their description. MR angiographic data acquired by a standard 3D inflow method were used. The evaluated parameters refer to the backbone fractal dimensionality and the correlation length. The fractal dimensionality of the backbone was found to be 1.71 for the human head vasculature. This value fits the theoretical range of random percolation networks. It is concluded that concepts of percolation theory might have some value for characterizing the structure and transport properties of the vascular system.

Brain↗
PubMed1999

CNTF and its receptor subunits in human gliomas.

Ciliary neurotrophic factor (CNTF) promotes the survival of various neuronal cell populations. It is produced by astrocytes and influences the development and differentiation of glial cells. CNTF and related neuropoietic cytokines affect growth and differentiation of various neoplasms. Moreover, they induce the reactive transformation of astrocytes (gliosis) and influence growth and differentiation of neuroectodermal tumor cell lines in vitro. However, their role in gliomas is largely unknown. We studied the expression of CNTF and its receptor subunits in human astrocytomas and glioblastomas. In more than 95% of the tumors, CNTF transcripts were found by RNAase protection assay; in more than 80% of the cases, tumor cells were CNTF immunoreactive. CNTF receptor alpha (CNTFR alpha), the specific component of the tripartite CNTF receptor system, was detectable by Northern blot analysis in 80% of the cases. In situ hybridization revealed CNTFR alpha mRNA in the cytoplasm of neoplastic cells. Transcripts of the remaining two components of the CNTF receptor system, gp130 and LIFR beta, were found by Northern blotting in 83% and 70% of the tumors, respectively. Simultaneous expression of CNTF and all its receptor components was detected in approximately half of the tumors. These results indicate that CNTF and its receptor components are expressed by human glioma cells. The simultaneous expression of ligands and receptor subunits suggests that CNTF might act on human glioma cells via an auto- or paracrine mechanism.

Adolescent↗
PubMed1999

Autosomal dominant burning feet syndrome.

Familial burning feet syndrome inherited as an autosomal dominant trait has been described in only one family. Due to an associated sensory neuropathy the autosomal dominant burning feet syndrome was suggested to represent a variant form of hereditary sensory and autonomic neuropathy type I (HSAN I). Clinical, histopathological, and molecular genetic studies were performed in a large German kindred with autosomal dominant burning feet syndrome. The autosomal dominant burning feet syndrome was associated with a neuropathy predominantly affecting small unmyelinated nerve fibres. Linkage to the HSAN I locus on chromosome 9q22 and to the Charcot-Marie-Tooth disease type 2B (CMT 2B) locus on chromosome 3q13-q22 was excluded. The autosomal dominant burning feet syndrome is neither allelic to HSAN I nor to CMT 2B and thus represents a distinct genetic entity.

Female↗
PubMed1999

Timing adjustment in gadolinium MR angiography by raw data recombination. Technical note.

To solve the problem of injection timing in gadolinium MR angiography, a simple procedure is proposed which allows the acquisition interval to be chosen after injection. Starting simultaneously with the injection, several consecutive acquisitions are made, after which raw data acquired in a contiguous interval with a variable starting time are recombined to one data set, which is then used for delayed image reconstruction.

Aged↗