Astronomy. Weird new exoplanets leave theory behind.
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News↗
Biomedical subjects
G Schilling
Publications and source records attributed to G Schilling.
Astronomical odd couple? Or alter egos?
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News↗
Distinct behavioral and neuropathological abnormalities in transgenic mouse models of HD and DRPLA.
Huntington's disease (HD) and Dentatorubral and pallidoluysian atrophy (DRPLA) are autosomal dominant, neurodegenerative disorders caused by the expansion of polyglutamine tracts in their respective proteins, huntingtin and atrophin-1. We have previously generated mouse models of these disorders, using transgenes expressed via the prion protein promoter. Here, we report the first direct comparison of abnormalities in these models. The HD mice show abbreviated lifespans (4-6 months), hypoactivity, and mild impairment of motor skills. The DRPLA mice show severe tremors, are hyperactive, and are profoundly uncoordinated. Neuropathological analyses reveal that the distribution of diffuse nuclear immunolabeling and neuronal intranuclear inclusions (NII's), in the CNS of both models, was remarkably similar. Cytoplasmic aggregates of huntingtin were the major distinguishing neuropathological feature of the HD mice; mutant atrophin-1 accumulated/aggregated only in the nucleus. We suggest that the distinct behavioral and neuropathological phenotypes in these mice reflect differences in the way these mutant proteins perturb neuronal function.
Aggression↗
Creatine increase survival and delays motor symptoms in a transgenic animal model of Huntington's disease.
There is substantial evidence for bioenergetic defects in Huntington's disease (HD). Creatine administration increases brain phosphocreatine levels and it stabilizes the mitochondrial permeability transition. We examined the effects of creatine administration in a transgenic mouse model of HD produced by 82 polyglutamine repeats in a 171 amino acid N-terminal fragment of huntingtin (N171-82Q). Dietary supplementation of 2% creatine significantly improved survival, slowed the development of motor symptoms, and delayed the onset of weight loss. Creatine lessened brain atrophy and the formation of intranuclear inclusions, attenuated reductions in striatal N-acetylaspartate as assessed by NMR spectroscopy, and delayed the development of hyperglycemia. These results are similar to those observed using dietary creatine supplementation in the R6/2 transgenic mouse model of HD and provide further evidence that creatine may exert therapeutic effects in HD.
Animals↗
Antitumoral activity of a sulphur-containing platinum complex with an acidic pH optimum.
UNLABELLED: Platinum complexes are essential tools for cancer treatment despite their toxic side effects. Here we describe a new platinum complex with sulphurs as complexing atoms (thioplatin). PURPOSE: To demonstrate that the antitumoral activity of a new sulphur-containing platinum compound (thioplatin) depends on a slightly acidic pH. METHODS: Platinum uptake by tumour cells and interaction with DNA was determined at slightly acidic or alkaline pH. To demonstrate low in vivo toxicity the effects of thioplatin on body weight, blood urea nitrogen, white blood cell count and the histopathological appearance of small intestines and kidneys were evaluated at doses that displayed antitumoral effects against human small-cell lung cancer and human colorectal cancer xenotransplants in nude mice. RESULTS: The slightly acidic pH optimum of thioplatin was proven by the altered electrophoretic mobility of plasmid DNA, quantitation of the platinum content in the DNA of tumour cells and cytotoxicity studies. Thioplatin displayed antitumoral activity without severe side effects such as weight loss, renal ischaemia, destruction of villi in the small intestine or leukopenia as observed at comparable doses of cisplatin. Furthermore, probably due to its lipophilic nature, thioplatin was taken up readily even by cisplatin-resistant cells. In vivo studies with human tumour xenografts in nude mice showed a therapeutic index of thioplatin five to ten times higher than that of cisplatin.
Animals↗
Biosynthesis and subcellular distribution of hydrolyzable tannins.
Pathways to complex gallotannins have been elucidated by enzyme studies, indicating that beta-glucogallin is required as principal acyl donor. Evidence for the in vitro oxidation of pentagalloylglucose, the pivotal metabolite in this sequence, to ellagitannins, is presented. Immunohistochemical studies with antibodies raised against pentagalloylglucose and the galloyltransferase catalyzing the formation of this ester revealed that leaf mesophyll cell walls were a typical site of origin and deposition of hydrolyzable tannins. Seasonal changes of these compounds were studied with extracts from cell walls and intracellular space of oak leaves.
Cell Wall↗
Secrecy and openness in donor offspring.
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Adult↗
Alexithymia in male infertility.
The continuing confrontation with the thoughts and feelings surrounding an unfulfilled wish for a child makes coping very difficult. There is empirical evidence that, in medical illnesses associated with stress and loss of quality of life, patients react with alexithymia, which means a difficulty to communicate emotions. In this study we compared 84 infertile men with a group of 96 healthy men and 43 male psychosomatic outpatients concerning their ability to communicate feelings, measured by the Twenty-Item Toronto Alexithymia Scale and the amount of psychopathologically relevant symptoms, especially somatization, measured by the Symptom Checklist 90-R and a List of Complaints (Beschwerden-Liste). The results showed a significantly higher alexithymia in infertile men compared with healthy men (P < 0.05), but a significantly lower alexithymia compared with psychosomatic outpatients (P < 0.05). Furthermore the study group showed significantly more somatic complaints in the List of Complaints compared with healthy men (P < 0.05). The importance of alexithymia in male infertility is discussed on the basis of empirical results that it might play a defensive role as far as depression is concerned but on the other hand increases the possibility of somatic complaints. The need for prospective studies in further research is emphasized.
Adult↗
[Differences between patients classified as "recovered" or "improved" and "unchanged" or "deteriorated" in a psychotherapy outcome study].
The concepts of statistical and clinical significance of pre-post-changes have been used to class patients into four groups of therapy outcome: "recovered", "improved", "unchanged" and "deteriorated". Aim of this study is to investigate the advantages of this classification in comparison to a simple division into "successful" and "not successful". 43 patients were examined before and after an in-patient psychotherapy and again two years later with several test inventories. Therapy outcome was measured by the changes in the Global Severity Index of the SCL-90-R. "Recovered" and "improved" patients did only differ in regard to their initial symptom severity, but not in regard to the amount of symptom reduction or stability of therapy effect. "Deteriorated" patients could reduce their increase in symptoms until follow-up. Our results do not indicate a general advantage of the classification into four outcome groups over a division into "successful" / "not successful".
Adolescent↗
Sloan Digital Sky Survey. A hundred million points of light
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Journal Article↗
Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product, interacts with ETO/MTG8 in the nuclear matrix and represses transcription.
Dentato-rubral and pallido-luysian atrophy (DRPLA) is one of the family of neurodegenerative diseases caused by expansion of a polyglutamine tract. The drpla gene product, atrophin-1, is widely expressed, has no known function or activity, and is found in both the nuclear and cytoplasmic compartments of neurons. Truncated fragments of atrophin-1 accumulate in neuronal nuclei in a transgenic mouse model of DRPLA, and may underlie the disease phenotype. Using the yeast two-hybrid system, we identified ETO/MTG8, a component of nuclear receptor corepressor complexes, as an atrophin-1-interacting protein. When cotransfected into Neuro-2a cells, atrophin-1 and ETO/MTG8 colocalize in discrete nuclear structures that contain endogenous mSin3A and histone deacetylases. These structures are sodium dodecyl sulfate-soluble and associated with the nuclear matrix. Cotransfection of ETO/MTG8 with atrophin-1 recruits atrophin-1 to the nuclear matrix, while atrophin-1 and ETO/MTG8 cofractionate in nuclear matrix preparations from brains of DRPLA transgenic mice. Furthermore, in a cell transfection-based assay, atrophin-1 represses transcription. Together, these results suggest that atrophin-1 associates with nuclear receptor corepressor complexes and is involved in transcriptional regulation. Emerging links between disease-associated polyglutamine proteins, nuclear receptors, translocation-leukemia proteins, and the nuclear matrix may have important repercussions for the pathobiology of this family of neurodegenerative disorders.
Animals↗
Decreased expression of striatal signaling genes in a mouse model of Huntington's disease.
To understand gene expression changes mediated by a polyglutamine repeat expansion in the human huntingtin protein, we used oligonucleotide DNA arrays to profile approximately 6000 striatal mRNAs in the R6/2 mouse, a transgenic Huntington's disease (HD) model. We found diminished levels of mRNAs encoding components of the neurotransmitter, calcium and retinoid signaling pathways at both early and late symptomatic time points (6 and 12 weeks of age). We observed similar changes in gene expression in another HD mouse model (N171-82Q). These results demonstrate that mutant huntingtin directly or indirectly reduces the expression of a distinct set of genes involved in signaling pathways known to be critical to striatal neuron function.
Adenylyl Cyclases↗
Nature of monster sawteeth and their relationship to Alfven instabilities in tokamaks
A correlation is explored between the presence of energetic particle modes (EPM) and long-period sawtooth oscillations in tokamak plasmas heated by rf waves. The eventual crash of these sawteeth is explained in terms of the loss of the stabilizing fast particles due to the EPM. The absence of long-period sawteeth in high q(a) discharges is explained in terms of ion loss due to toroidal Alfven eigenmodes.
Journal Article↗
[Unresolved couple conflicts in male infertility].
BACKGROUND AND OBJECTIVE: There is empirical evidence that sterility causes a considerable amount of distress and affects correspondingly the partnership. Empirical results concerning male infertility show increased somatic complaints and reduced self-esteem of the men as well as a dominance of the accompanying partners. Which couple conflicts arise after the diagnosis of male infertility? PATIENTS/METHODS: 84 infertile men were examined with a partnership diagnostic questionnaire. The questionnaire was evaluated with regard to quantity and quality of unsolved couple conflicts. RESULTS: The results show that infertile men do not mention more unsolved conflict areas in their partnership than healthy men. If one looks qualitatively at the mentioned conflict areas, striking differences in comparison to the control group can be seen. CONCLUSIONS: In comparison to the control group of healthy men, the specificity of conflict areas in infertile couples can be best understood on the basis of exchange-theoretical considerations.
Adaptation, Psychological↗
[Central serous chorioretinopathy and psychological stress].
BACKGROUND: To date we know little about the etiology of central serous chorioretinopathy. Former investigations discussed inadequate coping strategies and critical life-events as important psychological aspects. In this study we investigated the relationship between central serous chorioretinopathy and stress. MATERIALS AND METHODS: 35 male patients with central serous chorioretinopathy (group 1) were compared to 21 male patients with traumatic eye diseases. The evaluated data included sociodemographic data as well as data regarding the patients coping strategies, critical live-events before outbreak of the disease, personality factors and general physical complaints. RESULTS: Group 1 showed a significantly higher amount of general physical complaints, measured with a complaints questionnaire (B-L). In a personality inventory (FPI-R) it scored significantly higher on the scales emotional instability and strain, significantly lower on the scale extraversion. CONCLUSION: The results indicate that patients with central serous chorioretinopathy are more stressed because of inadequate coping strategies, which can be seen in a higher amount of physical complaints.
Adaptation, Psychological↗
[Differences in 2 diagnostic groups of psychosomatic patients on the Symptom Checklist 90-R (SCL-90-R). Consequences for using SCL-90-R in follow-up research].
680 unselected outpatients of our Psychosomatic Clinic were divided into six diagnostic groups and examined by the SCL-90-R. By ANOVA we found differences of means between the diagnostic groups for the global severity score (GSI) and for the subscale scores. We describe the model of Jacobson et al. [1,2] for the determination of cut-off-points and reliable change indices for the assessment of changes over time, e.g. after psychotherapy. Our results lead to the conclusion that, although an overall reliable change index for the GSI can be applied to all psychosomatic patients, cut-off-points should be different following the diagnostic groups. Furthermore, information from the SCL-90-R-subscales as well as other specific symptom scales should be used for the interpretation of significant changes of the GSI.
Adult↗
Neutral sphingomyelinase-inhibiting guanidines prevent herpes simplex virus-1 replication.
We synthesized a series of new guanidinium derivatives and studied the inhibitory activity on both neutral sphingomyelinase and herpes simplex virus-1 (HSV-1) replication. The lipophilic quality of the molecules was found to be correlated with the inhibitory potential of the compounds. Undecylidene-aminoguanidine was superior to derivatives with 10, 8 or 6 carbon atoms whereas propylidene-aminoguanidine was completely inactive. Decylidene-aminoguanidine was the most active derivative, with 10 carbon atoms. Various cyclic saturated isomers were inferior to the linear molecule. Aromatic cyclic residues were superior to saturated cyclic residues. The most active compound was a derivative containing 11 carbon atoms, undecylidene-aminoguanidine (C11AG), which inhibited the replication of HSV-1 by 50% at a concentration of 2.6 microM while cytotoxic adverse effects were only observed at a concentration of 31 microM. Expression of immediate early gene ICP-4 and concomitantly of HSV-1 specific DNA replication was found to be a target of C11AG. This result suggests that C11AG interferes with cellular signal transduction mechanisms that regulate expression of HSV-1 immediate early genes. C11AG was shown to inhibit neutral sphingomyelinase without affecting phospholipase A2, phosphatidylcholine-specific phospholipase C and phospholipase D.
Animals↗
UFT/leucovorin plus weekly irinotecan in advanced or metastatic colorectal cancer.
This is an open-label, nonrandomized phase I trial to determine the safety and maximum tolerated dose of irinotecan with a fixed dose of UFT plus oral leucovorin in patients with advanced or metastatic colorectal cancer. A secondary objective of the study is to determine the response rate in this patient population. Adult patients with histologically confirmed advanced or metastatic colorectal carcinoma and no prior chemotherapy for advanced or metastatic disease, or those patients who have received adjuvant chemotherapy (> 6 months prior to the study entry) will be eligible to participate. All patients must have measurable or evaluable lesions. Symptoms will be evaluated at baseline and every 6 weeks thereafter. Computed tomography scans will be performed at baseline and every three cycles of treatment to assess tumor response. A total of six cycles of treatment may be given, depending on patient tolerance. Patients will be followed for a maximum of 12 months for time to progression, following the last dose of the study drug. Tumor response will be defined using standard World Health Organization criteria.
Administration, Oral↗