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Biomedical subjects

W Lange

Publications and source records attributed to W Lange.

298 records · Page 17Linked to original sources
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Bcl-2 mRNA-targeted ribozymes: effects on programmed cell death in chronic myelogenous leukemia cell lines.

We used synthetic RNA transcripts to prove the cleavage capability of ribozymes targeted against bcl-2-related RNAs. No cleavage occurred when control oligonucliotides were used. To assess the functional role of the specific ribozymes in chronic myelogenous leukemia (CML) cell lines we cultured K562, BV173, and Daudi cells for 48 h after lipofection with 10 microM oligonucleotide. An increase in apoptotic cells, dependent on ribozyme specificity, was shown in BV173 cells. This finding was underlined by the typical morphological changes, but there is no correlation with regard to the level of bcl-2 protein expressed. Though bcl-2 appears to interfere with cell death in myeloid cells, bcl-2-targeted ribozymes do not induce programmed cell death (PCD) by reducing bcl-2 protein levels, but rather by a presently unknown mechanism.

Apoptosis↗
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Immunohistochemical mapping of neurophysins and calcitonin gene-related peptide in the human brainstem and cervical spinal cord.

Our study investigates the distribution of neurophysins (Nph), proteins that are part of the precursors for vasopressin and oxytocin, and calcitonin gene-related peptide (CGRP) in the human brainstem by immunohistochemistry. Both peptides were found in discrete regions of the human hindbrain. Nph could be demonstrated exclusively in fibers and punctate perineural varicosities that were travelling within the mesencephalic central gray, substantia nigra, as well as locus coeruleus, medial longitudinal fascicle, raphe, nucleus of the solitary tract, lateral reticular nucleus and area postrema. A few varicosities were seen in the substantia gelatinosa of the spinal trigeminal tract and its continuation into the dorsal horn of the cervical spinal cord. In contrast to these observations. CGRP-immunoreactive fibers were found to be densest in the spinal tract of the trigeminal nerve and the dorsal horn of the spinal cord. In addition, fibers and varicosities could be demonstrated in numerous distinct brain regions, such as locus coeruleus and subcoeruleus, solitary tract, cuneate nucleus, raphe and periaqueductal gray. CGRP-immunoreactivity was also present in perikarya in the ventral horn of the spinal cord, as well as motor nuclei of cranial nerves, i.e., hypoglossal nucleus, ambiguous nucleus. Our results suggest that Nph-immunoreactivity in the human brainstem may be present predominantly within long fiber projections from hypothalamic neurosecretory nuclei, in analogy to data obtained from rodents, whereas CGRP may play a role in the branchiomotor system as well as in intrinsic or extrinsic projections involved in autonomic regulation and integration of sensory information.

Adult↗
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Cleavage of BCR/ABL mRNA by synthetic ribozymes--effects on the proliferation rate of K562 cells.

Ribozymes are effective tools for the cleavage of target RNAs in a sequence-specific way. In chronic myelogenous leukemia (CML) the reciprocal translocation of chromosomes 9 and 22 results in the formation of the unique BCR/ABL fusion gene which is believed to play a crucial role in the establishment of CML. In order to decrease the BCR/ABL gene product we designed short synthetic ribozymes and analyzed their effects on the proliferation rate of K562 cells. Ribozymes proved to have a higher inhibitory potential as conventional antisense constructs of comparable nucleotide sequence.

Base Sequence↗
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Comorbid anxiety and affective disorder in alcohol-dependent patients seeking treatment: the first Multicentre Study in Germany.

The goals of this study were to describe demographic variables, drinking history, and the 6-month prevalence of Axis I comorbidity among alcohol-dependent subjects in GERMANY: The variables: amount of alcohol consumption, age at onset of the first alcohol consumed, age at onset of daily alcohol consumption, age at onset of withdrawal symptoms and number of detoxifications were related to the different comorbid disorders and gender. In this study, 556 patients from 25 alcohol treatment centres were enrolled between 1 January 1999 and 30 April 1999. After a minimum of 10 days of sobriety patients who fulfilled ICD-10 and DSM-IV criteria of alcohol dependence were interviewed for data collection using the Mini-DIPS (German version of the Anxiety Disorders Interview Schedule) and a standardized psychosocial interview. The 6-month prevalence of comorbid Axis I disorders was 53.1%. Among the patients with comorbidity, affective and anxiety disorders were most frequent. Comorbid stress disorder was associated with an early start of drinking, an early beginning of withdrawal symptoms, highest number of detoxifications, and the highest amount of alcohol consumed. Female patients with anxiety disorder consumed more alcohol and started earlier than females without this comorbid disorder. The data do not answer the question of the pathogenesis of comorbid disorders and alcoholism, but indicate that stress disorders in alcoholic patients and anxiety disorders in female alcoholics influence the course and severity of alcoholism.

Adult↗
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The course of anxiety, depression and drinking behaviours after completed detoxification in alcoholics with and without comorbid anxiety and depressive disorders.

We studied the associations between comorbid anxiety and depressive disorders in treated alcoholics, the course of current anxiety and depression during the early and late post-detoxification periods, and drinking behaviours after discharge. Lifetime psychiatric comorbidity was assessed in 100 alcoholics using the Composite International Diagnostic Interview (CIDI). Three subgroups defined as group DA (comorbid depressive and anxiety disorders, n = 15), group A (anxiety disorder only, n = 23), and group NO (no comorbid disorder, n = 62) were studied. Beginning 21 +/- 13 days after cessation of drinking, state anxiety (STAI-X1), trait anxiety (STAI-X2) and depression (BDI) were assessed once per week (t1 to t4) and once more 6 months after discharge (t5, n = 68). The severity of psychopathology decreased during the first 4 weeks after detoxification in all subgroups. However, trait anxiety remained at higher levels in both the comorbid subgroups from t1 to t4. In the follow-up sample, 60.5% of the non-comorbid subjects remained abstinent, but only 26.7% of all comorbid patients and only 12.5% of those with comorbid depressive disorder plus severe current trait anxiety or depression at t1. Independent of their comorbidity status, relapsers at t5 had already reported more trait anxiety than abstainers at t1. We conclude that severe trait anxiety persisting after 3 weeks of abstinence, comorbid depressive and/or anxiety disorders, and combinations of these with moderate or severe current anxiety and depressive states represent the greatest risks of relapse and therefore may indicate a treatment need.

Adult↗
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Impaired serum cortisol stress response is a predictor of early relapse.

AIMS: to investigate a possible association of cortisol stress response during early abstention with relapse. METHODS: Thirty-six alcohol-dependent males, half of them with a comorbid anxiety disorder, and 15 healthy controls were exposed to a standardized psychosocial stress test. Thirty-one of the patients were assessed for relapse 6 weeks after discharge. RESULTS: The relapsers showed almost no cortisol responses in the stress test. Comorbid anxiety disorder influenced neither stress response nor relapse. CONCLUSIONS: During early abstention from alcohol, reduced stress-responsivity of the hypothalamo-pituitary-adrenocortical axis seems to be connected to early relapse.

Adult↗
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Comparison of psychiatric ICD-10 diagnoses in Denmark and Germany.

A dataset of psychiatric ICD-10 diagnoses from the Danish case register concerning psychiatric hospitals was compared with a sample of psychiatric diagnoses from 27 psychiatric hospitals in Germany. The comparison shows a higher proportion of F1 diagnoses in the German dataset and a difference in the coding of alcohol dependence and harmful use. Some further differences in the groups F0-F6 are demonstrated and some of them are discussed. The most frequent diagnoses found in both datasets but in different sequence are alcohol dependence syndrome and paranoid schizophrenia and, in third place, adjustment disorder. Various aspects of the problem of rarely used diagnoses are discussed.

Adjustment Disorders↗
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Growth inhibition of Ph+ progenitor cells from CML patients using the tyrosine kinase inhibitor CGP57148B.

BACKGROUND: Different methods have been investigated for their purging capacity of contaminating CML cells in autologous stem cell products. CGP57148B, a tyrphostin, has been shown to be efficient in the reduction of cell proliferation of CML cell lines and primary CML cells, as well as in the inhibition of bcr/abl-related tumor formation in animal models. MATERIALS AND METHODS: The effect of CGP57148B on purified CD34+ progenitor cells from BM, PB, or leukapheresis products of 8 CML patients was studied under serum-free cytokine-supplemented ex vivo culture conditions. RESULTS: FISH as well as RT-PCR analysis showed a significant reduction of Ph+ cells after 7 days ex vivo-culture in the presence of the tyrphostin. Growth of Ph- cells was almost unaffected by treatment with CGP57148B. CONCLUSION: Our results support the observation that CGP57148B can selectively inhibit proliferation of Ph+/bcr/abl+ primary CML cells under serum-free cytokine-supplemented culture conditions.

Adult↗
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Cerebral lymphoma in AIDS. Clinical, radiological, neuropathological and immunopathological study.

Neuropathological findings from 8 individual cases of cerebral lymphomas in AIDS patients with consideration of the clinical, radiological, immunopathological, and other pertinent data selected from a series of 80 patients between 1985 and 1989 were studied. A wide variation in pathology was noted among our cases. It has been shown that lymphoma as a neuropathological diagnosis can coexist with a wide range of other characteristics, including toxoplasmosis, glial nodules, neuronophagia, degeneration, bleeding, hypoxia, progressive multifocal leucoencephalopathy, and myelopathy, although none of these attributes appeared more than casually interrelated. In general, the late-stage manifestations of lymphoma as were observed in this study, tended to be poorly localized, often simultaneously meningeal, perivascular, and diffuse in character. An important distinction between cerebral lymphomas of AIDS and non-AIDS patients is the highly atypical, clinically unreliable computer tomographic signals observed in several of our cases. Five of the six immunopathological investigations showed a preponderance of B-cell markers, corresponding in toto to high-grade non-Hodgkin lymphoma. One case exhibited immunohistological markers typical of Hodgkin's lymphoma (antibody CD-30). Of 6 obtainable serum specimens from our 8 cases, 4 showed high (greater than 2000) IgG titers against the EBNA-1 antigen of Epstein-Barr virus (EBV), of these three had IgM titers further supporting viral reactivation. One showed a normal IgG titer, yet with a significantly raised IgM titer.

Acquired Immunodeficiency Syndrome↗