Biomedical subjects
Publications and source records attributed to W Vogel.
We report a variant of "guided exposure to mourning," designed for use with patients who have proved resistant to other treatments for unresolved, morbid grief. The work provides some indication as to when such behavioral techniques for resolution of morbid grief are likely to prove successful, and when not.
The pharmacokinetics, toxicity and biological effects of subcutaneous and intramuscular treatment of cancer patients with recombinant tumour necrosis factor alpha (rTNF-alpha) was investigated. 17 patients suffering from refractory malignant disease were treated with either 1.0 micrograms/m2, 10 micrograms/m2 or 100 micrograms/m2 rTNF-alpha. Vital signs, peripheral blood cell counts, TNF and interferon (IFN) gamma serum levels, neopterin, beta 2-microglobulin, C reactive protein (CRP) and cortisol levels were measured immediately before and 2, 12, 24, 48 and 168 h after the first administration of rTNF-alpha. Tumour response was evaluated after 4 and 12 weeks of treatment. The pharmacokinetics followed the same characteristics as those reported for other cytokines. Major toxicities were dose dependent and comprised fever, constitutional symptoms and hypotension. TNF dependent changes were observed in serum levels of IFN-alpha, CRP, neopterin, beta 2-microglobulin, cortisol and white blood cell counts. No objective tumour response was observed. This study indicated that rTNF-alpha administered subcutaneously or intramuscularly results in measurable TNF serum levels, significant toxicity and biological response in absence of clinical efficacy in patients with advanced cancer.
Cellular differentiation processes along with formation of extracellular matrix proteins were investigated in methylcholanthrene-induced murine rhabdomyosarcomata. We used primary tumours, allotransplants in nude mice, and the respective tumour recurrences generated by repeated incomplete surgical tumour removal. The expression of the differentiation markers desmin and myoglobin as well as the presence of fibronectin and laminin was ascertained by immunohistochemical methods. The question arises, whether or not correlations between the grade of cellular differentiation (desmin, myoglobin) and extracellular matrix formation (fibronectin, laminin) exist in tumours with striated muscle cell differentiation. The constant relations between cellular differentiation and matrix formation in original tumours also applied to allotransplants and tumour recurrences in which partially modulations of differentiation in comparison with original tumours could be recognized.
Although cachexia is a common feature of cytomegalovirus infection, little is known about its cause. To explore any contributory role that tumour necrosis factor-alpha (TNF) might have the serum concentrations of TNF in eight patients who developed CMV disease after liver transplantation were investigated. All patients exhibited pronounced and long lasting increases in TNF serum concentrations. Increased endogenous TNF concentrations were associated with weight loss and anorexia. In contrast, liver transplant recipients without CMV disease showed no weight loss.
The author recalls his experiences as an attendant at a state mental hospital in the early 1950s, before the introduction of psychotropic drugs. State hospitals of that era served not only as treatment centers for mentally ill patients but also as de facto nursing homes, retirement homes, orphanages, and shelters for chronic physically ill persons, medically ill poor people and wards of the state, adults and juveniles convicted of crimes, behaviorally disturbed retarded people, and alcoholics. The author argues that the deinstitutionalization movement removed an important, if unrecognized, source of palliative care for dispossessed individuals and recommends redesigning the state hospital to provide compassionate housing and treatment by trained persons for homeless and chronic physically and mentally ill individuals. Four patients typical of the heterogenous population of state hospitals in the 1950s are described.
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The lung was investigated as a matrix for transplanted hepatocytes in the rat model. Surgically induced fulminant hepatic failure was successfully treated by injection of 5 to 7 x 10(7) isolated hepatocytes into the pulmonary parenchyma in 86% of the animals. No animal, however, survived injection of hepatocytes into the jugular vein. It was found that liver failure is a prerequisite for the intrapulmonary survival of hepatocytes. After regeneration of the native liver, the majority of hepatocytes are cleared away within 6 months.
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We describe the use of different reporter groups in visualizing replication patterns on metaphase chromosomes after BrdU incorporation by the BrdU antibody technique for the electron microscope. There is an inverse correlation between the density of the label and the size of the reporter particles. This observation alludes to stereo problems interfering with the access of the labeled antibodies into the chromatin. The use of silver enhancement enables easy detection of 1-nm and 5-nm gold particles, which make replication patterns visible in the electron microscope as does the diaminobenzidine/H2O2 reaction. Possible consequences for the demonstration of replication patterns and for nonradioactive DNA in situ hybridization are discussed.
A psychomotor-retarded infant with minor dysmorphic signs and a karyotype 46,XY,r(21)mat in lymphocytes is reported. The mother is phenotypically normal but shows the same unstable r(21). This is another case demonstrating that a chromosomal aberration does not necessarily lead to infertility by meiotic failure. Nevertheless, segregation of ring chromosomes is problematic for two reasons: mitotic problems of the ring structure itself and synaptic difficulties during the pachytene stage.
The frequency and distribution of chiasmata and the nature of terminal "associations" was re-examined in Syrian hamster spermatocytes using the 5-bromo-2'-deoxyuridine (BrdU) antibody technique (BAT) for differential chromatid labelling. Differential chromatid substitution was achieved by BrdU incorporation at the penultimate pre-meiotic S-phase followed by one of three different staining protocols: (i) fluorescence plus Giemsa (FPG), (ii) acridine orange staining or (iii) BAT. For analysis of chiasmata frequency and localization in the diplotene/diakinesis stages the resolution of FPG and acridine orange staining was comparable to that of BAT. In metaphase II chromosomes BAT was more informative than FPG and acridine orange staining and revealed small, terminal crossover exchanges. This finding proves that many terminal associations of meiotic chromosomes actually represent chiasmata at the end of the first meiotic division. Some crossover exchanges were localized in the constitutive heterochromatin of autosomes. Using BAT we also detected crossover exchanges in close vicinity to each other. This observation is reminiscent of the fact that crossing over interference means a reduction in frequency and does not imply total inhibition.
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Plasma membrane fluidity of intact peripheral blood lymphocytes (PBL) of phenytoin-treated nonepileptic patients and phenytoin-treated CD4+ lymphoid cells H9 and K37 was determined by fluorescence anisotropy measurements. Anisotropy values of the membrane probe 6-(9-anthroyloxy) stearic acid were decreased in all cell types as compared with controls, indicating increased plasma membrane fluidity of phenytoin-treated cells. Specific binding of 125I-labeled vasoactive intestinal peptide (VIP) to its cellular receptor CD4 on PBL was decreased in PBL of phenytoin-treated patients as compared with untreated, healthy subjects. Adsorption of a different ligand to the CD4 receptor on PBL, the human immunodeficiency virus type 1 (HIV-1), was likewise abolished to PBL of phenytoin-treated patients and phenytoin-treated CD4+ H9 and K37 cells, as assessed by indirect immunofluorescence. Subsequent HIV-1 infection of phenytoin-treated H9 and K37 cells was reduced as measured by indirect immunofluorescence and p24 antigen production. These data indicate that CD4 receptor availability for VIP and HIV-1 was reduced in phenytoin-treated cells. Using the DNA-specific dye Hoechst 33258, we examined cell cycle phase distributions of HIV-1 adsorbing and nonadsorbing H9 cells, as separated by flow cytometry. The majority of HIV-1 adsorbing cells were found to be in the G2/M phase, while nonadsorbing cells were mainly in the G0/G1 phase, during which plasma membrane fluidity is supposed to be increased. This study indicates that plasma membrane fluidization by phenytoin may serve to disrupt CD4 receptor function and emphasizes the impact of plasma membrane properties on HIV-1 adsorption and infection.
Thirty patients with chronic non-A, non-B hepatitis (24 male, six female; median age 38 years, range: 15-68 years) were treated with recombinant interferon alfa-2b for 1 year. Treatment was started with 5 million units interferon alfa-2b daily for 2 weeks followed by 2 million units daily for another 2 weeks. Further doses were titrated according to alanine aminotransferase values. After 1 year, treatment was stopped and a follow-up biopsy was obtained. Thereafter, patients were followed for 6 months. Of the 24 patients who completed the 1-year treatment period, 14 (58%) had normal alanine aminotransferase values at the end of the study, eight of whom showed transient increases while on treatment. In another seven (29%), alanine aminotransferase levels decreased by more than 50% of pre-treatment values but remained above the normal range. Biopsies at the end of treatment showed a complete disappearance of inflammatory activity in four and a marked improvement in eleven other patients. The results of this study indicate that a 1-year treatment with recombinant interferon alfa-2b of patients with non-A, non-B hepatitis was very effective at normalizing or improving serum transaminases and liver histology. However, the overall relapse rate was 57%, with relapse occurring in a greater proportion of patients with temporary breakthroughs during therapy (requiring dosage increase), and particularly of patients with only a partial response to treatment (serum transaminases decreased by greater than or equal to 50%). Thus, further studies are needed to establish the optimal dose and duration of treatment to induce a complete resolution of the disease.
In patients with hypertensive fundus changes considerable morphologic changes of the entire vascular system may be assumed. In the present study, the effects of these processes on the partial oxygen pressure of the skeletal musculature were investigated in 62 patients via a macro puncture electrode placed in the tibial muscle. The extent of fundus changes and the reduction in muscular partial oxygen pressure were found to be correlated. With advancing stages of fundus changes, blood flow measured in the common carotid artery decreased. Vascular changes which are clearly recognizable in the hypertensive fundus thus appear to be accompanied by a deterioration in partial oxygen pressure in muscular tissue and restriction of flow in the macrocirculation.
Based on a preliminary structural model of cyclodextrin glycosyltransferase from Bacillus circulans (EC 2.4.1.19), Ser428 and Ser475 of the enzyme were mutated to cysteines in order to produce suitable heavy atom derivatives. Mutant Ser475----Cys could not be expressed as protein. Mutant Ser428----Cys was expressed in Escherichia coli and purified. It crystallized isomorphously and gave rise to a mercury derivative that improved the electron density map. The structural results show that the new mercury-binding site is in a pocket at the protein surface.