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Biomedical subjects

H Rössler

Publications and source records attributed to H Rössler.

At least 19 recordsLinked to original sources

Functional differentiation and selective inactivation of multiple Saccharomyces cerevisiae genes involved in very-long-chain fatty acid synthesis.

While de novo fatty acid synthesis uses acetyl-CoA, fatty acid elongation uses longer-chain acyl-CoAs as primers. Several mutations that interfere with fatty acid elongation in yeast have already been described, suggesting that there may be different elongases for medium- and long-chain acyl-CoA primers. In the present study, an experimental approach is described that allows differential characterization of the various yeast elongases in vitro. Based on their characteristic primer specificities and product patterns, at least three different yeast elongases are defined. Elongase I extends C12-C16 fatty acyl-CoAs to C16-C18 fatty acids. Elongase II elongates palmitoyl-CoA and stearoyl-CoA up to C22 fatty acids, and elongase III synthesizes 20-26-carbon fatty acids from C18-CoA primers. Elongases I, II and III are specifically inactivated in, respectively, elo1, elo2 and elo3 mutants. Elongases II and III share the same 3-ketoacyl reductase, which is encoded by the YBR159w gene. Inactivation of YBR159w inhibits in vitro fatty acid elongation after the first condensation reaction. Although in vitro elongase activity is absent, the mutant nevertheless contains 10-30% of normal VLCFA levels. On the basis of this finding, an additional elongating activity is inferred to be present in vivo. ybr159Delta cells show synthetic lethality in the presence of cerulenin, which inactivates fatty acid synthase. An involvement of FAS in VLCFA synthesis may account for these findings, but remains to be demonstrated directly. Alternatively, a vital role for C18 and C20 hydroxyacids, which are dramatically overproduced in ybr159Delta cells, may be postulated.

3-Oxoacyl-(Acyl-Carrier-Protein) Reductase↗

Buprenorphine versus methadone maintenance treatment in an ambulant setting: a health-related quality of life assessment.

BACKGROUND: To compare the effects on quality of life (QOL) of oral methadone with sublingual buprenorphine. METHODS: We performed an open-label, non-randomized, two-site (methadone-buprenorphine) study. During 6 months we assessed the quality of life status of 53 opioid-dependent patients admitted to a methadone or buprenorphine maintenance programme using the German version (Berlin Quality of Life Profile) of the Lancashire Quality of Life Profile. Physical symptoms were measured using the Opioid Withdrawal Scale. Five hundred and thirty urine screening tests were carried out randomly to detect additional consumption. RESULTS: Sixty-seven opioid-dependent subjects (38 on methadone and 29 on buprenorphine) were enrolled in the study, and 53 completed it (30 subjects treated with buprenorphine and 23 subjects with racemic methadone). The subjects were comparable on all baseline measures. At the first follow-up (week 8), the buprenorphine-maintained group showed significantly less additional consumption of opioids (P = 0.013) compared with the methadone group. Patients retained in the buprenorphine or methadone programme (week 24) showed no significant differences in all quality of life scores. At the end of the study period, the buprenorphine-maintained group showed significantly less additional consumption of opioids (P = 0.001) and cocaine (P = 0.018) compared with the methadone group. The outcome measures for withdrawal symptoms after 24 weeks of treatment with buprenorphine showed slight advantages in stomach cramps, fatigue or tiredness, feelings of coldness and heart pounding. CONCLUSIONS: These results suggest that buprenorphine treatment is as effective as methadone regarding effects on quality of life and withdrawal symptoms. Buprenorphine has the potential to reduce the harm caused by drug abuse. Further research is needed to determine if buprenorphine is more effective than methadone in particular subgroups of patients.

Adult↗

[Subjective wellbeing and somatic markers in methadone substitution. Evaluation of 61 heroin addicts].

AIM: In 61 patients with the ICD-10 diagnosis "heroin dependence" an evaluation of subjective well-being with consideration given to coexisting symptoms prior to and 4 months after initiation of methadone maintenance. METHOD: The Lancashire Quality of Life Profile and, for the clinical physical side effects, the opioid withdrawal scale proposed by Bradley and Seldenburg, were used. Additionally, urinalysis was performed. RESULTS: Statistically appreciable differences were found between the two groups in terms of drug-specific side effects, somatic satisfaction scales, and consumption of medications and co-use of addictive drugs. Further statistically evident inter-group differences were seen with regard to mental well-being. CONCLUSION: Overall, methadone maintenance leads to a rapid improvement in subjective well-being and to a relevant reduction in concurrent physical symptoms.

Adult↗

Low degree of activation of circulating neutrophils determined by flow cytometry during cardiac surgery with cardiopulmonary bypass.

BACKGROUND: Enhanced expression of adhesion molecules LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) following cardiac surgery with cardiopulmonary bypass (CPB) is held responsible for postoperative complications. Surface expression of these molecules, intracellular pH (pH(i)), and oxidative burst capacity was analyzed to test for neutrophil activation during pediatric cardiac surgery. METHODS: Blood samples were drawn from 36 patients (age: 3--16 years) 24 h preoperatively, after onset of anesthesia, after connection to CPB (CPB1, before and after passing CPB, n = 15), at reperfusion (CPB2), and up to 7 days postoperatively. Cells adhering to CPB filters were isolated (n = 11). Antigen expression, pH(i), and oxidative burst capacity on neutrophils was analyzed by flow cytometry. RESULTS: During surgery, oxidative burst capacity was at low level with a mild increase only 1 day after surgery. pH(i) was decreased throughout the surgery. Surgery induced more than 36% decrease of LFA-1 and Mac-1 expression (P < 0.03). Up to postoperative day 7, no increase of antigen expression above baseline was found. Neutrophils isolated from filters of the CPB had increased LFA-1 and Mac-1 expression (all P < 0.05). Integrin expression on neutrophils passing the CPB at CPB1 was decreased (P < 0.05). CONCLUSION: Reduced adhesion molecule expression on neutrophils may be due to selective filtration of highly adhesive cells. This, in combination with low-level oxidative burst capacity, induced by immunosuppressive cytokines (e.g., interleukin-10), reduced the neutrophil activity. Our data indicate that increased activity of circulating neutrophils cannot exclusively be held responsible for postoperative complications after surgery with CPB.

Adolescent↗

Interpretation of sputter depth profiles by mixing simulations.

The interpretation of sputter depth profiles can be simplified by use of computer simulations. Distortions caused by mixing effects and distortions caused by the information depth of the analytical method have to be distinguished. Atomic mixing and the information depth distort the depth profile simultaneously. Therefore, it is necessary to take into consideration a superposition of both distortion effects. The sputtering of a GaAs/A1As multilayer has been calculated on a personal computer with the binary collision approximation code T-DYN by Biersack and with an own layer model. A new computer code LAMBDA has been used for the investigation of the influence of the AES information depth in addition to atomic mixing and preferential sputtering. A comparison of the calculated and the measured depth profile explains the observed effects. Therefore conclusions can be drawn about the original elemental distribution in the sample from the measured depth profile.

Journal Article↗

Simulation of sputter-induced roughness for depth profiling of thin film structures.

Sputtering induced surface roughening is the dominant factor that degrades depth resolution in sputter profiling of polycrystalline film samples. Due to the dependence of the sputtering yield on the crystallographic orientation, ion beam incidence angle and composition, the local sputtering rate differs from grain to grain. A simple computer program based on a model of Marton and Fine can simulate such a roughness development within one layer, an improved version can even be applied for interfaces. A further extension of the program using a model of Hauffe includes effects like shadowing and enhanced peak erosion leading to surface smoothing.

Journal Article↗

Serum concentrations of circulating endogenous granulocyte-macrophage colony-stimulating factor in HIV-1-seropositive injecting drug users.

OBJECTIVES: We compared serum concentrations cytokines in seronegative and seropositive HIV-I intravenous drug abusers. METHODS: The cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and the immune activation markers soluble interleukin-2 receptor (sIL-2R) and neopterin were determined in sera of HIV-1-seropositive and HIV-1-seronegative injecting drug users (IDUs). RESULTS: HIV-1-seropositive IDUs showed significantly lower serum concentrations of GM-CSF (p = 0.0064) and significantly higher concentrations of neopterin (p = 0.0005) than HIV-1-seronegative IDUs. All HIV-1-seropositive IDUs had neopterin levels above the normal range. Levels of TNF-alpha in HIV-1-seronegative IDUs did not differ from HIV-1-seropositive IDUs. Increased levels of IL-1 beta were found in 83.3% HIV-1-seronegative and in 94.4% HIV-1-seropositive IDUs with no significant difference between the two groups. An increase of serum levels of sIL-2R was found in 60% HIV-1-seronegative and in 63.6% HIV-1-seropositive IDUs. Again, no difference was found between the two groups. Neopterin concentrations correlated with TNF-alpha in HIV-1-seropositive as well as in HIV-1-seronegative IDUs, neopterin concentrations correlated with sIL-2R only in the HIV-1-seropositive IDUs. No correlations were found for GM-CSF. CONCLUSIONS: An impaired production of GM-CSF may contribute to the loss of the myelopoetic progenitor cells and to the functional abnormalities of leukocytes associated with HIV-1 infection. Injecting drug use contributes to the levels of immune activation markers, therefore their use in HIV-1 infection may be limited in IDUs. However, neopterin remains a useful marker for HIV-1 infected IDUs.

Adult↗

Methadone-substitution and driving ability.

A general statement about the driving ability of HIV-positive as well as HIV-negative addicts undergoing methadone-substitution treatment cannot be made with certainty. Even isolated observations are not significant; only an individually performed assessment, free of prejudice and conscientiously done is decisive. The formal assertion that addiction equals driving-inability, which is largely practised at present, is inadmissible and therefore harmful to the therapeutic efforts for rehabilitation.

Austria↗

A survey of drug deaths in western Austria.

We evaluated the drug deaths in western Austria during the period from 1981 to 1991. The increase of fatal cases is partly due to a change in statistical methods and the definition of 'drug victims'. In this paper a survey is given concerning the drug deaths investigated forensically and toxicologically in our area of responsibility.

Adolescent↗

[Fatalities in drug-dependent patients. A critical analysis].

The disquieting increase in the mortality of drug addicts observed in recent years cannot be ascribed to only one or a few well defined causes, such as the spread of the HI virus or AIDS, changes in drug consumption habits of multiple dependents or ineffective therapeutic measures. Primarily, an interaction of medical, social and psychological causes is emerging. In a well-defined addict population, 35 deaths of intravenous drug users were registered in the period 1987-1990. By comparison, 7 deaths were recorded in the same geographical area between 1983 and 1986. A report of the UN Commission on Narcotic Drugs shows that in Western Europe, mortality in this high-risk group has doubled annually in the past few years.

Acquired Immunodeficiency Syndrome↗

Trends in HIV infection among intravenous drug users in Innsbruck, Austria.

The first HIV test among intravenous drug users (IVDUs) at the AIDS clinic and/or the drug dependency clinic of the University of Innsbruck was the basis for the calculation of the proportions of those testing HIV seropositive annually over the period 1985-1990. The numbers testing HIV seropositive at the drug dependency clinic declined drastically, from 72.2% in 1985 to 12.5% in 1990 (chi 2 = 29.62, p less than 0.0001), whereas they rose at the AIDS clinic during this period, from 48.4% to 100% (chi 2 = 5.82, p = 0.016). Overall 132 of the 268 (49.2%) individuals examined tested HIV seropositive. There were 102 individuals of the original 146 seronegative IVDUs who were retested, for an overall incidence rate of HIV seroconversion of 5.8/100 persons-years. Risk of seroconversion was associated with a steady sexual partnership with an HIV seropositive IVDU and with an age of less than or equal to 25 years at study entry (13.1 versus 8.7/100 persons-years). No seroconversions occurred in the subgroup of patients treated by the methadone maintenance treatment program. The cumulative incidence (Kaplan-Meier) rate for HIV seropositivity after 64 months was 22%, lower than the proportions testing HIV seropositive found in 1985 at each of the two clinics, which suggests that the speed of the spread of the epidemic of HIV infection among IVDUs has slowed in our region. Counseling of IVDUs should emphasize the risks of sexual acquisition, particularly among persons with steady relationships who may not perceive their risk.

Adult↗

Expression of env sequences of the bovine leukemia virus (BLV) in the yeast Saccharomyces cerevisiae.

DNA sequences of the envelope (env) gene of the bovine leukemia virus (BLV) were expressed in the yeast Saccharomyces cerevisiae. Two yeast promoters, the repressible PHO5 promoter and the constitutive PGK promoter, were used to construct four expression plasmids comprising either a sequence of the surface antigen gp51 or a (gp51 + gp30) sequence. The expressed heterologous gene products were characterized by Western blot analysis and competitive radioimmunoassay. By means of Northern blot analysis the steady-state level of env-specific mRNA was analysed. The highest expression rate was obtained from recombinant plasmid YEpSG 94 comprising a gp51 sequence--a 630 base pair fragment containing 70% of the gp51 but lacking the N terminus--as well as the PHO5 promoter including PHO5 signal sequence and the PHO5 terminator. The recombinant gp51 was partially glycosylated but the PHO5 signal peptide did not seem to be cleaved off. No immunoreactive material could be found in the periplasm or in the culture medium. By means of monoclonal antibodies directed against eight different epitopes of viral gp51, all four sequential antigenic determinants were detected in the AH 216 (YEpSG 94) expression product.

Amino Acid Sequence↗

Single photon emission computed tomography in AIDS dementia complex.

Single photon emission computed tomography (SPECT) studies were performed in AIDS dementia complex using IMP in 12 patients (and HM-PAO in four of these same patients). In all patients, SPECT revealed either multiple or focal uptake defects, the latter corresponding with focal signs or symptoms in all but one case. Computerized tomography showed a diffuse cerebral atrophy in eight of 12 patients, magnetic resonance imaging exhibited changes like atrophy and/or leukoencephalopathy in two of five cases. Our data indicate that both disturbance of cerebral amine metabolism and alteration of local perfusion share in the pathogenesis of AIDS dementia complex. SPECT is an important aid in the diagnosis of AIDS dementia complex and contributes to the understanding of the pathophysiological mechanisms of this disorder.

Acquired Immunodeficiency Syndrome↗

[Results of testing tumor resistance (in vitro--in vivo) in breast cancer].

In-vitro sensitivity to cytostatics was tested in 281 carcinomas of the breast using the test method introduced by Volm. The Adriamycin 3H-uridine test system was chosen for the analysis. Altogether, 84.7% of the tumors were testable. A correlation with the subsequent in-vivo result was found in 219 of the breast cancer patients. Only 8% of the breast cancers were unequivocally sensitive to the test (uridine incorporation rate less than 55% for verification). The mean uridine incorporation rate was 577 CPM. Neither tumor size, lymph node status, nor the estrogen and progesterone receptor content of the tumor cells influenced the test result. With regard to the breast carcinoma, no relationship was found between the predictive information and the subsequent in-vivo response to chemotherapy. This applied to both short-term observation periods of three to six months as well as longer-term follow-ups. Furthermore, no connection was found between sensitivity in vitro and probability of recurrence (p = 0.69) under cytostasis. Probability of survival was higher among patients with tumors that were not sensitive to the test than among those with tumors which were (p less than or equal to 0.001). In the authors' experience the Volm chemosensitivity test only appears to furnish prognostic information about the breast carcinoma; in the light of their data the test appears rather unsuitable as an aid to deciding whether or not to institute cytostatic therapy.

Antineoplastic Agents↗

Immune status of drug abusers.

This study followed 184 drug abusers. Examined in all of them were urinary neopterin levels, HBV, SGOT, and Luestest. Seventy-three percent of IV drug addicts showed elevated neopterin levels reflecting activated cellular immunity. Statistically, no correlation of neopterin levels with, eg, excessive alcohol consumption, duration of drug abuse, or studied laboratory parameters was found. Individuals using cocaine revealed higher neopterin levels than those not doing so. Twenty-one of twenty-two patients with no parenteral drug use had normal neopterin excretion. In 34 drug detoxification patients, we examined in addition: T-lymphocyte subsets (T4/T8 ratio) and serum neopterin levels. Thirty-eight of ninety-four parenteral drug addicts presented with anti-LAV/HTLV-III antibodies (ELISA + Western blot + IFT). Our data demonstrate an activated cellular immune status in parenteral drug addicts that cannot be attributed to LAV/HTLV-III infection in all cases. The development of AIDS seems to depend not only on the exposure to LAV/HTLV-III but also on activated cellular immunity, which is easily assessed by neopterin measurement.

Antibodies, Viral↗