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Biomedical subjects

Bernhard Weber

Publications and source records attributed to Bernhard Weber.

At least 19 recordsLinked to original sources
PubMed2006

[Blood glucose in chronic schizophrenic patients treated with antipsychotics].

OBJECTIVE: There is some evidence that the treatment with new ("atypical") antipsychotics is associated with a higher frequency of type 2-diabetes mellitus. AIM: In this study the blood glucose levels of consecutively admitted inpatients with chronic schizophrenia were investigated. METHODS: The base blood glucose levels of 177 consecutively admitted chronic schizophrenic patients were evaluated. RESULTS: After long-term treatment (mean duration: 17.8 +/- 8.7 years [range 5 - 44 years]) 24.3 % of the investigated patients showed elevated base blood glucose levels (> or = 126 mg/dl). The proportion of patients with elevated blood glucose levels among the schizophrenic patients treated with antipsychotics was significantly higher than the proportion of diabetics in the corresponding age groups in the general population. The comparison of different groups of antipsychotics revealed that those patients treated with conventional neuroleptics and non-dibenzodiazepine derivates (i. e. risperidone) had a lower risk of developing diabetes mellitus than those also receiving dibenzodiazepine derivates (like clozapine, olanzapine). CONCLUSION: Our data showed that schizophrenic patients treated with antipsychotics 5 years or longer had elevated blood glucose levels more frequently than the general population.

Adult↗
PubMed2006

[Dyslipidemia and schizophrenia].

OBJECTIVE: There is some evidence that the treatment with new ("atypical") neuroleptics is associated with a higher frequency of hyperlipidemia. AIM: In this study the serum lipid levels of patients with chronic schizophrenia were investigated. METHODS: The serum lipid levels of 177 consecutively admitted schizophrenic patients treated at least 5 years were evaluated. RESULTS: No gender differences of lipid concentrations could be detected. A considerable rate of the patients (35.6 %) showed elevated triglycerides (> 150 mg/dl) or elevated cholesterol levels (> 200 mg/dl; 43.9 %). The rate of patients with elevated cholesterol or triglyceride concentrations is associated with the duration of treatment. The comparison of different groups of neuroleptics yielded at best a trend to higher triglyceride levels in the patients treated with dibenzodiazepines compared to those receiving only classical neuroleptics. The triglyceride concentrations correlated with the body mass index (rho = 0.25, p < 0.01). CONCLUSIONS: This study revealed evidence for an association of the rate of patients with elevated lipid levels and duration of neuroleptic treatment in schizophrenia patients.

Adult↗
PubMed2006

Bacterially expressed and optimized recombinant Phl p 1 is immunobiochemically equivalent to natural Phl p 1.

Recombinant production in bacteria of soluble and monomeric Phl p 1, a major allergen of Timothy grass pollen, has proved to be very problematic. In order to facilitate expression and purification of this allergen, a recombinant variant was designed with a single amino acid substitution. Several comparative analyses with natural counterparts using electrophoretic and HPLC separations, together with immunological assays, demonstrated high equivalence. This is the first description of an approach aiming at an improvement of a natural like recombinant allergen.

Allergens↗
PubMed2006

Development of a rating scale to predict the severity of alcohol withdrawal syndrome.

AIM: Various factors that may influence the severity of the alcohol withdrawal syndrome (AWS) have been identified. We tested the predictive value of these factors compiled in a newly developed scale, LARS (Luebeck alcohol withdrawal risk scale). METHOD: A total of 100 individuals (81 males, 19 females, mean age: 47.6 +/- 9.9 years) consecutively transferred to inpatient detoxification were included in this prospective study. All fulfilled the ICD-10 criteria for alcohol dependence. The LARS was applied at the time of admission. The course of the AWS was assessed by AWS-scale at least every 4 h. The maximum AWS-score was taken as indicator of the severity of AWS. RESULTS: The mean AWS-score(max) was 6.5 +/- 3.3. In all 20% of the patients developed a severe AWS (AWS-score(max) > or =10). The maximum score usually occurred within 36 h after the last drink. A short version, the LARS11, was developed by statistically grounded item reduction. The optimal cut-off of the LARS11 was calculated as 10. The positive predictive value for severe AWS was 76%, while the negative predictive value was 98.7%. The sensitivity and specificity were high (95 or 92.5%, respectively). CONCLUSION: LARS11 assessed immediately before detoxification appears to provide a useful estimate of mild/moderate versus severe AWS, and is now ready to be validated in an independent sample.

Alcoholism↗
PubMed2006

Bacterial fermentation of recombinant major wasp allergen Antigen 5 using oxygen limiting growth conditions improves yield and quality of inclusion bodies.

A process for bacterial expression and purification of the recombinant major wasp allergen Antigen 5 (Ves v 5) was developed to produce protein for diagnostic and therapeutic applications for type 1 allergic diseases. Special attention was focused on medium selection, fermentation conditions, and efficient refolding procedures. A soy based medium was used for fermentation to avoid peptone from animal origin. Animal-derived peptone required the use of isopropyl-beta-D-thiogalactopyranoside (IPTG) for the induction of expression. In the case of soy peptone, a constitutive expression was observed, suggesting the presence of a component that mimics IPTG. Batch cultivation at reduced stirrer speed caused a reduced biomass due to oxygen limitation. However, subsequent purification and processing of inclusion bodies yielded significantly higher amount of product. Furthermore, the protein composition of the inclusion bodies differed. Inclusion bodies were denatured and subjected to diafiltration. Detailed monitoring of diafiltration enabled the determination of the transition point. Final purification was conducted using cation-exchange and size-exclusion chromatography. Purified recombinant Ves v 5 was analyzed by RP-HPLC, CD-spectroscopy, SDS-PAGE, and quantification ELISA. Up to 15 mg highly purified Ves v 5 per litre bioreactor volume were obtained, with endotoxin concentrations less than 20 EU mg(-1) protein and high comparability to the natural counterpart. Analytical results confirm the suitability of the recombinant protein for diagnostic and clinical applications. The results clearly demonstrate that not only biomass, but especially growth conditions play a key role in the production of recombinant Ves v 5. This has an influence on inclusion body formation, which in turn influences the renaturation rate and absolute product yield. This might also be true for other recombinant proteins that accumulate as inclusion bodies in Escherichia coli.

Allergens↗
PubMed2006

[Risk factors for suicide in substance-related disorders].

OBJECTIVE: To assess the contribution of sociodemographic and psychopathologic predictors for suicide in alcohol-related disorders and in substance-related disorders in general and to examine the constellations of risk factors for suicide. METHODS: Out of 163 suicides (using psychological autopsy method) and 396 population-based control persons, 67 suicides and 67 controls with substance-related disorders (DSM-IV; alcohol-related disorders: suicides: n = 36, controls: n = 27) were assessed. RESULTS: Affective disorders, suffering from substance dependence, and low education independently predicted increased suicide risk in alcohol-related disorders as well as in substance-related disorders in general, severe nicotine consumption only in alcohol-related disorders. CONCLUSIONS: There are common risk factors for suicide in alcoholism and substance-related disorders in general. Effective suicide prevention strategies must include a focus on substance dependence as well as on affective disorders.

Adult↗
PubMed2005

Submicron positioning of single atoms in a microcavity.

The coupling of individual atoms to a high-finesse optical cavity is precisely controlled and adjusted using a standing-wave dipole-force trap, a challenge for strong atom-cavity coupling. Ultracold Rubidium atoms are first loaded into potential minima of the dipole trap in the center of the cavity. Then we use the trap as a conveyor belt that we set into motion perpendicular to the cavity axis. This allows us to repetitively move atoms out of and back into the cavity mode with a repositioning precision of 135 nm. This makes it possible to either selectively address one atom of a string of atoms by the cavity, or to simultaneously couple two precisely separated atoms to a higher mode of the cavity.

Journal Article↗
PubMed2005

Giant ragweed specific immunotherapy is not effective in a proportion of patients sensitized to short ragweed: analysis of the allergenic differences between short and giant ragweed.

BACKGROUND: Short ragweed and giant ragweed pollen allergens are considered largely cross-reactive, and it is generally believed that 1 species is sufficient for skin testing and immunotherapy. However, in the area north of Milan (a zone widely invaded only by short ragweed), about 50% of patients submitted to injection specific immunotherapy with giant ragweed showed little or no clinical response, but showed an excellent outcome if they were shifted to short ragweed specific immunotherapy. OBJECTIVE: To investigate allergenic differences between short and giant ragweed. METHODS: IgE reactivity to short ragweed of sera from 16 patients allergic to ragweed was assessed by immunoblot before and after absorption with short and giant ragweed. Moreover, 41 ragweed-monosensitive patients underwent skin prick test with both ragweed species. RESULTS: In several cases, preabsorption of sera with giant ragweed extract was unable to inhibit IgE reactivity fully against both a 43-kd allergen and other allergens at different molecular weights in short ragweed. On skin prick test, short ragweed induced larger wheals than giant ragweed in the majority of patients, and 6 of 41 (15%) patients were strongly short ragweed-positive but giant ragweed-negative. The immunoblot with the serum from 1 of these subjects showed a strong IgE reactivity to short ragweed at about 43 kd in the absence of any reactivity to giant ragweed. CONCLUSION: Short and giant ragweed are not allergenically equivalent. Allergenic differences involve both the major allergens Amb a 1-2/Amb t 1-2 and some minor allergens. In patients allergic to ragweed, both diagnosis in vivo and immunotherapy should always be performed by using the ragweed species present in that specific geographic area.

Adolescent↗
PubMed2005

Primary structure, recombinant expression, and molecular characterization of Phl p 4, a major allergen of timothy grass (Phleum pratense).

Grass pollen allergy is one of the most important allergic diseases world-wide. Several meadow grasses, like timothy grass and rye grass, contribute to allergic sensitizations, but also allergens from extensively cultivated cereals, especially rye, make a profound contribution. The group 4 allergens are well known as important major allergens of grasses. We have cloned for the first time group 4 sequences from Phleum pratense, Lolium perenne, Secale cereale, Triticum aestivum, and Hordeum vulgare, and investigated the IgE-reactivity of recombinant Phl p 4 as a candidate for allergy diagnostic and therapeutic applications.

Allergens↗
PubMed2005

Nicotine use in suicides: a case-control study.

PURPOSE: Despite of higher rates of substance-related disorders in psychiatric patients and suicides than in the general population, there is no clear specificity to the relationship between nicotine use and other psychiatric disorders for suicide risk. METHODS: One hundred and sixty-three suicides (mean age 49.8 +/- 19.3 years; 64.4% males; using psychological autopsy method) and 396 control persons (mean age 51.6 +/- 17.0 years; 55.8% males) were assessed with a standardised semi-structured interview including SCID-I and SCID-II (for DSM-IV). Suicides and controls were compared in terms of nicotine consumption and psychiatric disorders. Logistic regression was used to evaluate the interactions of tobacco consumption with psychiatric disorders. RESULTS: Suicides were significantly more often current smokers and heavy users of cigarettes (> 20 cigarettes per day; P < 0.001, each). Alcohol dependence, other axis I disorders than substance-related disorders, and cluster B personality disorder(s) remained independent predictors for suicide in both genders, current nicotine consumption only in men (OR = 2.6, 95% CI 1.3-5.2). DISCUSSION AND CONCLUSIONS: In males, but not in females, nicotine consumption contributed to risk of completed suicide after control for psychiatric disorders and has to be considered as independent risk factor for suicide.

Autopsy↗
PubMed2004

Detection of alcohol consumption in suicides.

Screening instruments for detection of alcohol consumption, abuse, and dependence for use in psychological autopsy studies with case control design are not validated. Therefore, interrater and test-retest reliability of the Luebeck Alcohol Dependence and Abuse Screening Test (LAST) and the usability of this test for the psychological autopsy method were investigated. Alcohol consumption was evaluated by a semi-structured interview including the Structured Clinical Interview for DSM-IV Axis I (SCID-I) and the LAST in 163 completed suicides (mean age 49.6 +/- 19.3 years; 64.4% men) and by personal interview in 396 population-based controls (mean age 51.6 +/- 17.0 years; 55.8% men). Of the controls, 35 were additionally assessed by interviewing informants; these results were compared with those generated by personal interview. Comparison of LAST scores by personal and informant's interview of controls generated a Spearman correlation coefficient of 0.74 (P < 0.0001). The LAST (7 item-version, cut-off of 2) revealed high sensitivity and specificity for alcohol abuse and dependence, in both controls and suicides. LAST scores were significantly associated with high, frequent, and hazardous alcohol consumption (P < 0.001) in suicides. Our findings provide support for reliability and validity of identifying individuals with alcohol dependence and abuse obtained through the best-estimate method using the LAST. This 7-item questionnaire can be recommended as a useful tool for the psychological autopsy procedure in postmortem research.

Adult↗
PubMed2004

Concordance of DSM-IV Axis I and II diagnoses by personal and informant's interview.

The validity and reliability of using psychological autopsies to diagnose a psychiatric disorder is a critical issue. Therefore, interrater and test-retest reliability of the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders and the usefulness of these instruments for the psychological autopsy method were investigated. Diagnoses by informant's interview were compared with diagnoses generated by a personal interview of 35 persons. Interrater reliability and test-retest reliability were assessed in 33 and 29 persons, respectively. Chi-square analysis, kappa and intraclass correlation coefficients, and Kendall's tau were used to determine agreement of diagnoses. Kappa coefficients were above 0.84 for substance-related disorders, mood disorders, and anxiety and adjustment disorders, and above 0.65 for Axis II disorders for interrater and test-retest reliability. Agreement by personal and relative's interview generated kappa coefficients above 0.79 for most Axis I and above 0.65 for most personality disorder diagnoses; Kendall's tau for dimensional individual personality disorder scores ranged from 0.22 to 0.72. Despite of a small number of psychiatric disorders in the selected population, the present results provide support for the validity of most diagnoses obtained through the best-estimate method using the Structured Clinical Interview for DSM-IV Axis I and Personality Disorders. This instrument can be recommended as a tool for the psychological autopsy procedure in post-mortem research.

Adjustment Disorders↗
PubMed2004

Analytical and preparative native polyacrylamide gel electrophoresis: Investigation of the recombinant and natural major grass pollen allergen Phl p 2.

Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blot are amongst the most popular methods for allergen characterization, such as comparison of recombinant allergens with their natural counterparts. Native PAGE was evaluated as a possible robust and simple method offering high-resolution capacity for characterization of the major grass pollen allergen Phl p 2. Analytical separation of recombinant Phl p 2 provided a superior quality control in terms of homogeneity and, after Western blotting, immunoglobulin E (IgE) reactivity. Separation of natural Phl p 2 identified two major isoforms which were shown to have different N-terminal sequences and IgE-binding properties. After isolation using preparative native PAGE in combination with electrodialysis, both isoforms were investigated by specific proteolysis and reversed-phase high-performance liquid chromatography (RP-HPLC). The results demonstrate differences in the primary structures and that the recombinant counterpart corresponds exactly to one isoform. Analytical and preparative native PAGE thus proved to be powerful tools for the investigation of allergen isoforms and quality control of recombinant counterparts.

Allergens↗
PubMed2004

Transition of recombinant allergens from bench to clinical application.

The cloning and production of an increasing number of allergens through the use of DNA technology has provided the opportunity to use these proteins instead of natural allergen extracts for the diagnosis and therapy of IgE-mediated allergic disease. For diagnostic purposes, it is essential that the molecules exhibit IgE-reactivity comparable with that of the natural wild-type molecules, whereas T cell reactivity and immunogenic activity may be more important for allergen-specific immunotherapy. In relation to the latter, the development of hypoallergenic recombinant allergen variants is an approach which shows great promise. Clinical application of the proteins requires that they must be produced under conditions of Good Manufacturing Practice and meet the specifications set down in the appropriate Regulatory Guidelines, principally the ICH-Guidelines. Special consideration has to be given to the choice of expression system, the design of the expression vectors, and the purification strategy to obtain a pure product free from toxins and contamination. The availability of the pure recombinant molecules provides the opportunity to formulate preparations that are free from the non-allergenic ballast proteins present in natural allergen extracts and which contain relative concentrations of the allergens in clinically appropriate proportions.

Allergens↗
PubMed2004

[Bodyweight in inpatients with schizophrenia].

OBJECTIVE: Epidemiological studies show overweight to be a major health problem in Germany. There is some evidence that psychiatric patients often are overweight. In view of the high frequency of weight gain during the treatment with neuroleptics, particularly atypicals, in this study the bodyweight of schizophrenics should be examined. METHODS: The body-mass-index (BMI) of two samples of schizophrenic inpatients was compared to BMI-data of the German general population. RESULTS: 90 inpatients with the first episode of schizophrenic psychoses showed an average BMI of 22.2 +/- 3.3. The BMI in all age groups were lower compared to the general population, but in a follow-up these patients showed a higher weight gain. 238 chronic schizophrenic inpatients with at least 5 years duration of illness (mean 15.3 +/- 8.3 years) showed BMI-values in the range of the general population. Only the age group 30 - 35 years showed a significantly higher BMI. However, in many age groups of schizophrenic inpatients the proportion of obesity (BMI > 30) was higher compared to the general population. CONCLUSIONS: The bodyweight of first episode schizophrenics is lower compared to the general population. In contrast, chronic schizophrenic patients frequently are overweight or show obesity. However, thus far the causes of pronounced weight gain in schizophrenic patients remain to be elucidated.

Adolescent↗
PubMed2003

Size exclusion chromatography as a tool for quality control of recombinant allergens and hypoallergenic variants.

Proteins or glycoproteins bearing epitopes for human IgE antibodies are designated as allergens causing type I allergic diseases. In this study, recombinant allergens were compared with their natural counterparts either as part of extracts or as purified molecules with respect to several biochemical and immunological properties. Natural and recombinant Bet v 1 and Phl p 1, major allergens of birch pollen extracts and Phleum pratense pollen extracts, were analyzed by SDS-PAGE, immunoblotting, EAST inhibition and size exclusion chromatography (SEC). Differences of IgE-binding capacities between recombinant Bet v 1 as well as recombinant Phl p 1 variants were detected by EAST inhibition. These results were confirmed by size exclusion chromatography in that the recombinant proteins showed differences of their elution volumes being equivalent to the natural molecules only with the more active recombinant form. In contrast, SDS-PAGE and immunoblot analysis resulted in divergent characteristics, as either migrations of the variants were similar or no differences of IgE binding were detectable. In conclusion, size exclusion chromatography is the method of choice for quality control of well characterized recombinant allergens, comprising control of purity, protein content and conformation.

Allergens↗
PubMed2003

Purification strategy for recombinant Phl p 6 is applicable to the natural allergen and yields biochemically and immunologically comparable preparations.

The recombinant major grass pollen allergen Phl p 6 has been expressed with a N-terminal 6 x His-tag sequence and subsequently purified using nickel-chelating Sepharose. After cleavage of the tag-sequence, a second pass over the affinity chromatography revealed that even untagged rPhl p 6 bound tightly. In order to determine if that property is typical for Phl p 6, the natural allergen was purified in the same way starting with a grass pollen extract. Indeed, nPhl p 6 could be highly enriched in one step using nickel-chelating Sepharose. In addition to this new powerful purification method, the results provide further information in that the recombinant and natural allergens share a lot of properties, since biochemical characteristics are reflected in the purification strategies. The preparations of natural and recombinant Phl p 6 were used for comparative electrophoretic, chromatographic and immunological analysis which demonstrated high similarity.

Allergens↗