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Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

At least 19 recordsLinked to original sources
PubMed2006

Altered glucose metabolism in childhood pre-B acute lymphoblastic leukaemia.

The cells of solid tumours are known to have an altered metabolism, with high rates of glucose uptake and glycolysis, which results in the excessive production of lactate. To date there has been no definitive research documenting metabolic changes in acute lymphoblastic leukaemia (ALL) cells. In order to investigate whether ALL cells have an altered metabolism, we initially compared the transcriptional profiles of 22 specimens from paediatric patients diagnosed with ALL to five CD34+ specimens isolated from bone marrow, which was verified in an independent cohort of 101 specimens. Profiling revealed the upregulation of genes facilitating glycolysis in the ALL specimens compared to the CD34+ specimens, while those involved in the tricarboxylic acid cycle were downregulated. Functional studies supported the microarray findings threefold: (1) higher expression of the glucose transport protein glucose transporter 1 in ALL compared to CD34+ specimens, (2) the excessive production of lactate in ALL cell lines and (3) sensitivity of ALL cell lines to the glycolysis inhibitor 2-deoxy-D-glucose. While metabolic alterations have been well documented in solid tumours, this is the first study to provide direct evidence for the existence of metabolic changes in the leukaemic cells of ALL patients. The finding offers new options for targeted therapy for ALL patients.

Antigens, CD34↗
PubMed2006

The Calibration Kit Spectral Fluorescence Standards--a simple and certified tool for the standardization of the spectral characteristics of fluorescence instruments.

With the Calibration Kit Spectral Fluorescence Standards BAM-F001-BAM-F005, we developed a simple tool for the characterization of the relative spectral responsivity and the long-term stability of the emission channel of fluorescence instruments under routine measurement conditions thereby providing the basis for an improved comparability of fluorescence measurements and eventually standardization. This first set of traceable fluorescence standards, which links fluorescence measurements to the spectral radiance scale in the spectral range of 300-770 nm and has been optimized for spectrofluorometers, can be employed for different measurement geometries and can be adapted to different fluorescence techniques with proper consideration of the underlying measurement principles.

Calibration↗
PubMed2006

Fluorescence spectroscopic studies on plasma-chemically modified polymer surfaces with fluorophore-labeled functionalities.

Molecular engineering of polymer surfaces that includes the attachment of functional molecules to existing or previously generated reactive chemical groups like e.g., -OH, -NH2, or -CHO requires simple strategies and tools for the controlled generation of surface functionalities and their derivatization as well as for their identification and eventually quantification. Here, we systematically investigate the plasma-chemical surface modification of polypropylene films in combination with dansyl labeling chemistry and conventional, yet costly, XPS and highly sensitive fluorescence spectroscopy for the detection of surface groups. Based on these results, the potential of and requirements on the fluorometric characterization and quantification of surfaces functionalities are discussed.

Fluorescent Dyes↗
PubMed2006

Association of Jacobsen syndrome and bipolar affective disorder in a patient with a de novo 11q terminal deletion.

We report on a young woman with Jacobsen syndrome (JBS) who was admitted to our psychiatric department because of a bipolar affective disorder (BPAD). Chromosome analysis was performed due to the fact that she had mental retardation, short stature, and subtle facial anomalies. A deletion of the distal long arm of chromosome 11 was found. A detailed mapping of the deletion breakpoint by quantitative real time PCR revealed a true terminal 11q deletion of approximately 8 Mb corresponding to the karyotype 46,XX,del(11)(q24.2). Polymorphic DNA marker analysis showed that the deletion is located on the paternal chromosome. Additionally, laboratory investigations revealed a low platelet count and magnetic resonance imaging of the brain showed white matter T2 hyperintensities in frontotemporal regions, which are unlikely to result from a demyelinating process as indicated by localized proton magnetic resonance spectroscopy. To our knowledge, this is the first report describing a BPAD in a case with JBS.

Abnormalities, Multiple↗
PubMed2006

[Migrant patients in forensic psychiatry. An epidemiological survey from Baden-Württemberg].

The treatment of mentally ill migrants is being increasingly discussed in general psychiatry and psychotherapy. Most studies show that this group under-utilizes the mental health system. This first epidemiological survey of the German forensic system shows a higher percentage of migrant patients than in the general population. Reasons for this development are discussed. In clinical practice, the migrant patients require special therapeutic and pedagogic options including specific legal advice.

Crime↗
PubMed2006

[The process of deinstitutionalization in German State Mental Hospitals. Critical overview of empirical research studies].

The process of discharging previously long-term hospitalized patients from German state mental hospitals, and of transferring these patients to other forms of supported housing has meanwhile come to its end. Therefore, this paper presents an overview of the scientific evaluation of this process. By using clearly defined research methodological criteria, eight empirical studies from several German federal states are assessed focusing on the meaningfulness of their results. Because of the heterogeneity of the aims regarding contents of this transformation process, of the research methodological approaches, and of the characteristics of the assessed patient groups, only few general results could be identified. Chronically mentally ill patients (mostly suffering from schizophrenic disorders) who had been successfully discharged to the community were younger, and showed shorter periods of illness and hospitalization than control patients. After discharge they might have experienced positive changes of their objective and subjective quality of life and of their perceived needs of care. Referred to several other outcome domains, no homogeneous tendencies concerning clinically relevant improvement or deterioration were found. In particular, changes related to psychopathological symptoms and social competencies were generally small. However, mortality and re-hospitalization rates of de-hospitalized patients were considerably high, and ranged between 3-24 %, and 4-46 %, respectively. The assessed studies could not identify replicated predictors of successful de-hospitalization. Female sex and long-term last hospitalization seemed to be important for stable placement in forms of supported housing requiring a higher level of autonomy. From the generally unclear procedural quality of the German deinstitutionalization process, the authors deduce implications for the scientific evaluation of future projects of restructuring mental health care services. Besides the clear definition of empirically assessable aims which should be based on theoretical considerations, it is of utmost priority to guarantee high performance quality of research methodological standards.

Adult↗
PubMed2006

Preliminary evidence of FABP2 A54T polymorphism associated with reduced risk of type 2 diabetes and obesity in women from a German cohort.

The T54 variant of the FABP2 gene has shown an association with the insulin resistance syndrome in some, but not all, studies. Here, we tested the hypothesis that the association between FABP2 A54T genotype and type 2 diabetes (T2DM) is confounded by body mass index (BMI) and is different between the two genders. 192 incident cases of T2DM and 384 sex- and age-matched controls were taken from the EPIC-Potsdam study cohort. Logistic regression analyses revealed that BMI was a strong confounder for diabetes risk association among women. When adjusted for BMI, the homozygous T54 variant was significantly associated with reduced risk of T2DM in women (OR = 0.24, 95 %CI: 0.07 - 0.82), but not in men in the co-dominant inheritance model. Accordingly, HbA (1c) values were significantly lower in women carrying two T54 alleles with BMI regarded as covariate. While accounting for potentially confounding effects, linear trends of increased BMI and leptin values were observed in women according to the presence of T54 alleles. The interaction term (p = 0.04) of continuous BMI and T54-coding genotypes suggested that the T54 variant is an effect-modifier for BMI in females. We conclude that the T54 allele of FABP2 A54T is associated both with higher BMI and reduced risk of T2DM in women from the German EPIC-Potsdam study.

Adult↗
PubMed2006

Evaluation of the epidermal refractive index measured by optical coherence tomography.

BACKGROUND/AIMS: It has recently been proposed that the refractive index (RI) measured by means of optical coherence tomography (OCT) may be a valid measure for hydration of skin. In this pilot study, using OCT in vivo, we aimed to investigate the interday variability of RI measurements and acute changes of RI following the application of a moisturizer. METHODS: Twenty healthy Caucasian volunteers were investigated on their forearms using a commercially available OCT system (SkinDex 300, ISIS optronics GmbH, Mannheim, Germany) fitted with an integrated algorithm for the evaluation of the RI. The interday repeatability of the OCT method was determined performing symmetrical measurements on both forearms on day 1, 5, 9, and 13. In order to investigate the acute effect of a moisturizer on RI, OCT assessments were performed before and 10 min after the application of an aqueous lotion with a lipophilic phase. As a control, the contralateral site was investigated in the same way, except for the use of distilled water instead of the lotion. RESULTS: Assessments of interday variability revealed insignificant (P>0.05) variances between the four measurement times as expressed in very small repeatability coefficients (right arm: 0.039; left arm 0.053) and small coefficients of variance (right arm: 1.02%; left arm: 1.38%). With regard to the RIs measured over time, we could not observe significant (P>0.05) differences between the two symmetrical anatomic sites (mean+/-SD of RI: 1.3893+/-0.0142 (right arm); 1.3875+/-0.0192 (left arm)). The acute effect of the moisturizer was indicated by a significant decrease of the RI 5 min after the application of the lotion (1.399+/-0.01 vs. 1.387+/-0.02; difference between means: 0.012; P=0.033; 95% confidence interval: 0.001-0.0023). However the control site treated with distilled water did not show significant differences between the two measurement times (1.387+/-0.013 vs. 1.391+/-0.023; difference between means: -0.004; P=0.57; 95% confidence interval: -0.019-0.011). CONCLUSIONS: In this pilot study, we have demonstrated that RI evaluation via OCT is a promising technique that may be used for the assessment of skin hydration in vivo. However, the direct comparison of OCT with standard methods, ideally such as nuclear magnetic resonance spectroscopy, is necessary.

Adult↗
PubMed2006

The European standard for sun-protective clothing: EN 13758.

Clothing is considered one of the most important tools for sun protection. Contrary to popular opinion, however, some summer fabrics provide insufficient ultraviolet (UV) protection. The European Committee for Standardization (CEN), has developed a new standard on requirements for test methods and labelling of sun-protective garments. This document has now been completed and is published. Within CEN, a working group, CEN/TC 248 WG14 'UV protective clothing', was set up with the mission to produce standards on the UV-protective properties of textile materials. This working group started its activities in 1998 and included 30 experts (dermatologists, physicists, textile technologists, fabric manufacturers and retailers of apparel textiles) from 11 European member states. Within this working group, all medical, ethical, technical and economical aspects of standardization of UV-protective clothing were discussed on the basis of the expertise of each member and in consideration of the relevant literature in this field. Decisions were made in consensus. The first part of the standard (EN 13758-1) deals with all details of test methods (e.g. spectrophotometric measurements) for textile materials and part 2 (EN 13758-2) covers classification and marking of apparel textiles. UV-protective cloths for which compliance with this standard is claimed must fulfill all stringent instructions of testing, classification and marking, including a UV protection factor (UPF) larger than 40 (UPF 40+), average UVA transmission lower than 5%, and design requirements as specified in part 2 of the standard. A pictogram, which is marked with the number of the standard EN 13758-2 and the UPF of 40+, shall be attached to the garment if it is in compliance with the standard. The dermatology community should take cognizance of this new standard document. Garment manufacturers and retailers may now follow these official guidelines for testing and labelling of UV-protective summer clothes, and the sun-aware consumer can easily recognize garments that definitely provide sufficient UV protection.

European Union↗
PubMed2006

Epidermal thickness assessed by optical coherence tomography and routine histology: preliminary results of method comparison.

BACKGROUND: Optical coherence tomography (OCT) is a promising non-invasive imaging technique for studying the epidermis and upper dermis in vivo. As proposed previously by Welzel et al. (J Am Acad Dermatol 1997; 37: 958-963), distance measurements between the entrance peak and the second peak of the A-scan seem to correspond to epidermal thickness (ET). However, there is a lack of systematic studies comparing OCT with histology. METHODS: Sixteen healthy subjects were included in this pilot study. OCT assessments were conducted on the upper back. To determine ET by OCT, the distance between the entrance peak and the second peak of the A-scan was calculated (ET-OCT). After OCT measurement a 4 mm punch biopsy was taken on each subject from the same site previously assessed. The maximum thickness of the epidermis (ET-Histo) was determined microscopically using routine histological slices (formalin-paraffin technique, haematoxylin-eosin staining). Correlation and agreement between the two methods were assessed by means of the Pearson correlation procedure and Bland-Altman plots, respectively. RESULTS: ET-Histo was 79.4 +/- 21.9 microm, including a stratum corneum thickness of 20 +/- 12.1 microm. OCT measurements resulted in an ET of 106 +/- 15.4 microm. No correlation between ET-Histo and ET-OCT was observed (r = 0.29, P = 0.27). There was a considerable lack of agreement between histology and OCT measurements as expressed in a high bias of 26.63 microm [95% confidence interval (CI) 14.49-38.77]. Furthermore, the lower 95% limits of agreement were -18.03 microm (95% CI -37.11 to 1.05) and the upper 95% limits of agreement were 71.28 microm (95% CI 52.2-90.36) indicating that ET-OCT may be 71.28 microm above or 18.03 microm below ET-Histo. CONCLUSIONS: Our preliminary data suggest that the above-described OCT algorithm is probably not a valid measure for the evaluation of ET. The second peak of the A-scan seems not to correspond to the dermo-epidermal junction zone, but rather to fibrous structures in the upper dermis. Nevertheless, further systematic comparison studies between OCT and histology are warranted, using different OCT algorithms for ET determination and cryopreparation, which has a higher reliability than the formalin-paraffin technique.

Adult↗
PubMed2005

Cerebellar hypoplasia and quadrupedal locomotion in humans as a recessive trait mapping to chromosome 17p.

BACKGROUND: Congenital hereditary non-progressive hypoplasia of the cerebellum is a rare condition, frequently associated with other neuropathology such as lissencephaly. Clinically, the condition is associated with variable degrees of mental retardation, microcephaly, seizures, and movement disorders due to ataxia. In severe cases, patients are unable to ambulate independently, but nevertheless do use bipedal locomotion. METHODS AND RESULTS: Here we present a family with seven affected members, five of whom never learned to walk on two legs but have fully adapted to quadrupedal palmigrade locomotion. These subjects show signs of cerebellar ataxia and are mentally retarded. MRI analysis demonstrated hypoplasia of the cerebellum and the cerebellar vermis as well as a small nucleus dentatus and a thin corpus callosum but no other malformations. We show, by a genome-wide linkage scan, that quadrupedal locomotion is a recessive trait linked to chromosome 17p. CONCLUSIONS: Our findings have implications for understanding the neural mechanism mediating bipedalism, and, perhaps, the evolution of this unique hominid trait.

Adaptation, Physiological↗
PubMed2005

Long-term weight change and breast cancer risk: the European prospective investigation into cancer and nutrition (EPIC).

We examined prospectively the association between weight change during adulthood and breast cancer risk, using data on 1358 incident cases that developed during 5.8 years of follow-up among 40,429 premenopausal and 57,923 postmenopausal women from six European countries, taking part in the European prospective investigation into cancer and nutrition study. Multivariate Cox regression models were used to calculate hazard ratios according to weight change (kg), defined as the weight difference between age at enrollment and age 20 adjusted for other risk factors. Changes in weight were not associated with premenopausal breast cancer risk. In postmenopausal women, weight gain was positively associated with breast cancer risk only among noncurrent hormone replacement therapy (HRT) users (P-trend < or = 0.0002). Compared to women with a stable weight (+/-2 kg), the relative risk for women who gained 15-20 kg was 1.50 (95% confidence interval (CI) 1.06-2.13). The pooled RR per weight gain increment of 5 kg was 1.08 (95% CI 1.04-1.12). Weight gain was not associated with breast cancer risk in current HRT users, although, overall, these women experienced a much higher risk of breast cancer compared with nonusers. Our findings suggest that large adult weight gain was a significant predictor of breast cancer in postmenopausal women not taking exogenous hormones.

Adult↗
PubMed2005

easyLINKAGE-Plus--automated linkage analyses using large-scale SNP data.

UNLABELLED: We extended the original easyLINKAGE program by enabling linkage analyses for large-scale SNP data in addition to those of microsatellites. We implemented new modules for Allegro, Merlin, SimWalk, GeneHunter Imprinting, GeneHunter TwoLocus, SuperLink and extended FastSLink by automatic loop breaking and new outputs. We added conditional linkage analyses as well as multipoint simulation studies, and extended error test routines by checking for Mendelian/non-Mendelian genotyping errors and for deviations from Hardy-Weinberg equilibrium. Data can be analyzed in sets of markers, in defined centimorgan intervals and by using different allele frequency algorithms. The outputs consist of genome-wide as well as chromosomal postscript plots of LOD scores, NPL scores, P-values and other parameters. AVAILABILITY: http://www.uni-wuerzburg.de/nephrologie/molecular_genetics/molecular_genetics.htm CONTACT: tom.lindner@mail.uni-wuerzburg.de SUPPLEMENTARY INFORMATION: Supplementary information is available on the website. The current version is v4.01beta.

Algorithms↗