Biomedical subjects

K Hoffmann

Publications and source records attributed to K Hoffmann.

At least 199 records · Page 11Linked to original sources

PubMed1996

[Subjective quality of life of patients with chronic schizophrenia].

The main results of quality of life research in sociology and social psychology and the findings of psychiatric studies on subjective quality of life are summarized. The present study examined subjective quality of life in patients with chronic schizophrenia in different treatment settings (n = 318/ICD 10:F20). The satisfaction scales of the instrument used (Berliner Lebensqualitätsprofil) are shown to have adequate consistency coefficients. Psychopathological variables accounted for more variance than demographic and illness-related characteristics and features of objective quality of life. Negative schizophrenic symptoms were not of particular concern, and anxiety/depression scores did not interact with satisfaction ratings in different settings. Two of nine domains (living situation and mental health) and the total scores showed significant differences between patients in different settings. The degree of contrast between in- and out-patients seemed to be influenced by the current length of stay of the in-patients. In addition to cross-sectional studies, there is a need for further examination of differences in subjective quality of life and in treatment effects in longitudinal studies, which should make use of panel designs.

Activities of Daily Living↗

PubMed1996

Increase of melanocytic nevus counts in children during 5 years of follow-up and analysis of associated factors.

OBJECTIVES: To investigate nevus development in childhood and to examine causative related factors such as pigment phenotype and the role of sun exposure in the development of melanocytic nevi. DESIGN AND PARTICIPANTS: Nevus counts were performed in kindergarteners (n = 866) before the age of 7 years and again 5 years later (n = 377). Eligible for analysis were 357 children who were examined twice. Possible related factors were searched for by standardized interviews with parents. RESULTS: The mean number of nevi measuring 1 mm or more was 9 in the first examination and the number measuring 2 mm or more, 4. Five years later, the mean number of nevi measuring 1 mm or more was 40 and the number measuring 2 mm or more was 16. Children with poor sun tolerance had statistically significant more nevi (relative risk, 3.7;95% confidence interval, 1.9-7.2). The presence of freckles was a strong predictor for a high increase of melanocytic nevi (relative risk, 2.1; 95% confidence interval, 1.3-3.3). The number of days per year with intensive solar exposure was an independent prognostic factor. The relative risk for the development of melanocytic nevi was increased by a factor of 1.6 in children who had more than 21 days of intensive sun exposure per year (95% confidence interval, 1.0-2.5). CONCLUSION: The development of melanocytic nevi in childhood is strongly related to characteristics of pigmentation associated with poor sun tolerance. In addition, we found evidence for the influence of UV radiation on the number of acquired melanocytic nevi in childhood.

Child↗

PubMed1996

[Advantages and limits of primary final correction of congenital abnormalities].

Complete correction of malformations in the first hour or days of life has always been the target of pediatric surgeons. The possible halt of palliative operations involving the application of stomata in the trachea, esophagus, stomach, bowels and at the diverting urinary tract is to lighten the situation for parents and neonatologists. Requirements for a definitive primary surgical correction are an accurate diagnosis and careful selection of the child. Criteria include not only age and bodyweight, but also the presence of co-existing malformations, diseases and complications. Thus it is also possible to correct complex malformations primarily in one operation and to withdraw the use of stomata.

Congenital Abnormalities↗

PubMed1996

[Problems in technical development of laparoscopy and thoracoscopy in infancy].

In neonates a new fixation of the trocars must be found since the umbilical ring is large and distensible and the abdominal wall is very thin. The pressure-controlled pneumoperitoneum is maintained by using a special "surgiflator" system which prevents high pressure peaks in the small abdominal cavity of neonates. By using a Nd:YAG laser for transection during coagulation an additional trocar can be dispensed with.

Endoscopes↗

PubMed1995

The cyclosporin A-binding immunophilin CyP-40 and the FK506-binding immunophilin hsp56 bind to a common site on hsp90 and exist in independent cytosolic heterocomplexes with the untransformed glucocorticoid receptor.

We have recently shown that hsp56, the FK506-binding immunophilin component of both the heat shock protein (hsp90.hsp70.hsp56) heterocomplex and the untransformed glucocorticoid receptor heterocomplex, is bound directly to hsp90 (Czar, M. J., Owens-Grillo, J. K., Dittmar, K. D., Hutchison, K. A., Zacharek, A. M., Leach, K. L., Deibel, M. R., and Pratt, W. B. (1994) J. Biol. Chem. 269, 11155-11161). In this work, we show that both untransformed glucocorticoid receptor and hsp90 heterocomplexes contain CyP-40, a 40-kDa immunophilin of the cyclosporin A-binding class. CyP-40 is present in both native glucocorticoid receptor heterocomplexes and receptor heterocomplexes reconstituted with rabbit reticulocyte lysate, and the presence of CyP-40 in the receptor heterocomplex is stabilized by molybdate. Immunoadsorption of hsp90 from cell lysate yields coimmunoadsorption of both hsp56 and CyP-40, showing that both immunophilins are in native heterocomplex with hsp90. However, immunoadsorption of hsp56 does not yield coimmunoadsorption of CyP-40; thus, the two immunophilins do not exist in the same heterocomplex with hsp90. Both purified CyP-40 and hsp56 bind directly to purified hsp90, and excess CyP-40 blocks the binding of hsp56, consistent with the presence of a common immunophilin binding site on hsp90. Our data also suggest that there are at least two types of untransformed glucocorticoid receptor-hsp90 heterocomplexes, one that contains hsp56 and another that contains CyP-40. The role played by the immunophilins in steroid receptor action is unknown, but it is clear that the peptidylprolyl isomerase activity of immunophilins is not required for glucocorticoid receptor-hsp90 heterocomplex assembly and proper folding of the hormone binding domain by the hsp90-associated protein folding system of reticulocyte lysate.

Animals↗

PubMed1995

Cyclosporin A potentiates the dexamethasone-induced mouse mammary tumor virus-chloramphenicol acetyltransferase activity in LMCAT cells: a possible role for different heat shock protein-binding immunophilins in glucocorticosteroid receptor-mediated gene expression.

As previously observed for FK506, we report here that cyclosporin A (CsA) treatment of mouse fibroblast cells stably transfected with the mouse mammary tumor virus-chloramphenicol acetyltransferase (MMTV-CAT) reporter plasmid (LMCAT cells) results in potentiation of dexamethasone (Dex)-induced CAT gene expression. Potentiation by CsA is observed in cells treated with 10-100 nM Dex but not in cells treated with 1 microM Dex, a concentration of hormone which results in maximum CAT activity. At 10 nM Dex, 1-5 microM CsA provokes an approximately 50-fold increase in CAT gene transcription, compared with transcription induced by Dex alone. No induction of CAT gene expression is observed in cells treated with CsA or FK506 in the absence of Dex. The antisteroid RU 486 abolishes effects obtained in the presence of Dex. Using a series of CsA, as well as FK506, analogs, including some devoid of calcineurin phosphatase inhibition activity, we conclude that the potentiation effects of these drugs on Dex-induced CAT gene expression in LMCAT cells do not occur through a calcineurin-mediated pathway. Western-blotting experiments following immunoprecipitation of glucocorticosteroid receptor (GR) complexes resulted in coprecipitation of GR, heat shock protein hsp90 and two immunophilins: the FK506-binding protein FKBP59 and the CsA-binding protein cyclophilin 40 (CYP40). Two separate immunophilin-hsp90 complexes are present in LMCAT cells: one containing CYP40-hsp90, the other FKBP59-hsp90. Thus, both FKBP59 and CYP40 can be classified as hsp-binding immunophilins, and their possible involvement as targets of immunosuppressants potentiating the GR-mediated transcriptional activity is discussed.

Animals↗

PubMed1995

Cyclophilin-40: evidence for a dimeric complex with hsp90.

The expression of human cyclophilin 40 (CyP-40) as a glutathione S-transferase fusion protein has provided a means to identify cellular components that are in association with this ubiquitous protein. When the fusion protein was coupled to a GSH affinity matrix, heat-shock protein 90 (hsp90) was found to be the predominant associated protein in all tissue extracts examined. The relatively high concentration of each of these proteins in various tissues indicates that the dimeric complex exists in concentrations that exceed those of the inactive steroid receptors of which each protein is a component. Association does not occur with heat-shock protein 70 and is not affected by cyclosporin A (CsA). Independent expression of two domains of CyP-40 permitted dissociation of N-terminal isomerase and CsA binding activity from the hsp90 binding site, which is located at the FKBP-59-like C-terminal region. The biological association of CyP-40 with hsp90 in many tissues may reflect a conjoint role in protein folding and trafficking.

Amino Acid Isomerases↗

PubMed1995

Expression of human cyclophilin-40 and the effect of the His141-->Trp mutation on catalysis and cyclosporin A binding.

The cDNA encoding a human cytosolic 40-kDa cyclophilin (CyP-40) has been inserted into a modified pGEX-3X expression vector and expressed in Escherichia coli to yield recombinant CyP-40 at levels up to 4 mg/l medium. The protein was purified to homogeneity using a cyclosporin affinity matrix and gel filtration. The recombinant CyP-40 showed peptidyl-prolyl cis-trans isomerase activity (kcat/Km = 1.12 x 10(6) M-1.s-1) comparable to that of bovine brain CyP-40. The weak affinity of CyP-40 for cyclosporin A was postulated to arise from a histidine residue that replaces a tryptophan residue critical for cyclosporin A binding and highly conserved in other cyclophilins that have high affinity for cyclosporin A. Site-directed mutagenesis to replace His141 by tryptophan yielded a protein with an approximately 20-fold greater affinity for cyclosporin A (Kdapp 11.5 +/- 2 nM as determined by tryptophan fluorescence measurements). The intrinsic isomerase activity of this mutant protein with succinyl-Ala-Ala-Pro-Phe 4-nitroanilide as substrate was about nine times greater than the value obtained for the nonmutated recombinant CyP-40 and had an activity similar to that of CyP-18. NMR difference spectroscopy and molecular modelling revealed a cyclosporin-A-binding domain that is similar to that of CyP-18.

Amino Acid Isomerases↗

PubMed1995

Nonallergic individuals recognize the same T cell epitopes of Bet v 1, the major birch pollen allergen, as atopic patients.

The immune response toward allergens in nonallergic healthy individuals was investigated. To boost immune responses, two injections of birch pollen extract were administered to five nonallergic volunteers. T cell lines (TCL) with specificity for Bet v 1, the major birch pollen allergen, were established and analyzed for epitope specificity using overlapping peptides. Forty-nine T cell clones (TCC) specific for Bet v 1 were isolated from TCLs. Comparison with TCL and TCC established from birch pollen-allergic patients was performed. All TCC revealed the Th phenotype. Epitope specificities of TCL and TCC from nonatopics were identical to those found in allergic individuals. No association between MHC class II molecules and particular epitopes could be observed. In nonallergic as well as in allergic individuals, cytokine production in response to specific stimulation revealed a majority of Th-clones producing IL-4 and IFN-gamma. However, TCC derived from atopic individuals revealed a higher IL-4/IFN-gamma ratio. Immunoblot and ELISA revealed Bet v 1-specific IgG in nonallergic individuals before and after booster injections, but no IgE could be detected. High levels of Bet v 1-specific IgG and IgE could be detected in birch pollen-allergic patients. It can be concluded, that nonatopic and allergic individuals display the same repertoire of T cell specificities. In allergic individuals, the activation of allergen-specific TCC leads to a higher ratio of produced IL-4 vs IFN-gamma, which is responsible for enhanced IgE production.

Allergens↗

PubMed1995

Displaying electrocorticographic findings on gyral anatomy.

Human electrocorticographic findings recorded from subdural arrays of electrodes were topographically mapped directly onto magnetic resonance images of gyral anatomy. With this technique gyri involved in generating somatosensory evoked potentials and epileptic phenomena are easily identified. Regions of the cortex which exhibit local spectral changes associated with cognitive tasks can also be visualized. These composite images of structure and function can provide insight regarding the functional organization of human cortex in relation to gyral anatomy and localized pathologic rhythms.

Brain Mapping↗

PubMed1995

20 MHz sonography, colorimetry and image analysis in the evaluation of psoriasis vulgaris.

For objective evaluation of the treatment of psoriasis vulgaris standard techniques are desirable. They should be reproducible, sensitive and non-invasive. In this study non-invasive bioengineering techniques, especially high frequency/high resolution ultrasound for measurement of the healing of psoriasis vulgaris were evaluated. Fifty patients with chronic stationary plaque type psoriasis participated in a prospective study; in each patient two psoriatic plaques were examined by means of sonography, colorimetry and image analysis during treatment until complete resolution had occurred. Skin thickness and density could be quantified by means of high frequency ultrasound. In active psoriatic lesions, an echopoor area underneath the entry echo in the ultrasound image caused by acanthosis and inflammatory infiltrate is typical. Under therapy the thickness of this echopoor area diminishes while its density increases. Intensity of the erythema especially the decrease of erythema through healing could not exactly be quantified with the colorimeter because the 'Lab'-CIE-colour representation system cannot distinguish well enough between the colours red and brown. Image analysis allowed to measure the sizes of the psoriatic plaques and to quantify their resolution under therapy. The measuring of plaque size by the aid of computer based image analysis is possible and useful.

Colorimetry↗

PubMed1995

Precision of laser Doppler scanning in clinical use.

Reactions of the cutaneous microcirculation to local stimuli have been quantitated in terms of area of erythema (planimetry), change in colour (colorimetry) and time-dependent changes in perfusion (one-dimensional laser Doppler fluxmetry (LDF)). Using the new technique of laser Doppler scanning (LDS) it is now possible to quantify and demonstrate two-dimensional patterns of microvascular perfusion in terms of intensity and extent. The precision of this new technique was compared with the previously established techniques by examining the reactions of 15 healthy volunteers to the intracutaneous injection of carbacholin and isotonic NaCl solutions. Both stimuli were applied paravertebrally, on the left and right side. Reactions were examined after 10 min. As a control for temporal reproducibility the examination was repeated on another day. All methods allowed the differentiation of reactions to carbacholin from those to NaCl (P < or = 0.0001). Only colorimetry and LDS provided data that were unequivocally reproducible when comparing both sides (r > or = 0.78). Using LDF or planimetry, reproducibility of values was lower (r < or = 0.58). When looking at measurements performed on different days, only values of LDS were reproducible (r > or = 0.77). Hyperaemic areas seen with LDS were significantly larger than those determined by planimetry. Results of LDS are reproducible spatially and temporally: the technique will allow time-course observations of skin reactions that are accompanied by medium-term changes in perfusion.

Adult↗

PubMed1995

Cutaneous microcirculation in skin lesions associated with chronic venous insufficiency.

BACKGROUND: There are various types of skin lesions in chronic venous insufficiency. OBJECTIVE: To determine an association between different skin lesions and different changes in the cutaneous vascular bed. METHODS: Twenty-eight patients with chronic venous insufficiency (CVI) without and with various types of skin lesions (ie, hyperpigmentation, lipodermatosclerosis, white atrophy, and venous ulcer) and 12 healthy control subjects were examined by video-capillaroscopy, transcutaneous oxygen tension measurement, photoplethysmography, and Doppler ultrasonography to detect disturbances of cutaneous microcirculation and venous macrocirculation. RESULTS: There were no significant differences between the different CVI groups with respect to their venous function disorder. However, important variations were noted in the cutaneous microcirculation. In all the patient groups, an increase in the mean halo diameter could be demonstrated even in clinically healthy skin. In all types of skin lesions, the mean capillary diameter was significantly enlarged. Severe morphological capillary changes and a significant reduction of the mean transcutaneous oxygen tension values were found in conjunction with lipodermatosclerosis and white atrophy and in the areas surrounding venous ulcers. CONCLUSION: The results of this study point to the conclusion that, once they have become established, microvascular disturbances play an independent role in the development of the skin lesions associated with CVI.

Adult↗

PubMed1995

Two-dimensional blood flow determinations in allergic reactions using laser Doppler scanning.

The new technique of laser Doppler scanning (LDS) provides a 2-dimensional pattern of cutaneous microcirculation, which offers a visual image and can quantify the intensity and expansion of perfusion. With the help of this technique, we examined the microcirculatory pattern of Type IV reactions to recall antigens, which were applied using a test stamp (Multitest Merieux). The measurements were performed before application of the test stamp as well as 10 min, 24, 48 and 72 h afterwards. The inflammatory hyperemia was evaluated using LDS and unidimensional laser Doppler fluxmetry. The diameter of the inflammatory infiltrate was quantified by means of palpation, the thickness by means of high-resolution 20 MHz sonography. The clinically visible erythema was measured planimetrically. An unspecific hyperemia resulting from the trauma of the stamp revealed no evident infiltrate under sonography 10 min after the test application. Depending of the individual reaction, the mean flux and the expansion of the hyperemia were at their peak after 48 h. The flux values were at a maximum in the center of the inflammatory reaction and dropped continuously toward the periphery. The area of the hyperemia seen in the LDS image was significantly larger than the expansion of the erythema measured planimetrically, but there was a significant correlation. The perfusion correlated significantly with the infiltration diameter (24 h, 48 h, 72 h) and the infiltration thickness 48 h after testing. All in all, it was possible to measure directly and without touching the skin and to quantify a subclinical pattern of skin perfusion as a response to and inflammatory reaction on a 2-dimensional display.

Adult↗

PubMed1995

Interferometry: a new method for no-touch measurement of the surface and volume of ulcerous skin lesions.

A new interferometry procedure (Holon View measuring system) permits non-invasive and objective measurement of the surface, height/depth and volume of ulcerous lesions. The method, which uses a combination of the so-called phase-shift and gray-code technique, is new in dermatology. The measuring system consists of a diffraction grating projection system, a video camera and a computer-aided, digital image processing and analysis system. A diffraction grating consisting of 320 lines is projected onto the skin surface or a silicone impression of the ulcerous lesion. The course of the light-intersection lines is recorded by a video camera and read into an image computer. The special feature of the method is the combination of grey-code projection and a phase-shift procedure. For evaluation of the method in dermatology, 2,000 interferometric measurements of volume were carried out on objects of known volume, on silicone impressions and on leg ulcers. The accuracy of the method has been proven by means of the evaluation of objects of known volume. The results of interferometric measurements were compared with the values of the volume determined by water capacity and those of the surface determined by image analysis. The healing of a leg ulcer was followed over an 8-week period. The Holon View measuring system permits no-touch measurement of the volume and surface of ulcerous skin lesions with a high degree of accuracy and precision, in a short time.

Body Water↗

PubMed1995

[Not Available].

Explore the source record for details and available documents.

Germany↗

PubMed1995

[Objectivity, reproducibility and validity of 3D ultrasound in dermatology].

Recently it has become possible to visualize the three-dimensional (3D) architecture of sonographic structures using high-resolution ultrasound above 20 MHz (Dermascan C, Denmark; DUB 20, Germany). We studied the objectivity, reproducibility, and validity of these two 3D analysis systems on 22 skin tumors. To validate both systems, we compared the sonometric and histometric volume in 4 tumors. The objectivity was calculated by repeated evaluation of the volume on the same serial B-scan sections at 3-month intervals. The two-dimensional B-scans and 3D images exhibited similar characteristics. Volumetric evaluations were reproducible with both systems (variation coefficient < or = 9.9%), when the applicator was oriented longitudinal to the body axis. By changing the orientation, the coefficient increased up to 58.1% (DUB 20). Sonometric and histometric volumes of a phantom model and of the tumors exhibited small deviations in the Dermascan C (< or = 8.1%) and in some tumors large deviations in the DUB 20 (< or = 93.1%). We can conclude that the 3D sonography is a reproducible method, which can be used to evaluate the volume of skin tumors and metastases under chemotherapy or radiotherapy. We suggest in particular to use the in-vivo tumor volume as a prognostic parameter for the malignant melanoma.

Adult↗

PubMed1995

Persistence of müllerian duct derivative syndrome in 2 male patients with bilateral cryptorchidism.

The persistent müllerian duct syndrome represents a rare form of male pseudohermaphroditism secondary to anti-müllerian hormone deficiency. We describe 2 cases of phenotypically male postpubertal patients with a uterus and tubes. Both patients presented with bilateral cryptorchidism, 1 was seen for gynecomastia and 1 was seen for an abdominal mass that was found to be a testicular tumor.

Adolescent↗