Search PubMed⌕ Search

Biomedical subjects

U Koch

Publications and source records attributed to U Koch.

At least 91 records · Page 5Linked to original sources
PubMed1997

A synthetic CD4-CDR3 peptide analog enhances bone marrow engraftment across major histocompatibility barriers.

The efficacy of a synthetic peptide analog mimicking the CDR3-D1 domain of the CD4 molecule was investigated in murine models of allogeneic bone marrow engraftment after transplantation across major histocompatibility complex (MHC) barriers. A single dose of a CD4-CDR3 peptide analog was administered at the time of marrow transplantation to three different allogeneic mouse strain combinations after appropriate sublethal total body irradiation: (1) B10.BR --> C57BL/6J (B6), a full allogeneic MHC difference; (2) (B6xDBA/2)F1 --> (B6xCBA)F1, a haploidentical MHC combination; and (3) B6.C-H2bm12 --> B6-Ly5.2, involving only a MHC class II difference. Donor-host chimerism was assessed after 1 and 2 months posttransplantation by flow cytometric analysis of spleen and/or lymph node cells. Peptide-treated animals in all three strain combinations exhibited significantly enhanced donor lymphoid engraftment, which was similarly reflected in the total lymphocyte compartment and its T-cell (CD4+, CD8+) and B-cell subsets. In addition, peptide-treated mice in the haploidentical and MHC class II-mismatched strain combinations exhibited prolonged tolerance of both donor and syngeneic host-type tail skin grafts while rejecting third-party allogeneic grafts, thus supporting the reconstitution of immunocompetence in these chimeras. Lymphocytes from the peptide-treated haploidentical chimeric mice also displayed donor-specific tolerance upon stimulation in a one-way mixed lymphocyte reaction. In a 6-day colony-forming unit-granulocyte-macrophage (CFU-GM) assay to quantitate the level of hematopoietic cell engraftment in both the haploidentical and class II-disparate strain combinations, bone marrow cells from the peptide-treated mice exhibited significant increases in CFU-GM compared with the saline-treated control groups. Finally, early multiple treatments with the peptide after transplantation significantly enhanced donor chimerism in donor-presensitized recipient mice across the MHC class II barrier and proved to be significantly more effective than anti-CD4 monoclonal antibody treatment. These results indicate that the structure-based CD4-CDR3 peptide analog may represent a valuable approach to the inhibition of graft rejection after MHC-mismatched bone marrow transplantation.

Animals↗
PubMed1997

A computer screening approach to immunoglobulin superfamily structures and interactions: discovery of small non-peptidic CD4 inhibitors as novel immunotherapeutics.

The interaction between CD4 and major histocompatibility complex (MHC) class II proteins is critical for the activation of CD4+ T cells, which are involved in transplantation reactions and a number of autoimmune diseases. In this study we have identified a CD4 surface pocket as a functional epitope implicated in CD4-MHC class II interaction and T-cell activation. A computer-based strategy has been used to screen approximately 150,000 non-peptidic organic compounds in a molecular data base and to identify a group of compounds as ligands of the proposed CD4 surface pocket. These small organic compounds have been shown to specifically block stable CD4-MHC class II binding, and exhibit significant inhibition of immune responses in animal models of autoimmune disease and allograft transplant rejection, suggesting their potential as novel immunosuppressants. This structure-based computer screening approach may have general implications for studying many immunoglobulin-like structures and interactions that share similar structural features. Furthermore, the results from this study have demonstrated that the rational design of small non-peptidic inhibitors of large protein-protein interfaces may indeed be an achievable goal.

Animals↗
PubMed1997

HLA-DR/DQ/DP interactions in rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with the presence of particular HLA-DRB1 alleles. In order to characterize HLA-DQB1 and/or-DPB1 alleles that contribute to disease susceptibility besides HLA-DRB1 alleles, we have analysed the HLA-DRB1, -DQB1 and -DPB1 polymorphism in 84 RA patients and 135 controls. HLA typing for HLA-DRB1 and -DQB1 alleles was performed using sequence-specific primers in combination with sequence-based typing. HLA-DPB1 alleles were characterized by reverse dot-blot hybridization. Our data confirm the predominant role of the (Q)R/KRAA sequence from AA position 70-74 of the HLA-DRB chain for disease susceptibility. In particular, the lysine (K) substitution at position 71 was highly significantly associated with RA. Analysis of the DQB1 locus revealed no association with RA when linkage disequilibrium between HLA-DRB1 and -DQB1 alleles was considered. In contrast, we observed an increased frequency of HLA-DPB1*0401 among (Q)R/KRAA-positive patients. (Q)R/KRAA-negative RA patients exhibited an overrepresentation of HLA-DPB1*0201 and HLA-DPB1*0601. Rheumatoid factor (RF) production correlated with the presence of the disease-associated (Q)R/KRAA amino acid cassette of the HLA-DRB chain. When HLA-DPB1 allele frequencies were compared between RF-positive and RF-negative RA patients, we observed an increased frequency of HLA-DPB1*0401 among RF-positive RA patients and HLA-DPB1*0201 among RF-negative patients. These results suggest that besides the predominent role of HLA-DR molecules in RA, HLA-DP molecules may have an influence on disease susceptibility and could modulate disease progression. HLA-DPB1*0401 may function in addition to HLA-DRB1*04, whereas HLA-DPB1*0201 and -DPB1*0601 may represent additional risk factors among (Q)R/KRAA-negative RA patients.

Adult↗
PubMed1997

HLA-DRB1*04 subtypes are associated with increased inflammatory activity in early rheumatoid arthritis.

The sequence polymorphism of HLA-DRB1 molecules in 84 rheumatoid arthritis (RA) patients with early RA has been analysed to evaluate whether particular HLA-DR alleles influence disease progression in the early stage of the disease. Clinical data were analysed by grouping the patients according to disease-associated haplotype combinations (DRB1*04,04/DRB1*04,01/DRB1*04,X/DRB1*01,X) in comparison to patients who did not carry these haplotypes (DRB1*X,X). Our results indicate that patients with early RA who are homozygous for DRB1*04 exhibit an elevated inflammatory activity and an increase of joint affections. In addition, the amino acid polymorphism (QR/KRAA) at position 70-74 seems to affect the production of rheumatoid factors. These results support the role of HLA-DRB1 alleles in the pathogenesis of RA and indicate that patients with particular HLA-DRB1*04 haplotype combinations may require intensified therapeutic interventions in the early stage of the disease to prevent disease progression.

Adult↗
PubMed1996

Neural delays shape selectivity to interaural intensity differences in the lateral superior olive.

Neurons in the lateral superior olive (LSO) respond selectively to interaural intensity differences (IIDs), one of the chief cues used to localize sounds in space. LSO cells are innervated in a characteristic pattern: they receive an excitatory input from the ipsilateral ear and an inhibitory input from the contralateral ear. Consistent with this pattern, LSO cells generally are excited by sounds that are more intense at the ipsilateral ear and inhibited by sounds that are more intense at the contralateral ear. Despite their relatively homogeneous pattern of innervation, IID selectivity varies substantially from cell to cell, such that selectivities are distributed over the range of IIDs that would be encountered in nature. For some time, researchers have speculated that the relative timing of the excitatory and inhibitory inputs to an LSO cell might shape IID selectivity. To test this hypothesis, we recorded from 50 LSO cells in the free-tailed bat while presenting stimuli that varied in interaural intensity and in interaural time of arrival. The results suggest that, for more than half of the cells, the latency of inhibition was several hundred microseconds longer than the latency of excitation. Increasing the intensity to the inhibitory ear shortened the latency of inhibition and brought the timing of the inputs from the two ears into register. Thus, a neural delay of the inhibition helped to define the IID selectivity of these cells, accounting for a significant part of the variation in selectivity among LSO cells.

Animals↗
PubMed1996

Attitudes to current oral contraceptive use and future developments: the women's perspective.

OBJECTIVES: The study was planned to determine current trends in contraceptive usage and to examine the attitudes, needs and preferences of women with respect to oral contraceptives. METHODS: Semi-structured interviews were carried out with women (n = 1201, aged 16-45 years) in Germany, the UK and France. RESULTS: The study revealed that oral contraceptives were the most popular method of contraception employed, followed by condoms, and that the majority of respondents were aged 16-19 years when they first used an oral contraceptive. An important finding of the study was that an oral contraceptive was first used only after having sexual intercourse for the first time (within 1 year), emphasizing the importance of effective contraceptive information and education for adolescents. Regarding non-contraceptive health benefits, protection from ovarian and endometrial cancer was perceived by respondents to be of the greatest importance; however, few women were spontaneously aware of this benefit. When given a number of different oral contraceptive intake options to assess, the established 'once daily for 21 consecutive days' option remained the most popular, although a 'once weekly' alternative was cited by many women. When asked about the preferred frequency of menstrual bleeding, there was a polarization between women favoring the normal monthly bleed and those wanting a 'no-bleed' regimen. CONCLUSION: Women are poorly informed about oral contraceptive use, and are largely unaware of the important long-term non-contraceptive benefits. Many women would prefer alternative pill intake options and a significant number would favor a 'no-bleed' regimen.

Adolescent↗
PubMed1996

[Dangerousness prognosis in the clinical context of fulfillment of psychiatric criminal commitment].

The compilation and the reliability-based evaluation of the questionnaire including potentially prognosis-relevant clinical criteria for the release of male patients from rehabilitation and security measure (section 63 German Criminal Code) are presented. The restriction to clinical (rather than social statistical) criteria results in a concentration of the criminal aspects of treatment and/or therapy. The open and, more importantly, the "unconscious" focuses of forensic clinical action become transparent. However, the prognostic constructs of clinicians prove to be somewhat lacking in criteria and rather inconsistent. Until it is validated as a prognostic instrument and integrated in a multidimensional inventory of prognoses, this questionnaire can contribute towards conceptual transparency and help create a better link between treatment and release criteria.

Adult↗
PubMed1995

[Systemic infection due to group A Streptococcus pyogenes].

A 47-year-old woman developed oedematous swelling of the skin over the left hip and leg, with joint pains and reddening over joints of the hands and left ankle. 2 months before her son had had scarlet fever, following which the patient had two episodes of fever. Shortly before hospitalization she was treated with a glucocorticoid because a rheumatic disease had been suspected. On admission the blood sedimentation rate was 58/90, the white cell count was 15.100/microliters with left shift in the differential count. The swellings in arms and legs became abscesses which were incised. An abscess over the left buttock, diagnosed by 67-gallium whole-body scintigraphy, was also treated surgically. On the day of admission penicillin (10 mill. IU three times daily intravenously) and, from the 4th day onwards, gentamicin (80 mg three times daily intravenously) were administered. Histological examination of fascia and muscle biopsies revealed nonspecific inflammation without signs of malignancy, white blood culture grew group A Streptococcus pyogenes. 20 days after the surgical intervention the patient was discharged in full health. Necrotizing fasciitis caused by Streptococcus pyogenes has become more frequent in the last few years and has often been accompanied by severe systemic complications.

Fasciitis↗
PubMed1995

Health counseling and health promotion of musculoskeletal disorders.

The steady increase in the number of musculoskeletal disorders has heightened the importance of health promotion accordingly. In Germany, health promotion efforts have become the responsibility of health insurers. Commissioned by the health insurance organization, Hamburg-Münchener Ersatzkasse, we developed and evaluated a new health counseling service for persons with musculoskeletal (rheumatic) complaints. In order to draft the scope and principles of the counseling program, we questioned more than 1000 enrollees per questionnaire. The aim of the survey was to estimate the actual demand for participation in the health counseling. The results show that the subjective need for health counseling is strongly linked to the kind of physical limitation involved, so that it can be assumed that particularly persons with relevant complaints and musculoskeletal disorders will participate in the program. To evaluate the counseling sessions, a range of measurements was developed. The aim was to obtain a comprehensive and precise record of the problems and complaints of those taking part in the program. The evaluation shows that the new service is used mainly by persons who have suffered limitations to their health for years due to musculoskeletal disorders. Especially middle-aged persons use the counseling service, with women showing the most interest. When participants were asked after counseling which health support measures they had taken or were planning, their answers indicated that in most cases the recommendations of the counselor were being put into practice. We conclude that health counseling can be considered a meaningful option for health promotion.

Adult↗
PubMed1995

HBV and HCV genome in peripheral blood mononuclear cells in patients undergoing chronic hemodialysis.

Patients undergoing chronic hemodialysis are at risk for infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). As peripheral blood mononuclear cells (PMNC) are known to be susceptible to infection of both HBV and HCV, assessment of viral genomes in those cells could uncover occult infections not detected by serologic methods or virus determination in serum. We investigated all 67 patients undergoing chronic hemodialysis at a single dialysis unit by PCR for the presence of HBV or HCV genomes in serum as well as in PMNC. None of the 67 patients was HBsAg positive or showed HBV-DNA in serum, but in 5 patients HBV-DNA in PMNC was detected as the only marker of HBV-infection; those patients were also anti-HBc negative. In 9 patients HCV-RNA was positive in serum; in 5 of those patients it was also found in PMNC. Three of these infected patients were negative for anti-HCV. One other patient had no anti-HCV or HCV-RNA in serum, but was positive for HCV-RNA in PMNC. Thus, in 6 patients (8.9%) undergoing chronic hemodialysis we found evidence of infection with HBV or HCV by detecting viral genomes in PMNC without the presence of viremia, antigenemia or specific viral antibodies in serum. The detection of viral genomes in PMNC could be useful in the positive identification of additional potentially infectious patients.

Adult↗
PubMed1994

THE FUNCTIONAL MORPHOLOGY OF SINGING IN THE CRICKET

We describe the functional morphology of the singing apparatus of the cricket. There are three main functional sections of song mechanics, which partly overlap: (1) preparation for singing (lifting of the wings) and the reverse process (lowering of the wings at the end of the song); (2) singing movements (closing and opening of the wings); and (3) movements that adjust the pressure of the plectrum on the file (engagement force). In the case of song preparation, the mesotergum + first axillaries + second axillaries + wings form a functional unit. This unit is moved around a transverse hinge axis, which runs through both fulcrum joints. The muscles suitable for wing lifting are the prothoracic furca muscle and the mesothoracic tegula muscle. Those suitable for wing lowering are the prothoracic dorsolongitudinal muscles and the mesothoracic axillary 4, subalar and furca muscles. Lifting and lowering of the wings are superimposed by bistable mechanisms, which are adjustable (mesothoracic medial dorsolongitudinal muscles). In the case of closing movements (dorsoventral muscles) and opening movements (basalar and subalar muscles), the mesotergum and the wings are moved relative to each other, as for flight movements, but with the wings remaining folded back. The mesotergum is rotated down (closing) and up (opening) around a transverse hinge axis that runs through the caudal joints between the mesotergum and postnota. The path of movement of the wing and its sound-generating structure (i.e. plectrum or file respectively) is determined by an obliquely oriented hinge axis between the mesotergum and first axillary. During opening and closing, the lifted singing position of the wings is stabilized by the medial dorsolongitudinal muscles. We also discuss the role of other muscles that affect singing movements. The third axillary (and its muscle) and the postnotum [and its muscles, the furca muscle and the lateral (short) dorsolongitudinal muscle] are the main elements in the system that adjusts the engagement force of the wings. When left axillary 3 muscle contracts, the medial part of the left third axillary is rotated caudally (in its vertical hinge joint with the first median plate) against the anal part of the wing. The anal part is bent and rotated upwards, increasing the pressure of the left plectrum against the right file. Conversely, the right axillary 3 muscle, which moves the file away from the plectrum, is able to reduce the pressure. The left furca muscle (the antagonist of left axillary 3 muscle) and the left lateral (short) dorsolongitudinal muscle (the 'synergist' of left axillary 3 muscle), and the corresponding muscles on the right side (which have opposite functions), allow a large range of different engagement forces. The results are compared with the work of other authors on the functional morphology of this system and with the results of electrophysiological investigations. New aspects of the evolution of the singing mechanisms are discussed.

Journal Article↗
PubMed1994

[Evaluation of reading devices for the blind and community utilization at the Freiburg University Library].

An interdisciplinary study was conducted to investigate the use of two reading machines placed at the disposal of visually handicapped individuals in a public location (Freiburg University Library). The machines were designed to translate written text into artificial speech or braille, as selected by the user. Two different configurations were tested, with data collection through interviews and systematic observation. The questions addressed were: whether machine improvement was necessary with respect to user friendliness, speech generalization, and text recognition; whether the machines, designed to be single-person workstations, would be accepted and shared in a public location; and whether it was possible to configure the machines to individuals with different baselines and needs. The results of this study were expected to aid decision-making regarding the suitability of the machines and their location, as well as the kind and extent of technical support needed. The invitation to participate in the study was taken up by 19 persons with visual handicap ranging from severe impairment to blindness. The two reading machines provided substantially increased literature access to users. One of the machines emerged as better suited for the university library setting. Regular assistance for users as well as clarification of organizational details proved necessary to guarantee productive and lasting usage of the machines.

Adult↗
PubMed1994

[Diseases of the petrous bone--demands made on radiologic diagnosis from the otosurgical point of view].

Advances in microsurgical techniques in otosurgery as well as further developments in imaging methods enable the surgeon to perform procedures at the petrous bone that are as radical as they can contribute to retaining the function. The present study aims at explaining by means of case reports the specific otosurgical problems in typical diseases of the otobase and at presenting the ranking of the individual imaging methods from the surgeon's point of view. For example, special features in the preoperative diagnosis of glomus tumours, acoustic neurinomas, Ménière's disease, cholesteatomas and so-called petrous bone tip processes are pointed out. A special aspect of radiological and surgical collaboration is seen in highly vascularised tumours of the otobase in respect of the possibilities offered by interventional angiography. The importance of MR-tomography in preoperative diagnostics is assessed with some reservation because this does not show up surgically relevant landmarks.

Aged↗
PubMed1993

Diagnostic tests in enzyme allergy.

BACKGROUND: Allergies to enzymes occur frequently in enzyme manufacturing plants. In epidemiologic studies the number of exposed subjects with symptoms is considerably higher than the number of sensitizations as assessed by skin tests or RAST. It was the aim of this study to evaluate the sensitivity and specificity of skin prick tests, enzyme allergosorbent test, and immunoprint with enzymes by using the results of bronchial provocation tests as the "gold standard." METHODS: We performed 82 bronchial provocation tests with nine different enzymes in 42 chemical plant workers, all of whom had reported work-related symptoms. All tests with the exception of bronchial provocation tests were also performed in 10 atopic and 10 healthy control subjects. RESULTS: Thirteen workers showed positive results to bronchial provocation tests (50% or greater fall in specific airway conductance) with an enzyme at a maximal concentration of 10 mg/ml. Equivocal test results, that is, tests with a 30% or greater and less than 50% fall in specific airway conductance were seldom. Skin prick tests with nondialyzed aqueous enzyme extracts at a concentration of 10 mg/ml yielded a sensitivity of 100% and a specificity of 93%. Control subjects had no cutaneous reactions to enzymes. Discrepancies between skin tests and bronchial provocation tests occurred in 5 of 82 tests, all with a positive skin test and a negative bronchial provocation test. False-positive skin tests were considered more likely in four subjects and a false-negative bronchial challenge more likely in one case. Enzyme allergosorbent test was 62% sensitive and 96% specific, and atopic control subjects showed positive results in two cases. Results of immunoprint with amylase showed one main band at pH 3.4; this band was also found in exposed subjects without further signs of sensitization, but was not found in control subjects. All but one person with positive results to bronchial provocation tests with enzymes showed bronchial hyperresponsiveness. We identified 13 subjects with bronchial hyperresponsiveness, but without occupational allergy: five of these had sensitizations to nonoccupational allergens and the remainder showed bronchial hyperresponsiveness without any detectable cause. CONCLUSIONS: Occupation-related symptoms were not indicative of occupational allergy. Bronchial provocation tests and skin prick tests with nondialyzed aqueous enzyme extracts were appropriate techniques for the diagnosis of enzyme allergy.

Bronchial Provocation Tests↗
PubMed1993

High incidence of aneurysm formation following patch plasty repair of coarctation.

Repair of aortic coarctation was performed in 152 adolescent and adult patients (mean age 28.5 years, range 14-67 years). Ninety patients were treated with patch plasty, 33 with end-to-end anastomosis, 18 with interposition of a tubular graft, 6 with prosthetic bypass and 5 with direct plasty. There were two (1.3%) early and ten (6.6%) late deaths after 2.9 to 11.8 (mean 6.6) years. Of the remaining 140 patients, 129 (92.1%) were reexamined with computed tomography and angiography after 1.5 to 17.2 (mean 9.1) years postoperatively. In 27 patients (35.1%) of the patch plasty group significant dilatation at the operative site was observed and reoperation for aneurysm formation was required in 15 patients (19.5%). Resection of the intimal crest did not increase the probability of aneurysm formation, whereas Dacron as patch material and late hypertension had a significant influence. Six of the ten late deaths occurred in the patch plasty group. Rupture of an aneurysm at the operative site was proved in two of these patients, and three patients died suddenly for unknown reasons. In the other groups significant dilatation was observed in 13 patients and 3 local aneurysms required reoperation (2 after end-to-end anastomosis and 1 after direct plasty). We conclude that patch plasty repair of coarctation should be abandoned in adults. End-to-end anastomosis is advisable only if possible without excessive tension. Reoperation with interposition of a tubular graft on left heart bypass proved to be a safe method.

Adolescent↗