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Biomedical subjects

P Lang

Publications and source records attributed to P Lang.

At least 199 records · Page 11Linked to original sources

The gene LEO1 on yeast chromosome XV encodes a non-essential, extremely hydrophilic protein.

A 5.6 kbp segment of DNA from Saccharomyces cerevisiae chromosome XV has been isolated and sequenced. Genetic and nucleotide sequence analyses revealed that this region is closely linked to the ADE2 marker on chromosome XV and densely packed with genetic information. We show the gene organization of the entire region and report the nucleotide sequence of the gene, LEO1, which occurs in single copy in the haploid genome. The deduced amino acid sequence specifies an extremely hydrophilic protein with pronounced domain structure (molecular mass 53.9 kDa). The gene is constitutively expressed at a low level and is non-essential, as indicated by the absence of a phenotype from gene disruption mutants.

Amino Acid Sequence↗

High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schönlein purpura.

OBJECTIVE: To determine if polyvalent IgG is promising therapy for severe IgG nephropathy. DESIGN: Open prospective cohort study. SETTING: Referral nephrology unit. PATIENTS: 11 adult patients with severe IgA nephropathy (9 who had idiopathic disease and 2 who had Henoch-Schönlein purpura) and indicators of poor prognosis. INTERVENTION: Patients were given high-dose immunoglobulins (2 g/kg each month) for 3 successive months, followed by intramuscular immunoglobulins (preparation content, 16.5%; 0.35 mL/kg every 15 days) for another 6 months. MEASUREMENTS: Histologic changes were analyzed by comparing pre- and post-therapy renal biopsy specimens blindly, using an activity index (14-point scale), a sclerosis index (10-point scale), and a semiquantitative immunofluorescence test of immune deposits. Proteinuria, hematuria, leukocyturia, enzymuria, and global renal function (creatinine and polyfructosan clearances) were evaluated before and after intervention. RESULTS: Proteinuria (median level before intervention, 5.20 g/d; median level after intervention, 2.25 g/d), hematuria, and leukocyturia decreased substantially. The decrease in glomerular filtration rate was greatly slowed or stopped (median rate of decline in glomerular filtration before, -3.78 mL/min per month; after, 0 mL/min per month). The histologic index of activity (median index before, 5; after, 2) and the staining intensity of glomerular IgA and C3 deposits also decreased. Immunoglobulin therapy was well tolerated. CONCLUSIONS: Immunoglobulin therapy may be effective in treating severe IgA nephropathy and protecting renal function. However, prospective controlled trials must confirm these preliminary results.

Adolescent↗

[Cancer after transplantation].

Transplantation is associated with an increased risk of cancer. The major factor favouring carcinogenesis is the degree of immunosuppression rather than the nature of the drug used. A large number of these tumours are virus-induced, reflecting an immune system deficiency in combating viral infection. The transplanted patient should be closely followed, both early after transplantation and consistently thereafter, for early detection of such complications.

Humans↗

Replacement-like recombination induced by an integration vector with a murine homology flank at the immunoglobulin heavy-chain locus in mouse and rat hybridoma cells.

Vectors for homologous recombination are commonly designed as replacement or integration constructs. We have evaluated integration vectors for the substitution of the immunoglobulin heavy-chain constant region by various human isotypes in mouse and rat hybridomas. It is known that under certain circumstances replacement vectors exhibit a lower target efficiency and can be incorporated by integration events. Conversely, we show here that an integration vector can undergo a replacement event despite having free homologous adjacent DNA ends, which would be expected to initiate integration according to the double-strand break repair model. Moreover, in cases of replacement recombination the 5' crossover is not necessarily located within the homology region, thereby giving rise to a truncated gene product. Whether or not the replacement leads to such deletions is clearly dependent on the isotypes involved in the targeting reaction. The fact that the vector is correctly targeted to the heavy-chain locus, but that the homology region is not always the site of recombination, points to a novel recombination mechanism that may be specific for the immunoglobulin loci and that seems to be predominant even in the presence of the free homologous adjacent ends of an integration vector. Furthermore we demonstrate that homologous recombination at the heavy-chain locus is also possible between sequences from different species. The implications of our findings for the production of chimeric antibodies are discussed.

Animals↗

Musculoskeletal MR imaging: turbo (fast) spin-echo versus conventional spin-echo and gradient-echo imaging at 0.5 tesla.

The value of T2-weighted fast spin-echo imaging of the musculoskeletal system was assessed in 22 patients with various neoplastic, inflammatory, and traumatic disorders. Images were acquired with high echo number (i.e., echo train length) fast spin-echo (FSE; TR 2000 ms, effective TE 100 ms, echo number 13, linear k-space ordering), conventional spin-echo (SE; TR 2000 ms, TE 100 ms) and gradient-echo (GRE) sequences (TR 600 ms, TE 34 ms, flip angle 25 degrees). Signal intensities, signal-to-noise ratios, contrast, contrast-to-noise ratios, lesion conspicuousness, detail perceptibility, and sensitivity towards image artifacts were compared. The high signal intensity of fat on FSE images resulted in a slightly inferior lesion-to-fat contrast on FSE images. However, on the basis of lesion conspicuity, FSE is able to replace time-consuming conventional T2-weighted SE imaging in musculoskeletal MRI. In contrast, GRE images frequently showed superior lesion conspicuity. One minor disadvantage of FSE in our study was the frequent deterioration of image quality by blurring, black band, and rippling artifacts. Some of these artifacts, however, can be prevented using short echo trains and/or short echo spacings.

Adolescent↗

Prospective study of pulmonary function for cyclomegalovirus infection after renal transplantation.

Pulmonary involvement remains the main complication of cytomegalovirus (CMV) infection in renal transplantation (RT). Early diagnosis is required for the best management of patients, and preemptive therapy could be a successful approach. In order to define the predictive value of lung alveolocapillary abnormalities. We prospectively studied 26 renal transplant recipients for their diffusing capacity of carbon monoxide (DLCO) and their pulmonary clearance of a 99mTc-DTPA aerosol. Patients were studied before transplantation and then every 2 weeks up to the end of the 3rd month following RT. Viral blood cultures and serological determinations were performed every week during these first 3 months. Bronchoalveolar lavage (BAL) was done in case of CMV disease. Statistic analysis was done using Student's t-test and Pearson's chi-square test. During the 3-month follow-up, 13 patients remained free of CMV infection. Three non-infected and 8 infected patients showed DTPA clearance abnormalities (P < 0.05). Six non-infected and 7 infected patients showed DLCO disturbance (P > 0.50). DTPA clearance were significantly modified on days 45 and 60 in the infected group. Serial DTPA scanning, in association with viral blood cultures, could be a useful test to avoid unnecessary BAL in a preemptive therapy strategy.

Bronchoalveolar Lavage↗

Split tolerance in chimeric GVH mice.

The i.v. inoculation of parental spleen cells into unirradiated adult F1 hybrid mice results in a graft-versus-host reaction (GVHR). In the strain combination B10D2 --> (B10.BRx B10.D2) F1, this reaction is associated with thymic injury and transient but profound cellular immune deficiency. We further analysed the immune status of these mice 60 days after GVHR induction. Phenotypic studies of spleen cells showed that these mice were repopulated with parental lymphocytes resulting in a high degree of chimerism (85%). At this time, the mice looked healthy and recovered a normal cytotoxic T cell response (CTL) against allogeneic cells. GVH chimeric splenocytes were unresponsive against F1 hybrid cells in mixed lymphocyte culture (MLC), but exhibited anti-F1 CTL reactivity. We also analysed the anti-F1 reactivity of these mice in vivo. GVH chimeric splenocytes were unable to induce GVHR after injection into a new F1 hybrid and F1 GVH mice specifically rejected F1 bone marrow (BM) cells after lethal irradiation. Grafting a neonatal parental thymus prevented the rejection of F1 BM cells and restored CTL alloreactivity. It is concluded that the chimeric state induced by GVHR is associated with a split tolerance and that a radiosensitive thymic-dependent mechanism is involved in maintaining self-tolerance in these mice.

Animals↗

MR imaging of the arthritic knee: improved discrimination of cartilage, synovium, and effusion with pulsed saturation transfer and fat-suppressed T1-weighted sequences.

PURPOSE: To assess the applicability of three-dimensional (3D) magnetic resonance (MR) imaging with pulsed saturation transfer (ST) or fat saturation in depicting articular structures in arthritic knees. MATERIALS AND METHODS: Eleven patients underwent MR imaging with T1-weighted spin-echo (SE); unenhanced and contrast material-enhanced T2*-weighted 3D gradient-echo with and without on-resonance pulsed ST; and T1-weighted, fat-presaturated 3D gradient-echo techniques. Images with ST were subtracted from those without ST. RESULTS: Both fat-suppressed imaging and ST-subtraction (STS) techniques generated a high contrast-to-noise ratio among cartilage, synovium, effusion, bone, and adipose tissue. Both techniques depicted hypertrophic synovial tissue on unenhanced images; contrast material was necessary to differentiate between synovium and cartilage on STS images. CONCLUSION: 3D MR imaging with fat-suppressed or STS techniques provides good discrimination among articular structures in arthritic knees. Fat-suppressed imaging is faster than STS imaging and offers better contrast between cartilage and synovium. These techniques may improve monitoring of arthritic disease progression and therapeutic response.

Arthritis, Rheumatoid↗

Quantification of articular cartilage in the knee with pulsed saturation transfer subtraction and fat-suppressed MR imaging: optimization and validation.

PURPOSE: To assess the reproducibility and accuracy of volumetric quantifications of articular cartilage in the knee determined with three-dimensional (3D) magnetic resonance (MR) imaging combined with pulsed saturation transfer subtraction (STS) or T1-weighted fat suppression (FS) imaging. MATERIALS AND METHODS: Eight osteoarthritic knees were imaged repeatedly with optimized STS and FS sequences. Cartilage volumes were determined from 3D reconstructions of FS and STS images and by means of water displacement of surgically retrieved tissue. RESULTS: Mean over- or underestimation of cartilage volume at STS and FS imaging was 0.40 mL +/- 0.11 (standard deviation) (8.2%) and 0.31 mL +/- 0.08 (5.9%), respectively. Intraobserver reproducibility error was 0.20-0.65 mL (3.6%-6.4%) for STS and 0.21-0.58 mL (4.2%-6.4%) for FS imaging. Interobserver error was less than 0.62 mL and 7.8%. CONCLUSION: Three-dimensional data analysis of MR images acquired with STS or FS allows accurate and reproducible volumetric quantification of articular cartilage in the knee.

Aged↗

Characterization of a monoclonal antibody specific for the Ras-related GTP-binding protein Rho A.

The Rho family of small GTP-binding proteins is one of the three subgroups which, together with the Ras and Rab families, constitute the Ras-related superfamily. The Rho subgroup contains at least seven highly homologous members including 4 Rho proteins (RhoA, RhoC, RhoB, and RhoG), the Rac1 and Rac2 proteins, and CDC42Hs, which are involved in various aspects of cytoskeleton organisation and cell polarity. We have raised antibodies to individual members of the Rho family, and we report here the characterization of a monoclonal antibody (26C4) specific for RhoA. When used in western blot experiments, the 26C4 antibody recognizes the recombinant RhoA protein but not the almost identical RhoC or the RhoG, Rac and CDC42Hs proteins. Furthermore the 26C4 antibody identifies the natural RhoA protein in human lymphocyte cell extracts and was used to study the level of RhoA expression in several lymphoblastoid cell lines, and its association with the cell membrane.

Amino Acid Sequence↗

Hematopoietic bone marrow in the adult knee: spin-echo and opposed-phase gradient-echo MR imaging.

Hematopoietic bone marrow in the distal femur of the adult may be mistaken for a pathologic marrow process in magnetic resonance imaging of the knee. We investigated the incidence of hematopoietic marrow in the distal femur in a series of 51 adult patients and compared spin-echo (TR/TE in ms: 500/35, 2000/80) and opposed-phase gradient-echo (0.35 T, TR/TE in ms: 1000/30, theta = 75 degrees) magnetic resonance images. Zones with intermediate to low signal intensity on T1-weighted spin-echo and opposed-phase gradient-echo sequences representing hematopoietic marrow within high signal intensity fatty marrow were observed in 18 of the 51 patients. Five patterns of marrow signal reduction were identified; type 0: uniform high signal, i.e., no signal change; type I, focal signal loss; type II, multifocal signal loss without confluence; type III, confluent signal loss; and type IV, complete homogeneous reduction in marrow signal. Opposed-phase gradient-echo sequences demonstrated markedly greater red-yellow marrow contrast than conventional spin-echo sequences. Follow-up studies in three patients using a gradient-echo sequence with TE varying from 10 to 21 ms at 1-ms increments showed a cyclic increase and decrease in red and yellow marrow signal intensity depending on the TE. The contribution of intravoxel chemical shift effects on red-yellow marrow contrast in opposed-phase gradient-echo images was verified by almost complete cancellation of the TE-dependent marrow signal oscillation with use of a chemically selective pulse presaturating the water protons. Hematopoietic marrow in the adult distal femur in the absence of hematologic abnormalities is found primarily in women of menstruating age.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Local measures for the reduction of drug emergency risks and drug mortality risks.

The alarming increase of drug mortality rates in Germany was followed by research projects to enlighten the causes of this increase. The results of the Bremen, Hamburg and Berlin studies 1991-92, led to the conclusion that specific risk constellations have to be considered in the process of improving the drug counselling and health care system in the community. Primary prevention measures in kindergartens and schools, special services for families with addiction problems, decriminisation of drug abuse, the strengthening and specialisation of the counselling system and health services and new intervention strategies including methadone substitution should be integrated into local drug plans.

Community Health Services↗

Drug emergency patients are a burden for the medical care system: inadequate care for drug emergency patients.

During the course of the Drug Emergency Study in Bremen it became obvious that there are many problems left unsolved related to the medical care of intoxicated heroine addicts. From January to June 1992 there were 1230 drug emergencies, 409 hospital admissions and 644 emergency transportation. With or without antidote treatment, most patients leave the medical care system as soon as possible because of withdrawal symptoms. The physicians involved answered a short questionnaire about these problems: 80% of the physicians are dissatisfied with the present medical care situation for intoxicated drug addicts and feel that these patients are a burden for the hospitals (81%) and for themselves (73%); 93% of the physicians think that a central drug emergency unit, offering medical and psycho-social care would solve the present problems and would be a possibility for lowering drug emergencies and, as a further result, drug mortality.

Attitude of Health Personnel↗