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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 361 records · Page 20Linked to original sources
PubMed1992

Life history of cutaneous vascular lesions in Sneddon's syndrome.

Sneddon's syndrome is a potentially fatal arterio-occlusive disorder characterized by generalized livedo racemosa and cerebrovascular lesions. Skin biopsies often fail to yield diagnostic arterial lesions. In the present series, affected vessels were found in skin biopsies from 12 of 15 patients with Sneddon's syndrome. Selection of the correct biopsy site (seemingly uninvolved skin at the center of a livedo racemosa area), adequate biopsy size (1 to 2 cm), and serial sections are essential for the detection of relevant vascular pathology. Only small to medium-sized arteries of the dermis-subcutis boundary were found to be involved. Lesions follow a distinct course. The initial stage displays partial detachment of endothelial cells, adhesion of mononuclear cells interspersed with fibrin ("endothelitis"), a marked edema of the surrounding connective tissue with numerous dilated capillaries, and a predominantly lymphohistiocytic infiltrate with polymorphonuclear leukocytes. In the early phase a sponge-like plug is formed from mononuclear cells, fibrin, and red blood cells, leading to partial to complete obstruction. A perivascular inflammatory infiltrate, devoid of polymorphonuclear leukocytes, is located around affected arteries; in the adventitia of the occluded vessel, a very regular corona of dilated capillaries appears that is continuous with more peripheral dilated and branching vessels. Organization of the occluding plug ensues in the intermediate stage by "subendothelial cell proliferation," most likely due to immigrating smooth muscle cells. In the final stage, the occluding artery undergoes fibrosis, shrinkage, and atrophy.

Adult↗
PubMed1992

Laminin in the male germ cells of Drosophila.

To study genes that may be crucial for the male germ cell development of Drosophila we screened a cDNA expression library with a polyclonal antiserum against testis proteins of Drosophila hydei. We identified a cDNA fragment that exhibited a complete sequence similarity with the cDNA of the laminin B2 chain, an important component of the extracellular matrix. Transcripts of laminin B2 were detected in the RNA of male germ cells with the polymerase chain reaction and by in situ hybridization. We studied the reaction of different polyclonal antibodies including those against a Drosophila laminin B2-lac fusion protein, the entire Drosophila laminin complex, or against the mouse laminin complex and against laminin A and B1 chains with specific structures in developing male germ cells of Drosophila. Antigenic sites against laminin B2 were found in the lampbrush loops in primary spermatocyte nuclei, in nuclei of spermatids, and in heads of spermatozoa. The axonemes of elongating spermatids react with antibodies against the Drosophila laminin B1, B2 and laminin A chains. The possible biological functions of the laminin in the male germ cells of Drosophila are discussed.

Animals↗
PubMed1992

Ubiquinone (coenzyme Q10) in the long-term treatment of idiopathic dilated cardiomyopathy.

Using a placebo-controlled, double-blind cross-over study the potential therapeutic effect of ubiquinone (coenzyme Q10) was investigated in 25 patients suffering from idiopathic dilated cardiomyopathy (New York Heart Association functional classification I, II and III). Over an initial period of 4 months, 15 patients were administered verum (3 x 33.3 mg coenzyme Q10 x day-1 p.o.) and subsequently given a placebo during the ensuing 4 months (V/P). The sequence of treatment was reversed within the remaining 10 patients (P/V). Therapeutic efficacy was assessed by means of echocardiogram, chest X-ray, radionuclide ventriculography in combination with exercise test and impedance cardiography. Control values for left ventricular function parameters were similar in both groups; left ventricular ejection fraction: 39.5 +/- 11.5% (P/V), 37.6 +/- 17.0% (V/P); left ventricular end-diastolic diameter: 65 +/- 9 mm (P/V), 67 +/- 8 mm (P/V); and cardiac output: 5.1 +/- 1.41 x min-1 (P/V), 5.1 +/- 1.11 x min-1 (V/P). Chronic treatment with ubiquinone had no influence on haemodynamic parameters, electrocardiogram, incidence of ventricular arrhythmias or on exercise tolerance. It was therefore impossible to demonstrate any therapeutic effect of ubiquinone in patients suffering from idiopathic dilated cardiomyopathy.

Cardiomyopathy, Dilated↗
PubMed1992

RNA polymerase III-transcribed EBER 1 and 2 transcription units are expressed and hypomethylated in the major Epstein-Barr virus-carrying cell types.

The genome of Epstein-Barr virus (EBV) codes for two non-translated small RNA molecules, EBER 1 and 2. We found that both EBERs are expressed in the major EBV-carrying cell types, group I and III Burkitt's lymphoma (BL) cell lines, lymphoblastoid cell lines (LCLs) and in two nude mouse-passaged nasopharyngeal carcinoma (NPC) tumours. The relative amount of EBER 1 and EBER 2 varied in different host cells but did not correlate with the cellular phenotype. The EBER coding and flanking sequences were predominantly hypomethylated at HpaII sites not only in LCLs which usually carry hypomethylated EBV genomes but also in BL and NPC cell lines harbouring EBV episomes that are highly methylated in other regions. Thus, the EBER transcription units, actively transcribed by RNA polymerase III in the major EBV-carrying cell types, represent a methylation-free region in the EBV genome similarly to regulatory sequences of the latent membrane protein gene when the latter is transcribed by RNA polymerase II.

Animals↗
PubMed1992

The influence of daily dish-washing with synthetic detergent on human skin.

The effects of regular dish-washing on the stratum corneum barrier function, as determined by transepidermal water loss (TEWL), and objective and subjective skin parameters, were investigated in a 'use test' performed by 18 healthy volunteers. Hands were soaked in a 0.05% solution of a commercial dish-washing product (three times/day, for 15 min, at 37 degrees C) over a period of 3 weeks; one hand was unprotected and the other was protected with a commercial rubber glove. TEWL increased in 13/18 volunteers by more than 25% above baseline on exposed hands within the first 2 weeks of the study. Objective skin signs (erythema, scaling, fissures) and subjective symptoms (itching, dryness, smarting) occurred almost exclusively in subjects with substantial TEWL increases and were most prominent 1-2 weeks following peak TEWL values. There was a highly significant correlation between cumulative relative symptom scores and TEWL changes. TEWL increase and symptom scores were not correlated with a history of inhalant allergy and/or elevated serum IgE levels. Three volunteers, who had shown the highest increase of TEWL values and the most intense clinical reactions to the detergent were subjected to a control experiment in which one hand was soaked in warm tap-water following the same experimental protocol. No significant effects on TEWL values or skin symptoms were observed. We conclude that regular exposure to low concentrations of detergents as used for dish-washing is capable of inducing skin lesions in a substantial proportion of individuals.

Adult↗
PubMed1992

Feasibility of an implantable arrhythmia monitor.

Conventional Holter monitoring is of limited benefit in patients with infrequent symptoms suspected to be related to arrhythmia. A small recorder implanted subcutaneously might obviate many limitations of conventional monitoring. To determine the feasibility of obtaining adequate electrocardiographic signals from such a device, a prototype was temporarily implanted in 17 patients undergoing pacemaker implantation. The prototype contained four disc-shaped titanium electrodes, 0.21 inches in diameter embedded in epoxy. The four electrodes were in a square configuration spaced 0.72 inches center to center and were placed face down in a subcutaneous pocket in the left pectoral region. Bipolar recordings were made from a horizontal pair, a vertical pair, and both diagonal paris of electrodes (interelectrode distance 1.02 inches) and recorded on electromagnetic tape after filtering at 0.5-250 Hz. The mean peak-to-peak amplitude in each configuration was determined over a five-beat interval. Clear recordings were obtained from all 17 patients with recognizable P, QRS, and T waves. The amplitude of the signals obtained from the diagonal pairs of electrodes (175 +/- 51 and 170 +/- 54 microV) were greater than obtained from either the vertical pair (142 +/- 62 microV, P = 0.08 compared to diagonal electrodes) or the horizontal pair of electrodes (105 +/- 54 microV, P < 0.01). The maximum amplitude recorded from any configuration was 189 +/- 54 microV. In six patients the device was also tested with the electrodes face up in the subcutaneous pocket.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1992

Functional homology between N-myc and c-myc in murine plasmacytomagenesis: plasmacytoma development in N-myc transgenic mice.

Mouse plasmacytomas induced by pristane oil alone, or in combination with Abelson murine leukemia virus (A-MuLV), regularly carry one of three alternative chromosomal translocations that juxtapose c-myc to immunoglobulin heavy- or light-chain loci. E mu-c-myc transgenic mice develop translocation-free plasmacytomas after induction by pristane oil and/or A-MuLV [Sugiyama, H., Silva, S., Wang, Y., Weber, G., Babonits, M., Rosen, A., Wiener, F. & Klein, G. (1990). Int. J. Cancer, 46, 845-852]. In order to test whether another member of the myc family, N-myc, could play a similar role as c-myc, we treated E mu-N-myc transgenic mice with pristane and helper-free A-MuLV. Of 20 mice that received a single pristane injection followed by A-MuLV, 17 developed plasmacytomas with a mean latency period of 54 +/- 20 days. In a corresponding group that only received a single pristane injection, five out of six transgenic mice developed plasmacytomas with a mean latency period of 142 +/- 32 days. However, after three monthly injections of pristane, all 15 transgenic mice developed plasmacytomas with a mean latency period of 128 +/- 20 days. All plasmacytomas expressed the N-myc transgene, while none of them expressed either c-myc or endogenous N-myc. None of the tumors carried the usual plasmacytoma-associated translocations.

Abelson murine leukemia virus↗
PubMed1992

[Quality control in the allergy laboratory--4 years "Allergy Ring Trial" in Austria].

In 1988 the Austrian Society for Allergology and Immunology initiated an external quality control program for the in vitro allergy diagnosis. In 12 mailings, 62 sera from allergic patients were sent to selected laboratories in order to determine total and antigen specific IgE according to the laboratory-specific methods. The values for total IgE varied considerably (73.9% were within +/- 1 SD, 94.3% within +/- 2 SD and 99.1% within +/- 2 SD, but only 0.9% beyond that). Sources of error were mainly attributable to inappropriate equipment and low quality reagents, but also bad test performance, with respect to personnel and the routines. In contrast, antigen specific IgE against pollen, mites, moulds, insect venoms, animal danders, drugs, parasites, environmental and food antigens revealed quite homogeneous results. Out of 1492 data, only 46 (3.1%) had to be declared as "wrong", and the variability of the RAST-classes was low. Whereas the quality of the reagents from all the different suppliers was not absolutely reliable at the beginning of the study, it improved considerably with time, as consequence of our complaints. The comparability of the methods for detecting total-IgE were non-satisfactory, whereas those for antigen specific IgE were generally good. The variety of methods employed (radio- and enzyme immunologic, fluoro- and nephelometric methods, etc.) should entail appropriate consequences, especially critical comparisons within one and the same laboratory; in addition, international standardization of the "normal" values should replace company-standards, and quality control programs for each test system before it is marketed should be mandatory. Our results confirm, that external control should be obligatory for any laboratory.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1992

Results of the multicenter evaluation of the CEDIA Theophylline assay.

We report on the results of the multicenter evaluation of the CEDIA Theophylline assay on Boehringer Mannheim/Hitachi analyzers in 15 clinical laboratories in Europe and U.S.A. Main items of investigation were imprecision, recovery of control sera, interlaboratory survey and method comparisons using patient samples. Imprecision was found to be comparable to other routine methods. An advantage of the CEDIA assay can be seen in the good interlaboratory transferability of results. The new test has been shown to measure very accurately particularly by comparison with HPLC procedures revealing highly correspondent results. The reagent can be used up to one month using multiple recalibration. Due to its high practicability and reliability the CEDIA Theophylline assay can be recommended as a very suitable routine method for therapeutic drug monitoring on random access analyzers like Boehringer Mannheim/Hitachi analysis systems.

Dose-Response Relationship, Drug↗
PubMed1992

Results of the multicenter evaluation of the CEDIA Phenytoin assay.

Thirteen clinical evaluation sites in Europe and U.S.A. investigated the CEDIA Phenytoin assay on Boehringer Mannheim/Hitachi analyzers with respect to imprecision, recovery of control sera, interlaboratory survey, linearity and method comparisons using patient samples. The linear dose-response relationship up to 40 micrograms/mL was confirmed by all participants. Imprecision at therapeutic analyte concentrations equalled that of other routine methods. Recovery of controls was found in a +/- 6% range for target values assigned by the CEDIA assay. The good interlaboratory transferability of the CEDIA assay was confirmed with control material and human samples. The reconstituted reagent can be used up to one month using weekly recalibration. In method comparison studies good correlations to other routine methods were obtained. Results in analyte-free human sera did not deviate systematically from the zero-point. Thus, the accuracy in patient sera has been shown for the CEDIA Phenytoin assay.

Dose-Response Relationship, Drug↗
PubMed1992

Results of the multicenter evaluation of the CEDIA Phenobarbital assay.

The CEDIA Phenobarbital assay has been evaluated in twelve clinical laboratories in Europe and U.S.A. on Boehringer Mannheim/Hitachi analysis systems. The evaluation focused on the analysis of imprecision and accuracy. Within-run and between-day coefficients of variations of the new assay were comparable to those of established routine methods. As demonstrated in an interlaboratory survey study with controls and human sera, results obtained in different laboratories showed a good agreement. The CEDIA Phenobarbital assay measured very accurately, as particularly confirmed by comparison with HPLC. It can be recommended as a reliable and practicable test for monitoring of phenobarbital on Boehringer Mannheim/Hitachi analyzers used in routine clinical chemistry.

Calibration↗
PubMed1992

Cell type and differentiation dependent heterogeneity in retinoblastoma protein expression in SCID mouse fetuses.

The expression pattern of retinoblastoma (Rb) protein has been studied at the single cell level in frozen sections of 16- to 18-day-old SCID mouse fetuses by immunofluorescence staining with mouse monoclonal and rabbit polyclonal antibodies, using conventional epifluorescence and confocal laser scanning microscopy. The nuclei of megakaryocytes, hemopoietic islands of the fetal liver, osteo-, amelo-, and odontoblasts, and skeletal muscle were strongly stained. There was no detectable Rb staining in the basal cell layers of stratified squamous epithelia, but the differentiating, more superficial layers were positive. Intestinal crypts were negative, whereas the villi were positive. In the retina, Rb protein was detectable in the inner ganglion layer but not in the outer neuroblastic layer. In the central nervous system, Rb protein was present in neurons and glia cells as well. The nuclei in the collecting tubules of the kidney, the pancreas, and the adrenal cortex were Rb positive. Analysis of the differentiation dependent expression of Rb protein in relation to the prospective life cycle of the cells in which it appears may pave the way toward an understanding of the tissue specific oncogenic effect of Rb loss in families with hereditary retinoblastoma.

Animals↗
PubMed1991

Tumorigenicity of EBV-carrying lymphoblastoid cell lines (LCLs): distinctive grading in SCID mice.

The in vitro and in vivo growth of lymphoblastoid cell lines (LCLs), Burkitt lymphomas (BLs) and PBL-derived immunoblastomas in SCID mice was studied in parallel. Most, but not all, of the LCLs tested were tumorigenic in SCID mice. Long-term culturing in vitro was not a necessary prerequisite for tumorigenicity. There was a good correlation between in vivo and in vitro growth. Three major classes of cells could be distinguished on the basis of their growth properties.

Animals↗
PubMed1991

Differential susceptibility of BALB/c and DBA/2 cells to plasmacytoma induction in reciprocal chimeras.

Reciprocal chimeras were generated between BALB/c and DBA/2 mice by inoculating newborn recipients of either strain with bone-marrow (BM) cells of the other through the periorbital vein. DBA/2 mice inoculated with the BALB/c with proven chimerism will be referred to as C----D, the reciprocal as D----C. The BALB/c cells carried a Robertsonian 6;15 (Rb6;15) chromosome marker to facilitate identification. The chimeric mice contained between 5% and 70% of donor cells when examined at 4 to 5 weeks of age. Six of 10 C----D developed plasmacytomas (MPC) after 3 x 0.5 ml monthly pristane treatment (incidence 60%) and 8 of 25 (incidence 32%) after 2 to 3 x 0.5 ml pristane followed by Abelson virus (A-MuLV) infection. Seven of 15 D----C developed MPC after pristane treatment (incidence 47%) and 4 of 17 after pristane + A-MuLV (incidence 24%). All tumors that have arisen in both reciprocal chimeras originated from BALB/c cells independently of the degree of chimerism. All tumors contained an Ig/myc translocation. Among the C----D chimeras, 5 carried t(12;15) and I t(6;15) in the pristane-treated group, while 4 carried t(12;15), I t(6;15) and 3 t(15;16) in the pristane + A-MuLV. Among the D----C chimeras 6 carried t(12;15) and I t(6;15) in the pristane-treated group, while 3 t(12;15) and I t(6;15) in the pristane + A-MuLV. No tumors developed in 18 pristane- and 22 pristane + A-MuLV-treated DBA/2 mice nor in 15 pristane- and 17 pristane + A-MuLV-treated (BALB/c x DBA/2)F1 mice. The data indicate that BALB/c and DBA/2 cells differ in their propensity to transform into plasmacytoma in identical host environments after both pristane and pristane + A-MuLV treatment. They also show that the oil granuloma can support MPC development in either type of chimeric host.

Abelson murine leukemia virus↗
PubMed1991

Intraocular tumor formation of RB reconstituted retinoblastoma cells.

It has been reported that replacement of a functional retinoblastoma (RB) gene in RB defective WERI-27 retinoblastoma cells results in complete loss of their tumorigenic potential in nude mice following s.c. injection. We have repeated the identical studies and found that although tumors did not develop s.c., the RB reconstituted cells, either soon after RB virus infection or after long term cultivation, consistently produced tumors when injected intraocularly. These tumor cells, when reestablished in culture, were found to retain a normal RB protein as determined by direct Western blotting and immunocytochemical staining. The tumors, however, occurred with a longer average latency period and with less frequency compared to those produced by the parental RB defective cells. Our results suggest that reintroduction of the RB gene into WERI-27 cells reduces but does not completely suppress their tumorigenic potential. Since retinoblastoma is an eye tumor it also provides further documentation that the use of an orthotopic injection site can be critical when determining the tumorigenicity of a given cell type.

Animals↗
PubMed1991

The epstein-Barr-virus-encoded membrane protein LMP but not the nuclear antigen EBNA-1 induces rejection of transfected murine mammary carcinoma cells.

The EBV-encoded membrane protein (LMP) and the nuclear antigen EBNA-1 were compared for their capacity to induce rejection of transfected murine mammary carcinoma cells in syngeneic hosts. The tumorigenic potential of stable LMP and EBNA-1 expressing sublines of the ACA (H-2f)-derived mammary carcinoma line S6C was tested in pre-immunized syngeneic and semi-syngeneic animals. LMP expressing S6C cells elicited a strong rejection response as demonstrated by the lower tumor take and slower growth in immunized vs. control mice. In contrast, EBNA-1-expressing cells were non-immunogenic in syngeneic hosts and in one semi-syngeneic F1-hybrid. Rejection in 2 additional F1-hybrids did not appear to be due to EBNA-1-specific immune responses. Our findings support the hypothesis that the escape of EBV carrying tumor cells from EBV-specific immune surveillance may be facilitated by the fact that viral gene expression is limited to EBNA-1.

Animals↗
PubMed1991

v-abl does not abolish IL-6 requirement by murine plasmacytoma cells.

Activation of c-myc by juxtaposition to an immunoglobulin locus and introduction of the v-abl oncogene act synergistically in generating a mouse plasmacytoma (PC). The question arose whether the effect of v-abl could be attributed to a deregulation of interleukin-6 (IL-6) production or responsiveness, in view of the fact that IL-6 exerts potent growth-stimulatory activity on PC cells. We studied the effect of IL-6 on the in vitro growth of primary PCs induced by pristane alone (TEPCs) or by pristane + A-MuLV (ABPCs). Five of 13 TEPCs and 3 of 7 ABPCs responded to IL-6. Macrophage supernatants prepared from both TEPCs and ABPCs had similar stimulatory effects on PC cells. From 30 primary PCs (including both TEPCs and ABPCs), we established 9 in vitro lines, 2 of which expressed v-abl. All were able to grow on macrophage feeder layers. Three types of behavior could be distinguished on the basis of growth in feeder-free cultures in the presence and absence of IL-6. Group I contained 4 IL-6-dependent lines. Group II contained 2 IL-6-independent lines (one v-abl expressor) that grew faster in the presence of IL-6. Group III consisted of 3 feeder-dependent lines (one v-abl expressor) that were not significantly stimulated by IL-6. These findings indicate that v-abl expression does not influence IL-6 dependence or responsiveness by itself. The supernatant of one line in group II was able to stimulate PC cells. All 6 lines of Groups I and II carried a typical (12;15) translocation, while all 3 lines in group III had a variant (6;15) or (15;16) translocation.

Abelson murine leukemia virus↗