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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 559 records · Page 31Linked to original sources
PubMed1988

Aberrant class switching juxtaposes c-myc with a middle repetitive element (LINE) and an IgH intron in two spontaneously arising rat immunocytomas.

Our previous studies of spontaneously arising rat immunocytomas of the Lou/Wsl strain have shown that Ig switch regions are frequently the targets for c-myc recombination. In several tumors, however, we were unable to show recombination of the c-myc with Ig switch regions. We have cloned the rearranged c-myc fragments from 2 of these tumors, IR209 and IR223, and found that the c-myc recombines with a LINE region in the IR209 and with intron 1 of the epsilon locus in the IR223. Although switch regions are not found at the breakpoints, the sequences at the breakpoints share limited homology with Ig switch recognition sequences. This suggests that the switch recombinase enzymes are able to recognize sequences in addition to the defined switch recombination sites. At the same time, both the LINE and epsilon intron 1 sequences are located within the Ig cluster, providing further evidence for the selection of c-myc activation by Ig sequences in the pathogenesis of rat immunocytoma, mouse plasmacytoma, and Burkitt's lymphoma.

Animals↗
PubMed1988

The role of science.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗
PubMed1988

[Repeated injection of atracurium for muscle relaxation in abdominal surgery].

21 patients selected for abdominal surgery received intravenously after initiation of neuroleptic analgesia for intubation, 0.5 mg/kg body weight (BW) of atracurium. Relaxation was maintained by repeat doses of 0.2 mg/kg BW atracurium. Both the time of intubation and the time of giving the repeat dose depended on the electromyographically measured stimulus response to supramaximal stimulation of the ulnar nerve (Datex-NTM, "Train-of-Four" stimulation). Intubation was effected at maximal inhibition of stimulus response, on the average after 195 +/- 90 sec. The duration of clinical efficacy was 33 +/- 8 min on the average, the recovery index 13 +/- 7 min and the duration of the full effect 54 +/- 6 min. The repeat doses were administered as soon as stimulus response recovered to 25% of the original value. Up to a cumulative total dose of 1.5 mg/kg BW atracurium no extension of the duration of clinical efficacy and of the full effect was seen, but there was a prolongation of the recovery index. The "Train-of-Four" quotient during recovery of relaxation was independent of the cumulative total dose. In the dosage levels described here, atracurium hardly exercised any action on pulse rate and blood pressure.

Abdomen↗
PubMed1988

Surgical service nosocomial infections at a Veterans Administration medical center.

Nosocomial surgical infections at a Veterans Administration medical center were monitored from February 1986 to June 1987 (17 months). Three hundred twenty-four patients had 508 nosocomial infections, including 66 patients in whom cultures were not performed. The remaining 258 patients had 584 microorganisms, including gram-negative bacilli (56.8 percent), gram-positive cocci (33.6 percent), and yeasts (8.4 percent). The most common isolates were Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, group D enterococci, and Staphylococcus epidermidis. Antimicrobial susceptibilities were similar for nosocomial and all hospital isolates combined 84.5 percent of the time; all hospital isolates combined were more resistant in 5.5 percent and nosocomial isolates in 10.0 percent. The infection rate for surgical wounds was only 2.5 percent. When all nosocomial infection sites were compared, however, the rate for lower respiratory tract and some other infections appeared high and disproportionate. The significance of this finding is questionable because of a lack of comparable published reports from other Veterans Administration medical centers. The importance of patient population at risk of obtaining some nosocomial infections (especially lower respiratory) may be greater in adult men than in other patient populations.

Adult↗
PubMed1987

The approaching era of the tumor suppressor genes.

Genes that can inhibit the expression of the tumorigenic phenotype have been detected by the fusion of normal and malignant cells, the phenotypic reversion of in vitro transformants, the induction of terminal differentiation of malignant cell lineages, the loss of "recessive cancer genes," the discovery of regulatory sequences in the immediate vicinity of certain oncogenes, and the inhibition of tumor growth by normal cell products. Such tumor suppressor genes will probably turn out to be as, if not more, diversified as the oncogenes. Consideration of both kinds of genes may reveal common or interrelated functional properties.

Genes, Recessive↗
PubMed1987

Paired Epstein-Barr virus (EBV)-negative and EBV-converted Burkitt lymphoma lines: stimulatory capacity in allogeneic mixed lymphocyte cultures.

Epstein-Barr virus (EBV)-negative Burkitt lymphoma lines (BLE-) and their in vitro EBV-converted sublines (BLEc), obtained by infection with the P3HRI and B95-8 strains of EBV, were compared for their capacity to induce T-lymphocyte proliferation in allogeneic mixed lymphocyte cultures (MLC). Regardless of the virus strain used for conversion, the BLEc lines induced a considerably stronger primary MLC response than their EBV-negative parentals. Only the BLEc lines were able to maintain T-lymphocyte proliferation in repeated stimulations. The low proliferative response observed in cultures stimulated with BLE- cells was not due to the generation of suppressor cells or to the release of inhibitory factors. The increased stimulatory capacity of BLEc lines was unrelated to changes in expression of MHC class-I and class-II antigen, or of B-cell activation markers, and was not due to the reactivation of EBV-specific memory T cells, since lymphocytes from EBV-seropositive and seronegative donors responded similarly. The results indicate that the capacity of BL cells to elicit cellular immune responses may be influenced by their EBV-carrying status.

Antigens, Viral↗
PubMed1987

Identification of inositol hexaphosphate in 31P-NMR spectra of Dictyostelium discoideum amoebae. Relevance to intracellular pH determination.

A sugar phosphomonoester, myo-inositol hexakisphosphate (phytic acid), has been identified as a major phosphorylated metabolite in Dictyostelium discoideum amoeba. Its intracellular concentration was estimated to be 0.7 mM. The identification was made in perchloric acid extracts on the basis of 31P-NMR chemical shift values and their variations with pH, by addition of authentic compound and by hydrolysis with wheat phytase. Perchloric acid extracts were prepared so as to avoid losses of insoluble salts of polyphosphorylated compounds with divalent cations. The glycolytic intermediate, 3-phosphoglycerate accumulated intracellularly in amoebae incubated in the presence of fluoride. The pH sensitive NMR signal of 3-phosphoglycerate was used to monitor cytosolic pH and a value of pH 7.4 was found in aerobic Dictyostelium amoebae.

6-Phytase↗
PubMed1987

Cellular and humoral immune responses to synthetic peptides deduced from the amino-acid sequences of Epstein-Barr virus-encoded proteins in EBV-transformed cells.

Ten synthetic peptides containing 18-22 residues deduced from the amino-acid sequences of the EBV-encoded latent-infection-associated membrane protein (LMP) and the 2 principal nuclear antigens, EBNA-1 and EBNA-2, were tested for their ability to induce lymphokine release from sensitized T-cells of EBV-seropositive donors, as measured by the leukocyte migration inhibition assay (LMI). Only one of the 10 free peptides induced EBV-specific LMI. After Sepharose-coupling, 4 additional peptides were regularly active. In parallel, the sera of the same and other donors were screened for synthetic peptide-binding antibodies, as measured by an ELISA assay. Antibodies to 9 of the 10 peptides were detected in 25-80% of EBV-antibody-positive, but not in EBV-antibody-negative sera. A comparison of the two responses indicates that the humoral immune system tends to react with more epitopes on a given protein than the cellular immune system. Furthermore, the antibody reactivity pattern to different epitopes is more variable from individual to individual than the T-cell response. Also, the epitopes detected by antibodies and sensitized T-cells are often not identical.

Amino Acid Sequence↗
PubMed1987

The role of chromosome 15 in murine leukemogenesis. II. Relationship between tumorigenicity and the dosage of lymphoma vs. normal-parent-derived chromosomes 15 in somatic cell hybrids.

Somatic cell hybrids were generated between an MCF-virus-induced 15-trisomic T-cell lymphoma of AKR origin with a proviral insertion near the c-myc locus, and normal diploid fibroblasts or lymphocytes of CBAT6T6 origin. Three lymphoma/fibroblast fusions were performed. Six independently-derived clones from 2 fusions were tested for tumorigenicity. Three of the 6 clones were weakly malignant (take incidence 20% below), and 3 were strongly malignant (take incidence over 80%). All 3 lymphoma/lymphocyte hybrids and 6 derived clones were strongly malignant. All hybrids contained a nearly complete chromosomal complement of both parental cells. This was confirmed at the molecular level by determining the ratio of germ-line (G) vs. rearranged (R) myc-carrying Eco RI fragments that showed the expected 1.9-2.7:1 proportion. Malignant segregants selected from the weakly malignant lymphoma/fibroblast hybrids by in vivo inoculation showed changed 15-chromosome ratios. Four out of the 6 clones showed amplification of the lymphoma-derived 15-chromosome that carries the R-myc fragment and a concomitant decrease in the average number of the G-myc-carrying chromosomes. This was deduced from the fact that the G:R ratio was between 2 and 3:1 in the in vitro hybrids but became inverted (1:2-3) in the tumors. Two tumors showed no amplification of R-myc. G-myc was decreased. One of these tumors showed a change in the G:R ratio from 2.5:1.0 to 1.2:1.0, while the other was essentially unchanged (1.9:1.0 in the in vitro clone and 2.2:1.0 in the derived tumor). These findings support the notion that both the amplification of the lymphoma-derived 15-chromosome with the retrovirally rearranged c-myc carrying fragment and/or the loss of the G-myc-carrying 15-chr can contribute to the tumorigenic potential of the hybrids.

Animals↗
PubMed1987

Down-regulation of the EBV-encoded membrane protein (LMP) in Burkitt lymphomas.

A radioimmunoassay (RIA) has been developed and used to determine the expression of LMP-a membrane protein encoded by the LT3 region of the Epstein-Barr virus (EBV) genome-in cell lines of various origins. The RIA was highly sensitive, specific and reproducible. All EBV-negative cell lines were LMP-negative and 18 of 21 EBV-carrying cells were LMP-positive. LMP concentrations varied widely, ranging approximately from less than 4 ng up to 650 ng/mg protein. In several instances comparisons were made between lymphoblastoid (LCLs) and Burkitt lymphoma (BL) cell lines (EBV-positive or EBV-converted sublines of originally EBV-negative BL) originating from the same patient. In all such cases LMP and LMP-specific mRNA levels were higher in the LCLs. Most of the LMP was found in the cytosol fraction, yet this fraction was negative in immunoblotting tests. However, antiserum preincubated with the cytosol lost its ability to react in immunoblotting with membrane LMP, indicating that the 2 LMP forms (membrane and cytosol) are completely cross-reactive.

Antigens, Viral↗
PubMed1987

Stable transfection of a human lymphoma line by sub-genomic fragments of Epstein-Barr virus DNA to measure humoral and cellular immunity to the corresponding proteins.

An Epstein-Barr virus (EBV)-negative human lymphoid B-cell line, DG75, was stably transfected with recombinant selection vectors that carry a subfragment of the BamHI WYH region (nucleotides 44664 to 50628), the BamHI K fragment, or a subfragment of the EcoRI D region (nucleotides 166614 to 170149) of B95-8 EBV DNA. These fragments contain the coding exons for the EBV-determined nuclear antigens EBNA2 and EBNA1, and the membrane antigen LMP, respectively. Antigen expression of the cells was detected by immunofluorescence. EBNA2 was expressed in 80-100% of the transfected cells, in contrast to EBNA1 which was expressed in only 25%, and LMP in only about 5% of the cells. Humoral antibody responses were measured by immunofluorescence and compared to cellular immunity as determined by the leukocyte migration inhibition (LMI) technique. Extracts from transfected cell lines expressing EBNA1, EBNA2 or LMP elicited an LMI response with cells from healthy EBV-seropositive individuals whereas the extract from the parental DG75 cell line did not. The results demonstrate the value of stably transfected cell lines expressing a defined EBV antigen for the monospecific analysis of host responses to the EBV-encoded antigen complex in growth-transformed cells.

Antibody Formation↗
PubMed1987

Defective cell-mediated response to EBV-transformed B cells in a healthy individual with regular EBV antibody titers.

We have analyzed the EBV-related immune parameters of a healthy EBV-seropositive individual (ST) who has regular antibody titers but defective inhibitory capacity toward the growth of autologous EBV-infected B cells. This in vitro function reflects the EBV-specific memory because it does not occur in experiments performed with cells of seronegative individuals. An analysis of events following in vitro EBV infection showed that lymphocytes of ST behaved in some tests in the same way as those collected from seronegative individuals. These parameters were: lack of gamma-IFN production 24 hr after EBV infection; low production of soluble factors that inhibit EBV-induced B-cell proliferation; lack of generation of LCL selective cytotoxicity after repeated stimulation with autologous LCL; and high proportion of EBNA-positive cells in 7-day-old EBV-infected cultures. On the other hand, cellular memory to the virus detected by the production of IL-2 24 hr after infection, and by the production of LIF upon exposure to EBV-encoded antigens, conformed with the results obtained with seropositive individuals. T-cell-mediated inhibition of EBV-induced B-cell growth in vitro has been regarded as a corollary of in vivo control of EBV-infected B cells. However, it is absent or has a low efficiency in certain disease categories which are not accompanied by risk of B-EBV growth. Our results with a healthy individual also indicate that several mechanisms contribute to a harmless life-long virus carrier state.

Adult↗
PubMed1987

Conversion of the lymphoma line "BJAB" by Epstein-Barr virus into phenotypically altered sublines is accompanied by increased c-myc mRNA levels.

The steady-state level of c-myc proto-oncogene mRNA was investigated in the EBV-negative human B-lymphoma line BJAB and 2 sublines that have been converted by EBV into stable EBV-genome-carrying and EBNA-positive status. The EBV-converted sublines expressed c-myc at a 2- to 6-fold higher level than the original BJAB during exponential growth. The EBV-positive BJAB lines are known to differ from the parent line in several phenotypic characteristics, including increased agarose clonability, lower serum requirement and, in one case, increased tumorigenicity in nude mice. The pattern of increased c-myc expression accompanying EBV conversion was not observed in the myc/Ig translocation-carrying Burkitt lymphoma line RAMOS or in 2 of its EBV-converted sublines.

Actins↗
PubMed1987

Studies on the polyoma tumor-specific transplantation antigen (TSTA): selection and characterization of TSTA-negative segregants from somatic hybrids.

Two polyoma-TSTA-negative variants were selected independently from a polyoma fibrosarcoma/Moloney lymphoma somatic hybrid, by repeated passages in polyoma-virus-preimmunized mice. One of the variants had lost all its polyoma DNA, while the other only retained a deleted piece of its integrated polyoma DNA. In contrast to the parental hybrid clone, none of the variants produced detectable amounts of T-antigens. This finding indicates that a detectable expression of the products of the polyoma virus early genome, the T-antigens, is important either directly or indirectly for the expression of TSTA.

Animals↗
PubMed1987

[Effect of pulsed dye laser radiation on the capillary vessels of the skin].

Up to now microvaporization has been considered the basic mechanism of vascular damage induced by pulsed dye laser. Regarding the laser-tissue interaction, we present experimental results giving evidence of the significance of sound waves. Thus the transformation of photoacoustic energy is proved, facilitating the explanation of experimental and therapeutic effects.

Capillaries↗
PubMed1987

23Na NMR study of intracellular sodium ions in Dictyostelium discoideum amoeba.

The intracellular sodium concentration in the amoebae from the slime mold Dictyostelium discoideum has been studied using 23Na NMR. The 23Na resonances from intracellular and extracellular compartments could be observed separately in the presence of the anionic shift reagent Dy(PPPi)7-2 which does not enter into the amoebae and thus selectively affects Na+ in the extracellular space. 31P NMR was used to control the absence of cellular toxicity of the shift reagent. The intracellular Na+ content was calculated by comparison of the intensities of the two distinct peaks arising from the intra- and extracellular spaces. It remained low (0.6 to 3 mM) in the presence of external Na+ (20 to 70 mM), and a large Na+ gradient (20- to 40-fold) was maintained. A rapid reloading of cells previously depleted of Na+ was readily measured by 23Na NMR. Nystatin, an antibiotic known to perturb the ion permeability of membranes, increased the intracellular Na+ concentration. The time dependence of the 23Na and 31P NMR spectra showed a rapid degradation of Dy(PPPi)7-2 which may be catalyzed by an acid phosphatase.

Cations, Monovalent↗
PubMed1987

[Fibrinolytic treatment of deep venous thromboses with streptokinase at an ultrahigh dosage].

Twenty-one patients with deep vein thrombosis were treated for six hours per day in accordance with an "ultrahigh" dose scheme with 1,500,000 units/hour streptokinase. A maximum of two such cycles were administered in the first ten patients, and the subsequent patients received up to five cycles as required. In terms of clinical chemical parameters, a pronounced lowering of fibrinogen with corresponding elevation of fibrin(ogen) cleavage products regularly occurred during the first cycle. There were great differences in the individual times for which these alterations persisted (12-72 hours). The alterations during the subsequent cycles were very much less, probably because of the pronounced lowering of the plasminogen concentration. The clinical tolerance (including hemorrhagic complications) was roughly comparable with that of a streptokinase treatment with conventional doses. Phlebographic checking of the result of treatment showed that the ultrahigh dosed intermittent dosage scheme is a highly effective treatment procedure with which the duration of treatment can be appreciably shortened compared to conventional dosage schemata: in four cases, a full recanalization could already be attained after a single cycle.

Adolescent↗