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Biomedical subjects

G Klein

Publications and source records attributed to G Klein.

At least 631 records · Page 35Linked to original sources
PubMed1986

Detection of a polyoma virus-induced tumor-associated membrane antigen in mouse cells by the macrophage migration inhibition test.

Soluble membrane fractions derived from polyoma tumor cells trigger lymphocytes, derived from polyoma-immunized animals, but not from nonimmunized controls, to release the lymphokine, macrophage migration-inhibitory factor. The reaction can be blocked by sera from polyoma-bearing animals. Absorption of these sera with polyoma cells, but not with nonpolyoma cell lines, abrogates this activity. These findings suggest that there is a polyoma virus-induced membrane component that can induce polyoma-specific macrophage migration inhibition.

Animals↗
PubMed1986

Constitutive activation of oncogenes by chromosomal translocations in B-cell derived tumors.

The mechanisms of chromosomal translocations and its role in Burkitt lymphoma (BL), mouse plasmacytoma (MPC) and rat immunocytoma (RIC) are discussed with particular emphasis on the following questions: 1) Does the cis-relationship between the c-myc oncogene and one of the 3 Ig-loci play a causative role in the genesis of these tumors? 2) How does the juxtaposition activate the myc-gene? 3) What is the functional role of the translocation in the tumorigenic process? Question 1) can be answered with some certainty. In BL, the translocation has been found in 100% of cases so far, with no difference between endemic or nonendemic, EBV-carrying or EBV-negative cases. One exceptional line, BJAB, can be disregarded, since it is not a typical BL. In RIC, all examined tumor had the translocations so far. Only 90% of the MPCs carry the translocations, but high resolution banding of some translocation negative MPCs has shown that they carry an interstitial deletion in the D2/D3 region of Chr. 15, corresponding to the myc locus. Molecular analysis showed a complex rearrangement that has led to the juxtaposition of c-myc and IgH-switch sequences. Sequencing data indicated that they must have arisen by at least two independent translocations and one inversion. A similarly complex rearrangement was found in the first RIC that has been examined. The regularity of the association between the translocation events and the tumors where they occur, together with the similarities between the human, mouse and rat systems can be interpreted by postulating that the activation of c-myc by the translocation represents an essential step in the genesis of these tumors. 2) The transposed myc gene becomes constitutively activated. In all probability, this renders the gene resistant to cell cycle and differentiation dependent regulations that govern its expression in the normal chromosomal location. 3) The hypothesis is advanced that the translocation affects B-cells at the point where an antigen activated cell is about to leave the proliferative process, upon the waning of the antigenic stimulus, and enters a program towards a long lived memory cell.

Animals↗
PubMed1986

[Occupational factors in rheumatic diseases as a principle of rehabilitation--analysis of patients of the pension insurance administration for workers in Austria].

The study evaluates unselected "blue-collar" patients (n = 642) included under the social insurance law guidelines of rehabilitation. Rehabilitation measures had become necessary in these patients because of existing or impending invalidity in diseases of rheumatic origin. In 421 patients (= 66%), a connection with the place of work appeared possible. This entailed adaptation or change of the place of work in 297 patients (= 71%), the result of these measures after a period of two to three years being described. General aspects of occupational rehabilitation measures are discussed.

Arthritis, Rheumatoid↗
PubMed1986

Burkitt lymphoma and genetic markers of immunoglobulin.

The Ig allotype G3m (c3) was numerically more frequent among 70 Kenyan Burkitt lymphoma (BL) cases than in 70 Kenyans with other tumors of the neck (0.02 greater than p greater than 0.01). The distribution of allotypes G1m (a, x) and G3m (b5) did not differ between 50 Caucasian BL cases and blood donors.

Antibodies, Neoplasm↗
PubMed1986

Chromosomal translocations in B-cell derived tumors.

The regular activation of the c-myc oncogene by juxtaposition to one of the immunoglobulin loci by chromosomal translocation in Burkitt's lymphoma (BL), mouse plasmacytoma and rat immunocytoma indicates that these translocations represent an essential, i.e. rate limiting step in the development of these tumors. Since the myc-carrying chromosome appears to break at random, but preserves the integrity of the two coding exons, the exclusive involvement of myc (rather than other oncogenes) requires special comment. It must be relatable to the specific functional features of the precursor cells and to the normal role of the myc protein. Recent evidence indicates that the myc gene is regularly turned off before or at the time when the cell enters a pathway that is programmed to lead it towards a resting G0 state. Clonally expanded B-cells are believed to turn into resting memory cells upon waning of the antigenic stimulus. The normal, non-translocated myc-allele is regularly switched off in both BL and murine plasmacytoma (MPC), indicating that the cell has already obeyed a program that involves the down regulation of myc. The Ig-juxtaposed, translocated myc remains highly expressed, however, and may be responsible for keeping the cells in cycle. The possibility that BL and MPC may arise from candidate memory cells, rather than pre-B cells, is also suggested by the fact that all BL-tumors and derived lines make a heavy chain. Since the myc/Ig juxtaposition is a special case of a non-functional rearrangement, this is only expected if the precursor cell would have been preselected for a functional Ig-product. The memory cell hypothesis is further supported by the fact that the majority of BLs make IgM, most MPC make IgA and the rat immunocytomas make IgE. This could correspond to the most frequent type of the memory cell in the anatomical areas and under the physiological or pathophysiological conditions associated with the natural history of each tumor. This brief review is restricted to oncogene activation by chromosomal translocations in B-cell derived tumors.

B-Lymphocytes↗
PubMed1986

[Relative bioavailability of paracetamol from tablets and suppositories as well as of paracetamol and codeine in a combination tablet].

Eight healthy male volunteers took part in this study to determine the relative bioavailability of Treuphadol oblong tablets (500 mg paracetamol), Treuphadol Plus oblong tablets (500 mg paracetamol, 30 mg codeine phosphate) and Treuphadol suppositories (750 mg paracetamol) against commercial tablets (500 mg paracetamol). Plasma levels of paracetamol and codeine, plus saliva levels of paracetamol for the two paracetamol only formulations, were determined by HPLC and the pharmacokinetic parameters established. The AUC data for paracetamol showed that all four preparations were bioequivalent. The saliva levels of paracetamol demonstrated a good correlation to the corresponding plasma levels. The pharmacokinetic data of codeine from the Treuphadol Plus tablet were compared with corresponding data from the literature. The bioequivalence of codeine when based on this comparison can also be assured.

Acetaminophen↗
PubMed1986

Suprofen sustained release kinetics in healthy male volunteers. 1st communication: a single dose open crossover bioavailability study of suprofen sustained release tablets versus capsules.

An open crossover study was performed in 12 healthy male volunteers to compare the bioavailability of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) 600 mg sustained release tablets versus the suprofen capsule (2 X 200 mg). The pharmacokinetic profiles in plasma and urine were determined by a HPLC assay. In the dose range studied, the two suprofen formulations were not associated with any clinically significant effects on the blood pressure, heart rate or ECG. The results of the physical and neurological examinations showed no abnormal results. The results of haematology, clinical chemistry and urinalysis also showed no significant modifications. However, increased serum creatinine values were observed in some volunteers following suprofen administration. A drug relationship to this finding cannot be excluded with certainty. Two volunteers complained of nausea and vomiting following administration of two suprofen capsules. For this reason, volunteer no. 9 was withdrawn by the investigator from the study and replaced by an eligible substitute. In general, single doses of the two suprofen formulations investigated, were subjectively and objectively well tolerated. From the suprofen plasma-concentration time profiles, it was apparent that, whilst the elimination of suprofen was similar for both formulations, there was a marked delay in absorption of the tablet formulation. This formulation resulted in statistically significantly later maximum plasma levels and longer mean residence time (p less than 0.001). In comparison to the reference capsule formulation, the tablet had statistically significantly lower (75%) bioavailability. Measurement of suprofen concentrations in the urine indicated that less than 1% of the administered dose was excreted by this route.

Adolescent↗
PubMed1986

Suprofen sustained release kinetics in healthy male volunteers. 2nd communication: a multiple dose steady-state kinetics of suprofen sustained release tablets during 6 days in healthy male volunteers.

To 12 healthy male volunteers, who had given their consent, 11 administrations of alpha-methyl-4-(2-thienyl-carbonyl)phenylacetic acid (suprofen, Suprol) sustained release tablets 600 mg were given twice a day with a dosage interval of 12 h. It could be demonstrated that suprofen given as multiple dose application of sustained release tablets was well tolerated. Effective mean plasma levels were reached after the second dosage. There was no indication of accumulation nor accelerated elimination during the 6-day period. There was no statistically significant difference between the mean plasma curve after the last administration of the 6-day period and the mean plasma curve after the 3rd application. Also the AUC's in the respective intervals turned out not to be statistically significantly different from each other. Clinical and laboratory tests showed no clinically relevant deviations from the normal range. No adverse reactions whatsoever were observed.

Adult↗
PubMed1985

Mapping of the c-myc, pvt-1 and immunoglobulin kappa genes in relation to the mouse plasmacytoma-associated variant (6;15) translocation breakpoint.

A variant mouse plasmacytoma (MPC)-associated translocation chromosome has arisen by pericentric inversion and exchange of the distal segments of a Robertsonian 6;15 fusion chromosome in the CAK TEPC 1198 mouse plasmacytoma, as described earlier. In situ hybridization was performed on the normal and the inverted Rb chromosomes, using myc and kappa probes. On the normal Rb chromosome, myc was in the 15 D2/3 region, whereas kappa hybridized in the 6 C2 area, as expected. On the inverted Rb chromosome, myc remains on the centrometric side of the translocation breakpoint on the chromosome 15-derived portion, whereas kappa has moved to the chromosome 6-derived segment that joined the same breakpoint on the telomeric side. Taken together with our recent demonstration that the murine c-myc locus is oriented 'head up' on chromosome 15, and with the results of Cory and co-workers concerning the relationship between the kappa gene and the associated pvt-1 region in the CAK TEPC 1198 tumor, the following conclusions can be drawn: (i) in the variant translocation of the CAK TEPC 1198 MPC, the breakage occurs 3' of the c-myc gene, as in the human Burkitt lymphoma-associated variant translocations; (ii) the pvt-1 gene on chromosome 15 is distal to the myc gene; (iii) the kappa light chain locus is oriented 'head up' on mouse chromosome 6 and faces pvt-1 and, beyond it, c-myc, in a head-to-tail configuration.

Animals↗
PubMed1985

Lung colonization and metastasis by disseminated B16 melanoma cells: H-2 associated control at the level of the host and the tumor cell.

We have studied the experimental metastasis of H-2+ and H-2- melanoma sublines in H-2b/b and H-2a/b hosts by enumerating pulmonary colonies 20-50 days after i.v. inoculation of tumor cells. In H-2b/b hosts, the H-2+ "B16-S" cells gave rise to a moderate number of metastatic colonies (mean: 6.3 +/- 6). The "BL16-L" sublines that had lost the expression of MHC class-I antigens, according to FACS-analysis and quantitative absorption tests, gave no metastases under the same conditions. Pretreatment of the H-2+ met+ B16-S with interferons (beta or alpha + beta) increased their H-2 antigen expression and the number of metastatic colonies (mean: 25 +/- 16). Interferon pretreatment of B16-L cells partially restored their H-2b expression and induced them to form a small number of metastatic colonies. The reduction in pulmonary colonization by the H-2 negative B16-L cells could be attributed to their rapid elimination by natural killer cells, already observed within 24 hr of inoculation of radiolabelled cells. H-2- B16-L cells were more susceptible than H-2+ B16-S cells to in vitro lysis by poly I:C-treated splenocytes, and they acquired full metastatic abilities if the hosts were treated with anti-asialo GM-I serum. In H-2a/b heterozygous hosts, the H-2+ B16-S cells also failed to metastasize. Reduced pulmonary colonization was evident by 24 hr after injection in comparison with H-2b/b hosts, and could be reversed by anti-asialo GM-I treatment of the hosts. In vitro, H-2a/b splenocytes were more cytotoxic to the B16 cells than syngeneic effectors. The results are discussed in relation to a recent hypothesis on a surveillance mechanism for elimination of cells on the basis of their lack (or insufficient expression) of host MHC genes.

Animals↗
PubMed1985

Amplification of the c-myc oncogene in human plasma-cell leukemia.

We have examined primary leukemia cells from multiple myeloma and plasma-cell leukemia patients for rearrangement, amplification and expression of c-myc oncogene. No rearrangement or detectable amplification of the c-myc could be found in 21 cases of multiple myeloma. In contrast, 2/3 cases of plasma-cell leukemia showed amplification of the oncogene with concomitant higher level of expression.

Cell Line↗
PubMed1985

Effect of cyclosporin-A (CsA) on the ability of T lymphocyte subsets to inhibit the proliferation of autologous EBV-transformed B cells.

We have analyzed the effect of Cyclosporin-A (CsA) on the in vitro suppression of Epstein-Barr virus (EBV)-induced B-cell proliferations separated on the basis of cell density. CsA abolished the growth-inhibitory capacity of high-density T cells but influenced only marginally the activity of low-density lymphocytes; this suggested that different mechanisms mediate suppression in the two subsets. Stimulation with irradiated EBV-transformed cells had a different impact on the activity of low- and high-density lymphocytes. Proliferative and cytotoxic responses were inversely correlated, i.e. high-density cells proliferated but exerted low cytotoxicity, while the lytic activity of the low-density subset was stronger in the absence of significant cell proliferation. Proliferation and generation of cytotoxicity were abrogated by CsA in both subsets. The activities could be restored by addition of exogenous IL-2, suggesting that the drug may interfere with the cascade of lymphokine--cell interactions which leads to activation of immune responses. From the analysis of athe CsA effects on the two subsets it seems that the high-density one contains specific memory T cells which are activated and proliferate upon encounter with EBV-infected cells. On the other hand, low-density lymphocytes are induced to release soluble factors with antiproliferative activity. The secretory function was resistant to the suppressive effect of CsA.

B-Lymphocytes↗