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Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 541 records · Page 30Linked to original sources
PubMed1990

Differences in PCR reactivity between HIV proviruses from individuals in Ethiopia and Sweden.

The polymerase chain reaction (PCR), using primer pairs in the gag, pol, and env regions, was used in a comparative study of HIV-1 DNA in peripheral mononuclear blood cells from HIV-1-seropositive individuals in Ethiopia and Sweden. Although all Swedish samples were positive by PCR, the reactivity was more pronounced in samples from late stages than in those from early stages of infection. Six of nine Ethiopian samples from HIV-1-seropositive patients were positive by PCR, but the reactions were much weaker than those observed for Swedish samples, and in most cases seen with one primer pair only. These results suggest that the burden of HIV-1 DNA in peripheral mononuclear blood cells increases with advancing disease. PCR using primer pairs designed to detect HIV-1 infection in Europe and North America is not always suitable for the detection of HIV-1 infection in Ethiopia. The differences in PCR reactivity could possibly be a consequence of differences regarding host responses to the virus in the two countries, but more likely due to genomic differences between HIV-1 strains prevalent in Ethiopia and Sweden.

AIDS-Related Complex↗
PubMed1990

Trisomy 14 in atypical chronic myeloid leukemia.

Trisomy 14 was the sole karyotypic anomaly in three patients with Ph1-negative chronic myeloid leukemia, and the only abnormality in one of three clones in a fourth case. The hematologic features were partly myeloproliferative, partly myelodysplastic, and included myeloid hyperplasia, neutrophilia without basophilia, a relatively high number of immature granulocyte precursors in the peripheral blood, and monocytosis in three and dysgranulopoiesis in two of the patients. These data, in combination with the patients' high age at diagnosis, their short survival, and the lack of rearrangements of the major breakpoint cluster region (M-bcr) in the two cases where cells were available for molecular analysis, indicate that all four patients suffered from atypical chronic myeloid leukemia (aCML). We suggest that trisomy 14 may be a characteristic karyotypic abnormality in this hematologic disorder.

Aged↗
PubMed1989

Integration of the transposon-like element ETn upstream of V lambda 2 in the cell line P3X63Ag8.

The cell line P3X63Ag8 and hybridomas obtained with it contain two rearranged V lambda 2 EcoRI fragments--6.8 kb and 7.4 kb in size. Southern blot analysis, molecular cloning, and mapping revealed that the rearrangements are related to one another and are not due to normal VJ joining. Sequence analysis indicated that the rearrangement was due to the integration of the transposon like element ETn upstream of V lambda 2. Because a normal embryonic V lambda 2 is still retained in this cell line one of the rearranged fragments must be due to a secondary event after the aneuploidization of the plasmacytoma. RNA dot blot analysis showed that the transposon is strongly expressed not only in embryonic cells but also in plasmacytomas, B lymphomas and T cell lines.

Animals↗
PubMed1989

Inhibition of human erythrocyte and leukocyte aldehyde dehydrogenase activities by diethylthiocarbamic acid methyl ester. An in vivo metabolite of disulfiram.

The inhibitory effects of diethylthiocarbamic acid methyl ester (DTC-Me), an in vivo metabolite of disulfiram (Antabuse), on the aldehyde dehydrogenase (ALDH; EC 1.2.1.3) activities in human erythrocytes and leukocytes were studied. ALDH assays were performed by incubating intact isolated blood cells in the presence of different concentrations of DTC-Me, using 3,4-dihydroxy-phenylacetaldehyde, the aldehyde derived from dopamine, as the substrate. DTC-Me was more selective as inhibitor of the leukocyte ALDH activity (which resembles the liver "mitochondrial" low Km ALDH), whereas both disulfiram and diethyldithiocarbamic acid, the reduced monomer of disulfiram, were more selective for the erythrocyte ALDH (which is similar to the "cytosolic" high-Km ALDH). Diethylthiocarbamic acid, the free acid of DTC-Me, was less potent than DTC-Me, and caused similar inactivation of the erythrocyte and leukocyte ALDH activities. The inhibition of ALDH by DTC-Me could not be completely restored by extensive dilution of intact or sonicated blood cell samples, which indicated that ALDH was irreversibly inhibited. Since the inhibition patterns with DTC-Me agrees with the previously reported patterns of inhibition of the high-Km and low-Km isozymes after the administration of disulfiram, the results suggest that DTC-Me might be the active in vivo inhibitory metabolite of disulfiram.

Aldehyde Dehydrogenase↗
PubMed1989

Diethylthiocarbamic acid methyl ester. A potent inhibitor of aldehyde dehydrogenase found in rats treated with disulfiram or diethyldithiocarbamic acid methyl ester.

Rats were treated with disulfiram (Antabuse, DSF) or its metabolite diethyldithiocarbamic acid methyl ester (Me-DDC) and challenged with ethanol. The blood pressure response to ethanol was followed and blood was analyzed for DSF, Me-DDC and diethyldithiocarbamic acid (DDC). The rat liver aldehyde dehydrogenase (ALDH) isozyme activities were measured 2 hr after the ethanol challenge. Both treatments produced a significant fall in the blood pressure when challenged with ethanol, probably caused by a marked decrease in hepatocyte low Km and high Km activities. The mean plasma concentration ranges of Me-DDC and DDC were found to be 49-1241 nmol/l and 182-841 nmol/l, respectively, whereas DSF was undetectable. In addition, it was found that inactivation of hepatocyte low Km ALDH activity was dependent on preoxidation of Me-DDC by the microsomal cytochrome P-450 mixed function oxidases. Me-DDC was found to be oxidized under aerobic conditions in the presence of NADP to form diethylthiocarbamic acid methyl ester (Me-DTC). The structure was confirmed from its MS/EI fragmentation spectrum. Me-DTC was found to be a potent inhibitor of low Km ALDH when added to rat liver homogenate. The compound was also identified as a metabolite in rat blood collected from the DSF and Me-DDC treated rats, and in blood from human alcoholics on DSF treatment. Me-DTC appears to be more selective for the low Km isozymes whereas the opposite seems to be the case for the hydrolytic product, DTC.

Aldehyde Dehydrogenase↗
PubMed1989

Inhibition of erythrocyte aldehyde dehydrogenase activity and elimination kinetics of diethyldithiocarbamic acid methyl ester and its monothio analogue after administration of single and repeated doses of disulfiram to man.

The elimination kinetics of the methyl esters of diethyldithiocarbamic acid (Me-DDC) and its monothio analogue (Me-DTC) has been compared in ten alcoholic patients after a single oral dose of 400 mg disulfiram (Antabuse). Erythrocyte aldehyde dehydrogenase (ALDH) activity was continuously followed in the subjects until complete inactivation. The relation between individual steady-state concentrations of Me-DTC in plasma, blood acetaldehyde concentration and the dose of disulfiram sufficient to give the disulfiram alcohol reaction was investigated in 12 healthy volunteers treated with increasing doses of disulfiram and then challenged with ethanol. The mean peak plasma concentration of Me-DDC occurred at 1.8 h and its plasma half-life was 6.3 h. The corresponding values for Me-DTC were 3.3 h and 11.2 h, respectively. This suggests oxidative formation of Me-DTC from Me-DDC. In alcoholics with a rapid decrease in erythrocyte ALDH activity (in less than 5 days), the mean peak plasma concentration of Me-DTC was 278 nmol.l-1, whereas the peak concentration was below the detection limit in subjects with a prolonged inactivation time (7-20 days). The healthy volunteers were divided into three groups of four subjects, with clinically valid disulfiram alcohol reactions at 100, 200, and 300 mg doses of disulfiram, respectively. The mean plasma concentrations of Me-DTC at steady-state were proportional to the disulfiram doses given, compared within groups at different doses, and between groups at equal and different optimal doses of the drug. The concentrations of Me-DTC were significantly increased, as compared above, whereas the blood concentrations of acetaldehyde were not significantly increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural chromosome aberrations in fibroblasts from sarcoma and non-Hodgkin's lymphoma patients.

The frequency and distribution of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced structural aberrations, i.e., chromatid and chromosome gaps, breaks, and exchanges, were studied in fibroblasts from 16 patients with sarcoma, 15 with non-Hodgkin's lymphoma (NHL), and 14 controls. The mean frequencies of aberrant cells, and gap, break, and gap + break events per 100 cells were 22.9, 5.1, 28.6, and 33.7 in the sarcoma group; 19.1, 5.0, 22.5, and 27.5 in the NHL group; and 23.5, 6.1, 33.5, and 39.6 in the control group. None of the differences between the groups were statistically significant. The distribution of MNNG-induced aberrations was non-random (P less than 0.001) in all 3 groups. Eight, 11, and 17 chromosome bands in the sarcoma, NHL, and control groups, respectively, were particularly break-prone. Only 2 hot spots in the sarcoma group (1p32, 11q23), and 3 in the NHL group (1p36, 3q25, 6p21), coincided with the 25 and 60 bands known to be involved in primary rearrangements in sarcomas and NHL. We conclude that neither the frequency nor the distribution of MNNG-induced chromosomal aberrations indicates any latent chromosomal instability in sarcoma and NHL patients.

Chromosome Aberrations↗
PubMed1989

Flow cytometric DNA analysis: a prognostic tool in non-Hodgkin's lymphoma.

Surgical biopsies from 234 untreated patients with non-Hodgkin's lymphoma (NHL), classified according to the Kiel nomenclature, were analysed with respect to proliferative activity (S-phase) and DNA content by flow cytofluorometric (FCF-DNA) analysis. The percentage of cells in S-phase was significantly higher in lymphomas of high compared to low grade NHL (p less than 0.001). Patients with lymphomas of high grade histology and low S-phase values (less than 5.6%) achieved complete remission (CR) more often (p less than 0.05) and survived significantly longer than those with high S-phase values (p less than 0.05). In the low grade NHL group the S-phase value did not correlate to response. S-phase correlated to survival for patients with the lymphocytic (CLL & IC) (p less than 0.05) and follicle center cell (FCC) derived (p less than 0.01) but not in blastic (LB, IB, Burkitt) NHL. DNA-aneuploidy was associated with poor response to therapy and shorter CR duration in low grade NHL (p less than 0.05 for both). However, the degree of DNA-ploidy (neardiploid or aneuploid) did not correlate to survival in any of the NHL groups analysed (high- or low grade, lymphocytic, FCC derived or blastic). The Cox regression analysis indicated that the S-phase value was a stronger predictor of survival than histopathology, stage or age, especially in low grade NHL. These results suggest that S-phase analysis should be included in the clinical evaluation of NHL patients as a prognostic indicator.

DNA↗
PubMed1989

Constitutional chromosome instability and cancer risk.

Acquired, clonal chromosome abnormalities are thought to be of pathogenetic importance in human cancer; at the cellular level, neoplasia is best viewed as a genetic disease. It is therefore logical to suggest that cancer risk must somehow be related to individual variations in genomic stability. Those persons whose chromosomes are less stable will, on average, be the ones who are most likely to develop cancer. The testing of this hypothesis shows that, apart from the autosomal recessive chromosome breakage syndromes, only patients with adenomatosis of the colon and rectum have, consistently and by different groups, been found to display elevated spontaneous and clastogen-induced chromosome breakage frequencies. Some evidence indicates a similar tendency in patients with dysplastic nevus syndrome, basal cell carcinoma, cervix cancer, and Kaposi's sarcoma. For several other cancers the data strongly argue against any inherent genomic instability. Although most results thus fail to support constitutional chromosome fragility as a factor of importance in tumorigenesis, conclusive falsification of the hypothesis cannot be said to have been obtained. The possibility remains that variations in chromosome stability and clastogen sensitivity between different cell types, and also difficulties in selecting the most appropriate carcinogens in clastogen-exposure tests, may have masked systematic constitutional differences between patients and controls in the breakage assays.

Chromosome Aberrations↗
PubMed1989

Chromosome abnormalities in a pancreatic adenocarcinoma.

Short-term cultures initiated from a pancreatic adenocarcinoma were cytogenetically investigated. The composite karyotype was 74-76,XX,+X,+2,+3,+del(3)(p21),+5,+5,+der(7) t(1;7)(q21;p22),+der(7),del(8)(p21),+del(8)(p21),+der(8)t(8;?)(q24; +),+9,+9,+10,+10,+11,+11,+12,+13,+14,+der(14)t(14; +)(p11;?),+der(16)t(15;16)(q11;p13),+der(16),+der(17)t(17;?) (p11;?),+der(17),+18,+20,+20,-21,-21,+22,+22,+1-3mar. A comparison with the few previously cytogenetically characterized cases of this tumor type reveals no consistent abnormalities.

Adenocarcinoma↗
PubMed1989

Basosquamous papilloma. A benign epithelial skin tumor with multiple cytogenetic clones.

Cytogenetic analysis of short-term cultures from a basosquamous papilloma revealed the following mosaic karyotype: 46,XX,t(2;5)(q31;q31),t(8;15)(p21;q21)/46,XX,t(7;17)(p13;p13)/47,XX, t(3;20)(q12;p13),+7/46,XX,t(1:12)(p12;q13). The finding of four abnormal, cytogenetically unrelated clones suggests a multicellular origin of this benign skin tumor. None of the structural rearrangements encountered have previously been associated with neoplasia.

Aged↗