Search PubMed⌕ Search

Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 271 records · Page 15Linked to original sources
PubMed1996

A novel ribozyme target site located in the HIV-1 nef open reading frame.

We have tested the sequence UUC CAG UCA GAC CU, at position 9016--9029 within the HIV-1(SF2) nef open reading frame, for accessibility to antisense and hammerhead ribozyme attack. The accessibility was first studied using a phosphorothioate-modified 14-nt DNA oligo (complementary to the nef9016--9029 site). A dose-dependent repression of HIV-1(SF2) growth was observed in human peripheral blood mononuclear cells after exogenous administration of the oligo to the cell culture medium. A hammerhead ribozyme with a 6+7-nt antisense specificity for the nef9016--9029 site (hhRz.nef9016--9029) was constructed and transfected into the human T-cell line HUT78. Again, a dose-dependent repression of virus growth was observed when different individual clones expressing hhRz.nef9016--9029 were infected with HIV-1(SF2). A complete abrogation of virus production was observed after infection with a low (0.5 TCID50) HIV-1 titer. Increasing doses (2.5 and 12.5 TCID50) of HIV-1 virus yielded a low production (10(3)-fold reduced) of virus particles in most cases; but a complete, or close to complete, abrogation was observed even in individual cultures infected with the highest dose. Presence of proviral pol and gag sequences in hhRz.nef9016--9029-expressing HUT78 clones was assayed, using PCR. Interestingly, since no pol and gag PCR products could be detected, the results strongly indicated that the hammerhead ribozyme was already acting on the infecting HIV RNA before its reverse transcription and integration as proviral DNA. In summary, the results obtained in this study support the nef9016--9029 site as a strong new candidate for ribozymal gene therapy against HIV-1 infection.

Base Sequence↗
PubMed1996

[A case-control study for the recognition of nonoccupational risk factors for tumors of the lower urinary tract].

OBJECTIVE: A case-control study was performed to assess various nonoccupational factors (smoking, eating and drinking habits, intake of analgesics) that may be aetiological factors in the development of tumours of the lower urinary tract, while vitamins may be protective. PATIENTS AND METHODS: 150 patients (125 men, mean age 66.4 years; 25 women, mean age 68.2 years) with histologically confirmed malignant tumour of bladder or other part of the lower urinary tract and a comparable group of controls, matched for age, sex and home location, were asked in a standardised personal interview about their life-long habits of smoking, eating and drinking, as well as intake of analgesics. RESULTS: Smoking was the greatest risk factor. In men there was a significant positive dose-effect relationship between the number of cigarettes smoked and relative carcinoma risk, compared with nonsmokers, by a factor of 3.68 among those with the highest dosage (> 40 pack-years). Because of the small number of cases this relationship could not be proven in women, but twice as many female tumour patients than controls were smokers (8 vs 4). In men, even after adjusting for smoking, increased coffee consumption increased the risk by a factor of 2 (2-4 cups: odds ratio 2.14 [P < 0.05]; > 5 cups: odds ratio 2.22 [not significant]). An increased beer consumption had no apparent effect on the development of tumours. Findings regarding vitamin C were ambiguous. More prolonged and increased intake of phenacetin-containing analgesics in men showed a tendency towards a higher tumour risk. CONCLUSION: Smoking cigarettes is one of the main risk factors for the development of bladder and other lower urinary tract tumours. The influence of other risk factors needs to be elucidated.

Age Distribution↗
PubMed1996

Molecular characterization of 12p abnormalities in hematologic malignancies: deletion of KIP1, rearrangement of TEL, and amplification of CCND2.

Twenty patients with hematologic malignancies with 12p abnormalities were investigated by fluorescence in situ hybridization (FISH) using probes mapped to specific regions in 12p. The initial analysis using the YAC 964c10 (D12S736) revealed that all four cases with cytogenetically identified del(12p) had lost one copy of this YAC and that submicroscopic deletions had occurred in 10 of the 16 neoplasms with other 12p abnormalities, ie, translocations, additions, and insertions. The deletions were partially mapped with cosmids localized to subregions of 12p. One copy of the gene for p27kip1 (KIP1), involved in cell cycle entrance, was found to be lost in all cases in which deletions could be detected by other probes and in one case with a translocation as the only detectable change. This implicates KIP1 as a possible tumor suppressor gene affected by del(12p). Four translocations with no apparent concomitant deletions were detected. All four breakpoints resulted in a split D12S736 signal. In two of these cases, we showed that TEL was disrupted as a result of a t(5;12)(q32-33;p12) and a t(12;22)(p12;q12), respectively. Two lymphoid neoplasm--one non-Hodgkin's lymphoma and one Burkitt's lymphoma--with 12p amplifications were detected. In both cases cyclin D2 (CCND2) was within the amplified region. Thus, cytogenetic abnormalities of 12p in hematologic malignancies result in at least three different molecular changes: deletions of KIP1, amplifications of CCND2, and structural rearrangements of TEL.

Adult↗
PubMed1996

Discrepancy of hepatitis C virus genotypes as determined by phylogenetic analysis of partial NS5 and core sequences.

The use of phylogenetic analyses of partial NS5 and core regions for hepatitis C virus (HCV) genotyping was evaluated by analysing seven Honduran and 24 European HCV strains. Core primers were designed with which HCV genotypes 1, 2, and 3 were readily amplified. The reliability of phylogenetic analysis of a 111-bp core sequence was verified by comparing the typing results with those obtained using the whole core gene of 52 reference strains. Accordant genotypes (1a, 1b, 2b, and 3a) were obtained when phylogenetic analyses were undertaken on both the partial core and a 222-bp NS5 sequence in all of the European HCV strains. Genotypes 1a, 1b, and 3a were identified among the Honduran strains by phylogenetic analysis of the partial NS5 sequence. Interestingly, two of three Honduran type 3a strains, as determined by the NS5 sequence analysis, turned out to be type 1a by core sequence analysis. These two strains were also classified as type 1a, but not 3a, by a core type-specific PCR. Furthermore, the E2/NS1 regions were similar to HCV-PT, a representative strain of genotype 1a. The results indicate that chimeral HCV strains exist, although in most cases a good concordance is found when phylogenetic analysis of partial core and NS5 sequences are used for genotyping. This finding should be taken into account when HCV is genotyped by phylogenetic analysis of a partial HCV sequence from a single genomic region.

Amino Acid Sequence↗
PubMed1996

Primary vs. secondary neoplasia-associated chromosomal abnormalities--balanced rearrangements vs. genomic imbalances?

Two quite distinct neoplasia-associated karyotypic patterns are emerging. One is characterized by simple and disease-specific abnormalities, and the other is characterized by multiple and nonspecific aberrations. The former pattern is typical of most leukemias and lymphomas and of some mesenchymal tumors, but it is rare in epithelial neoplasms. The latter pattern is found in most epithelial tumor types, in several mesenchymal neoplasms, but in only a few hematologic malignancies. Primary chromosome aberrations, which are believed to be essential in establishing the neoplasm, and secondary changes, which are considered to be important in tumor progression, may be distinguished in the tumors characterized by simple and disease-specific abnormalities. Here, we propose that these aberrations are genetically and hence, most likely, functionally distinct. Primary abnormalities lead to specific gene rearrangements, whereas secondary chromosomal changes result in large-scale genomic imbalances. According to this hypothesis, there are no unbalanced primary aberrations, only secondary imbalances masquerading as primary. This proposition has a number of conceptual ramifications. First, the genetic mechanisms underlying tumor initiation and progression would seem to be totally different. Second, the elucidation of the molecular consequences of the secondary aberrations will be an arduous task, even if one were to adhere to the view that cytogenetically identified genomic imbalances may be reduced to simple gains or losses of single oncogenes or tumor suppressor genes. Third, the cytogenetic diagnosis of neoplasms will have to take into account that an unbalanced "primary" abnormality is secondary to a submicroscopic, truly primary change of major diagnostic and prognostic importance.

Chromosome Aberrations↗
PubMed1996

Evidence for high-affinity binding sites for the adenosine A2A receptor agonist [3H] CGS 21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors.

The binding of the adenosine A2A receptor selective agonist 2-[4-(2-p-carboxyethyl)phenylamino] -5'-N-ethylcarboxamidoadenosine (CGS 21680) to the rat hippocampal and cerebral cortical membranes was studied and compared with that to striatal membranes. [3H] CGS 21680, in the concentration range tested (0.2-200 nM), bound to a single site with a Kd of 58 nM and a Bmax of 353 fmol/mg protein in the hippocampus, and with a Kd of 58 nM and a Bmax of 264 fmol/mg protein in the cortex; in the striatum, the single high-affinity [3H] CGS 21680 binding site had a Kd of 17 nM and a Bmax of 419 fmol/mg protein. Both guanylylimidodiphosphate (100 microM) and Na+ (100 mM) reduced the affinity of [3H] CGS 21680 binding in the striatum by half and virtually abolished [3H] CGS 21680 binding in the hippocampus and cortex. The displacement curves of [3H] CGS 21680 binding with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), N6-cyclohexyladenosine (CHA), 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CADO) were biphasic in the hippocampus and cortex as well as in the striatum. The predominant [3H]CGS 21680 binding site in the striatum (80%) had a pharmacological profile compatible with A2A receptors and was also present in the hippocampus and cortex, representing 10-25% of [3H]CGS 21680 binding. The predominant [3H]CGS 21680 binding site in the hippocampus and cortex had a pharmacological profile distinct from A2A receptors: the relative potency order of adenosine antagonists DPCPX, 1,3-dipropyl- 8-¿4-[(2-aminoethyl)amino]carbonylmethyl- oxyphenyl¿ xanthine (XAC), 8-(3-chlorostyryl)caffeine (CSC), and (E)-1,3-dipropyl-8-(3,4-dimethoxystyryl)- methylxanthine (KF 17,837) as displacers of [3H] CGS 21680 (5 nM) binding in the hippocampus and cerebral cortex was DPCPX > XAC >> CSC approximately KF 17,837, and the relative potency order of adenosine agonists CHA, NECA, CADO, 2-[(2-aminoethylamino)carbonylethylphenylethylamino]-5'-N- ethylcarboxamidoadenosine (APEC), and 2-phenylaminoadenosine (CV 1808) was CHA approximately NECA > or = CADO > APEC approximately CV1808 > CGS 21680. In the presence of DPCPX (20 nM), [3H] CGS 21680 (0.2-200 nM) bound to a site (A2A-like) with a Kd of 20 nM and a Bmax of 56fmol/mg protein in the hippocampus and with a Kd of 22 nM and a Bmax of 63fmol/mg protein in the cortex. In the presence of CSC (200 nM), [3H]CGS 21680(0.2-200 nM) bound to a second high-affinity site with a Kd of 97 nM and a Bmax of 255 fmol/mg protein in the hippocampus and with a Kd of 112 nM and a Bmax of 221 fmol/mg protein in the cortex. Two pharmacologically distinct [3H]CGS 21680 binding sites were found in synaptosomal membranes of the hippocampus and cortex and in the striatum, one corresponding to A2A receptors and the other to the second high-affinity [3H]CGS 21680 binding site. In contrast, the pharmacology of [3H]CHA binding was similar in synaptosomal membranes of the three brain areas. The present results establish the existence of at least two high-affinity [3H]CGS 21680 binding sites in the CNS and demonstrate that the [3H]CGS 21680 binding site predominant in the hippocampus and cerebral cortex has different binding characteristics from the classic A2A adenosine receptor, which predominates in the striatum.

2-Chloroadenosine↗
PubMed1996

Laparoscopic suture closure of perforated peptic ulcer. A nonrandomized comparison with open surgery.

BACKGROUND: Laparoscopic vs open suture in the surgical treatment of perforated peptic ulcer were compared in a retrospective study. METHODS: The outcome of 10 patients having the laparoscopic procedure was compared with the outcome of 17 patients treated with suture via laparotomy during the same time period. RESULTS: The mortality rate and the complication rate were comparable. The laparoscopic procedure was more time consuming; hospital stay did not differ. CONCLUSIONS: The results indicate that surgery for perforated peptic ulcer can be performed with the laparoscopic technique with an outcome comparable to open surgery. No obvious advantages to the patient were noted with the laparoscopic method.

Aged↗