[Decisions made by insurance companies should be questioned. An offended patient should receive assistance to a legal trial].
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Humans↗
Biomedical subjects
B Johansson
Publications and source records attributed to B Johansson.
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↗
[Occupational medical tests in the past].
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Humans↗
[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↗
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↗
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↗
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↗
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↗
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↗
Adenosine A1 and A2A receptors and nitrobenzylthioinosine-sensitive transporters in gerbil brain: no changes following long-term treatment with the adenosine transport inhibitor propentofylline.
There is evidence that adenosine is an endogenous neuroprotective substance in the gerbil and that propentofylline, a novel xanthine derivative that acts as a transport inhibitor, exerts part of its neuroprotective activity in this species by enhancing adenosine actions. Using autoradiography we have examined the distribution of adenosine A1 and A2A receptors and of equilibrative adenosine transporters in gerbil brain as well as the possible changes induced by repeated treatment with propentofylline. Nucleoside transporters, studied by [3H]NBMPR binding, were found to be widely distributed in the gerbil brain, with no clear relationship to the distribution of adenosine receptors. Adenosine A2A receptors, studied by [3H]CGS 21680 binding and by in situ hybridization, were found to be present in intrinsic neurons in the caudate putamen, nucleus accumbens and tuberculum olfactorium. Adenosine A1 receptors were studied by examining the binding of [3H]CHA, an agonist, and [3H]DPCPX, an antagonist. There was an overall similarity in the distribution of binding sites for these two ligands, and a similarity with the distribution in the rat. However, the antagonist was found to label certain structures, especially white matter structures, more than the agonist. It is argued that these binding sites for antagonists represent receptors that are in transit from the site of synthesis in the perikaryon to the destination in the nerve terminal, and are not coupled to G proteins. There were no differences in the binding of any of these ligands or in A2A mRNA following 2 weeks' treatment with propentofylline, indicating that the drug has minimal effects on adenosine mechanisms under basal physiological conditions. This also suggests that tolerance to adenosine-related effects of the drug is less likely to occur.
Adenosine↗
No FISH evidence for trisomy 7 in normal or leukemic bone marrow.
Trisomy 7 has been found as the sole chromosomal anomaly in both benign and malignant tumors, as well as in nonneoplastic lesions. It has been reported that +7 may occur in tumor-infiltrating as well as in peripheral T cell and in the thymus. The precursor cells, which mature in the thymus to T lymphocytes, originate in the bone marrow and the present study was undertaken to investigate whether cells carrying an extra chromosome 7 can be detected there. Bone marrow samples from five hematologically normal individuals and 12 children with acute lymphoblastic leukemia (ALL) were analyzed by interphase fluorescence in situ hybridization (FISH) using a chromosome 7 centromere-specific probe. Half of the ALLs were karyotypically normal, whereas the other half displayed clonal abnormalities (one pseudodiploid and five hyperdiploid karyotypes, none of which had +7). The FISH analysis showed no evidence of cells with trisomy 7 in the bone marrow samples from the controls or ALLs. This suggests that the gain of a chromosome 7 by T lymphocytes does not occur before the bone marrow precursor cells are conditioned in the thymus.
Adolescent↗
Caffeine-induced expression of c-fos mRNA and NGFI-A mRNA in caudate putamen and in nucleus accumbens are differentially affected by the N-methyl-D-aspartate receptor antagonist MK-801.
Caffeine (100 mg/kg, i.p.) induces a rapid increase in the expression of mRNA for the immediate early genes (IEGs) c-fos and NGFI-A in rat striatum. We have examined how this response is affected by pretreatment with either the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (1 and 3 mg/kg, i.p.), the competitive NMDA receptor antagonist D-CPP (6 mg/kg, i.p.), or the non-selective excitatory amino acid receptor antagonist kynurenic acid (300 mg/kg, i.p). The two NMDA receptor antagonists significantly reduced the caffeine-induced expression of both c-fos mRNA and NGFI-A mRNA in the medial part of the caudate putamen. The effect was less pronounced in the lateral part of the caudate putamen. MK-801 caused an enhancement of c-fos and NGFI-A mRNA expression in nucleus accumbens. Pretreatment with kynurenic acid caused no marked alterations in the caffeine-induced expression of c-fos mRNA and NGFI-A mRNA in any brain region. These findings suggest that glutamatergic transmission via NMDA receptors contributes to the induction of c-fos mRNA and NGFI-A mRNA by caffeine in striatum. In addition we show that MK-801 can either increase or decrease the caffeine effect on IEGs depending on the region studied.
Animals↗
Blood clonal B-cell excess in patients with monoclonal gammopathy of undetermined significance (MGUS): association with malignant transformation.
Fifty-seven patients with monoclonal gammopathy of undetermined significance (MGUS) were analysed for the presence of blood clonal B-cell excess (CBE), defined as a lymphocyte surface membrane kappa/lambda light chain ratio outside the normal range (> 3.5 in kappa-type MGUS and < 0.9 in lambda-type MGUS). 15 patients (26%) had a CBE. The patients were followed for a median time of 8.4 years (range 0.5-20.2). Eight of the 15 CBE+ MGUS patients (53%) developed a B-cell malignancy as compared to 7/42 patients (17%) in the CBE group and the difference in event-free (malignancy-free) observation time was statistically significant (P = 0.01). Cox's regression analysis showed that the presence of CBE was the most powerful predictor of progression to a malignant disease. Two patients with a normal kappa/lambda ratio at first test were analysed repeatedly during follow-up. Subsequently, a CBE appeared which gradually increased in size preceding the clinical diagnosis of a malignant disease.
Adult↗
t(3;21)(q26;q22) with AML1 rearrangement in a de novo childhood acute monoblastic leukaemia.
t(3;21)(q26;q22) is a recurrent chromosomal abnormality in Philadelphia-positive chronic myeloid leukaemia in blast crisis and in treatment-related myelodysplastic syndrome and acute myeloid leukaemia. The molecular consequences of the t(3;21) are presently being unravelled; various transcripts between the AML1 gene in 21q22 and several unrelated genes, i.e. EAP, EVI1 and MDS1, in 3q26 are generated, resulting in the formation of a chimaeric transcription factor. The t(3;21) has only rarely been described in de novo leukaemias and never before in an acute leukaemia in a child. We here present the clinical, cytogenetic and molecular genetic findings in a boy with a de novo acute monoblastic leukaemia with t(3;21)(q26;q22) and AML1 rearrangement.
Blotting, Southern↗
Urolithiasis and distal renal tubular acidosis preceding primary Sjögren's syndrome: a retrospective study 5-53 years after the presentation of urolithiasis.
OBJECTIVES: Distal renal tubular acidosis (dRTA) can be associated with autoimmune diseases such as primary Sjögren's syndrome (SS). Our objective was to study SS-associated symptoms, autoantibodies and renal histopathology in patients with urolithiasis and dRTA. SETTING: The patients were from the Departments of Nephrology and Rheumatology. University Hospital of Linköping, which is a tertiary referral hospital, as well as a secondary referral centre for the immediate area around the city of Linköping. SUBJECTS: Ten female patients with dRTA, who presented with urolithiasis and not with subjective sicca symptoms, were from the Department of Nephrology, University Hospital, Linköping. Autoantibodies were detected in eight of these patients, and they were studied with respect to clinical and laboratory evidence of SS (urolithiasis group). Fifteen women with SS, who presented with sicca symptoms and not with urolithiasis or dRTA, served as the reference group. RESULTS: In the urolithiasis group, all of the eight patients had anti-SS-A antibodies, and SS (or possible SS) developed in seven of the eight patients 1-48 (mean 15) years after the onset of urolithiasis. Histological features of tubulointerstitial nephritis were found in four of five biopsied patients in the urolithiasis group, and in two of four patients (with dRTA) in the reference group. CONCLUSIONS: Urolithiasis and dRTA can precede subjective sicca symptoms, and patients with dRTA may have SS in the absence of subjective sicca symptoms. Anti-SS-A antibodies are common in patients with urolithiasis and dRTA. Therefore, we hypothesize the possibility of a Sjögren-related renal disease in these patients.
Acidosis, Renal Tubular↗
Regional cerebral blood flow, white matter abnormalities, and cerebrospinal fluid hydrodynamics in patients with idiopathic adult hydrocephalus syndrome.
OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.
Aged↗
HPV-types, cytological and histopathological findings in three groups of women with possible HPV-related disease.
OBJECTIVE: The aim of this investigation was to study three groups of women presenting with possible HPV-infection with regard to HPV-types and cervical dysplasia. METHODS: Eighty women were included. Eighteen of them were present partners to men with condylomas, 20 had clinical vulvar HPV-lesions and 42 were referred due to an abnormal PAP-smear. Samples for HPV-analysis by PCR-technique were taken from the vulva, the portio and the cervical canal. A universal HPV-primer as well as specific primers for HPV 6/11, 16, 18, 31, and 33 were utilized. PAP-smears were taken as well as biopsies from cervix/portio. RESULTS: Seventy-eight percent had HPV-DNA identified. Sixty-seven percent of those with HPV 16 and/or 18 had dysplasia verified by histopathology and 50% of those with 31 and/or 33. Twenty of 21 women with dysplasia had HPV 16, 18, 31 and/or 33 identified. One woman with dysplasia was HPV-negative. Histopathologically verified CIN were diagnosed in all groups investigated. Women referred for suspicion of CIN significantly more often had HPV detected at the cervix/portio. HPV 6/11 was mostly found in women with condylomas. Apart from this the occurrence of the different HPV types were alike in the three groups. CONCLUSION: Infection with HPV is a process and the usefulness of different diagnostic methods seems to depend on when during the course of the disease they are used. HPV-findings in women with dysplasia were all associated with oncogenic virus-types. High-risk virus was often found simultaneously with low-risk virus indicating a covariation in the acquisition of the different HPV-types.
Adolescent↗
Emergence of novel transient clonal chromosomal bone marrow changes in remission of acute lymphoblastic leukemia.
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Antineoplastic Combined Chemotherapy Protocols↗