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Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 181 records · Page 10Linked to original sources
PubMed1999

The importance of genetic and environmental effects for self-reported health symptoms: a 30-year follow-up considering survival and selection effects.

OBJECTIVES: This study delineated the nature of individual differences in self-reported health status across a 30-year period. Potential survival and selection effects on mean levels, variances, and genetic and environmental sources of variance were evaluated. METHODS: Self-reported health status in 1963 was evaluated in 5,229 pairs of twins from the Swedish Twin Registry and in a subsample of 351 pairs surviving to the age of 80 years in 1993. Structural equation modeling evaluated genetic and environmental contributions to total variance and change in variance. RESULTS: For men but not women, the genetic and environmental influences on health symptoms differed between survivors and nonsurvivors. Total variance increased, reflecting an increase in environmental variance, across the 30 years for both genders. Genetic variance decreased longitudinally for men. DISCUSSION: The increase in variation from the mid-50s to the mid-80s appears to be due to an accumulation in environmental variation. There are gender differences that deserve further exploration.

Age Factors↗
PubMed1999

Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas.

Cytogenetic analysis was performed on 363 biopsy specimens with histologically confirmed diffuse large B-cell lymphoma (DLBCL), consecutively ascertained at the Memorial Sloan-Kettering Cancer Center, New York, between 1984 and 1994. Among 248 samples successfully karyotyped, clonal chromosomal abnormalities were noted in 215 (87%). The salient cytogenetic features of DLBCL from this analysis comprised the following. Breakpoints clustered, in decreasing frequency, at 10 recurring sites: 14q32, 18q21, 1q21, 3q27, 1p36, 8q24, 3p21, 6q21, 1p22, and 22q11. Of these, deletion breaks affecting bands 3p2 and 1p22 and translocation breaks affecting bands 14q32, 3q27, and 1q2 were frequent and distinctive for this subset of lymphomas. Translocations affecting band 14q32 were noted in 110 cases (51%) of which 42 (20%) had t(14;18)(q32;q21), 21 (10%) had t(8;14)(q24;q32) or t(8;22)(q24;q11), 14 (6.5%) had t(3;14)(q27;q32) or t(3;22)(q27;q11), and 33 (15%) had other rearrangements of 14q32. Among 144 new translocations detected in the entire group, the breakpoints in 19 were recurrent and clustered at three sites: 1q21, 3q27, and 14q32. Regions of common cytogenetic deletions were identified at 11 sites, 1p36, 1p33-34, 1p31, 1q32, 3p25-26, 3p21, 3q21, 6q15, 6q21, 6q23-24, and 7q32, suggesting possible loss of candidate tumor suppressor genes associated with DLBCL development. Of these, only those at 6q21, 6q23, and 7q32 have previously been described in lymphoid neoplasms. The group of DLBCL with translocations affecting band 14q32 showed a significantly different pattern of additional cytogenetic changes compared to the group lacking such translocation. This new comprehensive cytogenetic characterization provides the basis for investigations aimed at identifying molecular mechanisms as well as the clinical impact of cytogenetic changes in DLBCL.

Chromosome Aberrations↗
PubMed1999

Caffeine, acting on adenosine A(1) receptors, prevents the extinction of cocaine-seeking behavior in mice.

Drug-naive DBA/2 mice were trained to self-administer cocaine (40 microgram/kg/infusion) i.v. by nose poking. The number of nose-poke responses was higher in mice receiving response-contingent injections of cocaine (active group) than in yoked controls or in animals receiving response-contingent saline injections. Twenty-four hours after the training session (cocaine or saline self-administration), mice were injected i.p. with saline, cocaine, caffeine, 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX), 8-cyclopentyl theophylline (8-CPT), 5-amino-7-(2-phenylethyl)2-(2-furyl)-pyrazolo-[4,3-e]-1,2, 4-triazolo[1,5-c]pyrimidine (SCH 58261), or 9-chloro-2(2-furyl)[1,2, 4]triazolo[1,5-c]quinazolin-5-amine (CGS 15943) and placed again in exactly the same operant boxes as during the training session but without response-contingent i.v. infusions. Saline injection elicited similar responding in animals from the active group and from the yoked control group. A low dose of cocaine (5 mg/kg) or caffeine (3 mg/kg), but not higher doses, produced greater responding in the active group than in the yoked control group during a single extinction trial. The adenosine A(1)-receptor antagonists DPCPX and 8-CPT and the nonselective antagonist CGS 15943 partially reproduced the effect of a low dose of caffeine on the cocaine-associated behavior in a dose-dependent manner and did not alter the nose-poke activity of yoked control mice in the extinction experiment. In contrast, the adenosine A(2A) antagonist SCH 58261, in doses above 1 mg/kg, reduced nose-poke activity equally in active and yoked control animals. This confirms that a drug from a different pharmacological class (adenosine-receptor antagonist) can induce behavior changes similar to the effects of the original self-administered drug (indirect dopamine-receptor agonist). The data also suggest that the effects of caffeine on cocaine-seeking behavior might be related to interaction with adenosine A(1) receptors, but not A(2A) receptors.

Animals↗
PubMed1999

Cytogenetic polyclonality in hematologic malignancies.

The present study was undertaken to ascertain the frequency of cytogenetic polyclonality in various hematologic malignancies and to investigate whether morphologic subgroup, age, gender, or previous genotoxic exposure influences the incidence. Among 2,243 cytogenetically investigated hematologic malignancies, 10 acute myeloid leukemias (AML), 5 myelodysplastic syndromes (MDS), 2 acute lymphoblastic leukemias (ALL), 1 acute undifferentiated leukemia (AUL), 1 atypical Philadelphia chromosome-negative (Ph-) chronic myeloid leukemia (CML), 1 chronic myeloproliferative disorder (CMD), and 1 chronic lymphoproliferative disorder (CLD) with karyotypically unrelated clones were identified, constituting 2.6% of AML, 1.6% of MDS, 0.8% of ALL, 13% of AUL, 9.1% of Ph- CML, 1.5% of CMD, and 2.8% of CLD with chromosomal abnormalities. In contrast to the cytogenetic features, the X-inactivation pattern was monoclonal in the two informative female patients that could be investigated. Among 17,733 karyotypically aberrant published cases surveyed, significant frequency differences (P < 0.001) were discerned: 1.7% of 6,526 AML, 3.4% of 2,391 MDS, 0.4% of 1,920 Ph+ CML, 2.9% of 856 CMD, 0.9% of 4,226 ALL, and 5.8% of 1,814 CLD displayed unrelated clones. The incidence of cytogenetic polyclonality did not differ significantly among the MDS, CMD, or ALL subgroups, between males and females, between children (< 16 years) and adults, or between B- and T-cell ALL, whereas the frequencies varied among the AML FAB types (P < 0.05), among the different CLD entities (P < 0.001), and between B- and T-cell CLD (P < 0.001). Furthermore, the incidence was higher in therapy-related AML and MDS than in de novo AML and MDS (P < 0.001 and P < 0.01, respectively).

Adolescent↗
PubMed1999

Comparative studies on neutralisation of primary HIV-1 isolates by human sera and rabbit anti-V3 peptide sera.

IgG binding to V3 peptides and serum neutralising responses were studied in four HIV-1 infected individuals with progressive disease over a period of 31-70 months. The 18-20 mer peptides comprised residues 299-317 (numbering of HIV1 MN) in the N-terminal half of the V3 loop of the envelope glycoprotein gp120 and were derived from the sequences of autologous, as well as heterologous isolates. All four individuals studied lacked anti-V3 IgG binding to at least one autologous V3 sequence. V3 peptides to which autologous sera lacked binding IgG were all immunogenic in rabbits and induced antisera that were broadly cross-reactive by EIA and broadly cross-neutralising to primary HIV-1 isolates. This indicates that the peptides are immunogenic per se and that the respective human hosts have selective defects in recognising the corresponding V3 sequences. Despite the absence of antibody binding to autologous V3 peptides, the human sera had neutralising antibodies to autologous (three out of four cases), as well as heterologous isolates (all cases). Moreover, in vitro exposure of the patients' isolates to autologous neutralising serum or the homologous rabbit antiserum selected for variants with amino acid substitutions close to the crown of the V3 loop or in regions outside the sequence corresponding to peptides used for immunisation. The amino acid exchanges affected V3 positions known to be antigenic and which are also prone to change successively in infected persons. It is likely that neutralising antibodies recognise both linear and conformational epitopes in the V3 loop. Apparently, there are several, but restricted, numbers of ways for this structure to change its conformation and thereby give rise to neutralisation resistant viruses.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Assessing mechanical allodynia in the rat paw with a new electronic algometer.

Von Frey filaments used for testing mechanical thresholds are mechanically unstable and their use is difficult to standardize. We have therefore constructed a hand-held electronic pressure algometer. The pressure algometer is connected to a computerized data collection system, allowing on-line display of the applied force as well as the application rate. Data stored on the computer can be replayed and further analyzed. Using this apparatus, we have measured the pressure-induced withdrawal thresholds in rats with surgically induced neuropathy. The probe, with a circular tip of 1.0 mm diameter, was applied manually with a pressure increasing by approximately 0.05 N/s. Presurgical thresholds were normally distributed with a mean of 0.415 N, showing no significant difference between paws. During 2 weeks after surgery, the thresholds of the operated side were significantly reduced (range, 0.209-0.318 N), while the thresholds of the non-operated side remained at higher values (range, 0.432-0.491 N). Thresholds of control rats without surgery were in the 0.380-0.520 N range, with no significant difference between paws. In an additional experiment it was shown that interobserver reliability was high, both between withdrawal threshold values obtained and between rates of application used. In conclusion, the electronic algometer allows standardization of testing, detailed documentation of each experiment and provides an objective and accurate method for measuring the reactions of test animals to mechanical stimuli.

Animals↗
PubMed1998

[Genetic factors are often found inl Alzheimer disease. An extensive twin study to clarify the heredity-environment relationship].

Genetic and environmental risk factors are central concerns in dementia research. Through twin studies one can study the relative importance of genetic and environmental risk factors. One such study, based on the Swedish Twin Registry, shows that genetic effects are of considerable importance for developing Alzheimer's disease, even late in life, but that environmental factors are also important. For vascular dementia, the results indicate that non-genetic factors are of primary importance.

Aged↗
PubMed1998

Changes in CD8 and CD4 lymphocyte subsets, T cell proliferation responses and non-survival in the very old: the Swedish longitudinal OCTO-immune study.

Results from a previous longitudinal study indicated that a combination of high CD8 and low CD4 percentages and poor T cell proliferation in peripheral blood lymphocytes was associated with higher mortality in a subgroup of a sample of very old Swedish individuals. The present study examined whether those results could be confirmed at a subsequent 2-year time interval by investigating if additional individuals from the same original sample had developed the immune profile associated with higher mortality. Subgroups were formed by cluster analysis and similar to our previous results, this follow-up study identified a subgroup of subjects (n = 18) with an immune profile which again included high CD8, low CD4 percentages and poor mitogen response and was associated with higher mortality. Over the 2-year period 12 additional individuals: (1) Developed this immune profile; and (2) Could be identified by changes in their CD4:CD8 ratios which progressively decreased over the study period. These results confirm our original study and indicate that in this very old sample, over a subsequent 2 year period, additional individuals moved into the cluster at risk for higher mortality.

Aged↗
PubMed1998

Age-dependent changes in adenosine receptors are not modified by life-long intermittent alcohol administration.

Autoradiography and in situ hybridisation were used to examine age-dependent changes in adenosine receptors in male rats and to determine if life-long (94 weeks) intermittent ethanol consumption had any additional effect. Adenosine A2A receptors in striatum, as assessed by [3H]CGS 21680 binding, decreased by approximately 20% between the ages 6 and 99 weeks. Since dopamine D2 receptors and the mRNA for preproenkephalin also decreased there appears to be a loss of A2A-D2 receptor-bearing striatopallidal cells. Life-long ethanol consumption had no additional effect. Adenosine A1 receptors, as determined by [3H]DPCPX binding, did not decrease with age in any region of the brain, but increased slightly in the cerebellum. In substantia nigra, the increase in [3H]DPCPX binding upon addition of GTP was eliminated. Surprisingly, the amount of A1 receptor mRNA decreased significantly with age in most of the examined regions, including the cerebellum. There was no additional effect of ethanol treatment. It is suggested that age alters the number of cells that express A2A receptors, the turnover of A1 receptors, and in some regions their coupling to G proteins, but that life-long intermittent ethanol exposure has little additional effect.

Aging↗
PubMed1998

Genomic amplification of CCND2 is rare in non-Hodgkin lymphomas.

Cyclin D2, encoded by CCND2 at 12p13, takes part in the regulation of the cell cycle and has been suggested as a candidate for gene amplification in lymphoid malignancies. CCND2 is often overexpressed in chronic B-cell disorders, and we recently detected genomic amplification of the chromosomal region containing CCND2 in two of three investigated non-Hodgkin lymphomas (NHLs) with cytogenetic abnormalities involving 12p. In the present study, 58 NHLs without karyotypic evidence of 12p aberrations were analyzed by fluorescence in situ hybridization with probes for CCND2. No genomic amplification was found, strongly suggesting that this abnormality is rare in such NHLs.

Chromosome Aberrations↗
PubMed1998

T-cell-rich B-cell lymphoma: fine-needle aspiration cytology and immunocytochemistry.

Cytomorphologic and immunocytochemical characteristics of FNA aspirates from 5 patients with T-cell-rich B-cell lymphoma are described. The aspirates were dominated (over 90%) by small mature lymphocytes, but there was a sparse admixture of large, immature lymphoid cells, some of which mimicked Hodgkin's or Reed Sternberg's cells. The cytologic picture of 3 cases was similar to that of Hodgkin's disease of lymphocytic predominance. Two cases presented, in addition to the components described above, fragments of small vessels and epithelioid cells, which raised the possibility of true T-cell lymphoma. Immunocytochemical analysis of cytospin preparations showed that the mature small lymphocytes were of T-phenotype, while the large cells were of B-phenotype. Light-chain restriction was demonstrated in all cases, and monoclonality for kappa and lambda was shown in 4 cases and 1 case, respectively. Three cases had a previous histological diagnosis of Hodgkin's disease, which was revised to T-cell-rich B-cell lymphoma as a consequence of the cytologic and immunologic findings in aspirates from recurrent/remaining lymphoma manifestations. It can thus be concluded that immunocytochemistry in conjunction with cytomorphology on fine-needle aspirates will allow a conclusive diagnosis of T-cell-rich B-cell lymphoma and its differentiation from Hodgkin's disease and T-cell lymphomas. This distinction, from a prognostic and therapeutic standpoint, is of utmost importance.

Adult↗
PubMed1998

Frequent rearrangements of chromosomes 1, 7, and 8 in primary liver cancer.

Fifteen primary liver carcinomas (PLCs), including 12 hepatocellular carcinomas and three cholangiocellular carcinomas, were investigated cytogenetically after short-term culture. Ten tumors displayed clonal chromosomal abnormalities, whereas only normal karyotypes were detected in four cases, and one sample failed to grow in vitro. Structural rearrangements most often involved chromosomes 1, 7, and 8 and chromosome bands 1p36, 1q25, 3q10, 5q13, 6p10, 7p15, 7q22, 7q32, 8q10, 8q13, 14q10, and 17p11. Frequent genomic imbalances included gains of 1q, 3q, 6p, 7p, and 8q and losses of 1p, 8p, 10q, 14p, 17p, and 19p. A compilation of findings for all 19 cytogenetically abnormal PLCs reported to date, including the present cases, reveals that structural aberrations particularly affect 1p11, 1p22, 1p32, 1p34, 1p36, 1q25, 7p15, 7q22, 8q10, 8q13, 14q10, 16q24, and 17p11, and that the abnormalities frequently result in overrepresentation of 1q, 3q, 6p, 7p10-14, 8q, and 17q and underrepresentation of 1p34-36, 6q27, 7q32-qter, 8p, 13p, 14p, 16q24, and 17p. These genomic regions are likely to harbor genes of importance in hepatocarcinogenesis, and the present cytogenetic mapping may hence be of value for further molecular genetic investigations of PLC.

Adolescent↗
PubMed1998

Cytogenetic analysis of pancreatic carcinomas: intratumor heterogeneity and nonrandom pattern of chromosome aberrations.

Twenty-nine nonendocrine pancreatic carcinomas (20 primary tumors and nine metastases) were studied by chromosome banding after short-term culture. Acquired clonal aberrations were found in 25 tumors and a detailed analysis of these revealed extensive cytogenetic intratumor heterogeneity. Apart from six carcinomas with one clone only, 19 tumors displayed from two to 58 clones, bringing the total number of clones to 230. Karyotypically related clones, signifying evolutionary variation, were found in 16 tumors, whereas unrelated clones were present in nine, the latter finding probably reflecting a distinct pathogenetic mechanism. The cytogenetic profile of pancreatic carcinoma was characterized by multiple numerical and structural changes. In total, more than 500 abnormal chromosomes, including rings, markers, homogeneously stained regions, and double minutes, altogether displaying 608 breakpoints, were detected. This complexity and heterogeneity notwithstanding, a nonrandom karyotypic pattern can be discerned in pancreatic cancer. Chromosomes 1, 3, 6, 7, 8, 11, 12, 17, and 19 and bands 1q12, 1q21, 3q11, 6p21, 6q21, 7q11, 7q22, 7q32, 11q13, 13cen, 14cen, 17q11, 17q21, and 19q13 were most frequently involved in structural rearrangements. A total of 19 recurrent unbalanced structural changes were identified, 11 of which were not reported previously: del(1)(q11), del(3)(p11), i(3)(q10), del(4)(q25), del(11)(p13), dup(11)(q13q23), i(12)(p10), der(13;15)(q10;q10), del(18)(q12), del(18)(q21), and i(19)(q10). The main karyotypic imbalances were entire-copy losses of chromosomes 18, Y, and 21, gains of chromosomes 7, 2, and 20, partial or whole-arm losses of 1p, 3p, 6q, 8p, 9p, 15q, 17p, 18q, 19p, and 20p, and partial or whole-arm gains of 1q, 3q, 5p, 6p, 7q, 8q, 11q, 12p, 17q, 19q, and 20q. In general, the karyotypic pattern of pancreatic carcinoma fits the multistep carcinogenesis concept. The observed cytogenetic heterogeneity appears to reflect a multitude of interchangeable but oncogenetically equivalent events, and the nonrandomness of the chromosomal alterations underscores the preferential pathways involved in tumor initiation and progression.

Abdominal Neoplasms↗
PubMed1998

Carbon dioxide mediates duodenal mucosal alkaline secretion in response to luminal acidity in the anesthetized rat.

BACKGROUND & AIMS: Acid exposure of the duodenum elicits various functional responses, e.g., an increased mucosal alkaline secretion. Despite low pH in luminal contents, the mucosal secretion of bicarbonate-rich fluid results in pH neutrality at the surface epithelium. It follows that it is probably not luminal pH that triggers the secretory response. The present study was undertaken to investigate if CO2 could serve as an intermediate messenger between luminal acid and the mucosal secretory response. METHODS: Experiments were performed on chloralose-anesthetized rats. The duodenal mucosal alkaline secretion was measured by in situ pH-stat titration. RESULTS: Exposure of the duodenal mucosa to CO2, administered either as a pregassed solution (pH 4, PCO2 700 mm Hg) or as an acidified bicarbonate solution (pH 6.4, PCO2 240 mm Hg), raised the alkaline output by approximately 65%. This response was blocked by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (0.3 mmol/L intraluminally) but not by indomethacin (5 mg/kg intravenously). CONCLUSIONS: Exposure of the duodenal mucosa to solutions with high concentrations of CO2 increases the mucosal alkaline secretion despite an almost neutral pH. Data indicate that the L-arginine/NO pathway is involved in the mediation of this response.

Animals↗
PubMed1998

Cytogenetic and FISH analyses of pancreatic carcinoma reveal breaks in 18q11 with consistent loss of 18q12-qter and frequent gain of 18p.

Chromosome 18 was analysed using a banding technique and fluorescence in situ hybridization (FISH) in 13 pancreatic carcinoma samples. The cytogenetic analysis revealed that chromosome 18 abnormalities were present in all cases and that several different rearrangements, such as translocations, deletions, dicentrics and ring chromosomes, were often found together. FISH mapping using 18q YAC probes showed that all tumours had lost at least one copy of 18q and that 18p was over-represented in 6 of the 13 cases. Furthermore, out of 13 identified deletion breakpoints on 18q, 11 were mapped to 18q11. The clustering of breaks close to the centromere indicates that loss of genes in bands 18q11 and 18q12, in addition to those located in 18q21, e.g. DPC4 and DCC, are important in the development of pancreatic tumours.

Aged↗