Search PubMed⌕ Search

Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 523 records · Page 29Linked to original sources

Small intestinal differentiation in human colon carcinoma HT29 cells has distinct effects on the lateral diffusion of lipids (ganglioside GM1) and proteins (HLA class 1, HLA class 2, and neoplastic epithelial antigens) in the apical cell membrane.

We have studied the effect of maturation to small intestinal-like epithelial cells of the human colonic carcinoma cell line HT29 on the lateral mobility of different representative membrane components (lipid, proteins), as assessed with fluorescence recovery after photobleaching (FRAP). Maturation was induced in vitro in the HT29 cells by replacing glucose (Glu) with galactose (Gal) in the growth medium (DMEM) during a 21-day period. Scanning electron microscopy revealed an increased number of microvilli in the apical cell membrane, and enzyme analyses (alkaline phosphatase, aminopeptidase) in combination with aqueous countercurrent distribution, indicated that maturation was induced with DMEM-Gal. In comparison to control cells grown in DMEM-Glu medium, the more small intestinal-like cells grown in DMEM-Gal displayed no alteration of the lateral mobility of either cholera toxin (B subunit)-labelled ganglioside GM1 (diffusion coefficient, D [x 10(8)] = 0.8-0.9 cm2s-1; mobile fraction, R = 50-60%) or antibody-stained Class 2 histocompatibility (HLA-DR) antigen (D [x 10(9)] = 2 cm2s-1; R = 60-70%). However, antibody-labelled beta 2-microglobulin of HLA Class 1 antigen displayed increased mobility in HT29-Gal cells; D was x 1.4 and R x 1.8 larger in the HT29-Gal cells. By contrast, the mobility of a neoplastic antigen was reduced; D and R were x0.60 and x0.69 of the values seen in HT29-Glu cells. It is thus concluded that DMEM-Gal-induced differentiation in confluent HT29 cells is accompanied by specific rather than general effects on the lateral mobility of different membrane components.

Carcinoma↗

Detection of human immunodeficiency virus-1 by polymerase chain reaction and virus cultivation.

Peripheral blood of 57 patients with antibodies to human immunodeficiency virus 1 (HIV-1) and of five HIV-1 seronegative subjects at risk for HIV-1 infection were analysed by polymerase chain reaction (PCR) and virus isolation. The virus was recovered from peripheral blood cells in 89% and from plasma in 75% of the HIV-1 seropositive cases. In contrast, proviral HIV-1 DNA was detected in all HIV-1 seropositive patients by dot blot hybridization of the amplified fragments. The intensities of the dot blot reactions were less pronounced in asymptomatic HIV-1 seropositive individuals than in patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC), suggesting an increase in proviral DNA with advancing disease. Three of five seronegative patients with signs or symptoms suggesting HIV-1 infection, but none of the controls, were positive for HIV-1 DNA by one or two primer pairs. These results show a high sensitivity of the PCR for detecting HIV-1 DNA in patients of all stages of HIV-1 infection. Proviral DNA can also be detected in some individuals without detectable antibodies to the virus. The virus load in peripheral blood, as determined by virus cultivation and PCR, seems to increase with progression of the infection.

Adult↗

Oxygen metabolites induced by phorbol myristate acetate increase lateral diffusion of wheat germ agglutinin-labeled glycoconjugates in human polymorphonuclear leukocytes.

To assess the general effects of protein kinase C (PKC) activation on cell membrane receptor mobility in human neutrophilic polymorphonuclear leukocytes (PMNLs), the lateral diffusion of fluoresceinated succinylated wheat germ agglutinin (S-WGA-FITC)-labeled membrane glycoconjugates was measured using fluorescence recovery after photobleaching (FRAP). Activation of PKC was achieved by incubating the PMNLs with different concentrations (5-100 nM) of phorbol myristate acetate (PMA). The membrane effects of dimethyl sulfoxide (DMSO), another possible membrane perturbant, were also studied. We found that PMA treatment (greater than or equal to 10 nM) increased the glycoconjugate diffusion coefficient (D) 2-2.5-fold. The mobile fraction (R) remained constant, around 30%. With DMSO, no effect on the diffusion was seen. The increase in lateral mobility due to cell stimulation with PMA was totally inhibited by catalase (200 units/ml) but only partly with superoxide dismutase (2000 units/ml). Exogenous hydrogen peroxide (0.01-5 mM) had no effect on glycoconjugate mobility in unstimulated cells. We therefore propose that activation of PKC mediates augmented mobility of glycoconjugate receptors in PMNL, a reaction that seems to be critically dependent on formation of reactive oxygen metabolites. The results indicate that endogenous formation of reactive metabolites upon receptor stimulation may have a general effect on receptor mobility.

Catalase↗

The relation of atrial natriuretic factor to isolated atrial amyloid.

Isolated atrial amyloid (IAA) is a very common age-related amyloid form which is seen only in the atria of the heart. Chemical characterization has indicated that the major subunit protein is atrial natriuretic factor (ANF). In this ultrastructural study we show that the fibrils in IAA most frequently are located extracellularly especially along the cell membranes of the myocytes, but that small deposits also seem to be present intracellularly. No obvious relation was noted between the fibrils and the endocrine granules. Antiserum to a low molecular fraction of IAA labeled amyloid fibrils and granules in the same way as a commercial antiserum to ANF, but no other structures in the myocyte. Finally we show that ANF can polymerize to fibrils with an amyloid appearance. The study thus supports the fact that ANF is an important and integrated part in the IAA fibrils.

Absorption↗

Oral dosage of melphalan and response to treatment in multiple myeloma.

Forty-nine consecutive patients with multiple myeloma were analysed for treatment response in relation to dose of orally administered melphalan (induction therapy). All patients were given at least six courses of melphalan-prednisone. Treatment response, defined as a reduction of the myeloma protein of greater than 50%, was seen in 26 patients while 23 were non-responders. When treatment response was related to the dosage of melphalan given by mg/kg of body weight, the numbers of responding and non-responding patients were similar in the group of patients without dose reduction as well as in that with dose reduction. Drug-induced suppression of white blood cell and platelet count was similar in the responding as well as in the non-responding group indicating that the reason for non-response is not simply explained by deficient drug absorption. When the cumulative dose of melphalan given during the induction therapy was analysed, however, a positive correlation (r = 0.47, P less than 0.001) was seen between the cumulative dose and the degree of response. Thus, the cumulative dose of melphalan given during induction therapy seems to be of importance for the response, but other factors as intrinsic differences in cell sensitivity may also explain the individual responsiveness.

Administration, Oral↗

Direct costs of stroke for a Swedish population.

Direct costs were estimated for the treatment, rehabilitation, and nursing of 125 patients with first stroke in the Lund and Orup health districts (population of 200,191). Patients were followed from the onset of stroke in 1983 until October 31, 1985. The data were used to calculate the present value of the expected lifetime direct costs for an individual contracting his or her first stroke at various ages. For example, at the age of 72, these costs were estimated at SEK 283,000 for a man and SEK 561,000 for a woman. Hospital care was the major cost component (75% for males and 89% for females) at this age of onset. The results could be used to estimate the economic benefits of preventing new strokes, hence, forming part of a cost-effectiveness or cost-utility analysis. Together with prognoses of the expected developments in the incidence of stroke, they could also serve as the basis of forecasts of future costs of the health care and social service sectors.

Adult↗

Fibril in senile systemic amyloidosis is derived from normal transthyretin.

The amyloid fibril in senile systemic amyloidosis (SSA), like that of familial amyloidotic polyneuropathy, is derived from transthyretin (TTR). SSA, however, is a common disease, affecting to some degree 25% of the population greater than 80 years old. In familial amyloidotic polyneuropathy, the amyloidogenesis has been considered to depend on point mutations leading to TTR variants. We show that the TTR molecule in SSA, on the other hand, has a normal primary structure. Factors other than the primary structure of TTR must therefore be important in the pathogenesis of TTR-derived amyloid.

Amino Acid Sequence↗

Distribution of disulfiram and its chief metabolites over erythrocyte cell membranes and inactivation of erythrocyte aldehyde dehydrogenase activity.

The distribution of disulfiram (Antabuse over erythrocyte cell membranes and the inhibitory action of the parent drug and its metabolites on a disulfiram sensitive erythrocyte isozyme of aldehyde dehydrogenase (ALDH) was investigated in intact and haemolyzed human erythrocytes. These studies showed that not only disulfiram but also its bis(diethyldithiocarbamato) copper complex (Cu(DDC)2) were distributed over the erythrocyte cell membranes. In addition, disulfiram was the only substance examined that inactivaed erythrocyte ALDH, a reaction which was dependent on the concentration of disulfiram added.

Acetaldehyde↗

Genetic load in northern populations of Drosophila subobscura.

O-chromosomes were sampled from two natural populations in Finland, one population in Sweden and one population from Spain. Viability was assessed using the Va/Ba balanced lethal strain. The genetic load for lethals and semilethals was 0.165/0.065 in Helsinki and 0.151/0.101 in Tvärminne, Finland; 0.309/0.118 in Gävle, Sweden and 0.351/0.112 in Barcelona, Spain. With the exception of the Gävle population, the results confirm the general picture that marginal populations are characterized by light loads in comparison with the central ones. Homozygotes for normal or almost normal chromosomes from the Gävle population were less viable than corresponding homozygotes from other marginal populations. Random combinations of wild chromosomes from the Spanish and Finnish populations did not show increased viability over random Spanish heterozygotes.

Alleles↗

Plasma protein binding of disulfiram and its metabolite diethylthiocarbamic acid methyl ester.

The human plasma protein binding of disulfiram and its metabolite, diethylthiocarbamic acid methyl ester has been studied by an ultrafiltration technique. Both compounds were bound principally to albumin (mean 96.1 and 79.5%) over the ranges 200-800 and 345-2756 nM, respectively. The average number of binding sites was approximately 1 for both substances, whereas the average association constants were 7.1 x 10(4) and 6.1 x 10(3) M-1, respectively. Log P (octanol/water) was 2.81 for disulfiram and 1.85 for diethylthiocarbamic acid methyl ester.

Aldehyde Dehydrogenase↗

Radio-immunolocalization in nude mice using anticytokeratin monoclonal antibodies.

Four monoclonal antibodies reactive with the rod portion of human cytokeratin No. 8 were evaluated using experimental tumour radio-immunolocalization. Nude mice carrying human HeLa cell tumours were injected with 125I-labelled F(ab')2 fragments or intact IgG antibodies. Positive immunolocalization was observed with all the specific antibodies, the intact antibodies being superior to their analogous F(ab')2 fragments. High localization efficiency was observed despite the fact that the targets are intracellular filaments. The presence of necrotic areas in the tumours may favour the high uptake in the tumours. By computerized gamma-scintigraphic evaluation of the antibody distribution in the animals, several kinetic parameters of the antibody behaviour in vivo could be determined. The biological half-lives in the tumours were determined to be greater than 600 h for some of the antibodies compared to a half-life of 40-80 h in non-tumour tissues. Optimal imaging was obtained as late as 10-14 days after administration of the antibody. Up to 10% of the injected antibody could be identified in the tumours, indicating a potential value in radio-immunolocalization and radio-immunotherapy using anticytokeratin antibodies.

Adenocarcinoma↗

Epstein-Barr virus involvement in salivary gland lesions associated with Sjögren's syndrome.

Recently, Epstein-Barr virus (EBV) has gained increasing attention as a potential causative agent of Sjögren's syndrome, which is an autoimmune disorder characterized by lymphocytic infiltration of salivary and lacrimal glands. To determine the association between Sjögren's syndrome and EBV, we re-evaluated the salivary gland biopsies from patients previously diagnosed to have Sjögren's syndrome. Altogether, 20 cases of Sjögren's syndrome were reviewed from the files of the University Central Hospital since 1975. After re-evaluation of these biopsies, however, 11 patients did not fulfil the current criteria of Sjögren's syndrome, but were diagnosed as having chronic sialadenitis. All biopsies were processed for in situ hybridization (ISH) and polymerase chain reaction (PCR) to detect EBV DNA. With ISH, all samples were negative for EBV DNA. With PCR, however, 9 biopsies proved to be positive for EBV. 3 additional positive cases were found when the amplification product was dot-blotted and hybridized with EBV DNA probe. 10 of the EBV-positive salivary gland biopsies showed the histological features of chronic sialadenitis and only 2 cases were classified as having Sjögren's syndrome. On the basis of the present results, the association between EBV and Sjögren's syndrome remains doubtful.

Biopsy↗

Time-related changes in the guinea pig cochlea after acoustic overstimulation.

Forty-eight female pigmented guinea pigs were used to study the development of the morphologic and electrophysiologic changes occurring during a 4-week period after exposure to a 3.85-kHz pure tone at an intensity of 120 dB sound pressure level for 22.5 minutes. The morphologic results suggest an alteration in the permeability of ions between the inner ear fluids through gradual development of holes in the reticular lamina.

Animals↗

Oral versus intravenous melphalan and prednisone treatment in multiple myeloma stage II. A randomized study from the Myeloma Group of Central Sweden.

Eighty-one previously untreated patients with multiple myeloma stage II entered a randomized trial comparing oral melphalan (0.25 mg/kg/day; n = 40) with intravenous melphalan (0.125 mg/kg/day; n = 41) in combination with oral prednisone (2 mg/kg/day). The courses were given for 4 days and repeated every sixth week. The treatment groups were well comparable with regard to major prognostic factors. There was no statistically significant difference in the response rates, the response duration times and the survival times. No significant difference in nonhematological and hematological toxicity was noted. Since intravenous administration of melphalan did not result in a substantial increase in response rate or survival, this study supports the use of oral melphalan/prednisone as first-line therapy for patients with multiple myeloma.

Actuarial Analysis↗

Remarkably long survival of a patient with Ph1-positive chronic myeloid leukemia and 5' bcr rearrangement.

Chronic myeloid leukemia (CML) was diagnosed in a 19-year-old man in 1961, and the disease remained in chronic phase, with occasional exacerbations, for 27 years. In 1976, when the first cytogenetic analysis was performed, t(9;22)(q34;q11) was found as the sole abnormality in all mitoses. During accelerated phase in 1988, a second cytogenetic investigation showed the karyotype 45,XY,t(9;22)(q34;q11),-15,-17,+der(15) t(15;17)(p13;q11). Molecular analysis revealed a rearrangement in the 5' end of the major breakpoint cluster region (M-bcr). With the case presented here, sublocalization of the bcr breakpoint has now been undertaken in altogether five CML patients with extremely long survival. It is noteworthy that in all these cases the chromosome 22 breakpoint was located in the 5' region of the M-bcr.

Adult↗