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Biomedical subjects

B Johansson

Publications and source records attributed to B Johansson.

At least 469 records · Page 26Linked to original sources
PubMed1992

A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites.

After ingestion, disulfiram (DSF) is rapidly converted, probably in the stomach, to its bis (diethyldithiocarbamato) copper complex. Consequently, absorption and distribution via the gastrointestinal mucosa into the blood might involve both the parent drug and its copper complex. In the blood, both compounds are rapidly degraded to form diethyldithiocarbamic acid (DDC), which is unstable and is further degraded to form diethylamine and carbon disulphide. DDC is also a substrate of phase II metabolism, which involves formation of diethyldithiomethylcarbamate (Me-DDC) and the glucuronic acid of DDC. Me-DDC also undergoes oxidative biotransformation to diethylthiomethylcarbamate (Me-DTC), which is further oxidized to its corresponding sulphoxide and sulphone metabolites. Me-DTC may to act as a suicide inhibitor with a preference for the mitochondrial low Km isozyme of aldehyde dehydrogenases (ALDH 1), whereas the two S-oxidized metabolites, especially the sulfone metabolite, are more potent inhibitors not only of ALDH 1, but also of the cytosolic high Km isozyme of ALDH (ALDH 2). The inhibitory reaction between the enzyme and each of the three metabolites is characterized by a covalent adduct formation, probably with the cysteine residue at the active site of the enzymes. The adduct formed is nonreducible at a physiological concentration of glutathione, and inactivation in the presence of this endogenous tripeptide was increased by action in vitro of the sulphoxide and sulphone metabolites. Those findings are all in concordance with the in vivo observations made on DSF. In human volunteers treated with increasing doses of DSF and challenged with ethanol between each of the dosage periods, the mean plasma concentrations of Me-DTC at steady state were proportional to the DSF doses given. There was also a close relationship between increased oxidative metabolic formation of Me-DTC, high oxidative formation of acetaldehyde, and the full complements of a valid disulfiram ethanol reaction (DER). Consequently, Me-DTC in plasma may not only serve as a marker of the oxidative metabolic function of the liver, but also of the therapeutic effectiveness of the treatment in subjects at steady state. Obviously, there is a need for individual dose-titration regimens. In patients with alcohol-related severe hepatocellular damage, the oxidative P 450 catalyzed formation of the Me-DTC and probably also of its sulfoxide and sulphone metabolites is impaired, and thus inactivation of ALDH activity in the liver appears to be delayed or even completely absent. The consequence for the patient may be an insufficient DER.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetaldehyde↗
PubMed1992

The acetic acid test in evaluation of subclinical genital papillomavirus infection: a comparative study on penoscopy, histopathology, virology and scanning electron microscopy findings.

OBJECTIVES: To evaluate colposcopic criteria in acetowhite lesions of the penis ("penoscopy") for the diagnosis of subclinical genitoanal papillomavirus infection (GPVI) compared with histopathological criteria of HPV involvement and to various hybridisation assays for HPV DNA detection, and to depict typical lesions by scanning electron microscopy. DESIGN: The study included 101 randomly selected male partners of females with known GPVI, or with penile symptoms such as itching, burning and dyspareunia who did not exhibit overt genital warts but appeared to be afflicted with acetowhite penile lesions after topical application of 5% acqueous acetic acid. Lesions were judged by penoscopy as either typical, conspicuous or nontypical for underlying HPV infection. Biopsy specimens from 91 men were examined by light microscopy and by either Southern blot (SB), polymerase chain reaction (PCR) and/or in situ hybridisation (ISH) assays for the presence of HPV DNA of the HPV types 6, 11, 16, 18, 31, 33 and 42 (Group A). From another ten men lesions clinically typical for GPVI were also examined topographically by scanning electronic microscopy (Group B). SETTING: The STD out-patient clinic of the Department of Dermatovenereology of Karolinska Hospital, Stockholm, Sweden. RESULTS: Group A Seventy eight (86%) of the biopsied lesions met the penoscopy criteria of being either typical of or conspicuous for GVPI. The agreement between penoscopy and histopathology was fairly good, as HPV diagnosis was made by both methods in 56 (62%) of the cases. The reliability of applying strict colposcopic hallmarks was further substantiated by the finding that 55 (60%) of the biopsy specimens taken from penoscopically typical/conspicuous lesions contained HPV DNA. However, there are diagnostic pitfalls for the acetic acid test. Coexistence of an eczematoid reaction with changes indicative of HPV influence was detected in six (7%) of the cases, while an inflammatory response only occurred in 17 (19%) of the specimens. Additional histopathological diagnoses (normal epithelium, lichen sclerosus et atrophicus, balanitis circinata parakeratotica, verruca plana) were established in another eight (9%) of the cases. Among the HPV DNA positive cases, all of the HPV types tested for were detected with the exception of HPV 18. A severe penile intraepithelial neoplasia (PIN III) was revealed in five (5%) of biopsies; HPV 16 was present in two and HPV 42 in one of these biopsy specimens. GROUP B: Scanning electron microscopy depiction harmonised with the penoscopy findings showing that subclinical GPVI characteristically exhibits a well demarcated, slightly elevated border and that the central area of lesions often displays a "groove" in which the epithelium appears to be thin with protrusions from beneath that probably represent capillaries. CONCLUSION: Use of the acetic acid test for evaluation of GPVI should be combined with a colposcopic evaluation based on strict topographic hallmarks, followed by a directed biopsy for light microscopic evaluation. We found that the positive predictive value of colposcopy was as high when correlated with histopathological findings (72%) as when virological methods were used, whether HPV DNA hybridisation testing was performed with the well established SB and ISH assays (45%), or by applying the newly introduced and highly sensitive PCR assay as well (71%). False positivity from the acetic acid test occurs and is mainly due to inflammatory conditions but also to the presence of other conditions. Epithelial fissures are evidently associated with some subclinical GPVI lesions and may potentially represent loci minores for infectious stimuli and perhaps facilitate the transmission of some blood-borne STDs. We prose that the term "papillomavirus balanoposthitis" should be used for penile HPV infection associated with inflammatory responses. Our study indicates that PIN III frequently occurs in a subclinical form and may be associated with not only previously identified "high-risk" HPV types such as type 16, but also with the HPV type 42 that has not previously been considered as oncogenic.

Acetates↗
PubMed1992

Fetal heart rate response to acoustic stimulation in relation to fetal development and hearing impairment.

In twelve healthy pregnant women the fetal heart rate response to sound stimulation was tested every second week between the 22nd and the 34th week of the pregnancy. Habituation to the acoustic stimuli used was also investigated at the last examination. A high risk material for hearing impairment comprised 31 pregnant women. The stimuli were presented by a vibrator placed on the maternal abdomen over the fetal head. As stimuli pure tones were used in the form of pulses of one second at a frequency of 3000 Hz and with an onset and a decay time chosen not to cause audible clicks to a normal ear. The intensity of the tone pulse was set at a level calculated to correspond at the position of the fetal head to 110 dB sound pressure level in free field. Roughly 50% of the fetuses tested started to react with an increased heart rate in the 24th week of the development. Four weeks later all tested subjects responded to the test stimuli. Habituation of the motor 'startle' response was shown but the fetus heart rate change was consistent over 20 consecutive stimulations one min in between each. In 31 high risk subjects the responses from three fetuses must be considered as pathologic. These three children exhibited impaired auditory tests after birth and severe hearing impairment at the age of three years. All the others disclosed normal hearing at birth as well as at three years of age. Repeated significant increases in fetal heart rate following acoustic stimulation may appear as an indication of normal function of the hearing organ.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1992

Detection of enteroviruses in faeces by polymerase chain reaction.

A polymerase chain reaction (PCR) technique for the detection of human enteroviruses in stool specimens was developed. The test was based on the synthesis of cDNA, followed by PCR and slot blot hybridization. The primers used were selected from a highly conserved sequence in the 5'non-coding region of the enteroviral genome. By this method 27 different enterovirus serotypes (15 echo, 6 coxsackie A, 4 coxsackie B, poliovirus type 2 and enterovirus 71) from 89 patients could be detected. Using positive virus culture as reference, the sensitivity of PCR was 69% after 30 cycles of amplification, 91% using 30 + 10 cycles and 100% following 2 rounds of amplification with ensuing hybridization. None of 23 stool samples from healthy individuals or patients with meningitis of proven non-enteroviral etiology were positive by the PCR. By contrast, 13/26 culture-negative, randomly chosen stool samples from patients with suspected enteroviral disease were positive by the test. These findings demonstrate a high sensitivity and an apparently high specificity of PCR for detection of enteroviruses in stool samples. Therefore, the methodology may be useful in the laboratory diagnosis of enterovirus infections.

Base Sequence↗
PubMed1992

Amplification of DNA by the polymerase chain reaction for the efficient diagnosis of pertussis.

The standard diagnostic methods for pertussis have several shortcomings. With the increased knowledge of the Bordetella pertussis genome a specific and conserved DNA sequence, present in about 70-80 copies in each genome, was selected for amplification with the polymerase chain reaction (PCR) technique in order to evaluate its diagnostic potential in children with suspected pertussis. The 400 basepair DNA sequence chosen was present and amplified in all 112 B. pertussis strains and in no other bacterial species examined. The specificity of the amplified material was documented by restriction enzyme cleavage. In nasopharyngeal aspirates a B. pertussis specific PCR product was visualized in 19/25 culture positive and in 5/50 culture negative children. In conclusion the present PCR assay for B. pertussis can be clinically useful and permit a specific diagnosis within 1 day after sampling. Further studies are requested to document its sensitivity, specificity and predictive value for positive and negative results.

Base Sequence↗
PubMed1992

Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase.

To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Isomerases↗
PubMed1991

Trisomy 13 as a primary chromosome aberration in acute leukemia.

Four patients with acute leukemia displayed trisomy 13 as the primary chromosome abnormality. The two patients with acute nonlymphocytic leukemia FAB-type M1 (ANLL-M1) had the karyotypes 47,XY,+13/48,XY,+13,+13 and 47,XX,+13, a patient with the hypogranular form of ANLL M3 had 47,XX,+13, and the fourth patient, who had acute undifferentiated leukemia (AUL), had the karyotype 47,XY,+13/48,XY,+8,+13. Including these four cases, a total of 24 hematologic neoplasms with an extra chromosome 13 as the sole aberration have now been reported. Except for the AUL, all have been of myeloid origin--20 ANLL, one myelodysplastic syndrome, and two chronic myeloproliferative disorders. Trisomy 13 as the sole acquired karyotypic abnormality therefore seems to be strongly associated with myeloid differentiation of the neoplastic cells and with a differentiation block leading to acute leukemia.

Acute Disease↗
PubMed1991

Lymphocyte abnormalities predicting a poor prognosis in Hodgkin's disease. A long-term follow-up.

Two hundred sixty-two adult patients with Hodgkin's disease (HD) were studied. Incorporation of carbon-14-thymidine was measured in unstimulated monocyte-depleted lymphocyte cultures, and in cultures activated by concanavalin A (Con-A) before institution of therapy in all patients. Total blood lymphocytes and T-cell subsets were enumerated in the last 108 patients. Patients had significantly decreased total (CD3+, CD4+, CD8+) and relative (CD3+, CD4+) T-cell counts compared with healthy controls. Stage IV patients tended to have lower total lymphocyte and subset counts than remaining patients. However, significantly reduced total lymphocyte and CD8+ counts were only observed in comparison to patients in clinical stage II. Thirty-three percent of patients had an increased spontaneous and a decreased Con-A-induced blood lymphocyte DNA synthesis. Functional lymphocyte abnormalities were related to advanced clinical stage, high age, mixed cellularity, and lymphocyte depletion histopathology and presence of B symptoms. The 10-year survival of patients in this group was 36%, compared with 62% for the remainder. In a multivariate analysis of the whole series lymphocyte DNA synthesis was besides age the strongest predictor of prognosis. In univariate analyses of the second patient series total lymphocyte, T-cell and subset counts were related to prognosis. These relatively simple lymphocyte functional tests may help to identify young HD patients for whom intensive cytoreductive therapy with or without autologous stem cell support may be the best therapeutic option.

Actuarial Analysis↗
PubMed1991

Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes.

Since high-affinity adenosine A2 receptors (A2a) are localized exclusively in dopamine-rich regions in the central nervous system and mediate inhibition of locomotor activity, we have examined the effect of A2a receptor activation on D1 and D2 receptor binding in membrane preparations of the rat striatum. The A2a agonist 2-[p-(2-carboxyethyl)phenethylamino]-5'- N-ethylcarboxamidoadenosine (CGS 21680) increased the Kd of the dopamine D2 agonist L-(-)-N-[3H]propylnorapomorphine without affecting the Bmax. The increase in Kd was maximal (40%) at 30 nM CGS 21680. CGS 21680 (30 nM) decreased the dopamine-induced inhibition of [3H]raclopride (a D2 antagonist) binding due to an increase (about 3-fold) in KH and KL, the dissociation constants of high- and low-affinity binding sites. The effects of CGS 21680 were antagonized by the adenosine antagonist 8-phenyltheophylline (10 microM). (-)-N6-(2-Phenylisopropyl)adenosine produced an effect similar to that of CGS 21680, provided the concentration used was high enough to stimulate A2a receptors (300 nM). GTP (50 microM) also decreased the dopamine-induced inhibition of [3H]raclopride binding but, in contrast to CGS 21680, GTP decreased the proportion of D2 receptors in the high-affinity state. CGS 21680 (30 nM) did not affect the Kd or Bmax of [3H]raclopride and failed to affect ligand binding to D1 receptors. Thus, stimulation of A2a receptors potently reduces the affinity of D2 agonist binding sites within the plasma membrane of striatal neurons. This A2a-D2 interaction may underlie the neuroleptic-like actions of adenosine agonists and the enhancing effects of adenosine antagonists, such as caffeine, on locomotor activity.

Adenosine↗
PubMed1991

HIV in pregnant women and their offspring: evidence for late transmission.

To assess the role of maternal viraemia in vertical transmission of HIV and the extent to which viraemia occurs during the various stages of pregnancy, we have attempted to detect human immunodeficiency virus (HIV) in 44 pregnant HIV-1 infected women during 47 pregnancies (30 continued, 17 aborted) and in 30 children and 12 fetuses. Infectious HIV was detected at some time during pregnancy in 59% of women from plasma and in 83% from either peripheral blood mononuclear cells or plasma. HIV was not isolated from any of the newborn babies (0/27) at birth. The mothers had a significantly higher frequency of viraemia during pregnancy than their children had by 6 months of age (p = 0.002); by this time HIV was recovered from 5 (26%) of 19 infants. HIV was not detected by virus isolation, in-situ hybridisation, or polymerase chain reaction (PCR) in 10 fetuses; the other 2 fetuses were positive either by in-situ hybridisation or by PCR but neither result could be confirmed in a second organ or by the other methods of detection. The findings show that there is no consistent spread of HIV across the placenta during maternal viraemia, and indicate that in most cases transmission occurs close to or at delivery.

Female↗
PubMed1991

The transthyretin cDNA sequence is normal in transthyretin-derived senile systemic amyloidosis.

A variety of mutations leading to amino acid substitutions have been described in the transthyretin gene in association with different familial amyloidoses and have been implicated to be involved in the pathogenesis of amyloid deposits. However, there has been disagreement whether or not a transthyretin mutation is present in the most common form of transthyretin-derived amyloid, namely senile systemic amyloidosis. Therefore, the cDNA sequence of liver transthyretin was determined in a 91-year-old patient with typical senile systemic amyloidosis. This sequence was completely normal and lacked any variation. We conclude that in senile systemic amyloidosis factors other than the presence of a sequentially variant transthyretin must determine the amyloid fibril formation.

Aged↗
PubMed1991

Cytogenetic analysis of 33 basal cell carcinomas.

Cytogenetic analysis of short-term cultures from 33 basal cell carcinomas (BCC), a type of neoplasm for which no previous karyological data exist, revealed clonal chromosome aberrations, all of them different, in 8 tumors. In 2 cases, 2 cytogenetically unrelated clones were detected, suggesting a multicellular origin in at least a subset of BCC. A remarkably high level of nonclonal structural rearrangements, mostly in the form of seemingly balanced translocations, was found in 23 tumors; namely, in 6 of 8 BCC with clonal karyotypic abnormalities and in 17 of 25 without. It is possible that some of these aberrations represent additional neoplastic clones, thus indicating an even higher level of cytogenetic heterogeneity in BCC. We think that the most likely interpretation of the results is that BCC may have a multicellular origin, reflecting field cancerization of the skin. During subsequent tumor development, the selection pressure narrows down the number of clones that infiltrate the surrounding tissue. The finding by karyotypic analysis of some apparently monoclonal, some polyclonal BCC, may reflect that different tumors have been examined at different points in the clonal evolution of the neoplastic cells.

Aged↗
PubMed1991

Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid.

With the aim of improving early diagnosis of herpes simplex encephalitis a polymerase chain reaction (PCR) assay with two "nested" primer pairs was developed for the amplification of herpes simplex virus DNA in cerebrospinal fluid (CSF). Southern blotting was used to confirm the specificity of the amplification. The assay was applied to 151 CSF samples from 43 consecutive patients with herpes simplex encephalitis verified by the finding of herpes simplex virus/viral antigen in a brain biopsy sample or at necropsy (13) and/or intrathecal production of IgG antibody to the virus (40). As controls, 87 CSF samples from 60 patients with acute febrile focal encephalopathy (initially suspected to be herpes simplex encephalitis but excluded by the absence of intrathecal antibody synthesis) were tested. PCR detected herpes simplex virus DNA in 42 of the 43 patients with proven herpes simplex encephalitis; all but 1 were positive in the first CSF sample taken. The 1 PCR-negative patient had been treated with acyclovir from 20 h after the onset of symptoms. All the control subjects were PCR negative, as were 270 internal contamination controls. The PCR result remained positive in samples drawn up to 27 days after the onset of neurological symptoms. This method is a rapid and non-invasive means to diagnose herpes simplex encephalitis; it is highly sensitive and specific.

Acyclovir↗
PubMed1991

Purification of rat liver plasma membranes by wheat-germ-agglutinin affinity partitioning.

Rat liver plasma membranes were separated from other cellular membranes by affinity partitioning in an aqueous polymer two-phase system by using the lectin wheat-germ agglutinin covalently bound to dextran as the affinity ligand. In borate buffer the bulk of membranes partitioned in the poly(ethylene glycol)-rich top phase, whereas plasma membranes were pulled selectively into the dextran-rich bottom phase in the presence of ligand. The purity and yield of plasma membranes prepared by lectin affinity partitioning and by conventional sucrose-density-gradient centrifugation was similar, as judged from marker-enzyme activities. The affinity procedure, not dependent on lengthy centrifugations, is fast and gentle and will be advantageous when studying labile components.

Animals↗