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Biomedical subjects

I Johansson

Publications and source records attributed to I Johansson.

At least 127 records · Page 7Linked to original sources
PubMed1993

Salivary antimicrobial proteins in patients with Crohn's disease.

The aim was to study the level of salivary proteins with antimicrobial properties in persons with Crohn's disease. Twenty-five patients were recruited, 13 with ongoing symptoms (acute group) and 12 free of clinical signs of the disease at the time of the investigation (nonacute group). A control group matched to the nonacute group was also included in the study. Unstimulated and stimulated whole saliva samples were collected, and the secretion rates estimated. Unstimulated saliva was analyzed for concentrations of total protein, peroxidase, thiocyanate, slgA, lactoferrin, lysozyme, and for specific bacteria aggregation ability. Numbers of mutans streptococci and lactobacilli in saliva were determined, and dental caries status was examined. No differences were found among the groups regarding salivary flow rate, total protein, or any of the antimicrobial proteins. However, three patients with Crohn's disease had no detectable slgA in saliva compared with none in the control group. The lactobacillus count and the number of decayed tooth surfaces were higher in the nonacute group than in the control group.

Adult↗
PubMed1993

Debrisoquin and mephenytoin hydroxylation phenotypes and CYP2D6 genotype in patients treated with neuroleptic and antidepressant agents.

Debrisoquin and S-mephenytoin hydroxylation phenotypes were determined in 72 Spanish psychiatric patients treated with neuroleptic or antidepressant agents. One patient (1.4%) was classified as a poor metabolizer of S-mephenytoin. Between both neuroleptic- and antidepressant-treated patients, the distribution of the debrisoquin metabolic ratio was shifted toward higher values compared with 54 drug-free healthy subjects. Forty percent of patients treated with neuroleptics and 5% of patients treated with antidepressants were classified as poor metabolizers of debrisoquin. CYP2D6 genotype analysis in 36 neuroleptic-treated patients confirmed that the high metabolic ratios were attributable to inhibition of CYP2D6 and not to overrepresentation of subjects with poor metabolizer genotypes. In 48 selected Spanish drug-free subjects, CYP2D6 genotype predicted the phenotype with 95% accuracy. Neuroleptics and antidepressants interfere at therapeutic doses with phenotyping for CYP2D6 but not for S-mephenytoin hydroxylation capacity. In psychotropic-treated patients, genotyping provides a valuable tool for prediction of the CYP2D6 phenotype.

Adult↗
PubMed1993

Quinidine inhibition of debrisoquine S(+)-4- and 7-hydroxylations in Chinese of different CYP2D6 genotypes.

Pronounced differences in the CYP2D6 gene between Chinese and Caucasians have previously been described. There was a low frequency of detrimental mutations in the Chinese CYP2D6 gene causing the poor metabolizer (PM) phenotype. In contrast to Caucasians where the Xba I 44 kb allele is almost always associated with the PM phenotype, Chinese with the 44/44 kb RFLP pattern are extensive metabolizers (EM). In order to evaluate whether the debrisoquine hydroxylation seen in subjects with this haplotype is catalysed by a functionally similar enzyme to CYP2D6 or is catalysed by another type of P450 isozyme, product selectivity of the 4-hydroxylation was studied in 27 Chinese. The inhibition of CYP2D6 by quinidine was also investigated. In the 26 Chinese EM the S(+)-4-hydroxy enantiomer was found to be the major urinary metabolite of debrisoquine with an enantiomeric excess of 96.8-100%, which is similar to that in Caucasians. A correlation between the amount of S(+)-4-hydroxy and the minor 7-hydroxy metabolites excreted in urine (r = 0.72; p < 0.001) was seen. The amount of these two metabolites excreted was less in Chinese EM of debrisoquine with the 44/44 kb RFLP pattern, than in those with the wild type 29/29 kb pattern (p < 0.01). The stereoselectivity was very high in both groups. All Chinese homozygous for the 44 kb fragment (n = 5) were transformed to apparent PM after a single 100 mg dose of quinidine similarly to five Caucasian EM. Both the S(+)-4- and 7-hydroxylations of debrisoquine were inhibited by quinidine in both populations. This study shows that the cytochrome P450 catalysing the 4- and 7-hydroxylations of debrisoquine in Chinese EM has the same properties (product stereoselectivity and inhibition by quinidine) as the CYP2D6 in Caucasian EM.

Asian People↗
PubMed1993

Genetic polymorphism of cytochrome P450 CYP2D6 in Zimbabwean population.

The objective of this study was to determine the CYP2D6 genotype of a black Zimbabwean population. Genotyping was carried out using Eco RI and Xba I RFLP, and allele-specific PCR amplification. Of 114 Zimbabwean samples analysed, no individual homozygous for any of the defect allelic forms CYP2D6A, CYP2D6B or CYP2D6D or combinations thereof was found. The allele frequencies of the three defect genes were 0, 1.8 and 3.9%, respectively. No subject carrying the Xba I 44 kb haplotype, indicative for poor metabolizers among Caucasians, was identified, whereas five individuals being heterozygous with a 29/42 kb haplotype were seen. Three out of the four CYP2D6B alleles found were associated with the 29/42 kb haplotype. Our findings are in agreement with the 0-2% prevalence of poor metabolizers (PMs) in the black populations previously phenotyped. The very low frequency of the CYP2D6B allele in the Zimbabwean population is different from very recent data from black Americans (allele frequency = 8.5%) and might indicate the Caucasian ancestry of this allele. Taken together, our data indicate important interethnic differences in the CYP2D locus between Caucasian, Asian and different black populations.

Base Sequence↗
PubMed1993

Teaching prereading skills to disabled children.

A Swedish survey suggests that less than 10% of children with Down's syndrome between 7 and 10 years of age are able to read a simple text. Children with Down's syndrome in a programme for early language intervention show clear progress in reading ability. The programme focuses on general language development, auditory and visual perception, and fine-motor ability. Prereading skills are stimulated in a systematic way such as identifying and discriminating sound-patterns at the level of the word, the syllable and the segments, and children are helped to categorize forms, to discriminate and understand pictures, to recognize the direction of reading, and to realize the grapheme-phoneme correspondence.

Child↗
PubMed1993

Diet counselling and behaviour change.

A number of questions related to oral as well as general health seem to be relevant to a discussion on development of counselling techniques aimed at changing various types of health-related behaviour in man, such as dietary habits, smoking, and alcohol use. This paper discusses dietary counselling and behaviour change in dental practice.

Behavior Therapy↗
PubMed1993

Use of smokeless tobacco and cigarettes--effects on plasma levels of antioxidant vitamins.

In a population-based sample of 40-49-year-old men, plasma levels of antioxidant vitamins were measured in 17 regular users of smokeless tobacco (oral snuff), 26 regular smokers and 54 non-tobacco users. Vitamin intake by tobacco use was assessed by a food frequency questionnaire in 174 men in the 40-49 year age range. Compared with non-tobacco users, snuff dippers had similar plasma levels of ascorbate, tocopherols and carotenoids, whereas these were all significantly reduced in smokers. Smokers, but not snuff dippers, had plasma levels of ascorbate significantly below those expected from ascorbic acid intake, indicating enhanced expenditure of ascorbate in smokers but not in snuff dippers. The results show that plasma levels of antioxidant vitamins are not reduced in snuff dippers as they are in smokers, possibly as the combined result of higher intake and lower expenditure of ascorbate and tocopherols in those who use smokeless tobacco.

Adult↗
PubMed1992

[Genotyping for drug metabolism capacity can give valuable clinical information].

There is pronounced individual variation in the human metabolism (eg, acetylation and hydroxylation) of drugs, in many cases due to genetic factors. The genetic basis of cytochrome P4502D6 gene defects has recently been elucidated, for instance. The cytochrome P4502D6 is absent from 7 percent of the Caucasian population, usually owing to the presence of either of two different mutations in the corresponding gene. PCR amplification of genomic DNA with allele-specific primers enables rapid prediction of the patient's drug metabolism capacity and the individualization of drug treatment with respect to dosage.

Cytochrome P-450 Enzyme System↗
PubMed1992

Zonation of cytochrome P450 isozyme expression and induction in rat liver.

The regional expression of six different cytochrome P450 (CYP) forms in rat liver under constitutive and induced conditions was compared using immunological techniques. Immunostaining of consecutive thin sections from control liver revealed that the same hepatocytes, forming a 6-8 cells thick layer surrounding the terminal hepatic venules, were stained for CYP2B1/2, CYP2E1 and CYP3A1. Staining of CYP2A1 extended further into the midzonal region, whereas all cells of the acinus stained for CYPEtOH2. These results were supported by Western blot analysis of cell lysates from the periportal or perivenous region obtained by zone-restricted digitonin treatment during in situ perfusion. The data suggest three distinct patterns of constitutive P450 expression: perivenous-restricted (CYP2B1/2, CYP2E1 and CYP3A1); perivenous-dominated (CYP2A1) and panacinar (CYPEtOH2). Chronic exposure to ethanol caused induction of CYP2E1 in the same cells already being constitutively expressed, whereas CYPEtOH2 was more induced in the periportal area. The relative induction of CYP2B1/2, CYP3A1 and CYPEtOH2 after treatment with phenobarbital was stronger in periportal hepatocytes, resulting in levelling out of the initial perivenous dominance of CYP2B1/2 and CYP3A1, whereas CYPEtOH2 became periportal-dominated. Acetone induced CYP2E1, CYP2C11 and CYP3A1 selectively in the perivenous area. These studies indicate that a particular P450 isozyme is generally induced in the same cells where it is constitutively expressed, and that this regional selectivity is independent of the kind of inducer. The data suggest that, during maturation, the hepatocytes acquire various phenotypes in the periportal and perivenous region, to respond differently to endogenous and exogenous signals in the control of P450 expression.

Acetone↗
PubMed1992

N-myc gene amplification in neuroblastoma: a clinical approach using ultrasound guided cutting needle biopsies collected at diagnosis.

N-myc gene amplification was studied in a consecutive series of neuroblastomas and ganglioneuromas, representing all of such tumours diagnosed in Sweden over a 4-year period. Both frozen and formalin fixed specimens were used for Southern blot analysis. Thirty-seven of 46 neuroblastomas and 7 of 9 ganglioneuromas were analyzed. Seven neuroblastomas and none of the ganglioneuromas showed N-myc gene amplification. All children with amplified tumours, including three infants, had advanced disease at diagnosis and aggressive course of disease. However, follow-up time was short for the two cases still alive. The use of an ultrasound guided cutting needle biopsy technique for obtaining the required tissue at diagnosis was evaluated in some cases. This technique appeared to be safe and clinically useful since early prognostic information was obtained. Using an imprint from the needle biopsy, the representativity could be confirmed. Ultrasound guided cutting needle biopsies can thus be used routinely to obtain N-myc gene amplification data prior to initiation of therapy in neuroblastoma.

Biopsy, Needle↗
PubMed1992

Salivary hypofunction in patients with familial amyloidotic polyneuropathy.

Patients who suffer from familial amyloidotic polyneuropathy frequently complain of mouth dryness and an increased need for dental treatment. The aim of the present investigation was to study saliva secretion rate and composition and other factors related to the risk of dental caries in patients with familial amyloidotic polyneuropathy. Thirty patients with familial amyloidotic polyneuropathy volunteered for the study and were compared with a matched control group. Samples of unstimulated and stimulated whole saliva were collected in a standardized manner. The secretion rates were calculated, and the concentrations of electrolytes, glycoprotein markers, and proteins with antibacterial properties were analyzed. Dental caries and variables related to the risk of dental caries were also scored. The results show that familial amyloidotic polyneuropathy patients frequently have a decreased rate of saliva secretion and that the degree of salivary hypofunction is positively correlated to the progress of familial amyloidotic polyneuropathy. Forty-three percent of the familial amyloidotic polyneuropathy patients in this study had no detectable secretion of unstimulated saliva. A low secretion rate of stimulated saliva (< 0.7 ml/min) was found in 33% of the patients. The concentrations of salivary protein, amylase, lysozyme, salivary peroxidase, secretory IgA, hexosamines, sialic acid, fucose, phosphate, potassium, and the degree of protein glycosylation were higher in the familial amyloidotic polyneuropathy patients than in the control patients. We conclude that patients with familial amyloidotic polyneuropathy have a reduced saliva secretion and are subsequently at risk for increased development of dental caries.

Adult↗
PubMed1992

Analysis of the CYP2D6 gene in relation to debrisoquin and desipramine hydroxylation in a Swedish population.

The molecular basis of polymorphic debrisoquin hydroxylation was studied in 223 Swedish white subjects, 187 extensive metabolizers and 36 poor metabolizers phenotyped with debrisoquin and desipramine. Restriction fragment length polymorphism (RFLP) analysis of the CYP2D6 gene revealed that 52% of unrelated poor metabolizers were homozygous for Xba I 29 kb fragment, and only 8% had two mutant alleles detected with RFLP. Allele-specific polymerase chain reaction (PCR)-based DNA amplification, however, revealed that all but one of the poor metabolizers had two mutant alleles of the CYP2D6A or CYP2D6B type or both. Extensive metabolizers who were heterozygous for wild-type and CYP2D6B genes had metabolic ratios for debrisoquin and desipramine that were higher than those of subjects who were homozygous for the wild-type gene. The 16 + 9 kb Xba I RFLP pattern was associated with the poor metabolizer phenotype and CYP2D6B mutations. Three extremely rapid metabolizers of debrisoquin had a 44 kb Xba I fragment that did not carry either CYP2D6A or CYP2D6B mutations. In conclusion, in the Swedish population studied, allele-specific PCR amplification allowed prediction of the debrisoquin hydroxylation phenotype with 99% accuracy.

Adolescent↗
PubMed1992

Genetic polymorphism of cytochromes P450: interethnic differences and relationship to incidence of lung cancer.

The cytochromes P450 participate in the metabolic activation of precarcinogens. Recent results reveal that many P450 genes are polymorphically distributed. Different investigators have tried to link polymorphic variants of the CYP1A1, CYP2D6 and CYP2E1 genes to the incidence of cancer, particularly lung cancer, in Asian and Caucasian populations. In the current overview we briefly summarize this research. It appears that interesting functionally linked interindividual differences in the CYP1A1 gene have been found and could be of importance in understanding differences in susceptibility to lung cancer. On the other hand, the data presented regarding CYP2D6 and CYP2E1 are less promising. We also describe interethnic differences in the P450 gene structures as a major obstacle for extrapolation of results between different ethnic groups.

Cytochrome P-450 CYP1A1↗
PubMed1992

Prevalence of caries in adolescents in relation to diet.

The aim of the present study was to compare dietary habits between adolescents with high or low dental caries prevalence. All 15-yr-old adolescents living in a small community in Northern Sweden were studied in 1987, 1988, and 1989. The median values for energy and nutrient intake exceeded or were close to the recommendations (SNR89) given by the Swedish National Food Administration. The fiber intake did not reach the recommended daily amount even for the 90th percentile of the studied cohort. Nineteen percent of the adolescents had caries free teeth and 10% had nine or more decayed or filled surfaces. There was no difference in daily sucrose intake or average number of meals per day between these two groups. The group with nine or more decayed or filled surfaces had worse dietary habits, expressed as a higher fat intake, lower intake of complex carbohydrates, and lower density of iron (mg/MJ) than the group with no dental caries. Dietary counseling by dentists should be a valuable addition to other caries prophylactic measures taken by the dentists.

Adolescent↗
PubMed1992

Effects of dietary fat composition on activities of the microsomal ethanol oxidizing system and ethanol-inducible cytochrome P450 (CYP2E1) in the liver of rats chronically fed ethanol.

We studied the effects of dietary fat composition on the activities of the microsomal ethanol oxidizing system (MEOS), paranitrophenol hydroxylase (PH) activity and ethanol-inducible cytochrome P450 isozymes (CYP2E1 and CYP2B1) in the liver of rats to determine the role of this ethanol metabolizing pathway in the pathogenesis of alcoholic liver disease (ALD). Wistar male rats were pair-fed a liquid diet, containing either tallow (TF) or corn oil (CF) as the fat component, and ethanol or an isocaloric amount of dextrose, through an implanted intragastric cannula. Liver pathology of rats fed ethanol (CF-ALC) and CF diet showed severe fatty change whereas the rats fed TF-alcohol and the TF and CF controls did not. MEOS activity of the CF-ALC group was 8 times of that in the CF-CTL group (P less than 0.01). In TF-ALC rats, MEOS activity was increased to 2.6 times compared to that of TF-CTL (P less than 0.01). ApoCYP2E1 in CF-ALC and TF-ALC were 818 +/- 63 and 433 +/- 1- pmol/mg protein, respectively, and these values were significantly higher when compared with those of the pair-fed controls (P less than 0.005). In contrast, apoCYP2B1 was increased to an equal degree in both CF-ALC and TF-ALC. When PH-activity was measured, the level of activity on TF-ALC rats did not differ from that of CF-ALC rats. Thus, ethanol-induction of apoCYP2B1 (2x) and PH (6-8x) were the same for CF and TF (2x); but not for apoCYP2E1 (21 and 8x, respectively) and MEOS activity (8 and 2.6x, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Oxidoreductases↗
PubMed1992

Increased release of tissue plasminogen activator and its inhibitor in human parotid saliva upon stimulation.

Parotid saliva from 12 healthy volunteers was collected prior to and after 5 and 25 min of stimulation at a constant flow rate of 0.25 or 1.0 ml min-1. In the salivary samples the concentrations of tPA (tissue-type plasminogen activator), PAI-1 (plasminogen activator inhibitor type-1), albumin and total protein were determined and the activity of amylase, tPA and PAI assessed. Presence of both tPA and PAI-1 antigen was demonstrated in all samples, and in unstimulated saliva the ratio between the activator and its inhibitor was 1:7. Upon stimulation we found a significantly increased concentration of PAI-1, a less pronounced increase in tPA concentration, unchanged amylase and total protein levels and significantly decreased albumin concentration. tPA activity was significantly reduced after prolonged stimulation which had no effect on PAI activity. In stimulated saliva a significant positive correlation between concentration of tPA and PAI-1 was demonstrated. Stimulation with citric acid had no effect on output of albumin which is passively filtered from blood, whereas the increase in flow rate corresponded to the significantly increased secretion rate of total protein and amylase which is secreted by gland cells. The secretion pattern of tPA and PAI-1 differed significantly from that of albumin in showing markedly increased output rate during the stimulation period, and the relative increase in output of PAI-1 was significantly higher than that of amylase and total protein. Thus, the results from this study suggest an active release of both tPA and its main inhibitor PAI-1 into saliva.

Adult↗
PubMed1992

Effects of ultraviolet irradiation on natural killer cell function in systemic lupus erythematosus.

In vitro irradiation with long wavelength ultraviolet light (UV-A), in clinically relevant dosages, of a natural killer cell line containing cell preparations from 17 control subjects reduced natural killer cell cytotoxicity with the cell line K562 as target. The spontaneous function of natural killer cells from 12 patients with systemic lupus erythematosus (SLE) correlated inversely with the one hour erythrocyte sedimentation rate, but not with glucocorticoid doses. After UV-A exposure, natural killer cells from patients with SLE exert either increased or decreased cytotoxicity, and the direction of change is inversely correlated with the spontaneous natural killer cell function.

Adolescent↗