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Biomedical subjects

B Persson

Publications and source records attributed to B Persson.

At least 181 records · Page 10Linked to original sources
PubMed1995

Decreased glomerular filtration rate in solderers exposed to cadmium.

OBJECTIVES: to evaluate the degree of cadmium induced glomerular impairment and to assess the dose-response relation between cadmium dose and the prevalence of glomerular dysfunction. METHODS: A comparison of glomerular filtration rates (GFR) assessed by Cr-EDTA clearance was made in 42 solderers previously exposed to cadmium for at least five years. Blood and urine data were collected at health examinations in 1984, 1989, and 1993. Individual doses of cadmium were estimated by analysing cadmium in blood. RESULTS: Glomerular lesions induced by cadmium are irreversible and the GFR decreases with the degree of tubular damage. The GFR also decreases with cadmium dose and there is a dose-response relation between blood cadmium and prevalence of glomerular damage with 3.4% prevalence at blood cadmium concentrations below 50 nmol/l, 33% at blood cadmium concentrations between 50 and 75 nmol/l and 100% prevalence of glomerular damage when cadmium in blood exceeds 75 nmol/l. CONCLUSIONS: The kidney lesions induced by cadmium are irreversible and the prevalence of those lesions are dose dependent. There is also evidence of a dose related decrease in GFR even a long time after the end of exposure. Exposure to cadmium should therefore be minimised and workers exposed to cadmium should be examined regularly for many years after the end of exposure.

Cadmium↗
PubMed1995

Exposure to cobalt chromium dust and lung disorders in dental technicians.

BACKGROUND: Dental technician's pneumoconiosis is a dust-induced fibrotic lung disease of fairly recent origin. This study was carried out to estimate its occurrence in Sweden. METHODS: Thirty seven dental technicians in central and south eastern Sweden with at least five years of exposure to dust from cobalt chromium molybdenum (CoCrMo) alloys, identified by postal survey, agreed to undergo chest radiography and assessment of lung function and exposure to inorganic dust. RESULTS: Six subjects (16%; 95% confidence interval 6% to 23%) showed radiological evidence of dental technician's pneumoconiosis. The lung function of the study group was reduced compared with historical reference material. With local exhaust ventilation dust levels were generally low, whereas in dental laboratories without such equipment high levels of dust, particularly cobalt, were found. CONCLUSIONS: Pneumoconiosis may result from exposure to inorganic dust in the manufacturing of CoCrMo-based dental constructions. It is possible to reduce this hazard substantially by local exhaust ventilation.

Adult↗
PubMed1995

Association between lipoprotein(a) and insulin-like growth factor I during puberty and the relationship to microalbuminuria in children and adolescents with IDDM.

OBJECTIVE: To study pubertal changes in serum lipoprotein(a) [Lp(a)] and insulin-like growth factor I (IGF-I) in insulin-dependent diabetes mellitus (IDDM) and the relationship to microalbuminuria. RESEARCH DESIGN AND METHODS: Seventy-nine children and adolescents (59 with normoalbuminuria, 20 with microalbuminuria) with > or = 5 years of IDDM were investigated together with 54 healthy control subjects in a cross-sectional study. Fasting serum Lp(a); apolipoprotein (apo) A-1 and B; total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol; triglycerides; and IGF-I were analyzed as were HbA1c and overnight albumin excretion rate (AER). Pubertal development was assessed by Tanner staging. RESULTS: Lp(a), apoB, triglycerides, and total and LDL cholesterol were higher (P < 0.001) and apoA-1 was lower (P = 0.03) in normoalbuminuric IDDM patients than in healthy control subjects. Lp(a) was increased during puberty (stages 2-4) in IDDM patients but not in healthy subjects, whereas IGF-I was significantly increased during puberty in healthy control subjects only. In IDDM patients Lp(a) correlated to insulin dose, total cholesterol, and LDL cholesterol, but not to IGF-I, HbA1c, systolic and diastolic blood pressure, diabetes duration, age, or sex. In multiple regression analysis with Lp(a) as the dependent variable, puberty was the only significant contributor to the regression (r2 = 0.33, P = 0.008). Microalbuminuria was seen only in the pubertal stage 4-5. Lp(a) tended to be higher (P = 0.06) as did apoB, whereas IGF-I was lower (P < 0.001) in this group than in normoalbuminuric patients of the same pubertal stages. In multivariate analysis, with log AER as the dependent variable, apoB/apoA-1, systolic blood pressure, age, and IGF-I but not Lp(a) added to the regression (r2 = 0.47, P < 0.0001). CONCLUSIONS: Lp(a) is elevated during puberty in normoalbuminuric subjects with IDDM, independent of metabolic control and IGF-I. Lp(a) tends to be further increased in microalbuminuria but does not seem to be a contributing determinant of log AER whereas low IGF-I does. Prospective studies are required to establish the temporal relationship between increased Lp(a) and microalbuminuria in children and adolescents with IDDM.

Adolescent↗
PubMed1995

Blood glucose limits in the diagnosis of impaired glucose tolerance during pregnancy. Relation to morbidity.

OBJECTIVE: To evaluate the accuracy of diagnosing gestational diabetes mellitus (GDM) by a 2-h blood glucose value > or = 9.0 mmol/l in the 75 g oral glucose tolerance test (OGTT). The maternal and neonatal outcome in women with a 2-h blood glucose value just below this limit, 8.0-8.9 mmol/l, is analyzed. The outcome is compared to a randomly selected control group. DESIGN: A comparative study. SUBJECTS: There were 223 women in the group with a 2-h value of 8.0 to 8.9 mmol/l in the OGTT. This group was compared to a randomly selected control group of 391 women. MAIN OUTCOME MEASURES: Fetal outcome: perinatal mortality, birth weight, respiratory disturbances, symptomatic hypoglycemia, polycythemia, hyperbilirubinemia and traumatic deliveries. Maternal age, body mass index (BMI), pregnancy-induced hypertension (PIH) or preeclampsia and route of delivery. RESULTS: The women in the group with a 2-h glucose value of 8.0-8.9 mmol/l were, compared to the control group, significantly older, heavier, had a higher BMI, gave birth to heavier children and a significantly increased number of large-for-date infants, while there were no differences in neonatal mortality, morbidity or birth trauma. CONCLUSIONS: This study shows that using the 75 g 2-h OGTT with a B-glucose limit of > or = 9.0 mmol/l instead of > or = 8.0 mmol/l to diagnose GDM during pregnancy has no major adverse effects concerning maternal and neonatal outcome in the borderline interval of 8.0 to 8.9 mmol/l.

Birth Weight↗
PubMed1995

Protein structure prediction: recognition of primary, secondary, and tertiary structural features from amino acid sequence.

This review attempts a critical stock-taking of the current state of the science aimed at predicting structural features of proteins from their amino acid sequences. At the primary structure level, methods are considered for detection of remotely related sequences and for recognizing amino acid patterns to predict posttranslational modifications and binding sites. The techniques involving secondary structural features include prediction of secondary structure, membrane-spanning regions, and secondary structural class. At the tertiary structural level, methods for threading a sequence into a mainchain fold, homology modeling and assigning sequences to protein families with similar folds are discussed. A literature analysis suggests that, to date, threading techniques are not able to show their superiority over sequence pattern recognition methods. Recent progress in the state of ab initio structure calculation is reviewed in detail. The analysis shows that many structural features can be predicted from the amino acid sequence much better than just a few years ago and with attendant utility in experimental research. Best prediction can be achieved for new protein sequences that can be assigned to well-studied protein families. For single sequences without homologues, the folding problem has not yet been solved.

Amino Acid Sequence↗
PubMed1995

Cancer incidence and mortality of patients with suspected solvent-related disorders.

OBJECTIVE: The aim of this study was to study the incidence of cancer and deaths from cancer and other diseases among patients referred to the 11 clinics of occupational medicine in Sweden between 1967 and 1987 for examination because of exposure to organic solvents. METHODS: The cohort comprised 5791 persons, 5283 men and 508 women. Information about cancer incidence and causes of death was collected from the Cancer Register of the National Board of Health and Welfare and the National Death Register of Statistics Sweden, respectively. The expected values were calculated from the national death rates and incidence rates of cancer. RESULTS: The overall mortality rate was close to expected, but the mortality rate was decreased for diseases of the circulatory system [standardized mortality ratio (SMR) 0.7, 95% confidence limit (95% CI) 0.5-0.9] and increased for suicide (SMR 2.0, 95% CI 1.2-3.2). The total cancer incidence was slightly elevated [standardized incidence ratio (SIR) 1.2, 95% CI 0.99-1.4], and some specific cancer sites showed an increased incidence, although the lower confidence limits surpassed one. Malignancies of the lymphohematopoietic system and cancer of the uterine cervix had an increased risk (SIR 1.9, 95% CI 1.2-3.2, and SIR 3.7, 95% CI 2.2-6.2, respectively). Patients with presumerably high solvent exposure had an SIR of 1.4 for all malignancies (95% CI 0.9-2.1) and those with presumerably low exposure had an SIR of 1.1 (95% CI 0.9-1.4). CONCLUSIONS: The study showed an increased risk for malignancies of the hematopoietic system and the uterine cervix among patients originally examined with regard to solvent-induced disorders. There was also an increased risk of suicide and a decreased risk of death from diseases of the circulatory system. There was no increased risk for deaths from mental or neurological disorders.

Adult↗
PubMed1995

Dynamic Octreotide scintigraphy in neuroendocrine tumours.

The purpose of the present study was to investigate the optimal time for scintigraphy after injection of the radio-labelled somatostatin analogue, Octreotide. A secondary purpose was to evaluate the value of SPECT. One SPECT study and up to 4 whole body scans were performed in 22 patients with neuroendocrine tumours 0.5, 5, 24 and 48 hours after an injection of 110 MBq In-DTPA Octreotide. A total of 98 scintigrams were studied. A pathological uptake was found in 19 of the 22 patients. In 3 cases, early scintigrams (0.5 and 5 hours after injection) were of the most value whereas late scintigrams (24 and 48 hours) were the best in 4 cases. SPECT was found to be of value in 13 of 21 cases. For correct interpretation of Octreotide scintigraphy it is necessary to obtain both early and late scintigrams as well as a SPECT study.

Adult↗
PubMed1995

Elective abdominal operations alter the free amino acid content of the human intestinal mucosa.

OBJECTIVE: To assess the impact of a standard moderately severe surgical operation on the mucosal amino acid content of the duodenum and the colon. DESIGN: Open study. SETTING: University hospital, Sweden. SUBJECTS: Nine patients who were to undergo elective open cholecystectomy. INTERVENTIONS: Endoscopically obtained biopsy specimens from the intestinal mucosa. MAIN OUTCOME MEASURES: Changes in the content of free amino acids in the duodenum and colon at three days postoperatively. RESULTS: The concentration of glutamine in the duodenum increased by 27% and that of glutamic acid by 34% after operation, whereas their content in colon remained unaltered. The concentration of branched chain amino acids increased by 26% in the duodenal mucosa after operation and by 24% in the colonic mucosa. The total concentration of amino acids (excluding taurine) increased by 9% in the duodenum, but remained unaltered in the colon. CONCLUSION: This study shows characteristic and consistent alterations in the free amino acid content of the intestinal tract after a moderately severe operation.

Amino Acids↗
PubMed1994

A super-family of medium-chain dehydrogenases/reductases (MDR). Sub-lines including zeta-crystallin, alcohol and polyol dehydrogenases, quinone oxidoreductase enoyl reductases, VAT-1 and other proteins.

The protein super-family of medium-chain alcohol dehydrogenases (and glutathione-dependent formaldehyde dehydrogenase), polyol dehydrogenases, threonine dehydrogenase, archaeon glucose dehydrogenase, and eye lens reductase-active zeta-crystallins also includes Escherichia coli quinone oxidoreductase, Torpedo VAT-1 protein, and enoyl reductases of mammalian fatty acid and yeast erythronolide synthases. In addition, two proteins with hitherto unknown function are shown to belong to this super-family of medium-chain dehydrogenases and reductases (MDR). Alignment of zeta-crystallins/quinone oxidoreductases/VAT-1 reveals 38 strictly conserved residues, of which approximately half are glycine residues, including those at several space-restricted turn positions and critical coenzyme-binding positions in the alcohol dehydrogenases. This indicates a conserved three-dimensional structure at the corresponding parts of these distantly related proteins and a conserved binding of a coenzyme in the two proteins with hitherto unknown function, thus ascribing a likely oxidoreductase function to these proteins. When all forms are aligned, including enoyl reductases, a zeta-crystallin homologue from Leishmania and the two proteins with hitherto unknown function, only three residues are strictly conserved among the 106 proteins characterised within the superfamily, and significantly these residues are all glycines, corresponding to Gly66, Gly86 and Gly201 of mammalian class I alcohol dehydrogenase. Notably, these residues are located in different domains. Hence, a distant origin and divergent functions, but related forms and interactions, appear to apply to the entire chains of the many prokaryotic and eukaryotic members. Additionally, in the zeta-crystallins/quinone oxidoreductases, a highly conserved tyrosine residue is found. This residue, in the three-dimensional structure of the homologous alcohol dehydrogenase, is positioned at the subunit cleft that contains the active site and could therefore be involved in catalysis. If so, this residue and its role may resemble the pattern of a conserved tyrosine residue in the different family of short-chain dehydrogenases/reductases (SDR).

Alcohol Dehydrogenase↗
PubMed1994

Cysteine-scanning mutagenesis of putative helix VII in the lactose permease of Escherichia coli.

Using a functional lactose permease mutant devoid of Cys residues (C-less permease), each amino acid residue in putative transmembrane helix VII and the flanking cytoplasmic and periplasmic regions (from Leu212 to Glu255) was replaced individually with Cys. Of the 44 single-Cys mutants, 40 exhibit high transport activity, accumulating lactose to > 50% of the steady-state observed with C-less permease. In contrast, permease with Cys in place of Ala213 or Tyr236 exhibits low but significant activity, and Cys substitution for Asp237 or Asp240 yields permease molecules with little or no activity due to disruption of charge-neutralizing interactions between Asp237 and Lys358 or Asp240 and Lys319, respectively. Immunological analysis reveals that membrane levels of the mutant proteins are comparable to that of C-less permease with the exception of Tyr228-->Cys, which exhibits reduced but significant levels of permease. Finally, the effect of N-ethylmaleimide (NEM) was tested on each mutant, and the results indicate that the transport activity of the great majority of the mutants is not affected by the alkylating agent. Remarkably, the six positions where Cys replacements render the permease highly sensitive to inactivation by NEM are confined to the C-terminal half of helix VII, a region that is strongly conserved among transport proteins homologous to lactose permease. The results demonstrate that although no residue per se in the region scanned is essential, structural features of the C terminus of helix VII may be important for transport activity.

Amino Acid Sequence↗
PubMed1994

Prediction of transmembrane segments in proteins utilising multiple sequence alignments.

A method for prediction of transmembrane segments from multiply aligned amino acid sequences is presented. For the calculations, two sets of propensity values were used: one for the middle, hydrophobic portion and one for the terminal regions of the transmembrane sequence spans. Average propensity values were calculated for each position along the alignment, with the contribution from each sequence weighted according to its dissimilarity relative to the other aligned sequences. Eight-residue segments were considered as potential cores of transmembrane segments and elongated if their middle propensity values were above a given threshold. End propensity values were also considered as stop signals. Only helices with length of 15 to 29 residues were allowed and corrections for strictly conserved charged residues were also made. The method is shown to be more successful than predictions based upon single sequences alone. In the test set of 28 families with 126 transmembrane segments, only five spans were not predicted or constituted false positives. The method is applied to sequence families for which data on transmembrane segments do not exist or are sparse or contradictory included voltage-gated potassium-channels, cytochrome c oxidases, NADH-ubiquinone oxidoreductase, beta-glucosides-specific phosphotransferase enzyme and major surface antigen of hepatitis B virus.

Algorithms↗
PubMed1994

Evidence for a nicotinamide nucleotide transhydrogenase in Klebsiella pneumoniae.

Bacterial membranes from Klebsiella pneumoniae were investigated for the presence of a nicotinamide nucleotide transhydrogenase activity. Inverted membrane vesicles derived from these cells catalyzed a reduction of NAD+ or 3-acetylpyridine-NAD+ by NADPH, which showed a maximal activity of about 260 nmoles/minute per milligram protein at pH 7-8. In the presence of a protonic uncoupler the specific activity was stimulated about two-fold in this pH range. The presence of detergents did not further increase the specific activity of enzyme. The Klebsiella pneumoniae transhydrogenase activity was sensitive to phenylarsine oxide and palmityl-Coenzyme A, both of which are agents known to inhibit the mammalian enzyme. The Ki-value for palmityl-Coenzyme A with respect to NADPH was about 1.25 microM. Antibodies raised against beef heart transhydrogenase crossreacted with a 54 kD protein in the Klebsiella pneumonia membrane.

Animals↗
PubMed1994

Cysteine scanning mutagenesis of the N-terminal 32 amino acid residues in the lactose permease of Escherichia coli.

Using a functional lactose permease mutant devoid of Cys residues (C-less permease), each amino acid residue in the hydrophilic N-terminus and the first putative transmembrane helix was systematically replaced with Cys (from Tyr-2 to Trp-33). Twenty-three of 32 mutants exhibit high lactose accumulation (70-100% or more of C-less), and an additional 8 mutants accumulate to lower but highly significant levels. Surprisingly, Cys replacement for Gly-24 or Tyr-26 yields fully active permease molecules, and permease with Cys in place of Pro-28 also exhibits significant transport activity, although previous mutagenesis studies on these residues suggested that they may be required for lactose transport. As expected, Cys replacement for Pro-31 completely inactivates, in agreement with previous findings indicating that "helix-breaking" propensity at this position is necessary for full activity (Consler TG, Tsolas O, Kaback HR, 1991, Biochemistry 30:1291-1297). Twenty-nine mutants are present in the membrane in amounts comparable to C-less permease, whereas membrane levels of mutants Tyr-3-->Cys and Phe-12-->Cys are slightly reduced, as judged by immunological techniques. Dramatically, mutant Phe-9-->Cys is hardly detectable when expressed from the lac promoter/operator at a relatively low rate, but is present in the membrane in a stable form when expressed at a high rate from the T7 promoter. Finally, studies with N-ethylmalemide show that 6 Cys-replacement mutants that cluster at the C-terminal end of putative helix I are inactivated significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Insulin sensitivity is more related to fat distribution than to heredity for hypertension in normotensive men.

The insulin-mediated glucose disposal rate was assessed during a euglycemic hyperinsulinemic clamp in 16 normotensive men (mean age, 41 +/- 5 years) with positive family histories of hypertension and mild overweight (PFHO) and in 25 men with negative family histories of hypertension (NFH). The control group was divided into one group with normal body weight ([NFHN] n = 11) and a second group with a similar degree of overweight ([NFHO] n = 14) as in the group with PFHO. Systolic and diastolic blood pressures were significantly greater in subjects with PFHO as compared with the NFHN group. Blood glucose and plasma insulin at baseline and during the insulin clamp did not differ between the three groups. Insulin sensitivity, expressed as the glucose disposal rate per total body weight, was significantly (P < .01) decreased in PFHO subjects (7.7 +/- 3.0 mg/kg/min) and in NFHO subjects (7.1 +/- 3.5 mg/kg/min) as compared with NFHN subjects (11.1 +/- 4.0 mg/kg/min). In multivariate analysis using body mass index, waist to hip ratio, and blood pressure as predictor variables, the waist to hip ratio was significantly related to both baseline plasma insulin (r = .70, P < .0001) and insulin sensitivity (r = -.71, P < .0001). In the present study, insulin sensitivity was related to body weight and fat distribution, whereas no difference was found regarding insulin sensitivity in subjects with or without positive family histories of hypertension.

Adipose Tissue↗
PubMed1994

Cytogenetic heterogeneity in a clear cell hidradenoma of the skin.

Short-term cultures from a clear cell hidradenoma, a benign skin tumor for which no chromosome data exist, were cytogenetically analyzed. A total of eight unrelated aberrant clones were identified. The karyotypic profiles of two separately processed parts of the sample--a tumor nodule and seemingly normal adjacent dermal tissue--were different. Characteristic for the tumor nodule was a single abnormal clonal population consisting of three subclones: 46,XY,der(2)inv(2)(p13q23)t(2;9)(p13;q22), der(9)t(2;9)(q23;q22),t(11;19)(q21;p13),t(12;19)(q24;p13)/46,idem, inv(1)(p32q44)/92,idemx2. The adjacent tissue contained, in addition to the clone found in the tumor nodule, a spectrum of unrelated clones, the largest of which also showed clonal evolution: 45-47,XY,t(3;6)(p25;p25),t(12;17)(q15;q12),-17,+r(17)x2 [cp]/45-47,idem,inv(5)(p15q22)/90-94,idemx2. The remaining six clones found in this part were small and had simpler numerical or structural aberrations. The multiclonal pattern observed in this hidradenoma seems to reflect both cytogenetic convergence and divergence during neoplastic progression. The presence of unrelated clones may be an indication that the tumor was of multicellular origin.

Acrospiroma↗