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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 325 records · Page 18Linked to original sources

Impact of consumption factors on soft tissue changes in Swedish moist snuff users: a histologic study.

The purpose of this study was to analyze the relative importance for histologic changes of the oral mucosa of such consumption factors as years with regular snuff use, hours and grams of daily snuff use. The material consisted of biopsies of selected cases (two groups) from 252 regular snuff users of whom 184 used exclusively loose and 68 exclusively portion-bag packed snuff. Group 1 comprised 8 pairs of loose snuff users with large differences (14-45 yr) in terms of years with regular habit. Many years of snuff use did not per se seem to result in tissue changes which significantly differed from changes seen in subjects with only a few years of loose snuff use. Group 2 included 5-10 subjects showing the lowest and highest daily consumption of loose or portion-bag packed snuff. Among those with a low daily consumption, portion-bags seem to be related to less pronounced changes than loose snuff. High daily snuff use was associated with relatively somewhat more pronounced epithelial surface changes but histologic differences between the two habit groups were difficult to identify.

Adolescent↗

Congenital adrenal hyperplasia in Sweden 1969-1986. Prevalence, symptoms and age at diagnosis.

A retrospective study of all Swedish patients with congenital adrenal hyperplasia (CAH) born 1969-1986, was conducted to elucidate possible benefits of neonatal screening for CAH. Information was obtained about 150 patients (67 male, 83 female). One hundred and forty-three cases were regarded as classical and seven as non-classical (symptoms after 5 years of age or cryptic). All but two (one girl with 11-hydroxylase deficiency and one boy with beta-hydroxysteroid-dehydrogenase deficiency) had 21-hydroxylase deficiency. The prevalence was 1:11,500. Ninety-three patients (48 male, 45 female) displayed salt loss, all before the age of 3 months. Two boys had died and many children had been critically ill during the first weeks of life. The median age at diagnosis for boys in this group was 21 days. Gender assignment was a major problem in 38 of 57 girls with ambiguous genitalia noticed during the first day. Fifteen of these girls were considered to be male for their first 40 days (median), before the CAH diagnosis was established. Patients in whom the first symptom was manifested after the age of one year often showed growth acceleration, which frequently was overlooked. Median diagnostic delay in this group was 17 months. Possible benefits of neonatal screening are: avoidance of a serious salt-loss crisis; earlier diagnosis and correct gender assignment in virilized girls; decreased virilization, growth acceleration and premature pubarche in prepubertal children; and reduced negative consequences for psycho-social development and final height.

Adrenal Hyperplasia, Congenital↗

Neonatal skeletal maturation in congenital hypothyroidism and its prognostic value for psychomotor development at 3 years in patients treated early.

Neonatal skeletal maturation was assessed by different methods based on the bone centres in the knee and ankle region in 46 infants with true-positive (patients) and 17 infants with false-positive screening tests (controls). The patients and controls did not differ in mean age at X-ray examination and age at the start of treatment (14.5 +/- 5.7 days). One of the methods used to score the size of femoral and tibial epiphyses was just as good as the other ones tested, but has the advantage of being the easiest to use and therefore clinically most suitable. Skeletal maturity assessed by this method correlated best with serum T4 (r = 0.62, p less than 0.01). Griffiths tests were performed in 37 of the 46 patients at 28-48 months of life. The best correlation obtained between neonatal skeletal maturity and Griffiths global developmental quotient at 3 years of age was r = 0.58 (p less than 0.001). Although statistically significant, it was too weak to be of clinical value in identifying individual patients at risk. We conclude that an assessment of skeletal maturation is not useful for the prognosis of psychomotor development in individual patients with congenital hypothyroidism receiving treatment within the first 2 weeks of life.

Age Determination by Skeleton↗

Bell's palsy: an immune complex disease.

Serum levels of C4-containing circulating immune complexes in 48 patients with Bell's palsy were studied by an enzyme-linked immunosorbent assay (ELISA) using chicken antibodies. We have previously reported elevated levels of C1q- and C3-containing immune complexes when compared to the serum of 42 healthy persons. We now found the levels of C4-containing immune complexes in these sera to be slightly decreased, but these patients' sera had a slightly increased ability to activate and bind C4 to a model immune complex. The results indicate that the fairly low levels of C4-containing immune complexes were not due to a defect in C4 activation but point to a rapid modification of C4 in the immune complex in vivo or low binding of C4 to the immune complexes. This study also shows that it is preferable to use assays that detect C1q- and C3-containing immune complexes when analyzing sera from patients with Bell's palsy.

Adult↗

Influence of the age of cadaveric kidney donors on transplantation outcome and rate of surgical complications.

Cadaveric kidney graft recipients, treated according to a strict, high dose CyA protocol, were followed prospectively for one year. The aim was to study the impact of donor age on transplantation outcome in a homogenously immunosuppressed patient material. The patients were divided into 2 groups; G1: donor age less than or equal to 50 years (mean 34.5 y; range 10-50; n = 49) and G2; donor age greater than 50 years (mean 58.1 y; range 51-68; n = 37). The groups were comparable in terms of recipient age, warm and cold ischemia time, number of HLA A, B, DR mismatches and number of rejection episodes. The result showed no difference in mortality between the 2 groups (12% vs. 13%). One year graft survival was 70% vs. 51% (NS), immediate onset of function was 76% vs. 46% (p less than 0.01), creatinine concentration at one year was 146 +/- 39 vs. 206 +/- 73 mumol/l (p less than 0.05) for G1 and G2, respectively. The most striking finding was a highly significant difference in the rate of graft-related surgical complications, 12% vs. 35% (p less than 0.01) for G1 and G2, respectively. We conclude, that a patient receiving a graft from an elderly donor, runs a higher risk of graft-related complications and that long term graft survival and function also might be influenced by the age of the donor. A possible reason for the inferior results in group 2 might be an increased sensitivity for the toxic effects of CyA of aging kidneys.

Adult↗

T and B cell responses of Plasmodium falciparum malaria-immune individuals to synthetic peptides corresponding to sequences in different regions of the P. falciparum antigen Pf155/RESA.

The C-terminal (3') amino acid repeat region of the Plasmodium falciparum Ag Pf155/RESA, a vaccine candidate, contains immunodominant T and B cell epitopes. In order to identify additional T cell epitopes in the molecule, synthetic peptides corresponding to the centrally (5') located repeat region, as well as to four nonrepeated regions, were synthesized. T cells from 46 P. falciparum-primed individuals living in a holoendemic area of The Gambia where malaria transmission is seasonal were tested for their responsiveness to the peptides by thymidine incorporation and IFN-gamma release. There was a considerable variation in the response to different peptides. Proliferation and IFN-gamma release were not correlated in individual donors, underlining the importance of measuring both activities when screening donor populations for total T cell responsiveness to a given Ag. Whereas 72% of the donors responded with proliferation and/or IFN-gamma release to the intact protein the mean % responders to the peptides was 40%. The most frequent responses (up to 60%) were induced with peptides from the 3'- and 5'-repeat region of the protein. Analysis of some closely related sequences in the 3'-repeat region indicated that they contained at least two epitopes that were either distinct or cross-reacting in different donors, suggesting difference in the genetic control of these responses. When the same peptides were investigated for reactivity with antibodies, the best T cell inducing sequences also displayed the best antibody reactivities. However, in individual donors, T and B cell responses were not correlated. T cell responses were shown to persist after a period with no P. falciparum transmission, whereas antibody concentrations tended to decrease, suggesting differences in the requirements of boosting at the T and B cell levels, respectively.

Amino Acid Sequence↗

Antigenic sites in carcinoembryonic antigen.

The epitope reactivities of 52 well-characterized monoclonal antibodies (Mabs) against carcinoembryonic antigen from 11 different research groups were studied using competitive solid-phase immunoassays. About 60% of all possible combinations of Mabs as inhibitors and as the primary binding antibody were investigated. The inhibition data were analyzed by a specially developed computer program "EPITOPES" which measures concordance and discordance in inhibition patterns between Mabs. The analysis showed that 43 of the 52 Mabs (83%) could be classified into one of five essentially noninteracting epitope groups (GOLD 1-5) containing between four and 15 Mabs each. The epitopes recognized by the Mabs belonging to groups 1 to 5 were peptide in nature. With one or two possible exceptions non-classifiable Mabs were either directed against carbohydrate epitopes (4 Mabs) or were inactive in the tests used. Within epitope groups GOLD 1, 4, and 5 two partially overlapping subgroups were distinguished. Mabs with a high degree of carcinoembryonic antigen specificity generally belonged to epitope groups GOLD 1 and 3.

Antibodies, Monoclonal↗

Evidence for two different classes of redox-active cysteines in ribonucleotide reductase of Escherichia coli.

The large subunit of ribonucleotide reductase from Escherichia coli contains redox-active cysteine residues. In separate experiments, five conserved and 2 nonconserved cysteine residues were substituted with alanines by oligonucleotide-directed mutagenesis. The activities of the mutant proteins were determined in the presence of three different reductants: thioredoxin, glutaredoxin, or dithiothreitol. The results indicate two different classes of redox-active cysteines in ribonucleotide reductase: 1) C-terminal Cys-754 and Cys-759 responsible for the interaction with thioredoxin and glutaredoxin; and 2) Cys-225 and Cys-439 located at the nucleotide-binding site. Our classification of redox-active cysteines differs from the location of the active site cysteines in E. coli ribonucleotide reductase suggested previously (Lin, A.-N. I., Ashley, G. W., and Stubbe, J. (1987) Biochemistry 26, 6905-6909).

Allosteric Site↗

Binding of complement components C1q, C3, C4 and C5 to a model immune complex in ELISA.

When normal human serum is added to microELISA plates coated with monomeric or aggregated IgG various complement components become bound and can be detected with specific chicken anti-C1q, anti-C3, anti-C4 and anti-C5 antibodies. Using such assays we found increased C1q- and decreased C3- and C4-binding in sera from patients with SLE. In contrast, sera from patients with rheumatoid arthritis showed decreased C3 binding but normal C1q binding. The decreases in C3 and C4 binding observed in the sera from patients with SLE were larger than the corresponding decreases determined by radial immunodiffusion. Comparing these results with those of the CH50 assay, the correlation coefficient between CH50 and the C3-binding assay was 0.48. There was no correlation between the results of the CH50 and those of the C1q-, C4- or C5-binding assays.

Antigen-Antibody Complex↗

Relative positions of some epitopes on carcinoembryonic antigen.

To investigate whether anti-(carcinoembryonic antigen) monoclonal antibodies (mAb) react with single or repeated epitopes, sandwich radioimmunoassays in homologous and heterologous combinations were performed. Four mAb (I-27, I-47, II-17 and to some degree II-16) gave homologous binding while two mAb (I-38S1 and II-10) did not. Taken together with previous immunoprecipitation studies we conclude that all these mAb except II-10 react with repeated epitopes. The relative positions of the epitopes recognized by these mAb and of three additional mAb (II-6, II-7 and CB-CEA-1) were investigated using a plate antibody competition test with enzyme-labelled carcinoembryonic antigen (CEA). mAb I-38S1, II-6, II-7, II-10, II-16 and CB-CEA-1 were mutually cross-reactive, and were classified as belonging to one epitope group. mAb I-27 and I-47 fell outside this group and did not interfere with the binding of CEA conjugate to mAb II-17 either. They therefore represent a second epitope group. mAb II-17 showed no interference with the binding of CEA to any of the other mAb and must therefore represent a third epitope group. The slopes of the plate antibody competition curves were used for calculation of a correlation matrix, which in turn was used to depict the relative positions of the epitopes recognized by the mAb in the large group.

Antibodies, Monoclonal↗

A therapeutic trial with N-acetylcysteine in subjects with hereditary glutathione synthetase deficiency (5-oxoprolinuria).

In a therapeutic trial, the effect of short-term low-dosage N-acetylcysteine supplementation on glutathione metabolism was investigated in two patients with hereditary glutathione deficiency (5-oxoprolinuria). Clinical and neurophysiological examinations of the patients indicated progressive neurological damage. The pretreatment concentrations of total and free glutathione in leukocytes were 15-20% of normal, whereas the corresponding gamma-glutamylcysteine levels were increased. In plasma, the glutathione concentrations were similarly decreased, but no gamma-glutamylcysteine was detected. Total glutathione in erythrocytes was markedly decreased. Low urinary excretion of cysteinylglycine, cyst(e)ine, taurine, N-acetylcysteine, mercaptolactate and mercaptoacetate and reduced leukocyte taurine levels constituted additional evidence of decreased intracellular availability of cysteine, i.e. glutathione. Oral supplementation with N-acetylcysteine (5 mg/kg x 3/day) had no effect on acid-base balance, erythrocyte glutathione levels or 5-oxoproline concentrations in plasma and urine. In leukocytes, the glutathione concentrations were increased by 20-30%, whereas the gamma-glutamylcysteine levels were essentially unaltered. In parallel, the urinary excretion of cysteinylglycine was increased and the leukocyte levels and urinary outputs of sulphur amino acids were restored. No side-effects of the treatment were noted. The results indicate that N-acetylcysteine may be of value in increasing the low intracellular glutathione concentrations and cysteine availability in patients with hereditary glutathione synthetase deficiency.

Acetylcysteine↗

Divalent binding of monoclonal antibody to a cell surface antigen. Modelling of equilibrium data.

The principles of the binding of a monoclonal Ab to a single epitope of a cell surface antigen were deduced. The equilibrium between the Ab and the antigen was regarded as a two-step reaction, involving free Ab and antigen as well as Ab, monovalently or divalently complexed to its antigen. By a few simple equations the concn of bound Ab was calculated from the values of free Ab concn, cell concn, single cell antigen density and the two equilibrium constants. This cell surface binding was compared to the binding of an ordinary one-step equilibrium reaction. It was shown that a bonus effect due to cell surface divalent binding is obtained when the product of the first association constant and the free Ab concn is less than one and, simultaneously, the product of the second equilibrium constant and the single cell antigen density is greater than one. In addition, when these conditions are fulfilled, an increase in the single cell antigen density may cause an increase in Ab binding that is much more than proportional to the change in antigen density. The implications of these results to tumor immunolocalization and immunotherapy are discussed.

Animals↗

Dry eyes or mouth--an epidemiological study in Swedish adults, with special reference to primary Sjögren's syndrome.

The prevalence of dry eyes or dry mouth, and of primary Sjögren's syndrome (primary SS) according to the Copenhagen criteria were established in 705 randomly selected subjects, aged 52-72 years who answered a simple questionnaire, and of whom 247 (35%) reported symptoms. A subgroup with symptoms (n = 77) and a matched asymptomatic control group (n = 32) were examined with the Schimer-1 test (S1t), tear film break-up time (BUT), van Bijsterveld score (vB), unstimulated whole sialometry (Sialo) and, in about 40% of them labial salivary gland (LSG) biopsy and salivary gland scintigraphy. Apart from four cases of keratoconjunctivitis sicca (KCS) among controls, cases of KCS (15), xerostomia (12), autoimmune sialoadenitis (6) and primary SS (6) were exclusively confined to the symtomatic group. The calculated frequencies (with 95% confidence intervals) for the whole population were 14.9 (7.3-22.6)% for KCS, 5.5(3.0-7.9)% for xerostomia and 2.7 (1.0-4.5)% for autoimmune sialoadenitis and primary SS. The serum levels of ANA and RF were similar in the two groups, though those of anti-SS-B/La antibodies were higher in the group with symptoms (P less than 0.01).

Aged↗

Lung function in the supine and lateral decubitus positions in anaesthetized infants and children.

We have measured dynamic lung compliance or static lung thorax compliance, functional residual capacity (FRC), and two indices of pulmonary gas mixing (pulmonary clearance delay (PCD) and single breath alveolar mixing efficiency (SBAME)) in 25 children in the supine and lateral decubitus position during nitrous oxide-halothane anaesthesia. Fifteen children (5 month-8 yr) breathed spontaneously and 10 (4 month-9 yr) underwent mechanical ventilation. Tidal volume and rate of ventilation were, respectively, 3.5-6.6 ml kg-1 and 22-46 b.p.m. in spontaneously breathing supine children, and 8.3-15 ml kg-1 and 20-30 b.p.m. in mechanically ventilated supine children, and did not differ significantly in the lateral position. There was no significant change in compliance when the child was turned to the lateral position, but FRC increased from 22 (SD7) to 25 (8) ml kg-1 (P less than 0.01) in the spontaneously breathing group and from 19 (6) to 24 (8) ml kg-1 (P less than 0.01) in the other group. In spontaneously breathing children, PCD and SBAME indicated a somewhat impaired pulmonary gas mixing (P less than 0.05) after the child had been turned to the lateral position, but no change occurred in the other group. These findings suggest that the distribution of ventilation in anaesthetized children in the lateral position is similar to that reported previously in anaesthetized adults.

Anesthesia↗

Acute lung injury monitored with radiolabeled transferrin and lung volume measurements.

Anesthetized pigs (n = 12) were given oleic acid (OA) to induce acute lung injury. Three additional pigs were used as uninjured controls. Six of the animals were pretreated with terbutaline before OA infusion. 113mIn-labeled transferrin and 99mTc-labeled erythrocytes were used for tracing of extravascular plasma leakage. A computerized gamma camera supplied image analysis of the radioactivities over the heart and lungs. A lung transferrin index (LTI), which describes the net accumulation of plasma equivalents in the lung, was calculated. OA caused an immediate increase in LTI and concurrent, correlated decreases in functional residual capacity, lung thorax compliance and arterial PO2. LTI was also correlated to the content of plasma equivalents in lung tissue samples and also to the wet weight/dry weight-ratios of the same tissue samples. Finally, LTI was correlated to the calculated plasma loss from the circulation. Changes in all these parameters were correlated to the dose of OA. We conclude that this noninvasive double radioisotope technique can detect plasma protein leakage in lung injury of different degrees. We found no significant anti-edema effect of terbutaline.

Animals↗

Histologic changes associated with the use of loose and portion-bag packed Swedish moist snuff: a comparative study.

This study was to identify histologic tissue changes in the oral mucosa and to compare them in specimens from users of loose can-packed and portion-bag-packed moist snuff. The material consisted of biopsies from 252 regular snuff users. 184 using exclusively loose and 68 portion-bag snuff. An array of structural changes appearing in different combinations were identified among the 252 specimens. Two major patterns were recognized based on changes in the surface layer. Type 1 was characterized by an increased epithelial thickness with vacuolated cells and frequent chevron type changes. Type 2 showed a variably thickened surface layer with evidence of keratinization. Based on these findings, 14 carefully matched pairs of loose and portion-bag users were analyzed and compared. Loose snuff users showed predominantly histologic Type 1 changes while portion-bag users showed more histologic Type 2 or only very discrete changes.

Adult↗