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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 361 records · Page 20Linked to original sources

Immunogenic potential of some mercury compounds in experimental contact allergy of the rat oral mucosa.

The contact allergenic potential of substances included in a "dental screening test" has been investigated in a previously established animal model for producing contact allergy. We were unable to produce contact hypersensitivity with any of the original formulas. HgCl2 was selected for further studies and, in order to improve its penetration, butanol was used as a solvent. Sensitization was, however, not obtained with any of the HgCl2/butanol formulas. Our results are discussed in relation to the requirements of reaching immunogenic threshold levels of mercury in the tissue.

Animals↗

Chemically induced inflammation in rat oral mucosa.

The toxic, irritative, and sensitizing effects of topically applied sodium lauryl sulfate (SLS), dithranol triacetate (DTA), nonanoic acid in methyl- or propyl ester (NAM, NAP) in the buccal mucosa were investigated in a Sprague-Dawley rat model. Semi-quantitative evaluations of cellular infiltrates were performed in routine histologic preparations. The toxic potential was tested with 2% and 0.2% solutions. All substances, except 0.2% SLS, caused an increased cellularity, mainly of a mononuclear cell type. The low dose of NAM induced stronger inflammatory reactions than the high dose. Repeated applications of 2% solutions decreased the response compared to one application, except for NAM, where a clear irritative potential was observed. Pre-exposure of dorsal skin prior to buccal painting resulted in an enhanced reaction to NAM and NAP, whereas no sensitizing capacity was noted in SLS or DTA in this model.

Allergens↗

Tissue distribution of epimucosally applied 3H DNFB: an autoradiographic study.

The distribution of 3H-labeled 2,4-dinitrofluorobenzene (DNFB) has been autoradiographically investigated in buccal mucosa after topical application to sensitized or nonsensitized rats. The rats were killed between 3 min and 24 h after challenge. No significant labeling pattern differences were found between plastic embedded and frozen sections. Surface epithelium was heavily labeled and labeled cells were observed in the lamina propria shortly (3-6 min) after application. These cells were clearly dendritic. Specific accumulation of hapten in epithelial Langerhans cells (LC) could not be clearly demonstrated. The connective tissue labeling gradually diminished and at 24 h post-elicitation, remaining label could be detected only in the epithelial surface layers.

Administration, Cutaneous↗

Psychomotor development of children with congenital hypothyroidism diagnosed by neonatal screening.

The psychomotor development in 68 children with congenital hypothyroidism diagnosed during the first two years of a nationwide neonatal screening programme in Sweden was assessed during their first three years of life. Replacement therapy with thyroxine was initiated at the age of 15 +/- 7 days (mean +/- SD). Griffiths tests were performed in 15 patients at the age of 18 months and in 51 patients at 30-47 months. Their developmental quotients did not differ from those of control children, indicating that the psychomotor development in the children with congenital hypothyroidism was normal. In earlier studies of Swedish children with congenital hypothyroidism, diagnosed clinically before the age of three and a half years, the psychomotor development was found to be impaired. In contrast, the patients diagnosed by neonatal screening and given early therapy displayed normal results in Griffiths tests. This indicates that the age at the start of treatment is an important determinant for the prognosis.

Child, Preschool↗

Ventilation inhomogeneity during controlled ventilation. Which index should be used?

Six indexes for diagnosing uneven ventilation by tracer gas washout were studied. The indexes were lung clearance index, mixing ratio, Becklake index, multiple-breath alveolar mixing inefficiency, moment ratio, and pulmonary clearance delay, all of which increase with impaired pulmonary gas mixing. In model lung tests, indexes that compared the actual washout curve with a calculated ideal curve (mixing ratio, multiple-breath alveolar mixing inefficiency, and pulmonary clearance delay) were unaffected by changes in tidal volume and series dead space, whereas the others varied markedly. In both spontaneously breathing and mechanically ventilated patients all indexes showed a significant difference between smokers and nonsmokers (P less than 0.002), but the indexes were somewhat different in their assessment of different ventilatory patterns. However, the mean value for all indexes, with the exception of mixing ratio, was smallest with a fast insufflation followed by an end-inspiratory pause. Any of the indexes may be useful if its limitations are recognized, but mixing ratio, multiple-breath alveolar mixing inefficiency, and pulmonary clearance delay seem preferable, because they are not affected by changes in tidal volume and dead space fraction.

Adult↗

Neonatal screening for congenital adrenal hyperplasia using 17-hydroxyprogesterone assay in filter paper blood spots.

Screening of infants for congenital adrenal hyperplasia (CAH) using filter paper blood samples collected on the 5th day of life was performed with a radioimmunoassay for 17-hydroxyprogesterone without extraction with organic solvents. A total of 153,000 newborns were screened and 12 cases of CAH were detected (1:12,800). With recall levels related to gestational age, the recall rate could be lowered to 0.05%.

17-alpha-Hydroxyprogesterone↗

Quantification of circulating immune complexes by chicken anti-C4 micro ELISA.

A quantitative assay for C4-containing immune complexes (IC) by a solid phase anti-C4 micro ELISA is described. It is based upon the use of an affinity purified chicken anti-human C4 antibody to capture the immune complex, and protein A-alkaline phosphatase for detection. The chicken antibody was chosen as capture antibody because it does not react with rheumatoid factor, does not activate the human complement system and is not detected by anti-mammalian IgG antibodies or protein A. Increased levels of C4 containing circulating immune complexes (CIC) were detected in sera from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and lung cancer, when compared with normal sera. Normal levels of C4 containing immune complexes were found in sera from patients with Bell's palsy.

Animals↗

Tissue plasminogen activator and urokinase in normal, dysplastic and cancerous squamous epithelium of the uterine cervix.

The distribution of tissue plasminogen activator (t-PA) and urokinase (u-PA) was investigated immunohistochemically in squamous epithelium of the uterine cervix, in normal and dysplastic conditions as well as in preinvasive and invasive carcinomas. Normal epithelium showed presence of both t-PA and u-PA immunoreactivity only in the superficial cellular layer, whereas in preinvasive lesions they were present in all layers. In sections of normal specimens as well as preinvasive lesions the UK immunoreactivity was weaker compared to that of t-PA. Invasive lesions showed a patchy distribution of t-PA and u-PA immunoreactivity. Furthermore, it could be demonstrated that stromal cells close to the infiltrating malignant squamous epithelium contained t-PA immunoreactivity and also u-PA immunoreactivity. Further immunohistochemical studies disclosed that these cells were macrophages.

Cervix Uteri↗

A one-step purification method for monoclonal antibodies based on salt-promoted adsorption chromatography on a 'thiophilic' adsorbent.

A convenient and fast method for the purification of mouse monoclonal antibodies from the culture media of cloned cells or from ascites fluids by means of salt-promoted chromatography on a 'thiophilic' adsorbent is described. The adsorbent has a capacity to adsorb about 20 mg/ml of immunoglobulins and a broad specificity towards immunoglobulins derived from various animal species irrespective of the type or subclass to which they belong. The recovery of the purified IgG is better than 90% while that for IgM is considerably less, probably due to dissociation occurring during the adsorption-desorption process. This one-step procedure also leads to a considerable concentration of dilute solutions of immunoglobulins. Moreover, the purified Igs are eluted by an essentially salt-free buffer at near neutral pH thus obviating the need for post-treatment of the sample before storage or subsequent conjugation to enzymes for use in immunoassays. This purification method is also well suited for large-scale operations since sample preparation requires only the addition of 0.5 M K2SO4 to the ascited fluid or cell culture medium. The degree of purification obtained is, in certain instances, comparable to that obtained by biospecific affinity chromatography based on antigen-antibody interactions. In contrast to immunosorption and desorption methods, however, there is no risk of contamination of the immunoglobulins purified on the 'thiophilic' adsorbent by foreign proteins.

Animals↗

Immunization of mice and rabbits by intrasplenic deposition of nanogram quantities of protein attached to Sepharose beads or nitrocellulose paper strips.

Two novel immunization methods designed for immunization with small quantities of antigen, immobilized on a solid matrix and without the use of adjuvant, are presented. The major test antigen used in order to evaluate these methods was bovine serum albumin (BSA). It was deposited in the spleen of mice and rabbits, either attached to Sepharose beads (Pharmacia Sepharose 4B) or to nitrocellulose (NC) paper strips (Millipore). BSA was attached to NC by direct application or by electroblotting after SDS-polyacrylamide gel electrophoresis. The antibody response in mouse and rabbit serum, after intrasplenic immunizations with various quantities of antigen, was analyzed in an ELISA standard procedure. In mice, an antibody response in serum was detected after three intrasplenic immunizations with a total quantity of 73.6 ng BSA bound to Sepharose beads and after two immunizations with a total quantity of 800 ng BSA attached to NC. Determination of the antigen-binding to NC and the clearance rate of antigen attached to NC deposited in the spleen of mice was performed with 125I-labeled BSA. In rabbits, an antibody response in serum was detected after a single intrasplenic immunization with 2.6 micrograms BSA attached to NC. When testing human insulin and sheep prolactin, attached to NC, as antigens in intrasplenic immunization of rabbits, an antibody response was found after a total quantity of 3.2 micrograms insulin and 10.5 micrograms prolactin, respectively.

Animals↗

Ventilatory consequences of the lateral position and thoracotomy in children.

Functional residual capacity (FRC), breath-by-breath compliance of the respiratory system (Crs) and arterial oxygen tension (PaO2) were measured in ten children, two months to nine years of age, during anaesthesia for surgical correction of patent ductus arteriosus or coarctation of the aorta. The children were mechanically ventilated with halothane, nitrous oxide and oxygen. FIO2 was kept constant in each child. After induction of anaesthesia, FRC was 17 +/- 7 ml X kg-1 (mean +/- 1 SD), corresponding to 60 +/- 22 per cent of a predicted awake value. FRC increased to 21 +/- 8 ml X kg-1 (p = 0.0005) when the child was turned to its right side and decreased to 13 +/- 5 ml X kg-1 (p = 0.0003) when the pleura was opened. No significant change in Crs or PaO2 occurred during these manoeuvres. Retraction of the upper lung to visualize the great vessels caused a significant decrease in FRC, Crs, and PaO2. The lowest PaO2 observed during this stage was 70.0 mmHg. After surgery FRC and PaO2 were about the same as before surgery while Crs had decreased from 0.87 +/- 0.18 preoperatively to 0.64 +/- 0.15 ml X cmH2O-1 X kg-1 (p = 0.0069). This study shows that FRC increases when mechanically ventilated children are placed in the lateral position, and that thoracotomy is associated with marked changes in FRC, Crs and PaO2.

Child↗

Long-term effects of bleached kraft mill effluents on carbohydrate metabolism and hepatic xenobiotic biotransformation enzymes in fish.

In a laboratory investigation, fourhorn sculpin (Myoxocephalus quadricornis) were exposed for 5-9 months to waste water from pine and birch lines from a bleached kraft pulp plant. The bleached kraft mill effluents (BKME) affected both the carbohydrate metabolism and the xenobiotic metabolism. Thus, an elevated muscle glycogen content in fish exposed to effluent from the pine pulp line suggests a metabolic imbalance. A liver enlargement and a strong elevation of the hepatic cytochrome P-450-dependent ethoxyresorufin-O-deethylase activity after exposure to the bleached pine pulp effluents indicate the presence of cytochrome P-450-inducing agents in the BKME. The results also demonstrate that many physiological test parameters may be used as good indicators of sublethal disturbances in fish to BKME exposure.

Animals↗

Determination of intrinsic affinity constants of monoclonal antibodies against carcinoembryonic antigen.

A 2-phase method is described for the determination of the intrinsic affinity constants (K-values) for the interaction between monoclonal antibodies (MAbs) against carcinoembryonic antigen (CEA) and CEA. The Mabs were coupled covalently to CNBr-activated paper discs. MAb coupled discs and a 2-fold dilution series of 125I-CEA were incubated at 20 degrees C until equilibrium was reached. Nonlinear curve-fitting was used for estimation of K-values and different calculation models were thereby tested. The K-values for 12 different anti-CEA MAbs were determined to be 0.3-52 X 10(6) M-1, which is 1-2 orders of magnitude lower than the values obtained in a previous study with some of these MAbs using the ammonium sulphate method to separate free from bound antigen. The K-values obtained by the paper disc method are probably better estimates of the intrinsic association constant than those obtained previously. There are two main reasons for this: (1) free and bound antigen are separated from each other under physiological conditions and (2) the opportunity for multipoint interaction between MAb and CEA is minimized when the MAb is coupled to a rigid carrier substance. Thus, even when the MAb reacts with greater than or equal to 2 epitopes in CEA, as seems to be the case with several of our anti-CEA MAbs, the intrinsic K-value should be obtained. The fundamental validity of 2-phase assays, sometimes questioned in the literature, is demonstrated.

Animals↗

Critical determinants of antiherpes efficacy of buciclovir and related acyclic guanosine analogs.

Buciclovir is an example of an antiherpes, acyclic guanosine analog activated by the viral thymidine kinase and inhibiting viral DNA synthesis in infected cells. An investigation of closely related buciclovir-analogs with similar antiherpes activities in cell cultures and similar, or identical, modes of action but with disparate effects in vivo, revealed the following critical determinants of antiherpes efficacy. (1) The accumulation of guanosine analog-triphosphates in infected cells, which is cell-type-specific and analog-dependent. (2) The potencies of the triphosphates as inhibitors of the viral DNA polymerase. (3) The plasma kinetics of the analogs, which are widely different despite the similar structures. (4) The penetration into nervous tissue relative to penetration into non-nervous tissues, of importance in connection with the neurotropic behavior of the virus. (5) The concentration of the antagonist thymidine in certain tissues. (6) The difference in pathogenesis between primary infections and recurrent infections, exemplified in the different efficacies of topically applied drugs in cutaneous and genital HSV-2 infections in guinea pigs.

Acyclovir↗

Few intra-lake variations of physiological parameters in perch, Perca fluviatilis.

Intra-lake variations in physiological parameters, representing haematology, plasma ion composition and carbohydrate metabolism, were investigated in perch (Perca fluviatilis), inhabiting a comparatively unpolluted lake. Provided the perch were subjected to a standardized procedure for capture, handling, recovery after capture, and sampling, only few and minor differences were observed in 21 parameters investigated when 3 groups were compared to a control group of perch. It is concluded that the experimental design used is suitable for the examination of the physiological status of perch in the field.

Animals↗