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Biomedical subjects

C Johansson

Publications and source records attributed to C Johansson.

At least 181 records · Page 10Linked to original sources
PubMed1992

Gastrointestinal function in obesity: motility, secretion, and absorption following a liquid test meal.

Digestive responses to a 300-mL liquid fat-rich meal (432 kcal) in a group of massively obese patients were compared with those observed in a group of healthy lean subjects of variable body weight. Gastric and intestinal propulsion, digestive secretions, and absorption in the proximal 70 cm of intestine were measured using a multiple-marker dilution method. The average gastric emptying of energy, acid, volumes, and meal marker were similar in the two groups 80 minutes after intake, justifying a comparison of intestinal processing of the meal. Compared with lean subjects, the obese subjects responded with less pancreatic secretion (P less than .05) and gallbladder emptying, but absorbed a larger proportion of the emptied energy in the test segment (P less than .01) during a similar or shorter transit time. In addition, when the entire meals were compared, the obese group generally absorbed the test meal more effectively and rapidly in the upper part of the intestine. As a consequence, the flow volumes at the exit of the test segment were lower (P less than .05), and less of the test meal was propulsed to distal parts of the intestine. In the lean subjects, the body weight or height correlated positively with the gastric emptying rate, peak gastric acid output, and pancreatic responses, and negatively with (P less than .05) the segment transit time. The taller the subject, the greater the proportion of the meal which was rapidly propulsed unabsorbed to lower parts of the intestine, indicating that a large intestinal area was exposed for rapid energy uptake. No such correlations were observed in the obese group.

Adult↗
PubMed1992

Healing-in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog.

The aim of these animal experiments was to characterize and evaluate the healing-in of root analogue titanium implants fitting with high precision to the alveolar wall. Four beagle dogs were used in the study. The roots of the 3rd and 4th mandibular premolars in both quadrants of 3 dogs and in 1 quadrant of 1 dog (dog 4) were extracted after hemisection. Each root was machine-copied to 1 titanium analogue. In dog 4, however, 2 titanium analogues were fabricated from each of the 4 extracted roots. This enabled insertion of analogues also into the contralateral sockets obtained by extraction of the corresponding roots immediately before implant installation, which was undertaken 2 weeks after the first extractions. Thus, in all, 32 analogues were implanted in their respective (or contralateral) sockets following ridge incision and elevation of mucoperiosteal flaps. The analogues were carefully covered by the repositioned flaps. In dog 4, 2 analogues from the immediate sockets and 2 from the 2-week sockets were surgically exposed and supplied with titanium crowns after a healing period of 2 months. The healing after implantation was evaluated by clinical, radiographic and histological measures after 2, 12 or 36 months. Two analogues (6%) were lost due to early (during the 1st week) exposure to the oral cavity. Another 2 analogues (6%) were, although not exposed, encapsulated by soft tissue and were easily removed with a surgical forceps. Twenty-eight analogues (88%) were healed-in by contact between bone and implant (osseointegration).(ABSTRACT TRUNCATED AT 250 WORDS)

Alveolar Process↗
PubMed1992

Sensitivity and specificity of CA242 in gastro-intestinal cancer. A comparison with CEA, CA50 and CA 19-9.

A serological assay for the quantitative determination of the novel tumour-associated epitope CA242 was developed and used for determination of sensitivity and specificity of CA242 in gastrointestinal cancer. The CA242 assay showed a better tumour specificity than CA50 (and CA 19-9). This was most noticeable in benign hepatobiliary disease. The sensitivity at 90% specificity cut-off level was approximately three times higher for CA242 compared to CA50 in colo-rectal cancer Dukes A, B and C, while in pancreatic cancer the sensitivity of CA242 and CA50 was similar. CA242 was expressed independently of CEA, and the combination of CEA and CA242 gave in colo-rectal cancer considerably higher sensitivity than the use of only one of the markers. This was most pronounced in Dukes A and Dukes B patients. CA242 is a novel tumour marker of potential clinical use, particularly in colo-rectal cancer.

Animals↗
PubMed1992

Coffee drinking: a minor risk factor for bone loss and fractures.

The influence of coffee drinking as a possible risk factor for loss of bone mass was assessed in a cohort of 619 70-year-old men and women who were examined with dual photon absorptiometry of the right calcaneum. A high consumption of coffee was significantly associated with a lower bone mass, deteriorated dental state, lower socio-economic level and a higher consumption of tobacco. In non-smoking women a bivariate relationship was found between the daily consumption of three or more cups of coffee and a low bone mass (p less than 0.01). However, in a stepwise logistic regression model, only tobacco smoking, body mass index, body height, physical activity and a deteriorated dental state were found to be significant predictive factors for a low bone mineral content. Bone mass and tobacco smoking were the only significant predictive factors for fractures before the ages of 70 and 76 years. Coffee drinking was not a contributory independent risk factor for loss of bone mass and fractures in this population study.

Aged↗
PubMed1992

Changed integrated gastrointestinal response to a mixed meal in exocrine pancreatic insufficiency.

Using a multiple-marker dilution technique to quantitate flow volumes at a jejunal sampling site 70 cm from pylorus, propulsion and absorption of a 300-ml mixed liquid test meal were compared in seven patients with exocrine pancreatic insufficiency and in ten healthy subjects. In pancreatic insufficiency, outputs of lipase and amylase were 8% of control levels. Early gastric emptying rate was similar in both groups, but emptying was completed earlier, and less gastric acid was emptied in pancreatic insufficiency. In pancreatic insufficiency, initial biliary output was larger than in controls, and transit time through the test segment was twice that of controls. During the prolonged transit time, larger amounts of glucose (but less fat) were absorbed in pancreatic insufficiency. Forty minutes after the meal, almost a third of the fatty content of the meal was propelled to lower parts of the intestine. In conclusion, pancreatic insufficiency is associated with impaired inhibitory regulation of gastric and biliary outputs after a mixed meal. The impaired digestion of nutrients in pancreatic insufficiency is partially compensated for by slowing of intestinal transit, permitting more efficient absorption. Exposure of the gut to large quantities of fat is suggested to trigger the slowing of upper intestinal transit in pancreatic insufficiency.

Adult↗
PubMed1992

Expression of interferon-gamma receptors in normal and psoriatic skin.

Psoriatic keratinocytes have a reduced antiproliferative response to interferon (IFN)-gamma, and HLA-DR expression is usually not observed on keratinocytes in psoriatic plaques despite the presence of activated T cells. We have therefore compared the expression of IFN-gamma receptors in psoriatic skin with that of normal human skin. Using mouse monoclonal antibodies and immunoperoxidase staining on cryostat cut sections, we detected IFN-gamma receptors on keratinocytes throughout the epidermal layers except stratum corneum in normal skin (n = 11). Biopsy specimens from involved psoriatic skin (n = 17) consistently showed a staining pattern that differed from that of normal skin in that only the lower part of epidermis reacted with the antibodies to IFN-gamma receptors, whereas the upper layers showed no or minimal staining. Expression of IFN-gamma receptors in uninvolved psoriatic skin (n = 16) did not differ from that of healthy controls. Forty-five percent of the biopsies from lesional psoriatic skin displayed ICAM-1 positive keratinocytes, and only two specimens had a limited expression of HLA-DR reactive keratinocytes. The decreased binding of antibodies against the IFN-gamma receptors in the upper part of psoriatic epidermis might be secondary to abnormal maturation of psoriatic keratinocytes or a primary defect involving abnormal modulation of IFN-gamma receptors.

Adult↗
PubMed1992

Longitudinal study of stimulated whole saliva in an elderly population.

The aim of this investigation, which is part of the longitudinal gerontologic population study in Gothenburg (H-70), was to examine the effect of aging on salivary flow. Three 70-yr-old cohorts, born in 1901/02, 1906/07, and 1911/12, were studied both cross-sectionally and longitudinally. Representative subsamples (n = 931) were followed up to 82 yr in the first and up to 75 yr in the second and third cohorts. Whole saliva secretion was stimulated by paraffin wax chewing for 5 min and all sampling was carried out in the morning after an overnight fast. The mean secretion rate was 1.24 for men and 0.94 ml/min for women at the age of 70 (all cohorts pooled). The percentage values for extremely low secretion rate (< 0.2 ml/min) were 2 and 6%, respectively. Neither the cross-sectional nor the longitudinal comparison showed any decrease in secretion rate on a group basis either in the age interval 70-82 yr in the first or between 70 and 75 yr in the other two cohorts. However, an increased prevalence of complaints of mouth dryness was found, especially among women. The main conclusion from this study is that there is no decline on a population basis in paraffin-wax-stimulated salivary flow with increasing age.

Age Factors↗
PubMed1992

Autoimmunity and glomerulonephritis.

Autoimmunity is now unequivocally regarded as the predominant pathogenic process underlying most forms of primary and secondary glomerulonephritis in humans. Most of the investigations so far have been focused upon humoral mechanisms. Consequently, the role of cell-mediated immunity in nephritis is still incompletely understood. Nonetheless, as a result of contemporary studies, a number of previously unidentified auto-antibodies in association with glomerulonephritis have been discovered. However, apart from anti-NC1 antibodies in the classical Goodpasture syndrome, the exact role of these auto-antibodies in the pathogenesis of glomerulonephritis yet remains undefined. This fact, however, does not undermine the relevance of exploring these auto-antibodies. They have been of immense help in sub-classifying glomerulonephritis previously thought homogeneous (Figure 3). Besides, analysis of auto-antibodies has assisted tremendously in the early diagnosis of rapidly progressive glomerulonephritis. This, in turn, has aided in early commencement of therapy thus contributing to regression in morbidity and mortality resulting from these disorders. Moreover, investigation of these auto-antibodies is of enormous value for future studies aimed at understanding the pathogenic mechanisms involved in glomerulonephritis.

Autoantigens↗
PubMed1992

Effect of cortisol on the secretion of testosterone and estradiol-17 beta by human granulosa-luteal cell cultures. A model system for analyzing hormonal alterations in female athletes.

The combination of hypercortisolism and usually low androgen and estrogen levels is frequently observed in female long distance athletes. In order to find a useful model system for studying the underlying mechanisms, the following studies were performed. The effect of cortisol on the secretion of testosterone (T) and estradiol-17 beta (E2) by human granulosa-luteal cells was studied in vitro in cultures of cells recovered from mature follicles of gonadotrophin stimulated women (participating in the IVF program). Following 24 hours of culture in tissue culture medium without hormonal additives, the granulosa-luteal cells were incubated for 6 hours in media with addition of 4-androstene-3,17-dione (A-4) as precursor and hMG and cortisol in different combinations. The secretion of T was significantly stimulated by cortisol but not by human menopausal gonadotrophin (hMG). Cortisol, but not hMG, also increased the secretion of E2, although this effect was not statistically significant. These in vitro findings make a direct effect of cortisol upon ovarian sex steroid secretion less likely as the mechanism behind the subnormal sex steroid levels in female long distance athletes. Instead, inadequate gonadotrophic stimulation, related to hypothalamic amenorrhea, and/or a selective decrease in the adrenal secretion of precursor steroids, may be an explanation.

Estradiol↗
PubMed1991

Mutation of the pseudo-EF-hand of calbindin D9k into a normal EF-hand. Biophysical studies.

The two Ca(2+)-binding sites in calbindin D9k, a protein belonging to the calmodulin superfamily of intracellular proteins, have slightly different structure. The C-terminal site (amino acids 54-65) is a normal EF-hand as in the other proteins of the calmodulin superfamily, while the N-terminal site (amino acids 14-27) contains two additional amino acids, one of which is a proline. We have constructed and studied five mutants of calbindin D9k modified in the N-terminal site. In normal EF-hand structures the first amino acid to coordinate calcium is invariantly an Asp. For this reason Ala15, is exchanged by an Asp in all mutants and the mutants also contain various other changes in this site. The mutants have been characterized by 43Ca, 113Cd and 1H NMR and by the determination of the calcium binding constants using absorption chelators. In two of the mutants (one where Ala14 is deleted, Ala15 is replaced by Asp and Pro20 is replaced by Gly, the other where, in addition, Asn21 is deleted), we find that the structure has changed considerably compared to the wild-type calbindin. The NMR results indicate that the calcium coordination has changed to mainly side-chain carboxyls, from being octahedrally coordinated by mainly back-bone carbonyls, and/or that the coordination number has decreased. The N-terminal site has thus been turned into a normal EF-hand, in which the calcium ion is coordinated by side-chain carboxyls. Furthermore, the calcium binding constants of these two mutant proteins are almost as high as in the wild-type calbindin D9k. That is, the extensive alterations in the N-terminal site have not disrupted the calcium binding ability of the proteins.

Amino Acid Sequence↗
PubMed1991

Purification and characterization of a membrane-bound and a secreted mucin-type glycoprotein carrying the carcinoma-associated sialyl-Lea epitope on distinct core proteins.

Two mucin-type glycoproteins detected by the monoclonal antibody C50, which reacts with the carcinoma-associated sialyl-Lewis a and sialyl-lactotetraose epitopes, were found in secreted and solubilized materials from the colon carcinoma cell line COLO 205. The larger glycoprotein (H-CanAg; heavy cancer antigen) was predominantly found in extracts of cells grown in vitro or as nude mice xenografts whereas the smaller species (L-CanAg; light cancer antigen) was the major component in spent culture medium and serum from grafted mice. Using detergent in the extraction buffer doubled the yield of H-CanAg, suggesting that this glycoprotein is membrane bound whereas the yield of L-CanAg was relatively unaffected. The two glycoproteins were purified from xenograft extracts and spent culture medium using perchloric acid precipitation, monoclonal antibody affinity purification, ion exchange chromatography, and gel filtration. Both glycoproteins were unaffected by reduction and alkylation in guanidine HCl. Using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, relative molecular masses were estimated to be 600-800 kDa for H-CanAg and 150-300 kDa for L-CanAg. Carbohydrate analysis revealed that the CanAg glycoproteins were highly glycosylated (81-89% carbohydrate by weight), carrying carbohydrate chains with average lengths of 13-18 sugars which were rich in fucose and sialic acid (2-3 residues/chain for each sugar). L-CanAg isolated from spent medium was glycosylated to a higher degree than its counterpart from xenograft extract. Immunochemical studies of the intact glycoproteins showed that both H-CanAg and L-CanAg expressed the monoclonal antibody-defined, sialic acid-containing carbohydrate epitopes CA203 and CA242 as well as the Lewis a blood group antigen whereas only H-CanAg appeared to carry the sialyl-Lewis x epitope. The amino acid compositions were typical of mucins, containing high amounts of serine, threonine (more than 25% together), and proline (11-18%). Significant differences in amino acid composition between H-CanAg and L-CanAg were found. A rabbit antiserum against the cytoplasmic C-terminal part of the MUC1 gene product, core protein of the carcinoma-associated polymorphic epithelial mucin (PEM) and DU-PAN-2, reacted with H-CanAg. After deglycosylation with trifluoromethanesulfonic acid, H-CanAg but not L-CanAg was recognized by the monoclonal antibodies SM-3 and HMFG-2, directed to the tandem repeat of the PEM apoprotein. However, these antibodies which react with PEM from mammary carcinomas without prior deglycosylation were unable to recognize intact H-CanAg, probably as a consequence of a more extensive glycosylation of this glycoprotein.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1991

Comparison of serological expression of different epitopes on the CA50-carrying antigen CanAg.

C203 and C242 are mouse monoclonal antibodies (MAbs) generated using a human colon carcinoma cell line. They recognize novel tumour-associated epitopes present in elevated levels in sera from patients with colon and pancreatic cancer. These epitopes were found to be co-expressed with sialylated Lewisa on the CanAg molecule. To study the association and distribution of the epitopes of CanAg in sera, these new antibodies, together with C50, were used in different combinations in time-resolved fluoroimmunoassays. Relative serum concentrations were examined in patients with various types of carcinoma and in patients with ulcerative colitis and benign pancreatic, and hepatobiliary diseases. A double-determinant assay using C50 and C242 was shown to distinguish carcinoma from benign biliary and hepatocellular diseases better than a single-determinant assay based on C50 as both catching and tracing antibody. The number of sera with elevated CanAg levels from patients with benign obstructive biliary disease was 17 out of 29 using the single-determinant CA50 assay. This was reduced to 4 out of 29 in the double-determinant assay. When sera from patients with liver cirrhosis were analyzed, 16 of 23 patients showed elevated CanAg levels with the C50-C50 combination, but only 4 of 23 patients had elevated antigen values using the C50-C242 assay. The increased specificity was obtained without loss of sensitivity. MAb C203 was evaluated both in a double-determinant combination with C50 and in an homologous assay, but did not contribute either increased sensitivity or specificity as compared with C50-C50.

Animals↗
PubMed1991

Tumour-growth suppression in nude mice by a murine monoclonal antibody: factors hampering successful therapy.

The murine MAb C215 has been shown to mediate ADMMC in vitro and to have a tumour-growth-suppressive effect on xenografted COLO 205 human colocarcinoma cells in nude mice. To overcome the limitations of MAb therapy, it is necessary to understand the underlying mechanisms of tumour-growth suppression. In the present work, we have used C215 to define the importance of different parameters involved in tumour therapy with murine IgG2a antibodies. The results show that there exists a period of roughly 2 days after inoculation into animals during which the tumour cells are sensitive to an inhibitory antibody-mediated effect. After this initial period, the in-vivo sensitivity of tumour cells to antibody-mediated inhibition is much reduced. Tumour cells can remain "dormant" and, despite ongoing antibody treatment, develop into tumours with a reduced growth rate, which is not caused by outgrowth of antigen-deficient tumour cells. Finally, a pronounced dependence of antibody-mediated tumour suppression on antibody dose was observed.

Animals↗
PubMed1991

Electrostatic contributions to the binding of Ca2+ in calbindin D9k.

A set of accurate experimental data is provided for Ca2+ ion binding to calbindin D9k, a protein in the calmodulin superfamily of intracellular regulatory proteins. The study comprises both the role of protein surface charges and the effects of added electrolyte. The two macroscopic Ca2(+)-binding constants K1 and K2 are determined for the wild-type and eight mutant calbindins in 0, 0.05, 0.10, and 0.15 M KCl from titrations in the presence of Quin 2 or 5,5'-Br2BAPTA. The mutations involve replacement of surface carboxylates (of Glu17, Asp19, Glu26, and Glu60) with the corresponding amides. It is found that K1K2 may decrease by a factor of up to 2.5 x 10(5) (triple mutant in 0.15 M KCl as compared to the wild-type protein in 0 M KCl). Ca2(+)-binding constants of the individual Ca2+ sites (microscopic binding constants) have also been determined. The positive cooperativity of Ca2+ binding, previously observed at low salt concentration [Linse et al. (1987) Biochemistry 26, 6723-6735], is also present at physiological ionic strength and amounts to 5 kJ.mol-1 at 0.15 M KCl. The electrolyte concentration and some of the mutations are found to affect the cooperativity. 39K NMR studies show that K+ binds weakly to calbindin. Two-dimensional 1H NMR studies show, however, that potassium binding does not change the protein conformation, and the large effect of KCl on the Ca2+ affinity is thus of unspecific nature. Two-dimensional 1H NMR has also been used to assess the structural consequences of the mutations through assignments of the backbone NH and C alpha H resonances of six mutants.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1991

Ca2+ binding in proteins of the calmodulin superfamily: cooperativity, electrostatic contributions and molecular mechanisms.

In a large number of intracellular regulatory proteins of the calmodulin superfamily a pair of closely interacting helix-loop-helix Ca2+ binding sites ('EF hands') constitute the functional unit--an arrangement that enables cooperative binding. We have recently made detailed experimental studies of the binding of Ca2+ ions to calmodulin, its tryptic fragments TR1C and TR2C (which each constitute a globular domain of a pair of EF hands) and calbindin D9k. Macroscopic Ca2+ binding constants have been obtained over a range of ionic strengths (0 to 0.15 M KCl). For calmodulin the measurements indicate that the two separate globular domains TR1C and TR2C retain the Ca2+ binding properties they have in the intact molecule, with positive cooperativity within each domain. The absolute value of the free energy of interaction between the two sites in each domain, a measure of the cooperativity, increases with ionic strength and is greater than or equal to 10 kJ mol-1 at 0.15 M KCl. Two-dimensional 1H NMR studies show that the addition of KCl does not alter the conformation of the protein. In the case of calbindin D9k several categories of mutants have been studied. One group encompasses the effect of protein surface charges 5 to 15 A from the Ca2+ binding sites. Two-dimensional 1H NMR shows that neither the addition of KCl, nor mutations that neutralize the surface charges, change the protein conformation. Although the global structure of calbindin D9k is largely unchanged upon binding of calcium, the structure with only one cation bound is more similar to the (Ca2+)2 form. Interestingly, the dynamical properties of the Ca(2+)-free and the (Ca2+)2-forms of calbindin differ greatly. For example, the rate of NH/ND exchange of the Ca(2+)-free form is on average 200 times faster than that of the (Ca2+)2-form. The results obtained so far point to a non-negligible entropic contribution to the observed cooperativity of Ca2+ binding.

Amides↗
PubMed1991

Aspects on the role of tachykinins and vasoactive intestinal polypeptide in control of secretion, motility and blood flow in the gut.

Both intrinsic and extrinsic neurons of the gut respond to mechanical and chemical stimuli by the release of neurotransmitters. We summarize here some of our recent work on the role of vasoactive intestinal polypeptide (VIP), substance P (SP) and neurokinin A (NKA) in the secretory, motor and vascular effects of hydrochloric acid stimulation in the isolated rat duodenal loop and electrical nerve stimulation and mechanical stimulation of the cat colon. Isolated duodenal loops of conscious rats were perfused with isotonic saline, and challenged at hourly intervals with brief exposures to increasing concentrations of HCL. The concentrations of bicarbonate and prostaglandin E2 (PGE2) released from the duodenal mucosa were significantly augmented already by pH 5.0 whereas VIP was significantly augmented at pH 3.0 and the tachykinins SP and NKA at pH 2.0. Continuous electric stimulation of the pelvic nerve in cats at 4 Hz during 1 s with 10 s rest produced a marked release of NKA-LI and SP-LI from the colon to blood. Reflex activation of the pelvic nervae by mechanical stimulation of the anus or rectal distension produced a less pronounced release of NKA-LI and SP-LI from the colon to blood. There was a simultaneous colonic contraction and vasodilation during each nerve stimulation. Close intraarterial infusions of NKA, neurokinin B, SP, neuropeptide K (NPK), eledoisin and physalemin at doses of 0.1-100 pmol/min induced dose-dependent proximal and distal colonic contractions and vasodilation, NKA being the most potent. The effects of the tachykinins were reduced after tetrodotoxin and atropine, but unchanged after treatment with hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Cortisol and androgen concentrations in female and male elite endurance athletes in relation to physical activity.

To evaluate the effect of variations in physical activity on selected hormone concentrations in male versus female athletes, fasting serum concentrations of cortisol (C), total-testosterone, free-testosterone, non sex hormone binding globulin (SHBG) bound testosterone, dehydroepiandrosterone, 4-androstene-3,17-dione and SHBG were studied. The tests were performed in nine male and seven female elite endurance athletes during the off-season (test 1), early in the competition season (test 2) and at the end of the competition season (test 3). The C concentration increased significantly during the competition season in women but not in men. Further, the mean C concentrations at test 3 as well as the mean level during the whole observation period (tests 1, 2, 3) were significantly higher in women than in men. No significant changes were found in androgen concentrations or androgen:cortisol ratios within the two groups. The differences between the sexes in C response may indicate different adaptive mechanisms to similar physical stress.

Adult↗