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Biomedical subjects

C Johansson

Publications and source records attributed to C Johansson.

At least 19 recordsLinked to original sources

The structural organization of type IV collagen. Identification of three NC1 populations in the glomerular basement membrane.

Type IV collagen, which has long been assumed to contain two alpha 1(IV) and one alpha 2(IV) chains, also contains alpha 3(IV), alpha 4(IV), and alpha 5(IV) chains. Stoichiometry of collagenous alpha(IV) chains differs among tissues, suggesting the existence of subclasses of type IV collagen, each with a unique chain composition. This study seeks to define, by characterization of subunit compositions of NC1 domain populations, the structural organization of type IV collagen from bovine glomerular basement membrane. NC1 hexamers from type IV collagen were separated on two affinity chromatography columns, one containing monoclonal antibodies to the alpha 3 chain, and another, to the alpha 1 chain. SDS-polyacrylamide gel electrophoresis, immunoblotting, reversed phase high-performance liquid chromatography, and enzyme-linked immunosorbent assay identified three NC1 hexamer populations: 1) a hexamer composed of (alpha 1)2 and (alpha 2)2 homodimers; 2) a hexamer composed of (alpha 3)2 and (alpha 4)2 homodimers; 3) a hexamer containing all four alpha chains connected in heterodimers, alpha 1-alpha 3 and alpha 2-alpha 4. Results suggest that there are two distinct type IV collagen molecules, one composed of alpha 1(IV) and alpha 2(IV) chains and another composed of alpha 3(IV) and alpha 4(IV) chains. Furthermore, polymerization occurs between molecules with the same chain composition and between molecules with different chain composition. Moreover, crosslinking between different alpha chains is restricted, thus limiting the number of possible macromolecular structures.

Animals

Plasma concentrations of regulatory peptides in obesity following modified sham feeding (MSF) and a liquid test meal.

Plasma concentrations of regulatory peptides were monitored in groups of obese and normal-weight subjects following modified sham feeding and a liquid fatty meal. Following modified sham feeding a significant increase in immunoreactive cholecystokinin (CCK) in plasma was recorded in both groups. In the obese subjects, however, the concentrations following sham feeding were significantly lower than in normal-weight subjects, and the initial part of the response was negative. Basal and modified sham feeding stimulated immunoreactive pancreatic polypeptide (PP) concentrations in plasma did not differ between the groups. After the liquid fatty meal plasma CCK concentrations increased similarly in both groups. In contrast immunoreactive neurotensin and somatostatin concentrations following the meal were lower in the obese group, and a changed concentration-time pattern for somatostatin was observed in the obese group. Postprandial concentrations of PP and immunoreactive gastrin were not different in the groups. The results indicate that the plasma concentration patterns of CCK, somatostatin and NT are disarranged in obesity. The changes may promote rapid propulsion and absorption of ingested food, and facilitate deposition of fat in adipose tissue in obesity and thus may be of pathophysiological importance.

Adult

[Autoantibodies as serological markers in the diagnosis of glomerulonephritis].

Autoimmunity is now regarded as the unequivocally predominant pathogenic process underlying most forms of primary and secondary glomerulonephritis in humans, and a number of autoantibodies occurring in conjunction with glomerulonephritis have been discovered. However, apart from the anti-NC1 antibodies occurring in classic Goodpasture's syndrome, the exact pathogenic role of these autoantibodies in human glomerulonephritis remains to be established, though this in no way diminishes the importance of their study. They have been of enormous value in subclassifying glomerulonephritis, previously thought to be a homogeneous entity. Autoantibody analysis has become a vital aid in the early diagnosis of rapidly progressive glomerulonephritis, which in turn has enabled treatment to be started early, thus contributing to a decline in the morbidity and mortality resulting from these disorders. Moreover, investigation of these autoantibodies will be of immense value in future studies focused on the pathogenic mechanisms involved in glomerulonephritis.

Anti-Glomerular Basement Membrane Disease

Paradoxical sphincter reaction and associated colorectal disorders.

Of 71 patients with paradoxical sphincter reaction, 54 had symptoms of constipation or outlet obstruction and 17 were incontinent. The patients were investigated with defecography, colon transit time, anorectal manometry and electromyography. Ninety-six percent of the patients had additional changes in anorectal anatomy and physiology; 70% of the patients had abnormal defecography and 42% had delayed colon transit time. Decreased maximal anal pressure (MAP) and maximal squeeze pressure (MSP), indicating impaired function of the anal sphincters might be one reason for incontinence in patients with paradoxical sphincter reaction. The paradoxical reaction occurred in the puborectalis muscle and in three tested sites in the external sphincter. It is sufficient to record the EMG activity in one muscle and at one point to diagnose a paradoxical sphincter reaction. The absence of a normal closing reflex on electromyography is evidence for a paradoxical sphincter reaction. Denervation was more pronounced in the external sphincter than in the puborectalis muscle. The right pudendal nerve was subjected to damage more often than the left nerve.

Adolescent

Association between rectocele and paradoxical sphincter response.

Rectocele as well as paradoxical sphincter reaction may lead to rectal emptying difficulties and outlet obstruction. Forty-one patients with emptying disturbances and rectocele were investigated with defecography, anorectal manometry, colon transit time, and electromyography. Twenty-nine patients (71 percent) had concomitant paradoxical sphincter reaction, and 13 of these also had increased colon transit time. The functional results after surgical treatment of rectocele are not always satisfactory, probably because patients often have several causes for their emptying disturbances. It is emphasized that careful preoperative investigations are important before surgical treatment of rectocele in patients with emptying difficulties.

Adult

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

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

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

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

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

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

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

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

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

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