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Biomedical subjects

P Collin

Publications and source records attributed to P Collin.

At least 19 recordsLinked to original sources

Coeliac disease--associated disorders and survival.

The associated diseases in 335 coeliac patients diagnosed 1980-90 were compared with age and sex matched control patients with various gastrointestinal symptoms. Endocrine disorders were found in 11.9% of coeliac and 4.3% of control patients (p = 0.0003). Coeliac patients had insulin dependent diabetes mellitus significantly (p = 0.0094) more often (5.4%) than control patients (1.5%). connective tissue diseases were found in 7.2% of coeliac and in 2.7% of control patients (p = 0.011). Sjögren's syndrome occurred in 3.3% of coeliac patients and in 0.3% of controls (p = 0.0059). Autoimmune thyroid diseases were found in 5.4% and asthma in 3.6% of coeliac patients, but also in 2.7% and 3.6%, respectively, among control patients. The incidences of malignant diseases and the survival rate in coeliac patients were compared with those in the Finnish population. Ten coeliac patients developed a cancer during the follow up (mean 5.3 years, range 1-12) but none had a lymphoma. The risk of malignant diseases in coeliac patients did not differ from that in the Finnish population in general. Eleven coeliac patients died during the follow up. The five year survival rates of coeliac patients did not differ from those in the general population. At least 83% of the coeliac patients adhered strictly to the gluten free diet, which may explain the favourable outcome.

Adolescent

Autoimmune thyroid disorders and coeliac disease.

Eighty-three patients with autoimmune thyroid disorders were screened for coeliac disease. The screening was performed with IgA-class reticulin and endomysium antibody, IgA- and IgG-class gliadin antibody tests, and various biochemical tests for malabsorption. None of the tested subjects had selective IgA deficiency, which excludes the possibility of not detecting positives by an IgA-class test. Of the 83 patients, three asymptomatic coeliac patients were found, and one patient with coeliac disease previously diagnosed, an overall frequency of 4.8%. In addition, 25 patients with a solitary nodule of the thyroid gland were examined and one of them (4%) was found to have coeliac disease. By contrast, one (0.4%) out of 249 age- and sex-matched blood donors was found to have coeliac disease. All newly detected coeliac patients had IgA-class gliadin, reticulin and endomysium antibodies, but none of the patients had any gastrointestinal symptoms or abnormal biochemical findings suggesting coeliac disease. Treatment of thyroid disorders and coeliac disease was successful in these patients. The present results confirm that the frequency of subclinical coeliac disease is increased among patients with autoimmune thyroid disorders. IgA-class reticulin, endomysium or gliadin antibody tests are suitable screening methods for detecting these patients, as far as selective IgA-deficiency is excluded.

Adult

Bisphosphonates act on rat bone resorption through the mediation of osteoblasts.

Bisphosphonates are generally considered to act on bone resorption by binding to bone mineral and subsequently inhibiting the activity of the osteoclasts which ingest them. This has been supported by the fact that bisphosphonates adsorbed on mineralized tissue inhibit the resorbing activity of isolated osteoclasts in vitro. However, the effectiveness of different bisphosphonates determined in this system does not reflect their relative potencies in vivo. Employing the well-described isolated osteoclast resorption pit assay, with ivory as the resorption substrate, we show here that this lack of correlation prevails only when the bisphosphonates are added to the mineral before addition of osteoclasts, but not when the cells are treated for a short time (5 min) before allowing them to adhere onto ivory. By using this approach with five different bisphosphonates, a stringent correlation of relative potencies was obtained with those found, both in the rat and in the human, in vivo. Furthermore, by using an osteoblastic cell line (CRP 10/30) which is a powerful promoter of osteoclastic resorption in vitro, we obtained evidence that the inhibitory effect of bisphosphonates was the result of an action on osteoblasts rather than on osteoclasts. Thus, in experiments in which the osteoblastic cells were pretreated for 5 min with bisphosphonates and then cocultured with osteoclasts, inhibition of osteoclastic resorbing activity was obtained. Moreover, it was found that this treatment resulted in a decrease of the stimulatory effect found in CRP 10/30-conditioned medium. In conclusion the present study shows that part of the osteoclast inhibiting action of the bisphosphonates is mediated through an action on osteoblasts.

Alendronate

Follow-up of patients positive in reticulin and gliadin antibody tests with normal small-bowel biopsy findings.

Twenty-five patients with positive serum reticulin or gliadin antibody titres and having normal small-bowel mucosal villous architecture were re-biopsied after a follow-up period of 1 to 7 years. Seven were found on control examination to have small-bowel villous atrophy. At the initial examination, when coeliac disease was 'excluded', they thus belonged to the entity latent coeliac disease. Morphometrically minor mucosal changes in the initial biopsy specimen, suggesting an ongoing process, were seen in only three of them. Especially the serum IgA-class reticulin antibody test was a good predictor of latent coeliac disease. This study implies that patients with so-called false-positive IgA-class reticulin or gliadin antibody test should be re-examined.

Adult

Expression of collagen, osteocalcin, and bone alkaline phosphatase in a mineralizing rat osteoblastic cell culture.

Rat calvaria bone cells isolated by collagenase digestion form a bone-like matrix which mineralizes in vitro in the presence of beta-glycerophosphate, in less than 2 weeks. The purpose of this work was to investigate, in this mineralizing rat osteoblastic cell culture, the synthesis of collagen, osteocalcin, and bone alkaline phosphatase (ALP). The results obtained indicate (1) After 15 days in culture, the extracellular-matrix contains collagen type I, V, and to some extent type III. Metabolic labeling at day 14, during the phase of nodules mineralization as well as new nodules formation, shows that collagen types I and type V are synthesized; (2) During the phase of cell growth, no osteocalcin could be detected in the medium, however, at the point of nodule formation, the osteocalcin level reached values of 3.55 +/- 1.39 ng/ml, followed by a 30-fold increase after nodules became mineralized. At day 14, after metabolic labeling, de novo synthesized osteocalcin was chromatographed on an immunoadsorbing column. With urea-SDS PAGE the apparent molecular weight was determined to be 9,000 daltons. (3) Specific activity of ALP was found to be 10 nmol/min/mg of proteins at cell confluence. At day 15, when nodules are mineralized, this activity was increased by 40-fold. The Michaelis constant was 1.58 10(-3) M/L. ALP was inhibited by L-homoarginine and levamisole but not by L-phenylalanine. ALP was shown to be heat sensitive at 56 degrees C with two slopes of inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase

Constitutive expression of osteoclast-stimulating activity by normal clonal osteoblast-like cells: effects of parathyroid hormone and 1,25-dihydroxyvitamin D3.

Osteoblasts are known to produce osteoclast-stimulating activity (OSA). The aim of the current study was to relate the expression of OSA to the osteoblastic phenotype and examine its regulation by calciotropic hormones. The study was performed with the normal osteoblastic cell clone CRP 10/30 and the preosteoblastic clone CRP 4/7. OSA was determined with the well described isolated osteoclast pit assay, using sperm whale dentine as substrate. In contrast to previous studies, the assay was carried out at pH 7.36, rather than at pH 6.4 or 6.9. The results indicate that over 24 h, CRP 10/30 cells produce constitutively OSA, which compared to controls corresponds to an about 7-fold increase in resorption pits. There was considerably less activity expressed by either CRP 4/7 cells or fibroblasts. OSA proved to be heat labile, and its mol wt was estimated to be over 10 kilodaltons. While PTH-(1-34) did not influence the synthesis of OSA, the number of pits formed by osteoclasts incubated with medium conditioned by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]-treated CRP 10/30 cells was increased 3-fold above baseline values. A similar increase was obtained with 1.25-(OH)2D3 added directly to CRP 10/30-conditioned medium. These results could not be duplicated with 1,25-(OH)2D3 added to either control medium or medium conditioned by CRP 4/7 cells or fibroblasts. The present study shows that normal clonal bone cells synthesize constitutively OSA, which is not regulated by PTH or 1,25-(OH)2D3. Furthermore, the results suggest that the synthesis of bone cell-derived OSA is limited to cells expressing the mature osteoblastic phenotype. Finally, CRP 10/30-conditioned medium appears to permit 1,25-(OH)2D3 to function on osteoclasts.

Animals

Selective IgA deficiency and coeliac disease.

Twenty-five children and adults with concomitant coeliac disease and selective IgA deficiency are described. IgG-class reticulin antibodies were positive in 94%. The clinical course of coeliac disease did not differ from that of patients with normal serum IgA level. Patients with IgA deficiency also had other concomitant diseases, especially autoimmune diseases. Patients with selective IgA deficiency have at least a tenfold risk of coeliac disease compared with the population in general.

Adolescent

Rheumatic complaints as a presenting symptom in patients with coeliac disease.

Twenty-three cases of coeliac disease were found after a small bowel biopsy had been carried out on seventy patients with various rheumatic complaints. The prevalence of coeliac disease in patients with rheumatic disorders was estimated to be 1 in 243. The majority (19) of these cases were found by screening patient sera with a reticulin antibody test. Sjögren's syndrome was the most frequent rheumatic diagnosis, with a total of six cases. Coeliac disease may occur concomitantly with various rheumatic complaints, and serological screening is advisable.

Adult

Serological markers and HLA genes among healthy first-degree relatives of patients with coeliac disease.

Coeliac disease may remain undiagnosed because of the non-specific nature of the presenting symptoms. Several antibody tests are claimed as markers for this condition but a direct comparison of the available tests has not been reported. The probands and healthy first-degree relatives of 42 families with coeliac disease were studied. Histological examination of biopsy specimens revealed jejunal mucosal villous atrophy compatible with coeliac disease in 13 of 122 relatives. Reticulin-antibody-positive relatives with or without jejunal mucosal atrophy were genetically similar to the probands of the families (DR3 gene frequencies 55.3%-60.0%). Gliadin-antibody-positive relatives with normal mucosa were genetically different from the probands (DR3 gene frequency 16.7% versus 55.3%). IgA reticulin and endomysium antibodies detected 92.3% of subjects with silent coeliac disease. The only case that was missed had selective IgA deficiency and was positive for IgG-class reticulin antibodies. By contrast, gliadin antibodies detected only half of the cases. Follow-up of the 7 reticulin-antibody-positive relatives with normal mucosa revealed 2 further cases of coeliac disease and 1 of dermatitis herpetiformis during the next three years. Our family study shows that healthy reticulin-antibody-positive first-degree relatives of coeliac disease patients, irrespective of the state of the jejunal mucosa, are genetically similar to known coeliac disease patients. Reticulin-antibody positivity is an indicator of both silent and latent coeliac disease.

Antibodies

Increase in gamma/delta T cell receptor bearing lymphocytes in normal small bowel mucosa in latent coeliac disease.

A jejunal biopsy specimen from an asymptomatic 35 year old man was studied because of a low serum titre of reticulin antibody and the finding of coeliac disease in his son. In this specimen villous structure was quite normal as was the total number of intraepithelial lymphocytes, but the number of gamma/delta T cell receptor bearing lymphocytes was 10 times higher than the mean in control subjects. Two years later a further biopsy specimen was obtained because of clinical symptoms and an increased titre of reticulin antibody. This specimen showed villous atrophy with crypt hyperplasia and increased infiltration of intraepithelial lymphocytes compatible with coeliac disease. A control biopsy specimen taken during gluten free diet showed normalisation of the villous architecture. Latent coeliac disease may be characterised by an increase in gamma/delta positive cells similar to that seen in established coeliac disease.

Adult

Celiac disease, brain atrophy, and dementia.

We report 5 patients who developed dementia before age 60 and were subsequently found to have celiac disease (CD). Intellectual deterioration ranged from moderate to severe, and diffuse cerebral or cerebellar atrophy was found on brain CT. Diagnosis of CD was confirmed by findings of subtotal villous atrophy in jejunal biopsy specimens and positive serum reticulin and gliadin antibodies. Conspicuously, gastrointestinal symptoms were mild. The gluten-free diet failed to improve the neurologic disability except in 1 patient. CD is a multisystem disorder and may play a role in some cases of presenile dementia. Although the pathogenetic mechanisms are obscure, immunologic mechanisms are implicated.

Adult

Effects of acidic fibroblast growth factor and epidermal growth factor on subconfluent fetal rat calvaria cell cultures: DNA synthesis and alkaline phosphatase activity.

The effects of acidic fibroblast growth factor (aFGF) and epidermal growth factor (EGF) were examined in subconfluent fetal rat calvaria cell cultures, in the presence of 2% serum. Maximal effect of aFGF and EGF on DNA synthesis measured by [3H]thymidine incorporation was observed after 18 h. aFGF stimulated DNA synthesis by 3.5-fold with an ED50 of 0.75 ng/ml while a 2.3-fold EGF stimulation was recorded with an ED50 of 0.067 ng/ml. 5-Bromo-2-deoxyuridine staining showed a higher stimulation of proliferation in the scattered cells than in the cell clusters. An 18 h aFGF or EGF treatment decreased alkaline phosphatase (ALP) activity by 40 and 23%, respectively, as compared with control cultures. This inhibition was more pronounced after 48 h in the presence of the effectors but no modification of the ALP electrophoretic mobility was observed. These data suggest that aFGF is a less potent mitogen than EGF and a higher inhibitor of ALP activity in fetal rat calvaria cell culture.

Alkaline Phosphatase

Dental enamel defects in celiac disease.

The teeth of 40 adults aged 19 to 67 yr with celiac disease (CD) were examined for dental enamel defects (ED). A total of 33 of the 40 adults with CD (83%) had systematic ED in contrast to only 5 of the 112 clinical controls (4%). Unspecific enamel lesions were found in both groups, but they were more common in the control group (80% vs. 18%). Altogether 69% of the permanent teeth in adults with CD were found to be defected, in clinical controls only 19%. In adults with CD the ED were in contrast to those in controls symmetrically and chronologically distributed in all four sections of dentition. The present study clearly shows that symmetrically and chronologically distributed enamel defects are strongly associated with CD. Therefore in the absence of symptoms and signs of malabsorption dentists could easily select the right patients possibly suffering from CD for gastroenterologic consultations.

Adult

[Adult type I primary hyperoxaluria: 2 cases confirmed by liver biopsy at end-stage renal insufficiency].

It can be difficult to distinguish between primary hyperoxaluria at end-stage renal failure and secondary oxalosis, all the more as primary hyperoxaluria can be latent for a long time and occur at a late stage. A 57 year-old woman, without family nor personal history of urolithiasis, receives regular hemodialysis for a renal failure discovered at end-stage. Eighteen months later, calcium oxalate deposits appear in the skin, bone marrow and both kidneys, suggesting secondary oxalosis. An other 57 year-old woman presents a chronic renal failure due to bilateral urolithiasis, whose surgery has caused a dramatic decrease of renal function requiring regular hemodialysis. Because of apparition of severe bone alterations, a parathyroidectomy is realized, and because of calcium oxalate deposition in the skin and bone marrow, primary hyperoxaluria is suspected. In both observations, the enzyme activity determination in a liver biopsy gives the diagnosis of primary hyperoxaluria.

Alanine Transaminase

Glomerular IgA deposits in patients with celiac disease.

Glomerular immunopathology was studied in 25 patients with newly diagnosed celiac disease. None had clinical signs of renal disease. Glomeruli were obtained by fine-needle aspiration biopsy. The specimens were processed and studied by indirect immunofluorescence for immunoglobulins and complement. Mesangial IgA was found in 8 of the patients. It occurred occasionally together with slight IgG or IgM, but C3 was not seen in these patients. IgA-class circulating immune complexes (CIC), antireticulin antibodies (ARA), antigliadin antibodies (AGA), and rheumatoid factor (RF) occurred significantly more often in the patients with mesangial IgA than in the 17 patients having no mesangial IgA. The patients with mesangial IgA also had significantly higher mean levels of serum IgA, IgA-ARA and IgA-AGA than those without. The results suggest that glomerular mesangial deposits of IgA occur frequently in untreated celiac disease and that they are in some way associated with circulating IgA-class antibodies and immune complexes. In this situation IgA seems to be deposited without being able to induce clinically overt glomerulonephritis, a circumstance that may be related to the lack of complement in the deposits.

Adolescent

Atypical coeliac disease found with serologic screening.

Eighteen patients with coeliac disease were found by screening for reticulin antibodies of unselected sera at the time when determination of various tissue antibodies was requested. Joint disease, allergic and pulmonary disorders, and diabetes were particularly observed. IgA class reticulin antibody, in particular, proved to be specific for coeliac disease. Most patients with coeliac disease also had positive serum gliadin antibodies. Abdominal symptoms and signs of malabsorption were slight and infrequent. In most patients a gluten-free diet resulted in the improvement of jejunal mucosal histology, and serum reticulum and gliadin antibody titres decreased simultaneously, reflecting the appropriateness of the diet. Coeliac disease often has mild and atypical symptoms, and, particularly in certain disease groups, screening with reticulin antibody test seems to be appropriate.

Adult