Screening for genetic IDDM risk and prevention trials in infancy.
Explore the source record for details and available documents.
Diabetes Mellitus, Type 1↗
Biomedical subjects
O Simell
Publications and source records attributed to O Simell.
Costs of predicting IDDM.
Programmes aiming at prediction and prevention of insulin-dependent diabetes mellitus (IDDM), a multifactorial autoimmune disease, have been launched or are in the planning phase in several countries. We hypothesized that the costs of finding the correct target subjects for preventive interventions are likely to vary markedly according to the prediction strategy chosen. Average direct costs accruing in the Finnish IDDM Prediction and Prevention Project (DIPP) were analysed from the health care provider's viewpoint. The genetically targeted strategy included costs of assessing genetic IDDM susceptibility followed by measurement of marker(s) of islet autoimmunity in the susceptibility restricted population at 3 to 6-month intervals. In the pure immunological strategy markers of autoimmunity were repeatedly analysed in the entire population. The data were finally exposed to sensitivity analysis. The genetically targeted prediction strategy is cost-saving in the first year if autoimmune markers are analysed as frequently as under the DIPP project, and in all circumstances later. The 10-year direct costs per child are US$ 245 (present value $ 217, 5% discount rate) if the genetically targeted approach is used and $ 733 (present value $ 619) if the pure immunological strategy is chosen. In sensitivity analysis the 10-year costs (present value) per child of the genetically targeted strategy and of the pure immunological strategy varied from $ 152 to $ 241 and from $ 430 to $ 788, respectively. The genetically targeted IDDM prediction strategy is remarkably cost-saving as compared with the pure immunological strategy mainly because fewer subjects will need retesting during the follow-up.
Administration, Intranasal↗
Varicella and varicella immunity in patients with lysinuric protein intolerance.
Two patients with lysinuric protein intolerance (LPI) had near-fatal generalized varicella infection with severe interstitial pneumonitis, hepatitis, decreased platelet count, bleeding and hypoalbuminaemia. Active haemolysis resulted in anaemia and massive haemoglobinuria. Serum lactate dehydrogenase activity and ferritin concentration, which in patients with LPI in normal circumstances exceed the upper reference values 3-folds to 10-fold, increased to > 10,000 U/L and > 10,000 micrograms/L, respectively. The patients were treated with fresh frozen plasma, red-cell transfusions and intravenous acyclovir for 14 days, and recovered clinically in a month. Retrospectively, 3 of the 32 other known Finnish patients with LPI had had varicella infection that had been more severe than that in the other children in the family or in subjects in the neighbourhood and had led to hospital admission. Varicella antibodies were measured in 24 patients; 5 had no antibodies and 5 had very low antibody titres. Primary vaccination of three patients with living varicella vaccine increased antibody titres measurably in one patient. We suggest that patients with LPI who have no varicella zoster antibodies should be treated with acyclovir if exposed to varicella and should be (re)vaccinated against chickenpox.
Adult↗
The role of Fas ligand in the development of insulitis in nonobese diabetic mice.
The role of Fas ligand-induced lymphocyte apoptosis in the development of insulitis was studied in nonobese diabetic (NOD) mice. Fas ligand with a molecular weight of 45 kD appeared in the pancreas of NOD mice during the onset of insulitis as demonstrated by western blot analysis. In situ DNA end-labeling (ISEL) of the pancreases of NOD mice demonstrated positive cells in the islets of Langerhans, with an age-dependent increase in the density and frequency of animals with islets containing ISEL-positive cells. In the pancreatic islets of BALB/c mice, no ISEL-positive cells were observed in any of the age groups studied. In ultrastructural analysis degenerating cells with condensed or fragmented nuclei and plasma membranes detached from neighboring cells were observed both in and around the islets. In some cases, these cells were being phagocytosed by the neighboring islet cells. Degenerating cells with characteristics of lymphocytes were seen in contact with healthy lymphocytes around the islets. Neutralizing Fas ligand antibodies affected 3H-thymidine incorporation of CD3+CD28+ pancreatic lymphocytes from 12- to 30-week-old NOD mice in one of three cultures. There was no difference in the effect of neutralizing Fas ligand antibodies between pancreatic and blood lymphocytes. The present results on an increase in density of apoptotic cells in pancreatic islets of NOD mice simultaneously with the onset of insulitis and appearance of Fas ligand suggest that the pancreas infiltrating lymphocytes may be destroyed by Fas ligand-induced apoptosis.
Aging↗
Distribution of insulin-dependent diabetes mellitus (IDDM)-related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region.
The high incidence of insulin-dependent diabetes mellitus (IDDM) in Finland contrasts strikingly with the low rates in the neighbouring populations of countries in the Eastern Baltic region: Estonia, Latvia and Russia. To evaluate the possible contribution of genetic factors to these differences, the frequencies of HLA-DQB1 alleles and relevant DQB1-DQA1 or DQB1-DRB1 haplotypes associated with IDDM risk or protection were analysed among IDDM patients and control subjects from these four populations. An increased frequency of HLA-DQB1*0302, DQB1*02-DQA1*05 and DQB1*0302-DRB1*0401 was observed in subjects with IDDM in all studied populations, whereas the prevalence of DQB1*0301 and DQB1*0602 and/or *0603 was decreased among patients. The degree of IDDM risk associated with HLA alleles analysed here did not differ significantly between the populations. Comparisons of the distribution of IDDM-related HLA alleles and haplotypes in the background populations revealed its consonance with IDDM incidence. The combined frequency of high risk genotypes was significantly higher among Finns than in other populations studied. Our data support the hypothesis that variance in the dispersion of HLA alleles is the genetic basis of variation of IDDM incidence observed in the Eastern Baltic region.
Alleles↗
Associations between salivary calcium and oral health.
Recently, we have shown positive correlations between high salivary calcium content and periodontitis, and between high salivary calcium level and the number of intact teeth in selected groups of subjects. The aim of our present study was to determine whether these correlations could be seen in a randomized group of healthy adults. A thorough oral examination including orthopantomograms was carried out for a total of 137 healthy subjects, 63 men (35.4+/-5.6 years) and 74 women (33.2+/-4.7 years). Paraffin-stimulated saliva was collected from the subjects and salivary flow (ml/min), buffering capacity, calcium (mMol/l) and microbial variables including lactobacilli, yeasts, mutans streptococci, total streptococci, total number of aerobes, and anaerobes were determined. The calcium level of whole saliva had a median of 1.23 mMol/l. Subjects with calcium level below the median were categorized as 'low', while those with higher values formed the 'high' salivary calcium group. There were more men than women in the 'High' salivary calcium group (p=0.025). Subjects in the 'high' calcium group showed more bleeding on probing (p=0.026), had more intact teeth (p=0.045), and lower DMF-scores (p=0.025) than their counterparts. No other differences were found between the two groups. We found clear associations between the level of salivary calcium and factors reflecting gingival health on one hand, and dental health on the other in a randomly selected group of healthy subjects, and conclude that salivary calcium may be important with regard to both dental and gingival health.
Adult↗
Gyrate atrophy of the choroid and retina: lymphocyte ornithine-delta-aminotransferase activity in different mutations and carriers.
Deficiency of omithine-delta-aminotransferase (OAT) causes gyrate atrophy of the choroid and retina with hyperornithinemia (GA; McKusick 258870), a progressive autosomal recessive chorioretinal degeneration leading to early blindness. As residual enzyme activity may vary in different mutations of the OAT gene and explain individual variations in disease progression, a sensitive HPLC modification of the OAT assay in lymphocytes was developed, based on measurement of the dihydroquinozolinium reaction product. The OAT activities (ranges) of 43 Finnish GA patients with mutations L402P/L402P, R180T/L402P, N89K/ L402P, and L402P/x (x = previously unknown allele), were <1-10, <1-13, <1-17, and <1 pmol x min(-1) mg protein(-1), respectively. The OAT activities (mean+/-SD) of nine L402P/ wild heterozygotes were 70+/-50 (range 33-193), and those of 15 healthy control subjects 184+/-60 (range 85-291) pmol x min(-1) mg protein(-1). This lymphocyte assay is an easy, rapid, and sensitive method for reliable recognition of GA homozygotes. OAT mutations of the Finnish patients show similar residual enzyme activity in the lymphocytes. OAT activities in the L402P heterozygotes and healthy control subjects overlap, suggesting that, for reliable carrier detection, the OAT alleles have to be studied. However, as all OAT mutations are not known, direct measurement of enzyme activity has a role in heterozygote identification and possibly also in prenatal diagnosis of GA.
Adolescent↗
Longitudinal reproductive hormone profiles in infants: peak of inhibin B levels in infant boys exceeds levels in adult men.
The gonads are usually considered quiescent organs in infancy and childhood. However, during the first few postnatal months of life, levels of gonadotropins and sex hormones are elevated in humans. Recent epidemiological evidence suggests that environmental factors operating perinatally may influence male reproductive health in adulthood. The early postnatal activity of the Sertoli cell, a testicular cell type that is supposed to play a major role in sperm production in adulthood is largely unknown. Recently, the peptide hormone inhibin B was shown to be a marker of Sertoli cell function in the adult male. In the adult woman, inhibin B is secreted by the granulosa cells. Longitudinal serum levels of inhibin B were measured in healthy boys (n = 15) and girls (n = 15), in cord blood, and every third month during the first 2 yr of life. In addition, serum levels of FSH, LH, and testosterone (boys) were measured in the same group of children. In boys, inhibin B, FSH, LH, and testosterone levels were all elevated at 3 months of age. However, the peak of inhibin B was unexpectedly high, into the supraadult range (mean +/- SE, 378 +/- 23 pg/mL) and persisted much longer than the elevation of FSH, LH, and testosterone. Thus, although levels of FSH, LH, and testosterone decreased into the range observed later in childhood by the age of 6-9 months, serum inhibin B levels remained elevated up to at least the age of 15 months. In girls, the hormonal pattern was generally more complex, with a high interindividual variation in levels of inhibin B, FSH, and LH within each age. In conclusion, the sustained elevation of inhibin B to supraadult levels in infant boys indicates that the neonatal period may be a developmental window important for Sertoli cell proliferation and maturation. Thus, the gonads may be potentially vulnerable to exogenous endocrine interference, e.g. from environmental factors during this period of life. Measurement of serum levels of inhibin B in infants may give clinical clues about developmental deficiencies in the gonads that otherwise only become apparent around puberty or later in life.
Adult↗
[Salt intake in young children].
Among adult Finns salt intake is about twice as high as the recommended levels and almost five-fold greater than the physiological requirement. Information as to salt intake in children has hitherto been sparse. Daily sodium intake among 1-5-year-olds was investigated in this study, and the foodstuffs from which it was derived were identified. In all age groups, sodium intake was at least two-fold greater than the Nordic recommendations, and among five-year-olds it exceeded the recommended intake for adults. Approximately half of the sodium intake was found to have derived from salt used in cooking. Levels of sodium derived by children from dairy, meat and grain products were also relatively high. Sodium intake in children after infancy merits greater attention than previously accorded it, as permanent eating habits and taste preferences are already formed at this age, and reasonable limits for salt intake should therefore be established during childhood.
Adult↗
Time-resolved fluorescence imaging in islet cell autoantibody quantitation.
The prodromal period of insulin-dependent diabetes mellitus (IDDM) is characterized by circulating islet cell autoantibodies (ICA) and other beta cell specific autoantibodies. Despite biochemical characterization of the major beta cell autoantigens insulin, glutamic acid decarboxylase and protein tyrosine phosphatase and development of the respective antibody assays, ICA has remained the standard in IDDM prediction. Conventional ICA quantitation using classic fluorochromes is prone to errors since fluorescence intensity is estimated subjectively using the human eye, which is also unable to differentiate specific signals from non-specific signals and autofluorescence. Using Eu(3+)-chelate labelled anti-human polyclonal IgG (decay time 1000 microseconds) as the secondary antibody in time-resolved fluorescence imaging (TRFI), the chelate and autofluorescence signals (typical decay time < 100 ns) are fully separated. The image is recorded using an optically gated cooled digital CCD camera. The specificity of the ICA signal is further improved by interactive analysis of the image. Signal detection is objective, the signal-to-background ratio improves, and ICA quantitation is possible using undiluted serum. Of 57 consecutive new-onset IDDM patients, 55 (96.5%) were ICA positive in the new assay while 51 (89.5%) were positive in the conventional assay suggesting that the sensitivity of TRFI exceeds that of the IAA, GAD65 and IA-2 autoantibody assays combined. For later comparisons, the stained slides may be stored in the light for years without any decrease in specific fluorescence.
Adolescent↗
Epidemiology of idiopathic cardiomyopathies in children and adolescents. A nationwide study in Finland.
Although idiopathic cardiomyopathies are prognostically important and are a common indication for cardiac transplantation in all age groups, the incidence and age distribution of idiopathic cardiomyopathies in a well-defined pediatric population have been poorly characterized. A retrospective study was carried out in Finland in 1980-1991 to obtain information on the epidemiology of childhood cardiomyopathies. The medical records of all patients aged birth to 20 years with cardiomyopathy from the five university hospitals and 16 central hospitals covering the entire country were reviewed. Moreover, data on causes of death from the Finnish National Census Bureau were examined. Of the 808 potential cases screened, 118 infants, children, and adolescents, representing an average age-specific population of 1.4 million, were definitely identified as having idiopathic cardiomyopathy. The average annual occurrence of new cases was 0.65 per 100,000 population (95% confidence interval (CI) 0.53-0.79). If the 15 cases diagnosed only after death during the 12-year study period were included, the occurrence increased to 0.74 per 100,000 population per year. Fifty-six new cases of dilated cardiomyopathy and 40 new cases of hypertrophic cardiomyopathy were diagnosed during the study period, giving average annual occurrences of 0.34/100,000/year (95% CI 0.26-0.44) and 0.24/100,000/year (95% CI 0.17-0.33) for new cases of dilated and hypertrophic cardiomyopathies, respectively. At the end of 1991, the prevalence of dilated cardiomyopathy was 2.6/100,000 (95% CI 1.8-3.6) and that for hypertrophic cardiomyopathy was 2.9/100,000 (95% CI 2.0-4.0). The number of new cases of dilated cardiomyopathy per year increased over the study period, whereas the annual occurrence of hypertrophic cardiomyopathy remained relatively constant. Marked variability was seen in occurrence among the different age groups of children with dilated cardiomyopathy, suggesting that different pathophysiologic mechanisms, and possibly etiologies, may exist in different age groups.
Adolescent↗
Ly-6C regulates endothelial adhesion and homing of CD8(+) T cells by activating integrin-dependent adhesion pathways.
Ly-6C belongs to the Ly-6 family of glycosyl phosphatidylinositol-anchored surface glycoproteins and is expressed on a subset of mature CD8(+) T cells. Ly-6C ligation can mediate T cell activation and causes interleukin 2 secretion in cytolytic T cell clones. We characterize herein a new mAb 1G7.G10 against Ly-6C that recognizes an epitope involved in lymphocyte adhesion and in lymphocyte homing. Pretreatment of lymph node lymphocytes and of purified CD8(+) T cells (but not of lymphocytes depleted of CD8(+) T cells) with 1G7.G10 reduced their in vitro binding to lymph node high endothelial venules by 28% and 34%, respectively. This effect was bypassed by cross-linking Ly-6C molecules with 1G7.G10 and a second-step antibody. The in vivo homing of (donor) CD8(+) T lymphocytes to lymph nodes was reduced by Ly-6C blocking with 1G7. G10 (whole antibody) or with its fragments [F(ab) or F(ab)2] by 20% or by 32% and 48%, respectively. Cross-linking of Ly-6C in vitro induced very late antigen-4 and lymphocyte function-associated antigen 1-mediated aggregation of CD8(+) T cells, suggesting that ligand binding to Ly-6C leads to activation of integrins. This activation may facilitate homing of Ly-6C+ CD8(+) T cells in vivo.
Animals↗
Nutrient intakes by young children in a prospective randomized trial of a low-saturated fat, low-cholesterol diet. The STRIP Baby Project. Special Turku Coronary Risk Factor Intervention Project for Babies.
OBJECTIVE: To evaluate the impact of individualized and repeatedly given dietary counseling on fat intake and nutrient intake of children aged 8 months to 4 years. DESIGN: Prospective randomized clinical trial. PARTICIPANTS: Children (N = 1062) from 1054 families were randomized to an intervention (n = 540) or a control (n = 522) group when each child participant was 6 months old. INTERVENTIONS: The children in the intervention group were counseled to reduce their intake of saturated fat and cholesterol but to ensure their adequate energy intake. Dietary issues were discussed with the families of the children in the control group only briefly according to the current practice of well-baby clinics. MAIN OUTCOME MEASURES: Food consumption was evaluated by using 3- and 4-day food records that were kept at 5- to 12-month intervals, and nutrient intakes were analyzed with a Micro Nutrica computer program (Social Insurance Institution, Turku, Finland). RESULTS: The intake of fat (29% of the energy intake) and cholesterol (70 mg) showed no differences between the groups of children at 8 months of age. The fat intake in the children in the intervention group was then continuously 2% of the energy intake below that of the children in the control group (P < .001). After the age of 13 months, the cholesterol intake of the children in the control group exceeded that of the children in the intervention group by 20 mg (P < .001). The children in the intervention group consumed 3% (of the energy intake) less saturated (P < .001) and 1% (of the energy intake) more polyunsaturated fats (P < .001) than did the children in the control group at age 13 months and older. The carbohydrate intake was slightly higher in the children in the intervention group than in the children in the control group. Intakes of vitamins, minerals, and trace elements showed no differences between the 2 groups. CONCLUSIONS: The intakes of fat by the children in the intervention and control groups were markedly below values that were recommended for the first 2 years of life. Despite the low intake of fat, the intake of other nutrients fulfilled current recommendations, except for vitamin D and iron. Individualized dietary counseling that led to clear changes in the type of fat intake had a minimal effect on vitamin or mineral intakes.
Age Factors↗
Human cationic amino acid transporter gene hCAT-2 is assigned to 8p22 but is not the causative gene in lysinuric protein intolerance.
Lysinuric protein intolerance (LPI) is a recessively inherited amino acid disorder characterized by defective efflux of cationic amino acids at the basolateral membrane of the intestinal and renal tubular epithelium. Recently, cDNAs encoding the related proteins hCAT-2A and hCAT-2B have been cloned. These two carrier proteins are most likely to product of the same gene, hCAT-2. Using the hCAT-2B cDNA, we assigned the hCAT-2 gene to chromosome 8p22. Furthermore, by linkage analysis in Finnish LPI families, we ruled out that hCAT-2B is involved in LPI disease.
Amino Acid Metabolism, Inborn Errors↗
Food consumption in rural and urban Tanzania.
Food consumption of 177 rural and 94 urban subjects (98 aged 12 years, 105 aged 35-44 years, and 68 aged 65-74 years) was studied in rural and urban Ilala district, Dar-es-Salaam, Tanzania, to characterize rural-urban differences in the meal and snack patterns and intakes of energy and nutrients. Food consumption of each subject was studied using 24 h dietary recall once during the rainy season and once during the dry season. Micro Nutrica PC database, expanded with East African food composition tables, was used in the nutrient intake analyses. All urban and 92% of rural subjects had three daily meals, and snacks were as commonly eaten in both areas of the survey. Foods of animal origin, e.g. meat and milk, were seldom used by the rural subjects. The WHO/FAO recommended minimal daily allowances of energy and protein were not reached by 26 and 15% of the rural subjects, respectively (10 and 4% of the urban subjects). Mean intake of folic acid by rural subjects was clearly below that of the urban subjects. Intakes of sucrose, mono- and disaccharides combined, polysaccharides, fibre and cholesterol differed markedly in all age groups in rural and urban circumstances (P < 0.05). Intake of fat and saturated fat was extremely low in all age groups, particularly in the rural subjects. The data suggest that (sub)clinical protein-energy malnutrition is prevelant in Tanzania, and that the high intakes of sucrose and cholesterol and the low intake of fibre by the urban subjects may increase the prevalence of dental caries and cardiovascular diseases in that population.
Adult↗
Impact of gender, apolipoprotein E phenotypes, and diet on serum lipids and lipoproteins in infancy.
OBJECTIVE: To determine the influence of gender, apolipoprotein E phenotypes, and diet on the interindividual variances in serum lipid and lipoprotein concentrations in children at 7 and 13 months of age. STUDY DESIGN: Prospective randomized intervention trial. Half of 1062 families with 7-month-old infants received dietary and lifestyle counseling aimed at partially replacing saturated fat with mono- and polyunsaturated fat and reducing exposure to other known atherosclerosis risk factors. This study comprises all trial children who at 8 months of age received, in addition to solid food, only breast milk or only formula (N = 553). Forward stepwise multiple regression analysis was used in the evaluation of the contributions of gender, apolipoprotein E phenotype, and diet. RESULTS: Apolipoprotein E phenotypes, gender, and milk type provided independent information concerning serum lipid values at 7 and 13 months of age (three-way ANOVA, p < 0.01). At 7 months, milk type was the most significant predictor of total, non-high-density lipoprotein and high-density lipoprotein cholesterol and apolipoprotein B and A1 concentrations. At 13 months when the effects of gender (5%) and apolipoprotein E type (5%) were excluded, diet predicted only 2% of the variance in serum cholesterol concentration. The apolipoprotein E type predicted 8% of the variance in non-high-density lipoprotein cholesterol concentration and 7% of the variance in apolipoprotein B concentration (p < 0.001), together explaining only 3% of the variance in serum high-density lipoprotein cholesterol and apolipoprotein A1 concentrations. CONCLUSIONS: At 7 months of age diet is an important predictor of serum lipid and lipoprotein concentrations. At the age of 13 months the apolipoprotein E phenotype significantly predicts the concentrations of serum non-high-density lipoprotein cholesterol and apolipoprotein B. However, at both ages apolipoprotein E phenotype, gender, and diet together explain only from 1.4% to 15.5% of the variance in serum lipids and apolipoproteins, suggesting that other, presumably genetic, factors are major determinants.
Analysis of Variance↗
Milk type during mixed feeding: contribution to serum cholesterol ester fatty acids in late infancy.
OBJECTIVE: To evaluate the contribution of the type of milk on serum cholesterol ester fatty acids in infants receiving mixed feeding, we analyzed 3-day dietary records and serum cholesterol ester fatty acid composition of 397 seven-month-old infants. STUDY DESIGN: The infants received, in addition to solid food, only one type of milk: human milk (n = 218), a ready-to-use liquid formula (n = 139), a powdered formula (n = 33), or soy formula (n = 7). RESULTS: Mean fat intakes were low and varied from 28% to 31% of energy; the milks provided 43% to 64% of the fat. The mean polyunsaturated/saturated fat ratios of solid foods were from 0.52 to 0.63 and of milks from 0.20 to 0.45. Breast-fed infants' relative serum linoleic acid (18:2n-6) concentration was low (51.2%), whereas infants fed liquid formula had low serum oleic acid (18:1n-9) in accordance with low oleic acid content in that formula. The breast-fed infants had markedly higher serum concentrations of arachidonic acid (20:4n-6) and docosahexaenoic acid (22:6n-3) than the infants fed any of the formulas. CONCLUSION: The typical fatty acid patterns of breast- or formula-fed infants were still evident in 7-month-old infants who already received 60% to 70% of their energy from solid food. Marked differences were seen also in the relative concentrations of docosahexaenoic acid and arachidonic acid despite their small contribution in cholesterol esters.
Breast Feeding↗
CD106 (VCAM-1) in testicular immunoregulation.
The expression of CD18, CD49d/CD29, CD44, CD54 and CD106 was studied in the testis of normal mice at various ages, in the cryptorchid testis, in the testis of estrogen-treated mice and in the testis of non-obese diabetic (NOD) mice, using immunocytochemistry to see which of these lymphocyte and endothelial adhesion proteins may be involved in lymphocyte regulation in the testis. CD18-, CD49d/CD29-, CD44- and CD54-expressing cells were not found in the normal > 10-week-old BALB/c mouse testis. Leydig cells expressed CD106 strongly at this age. In contrast to the > 10-week-old testis, only very few interstitial cells of the 2-week-old normal mice expressed CD106. The expression of CD106 increased gradually with age so that at 6 weeks of age the expression of CD106 was moderate in the interstitial tissue. In the experimentally abdominal testis, CD106 was expressed in the interstitial tissue as strongly as in the contralateral scrotal testis. CD44- and CD18-expressing cells were occasionally present in the interstitial tissue of the abdominal testis, but not in the contralateral scrotal testis. CD54 was present in the epithelium of the ductuli efferentes. In the testis of the estrogen-treated mice, CD106 was expressed in the interstitial tissue as strongly as in the normal mice. Occasional CD44- and CD18-expressing cells were found in the testicular capsule. In the testis of adult NOD mice, CD106 was present in the interstitial tissue, but none of the other studied proteins. Immunoblotting of CD106 from the adult testis under reducing conditions demonstrated a single broad band with a M(r) of 51-65 kDa. This is a novel isoform of CD106. In a modified Stamper-Woodruff assay, lymphocytes bound to the testicular interstitial tissue. In co-incubations of native Leydig cells and lymphocytes, anti-CD106 antibodies prevented formation of Leydig cell-lymphocyte rosettes more than isotype-matched irrelevant control antibodies, suggesting that Leydig cell lymphocyte binding occurs through CD106-CD49d interactions. In lymphocyte cultures in the presence of anti-CD3, anti-CD28, the M(r) > 5 K fraction of testis extract (containing CD106 as shown by immunoblotting) and anti-CD106 or control antibody, anti-CD106 did not consistently affect T cell 3H-TdR incorporation. The present results suggest that CD106 expressed by the Leydig cells may act as an adhesion-promoting molecule or a co-stimulatory factor for T cells migrating to the testis.
Animals↗