FUT2 non-secretor status is associated with Type 1 diabetes susceptibility in Japanese children.

AIM: To examine the contribution of the FUT2 gene and ABO blood type to the development of Type 1 diabetes in Japanese children. METHODS: We analysed FUT2 variants and ABO genotypes in a total of 531 Japanese children diagnosed with Type 1 diabetes and 448 control subjects. The possible association of FUT2 variants and ABO genotypes with the onset of Type 1 diabetes was statistically examined. RESULTS: The se2 genotype (c.385A>T) of the FUT2 gene was found to confer susceptibility to Type 1A diabetes in a recessive effects model [odds ratio for se2/se2, 1.68 (95% CI 1.20-2.35); corrected P value = 0.0075]. CONCLUSIONS: The FUT2 gene contributed to the development of Type 1 diabetes in the present cohort of Japanese children.

Variants associated with autoimmune Type 1 diabetes in Japanese children: implications for age-specific effects of cis-regulatory haplotypes at 17q12-q21.

AIMS: The aim of this study was to clarify the significance of previously reported susceptibility variants in the development of autoimmune Type 1 diabetes in non-white children. Tested variants included rs2290400, which has been linked to Type 1 diabetes only in one study on white people. Haplotypes at 17q12-q21 encompassing rs2290400 are known to determine the susceptibility of early-onset asthma by affecting the expression of flanking genes. METHODS: We genotyped 63 variants in 428 Japanese people with childhood-onset autoimmune Type 1 diabetes and 457 individuals without diabetes. Possible association between variants and age at diabetes onset was examined using age-specific quantitative trait locus analysis and ordered-subset regression analysis. RESULTS: Ten variants, including rs2290400 in GSDMB, were more frequent among the people with Type 1 diabetes than those without diabetes. Of these, rs689 in INS and rs231775 in CTLA4 yielded particularly high odds ratios of 5.58 (corrected P value 0.001; 95% CI 2.15-14.47) and 1.64 (corrected P value 5.3 × 10-5 ; 95% CI 1.34-2.01), respectively. Age-specific effects on diabetes susceptibility were suggested for rs2290400; heterozygosity of the risk alleles was associated with relatively early onset of diabetes, and the allele was linked to the phenotype exclusively in the subgroup of age at onset ≤ 5.0 years. CONCLUSIONS: The results indicate that rs2290400 in GSDMB and polymorphisms in INS and CTLA4 are associated with the risk of Type 1 diabetes in Japanese children. Importantly, cis-regulatory haplotypes at 17q12-q21 encompassing rs2290400 probably determine the risk of autoimmune Type 1 diabetes predominantly in early childhood.

Superoxide dismutase in normal cycling human ovaries: immunohistochemical localization and characterization.

OBJECTIVE: To investigate the expression of manganese (Mn) and copper-zinc (Cu,Zn) superoxide dismutase (SOD) in normal cycling human ovaries throughout the menstrual cycle. DESIGN: Descriptive, controlled study. SETTING: Tohoku University School of Medicine. PATIENT(S): Twenty-four normal cycling human ovaries were obtained from patients who underwent oophorectomy and hysterectomy for squamous cell carcinoma of the uterine cervix. INTERVENTION(S): Immunohistochemistry for Mn-SOD and Cu,Zn-SOD. MAIN OUTCOME MEASURE(S): Immunostaining. RESULT(S): In the follicular stage, Mn-SOD immunoreactivity was detected in granulosa and theca interna cells of steroid-producing follicles, that is, preantral, nondominant, dominant, and atretic follicles, whereas Cu,Zn-SOD was detected in theca interna cells of these follicles and in granulosa cells of dominant follicles. In the luteal stage, immunoreactivity for Mn-SOD and Cu,Zn-SOD was observed in both luteinized granulosa and theca cells of the functioning corpus luteum. In the early degenerating corpus luteum, both Mn-SOD and Cu,Zn-SOD were positive in steroid-producing luteinized theca cells. Mn-SOD immunoreactivity was also detected in nonsteroid-producing luteinized granulosa cells and macrophages. CONCLUSION(S): Our results suggest that the expression of Mn-SOD and Cu,Zn-SOD closely correlates with steroidogenesis in the human ovary. In addition, Mn-SOD may play an important role in the process of luteal regression.

Development of posture in prone and supine positions during the prenatal period in low risk preterm infants.

The development of posture in the prone and supine positions was studied longitudinally in 10 low risk preterm infants between 31 and 39 weeks' postmenstrual age whose subsequent neurological development at 18 months old was normal. The infants were observed from one week after birth until the expected date of delivery. All postures were analysed according to the procedures described by Prechtl et al. There were large intraindividual and interindividual differences in posture in terms of the duration and incidence of the two positions. There was no age specific preferred posture found in either position. The posture duration in the prone position was longer than that in the supine position, but overall flexed and abducted posture were observed more often in the former. Turning of the head to the right side was also observed more often in the prone than in the supine position.

[A longitudinal study of hand-mouth contacts of pre-term infants].

The developmental change of spontaneous hand movements were investigated longitudinally in 5 low-risk pre-term infants. The observation period was divided into three: 33-40, 41-52 and 53-60 weeks in order of gestational age. Both hand-mouth contacts (H-M-C) and hand-face contacts (H-F-C) were frequent in the 33-40-week period, and decreased drastically in the 41-48 week period. In the 53-60-week period, the number of H-F-C remained at a low level, while H-M-C increased again to the level of the first period. Furthermore, the mouth was open as the hand came into contact with it as frequently in the 33-40-week period as in the 53-60-week period. These findings suggest that H-M-C are neurologically distinct from H-F-C, and that the H-M-C before 41 weeks and after 50 weeks share some common components of this neurological mechanism.

[Hand-mouth coordination in the low-risk preterm infants in preterm period].

The spontaneous motor activity of 20 low-risk preterm babies was filmed and their arm and hand movements were subjected to a comparative analysis of the interrelation between hand, head, eye and mouth movements. This analysis revealed that preterm babies can move the hand to mouth directly and the mouth and eye were open in 'anticipation' of arrival of the hand. This movement was associated with ipsilateral head orientation. This little-known coordination may have an important implication for the theory of intersensorimotor relation and for the origin of intentionality.

[A case of complete remission obtained with etoposide in uterine choriocarcinoma].

A 27-year-old female was admitted to Sendai National Hospital complaining of continuous slight genital bleeding for about one and a half year after incomplete abortion. At first visit, urinary hCG was elevated to 32,000 IU/l and ultrasonography revealed a heterogeneous tumor in the uterus body. After abdominal simple total hysterectomy, the sample was diagnosed pathologically as a uterine choriocarcinoma. The patient was treated with 2 courses of MTX, but this regimen was not so effective. Because of persistent elevation of urinary hCG, 2 courses of etoposide were performed and hCG was rapidly reduced to within LH level. Etoposide (25 mg/day per os) was given to the patient for about three months since hospitalization and now complete remission has been obtained.

Laterality of finger movements in preterm infants.

The laterality of head position, spontaneous finger movements, hand-face contact, and hand-mouth contact was studied in low-risk preterm infants of 31 to < 37 weeks postconceptional age (intrauterine + neonatal period at time of study). The head was predominantly turned towards the right side during the preterm period. Hand-mouth contact was more frequent on the right side and coincided well with the side to which the head was turned. Other hand movements, too, were more frequent on the right side than on the left, but these were also seen in the fingers contralateral to the direction in which the head was turned. These findings suggest that even before birth a spontaneous preference for head position is present and is already associated with asymmetry in coordinated finger movements.

Macrophages in normal cycling human ovaries; immunohistochemical localization and characterization.

We evaluated the immunolocalization and characterization of macrophages in 28 normal cycling human ovaries. Two primary antibodies were used to detect the macrophages: PGM1, a general marker for macrophages, and 25F9 which is specific for phagocytosing macrophages. Spindle-shaped cells positive for PGM1 but negative for 25F9 were observed in the stroma (123.6 +/- 1.05 cells/10(-6) m2) and theca layer of the follicle (mean ranged from 22.61 to 53.79) and the number of these cells did not change throughout the cycle. After ovulation, PGM1 positive cells with ballooning bodies began to appear in the early corpus luteum (111.8 +/- 0.83). The number of these macrophages increased in the mid and late corpora lutea, and reached maximum in the early degenerating corpus luteum (1231.0 +/- 3.29). A lower number of PGM1 positive ballooning macrophages were observed in the atretic follicle (177.9 +/- 1.42). 25F9 positive cells were also observed among the PGM1 positive balloon-shaped cells. The number of cells double positive for 25F9 and PGM1 was observed in the mid corpus luteum (44.6 +/- 0.46), increased in the late corpus luteum and early degenerating corpus luteum, and reached plateau in the late degenerating corpus luteum (549.0 +/- 5.82). A lower number of these double positive macrophages were also observed in the atretic follicle (64.8 +/- 0.36). The ratio of 25F9 to PGM1 positive cells increased in parallel with ageing of the corpus luteum (0.19 in the mid corpus luteum, 0.39 in the late corpus luteum, and 0.37 in the early degenerating corpus luteum), and the great majority of PGM1 positive cells were also immunopositive for 25F9 in the late degenerating corpus luteum (0.81). These results suggest that in normal cycling human ovaries, macrophages are mainly involved in luteal regression as scavengers.

Leukocytes in normal-cycling human ovaries: immunohistochemical distribution and characterization.

We investigated, using an image analysis system, the immunohistochemical localization of leukocyte subpopulations and human leukocyte antigen (HLA)-DR in 30 normal-cycling human ovaries in order to better understand local immunological events in human ovaries. All subtypes of T lymphocytes examined (CD3+, CD4+ and CD8+ cells) were sporadically observed in the stroma and theca layers of follicles throughout the menstrual cycle (ranging from 4.32 to 6.25 cells/10(-7) m2, 1.67 to 3.33 cells/10(-7) m2 and 2.33 to 3.44 cells/10(-7) m2, respectively for the three subtypes), and subsequently, increased in number in atretic follicles (78.70 +/- 6.90, 31.13 +/- 2.54 and 43.31 +/- 3.35). After ovulation, the number of T lymphocytes was markedly low in the early and mid corpus luteum (13.88 +/- 1.62, 4.18 +/- 0.50 and 6.53 +/- 0.45). The number increased in the late corpus luteum, and was highest in the late degenerating corpus luteum (255.67 +/- 27.10, 102.12 +/- 7.80 and 137.34 +/- 12.50). HLA-DR was sporadically positive in fibroblasts in the stroma and theca layers of follicles (means ranged from 1.25 to 1.82 cells/10(-7) m2), and increased in atretic follicles (24.68 +/- 2.25). HLA-DR+ cells were markedly low in the early and mid corpus luteum (2.16 +/- 0.88), increased in the late corpus luteum, and reached a plateau in the late degenerating corpus luteum (121.84 +/- 17.73). The great majority of these increased HLA-DR+ cells were macrophages. Results of our study suggest that T lymphocytes and/or macrophages play important roles in luteal regression and follicular atresia in normal-cycling human ovaries.

Cyclic changes of vasculature and vascular phenotypes in normal human ovaries.

In order to study alterations of angiogenesis and blood vessel regression through ovarian cycle in human ovaries we quantitatively examined vascularity in various stages in 24 normal human ovaries. Vascular density (VD; vessel numbers/10(-7) m2) and endothelial area of each vessel (EA; 10(-12) m2/vessel) were evaluated using immunohistochemistry of CD34 and CAS 200 image analysis system. Small-sized vessels were sporadically observed in stroma adjacent to primordial or primary follicles (6.73 +/- 1.83 for VD and 113.58 +/- 21.80 for EA). Formation of capillary network was observed in the theca layer of preantral follicles (PA; 15.28 +/- 2.77 for VD and 113.58 +/- 21.80 for EA), and higher density of the capillary network was detected in non-dominant follicles in follicular phase (ND-F) and dominant follicles (DF; 29.33 +/- 3.84 for VD and 179.69 +/- 41.25 for EA). Dense capillary network was still present in non-dominant follicles in luteal phase (ND-L) and atretic follicles (AF; 26.88 +/- 3.36 for VD and 110.88 +/- 50.53 for EA). After ovulation, developing capillaries were also observed in the luteinized granulosa layers in early corpus luteum (21.95 +/- 2.06 for VD and 167.08 +/- 29.59 for EA). Vessel density markedly increased in mid corpus luteum, reached plateau in late corpus luteum (60.85 +/- 5.92 for VD and 70.99 +/- 15.57 for EA) and remained constant during degenerating corpora lutea. Vascular endothelial growth factor was immunohistochemically observed in the theca cells in PA, ND-F, DF and ND-L in follicular stages, and functioning corpora lutea. Immunoreactivity of intercellular adhesion molecule-1 was detected only in post-capillary venules in early degenerating corpora lutea. These findings suggest that ovarian angiogenesis is a requirement for the early stages of folliculogenesis and luteal growth, and also plays an important role in the process of follicular atresia and luteal regression.

Juvenile adenomyotic cyst of the corpus uteri with dysmenorrhea.

The clinical and pathological features of an apparently unique case of an endometrial cyst of the uterus are reported. The cyst was located within the myometrium of a 16-year-old woman suffering from dysmenorrhea. After excision of the cyst, patient's symptoms improved. On histological examination, the cyst most closely resembled an adenomyotic cyst.

Expression of epidermal growth factors and epidermal growth factor receptor in normal cycling human ovaries.

Immunolocalization of transforming growth factor-alpha (TGF alpha), epidermal growth factor (EGF), cripto-1, amphiregulin and epidermal growth factor receptor (EGFR) was studied in 51 premenopausal human ovaries at various phases of the menstrual cycle. Localization of mRNA for TGF alpha and EGF was also studied by in-situ hybridization. Immunoreactive TGF alpha was observed predominantly in theca cells in 12 of 33 antral follicles in the follicular phase (6/14 dominant follicles, and 6/19 non-dominant) but not in any of the 18 follicles in the luteal phase or in primordial and pre-antral follicles. TGF alpha immunoreactivity was present predominantly in the luteinized granulosa cells in 13 of 15 corpora lutea in the luteal phase, which are considered to be active in steroidogenesis, but not in any of the regressed corpora lutea. Accumulation of TGF alpha mRNA hybridization signal was observed only in the theca cells in the follicles and luteinized theca cells in the ovaries that were immunohistochemically positive for TGF alpha. EGFR immunoreactivity was detected in 24 of 33 antral follicles in the follicular phase and in two of 18 follicles in the luteal phase but not in any of the corpora lutea. Immunoreactive EGF, cripto-1 and amphiregulin or EGF mRNA was not detected in any follicles, corpora lutea, or the stroma cells examined. These results indicate that, of the epidermal growth factors examined in this study, TGF alpha is locally synthesized in normal cycling human ovaries and TGF alpha may be synthesized in theca cells and act on the granulosa cells in a paracrine fashion through the EGFR in ovarian follicles.

Comparison of bioelectrical impedance analysis and dual energy X-ray absorptiometry for assessment of body composition in children.

BACKGROUND: There are a variety of methods for assessing body composition. Bioelectrical impedance analysis (BIA) is an easy and non-invasive technique, but has limitations in underweight and overweight subjects. Few reports have investigated the validity of BIA in children. In this report, the characteristics of BIA, especially in overweight and underweight children, are assessed and the results are compared with those of dual energy X-ray absorptiometry (DXA), as a reliable method for assessing body composition. METHODS: Determination of the fat-free mass (FFM), body fat content and percent body fat (%fat) was carried out using both BIA and DXA. The subjects (60 males and 44 females) were divided into five groups according to the percentage of ideal bodyweight (%IBW). Ten obese children, who were treated with exercise and a low-energy diet for 1 month, were also enrolled in this study. RESULTS: The %fat, FFM and body fat content showed a close correlation when measured by BIA and DXA with the correlation coefficients being 0.90, 0.95, and 0.95, respectively. In the underweight group, the %fat value determined by BIA tended to be greater than that determined by DXA, while in the overweight group, the BIA value was lower than the DXA value. The same trend was also seen in obese children before and after therapy with exercise and diet. CONCLUSION: Bioelectrical impedance analysis seems to be a reasonable method for daily clinical use, but attention should be paid to the interpretation of %fat values in underweight and overweight children.

Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome.

We evaluated the immunolocalization of the steroidogenic enzymes involved in the production of ovarian steroids, including the cholesterol side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (HSD), 17alpha-hydroxylase (P450c17) and aromatase (P450arom), oestrogen receptor (ER) and androgen receptor (AR), a steroidogenic transcription factor. Ad4-binding protein (Ad4BP) and a cell cycle-related nuclear antigen, Ki67, in five patients with polycystic ovarian syndrome (PCOS). Results were compared with those from normal cycling human ovaries to study in situ ovarian steroidogenesis and cell proliferation in polycystic ovaries (PCO). We classifed the follicles morphologically according to the development of granulosa types: type A, more than four layers (n = 7); type B, one to three layers (n = 11); and type C, theca interna cells only (n = 21). ER and P450arom were not observed in any of the follicles examined. In type A follicles, P450scc, 3beta-HSD, P450c17, AR and Ad4BP were observed in theca cells in all seven follicles examined, but the granulosa cells were positive only for Ad4BP (4/7) and AR (7/7). These immunohistolocalization patterns resembled those in non-selected antral follicles of normally cycling human ovaries. In theca cells from types B and C follicles, follicles positive for the steroidogenic enzymes, AR and Ad4BP were decreased in number. There were no significant differences between types A and B PCO follicles in the Ki67 labelling index of granulosa or theca cells, and between PCO and antral follicles from normally cycling human ovaries. Data demonstrate that the follicles of PCO are by no means atretic and are actively involved in both steroidogenesis and cell proliferation. The absence of ER and aromatase expression in the granulosa cells of PCO may be important in abnormal follicular development in patients with PCOS.