Deep learning-based diffusion tensor image generation model: a proof-of-concept study.

This study created an image-to-image translation model that synthesizes diffusion tensor images (DTI) from conventional diffusion weighted images, and validated the similarities between the original and synthetic DTI. Thirty-two healthy volunteers were prospectively recruited. DTI and DWI were obtained with six and three directions of the motion probing gradient (MPG), respectively. The identical imaging plane was paired for the image-to-image translation model that synthesized one direction of the MPG from DWI. This process was repeated six times in the respective MPG directions. Regions of interest (ROIs) in the lentiform nucleus, thalamus, posterior limb of the internal capsule, posterior thalamic radiation, and splenium of the corpus callosum were created and applied to maps derived from the original and synthetic DTI. The mean values and signal-to-noise ratio (SNR) of the original and synthetic maps for each ROI were compared. The Bland-Altman plot between the original and synthetic data was evaluated. Although the test dataset showed a larger standard deviation of all values and lower SNR in the synthetic data than in the original data, the Bland-Altman plots showed each plot localizing in a similar distribution. Synthetic DTI could be generated from conventional DWI with an image-to-image translation model.

Decreased serum testosterone levels in long-term adult survivors with fatty liver after childhood stem cell transplantation.

Fatty liver and male gonadal dysfunction are potential late effects of therapy in adult survivors treated with stem cell transplantation (SCT) in childhood. Obesity and metabolic syndrome also are associated with low serum testosterone levels in the general population. However, the relationship between the degree of fatty liver and changes in serum testosterone levels in adult survivors has not been fully studied. We reviewed the clinical records of 34 male patients who received allogeneic SCT in childhood or adolescence. The median age at SCT was 10.0 years, and the median follow-up after SCT was 15.9 years. All but one patient showed no tendency toward overweight/obesity during the follow-up period. Fatty liver was diagnosed by ultrasound in 15 patients at 4 to 20 years after SCT. Patients who received cranial radiation therapy before SCT were more likely to develop fatty liver and insulin resistance. Moreover, fatty liver was statistically associated with decreased serum testosterone levels, whereas nonfatty liver was not (median, 527 ng/dL [range, 168-944 ng/dL] versus 302 ng/dL [165-698 ng/dL]; P < .0001). Changes in testosterone levels after SCT are affected not only by primary gonadal dysfunction but also by subsequent development or exacerbation of fatty liver.

Resistance to thyroid hormone accompanied by atrial fibrillation

Resistance to thyroid hormone (RTH), which is primarily caused by mutations in the thyroid hormone (TH) receptor beta (THRB) gene, is dominantly inherited syndrome of variable tissue hyposensitivity to TH. We herein describe a case involving a 22-year-old Japanese man with RTH and atrial fibrillation (AF) complaining of palpitation and general fatigue. Electrocardiography results revealed AF. He exhibited elevated TH levels and an inappropriately normal level of thyroidstimulating hormone (TSH). Despite being negative for anti-TSH receptor antibody, thyroid-stimulating antibody and anti-thyroperoxidase antibody, the patient was positive for anti-thyroglobulin (Tg) antibody. Genetic analysis of the THRB gene identified a missense mutation, F269L, leading to the diagnosis of RTH. Normal sinus rhythm was achieved after 1 week of oral bisoprolol fumarate (5 mg/day) administration. After 3 years on bisoprolol fumarate, the patient had been doing well with normal sinus rhythm, syndrome of inappropriate secretion of TSH (SITSH) and positive titer of anti-Tg antibody. Learning points: •• Atrial fibrillation can occur in patients with RTH. •• Only a few cases have been reported on the coexistence of RTH and atrial fibrillation. •• No consensus exists regarding the management of atrial fibrillation in patients with RTH. •• Administration of bisoprolol fumarate, a beta-blocker, can ameliorate atrial fibrillation in RTH.

Purification of chicken carbonic anhydrase isozyme-III (CA-III) and its measurement in White Leghorn chickens.

BACKGROUND: The developmental profile of chicken carbonic anhydrase-III (CA-III) blood levels has not been previously determined or reported. We isolated CA-III from chicken muscle and investigated age-related changes in the levels of CA-III in blood. METHODS: CA-III was purified from chicken muscle. The levels of CA-III in plasma and erythrocytes from 278 female chickens (aged 1-93 weeks) and 68 male chickens (aged 3-59 weeks) were determined by ELISA. RESULTS: The mean level of CA-III in female chicken erythrocytes (1 week old) was 4.6 µg/g of Hb, and the CA-III level did not change until 16 weeks of age. The level then increased until 63 weeks of age (11.8 µg/g of Hb), decreased to 4.7 µg/g of Hb at 73 weeks of age, and increased again until 93 weeks of age (8.6 µg/g of Hb). The mean level of CA-III in erythrocytes from male chickens (3 weeks old) was 2.4 µg/g of Hb, and this level remained steady until 59 weeks of age. The mean plasma level of CA-III in 1-week-old female chickens was 60 ng/mL, and this level was increased at 3 weeks of age (141 ng/mL) and then remained steady until 80 weeks of age (122 ng/mL). The mean plasma level of CA-III in 3-week-old male chickens was 58 ng/mL, and this level remained steady until 59 weeks of age. CONCLUSION: We observed both developmental changes and sex differences in CA-III concentrations in White Leghorn (WL) chicken erythrocytes and plasma. Simple linear regression analysis showed a significant association between the erythrocyte CA-III level and egg-laying rate in WL-chickens 16-63 weeks of age (p < 0.01).

Biochemical and developmental characterization of carbonic anhydrase II from chicken erythrocytes.

BACKGROUND: Carbonic anhydrase (CA) of the chicken has attracted attention for a long time because it has an important role in the eggshell formation. The developmental profile of CA-II isozyme levels in chicken erythrocytes has not been determined or reported. Furthermore, the relations with CA-II in erythrocyte and egg production are not discussed. In the present study, we isolated CA-II from erythrocytes of chickens and determined age-related changes of CA-II levels in erythrocytes. METHODS: Chicken CA-II was purified by a combination of column chromatography. The levels of CA-II in the hemolysate of the chicken were determined using the ELISA system in blood samples from 279 female chickens, ages 1 to 93 weeks, 69 male chickens, ages 3 to 59 weeks and 52 weeks female Araucana-chickens. RESULTS: The mean concentration of CA-II in hemolysate from 1-week-old female was 50.8 ± 11.9 mg/g of Hb. The mean levels of CA-II in 25-week-old (188.1 ± 82.6 mg/g of Hb), 31-week-old (193.6 ± 69.7 mg/g of Hb) and 49-week-old (203.8 ± 123.5 mg/g of Hb) female-chickens showed the highest level of CA-II. The levels of CA-II in female WL-chickens significantly decreased at 63 week (139.0 ± 19.3 mg/g of Hb). The levels of CA-II in female WL-chicken did not change from week 63 until week 93.The mean level of CA-II in hemolysate of 3-week-old male WL-chickens was 78.3 ± 20.7 mg/g of Hb. The levels of CA-II in male WL-chickens did not show changes in the week 3 to week 59 timeframe. The mean level of CA-II in 53-week-old female Araucana-chickens was 23.4 ± 1.78 mg/g of Hb. These levels of CA-II were about 11% of those of 49-week-old female WL-chickens. Simple linear regression analysis showed significant associations between the level of CA-II and egg laying rate from 16 week-old at 63 week-old WL-chicken (p<0.01). CONCLUSIONS: Developmental changes and sexual differences of CA-II concentration in WL-chicken erythrocytes were observed. The concentration of CA-II in the erythrocyte of WL-chicken was much higher than that in Araucana-chicken (p<0.01).

A ghrelin gene variant may predict crossover rate from restricting-type anorexia nervosa to other phenotypes of eating disorders: a retrospective survival analysis.

BACKGROUND: Patients with anorexia nervosa restricting type (AN-R) often develop bulimic symptoms and crossover to AN-binge eating/purging type (AN-BP), or to bulimia nervosa (BN). We have reported earlier that genetic variants of an orexigenic peptide ghrelin are associated with BN. Here, the relationship between a ghrelin gene variant and the rate of change from AN-R to other phenotypes of eating disorders (EDs) was investigated. METHODS: Participants were 165 patients with ED, initially diagnosed as AN-R. The dates of their AN-R onset and changes in diagnosis to other subtypes of ED were investigated retrospectively. Ghrelin gene 3056 T-->C SNP (single nucleotide polymorphism) was genotyped. Probability and hazard ratios were analyzed using life table analysis and Cox's proportional hazard regression model, in which the starting point was the time of AN-R onset and the outcome events were the time of (i) onset of binge eating, that is, when patients changed to binge eating AN and BN and (ii) recovery of normal weight, that is, when patients changed to BN or remission. RESULTS: Patients with the TT genotype at 3056 T-->C had a higher probability and hazard ratio for recovery of normal weight. The ghrelin SNP was not related with the onset of binge eating. CONCLUSION: The 3056 T-->C SNP of the ghrelin gene is related to the probability and the rate of recovery of normal body weight from restricting-type AN.

Turner syndrome with ulcerative colitis.

Turner syndrome is a chromosomal disease frequently associated with autoimmune disorders including diabetes mellitus, thyroid disease and inflammatory bowel disease (IBD). Although the etiology of IBD has not been fully elucidated, genetic analysis has recently revealed several susceptibility genes. Recently, cases with Turner syndrome associated with IBD have been reported. We report here a 13-yr-old girl with Turner syndrome associated with ulcerative colitis. The patient was undergoing growth hormone treatment and presented with abdominal discomfort and bloody diarrhea. Her karyotype pattern was 46,X,i(Xq). Barium enema revealed punctate collections of barium suggesting microulcerations in the descending and sigmoid colon with loss of haustra. Flexible sigmoidoscopy showed that the mucosa was erythematous and friable upon touch and that the wall had frank hemorrhage and inflammatory polyp formation from the anal verge through the splenic flexure. Histologically, mucosal and submucosal inflammation was prominent, suggesting cryptitis and crypt abscess formation. Based on these findings, she was diagnosed as having ulcerative colitis, and 5-aminosalicylic acid, prednisolone and dietary therapy were initiated. Our observations in this patient suggest that X chromosome abnormality may influence the development of IBD and that screening for gastrointestinal disease in patients with Turner syndrome may help lengthen life expectancy in these patients.

Growth and Endocrine Function in Long-term Adult Survivors of Childhood Stem Cell Transplant.

The number of long-term surviving stem cell transplant (SCT) recipients has increased steadily, and attention has now extended to the late complications of this procedure. The objective of this study was to investigate relationship among growth and endocrine functions in long-term adult survivors of childhood SCT. The inclusion criteria of this study were survival at least 5 yr after SCT and achievement of adult height. Fifty-four patients (39 males) fulfilled these criteria and were included in this study. Growth was mainly evaluated by height standard deviation score (SDS) and individual longitudinal growth curves. Among the 54 patients, those that received SCT before 10 yr of age showed significantly greater reductions in changes in height SDS (mean -1.75, range -4.80 to -0.10) compared with those that received SCT at or after 10 yr of age (mean -0.50, range -1.74 to 1.20; P<0.001). The mean loss of height for all patients who received SCT during childhood was estimated to be approximately 1 SDS/6.5 yr (r=0.517). Individual longitudinal growth curves indicated that a significant growth spurt was absent in severe short stature patients during the pubertal period without severe endocrine dysfunctions including GH deficiency. The incidence of growth disorder in long-term adult survivors depends on the age at SCT and whether they received radiation therapy. Life-long follow-up is necessary for survivors to detect, prevent and treat the late endocrine complications in SCT survivors.

Possible role of preproghrelin gene polymorphisms in susceptibility to bulimia nervosa.

Previous investigations have suggested that ghrelin, an endogenous orexigenic peptide, is involved in the pathology of eating disorders. We conducted a study to determine whether any preproghrelin gene polymorphisms are associated with eating disorders. Three hundred thirty-six eating disorder patients, including 131 anorexia nervosa (AN)-restricting types (AN-R), 97 AN-binge eating/purging types (AN-BP) and 108 bulimia nervosa (BN)-purging types (BN-P), and 300 healthy control subjects participated in the study. Genotyping was performed to determine the polymorphisms present, and with this information, linkage disequilibrium (LD) between the markers was analyzed and the distributions of the genotypes, the allele frequencies, and the haplotype frequencies were compared between the groups. The Leu72Met (408 C > A) (rs696217) polymorphism in exon 2 and the 3056 T > C (rs2075356) polymorphism in intron 2 were in LD (D' = 0.902, r2 = 0.454). Both polymorphisms were significantly associated with BN-P (allele-wise: P = 0.0410, odds ratio (OR) = 1.48; P = 0.0035, OR = 1.63, for Leu72Met and 3056 T > C, respectively). In addition, we observed a significant increase in the frequency of the haplotype Met72-3056C in BN-P patients (P = 0.0059, OR = 1.71). Our findings suggest that the Leu72Met (408 C > A) and the 3056 T > C polymorphisms of the preproghrelin gene are associated with susceptibility to BN-P.

Persistence of mild hyperthyrotropinemia after discontinuation of three-year course of low-dose L-thyroxine therapy in infants with borderline hypothyroidism.

Treatment plan for neonates with borderline hypothyroidism (persistent hyperthyrotropinemia with normothyroxinemia) has not been established. In this study, changes in thyroid function after discontinuation of low-dose L-thyroxine (L-T4) supplement in infants with the condition were evaluated. Fourteen infants with hyperthyrotropinemia at neonatal screening had repeated hyperthyrotropinemia (> 8 mU/L) with normothyroxinemia. TSH response was exaggerated at TRH testing. The subjects were treated with low-dose L-T4 (3 to 9 microg/kg/day) for 2.2 to 6 years, and euthyroid status was maintained. After discontinuation of therapy, mild hyperthyrotropinemia persisted up to 24 months, while serum FT4 remained within the lower half of the normal range. TSH response to TRH stimulation, which tended to be exaggerated 1 month after discontinuation, became lower 6 to 12 months later. RAIU and thyroid scintigraphy were normal in all subjects. No patient developed hypothyroxinemia, although mild elevation of TSH lasted rather long after discontinuation of low-dose L-T4 therapy. Administration of L-T4 was not resumed provided the subjects were followed at regular interval. Further long-term investigation is needed to define whether re-administration is necessary or not.