Shigeo Akira

Video-assisted neck surgery: endoscopic resection of thyroid tumors with a very minimal neck wound

In recent years, endoscopic surgery has been widely applied with a view to minimizing tissue trauma and wound-related complications and improving cosmetic outcomes. Reports on its use in thyroid surgery are extremely scarce particularly with regard to exploiting the advantage of eliminating unattractive scars that we sometimes encounter in conventional operations on the exposed anterior part of the neck. We initially experimented and practiced endoscopic neck surgery on animals until we gained enough confidence for clinical application. After obtaining informed consent from patients and their families we began performing this new technique on patients with thyroid nodules; we termed this technique Video-Assisted Neck Surgery (VANS). We hereby report our early experience of VANS in the endoscopic resection of thyroid tumors in five patients, mainly looking at technical feasibility and the ability to reduce neck wounds to a minimum.

Effect of Testosterone on Growth Hormone Secretion in Female Rats during a Continuous Infusion of Growth Hormone Releasing Factor

The effect of testosterone on growth hormone (GH) secretory pattern during a 6-hour continuous infusion of human GH-releasing factor (GRF) (1-44) NH2 was observed in unrestrained adult female Wistar rats. Rats had been ovariectomized or sham operated 6 weeks previously. Three weeks after the ovariectomy, the rats received sesame oil or testosterone propionate at a dose of 1 or 2 mg s.c. daily for 21 days. All rats were provided with two indwelling cannulae: one in the right atrium for undisturbed blood collection and the other in the inferior vena cava for vehicle or GRF infusion. Vehicle or GRF was administered by an infusion pump at a dose of 50 ng/kg/min for 6 h. Serial blood specimens were obtained every 20 min. Sham-operated adult female Wistar rats exhibited a high-frequency, low-amplitude pulsatile GH secretion during a 6-hour vehicle infusion. When they received a 6-hour continuous infusion of GRF, the amplitudes of GH pulses and baseline GH values were markedly augmented, but the pulse frequency remained unaltered. The GH secretory pattern during a 6-hour vehicle infusion among ovariectomized rats was similar to that of sham-operated female rats, whereas the magnitude of elevation of GH pulse and baseline level in ovariectomized rats were significantly lower than in sham-operated rats. The ovariectomized female rats that had received 2 mg testosterone for 21 days showed a low-frequency, regularly timed, high-amplitude pulsatile GH secretion, and GH values during the intervening period were low. This GH secretory pattern was indistinguishable from that in adult male rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrence of ovarian endometrioma after laparoscopic excision: Risk factors and prevention

The aim of this study was to assess the cut‐off age of the risk factors for postoperative recurrence of ovarian endometriomas and to evaluate the end‐points of follow‐up after laparoscopic excision of ovarian endometriomas.

Allelic Imbalance in Regulation of ANRIL through Chromatin Interaction at 9p21 Endometriosis Risk Locus.

Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging “allele-specific” functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site. Chromosome conformation capture followed by high-throughput sequencing revealed that the protective G allele of rs17761446 exerted stronger chromatin interaction with ANRIL promoter. We demonstrated that the protective allele exhibited preferential binding affinities to TCF7L2 and EP300 by bioinformatics and chromatin immunoprecipitation (ChIP) analyses. ChIP assays for histone H3 lysine 27 acetylation and RNA polymerase II reinforced the enhancer activity of the SNP site. The allele specific expression analysis for eutopic endometrial tissues and endometrial carcinoma cell lines showed that rs17761446 was a cis-regulatory variant where G allele was associated with increased ANRIL expression. Our work illuminates the allelic imbalances in a series of transcriptional regulation from factor binding to gene expression mediated by chromatin interaction underlie the molecular mechanism of 9p21 endometriosis risk locus. Functional genomics on common disease will unlock functional aspect of genotype-phenotype correlations in the post-GWAS stage.

A nonsynonymous variant of IL1A is associated with endometriosis in Japanese population.

Our previous genome-wide association study has demonstrated that single-nucleotide polymorphisms (SNPs) located in intronic and downstream regions of IL1A (interleukin 1α) were associated with the risk of endometriosis. These SNPs on the genome-wide association study platform could be only surrogates for the true causal variant. Thus, we resequenced all the exons of IL1A in 377 patients with endometriosis and 457 healthy controls. We detected seven rare variants (minor allele frequency <0.01) and four common variants. All the rare variants were not associated with endometriosis. The four common variants (rs17561, rs1304037, rs2856836 and rs3783553) in IL1A were significantly associated with endometriosis (P=0.0024, 0.0024, 0.0014 and 0.0061, respectively). All the four SNPs were within a linkage disequilibrium block. Among them, only rs17561 was nonsynonymous (p.A114S), which has been reported to be associated with susceptibility to ovarian cancer. Taken together, we examined association between rs17561 and endometriosis in an independent validation data set (524 patients and 533 healthy controls) replicating significant association (P=4.0 × 10−5; odds ratio (OR), 1.91; 95% confidence interval (CI), 1.41–2.61). Meta-analysis by combining results from the two stages strengthened the evidence of association (P=2.5 × 10−7; OR, 1.90; 95% CI, 1.49–2.43). Our findings demonstrated that the nonsynonymous variant of IL1A might confer genetic susceptibility to endometriosis in Japanese population.

Effects of neonatal administration of monosodium glutamate on plasma growth hormone (GH) response to GH-releasing factor in adult male and female rats.

Female and male rats were treated with monosodium glutamate (MSG; 4 mg/g b. wt.) as neonates and the capability of the pituitary gland to secrete growth hormone (GH) in response to an intravenous injection of human GH-releasing factor (GRF) was evaluated under pentobarbital anesthesia on 109 days of life. Immunoreactive GRF content in the pituitary stalk-median eminence tissue in MSG-treated rats was less than 20% of that of control. A significant dose-dependent plasma GH response was observed after the administration of two doses of human GRF (0.25 and 1 microgram/kg b. wt., i.v.) in both control and MSG-treated rats. The responses between MSG-treated and control rats were comparable in female rats, but they were significantly reduced in male MSG-treated rats. These results show that the pituitarys responsiveness to exogenous GRF is well preserved in MSG-treated rats despite prolonged and severe depletion of endogenous GRF and there exists a sex difference in the effect of MSG on GH secretion elicited by GRF.

Prophylactic intratubal injection of methotrexate after linear salpingostomy for prevention of persistent ectopic pregnancy

Aim:  To examine the efficacy of local methotrexate (MTX) administration following linear salpingostomy for tubal pregnancy in the prevention of persistent ectopic pregnancy (PEP).

Endoscopic surgery in Japan: The 12th national survey(2012–2013) by the Japan Society for Endoscopic Surgery

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and usefulness of endoscopic surgery have been evaluated. With the acceptance of endoscopic surgery as less invasive than open surgery, the number of the endoscopic procedures continues to increase in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has had an important role in the development of endoscopic surgery in Japan. For example, JSES established a technical skills certification system for physicians to train instructors to teach safe endoscopic surgery. Additionally, JSES has performed a national survey every 2 years. In 2013, 178 084 patients underwent endoscopic surgery in all surgical domains, including abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The development and current status of laparoscopic surgery are reported here based on the results of the most recent questionnaire survey conducted by JSES.

A new evaluation score that uses salpingoscopy to reflect fallopian tube function in infertile women

OBJECTIVE To build an evaluation scoring system using the results of salpingoscopy, and to evaluate the relationship between this scoring system and the outcome of pregnancy. DESIGN Retrospective study. SETTING Sugiyama Clinic. INTERVENTION(S) Using salpingoscopy, we observed the tubal lumen, paying attention to the following six results: adhesions, loss of mucosal folds, rounded edges of mucosal folds, debris, foreign bodies, and abnormal vessels. PATIENT(S) From April 2008 through June 2009, 104 women in whom unexplained infertility had been diagnosed underwent salpingoscopy. The F scores were evaluated related with various clinical results or pregnancy rates. MAIN OUTCOME MEASURE(S) The F score expressed the sum of the abnormal results, and one abnormal result was given a 1-point F score. RESULTS Approximately 60% of the patients showed an F score of 0, and the percentages of patients who showed 1, 2, 3, and ≥4 points were 19.2%, 11.5%, 4.5%, and 4.5%, respectively. After evaluation, 23 patients achieved pregnancy within a year. The pregnancy rates for patients with F scores of 0 and 1 point were 30.6% and 20.0%, respectively, and the rate of patients with an F score of 0 was significantly higher than the rate of patients with high F scores (F score ≥2; 9.1%). CONCLUSION(S) The patients showing a lower F score (0 or 1) showed higher fecundity than those showing an F score of ≥2.

Preventive effect of monoclonal antibodies to intercellular adhesion molecule-1 and leukocyte function-associate antigen-1 on murine spontaneous fetal resorption

PROBLEM: Are cell adhesion molecules involved in the murine model of immunologically‐mediated spontaneous abortion?
 METHOD OF STUDY: Pregnant CBA/J female mice mated with DBA/2 male mice were injected with monoclonal antibodies (MAbs) to intercellular adhesion molecule‐1 (ICAM‐1) and leukocyte function‐associate antigen‐1 (LFA‐1). On day 13 of gestation, viable and resorbed embryos were counted. Natural killer (NK) cell activity in the spleen, mixed lymphocyte reactions (MLR), mixed lymphocyte‐placenta reactions (MLPR), and levels of interferon (IFN)‐Γ were assayed.
 RESULTS: Significant suppression of fetal resorption was observed by the injection of MAb to ICAM‐1 and LFA‐1. NK cell activity and the MLR anti‐(CBA/J×DBA/2)F1 were reduced in the antibody‐treated CBA/J spleen. Moreover, the level of IFN‐Γ was significantly lower in the MLPR supernatants from the antibody‐treated group than those of the control group.
 CONCLUSIONS: One mechanism in the murine model of spontaneous abortion may be through the interaction of cell adhesion molecules, which may modulate NK cell activities and cytokine production.