A new clustering model based on the seminal plasma/serum ratios of multiple trace element concentrations in male patients with subfertility.

Purpose: To investigate whether seminal plasma (SP)/serum ratios of multiple trace elements (TEs) can classify patients with male subfertility. Methods: SP/serum ratios of 20 TEs (lithium, sodium, magnesium, phosphorus, sulfur, potassium, calcium, manganese, iron, cobalt, copper, zinc, arsenic, selenium, rubidium, strontium, molybdenum, cesium, barium, and thallium) were calculated for healthy volunteers (n = 4) and those consulting for male subfertility (n = 245). Volunteer semen samples were collected by split ejaculation into early and subsequent fractions, and SP/serum ratio data were compared between fractions. The patients' SP/serum ratio data were used in an unsupervised clustering analysis and qualitatively compared with the data from the fractions of ejaculation from the volunteers. Semen quality parameters and pregnancy outcomes were compared between patient clusters. Results: The early fraction of volunteers was characterized by lower phosphorus and arsenic and 18 other higher TEs than the subsequent fraction. Cluster analysis classified patients into four distinct clusters, one sharing characteristics with the early fraction and another with the subsequent fraction. One cluster with the early fraction characteristics had significantly lower semen volume and higher pregnancy rates from spontaneous pregnancies or intrauterine insemination. Conclusions: Classification of patients based on SP/serum ratios of multiple TEs represents the dominance of fractions of ejaculation samples.

Association between Sperm Mitochondrial DNA Copy Number and Concentrations of Urinary Cadmium and Selenium.

Elevated sperm mitochondrial DNA copy number (mtDNAcn) is associated with damage to sperm and poorer measures of semen quality. Exposure to cadmium (Cd) can increase oxidative stress and damage sperm mitochondria. The adverse effects of Cd can potentially be reduced by sufficient selenium (Se). The objective of this study was to examine the associations between sperm mtDNAcn and urinary concentrations of Cd and Se, as well as the Cd/Se molar ratio. Participants were recruited from patients who sought infertility treatment at two hospitals in Japan. Urine and semen specimens and self-administered questionnaires were collected on the day of recruitment. Sperm mtDNAcn was measured in extracted sperm DNA by multiplex real-time qPCR. Urinary Cd and Se concentrations were measured using inductively coupled plasma mass spectrometry, and their molar weights were calculated to obtain the Cd/Se molar ratio. Linear regression was used to estimate associations after adjusting for age, body mass index, smoking, drinking, exercise, varicocele, and hospital of recruitment. Sperm mtDNAcn showed statistically insignificant associations with creatinine-adjusted concentrations of urinary Cd (ß = 0.13, 95% CI -0.18, 0.44) and Se (ß = -0.09, 95% CI -0.54, 0.35), and Cd/Se molar ratio (ß = 0.12, 95% CI -0.13, 0.37). The current study found no evidence of an association between mtDNAcn and urinary concentrations of Cd or Se, or the Cd/Se molar ratio.

The ratio of 2nd to 4th digit length and reproductive function of infertile male patients.

Purpose: To investigate the relationship between the ratio of index to ring finger lengths (2D:4D ratio), reflecting androgen exposure in utero, and reproductive function among men. Methods: Male patients (N = 180) who consulted for fertility issues participated in the study. The palms of both hands were scanned, and the 2D:4D ratio was calculated. Data on semen volume, sperm concentration and total motility, total and motile sperm counts, and serum hormone concentrations were obtained. Spearman correlation coefficients between the 2D:4D ratio and hormone and semen quality parameters were calculated. Results: The total sperm count was significantly negatively correlated with the 2D:4D ratio of the left hand (r = -0.154, p  = 0.039) but not with that of the right hand (r = -0.045, p  = 0.548). Testosterone showed weak negative correlations with the 2D:4D ratio in the left (r = -0.142, p  = 0.058) and right (r = - 0.149, p  = 0.046) hands. Follicle-stimulating hormone levels were negatively correlated with the 2D:4D ratios of the left (r = -0.173, p  = 0.020) and right (r = -0.164, p  = 0.027) hands. Other semen quality parameters or luteinizing hormone levels showed no significant correlation with the 2D:4D ratios. Conclusions: No clear associations were observed between the 2D:4D ratios and reproductive function.

Analysis of the correlation between gene copy deletion in the AZFc region and male infertility in Japanese men.

Deletion of the azoospermia factor c (AZFc), located on the long arm of the Y chromosome, is a cause of male infertility. The structure of the Y chromosome is diversified by the copy number of various genes, such as deleted in azoospermia (DAZ), basic protein Y2, chromodomain Y1, testis-specific transcript Y-linked 4, and Golgi autoantigen golgin subfamily a2 like Y, located in the AZF region. In this study, we investigated the deletion of each gene copy and analyzed its relationship with Japanese male infertility. Deletions of single nucleotide variants of each gene copy in 721 proven fertile men as controls, 139 patients with non-obstructive azoospermia (NOA), and 56 patients with oligozoospermia (OS) were analyzed via polymerase chain reaction-restriction fragment length polymorphism analysis. Their association with infertility was analyzed using logistic regression analysis adjusted for the Y-chromosome haplogroup, D1a2a. Deletions of DAZ/II in the r1 region and DAZ/V in the r1 and r2 regions showed significant associations with NOA (odds ratio [OR] = 4.15, 95 % confidence interval [CI] = 1.18-14.6, P = 0.026; OR = 4.19, 95 % CI = 1.19-14.7, P = 0.025, respectively). They did not show any association with OS. Partial deletion of the AZFc region affects spermatogenesis in Japanese male.

Effects of antioxidant co-supplementation therapy on spermatogenesis dysfunction in relation to the basal oxidation-reduction potential levels in spermatozoa: A pilot study.

Purpose: In this pilot study, the authors compared the effects of antioxidant co-supplementation therapy and methylcobalamin therapy in patients with impaired semen quality. Methods: Eighty-four subjects who visited male infertility clinics and showed abnormal semen test results were randomly subjected to one of the two therapies: antioxidant co-supplementation therapy with vitamin C, vitamin E, coenzyme Q10, and flaxseed oil or methylcobalamin therapy. The oxidation-reduction potential (ORP) and 8-hydroxy-2'-deoxyguanosine levels were used as indicators of oxidative stress levels in semen. Semen analysis was also performed. Results: The authors obtained results from 67 patients who had completed 3 months of treatment. Neither antioxidant co-supplementation therapy nor methylcobalamin therapy changed the semen parameters significantly (except for the sperm concentration, which was increased by the latter therapy). When the pre-treatment ORP value in semen was higher than the cutoff value, both therapies significantly increased the sperm concentration. The 8-hydroxy-2'-deoxyguanosine level did not yield any meaningful predictive value with regard to increased sperm concentrations. Conclusions: Both antioxidant co-supplementation therapy and methylcobalamin therapy increased the sperm concentration in patients with impaired semen quality when the basal ORP levels in their semen were elevated.

Light-guided renal cyst fenestration during laparoscopic ureterocalicostomy in a patient with left ureteropelvic junction obstruction.

INTRODUCTION: Laparoscopic ureterocalicostomy is a useful alternative to laparoscopic pyeloplasty for treating ureteropelvic junction obstruction under certain conditions. One concern regarding this technique is the inevitability of amputation of the renal lower pole to expose the lower renal calyx. CASE PRESENTATION: A 43-year-old man who presented ureteropelvic junction obstruction and multiple renal cysts underwent laparoscopic pyeloplasty, which could not be performed because of the intrarenal ureteropelvic junction. We switched the surgical technique to modified laparoscopic ureterocalicostomy, wherein amputation of the lower renal pole was substituted with fenestration of a renal cyst under the guidance of ureteroscopic light. Computed tomography performed 2 months postoperatively showed good patency of the anastomosis. CONCLUSION: Light-guided laparoscopic renal cyst fenestration followed by ureterocalicostomy is feasible in patients with ureteropelvic junction obstruction and lower pole renal cysts adjacent to the lower renal calyx.

Laparoscopy-assisted vasovasostomy for post-herniorrhaphy vas deferens obstruction.

INTRODUCTION: Repair of obstructive azoospermia caused by childhood herniorrhaphy may be difficult. Therefore, intracytoplasmic sperm injection using testicular sperm is performed. However, vasovasostomy combined with laparoscopic surgery is challenging. CASE PRESENTATION: A 42-year-old man underwent inguinal hernia repair at age 3. He had normal testicular size, azoospermia, normal hormone levels (follicle-stimulating hormone, luteinizing hormone, and testosterone), absence of Y chromosome micro deletion, and karyotype:46XY, t(1:21)(p34.1:q22.3). He was diagnosed with obstructive azoospermia. Repeated intracytoplasmic sperm injections using testicular sperm resulted in miscarriages. Vasovasostomy combined with laparoscopic surgery was subsequently performed. Postoperative semen analysis result was almost normal. After intracytoplasmic sperm injection of ejaculated sperm, his wife got pregnant. CONCLUSION: Even if patients have chromosomal abnormalities, performing microsurgical re-anastomosis first is recommended. To our knowledge, this is the first case of a laparoscopy-assisted vasovasostomy for post-herniorrhaphy vas deferens obstruction in Japan.

Genome-wide association study of semen volume, sperm concentration, testis size, and plasma inhibin B levels.

Semen quality is affected by environmental factors, endocrine function abnormalities, and genetic factors. A GWAS recently identified ERBB4 at 2q34 as a genetic locus associated with sperm motility. However, GWASs for human semen volume and sperm concentration have not been conducted. In addition, testis size also reportedly correlates with semen quality, and it is important to identify genes that affect testis size. Reproductive hormones also play an important role in spermatogenesis. To date, genetic loci associated with plasma testosterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels have been identified using GWASs. However, GWASs have not identified any relevant loci for plasma inhibin B levels. We conducted a two-stage GWAS using 811 Japanese men in a discovery stage followed by a replication stage using an additional 721 Japanese men. The results of the discovery and replication stages were combined into a meta-analysis. After setting a suggestive significance threshold for P values < 5 × 10-6　in the discovery stage, we identified ten regions with SNPs (semen volume: one, sperm concentration: three, testes size: two, and inhibin B: four). We selected only the most significant SNP in each region for replication genotyping. Combined discovery and replication results in the meta-analysis showed that the locus 12q21.31 associated with plasma inhibin B levels (rs11116724) had the most significant association (P = 5.7 × 10-8). The LRRIQ1 and TSPAN19 genes are located in the 12q21.31 region. This study provides new susceptibility variants that contribute to plasma inhibin B levels.

[Metastases of Urothelial Carcinoma with Trophoblastic Differentiation that Responded to Combination Chemotherapy with Gemcitabine and Oxaliplatin : A Case Report].

A 70-year-old man was admitted with complaint of gross hematuria. Cystoscopy and computed tomography (CT) revealed a 2.5 cm nodular tumor in the urinary bladder. Pathological diagnosis after the transurethral resection of bladder tumor (TURBT) was invasive urothelial cancer with trophoblastic differentiation of pT1. The tumor was positively stained with human chorionic gonadotropin (HCG). The serum HCG level was 12.8 IU/l in the fourth week after TURBT, and it increased to 35.7 IU/l in the 20th week after TURBT. However, radiological examination at this point did not reveal tumor recurrence or metastases. Three months later, the patient coughed up bloody sputum. Lung metastases (up to 2.4 cm) were identified, and they were surgically removed. The pathological specimen consisted of syncytiotrophoblastic giant cells with hemorrhage and necrosis, but no urothelial cancer element. Because the lung and lymph node metastases developed soon after surgery, chemotherapy was planned. Because the patient had impaired renal function with a creatinine clearance of 33.7 ml/min, we selected combination chemotherapy with gemcitabine and oxaliplatin (GEMOX) rather than cisplatin -based chemotherapy. CT after two courses of GEMOX showed stable disease, but HCG levels markedly decreased from 1,240 IU/l to 7.9 IU/l. This marker of response continued through six courses of GEMOX. Then, the chemotherapy was discontinued due to grade 2 neuropathy. He died of cancer 12 months after development of metastases. Autopsy revealed only tumor cells with trophoblastic differentiation, but no urothelial carcinoma in multiple metastatic sites.

Prevalence and prognostic influence of bacterial pyuria in elderly patients with pneumonia: A retrospective study.

AIM: The number of elderly patients with pneumonia is significantly increasing as the populations in many countries age. Although elderly patients with pneumonia are at risk of developing urinary tract infections, no studies have examined the prevalence or the prognostic impact of this complication. The aim of the present study was to investigate the prevalence of comorbid bacterial pyuria and the impact on the prognosis of elderly patients with pneumonia. METHODS: We retrospectively evaluated 132 patients aged >65 years who were hospitalized for pneumonia and who underwent a urinary sediment test on admission. The background characteristics, laboratory results and treatment regimens were documented, and the risk factors for the complication of bacterial pyuria and its association with 90-day mortality in pneumonia patients were elucidated. RESULTS: A total of 37 (28%) of 132 patients were complicated by bacterial pyuria. The patients with bacterial pyuria were more often women, showed a poorer performance status, were more frequently fed by percutaneous endoscopic gastrostomy, and more frequently used diapers and/or a bladder catheter. Regarding first-line drugs, 82.6% of the patients received beta-lactamase inhibitors and extended-spectrum penicillins. The use of a bladder catheter and a poor performance status were associated with bacterial pyuria. A multivariate analysis showed that a poor performance status was the only factor associated with 90-day mortality. CONCLUSIONS: Bacterial pyuria did not affect the prognosis of patients who were treated with penicillin-based regimens. Thus, broad-spectrum antibiotics are not necessarily required for elderly patients with pneumonia complicated by urinary tract infection. Geriatr Gerontol Int 2017; 17: 1076-1080.

Evaluation of prognostic differences in elderly patients with pneumonia treated by between pulmonologists and non-pulmonologists: a propensity score analysis.

INTRODUCTION: The incidence of pneumonia among elderly people is increasing in aged countries, and both pulmonologists and non-pulmonologists treat such patients. OBJECTIVES: The aim of this study was to assess prognostic differences between elderly patients treated by pulmonologists and those treated by non-pulmonologists. METHODS: This study was a retrospective cohort using a propensity score analysis. Patients 65 years of age or over with pneumonia were consecutively included. The propensity score was estimated based on the patient's background and severity of pneumonia. The difference in 30-day and 90-day mortality depending on the attending physician's specialty was analyzed after adjusting for other variables, including the propensity score. RESULTS: We assessed 68 and 182 patients treated by pulmonologists and non-pulmonologists, respectively. The pulmonologists tended to be in charge of patients with hypoxemia, chronic obstructive pulmonary disease or dementia without aspiration pneumonia or renal dysfunction (area under receiver operating characteristic curve to predict treatment by a pulmonologist according to the propensity score = 0.737, P < 0.001). In the multivariate analysis, white blood count cell (adjusted hazard ratio, 1.000, P = 0.030) and the serum albumin level (0.382, P = 0.001) were associated with 30-day mortality, and a bedridden status (3.000, P = 0.013) and the serum albumin level (0.382, P < 0.001) were associated with 90-day mortality; however, the attending physician's specialty was not associated with these prognoses. CONCLUSIONS: The overall prognosis of pneumonia in elderly patients may not necessarily improve, irrespective of treatment by pulmonologists, and host factors seemed to be associated with mortality.

Salvage chemotherapy with gemcitabine plus oxaliplatin for patients with testicular germ cell cancer.

BACKGROUND: The purpose of this study is to assess the feasibility of salvage chemotherapy with gemcitabine and oxaliplatin (GEMOX) for Japanese patients with refractory testicular germ cell cancer. METHODS: Eleven patients were treated with GEMOX. All had experienced disease progression or recurrence and had been treated with the standard induction chemotherapy and at least one cycle of cisplatin-based salvage chemotherapy (median 6 cycles) before the start of GEMOX. GEMOX consisted of gemcitabine 1,000 mg/m(2) intravenously on days 1 and 8 and oxaliplatin 130 mg/m(2) on day 1. RESULTS: Two patients (18 %) achieved a complete response (CR) after GEMOX and surgical resection of residual tumor. One additional patient responded to GEMOX, but was forced to discontinue treatment due to sensory neuropathy. This patient achieved CR after further treatment with irinotecan-based chemotherapy and surgery. All three patients have remained continuously free from disease progression at a median follow-up duration of 24 months. Sixty-four per cent of patients developed grade 3 leukocytopenia and 82 % developed grade 3 or higher thrombocytopenia but they were all managed with routine supportive care. Sensory neuropathy was frequently seen but no patient experienced neurotoxicity higher than grade 3. CONCLUSIONS: GEMOX as salvage chemotherapy is tolerable for intensively pretreated Japanese patients. GEMOX may offer a chance of long-term disease-free status even after failure of multiple cycles of chemotherapy.

[A case of incidentally diagnosed retroperitoneal lymphangioleiomyomatosis with no respiratory symptoms].

A 39-year-old woman presented with a large retroperitoneal tumor found incidentally in a routine examination. The 138×37×26 mm mass was located in the left paraaortic region. Blood tests and urinalyses including endocrinological examinations revealed no abnormalities. A chest computed tomography revealed multiple thin-walled pulmonary cysts, which is a characteristic of lymphangioleiomyomatosis (LAM). Because the findings strongly suggested that the retroperitoneal tumor was an extrapulmonary manifestion of LAM, we performed laparoscopic resection of the tumor for diagnosis and treatment. The pathological diagnosis was LAM. The tumor cells were immunohistochemically positive for α -smooth muscle actin and weakly positive for HMB45, which is consistent with LAM. The cells were also positive for estrogen receptor (ER) and progesterone receptor (PgR). LAM is a rare progressive disease that affects mainly the lung, and leads to chronic respiratory failure. Extrapulmonary LAM without respiratory symptoms, is extremely rare. In the past, the prognosis of LAM was poor, with a median survival of 8-10 years, but now 85% survive more than 10 years. In the present case, deterioration of pulmonary lesions was not observed during the 10 months follow-up. Because ERand PgRfindings were positive, we will consider hormonal therapy as a treatment option, when the pulmonary lesions progress in the present case.

[Case of metastatic malignant melanoma of the urinary bladder].

A 54-year-old woman underwent resection of malignant melanoma of the left leg and inguinal lymph node metastases and subsequent radiation therapy (60 Gy) following three courses of dacarbazine, nimustine, vincristine and interferon-beta chemotherapy in January 2010. In September 2011, she was referred to our department with the chief complaint of asymptomatic gross hematuria. A non-papillary bladder tumor was detected on cystoscopy and fluorodeoxyglucose (FDG) positron emission fomography-computed tomography revealed increased uptake of FDG only in the area of the bladder tumor. Melanoma cells were also found on urinary cytology. Our diagnosis was metastatic malignant melanoma of the bladder. Complete transurethral resection of the bladder tumor was performed, and pathological examination confirmed metastatic malignant melanoma. Metastatic bladder tumors constitute less than 5% of all bladder tumors. There are metastases in other organs at the time of diagnosis in almost all cases. In Japan, metastatic malignant melanoma of the urinary bladder is rare in clinical practice, there having been about a dozen reported cases. Solitary metastasis as in our case is even rarer.

[Long-term survival with gemcitabine and docetaxel for renal leiomyosarcoma : a case report].

A 64-year-old woman who complained of abdominal pain underwent right radical nephrectomy under the clinical diagnosis of renal cell carcinoma in January, 2006. The pathological diagnosis was leiomyosarcoma originating from the kidney. Follow-up computed tomography revealed 2 small nodules in the left lung 15 months after nephrectomy. A lung nodule resected with video-assisted thoracic surgery (VATS) was identified as metastatic leiomyosarcoma. Since the pulmonary metastases progressed after VATS, systemic chemotherapy with gemcitabine and docetaxel (GD therapy) was started. The lung metastases responded well, and a durable partial response was achieved for 29 months. Subsequently, the patient developed new pulmonary metastases and pancreatic metastasis. Despite this disease progression, we elected to continue GD therapy, since the patient's performance status and quality of life were favorable during the treatment. So far, the GD therapy has been continued for another 23 months, for a total of 41 treatment cycles, with few adverse events. Although multiple metastases have slowly progressed, the patient has maintained good performance status in the outpatient clinic. In the present case, GD therapy seems to have been beneficial for survival, as metastatic renal leiomyosarcoma is considered to have an extremely poor prognosis.

Sai-rei-to-induced lung injury: a case report and brief review of the literature.

An 81-year-old man was admitted to our hospital due to persistent fever and dyspnea with pulmonary infiltrates. He was treated successfully by discontinuing his current medications, including Sai-rei-to, and administering glucocorticoids. Drug lymphocyte stimulation tests showed a positive result for Sai-rei-to alone, and the resumption of other regular drugs did not re-induce the lung injury. Therefore, we diagnosed the patient with Sai-rei-to-induced lung injury. Sai-rei-to is a combination drug that consists of Sho-saiko-to and Gorei-san. This paper briefly reviews drug-induced lung injury caused by Sai-rei-to or its components with a case report.

Efficacy of rebamipide for low-dose aspirin-related gastrointestinal symptoms.

Gastrointestinal symptoms are a problematic issue for patients who take low-dose aspirin for long time. We conducted a pilot study to investigate the efficacy of combination therapy with proton pump inhibitor and rebamipide. This was a prospective, randomized, double-blind, placebo-controlled cross-over study. All the subjects received aspirin 100 mg and omeprazole 20 mg. The subjects were divided into two groups and received either rebamipide 300 mg or placebo, which was prescribed for 4 weeks. The subjects were instructed to record their gastrointestinal symptom rating scale before the study and 1 and 4 weeks after beginning the protocol. These scores of the groups were compared before and after the treatment to evaluate the severity of their symptoms and the number of symptom items present in each group. For the subjects receiving rebamipide, the total prevalence of lower gastrointestinal symptoms was significantly different from the placebo group (p=0.0093) at week 4. No troublesome symptoms were observed in the rebamipide group. Inconclusion, the administration of rebamipide prevented the occurrence of troublesome symptoms, especially lower gastrointestinal symptoms, in patients taking aspirin and omeprazole. Rebamipide is a candidate drug for combination therapy with proton pump inhibitors to prevent low-dose aspirin-induced gastrointestinal symptoms.

[Mixed type ureteral endometriosis : a case report and a review of the Japanese literature].

Ureteral endometriosis is a rare but important clinical problem that requires early detection and treatment. The urinary tract is affected in approximately 2% of women with endometriosis. Even though the bladder is the most frequent urinary tract organ affected in these patients,the ureter is also affected in 10-40% of the cases, thus requiring immediate clinical attention. The majority of endometrial lesions is typically located in the lower segment of the ureter and is often difficult to differentiate between endometriosis and malignancy. Ureteral endmetriosis should be considered for women with hydronephrosis. In this report we present one clinical case of mixed-type ureteral endometriosis. A 37-year-old woman was referred to our hospital due to left hydronephrosis. Contrast-enhanced CT scan confirmed left hydronephrosis and also showed a solid mass at the left lower ureter. Retrograde pyelography revealed stenosis of the left lower ureter and Renogram revealed severely impaired renal function. Laparoscopic nephroureterectomy was performed. Pathologically, mixed-type endometriosis of the left ureter was diagnosed.

Helicobacter pylori eradication improves gastric atrophy and intestinal metaplasia in long-term observation.

BACKGROUND AND AIM: Helicobacter pylori has been shown to cause atrophic gastritis and intestinal metaplasia (IM), both of which are precancerous lesions. To clarify the mechanism by which H. pylori eradication prevents gastric cancer, we monitored atrophy and IM improvement in gastric mucosa over a long period after H. pylori eradication. METHODS: We monitored 118 patients (72 males, 46 females; mean age 61.3 ± 5.1 years) for a mean of 8.6 years (range 5-13) after successful H. pylori eradication. Biopsy specimens were taken from the greater curvatures of the antrum (A2) and the corpus (B2). RESULTS: Atrophy was significantly decreased in patients with successful H. pylori eradication, both at A2 (from 1.60 ± 0.09 to 1.02 ± 0.08; p < 0.001) and B2 (from 0.71 ± 0.10 to 0.02 ± 0.02; p < 0.001), and IM score was significantly decreased at B2 (from 0.17 ± 0.12 to 0.00 ± 0.00; p < 0.05), but not at A2 (from 0.60 ± 0.11 to 0.43 ± 0.09; p = NS). In patients without successful eradication, however, there were no differences in scores over time. Before eradication, IM score was significantly higher in males than in females, both at A2 (0.81 ± 0.12 vs. 0.25 ± 0.10; p < 0.05) and B2 (0.32 ± 0.08 vs. 0.07 ± 0.04; p < 0.05). CONCLUSION: We were able to monitor the gastric mucosa for a mean of 8.6 years after H. pylori eradication, the longest period reported to date. Significant improvements in gastric atrophy and IM after H. pylori eradication may decrease the risk of gastric cancer.

Multiple functions of PBRM-1/Polybromo- and LET-526/Osa-containing chromatin remodeling complexes in C. elegans development.

The SWI/SNF-like chromatin remodeling complexes consist of two evolutionarily conserved subclasses, which are characterized by specific accessory components, the OSA/BAF250 and Polybromo proteins. These complexes regulate the expressions of distinct sets of target genes, with some overlap, and the regulatory components are thought to determine the target specificity for each complex. Here we isolated C. elegans mutants of the genes for the OSA/BAF250 homolog, LET-526, and the Polybromo homolog, PBRM-1, in a screen for the abnormal asymmetric cell division phenotype. In the asymmetric division of the T cell, both LET-526 and PBRM-1 regulated the asymmetric expression of psa-3/Meis between the T cell daughters, suggesting that the two subclasses share the same target. In the gonad, PBRM-1 regulated gonad primordium formation during embryogenesis, whereas LET-526 was required post-embryonically for distal tip cell (DTC) production from the gonad primordium, suggesting that these proteins have distinct targets for DTC development. Thus, the same cellular process is regulated by LET-526 and PBRM-1 in the asymmetric division of the T cell, but they regulate distinct cellular processes in the gonad morphogenesis. Although disruption of the core component PSA-1 or PSA-4 caused similar defects in the gonad and T cell, it also caused early embryonic arrest, which was not observed in the let-526, pbrm-1, or let-526 pbrm-1 double mutants, suggesting that some targets of SWI/SNF-like complexes do not require LET-526 or PBRM-1 for their transcription. Our results show that the target selection by SWI/SNF-like complexes during C. elegans development is intricately regulated by accessory components.