Biomedical subjects

Hiroshi Kitamura

Publications and source records attributed to Hiroshi Kitamura.

At least 19 recordsLinked to original sources

PubMed2007

Mammalian Polycomb Scmh1 mediates exclusion of Polycomb complexes from the XY body in the pachytene spermatocytes.

The product of the Scmh1 gene, a mammalian homolog of Drosophila Sex comb on midleg, is a constituent of the mammalian Polycomb repressive complexes 1 (Prc1). We have identified Scmh1 as an indispensable component of the Prc1. During progression through pachytene, Scmh1 was shown to be excluded from the XY body at late pachytene, together with other Prc1 components such as Phc1, Phc2, Rnf110 (Pcgf2), Bmi1 and Cbx2. We have identified the role of Scmh1 in mediating the survival of late pachytene spermatocytes. Apoptotic elimination of Scmh1(-/-) spermatocytes is accompanied by the preceding failure of several specific chromatin modifications at the XY body, whereas synapsis of homologous autosomes is not affected. It is therefore suggested that Scmh1 is involved in regulating the sequential changes in chromatin modifications at the XY chromatin domain of the pachytene spermatocytes. Restoration of defects in Scmh1(-/-) spermatocytes by Phc2 mutation indicates that Scmh1 exerts its molecular functions via its interaction with Prc1. Therefore, for the first time, we are able to indicate a functional involvement of Prc1 during the meiotic prophase of male germ cells and a regulatory role of Scmh1 for Prc1, which involves sex chromosomes.

Animals↗

PubMed2006

IL-21-induced Bepsilon cell apoptosis mediated by natural killer T cells suppresses IgE responses.

Epidemiological studies have suggested that the recent increase in the incidence and severity of immunoglobulin (Ig)E-mediated allergic disorders is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination; however, the underlying mechanisms remain uncertain. Here, we demonstrate that natural killer T (NKT) cells in mice and humans play a crucial role in the BCG-induced suppression of IgE responses. BCG-activated murine Valpha14 NKT cells, but not conventional CD4 T cells, selectively express high levels of interleukin (IL)-21, which preferentially induces apoptosis in Bepsilon cells. Signaling from the IL-21 receptor increases the formation of a complex between Bcl-2 and the proapoptotic molecule Bcl-2-modifying factor, resulting in Bepsilon cell apoptosis. Similarly, BCG vaccination induces IL-21 expression by human peripheral blood mononuclear cells (PBMCs) in a partially NKT cell-dependent fashion. BCG-activated PBMCs significantly reduce IgE production by human B cells. These findings provide new insight into the therapeutic effect of BCG in allergic diseases.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Diffuse hepatoid adenocarcinoma in the peritoneal cavity.

Hepatoid adenocarcinoma (HAC) is a rare tumor that occurs mostly in the gastrointestinal tract. We encountered a 68-year-old man suffering from HAC with severe ascites. The serum and ascitic alpha-fetoprotein (AFP) levels were markedly high. Computed tomography (CT) revealed that multiple nodular lesions were disseminated only in the peritoneal cavity. Based on laparoscopic and histological findings, this tumor was diagnosed as diffuse HAC which was developed primarily in the peritoneum. Despite treatments with appropriate chemotherapy, he died six months after diagnosis. According to literature updates, this is the first documented case of diffuse HAC which developed in the peritoneum.

Adenocarcinoma↗

PubMed2006

Establishment of lymphotoxin beta receptor signaling-dependent cell lines with follicular dendritic cell phenotypes from mouse lymph nodes.

Follicular dendritic cells (FDCs) have been shown to play a crucial role in the positive selection of high-affinity B cells that are generated by somatic hypermutation in germinal center (GC). Because of technical difficulties in preparing and maintaining pure FDCs, a role for FDCs in this complicated process has not been fully elucidated. In this study, we established a cell line designated as pFL that retained major FDC phenotypes from a three-dimensional culture of mouse lymph node cells. pFL cells proliferated slowly in response to an agonistic anti-lymphotoxin beta receptor mAb and TNF-alpha. A more rapidly growing clone, named FL-Y, with similar requirements for growth was isolated from a long-term culture of pFL. Analysis of surface markers in these two cell lines by immunostaining, flow cytometry, and DNA microarray revealed the expression of genes, including those of CD21, FcgammaRIIB, lymphotoxin beta receptor, ICAM-1, VCAM-1, IL-6, and C4, which have been shown to be characteristic of FDCs. In addition, B cell-activating factor was expressed in these two cell lines. At the pFL or FL-Y:B cell ratio of 1:100, the cell lines markedly sustained B cell survival and Ab production during 2 wk of culture, while most B cells collapsed within 1 wk in the absence of the FDC-like cells. Interestingly, expression of typical GC markers, Fas and GL-7, was notably augmented in B cells that were cocultured with Th cells on these two cell lines. Thus, pFL and FL-Y cells may be useful for providing insight into the functional role for FDCs in GC.

Animals↗

PubMed2006

Removal of more lymph nodes may provide better outcome, as well as more accurate pathologic findings, in patients with bladder cancer--analysis of role of pelvic lymph node dissection.

OBJECTIVES: To examine the role of pelvic lymph node dissection (PLND) in patients who underwent radical cystectomy for bladder cancer. The diagnostic and therapeutic role of PLND is still controversial in bladder cancer. The extent of PLND and the necessary number of lymph nodes to remove have not been defined. METHODS: This retrospective review included 146 patients with refractory superficial and muscle-invasive disease treated with radical cystectomy, regional PLND (internal iliac, external iliac, and obturator nodes) and urinary diversion from January 1990 to December 2002. RESULTS: Lymph node metastases were detected in 25 patients (17.1%). The average number of nodes removed in the node-positive and node-negative patients was 13.9 and 14.2, respectively. Although no difference was found in disease-specific survival in the node-negative patients when stratified by the number of nodes removed (13 or more versus less than 13), a significant survival advantage was found in the node-positive patients with 13 or more nodes removed versus less than 13 nodes removed. The patients with four or more positive nodes had a worse outcome than those with less than four positive nodes. However, even if the patients had less than four positive nodes, the survival of patients with less than 13 nodes removed was as poor as that of the patients with four or more positive nodes. CONCLUSIONS: In this series, the removal of 13 or more pelvic lymph nodes was essential for more accurate pathologic examination to predict patient outcome and contributed to an increased chance of survival.

Adult↗

PubMed2006

Human thioredoxin-1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production.

BACKGROUND & AIMS: Thioredoxin-1 (TRX) is a small multifunctional protein with antioxidative and redox-regulating functions. In this study, we investigated the significance of TRX in patients with inflammatory bowel disease (IBD) and the ability and mechanism to ameliorate experimental colitis. METHODS: Serum TRX and macrophage migration inhibitory factor (MIF) levels were measured in patients with IBD. The effects of TRX were evaluated in a dextran sulfate sodium (DSS)-induced colitis model by comparing TRX-overexpressing transgenic (TRX-TG) and control mice. We further evaluated the effect of recombinant human TRX (rhTRX) administration on DSS-induced colitis and colonic inflammation of interleukin (IL)-10 knockout (IL-10 KO) mice. Colonic inflammation was examined clinically and histologically. Proinflammatory cytokine levels were examined in colonic tissues, and MIF levels were measured in colonic tissues and sera in mice. The effect of TRX on MIF production was also analyzed in vitro. RESULTS: Serum TRX and MIF levels were significantly higher in patients with IBD than normal controls, and TRX levels correlated with disease activity. TRX significantly ameliorated DSS-induced colitis and colonic inflammation of IL-10 KO mice. Increase of tumor necrosis factor-alpha and interferon-gamma in colonic tissues was significantly suppressed in TRX-TG mice compared with wild-type mice. MIF levels in colonic tissues and sera were significantly lower in TRX-TG mice than in wild-type mice, irrespective of DSS administration. Anti-TRX treatment exacerbated DSS-induced colitis. In vitro studies demonstrated that rhTRX suppressed MIF production in human monocyte cells. CONCLUSIONS: TRX might have a potential as a novel therapeutic agent for the treatment of IBD.

Animals↗

PubMed2006

Effect of human leukocyte antigen class I expression of tumor cells on outcome of intravesical instillation of bacillus calmette-guerin immunotherapy for bladder cancer.

PURPOSE: Various immune systems play important roles in the clinical efficacy of intravesical Bacillus Calmette-Guerin (BCG) instillation for bladder cancer. However, human leukocyte antigen (HLA) class I molecules on tumor cells and various immune system cells infiltrating to/around the tumor have not been evaluated, although many prognostic factors, including clinical, pathologic, and molecular ones, have been investigated. The aim of this study was to determine immunologic prognostic factors of BCG immunotherapy for bladder cancer. EXPERIMENTAL DESIGN: Immunohistochemical staining for HLA class I, CD4, CD8, CD20, CD68, TIA-1, S-100, and FOXP3 was carried out on specimens from 30 patients who underwent BCG immunotherapy from whom both pretreatment and posttreatment specimens were obtained. We did univariate and multivariate analyses of factors affecting recurrence-free survival. The positive, weakly positive, and negative groups of cells that infiltrated to/around the tumor were compared with recurrence-free survival using the Kaplan-Meier method and log-rank test. RESULTS: HLA class I was a significant prognostic factor both in univariate and multivariate analyses. The 5-year recurrence-free survivals of the patients with HLA class I-positive tumors and those with HLA class I-negative tumors were 55.7% and 19.1%, respectively (P = 0.019). There was a significant association between infiltration of CD8, CD20, and CD68-positive cells after BCG therapy and therapeutic effects. CONCLUSIONS: Our data show that expression of HLA class I molecules on tumor cells contributes significantly to the therapeutic effect of BCG immunotherapy for bladder cancer. It is suggested that CTLs may be one of main effectors in this therapy.

Adjuvants, Immunologic↗

PubMed2006

Modified and bilateral retroperitoneal lymph node dissection for testicular cancer: peri- and postoperative complications and therapeutic outcome.

OBJECTIVE: To characterize surgical invasiveness and morbidity and to verify therapeutic efficacy, we reviewed perioperative and postoperative courses and therapeutic outcomes of patients who underwent retroperitoneal lymph node dissection (RPLND) for testicular germ cell cancers. METHODS: The study included 31 patients who underwent retroperitoneal lymph node dissection. A modified template was used if retroperitoneal metastasis was limited to the areas below the level of the renal hilus and above the level of the inferior mesenteric artery (IMA). Perioperative and postoperative courses and complications were reviewed as well as therapeutic outcomes. RESULTS: Overall, 27 perioperative and postoperative complications were observed in 15 patients (48.4%). Superficial surgical site infection and paralytic ileus were seen most frequently. All of them were resolved without special additional treatments; however, patients who underwent retrocrural dissection had a tendency to have severe symptomatic complications such as chylothorax, phrenic nerve palsy and orthostatic hypotension. Antegrade ejaculation was preserved in 94.1% of patients with modified template dissection, whereas no patients with additional dissection below the level of the IMA had the function preserved. One patient (3.2%) developed a postoperative recurrent disease in the retroperitoneum, which was outside the dissection field, as well as in the mediastinum. CONCLUSIONS: Although RLND had high morbidity, most peri- and postoperative complications were manageable conservatively. Modified template dissection enabled patients to preserve antegrade ejaculation without compromising its therapeutic efficacy, if the disease extension allowed us to use the template.

Adolescent↗

PubMed2006

Expression and antigenicity of survivin, an inhibitor of apoptosis family member, in bladder cancer: implications for specific immunotherapy.

OBJECTIVES: To assess the expression of survivin in transitional cell carcinoma of the bladder and to study whether survivin is a transitional cell carcinoma-specific antigen that could be a target for immunotherapy. Survivin, an inhibitor of apoptosis family member, has been reported to be expressed in various cancers but not in normal adult tissues. METHODS: Immunohistochemical staining for survivin and human leukocyte antigen (HLA) class I was performed on specimens from 88 patients who underwent transurethral resection and radical cystectomy. To determine whether survivin was recognized as a tumor antigen by the host immune system, we assessed anti-survivin antibodies in the sera of 52 patients and 18 healthy volunteers with an enzyme-linked immunosorbent assay using recombinant survivin. RESULTS: Survivin and HLA class I were expressed in 77 (87.5%) and 59 (67.0%) of the 88 bladder cancer specimens, respectively, and 56 (63.6%) expressed both survivin and HLA class I. The absorbance values of anti-survivin antibodies in patients with bladder cancer were significantly greater than those in the healthy volunteers. A relationship was found between the level of serum anti-survivin antibodies and the staining intensity of survivin in the specimen. CONCLUSIONS: Survivin is expressed in carcinoma of the bladder with high sensitivity. It is suggested that survivin is presented on HLA class I molecules of antigen-presenting cells in 64% of patients with bladder cancer. Therapeutic targeting of survivin in bladder cancer is a future possibility.

Adult↗

PubMed2006

Kinetic substituent and solvent effects in 1,3-dipolar cycloaddition of diphenyldiazomethanes with fullerenes C60 and C70: a comparison with the addition to TCNE, DDQ, and chloranil.

Kinetics of 1,3-dipolar cycloaddition of a series of meta- and para-substituted diphenyldiazomethanes (DDMs) with fullerenes C60 and C70 as dipolarophiles have been investigated in toluene at 30 degrees C. Fullerene C60 was ca. 1.5 times more reactive than C70. The rate constants (k) for the primary [3 + 2] additions increased with the increase of the electron-releasing ability of the meta and para substituent. The log k/k0 values were well correlated by the Yukawa-Tsuno (Y-T) equations with the smaller negative rho values (-1.6 and -1.7 for C60 and C70) and the reduced resonance reaction constants r (0.22 and 0.17) compared to similar reactions of common acceptors, TCNE, DDQ, and chloranil (CA). The plots of log k (acceptor) versus log k (C60) as reference gave good regression equations and the slopes became larger in the order of TCNE > DDQ > CA > C70 > or = C60. The rates were also found to decrease with the increase of solvent polarity due to the ground-state solvation of fullerenes. However, the relative reactivity of these acceptors toward the unsubstituted DDM increased in the order of DDQ > C60 > or = C70 > TCNE > CA. The unexpected higher reactivity of fullerenes was interpreted in terms of the inherent steric strain by the pyramidalization of the sp2 C-atoms as well as the shorter [6,6] bonds with larger pi-electron densities.

Journal Article↗

PubMed2006

Construction of quantitative proteome reference maps of mouse spleen and lymph node based on two-dimensional gel electrophoresis.

Quantitative features of the proteome are extremely useful for studying cellular processes at a molecular level. In this study, we attempted to construct quantitative reference proteome maps of the mouse spleen and lymph node based on 2-DE followed by protein identification using MS. We analyzed more than 1000 spots on the 2-DE images and consequently were able to determine that 919 spots were derived from 328 different genes. To obtain statistically reliable information of the protein levels from these 2-DE images, we measured the volumes of the respective spots on 2-DE images obtained by four to six independent experimental runs. These measurements were used to calculate the variability of the volumes of the respective spots on 2-DE following subcellular fractionation, which enabled us to discriminate differentially produced proteins from those within the range of intrinsic variability. More importantly, while the 2-DE data have been traditionally collected in a gel image-based manner, the resultant quantitative 2-DE data could be analyzed using the same procedure as that for mRNA expression profiles. This greatly assists in bridging the gap between the analyses of transcriptomes and proteomes and enables the integration of this data on the same informational platform.

Amino Acid Sequence↗

PubMed2006

Early bladder cancer: concept, diagnosis, and management.

Recent evidence on molecular pathways helps us to understand the pathogenesis of bladder cancer. However, the molecular mechanisms of recurrence of the disease and progression into muscle-invasive disease are not fully understood. The diagnostic accuracy and specificity of innovative markers for detection of the disease currently available in the clinical setting are still far from the level where cystoscopy would not be needed. Although risk factors for progression to muscle-invasive disease have been identified, we still cannot predict accurately the clinical behavior of superficial bladder cancer. In this review article, we summarize recent evidence on molecular pathogenesis, risk factors for recurrence and progression, urine markers for detection, and treatments in superficial bladder cancer.

Biomarkers, Tumor↗

PubMed2006

A case of "pure" preeclampsia with nephrotic syndrome before 15 weeks of gestation in a patient whose renal biopsy showed glomerular capillary endotheliosis.

A 35-year-old Japanese woman for whom a previous health checkup showed normal blood pressure and urinalysis results without serological abnormalities developed nephrotic syndrome with severe hypertension at 15 gestational weeks. The renal biopsy performed at 17 weeks of gestation showed severe glomerular capillary endotheliosis. By means of electron microscopy, no electron-dense deposits were observed in glomeruli, and foot-process arrangement was normal. Histological findings indicated the patient's glomerular damage was caused by the mechanisms of preeclampsia. The patient underwent an elective abortion at 18 weeks of gestation. Clinical abnormalities vanished completely within 3 months after the elective abortion, which provided additional evidence that proteinuria and hypertension were caused purely by pregnancy. In general, the term preeclampsia refers to new onset of hypertension and proteinuria after 20 weeks of gestation. When proteinuria or hypertension is newly observed before 20 weeks of gestation, they are practically associated with triploidy, trophoblastic disease, or antiphospholipid syndrome. However, our case was not associated with them. Therefore, we called this case "pure" preeclampsia. We confirm the notion for the first time that preeclampsia associated with glomerular capillary endotheliosis can occur before 20 weeks of gestation. In addition, this report describes the earliest onset of preeclampsia compared with previously published reports. We also discuss causes of preeclampsia in early gestation and refer to the issue of the application of renal biopsies during pregnancy.

Abortion, Induced↗

PubMed2006

Identification of a novel autoantibody against pancreatic secretory trypsin inhibitor in patients with autoimmune pancreatitis.

OBJECTIVES: Although autoimmune pancreatitis (AIP) has been recently recognized as a new disease entity of chronic pancreatitis, the clinical diagnosis of the disease remains disputed. Autoantibodies against carbonic anhydrase II and lactoferrin are detected in most patients with AIP, but not in about 10%. We undertook this study to determine whether additional autoantibodies are present in the serum level of AIP patients. METHODS: We recruited 26 patients with AIP for the study. For comparison, we also recruited 53 patients with various pancreatic diseases and 12 healthy subjects. We immunoscreened human pancreatic cDNA library using patients' sera. Positive clones were analyzed by DNA sequencing and were constructed into a pGEX-4T-1 expression vector. The recombinant proteins were used as antigens in enzyme-linked immunosorbent assay to screen the subjects' sera for autoantibodies. RESULTS: We cloned a cDNA encoding the pancreatic secretory trypsin inhibitor (PSTI). Among 26 patients with AIP, autoantibodies against PSTI were significantly positive in 11 (42.3%) by western blotting and in 8 (30.8%) by enzyme-linked immunosorbent assay, respectively. However, none of control subjects was positive for anti-PSTI antibodies. CONCLUSIONS: These findings suggest that PSTI may be related to the pathogenesis of AIP, and autoantibodies against PSTI can be a useful diagnostic marker for the disease.

Aged↗

PubMed2006

Acute cellular rejection occurring on the first day after living-related renal transplantation: a case report.

The patient was a 52-year-old man who received an ABO-compatible but non-identical living-related renal graft from his wife. The graft started to function immediately and the urine output rate was over 100 mL/h. However, this was gradually decreased within 12 h after transplantation. On day 2 post-transplant, the urine output almost stopped. A biopsy specimen revealed lymphocyte dominant cellular infiltration in the interstitium with mild tubulitis (according to Banff's schema grade Ia) and no C4d deposition in peritubular capillaries. Immunohistochemistry disclosed T-cell infiltration. The patient responded to a course of steroid pulse therapy (five days of 500 mg of methylprednisolone). The urine output gradually increased and the level of serum creatinine gradually decreased to 1.0 mg/dL. These clinical and histological findings strongly suggested acute cellular rejection. Acute cellular rejection occurring within 24 h post-transplant is extremely rare. In the present case acute cellular rejection occurred within the first day after living-related renal transplantation and was strongly suspected from histopathological findings in the allograft biopsy specimen.

ABO Blood-Group System↗

PubMed2006

Symposium: evaluating the reproducibility of pathological diagnosis using the 1997 Banff classification update.

The purpose of this symposium was to evaluate the reproducibility of a histological diagnosis in renal allograft nephropathy according to the Banff classification. Seven transplant nephrologists and pathologists independently diagnosed the same glass slide specimens from 10 cases (five cases of acute rejection and five cases of chronic allograft nephropathy). Their diagnoses were collated and analyzed for the reproducibility of histological diagnosis. Consequently, several issues that hinder diagnostic reproducibility were identified.

Biopsy↗

PubMed2006

Cockayne syndrome with recurrent acute tubulointerstitial nephritis.

A 12-year-old girl, who had been diagnosed as having Cockayne syndrome (CS), was admitted for emaciation and dehydration. On admission the patient had mild chronic renal failure (glomerular filtration rate: GFR 50 mL/min) and hyperuricemia. After rehydration, allopurinol was commenced for her hyperuricemia. Then, her renal function rapidly deteriorated (GFR 20 mL/min) with enhancement of proximal tubular dysfunction and hypertension. A renal biopsy showed that the patient had acute tubulointerstitial nephritis (ATIN). Based on this diagnosis, allopurinol was stopped and prednisolone was started (2 mg/kg per day), following which the renal tubular function improved. However, the proteinuria intensified to become nephrotic syndrome. After 1 month the patient developed a gastric ulcer. Famotidine was commenced but GFR deteriorated and renal proximal tubular dysfunction re-occurred. The renal pathology was evaluated by referring to the previous reports of renal pathology in CS. It is suggested that rapid deterioration of the renal function in CS patients might be the result of ATIN. In addition, the present nephrotic syndrome seemed to be accompanied by ATIN, as in other reports.

Acute Disease↗

PubMed2006

Prevalence of prostatitis-like symptoms in Japanese men: Population-based study in a town in Hokkaido.

AIM: To determine the prevalence of prostatitis-like symptoms in Japanese men living in one town. METHODS: A cross-sectional and population-based study was performed in a town that had 6385 men aged from 20 to 79 years. We sent two questionnaires, the validated Japanese version of the National Institutes of Health Chronic Prostatitis Symptom Index and the International Prostate Symptom Score (I-PSS) with questions about individual medical information, to 1424 randomly selected community-indwelling men. Subjects were defined as having prostatitis-like symptoms if they complained of perineal and/or ejaculatory pain or discomfort and their total pain score was four or greater. RESULTS: A total of 512 men (36%) responded completely to the questionnaires. Of the 512 responders, 25 men (4.9%) were identified as having prostatitis-like symptoms. Prevalence of symptoms was the same in men aged younger than 50 years (5.0%) as those 50 years and older (4.8%). The I-PSS score was 10.8 in men with prostatitis-like symptoms, which was higher than in those without symptoms. CONCLUSIONS: Prevalence of prostatitis-like symptoms was 4.9% in randomly selected men. International comparison of prevalence of the symptoms may contribute to further understanding of chronic prostatitis.

Adult↗