Population-based study of asymptomatic infection with Chlamydia trachomatis among female and male students.

There are few epidemiological studies of asymptomatic chlamydial infection among students in non-medical settings with minimal bias and improved accuracy; thus, useful data from screening among students are limited. We aimed to obtain accurate epidemiological information about asymptomatic chlamydial infection among students in non-medical settings. A population-based cross-sectional survey of 10,440 >or=18-year-old asymptomatic students who volunteered for a urine screening test for chlamydia was conducted. The prevalences of asymptomatic infection were 9.5% for women and 6.7% for men. Multivariate analysis revealed the risk factors to be a lifetime history of >or=4 sexual partners for women (odds ratio [OR] 3.17) and inconsistent condom use for men (OR 4.18). For both sexes, younger age at first intercourse was associated with a higher rate of inconsistent condom use. This study produced accurate epidemiological information on asymptomatic chlamydial infection. These results may contribute to the establishment of preventive countermeasures against such infection.

Prevalence of Mycoplasma genitalium among female students in vocational schools in Japan.

OBJECTIVE: In Japan it was reported that about 9% of sexually active female teenagers had Chlamydia trachomatis. Most of them were asymptomatic, which may lead to continuing spread of the infection. Like C trachomatis, Mycoplasma genitalium is a pathogen in male non-gonococcal urethritis. However, few studies of the prevalence of M genitalium in the general population have been reported. The objective of this study was to determine the prevalence of M genitalium infection among younger females and to determine risk factors for this infection. METHODS: The study was conducted between October 2005 and January 2006 using first voided urine specimens and questionnaires from female students of three vocational schools in the Miyazaki prefecture, Japan. C trachomatis was detected with Amplicor PCR. M genitalium was detected with inhibitor controlled real-time TaqMan PCR detecting the MgPa adhesion gene and with a PCR detecting the 16S rRNA. Risk factors associated with infection of M genitalium or C trachomatis were analysed with Fisher's exact test. RESULTS: Among 298 female, 249 (84%) had had experience of sexual intercourse. The prevalence of M genitalium was 2.8% (95% CI 0.76% to 4.86%) and the prevalence of C trachomatis was 8.8% (95% CI 5.31% to 12.36%). CONCLUSIONS: The risk factors of infection with M genitalium were more than five lifetime sexual partners and co-infection with C trachomatis.

Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma.

Activation of hepatocyte growth factor/scatter factor (HGF/SF) in the extracellular milieu is a critical limiting step in the HGF/SF-induced signaling pathway mediated by Met receptor tyrosine kinase, which has potentially important roles in tumor biology and progression. However, little is known concerning the regulation of HGF/SF activation in tumors. Immunoblot analysis revealed that the activation of HGF/SF was enhanced significantly in colorectal carcinoma tissues compared with the corresponding normal mucosa. Serum-free conditioned media of cultured human colorectal carcinoma cell lines contained HGF/SF-activating activity, and the addition of a single-chain precursor form of HGF/SF to the serum-free culture of these cells resulted in HGF/SF-dependent modulation of cellular phenotypes, such as increased scattering and enhanced secretion of vascular endothelial growth factor. This processing activity was enhanced by thrombin treatment but was inhibited significantly by a neutralizing antibody against HGF activator (HGFA), a factor XIIa-like serine proteinase believed to be expressed mainly in the liver. The activity was also inhibited by recombinant HGFA inhibitor type 1 (HAI-1). The presence of HGFA mRNA and secretion of HGFA protein were confirmed in the cell lines. Therefore, extrahepatic expression of HGFA in the colorectal carcinoma cells could be responsible for the single-chain HGF/SF-processing activity of the cells. We examined the expression of HGFA and HAI-1 in human colorectal mucosa and adenoma-carcinoma sequence. Immunohistochemically, HGFA was stained weakly in the normal enterocytes, and immunoreactivity was increased modestly in the neoplastic differentiation. The subcellular localization of HGFA immunoreactivity was altered in carcinoma cells showing basal or cell-stroma interface staining patterns, compared with normal and adenoma cells with a supranuclear or apical staining pattern. In contrast to HGFA, the expression of HAI-1 decreased significantly in carcinoma cells relative to the adjacent normal or adenoma cells, indicating that the net balance between HGFA and HAI-1 shifts in favor of HGFA in carcinomas. In fact, pro-HGFA and the active form of HGFA proteins increased in carcinoma tissue compared with the corresponding normal mucosa. It was concluded that HGFA is expressed in colorectal mucosa and tumors and could be involved in the activation of HGF/SF in colorectal carcinomas. Therefore, the balance between HGFA and HAI-1 could play an important role in the regulation of HGF/SF activity in colorectal carcinomas.

Mouse hepatocyte growth factor activator inhibitor type 1 (HAI-1) and type 2 (HAI-2)/placental bikunin genes and their promoters.

Hepatocyte growth factor (HGF) activator inhibitor type 1 (HAI-1) and type 2 (HAI-2) were recently discovered as specific inhibitors of HGF activator. Each of them contains two Kunitz-type serine protease inhibitor domains and a transmembrane domain, so that their overall structures are similar to each other. In this study, mouse genes encoding HAI-1 and HAI-2 were cloned by screening of a mouse genomic bacterial artificial chromosome library and by polymerase chain reaction of mouse genomic DNA, respectively. The genes (mHAI-1 and mHAI-2) were defined to consist of 11 and eight exons spanning 11 kbp and 9.5 kbp, respectively. Neither a TATA nor CAAT box was found in 5'-flanking regions of both genes and no apparent homologous portion was observed between mHAI-1 and mHAI-2 promoter regions. Promoter assay of mHAI-1 and human HAI-1 revealed that the potential binding sites of a complex of Egr-1-3 and Sp1, which was well-conserved between human (-42 to -58) and mouse (-44 to -57), might be a key portion of its transcriptional regulation to function as not only house-keeping but also early responsive genes.

Mouse hepatocyte growth factor activator gene: its expression not only in the liver but also in the gastrointestinal tract.

A cDNA encoding mouse hepatocyte growth factor activator (HGFA) has been cloned by RT-PCR, based on the screening result from the database of expressed sequence tags. Subsequently, its gene was cloned from a mouse genomic bacterial artificial chromosome library using the cDNA as a probe. Sequencing analysis revealed that mouse HGFA protein deduced from the cDNA, similar to its human and rat counterparts, has two epidermal growth factor-like domains, type 1 and 2 fibronectin homology domains, a single kringle domain and a catalytic domain of serine proteinase, and the gene consists of 14 exon spanning approximately 7.5 kb. Interestingly, mouse HGFA mRNA was detected not only in the liver but also in the gastrointestinal tract by RNA blot analysis. Since hepatocyte growth factor (HGF) is up-regulated in the damaged gastrointestinal mucosa, our present data suggest that HGFA might activate proHGF directly in the gastrointestinal mucosa and play an important role in wound repair throughout the gastrointestinal tract.

Simultaneous up-regulation of urokinase-type plasminogen activator (uPA) and uPA receptor by hepatocyte growth factor/scatter factor in human glioma cells.

Several lines of evidence indicate that hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, c-Met, may play an important role in progression of human glioma. In this study, effects of HGF/SF on urokinase- type plasminogen activator (uPA)-mediated proteolysis network were examined in c-Met-positive human glioma cell lines. Treatment of the glioma cells with various concentrations of HGF/SF resulted in an enhanced secretion of uPA proteins accompanying increased transcription of uPA mRNA in a dose dependent fashion. The levels of uPA receptor (uPAR) mRNAs were also elevated simultaneously upon HGF/SF stimulation, and the cell-surface associated uPA activity was also elevated by the treatment. Since concomitant expression of HGF and its receptor c-Met are frequently observed in malignant gliomas, these results suggest that HGF/SF participates in invasive process of malignant glioma cells not only by its motility-stimulating activity but also through enhanced degradation of the extracellular matrix induced by autocrine activation of uPA proteolysis network.

Conserved expression of hepatocyte growth factor activator inhibitor type-2/placental bikunin in human colorectal carcinomas.

Hepatocyte growth factor activator inhibitor type 2 (HAI-2) was recently identified as a potent inhibitor of hepatocyte growth factor activator. It was also independently reported as placental bikunin (PB) and as a protein over-expressed in pancreatic cancer. The expression of HAI-2/PB was analyzed in human normal colon mucosa, adenomas, and carcinomas. HAI-2/PB mRNA was consistently expressed in the colorectal mucosa. The expression was conserved in the neoplastic colorectal mucosa, and no relationship was found between HAI-2/PB mRNA levels and tumor stages. Moreover, 13 out of 14 colorectal carcinoma cell lines expressed HAI-2/PB mRNA. Immunohistochemically, HAI-2/PB proteins were predominantly stained beneath the apical surface of normal enterocytes. In tumor tissues, rather disarranged intracytoplasmic granular staining was observed. The HAI-2/PB immunoreactivity was well conserved in the colonic adenoma-carcinoma sequence, and this protein may have important unknown function in the intestinal mucosa.

Pericellular activation of hepatocyte growth factor/scatter factor (HGF/SF) in colorectal carcinomas: roles of HGF activator (HGFA) and HGFA inhibitor type 1 (HAI-1).

Activation of hepatocyte growth factor/scatter factor (HGF/SF) is a critical limiting step in the HGF/SF-induced signaling pathway mediated by MET receptor tyrosine kinase. Although HGF/SF-MET signaling could have potentially important roles in the invasive growth of tumors and tumor angiogenesis, little is known about the regulation of HGF/SF activation in the tumor tissues. This activation occurs in the extracellular milieu caused by proteolytic cleavage at the bond between Arg194-Val195 in the single-chain HGF precursor to generate the active two-chain heterodimeric form. Here we show that activation of HGF/SF is significantly enhanced in colorectal carcinoma tissues compared with normal colorectal mucosa, and HGF activator (HGFA), a recently identified factor XII-like serine proteinase, is critically involved in this process. Furthermore, we also show that HGF activator inhibitor type 1 (HAI-1) should have an important regulatory role in the pericellular activation of HGF/SF having diverse roles acting as a cell surface specific inhibitor of active HGFA and a reservoir of this enzyme on the cell surface. The latter property might paradoxically ensure the concentrated pericellular HGFA activity in certain cellular conditions in which shedding of HAI-1/HGFA complex from the plasma membrane is upregulated.

[Recurrence of vesicoureteral reflux detected 19 years after ureterocystoneostomy: a case report].

A 21-year-old male, who had been operated on for bilateral vesicoureteral refluxes (VURs) with bilateral ureterocystoneostomy (Politano-Leadbetter's method) 19 years before, was admitted to our hospital due to recurrent VUR. Since the former operation, he had undergone voiding cystography (VCUG) twice for two years, and no refluxes were found. Moreover, no evidence of upper urinary tract deterioration was found by either intravenous pyelography (IVP) or renal ultrasound scanning taken the year before this admission. Nineteen years after the operation, the dilation of the left lower ureter was found on IVP and, consequently, he suffered from pyelonephritis. The VCUG revealed the recurrence of left VUR. Because of his allergic reaction to collagen, we again performed left ureterocystoneostomy (Politano-Leadbetter's method). At three months postoperatively, there was no VUR found on VCUG.

[Acute renal failure due to over-infusion in a child with bilateral obstruction of the pyeloureteral junction].

A 2-year-old boy was hospitalized with the chief complaint of oliguria and dyspnea. Bilateral hydronephrosis and obstruction of the pyeloureteral junction were detected by ultrasonography. Pulmonary edema was also found on chest radiographs. The clinical diagnosis was acute post renal failure due to bilateral pyeloureteral obstruction and pulmonary edema due to overtransfusion. After we performed bilateral percutaneous nephrostomy, the patient recovered from renal failure and pulmonary edema. Both nephrostomies were removed after we confirmed a non-obstructing pattern using the Whitaker test.

[Small cell carcinoma of the prostate: a case report].

A 81-year-old man was admitted to our department with the chief complaints of pollakisuria and difficulty in voiding. He presented with increased serum PSA level (over 100 ng/ml). We performed biopsy of the prostate and found a moderately differentiated adenocarcinoma. Various urological examinations showed metastases to paraaortic lymph nodes and systemic bones. He was started-on hormonal therapy. Nine months from the start of hormonal therapy, this therapy was effective and the serum PSA level was decreased to 14 ng/ml. Thereafter, the serum PSA level and the tumor volume were increased and he died 29 months from the start of treatment. The autopsy revealed small cell carcinoma with adenocarcinoma of the prostate.

[Indication for surgery of pediatric testicular and funicular hydroceles in view of natural course].

PURPOSE: The purpose of this study is to confirm the definite indication for surgery of pediatric testicular and funicular hydroceles in view of natural course. METHODS: During the period from 1978 to 1994, we encountered 160 hydroceles in 149 pediatric patients. Patients ages ranged from 5 days after birth to 13 years and the mean follow-up periods was 4.7 years. We investigated the indication for surgery of pediatric hydroceles in six points of view: value of an aspiration of hydroceles, of what testicular or funicular or both, communication, size, age and testicular development. RESULTS: Nevertheless, of 160 hydroceles, 66 (41%) were performed an aspiration of hydroceles, the aspiration of hydrocele was ineffective in the majority of patients. Common hydroceles in neonates and infants required no specific treatment, as the majority of hydrocele resolve spontaneously, however surgical treatment was required for a communicating large hydrocele that had been often attacked by aspiration and appeared at older age. Funicular hydroceles were more difficult to spontaneous healing. Ipsilateral testis manifests a well-developed comparing control material. CONCLUSION: The indication for surgery of pediatric hydroceles were as follows: 1) hydroceles complicated by a inguinal hernia or cryptorchidism, 2) hydroceles appeared at older age and not resolved during 2-3 years over, 3) giant communicating funicular and testicular hydroceles present with an/hindrance for daily life.

[A case of intracranial malignant melanoma with increased uptake of IMP in SPECT].

A patient with intracranial malignant melanoma was assessed by 123I-IMP SPECT. Early image, performed 30 minutes after intravenous injection of 111 MBq 123I-IMP, demonstrated an accumulation similar to normal gray matter-defect. Delayed image, performed 4-hour after injection, demonstrated increased accumulation of 123I-IMP. 123I-IMP SPECT, especially delayed scan, was valuable for qualitative diagnosis of intracranial malignant melanoma.

Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.

BACKGROUND: Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown. AIMS: To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue. METHODS: Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells. RESULTS: In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones. CONCLUSION: In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.

Inhibition by iota-carrageenan of the spread of murine cytomegalovirus from the peritoneal cavity to the blood plasma.

The mechanism of iota-carrageenan (i-CAR)-induced protection against murine cytomegalovirus (MCMV) infection of mice was analysed. The virus titres in the target organs on the fourth day correlated with that in the plasma at 1 h after intraperitoneal inoculation of MCMV, irrespective of i-CAR treatment. Pretreatment of mice with i-CAR induced infiltration of polymorphonuclear neutrophils into the peritoneal cavity and inhibition of viral spread from the peritoneal cavity to the plasma. Although the direct relationship of these two phenomena was unclear, the inhibition by i-CAR of viral spread resulted in protection against MCMV infection of mice.

Protective effect of MDP-Lys(L18), a synthetic derivative of muramyldipeptide, on murine cytomegalovirus infection.

The host-mediated antiviral effect of N alpha-(N-acetylmuramyl-L-alanyl-D-isoglutaminyl)-N epsilon-stearoyl-L-lysine [MDP-Lys(L18)] was evaluated in mice against murine cytomegalovirus (MCMV) infection. Mice treated with 800 micrograms of MDP-Lys(L18) on day 2 before the virus challenge survived systemic lethal infection. The protective effect of MDP-Lys(L18) was evidenced by an increase in plaque-forming units per LD50 and a decrease in virus titers in the target organs. No significant difference in the serum interferon level and 2',5'-oligoadenylate synthetase activity was observed among the mice treated with test compounds or phosphate-buffered saline, thought they were higher in MCMV-infected mice than in mock-infected mice. The natural killer (NK) activity was augmented remarkably in the mice treated with MDP-Lys(L18) or its original component, muramyldipeptide (MDP). MDP-Lys(L18) showed neither virocidal nor virostatic activity on MCMV in vitro. Thus, MDP-Lys(L18)-induced resistance against MCMV infection seems to be host-mediated. The MDP-Lys(L18)-induced resistance was not abrogated by the treatment with anti-asialo GM1 serum. The NK activity augmented by MDP-Lys(L18) may contribute to some part of the protective effect, though the augmentation of the NK activity alone did not correlate completely with the protective effect of MDP-Lys(L18). In addition, no difference was observed in anti-MCMV activity among peritoneal exudate cells from mice treated with MDP-Lys(L18), MDP or phosphate-buffered saline. Therefore, another host-mediated factor(s) may also participate in the antiviral effect of MDP-Lys(L18).

Overexpression of intestinal trefoil factor in human colon carcinoma cells reduces cellular growth in vitro and in vivo.

BACKGROUND & AIMS: Intestinal trefoil factor (ITF) has a role in gastrointestinal mucosal integrity and the repair of damaged mucosa. However, little is known about its role in tumors. To analyze the role of ITF in colon carcinomas, overexpression of the ITF gene in colon carcinoma cells was used. METHODS: Human colon carcinoma cell lines LoVo and SW837, expressing no endogenous ITF, and WiDr expressing a low level of ITF were stably transfected with an expression vector harboring human ITF complementary DNA. The effects of ITF overexpression on in vitro growth, morphology in collagen gel, response to epidermal growth factor (EGF), mitogen-activated protein kinase (MAPK) activity, and growth in nude mice were assessed. RESULTS: Overexpression of ITF in LoVo and SW837 resulted in significantly reduced growth in vitro and in vivo. In collagen gels, the ITF-expressing LoVo clones formed smaller, more dispersed colonies. EGF-induced phosphorylation of MAPKs was modestly reduced in the ITF-expressing clones. The growth of WiDr was modestly suppressed only in vivo by ITF overexpression. CONCLUSIONS: Overexpression of ITF suppressed the growth of colon carcinoma cells. ITF may function as an inhibitory factor for the growth of colonic neoplasm.