Loss of Secreted Frizzled-Related Protein-1 expression is associated with poor prognosis in intrahepatic cholangiocarcinoma.

AIMS: Secreted Frizzled-Related Protein-1 (SFRP1) is a well-known negative regulator of the wingless type (Wnt)-ß-catenin pathway and its inactivation plays an important role in the development and progression of many cancers. In this study, we aimed to determine the clinical significance of SFRP1 expression in intrahepatic cholangiocarcinoma (IHCC) and to define the relationship to Wnt-ß-catenin pathway. METHODS: Fifty IHCC patients who had liver resection were enrolled in this study. SFRP1 protein expression was examined by immunohistochemistry in tumor tissues. The patients were divided into two groups: SFRP1 positive (n = 30) and negative (n = 20). Clinicopathological characteristics were analyzed. RESULTS: SFRP1 significantly correlated with curability (Cur A, B vs. C, p = 0.029); and recurrent pattern (intrahepatic vs. extrahepatic, p = 0.010). The negative SFRP1 group had significantly poorer prognosis, and 5-year survival rates were 8.1% of the negative SFRP1 group and 44.6% of the positive SFRP1 group, respectively. Moreover, the disease-free survival rate in the negative SFRP1 group was significantly poorer (p < 0.001). Multivariate analysis revealed that loss of SFRP1served as an independent prognostic factor in IHCC for both overall (HR, 2.923; 95% CI, 1.30-6.56; p = 0.009) and disease-free (HR, 2.631; 95% CI, 1.31-5.27; p = 0.006) survival. In addition, SFRP1 expression negatively correlated to ß-catenin expression (p = 0.005). CONCLUSIONS: Those results suggested that the loss of SFRP1 could be a poor prognostic factor for IHCC, through the Wnt-ß-catenin pathway.

Abundance and diversity of functional genes involved in the degradation of aromatic hydrocarbons in Antarctic soils and sediments around Syowa Station.

Hydrocarbon catabolic genes were investigated in soils and sediments in nine different locations around Syowa Station, Antarctica, using conventional PCR, real-time PCR, cloning, and sequencing analysis. Polycyclic aromatic hydrocarbon ring-hydroxylating dioxygenase (PAH-RHD)-coding genes from both Gram-positive and Gram-negative bacteria were observed. Clone libraries of Gram-positive RHD genes were related to (i) nidA3 of Mycobacterium sp. py146, (ii) pdoA of Terrabacter sp. HH4, (iii) nidA of Diaphorobacter sp. KOTLB, and (iv) pdoA2 of Mycobacterium sp. CH-2, with 95-99% similarity. Clone libraries of Gram-negative RHD genes were related to the following: (i) naphthalene dioxygenase of Burkholderia glathei, (ii) phnAc of Burkholderia sartisoli, and (iii) RHD alpha subunit of uncultured bacterium, with 41-46% similarity. Interestingly, the diversity of the Gram-positive RHD genes found around this area was higher than those of the Gram-negative RHD genes. Real-time PCR showed different abundance of dioxygenase genes between locations. Moreover, the PCR-denaturing gradient gel electrophoresis (DGGE) profile demonstrated diverse bacterial populations, according to their location. Forty dominant fragments in the DGGE profiles were excised and sequenced. All of the sequences belonged to ten bacterial phyla: Proteobacteria, Actinobacteria, Verrucomicrobia, Bacteroidetes, Firmicutes, Chloroflexi, Gemmatimonadetes, Cyanobacteria, Chlorobium, and Acidobacteria. In addition, the bacterial genus Sphingomonas, which has been suggested to be one of the major PAH degraders in the environment, was observed in some locations. The results demonstrated that indigenous bacteria have the potential ability to degrade PAHs and provided information to support the conclusion that bioremediation processes can occur in the Antarctic soils and sediments studied here.

One-stop shop for 3-dimensional anatomy of hepatic vasculature and bile duct with special reference to biliary image reconstruction.

BACKGROUND/AIMS: Three-dimensional CT has become an essential tool for successful hepatic surgery. Up to now, efforts have been made to simultaneously visualize hepatic vasculature and bile ducts. Herein, we introduce a new one-stop shop approach to hepatic 3D-anatomy, using a standard enhanced MDCT alone. METHODOLOGY: A 3D-reconstruction of hepatic vasculature was made using data from contrast enhanced MDCT and SYNAPSE VINCENT software. We identified bile ducts from axial 2D image, and then reconstructed the 3D image. Both hepatic vasculature and bile duct images were integrated into a single image and it was compared with the 3D image, utilized with MRCP or DIC-CT. RESULTS: The first branches of both the right and left hepatic ducts were hand-traced and visualized for all 100 cases. The second branches of these ducts were visualized in 69 cases, and only the right second branch was recognized in 52 cases. Anomalous variations of bile ducts, such as posterior branch joining into common hepatic duct, were recognized in 12 cases. These biliary tract variations were all confirmed by MRCP or DIC-CT. CONCLUSIONS: Our new one-stop shop approach using the 3D imaging technique might contribute to successful hepatectomy as well as reduce medical costs and radiation exposure by omission of MRCP and DIC-CT.

A large-scale study of bacterial contamination of drinking water and its public health impact in Nepal.

Bacterial contamination of drinking water is a major public health in Nepal. A large scale study on contamination of drinking water was done covering all three ecological belts (mountain, hill and Terai) in all five (eastern, central, western, mid-western and far-western) development regions of Nepal during 2009-2011. Of the total 506 water samples studied, one-forth (25.1%; 127/506) were visually turbid. Bacteriologically, 88.5% (448/506) samples were positive for total coliform (TC) whereas 56.5% (286/506) were positive for fecal coliform (FC) (Esch. coli). The TC positive rate ranged from 53.8% in Damak (Jhapa) to 100.0% in different districts. The FC positive rate varied more widely ranging from 10.0% in Bharatpur City (Chitawan) to 100.0% in Baglung Township (Baglung) with over 50.0% in most of the districts (over 75.0% in eight districts). Both TC and FC positive rate were highest in Far-western Development Region (DR). High TC positive rate (96.7%) in Far-western DR was followed by Western DR (93.9%), Eastern DR (89.2%), Central DR (87.0%) and Mid-western DR (74.6%). Highest FC positive rate (65.5%) in Far-western DR was followed by Med-western DR (63.5%), Western DR (55.9%), Central DR (53.2%) and Eastern DR (52.0%). TC positive was highest (90.7%) in hills followed by mountain (89.7%) and Terai (plain) (84.1%) belt. In contrast, FC positive rate was highest (66.2%) in mountain, followed by hills (58.0%) and Terai (49.7%). Of the total 506, 335 were piped tap water, 129 were boring water, 16 natural tap (spout), 16 were well (sallow/deep well) and 10 were mineral/uroguard treated water. TC positive rate was very high (81.2% to 100.0%) in different type water samples (piped tap: 90.1%; boring water: 85.2%; natural spout/tap: 81.2%; well water 100.0% and mineral water/uroguard treated water: 80.0%). FC positive rate ranged from 0.0% in mineral water/uroguard treated water to 93.7% in well water samples. These findings are of serious public health concern with regard to both endemicity and outbreak of waterborne diseases in the country.

Survey of Vibrio cholerae O1 and its survival over the winter in marine water of Port of Osaka.

The survey of Vibrio cholerae O1 in marine area was carried out in the Port of Osaka, Japan in 1987-2001, and 51 V. cholerae O1 strains were isolated. All strains were identified to be of El Tor biotype, Ogawa serotype and classic Ubon Kappa-phage type, and were cholera toxin (CT)-negative and CT gene-negative. In order to clarify certain ecological aspects of V. cholerae O1 in the marine environment of the temperate zone, we performed molecular analysis of the isolated strains using pulsed-field gel electrophoresis (PFGE) with NotI and SfiI restriction enzymes. We found the indistinguishable strains by DNA analysis using PFGE with strains passed for 1 year, and also found the closely related strains with that passed for 3 and 12 years. Those results indicated that V. cholerae O1 can survive over one winter at least, and that it survives in marine water for a long time by undergoing continuous mutation.

[Investigation on zoonosis by disseminating questionnaire to members of medical associations in Kobe and Fukuoka].

With the purpose of studying the involvement of physicians to zoonosis, investigation on the consciousness was performed by disseminating a questionnaire to members of Medical Associations of Kobe City (2,584 members) and Fukuoka City (1,814 members). From the members in Kobe, 1,165 replies were collected (answer ratio: 45.1%) and 774 replies from the members in Fukuoka (answer ratio: 42.7%). About 70-80% of all physicians answering the questionnaire stated that they had examined the patients with infectious diseases at a ratio of less than 10% to a total of patients examined. Among them, 70% of the doctors had asked the patients as to whether or not the patients were keeping pet animals or had traveled overseas recently when infectious diseases was suspected. There were 738 doctors (38.1%) (1,355 cases), who had suspected or made definitive diagnosis on 15 diseases of zoonosis as stipulated in the new Infectious Disease Control Law for the recent 5 years. In all, 365 doctors (18.9%) examined the patients who were suspected to have had an infection from pet animals. The causative animals primarily included dogs, cats, and birds such as parakeet, while monkeys, tortoises, etc. were found in several cases. About one half of the physicians felt that the cases of infectious diseases and zoonosis would increase in the future. In the entry of free opinions relating to the effective measures for the prevention of zoonosis, 712 physicians (39.8%) entered 1,050 proposals. The details of these proposals were: 444 proposals on "administrative measures". 244 on the need of "education" to citizens, and 201 on the importance of "medical management". About 80% of the physicians replied that they would cooperate for the secondary investigation. It appears that the physicians place much expectation on adequate measures against zoonosis. Namely, they expect much on the establishment of a reliable network, i.e. the network of administrative authorities--physicians--veterinarians--pet animal suppliers--pet animal keepers.

Effect of vibration on auditory organ systems in low-birth weight infants treated with high-frequency oscillatory ventilation: 5 year outcome.

BACKGROUND: To determine the effects of vibration exposure caused by high-frequency oscillatory ventilation (HFOV) on the auditory organ systems in low-birth weight (LBW) infants. METHODS: Between 1989 and 1990, 30 LBW infants who received assisted ventilation with HFOV (n = 14) or conventional mechanical ventilation (CMV; n = 16) in the level III neonatal intensive care unit at Tokyo Metropolitan Ohtsuka Hospital were enrolled in this study. The effects of vibration exposure on the auditory system structures were investigated with auditory brainstem responses (ABR) at 37-41 weeks of postconceptional age and at 6, 12, 18 and 24 months of age until they passed and follow-up studies were performed at least until 5 years of age. RESULTS: All infants enrolled in the study survived at discharge and one (7.1%) infant in the HFOV group and two (12.5%) in the CMV group failed the initial ABR test, but there were no significant differences between the two groups. Auditory brainstem response abnormalities were still observed in one infant in the HFOV group at 6 months of age, but this child died at 9 months of age because of meningitis. In contrast, in the CMV group, one patient passed the ABR test at 6 months of age, but another remained abnormal at 5 years of age. One of three infants with ABR abnormalities at 6 months of age had neurologic sequelae at 5 years of age and one of 28 infants who passed the initial ABR test was detected with cerebral palsy. No patients with hearing loss were clinically detected at 5 years of age. CONCLUSIONS: The results of the serial ABR examinations and the 5 year follow-up studies suggest that vibration exposure caused by HFOV may not increase the adverse effects on the auditory system in LBW infants.

Nonlinear three-dimensional finite element analysis of newly designed cementless total hip stems.

We designed 2 new types of proximally coated stems (the FMS and FMS-anatomic) based on the endosteal geometry of femora with congenital dislocation or dysplastic hip. The FMS was symmetric while the FMS-anatomic was asymmetric. We compared the proximal fit and fill to the femoral canal, contact stress, relative motion, and load transfer to the femur of 5 stems (FMS, FMS-anatomic, Omnifit, Omniflex, and individual stem) using three-dimensional computer simulation and finite element analysis. The FMS and FMS-anatomic showed a significantly greater fit and fill than conventional stems. The dispersion of the contact stresses and reduction of relative motions in the proximal area were the best in the FMS-anatomic compared to other stems with the exception of the individual stem. In addition, the FMS-anatomic stem transferred most of the load to the proximal femur. Our results suggest that the FMS-anatomic should provide better biomechanical stability at least in the early postoperative period.

Hereditary sensory neuropathy with deafness and dementia: a clinical and neuroimaging study.

We describe three sibling patients with autosomal dominantly inherited sensory neuropathy, sensorineural hearing loss and dementia. The features of cognitive-behavioral deficits in the patients, including executive dysfunction, apathy, indifference and inattention, were consistent with a frontal lobe dysfunction. Magnetic resonance imaging showed a diffuse brain atrophy. A fluorodeoxyglucose positron emission tomography in one patient and a single photon emission computed tomography in another demonstrated a glucose hypometabolism or a hypoperfusion in the medial frontal and thalamic regions. Primary frontal involvement or frontal dysfunction secondary to thalamic lesions may contribute to the nature of dementia in these patients.

Histological investigation of spinal cord lesions in the spinal hyperostotic mouse (twy/twy): morphological changes in anterior horn cells and immunoreactivity to neurotropic factors.

We examined the morphology of spinal accessory motoneurons and immunoreactivity to neurotrophins, brain-derived neurotropic factor (BDNF) and neurotrophin (NT)-3, as well as the presence of reactive astrocytosis in 70 tiptoe walking Yoshimura (twy) mice that develop calcification at C1-C2 vertebral level compressing the spinal cord. At the level of compression, the area of neuronal soma and total length of dendrites of wheat germ agglutinin-horseradish peroxidase (WGA-HRP)-labelled accessory motoneurons in the medial cell pool decreased significantly with decrement in motoneuron population, relative to the control. In contrast, at sites rostral to the compressive lesion, a significant enlargement of the neuron soma and dendritic elongation were noted, associated with increased motoneuron population and decreased transverse area of the cord at the level of compression. At this site, enhanced BDNF and NT-3 immunoreactivities were evident in the anterior horn cells. In mice with a more severe degree of compression, astrocyte-like cells showing BDNF immunoreactivity became abundant and axons in the anterior column demonstrated a marked NT-3 immunoreactivity. Our results suggest increased functional activity of anterior horn cells at levels rostra] to the site of compression. We speculate that the presence of BDNF and NT-3 in neurons and astrocyte-like cells is proportionate to the severity of chronic mechanical compression and may contribute to the heterotropic neuronal reserve and survival.

Vertical transmission of human immunodeficiency virus type 1 in Japan, 1989-1997: presence of two subtypes B and E with subtype E predominance. National Cooperative Study Investigators on Vertical Transmission of HIV-1.

A collaborative group for studying vertical transmission of human immunodeficiency virus (HIV)-1 in pregnant women and their babies was established in Japan in 1989. Forty-two infants, including 13 HIV-1-infected, 25 uninfected and four of undetermined status and 15 control children born to HIV-1 negative mothers were diagnosed and followed from birth to 1.5 years. All strains from HIV-positive infants were either clade E (eight infants, 61.5%) or B (five infants, 38.5%) according to DNA sequencing specific for the HIV-1 C2-V3 region. The 42 mothers with HIV-1 were women with sexual-risk behavior from all regions, but were concentrated in the Kanto District. In this group of HIV-infected children, there was no significant difference between the transmissibility of their mother's clade E and B viruses. Eight (61.5%) of the 13 virus-infected babies were Japanese and five (62.5%) of the eight were positive for HIV-1 clade E. The V3 loop region of the clade E virus of the babies was conserved but approximately 60% of the sequences which showed a substitution of aspartic acid by asparagine at position 29. The results suggest that HIV-1 clade E may be predominant in vertical transmissions and are phenotypically different from HIV-1 in persons with various other risk behaviors in Japan.

Relationship between gait and clinical results after high tibial osteotomy.

Thirty-two patients with primary osteoarthritis of the medial compartment of the knee were studied prospectively to assess the relationship between clinical results, limb alignment, and adduction moment of the knee. Clinical and radiographic examination and gait analyses were performed preoperatively and repeated at 6 months and at 1, 3, and 6 years after high tibial osteotomy. The preoperative peak adduction moment was high in 25 patients and low in seven. In both groups, the adduction moment of the knee decreased at 6 months after surgery but increased after that period. Alignment of the affected knee in both groups remained valgus after surgery (average femorotibial angle, 167 degrees-169 degrees). Clinical outcome in both groups improved after surgery and remained unchanged after 1 year. The peak adduction moment of the knee for the whole group significantly correlated with alignment and foot angle before and 6 years after surgery but did not correlate with stride length and walking velocity. In addition, only alignment was associated significantly with clinical results at 6 years. These results suggest that the preoperative peak adduction moment of the knee does not correlate with clinical or radiographic outcomes of high tibial osteotomy, provided sufficient valgus alignment is achieved at surgery.

Cervical myeloradiculopathy with entrapment neuropathy: a study based on the double-crush concept.

In an attempt to formulate a standardised approach to the diagnosis and management of patients with the double-crush syndrome, we reviewed 65 surgical cases (39 men and 26 women) with cervical myeloradiculopathy associated with entrapment neuropathy in the arm by examining the clinical features, results of nerve conduction velocity studies and distribution of the vertebral levels of compression. Fifty-three patients (average age, 43 years) presented with a carpal tunnel syndrome at the wrist and cervical lesions (41 with spondylosis and 12 with ossified posterior longitudinal ligament), while 12 had a cubital tunnel syndrome at the elbow with cervical lesions (eight with spondylosis and four with ossification of the posterior longitudinal ligament). In the former group, the lesions were found mostly at C5-6 and C6-7 levels, while in the latter group involvement of C6-7 was frequently observed. Two patients in each group required additional cervical decompression after carpal or cubital tunnel release. A retrospective review of our patients suggested that it is reasonable to pursue an accurate diagnosis followed by treatment based on individual neurological and electrophysiological findings, but taking into consideration the significant level of physical impairment associated with cord compromise, we believe that it may be reasonable to perform a cervical decompression rather than peripheral nerve release in such cases. Our findings suggest that one should be aware of a double-crush during examination of patients complaining of neck and hand problems.

Solitary plasmacytoma of the spine associated with neurological complications.

We report eight patients with a solitary plasmacytoma of the spine associated with neurological complications. The patients included five men and three women with an average age at presentation of 59 years (range, 47 to 73 years). The tumour was confined to the thoracic spine in six cases, cervical spine in one and lumbar spine in one. Duration of symptoms ranged from 2.5 to 22 months. Treatment consisted of a combination of radiotherapy, melphalan and surgery. One patient progressed to multiple myeloma 7 years after surgery. Surgical treatment (anterior surgery in three cases and posterior surgery in five) produced neurological improvement in all patients. We stress the importance of an early diagnosis followed by appropriate treatment including surgery for this clinical entity and long-term follow-up to detect a disseminated disease.

Visualization of the cervical spinal cord with FDG and high-resolution PET.

PURPOSE: Our aim was to evaluate the visibility of the cervical spinal cord with [18F]2-fluoro-2-deoxyglucose (FDG) and a high-resolution PET scanner and to quantify the glucose utilization by the cervical cord. METHOD: Twenty-one normal subjects and three cervical myelopathy patients were studied. The visibility of the cervical spinal cord in sagittal and coronal sections was evaluated. The metabolic rate of glucose (MRGlu) and standardized uptake value (SUV) of FDG in the cord were calculated. RESULTS: The entire cervical spinal cord was clearly visualized in 57% of the subjects: the upper cord in 81%, the middle cord in 73%, and the lower cord in 57%. The MRGlu of the normal cord was 1.93 +/- 0.37 mg/100 g/min. SUV was constant across all the vertebral levels and negatively correlated with subject age. In the myelopathy patients, the SUV of the entire cervical cord was lower than in the age-matched normal subjects. CONCLUSION: These preliminary results indicate that the cervical spinal cord can be visualized as a normal structure in routine head and neck PET imaging and that FDG-PET may provide quantitative information about spinal cord disorders.

Prosthetic knee Candida parapsilosis infection.

We report a 77-year-old man who developed Candida parapsilosis infection following total knee arthroplasty. Knee joint effusion was noted 2 weeks after surgery, and repeated cultures of aspirated fluid established the diagnosis of Candida parapsilosis infection 4 weeks after surgery. Treatment consisted of debridement and lavage of the involved joint together with continuous irrigation with fluconazole for 4 weeks, followed by oral fluconazole for another 6 months. At 3 years follow-up, the patient was doing well and radiological examination of the affected knee showed a firm attachment of the prosthesis. We suggest that early identification of the causative organism followed by continuous irrigation and use of appropriate antifungal medication may prevent joint instability and spares the removal of the prosthesis.

Relationship between radiographic classification and arthroscopic findings of articular cartilage lesions in osteoarthritis of the knee.

OBJECTIVE: To examine the relationship between radiographic abnormalities and arthroscopic findings of the cartilage lesions in patients with osteoarthritis (OA) of the knee. METHODS: Arthroscopy was performed in 190 patients with primary medial compartment (MC) OA of the knee to assess the severity of the cartilage lesion. Standing radiographs of all patients were graded according to the joint space narrowing (JSN) and Kellgren-Lawrence (K/L) scales. In addition to evaluating the correlation between arthroscopic articular cartilage lesions and the radiographic scale, multiple regression analysis was used to identify the arthroscopic findings and clinical factors that influenced the cartilage lesions. RESULTS: The positive predictive values of the JSN and K/L scales of the MC for the presence of essentially abnormal articular cartilage in the MC by arthroscopy were high (0.98, 0.96, respectively). The sensitivity and specificity of the JSN scale and the sensitivity and negative predictive value of the K/L scale were also high in the MC. In contrast, the positive predictive values of these radiographic scales for the presence of arthroscopic lesions in the lateral compartment (LC) were poor (0.20 and 0.19). In this study population with severe OA, there were more patients with a high K/L score than with a high JSN score in the MC. CONCLUSION: In MC-OA of the knee, the JSN and K/L scores for the MC correlated highly with cartilage lesions of the MC by arthroscopy. However, the cartilage lesion of the LC correlated poorly with both of these radiographic scales.