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Summary Objective Chondrocyte hypertrophy followed by cartilage destruction is a crucial step for osteoarthritis (OA) development, however, the underlying mechanism remains largely unknown. The objectives of this study are to identify the gene that may cause cartilage hypertrophy and to elucidate its role on OA pathogenesis. Design Gene expression profiles of cartilages from OA patients and normal subjects were examined by microarray analysis. Expression of deiodinases, enzymes for regulation of triiodothyronine (T3) biosynthesis, in human and rat articular cartilage (AC) were examined by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Rat ACs and chondrocytes were treated with T3 to investigate its role on chondrocyte hypertrophy and inflammatory reaction. Cartilage-specific Type II deiodinase (DIO2) transgenic rats were generated using bacterial artificial chromosome harboring the entire rat Col2a1 and human DIO2 gene. An experimental OA model was created in the animal to examine the role of DIO2 on cartilage degeneration. Results DIO2 is highly expressed in OA patient AC compared to normal control. In rat AC, DIO2 is specifically expressed among deiodinases and dominantly expressed the same as in brown adipose tissue. T3 induces hypertrophic markers in articular chondrocyte and cartilage explant culture, and enhances the effect of IL-1α on induction of cartilage degrading enzymes. Importantly, cartilage-specific DIO2 transgenic rats are more susceptible to knee joint destabilization and develop severe AC destruction. Conclusion Our findings demonstrate that upregulated expression of DIO2 in OA patient cartilage might be responsible for OA pathogenesis by enhancing the chondrocyte hypertrophy and inflammatory response.

Vascular endothelial growth factor (VEGF) and its receptors play an important role in tumor progression; however, there is no report regarding this factor in uterine sarcoma. Thirty-nine patients with uterine sarcoma, 14 carcinosarcomas, 4 endometrial stromal sarcomas, and 21 leiomyosarcomas, were studied. By immunohistochemical staining, VEGF was not detected in normal uterine smooth muscle, but VEGF receptor-1 (flt-1) and VEGF receptor-2 (flk-1) were observed in 14 and 4 of 14 normal smooth muscles, respectively. Of 39 sarcomas, 25 expressed VEGF, and 38 and 34 sarcomas expressed flt-1 and flk-1 at various intensities, respectively. The staining intensity of VEGF, flt-1, and flk-1 was significantly higher in sarcoma than in normal uterine smooth muscle, but that of phospho-flt-1 (p-flt-1) was significantly lower in sarcoma than in normal uterine smooth muscle. When sarcomas were divided into two groups according to staining intensity, a significant difference in survival curves was observed in only p-flt-1 of leiomyosarcoma (P = 0.008), and in all sarcomas, a lower survival curve was also observed in the high staining intensity group than in the low staining intensity group, although there was no significant difference (P = 0.102). In conclusion, VEGF and its receptors are suggested to be involved in progression of uterine sarcoma, but only the p-flt-1 level significantly affected the survival of leiomyosarcoma patients.

ResumenExaminamos la relación entre dosis y eficacia, y los predictores de la respuesta al milnaciprán. No hubo diferencias entre las dosis de 50 y 100 mg. Sin embargo, la dosis de 100 mg tuvo un comienzo más rápido de acción que la dosis de 50 mg. La edad y el episodio han sido predictores del milnaciprán.

Six calves, aged between 55 days and 15 months, were presented between September and November 2006 with neurological signs including limb weakness and circling. Microscopical examination of the brain and spinal cord revealed the presence of non-suppurative encephalitis in all animals. Perivascular cuffing of lymphocytes and macrophages and diffuse gliosis was prominent in the cerebrum and degeneration and/or necrosis of neurons with vacuolation of the neuropil was present in the brainstem. Neuronal necrosis and neuronophagia were noted in the ventral horn of the spinal cord. The distribution of the lesions was closely related to the clinical signs displayed by each calf. Five calves presenting with astasia with low head carriage or torticollis had lesions throughout the central nervous system (CNS). The oldest calf displayed astasia caused by weakness of the "hindlimb" one word and had lesions largely restricted to the caudal spinal cord. Akabane virus (AKAV) antigens were detected immunohistochemically within neurons and axons in lesional tissue. Virus was not isolated from CNS tissue but the AKAV S gene was detected in this tissue from five calves by reverse transcriptase polymerase chain reaction (RT-PCR). It is suggested that AKAV infection is likely to have occurred during the early life period in the calves of this study.

Objective The aim of this study was to compare the clinical efficacy of new caries detecting dye Caries Check Blue (CCB) with Caries Check (CC) and Caries Detector (CD) using a laser fluorescence device (DIAGNOdent). Method Primary and permanent teeth with dentin caries were stained with polypropylene glycol (MW = 300) based new caries detecting dyes CCB, CC, or propylene glycol (MW = 76) based CD. In the CCB and CC groups, stained dentin was completely removed. In the CD groups, pink-stained dentin was retained according to the manufacturers’ instructions. Cavities before and after caries removal were measured with the DIAGNOdent. Data were analyzed using ANOVA and Fisher’s PLSD multiple comparison test at α = 0.05. Regression analyses were performed between DIAGNOdent readings and scores obtained from the clinical parameters. Results The DIAGNOdent readings after caries removal were: primary-CCB (13.2 ± 10.4), primary-CC (14.3 ± 16.7), primary-CD (9.0 ± 5.2), permanent-CCB (22.7 ± 13.4), permanent-CC (10.6 ± 6.8) and permanent-CD (9.7 ± 9.0). Significant differences were identified between the permanent-CCB and all other groups. Correlation coefficients between DIAGNOdent readings and clinical parameters were low. Conclusions When dentin stained with Caries Check Blue or Caries Check was completely removed, the DIAGNOdent readings were higher than those recorded when palely-stained pink dentin was retained with the Caries Detector, with significant difference observed for the permanent-CCB group. Caries Check Blue may be used clinically to avoid excessive removal of caries-affected or sound dentin in permanent teeth but not in primary teeth.

Background Little is known of the fibrinolytic host immune mechanisms responsible for induction of chronic allograft nephropathy (CAN), defined as a loss in glomerular filtration rate (GFR) caused by tubular atrophy and interstitial fibrosis, often with fibrous intimal thickening in the small arteries. However, chronic rejection has been reported to be associated with decreased activity of the fibrinolytic system. In our previous study, [Deamino-Cys 1 , d -Arg 8 ]-vasopressin (dDAVP) induced urokinase-type plasminogen activator (uPA) release from human peripheral T lymphocytes via arginine vasopressin (AVP) V 2 -receptor-mediated reaction enhanced by an AVP V 1 -receptor antagonist. Therefore, we examined the level of uPA released from peripheral T lymphocytes by AVP in transplant patients with CAN in comparison with control groups. Patients and Methods In this study, we evaluated in vitro uPA releasing activity of lymphocytes obtained from renal allograft patients with well-functioning grafts (n = 9), CAN (n = 5), or acute rejection episodes (n = 5) compared with lymphocytes from healthy volunteers with normal renal function (n = 12) or patients with renal insufficiency (n = 5). Results Lymphocytes prepared from patients with chronic allograft nephropathy showed a significantly lower increase in uPA release induced by the combination of the V 1 -receptor antagonist and dDAVP compared with those from the other groups. Conclusion This finding suggested that a decrease in uPA release from human peripheral blood lymphocytes by AVP-related peptides may be potentially involved in the pathophysiology of CAN.

The objective of this study was to clarify the relationship between the serum level of the Lens culinaris agglutinin A-reactive fraction of alpha-fetoprotein (AFP-L3) and the clinical features including sex, age, Child's classification, virus markers, tumour size, tumour stage, distant metastasis, histopathologic findings, portal thrombus and outcome of hepatocellular carcinoma (HCC). We measured the AFP-L3 levels in 170 HCC cases at the time of diagnosis using lectin-affinity electrophoresis followed by antibody-affinity blotting. The patients were divided into two groups, those who were AFP-L3 positive (n=56; AFP-L3 >/=15% relative to the total alpha-fetoprotein (AFP) concentration) and those who were AFP-L3 negative (n=114; AFP-L3

Fifty-nine methacarn-fixed, paraffin-embedded human breast carcinomas were immunostained by QB-END/10 (an antibody to CD34 antigen) to observe microvessels and by PC10 (an antibody to proliferating cell nuclear antigen; PCNA) to determine tumor cell proliferation; 9 normal human breast tissue specimens were also immunostained by QB-END/10. The number of microvessels in the periphery of the breast carcinoma was significantly greater than both that in the center of the breast carcinoma and that in the normal breast. There was also a significant relationship between the number of microvessels in the periphery of breast carcinomas and the histological tumor size and lymph node status. However, there was no significant relationship between the tumor cell proliferation activity (PCNA positive cell ratio) and any clinical or histopathological variables. The number of microvessels and the tumor cell proliferation activity showed a weak negative correlation.

Traditional Chinese medicine has a systematized methodology of medical treatment, based subjective information from the five senses. We proposed a diagnostic system for tongue inspection using fuzzy theory and applied this system to healthy volunteers based on traditional Chinese medicine. This system diagnosed syndromes such as deficiency syndrome, excess syndrome, coldness syndrome, and heat syndrome. We mainly focused on the evaluation of the coldness syndrome and the heat syndrome. The results suggested that this diagnostic system is useful for tongue inspection of traditional Chinese medicine.

Background The prognosis of gastric cancer with peritoneal metastasis is extremely poor. Neither systemic chemotherapy nor surgery alone prolongs survival of patients significantly. Methods Patients diagnosed with advanced gastric cancer underwent staging laparoscopy and received chemotherapy when peritoneal dissemination and/or cancer cells on peritoneal cytology were confirmed. The chemotherapy regimen consisted of S-1, weekly intravenous and intraperitoneal paclitaxel, which was verified in our phase II trial (Ann Oncol 2009). S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. Clinical response of chemotherapy was assessed by computed tomography, gastroendoscopy, peritoneal cytology and second-look laparoscopy. Radical gastrectomy was carried out when macroscopic curative resection was made achievable by chemotherapy. Chemotherapy was restarted after operation as soon as possible. Overall survival, relapse free survival, morbidity and mortality of gastrectomy were evaluated. Results Out of 100 patients with peritoneal metastasis who received chemotherapy, 60 patients underwent gastrectomy after response to chemotherapy, including 54 with macroscopic metastasis and 6 with positive peritoneal cytology only. A median of three courses were administered preoperatively (range 1–16). Total or distal gastrectomy with lymphnode dissection was carried out in 54 or 6 patients, respectively. The median survival time was 34.5 months. The median relapse-free survival was 16.7 months. The first site of relapse was the peritoneum in 24 patients and the other organ site in 17 patients. Postoperative complications included anastomotic leakage and pancreatic fistula in two patients each, which were healed conservatively. There were no treatment-related deaths. Conclusions Gastrectomy combined with S-1, intravenous and intraperitoneal paclitaxel is safe and active for gastric cancer patients with peritoneal metastasis.

We describe a simple bone cyst in a patient who had an osteoblastic lesion which had been discovered 1 1/2 years earlier. Curettage and drilling proved effective treatment. We suggest that increased regional blood flow, in association with bone formation, produces a hydrodynamic disorder followed by venous obstruction leading to the formation of a bone cyst.

Loss of heterozygosity has recently been discussed in the field of carcinogenesis, since loss of tumor suppressor gene has been believed to play a key role in carcinogenesis. However, recent evidence suggests that the loss of heterozygosity is a non-specific process in tumor progression rather than a specific process of carcinogenesis. Most loss of heterozygosity demonstrated by RFLP does not show the loss of tumor suppressors in a strict sense. We have to change our concept that loss of heterozygosity exclusively induces malignant phenotypes in cells. A likely explanation is that loss of heterozygosity is a general and rather stochastic process in tumor progression, and is due to loss of DNA replication fidelity. Detection of loss of heterozygosity without functional analysis may only accumulate meaningless data in tumor biology.

Pelvic actinomycosis is a rare disease that can result in abscess formation, bowel obstruction, and other serious complications. Moreover, the correct diagnosis can seldom be established before radical surgery because the disease often mimics pelvic neoplasms. It has been recently recognized that pelvic actinomycosis is associated with long-term use of an intrauterine contraceptive device. We report a woman with a long-standing intrauterine contraceptive device who visited our hospital complaining of symptoms mimicking large bowel ileus with a subacute course. X-ray fluorography and sigmoidoscopy showed marked stenosis in the sigmoid colon but rejected the possibility of colon cancers. Abdomino-pelvic CT and MRI revealed a huge abscess lying over the urinary bladder and anterior to the uterus. Furthermore, a cervical Papanicolaou smear disclosed Actinomyces species. We removed the intrauterine device from the patient. Subsequent high-dose ampicillin administration led to dramatic shrinkage of the abscess and improved the management of the bowel movement quickly. This is a successful case of symptomatic pelvic actinomycosis that was correctly diagnosed and treated without unnecessary surgical intervention.