Developmental change in the gene expression of transient receptor potential melastatin channel 3 (TRPM3) in murine lacrimal gland.

Transient receptor potential (TRP) channels are cation channels with ubiquitous expression. Various TRP channels are functionally active at the ocular surface and are involved in tear secretion and multiple inflammatory processes. So far, the impact of TRP channels regarding the development of the lacrimal gland (LG) is unclear. While investigating TRP channels in the LG, the TRPM3 channel presented itself as a promising candidate to play a role in the development and functioning of the LG. Therefore, Trpm3 expression was analyzed in different embryonic and postembryonic LGs. Thus, gene expression of TRPM channels including Trpm2, Trpm3, Trpm4 and Trpm6 was analyzed by quantitative RT-PCR in murine LGs at different developmental stages. Localization of TRPM3 in LGs was examined by immunohistochemistry. Primary LG epithelial cells (LGEC) and mesenchymal cells (MC) from newborn mice were cultured (either separately or collectively) for three days, and Trpm3 expression was analyzed in LGEC and MC. As a result, gene expression of Trpm2, Trpm4 and Trpm6 showed no significant difference in LGs in the different stages of development. However, Trpm3 gene expression was significantly higher in the embryonic stage than in the postnatal stage with the peak at E18. Postnatal, Trpm3 expression significantly decreased up to 28-fold until two years of age. Immunohistochemistry for TRPM3 revealed apical membranous expression in the excretory ducts, as well as in the acini of up to P7 old mice. Trpm3 expression in LGEC were significantly higher than that of MC. Our results indicate that Trpm3 expression in murine LG is age-dependent and peaks at age E18. Its expression is localized in the apical membrane of the glandular epithelium. However, its functional role still requires additional study in the LG.

Postoperative intensive care unit admission does not affect outcomes in elective surgical patients with severe comorbidity / El ingreso postoperatorio en la unidad de cuidados intensivos no afecta a los desenlaces en pacientes con comorbilidades graves sometidos a cirugías programadas

OBJECTIVE: The impact of postoperative intensive care upon patient outcomes was evaluated by retrospectively investigating the rate of poor outcomes among miscellaneous elective surgical patients with severe comorbidities. DESIGN: A retrospective cohort study was carried out. SETTING: University hospital. PATIENTS: Surgical patients with severe comorbidities. Intervention: The outcomes of 1218 surgical patients treated in intensive care units (ICUs) and postsurgical wards (ICU group vs. non-ICU group) were reviewed for poor outcomes (i. e. , no discharge or death). A propensity score analysis was used to generate 248 matched pairs of ICU-admitted patients and controls. Variables of interest: Poor outcome rates on postoperative day 90 and mortality on postoperative days 30 and 90. RESULTS: No significant between-group differences were observed in terms of poor outcomes on postoperative day 90 [ICU vs. non-ICU: 33/248 (13%) vs.28/248 (11%), respectively; ICU odds ratio (OR): 1.19, 95% confidence interval (CI), 0.71-2.01, p = 0.596] or in between-group differences in terms of mortality on postoperative days 30 and 90 [ICU vs. non-ICU: 4/248 (1.6%) vs.2/248 (0.8%) on postoperative day 30 and 5/248 (2.0%) vs.3/248 (1.2%) on day 90, respectively; ICU OR (95% CI), 2.00 (0.37-10.9) and 1.67 (0.40-6.97) for postoperative 30- and 90-day mortality, respectively (p = 0.683 and 0.724)]. Low preoperative body weight was negatively correlated to patient outcomes [OR (95% CI): 0.82/10 kg (0.70-0.97), p = 0.019], whereas regional analgesia combined with general anesthesia was positively correlated to patient outcomes [OR (95% CI): 0.39 (0.69-0.96), p = 0.006]. Extra ICU admission was correlated to poor patient outcomes [OR (95% CI): 4.18 (2.23-7.81), p < 0.0001]. CONCLUSIONS: Postoperative ICU admission failed to demonstrate any meaningful benefits in patients with severe comorbidities undergoing miscellaneous elective surgeries

OBJETIVO: Se evaluó el impacto de los cuidados intensivos postoperatorios sobre los desenlaces de los pacientes investigando de forma retrospectiva la tasa de desenlaces desfavorables en un grupo variado de pacientes con comorbilidades graves que se sometieron a cirugías programadas. DISEÑO: Estudio retrospectivo de cohortes. Ámbito: Hospital universitario. PACIENTES: Pacientes quirúrgicos con comorbilidades graves. INTERVENCIONES: Se revisaron los desenlaces de 1.218 pacientes quirúrgicos tratados en unidades de cuidados intensivos (UCI) y plantas posquirúrgicas (grupo UCI frente a grupo no UCI) en busca de desenlaces desfavorables (esto es, ausencia de alta o muerte). Se llevó a cabo un análisis de puntuación de la propensión para generar 248 parejas de pacientes ingresados en la UCI y sus respectivos pacientes de control. Variables de interés: Tasas de desenlaces desfavorables al día 90 tras la intervención y mortalidad a los 30 y 90 días de la intervención. RESULTADOS: No se observaron diferencias significativas entre los grupos en cuanto a desenlaces desfavorables el día 90 tras la intervención (UCI frente a no UCI: 33/248 [13%] frente a 28/248 [11%], respectivamente; oportunidad relativa [OR]: 1,19; intervalo de confianza [IC] del 95%: 0,71-2,01; p = 0,596) ni diferencias entre los grupos en términos de mortalidad al cabo de 30 y 90 días tras la intervención (UCI frente a no UCI: 4/248 [1,6%] frente a 2/248 [0,8%] el día 30 tras la intervención y 5/248 [2,0%] frente a 3/248 [1,2%] el día 90, respectivamente; OR UCI [IC del 95%]: 2,00 [0,37-10,9] y 1,67 [0,40-6,97] para la mortalidad a los 30 y 90 días de la intervención, respectivamente [p = 0,683 y 0,724]). El bajo peso preoperatorio presentó una correlación negativa con los desenlaces de los pacientes (OR [IC del 95%]: 0,82/10 kg [0,70-0,97]; p = 0,019), mientras que la analgesia regional combinada con anestesia general y el ingreso fuera de la UCI presentó una correlación positiva con los desenlaces de los pacientes (OR [IC del 95%]: 0,39 [0,69-0,96]; p = 0,006). El ingreso extra en la UCI se correlacionó con malos resultados para el paciente (OR [IC del 95%]: 4,18 [2,23-7,81], p < 0,0001). CONCLUSIONES: El ingreso posoperatorio en la UCI no demostró asociarse con ningún beneficio significativo en un grupo variado de pacientes con comorbilidades graves sometidos a cirugías programadas

Postoperative intensive care unit admission does not affect outcomes in elective surgical patients with severe comorbidity.

OBJECTIVE: The impact of postoperative intensive care upon patient outcomes was evaluated by retrospectively investigating the rate of poor outcomes among miscellaneous elective surgical patients with severe comorbidities. DESIGN: A retrospective cohort study was carried out. SETTING: University hospital. PATIENTS: Surgical patients with severe comorbidities. INTERVENTION: The outcomes of 1218 surgical patients treated in intensive care units (ICUs) and postsurgical wards (ICU group vs. non-ICU group) were reviewed for poor outcomes (i.e., no discharge or death). A propensity score analysis was used to generate 248 matched pairs of ICU-admitted patients and controls. VARIABLES OF INTEREST: Poor outcome rates on postoperative day 90 and mortality on postoperative days 30 and 90. RESULTS: No significant between-group differences were observed in terms of poor outcomes on postoperative day 90 [ICU vs. non-ICU: 33/248 (13%) vs. 28/248 (11%), respectively; ICU odds ratio (OR): 1.19, 95% confidence interval (CI), 0.71-2.01, p=0.596] or in between-group differences in terms of mortality on postoperative days 30 and 90 [ICU vs. non-ICU: 4/248 (1.6%) vs. 2/248 (0.8%) on postoperative day 30 and 5/248 (2.0%) vs. 3/248 (1.2%) on day 90, respectively; ICU OR (95% CI), 2.00 (0.37-10.9) and 1.67 (0.40-6.97) for postoperative 30- and 90-day mortality, respectively (p=0.683 and 0.724)]. Low preoperative body weight was negatively correlated to patient outcomes [OR (95% CI): 0.82/10kg (0.70-0.97), p=0.019], whereas regional analgesia combined with general anesthesia was positively correlated to patient outcomes [OR (95% CI): 0.39 (0.69-0.96), p=0.006]. Extra ICU admission was correlated to poor patient outcomes [OR (95% CI): 4.18 (2.23-7.81), p < 0.0001]. CONCLUSIONS: Postoperative ICU admission failed to demonstrate any meaningful benefits in patients with severe comorbidities undergoing miscellaneous elective surgeries.

Neural changes in the primate brain correlated with the evolution of complex motor skills.

Complex motor skills of eventual benefit can be learned after considerable trial and error. What do structural brain changes that accompany such effortful long-term learning tell us about the mechanisms for developing innovative behavior? Using MRI, we monitored brain structure before, during and after four marmosets learnt to use a rake, over a long period of 10-13 months. Throughout learning, improvements in dexterity and visuo-motor co-ordination correlated with increased volume in the lateral extrastriate cortex. During late learning, when the most complex behavior was maintained by sustained motivation to acquire the skill, the volume of the nucleus accumbens increased. These findings reflect the motivational state required to learn, and show accelerated function in higher visual cortex that is consistent with neurocognitive divergence across a spectrum of primate species.

Development of simple, rapid and sensitive detection assay for grouper nervous necrosis virus using real-time loop-mediated isothermal amplification.

A quantitative rapid detection method based on loop-mediated isothermal amplification has been developed for red-spotted grouper nervous necrosis virus (RGNNV). The nested polymerase chain reaction (PCR) assay is the mainstream inspection of the brooder in the hatchery. In this study, a real-time loop-mediated isothermal amplification (LAMP) method has been applied for RGNNV detection, known as a high-speed gene amplification procedure. Of the three temperatures (60 °C, 63 °C and 65 °C) attempted, it has been found that 63 °C is giving higher amplification from 11th minute onwards. Sensitivity analysis performed in comparison with real-time polymerase chain reaction, reverse transcriptase PCR and nested RT-PCR using various concentrations of template revealed that real-time LAMP method is efficient in terms of cost and time consumption. Specificity analysis revealed that the method developed is specific to RGNNV, whereas it has sequence cross-match with tiger puffer NNV giving advantage in detecting both the viruses. This method could be much efficient in analysing RGNNV in combination with TPNNV.

The real impact of telaprevir dosage on the antiviral and side effects of telaprevir, pegylated interferon and ribavirin therapy for chronic hepatitis C patients with HCV genotype 1.

Triple therapy with telaprevir, pegylated interferon and ribavirin has been reported to improve antiviral efficacy but have potentially severe adverse effects in patients with chronic hepatitis C. To avoid the severe effects of telaprevir, lowering the dose has been suggested. However, impact of dosage changes on antiviral and adverse effects remains unclear. One hundred and sixty-six Japanese patients with HCV genotype 1 were treated with triple therapy. The drug exposure of each medication was calculated by averaging the dose actually taken. The overall SVR rate was 82%. The telaprevir discontinuation rate was 26%. The factors associated with discontinuation were an older age (≥65 y.o.) and a higher average dose during treatment. The telaprevir discontinuation rates were 42%, 25% and 14% in patients at ≥35, 25-35 and <25 mg/kg/day of telaprevir and 58% in older patients at ≥35 mg/kg/day of TVR. The factors associated with SVR were treatment-naïve, relapse to previous treatment, higher average telaprevir dose during treatment and completion of treatment. The SVR rate was higher, at 91%, in patients at 25-35 mg/kg/day of telaprevir than the 71% and 78% observed in those at <25 and ≥35 mg/kg/day of drug. In Japanese patients, a mean telaprevir dose of 25-35 mg/kg/day during treatment can augment its efficacy in triple therapy for patients with HCV genotype 1.

The SOCS and STAT from JAK/STAT signaling pathway of kuruma shrimp Marsupenaeus japonicus: molecular cloning, characterization and expression analysis.

Signal transducer and activators of transcription (STAT) gene, suppressors of cytokine signaling (SOCS) has been isolated from kuruma shrimp, Marsupenaeus japonicus and characterized. The kuruma shrimp STAT (MjSTAT) cDNA was composed of 2901 bp consisting of 801 amino acid residues which includes a protein interaction domain, all alpha domain, DNA binding domain and SH2 domain. Homology analysis of MjSTAT showed 94.1% and 34.0% identities with Penaeus monodon STAT (PmSTAT) and Drosophila melanogaster STAT92E (DmSTAT), respectively. The kuruma shrimp SOCS (MjSOCS) cDNA was composed of 1675 bp consisting of 342 amino acid residues including a SH2 domain and C-terminal SOCS domain. Homology analysis of MjSOCS showed 52.6% and 21.3% identities with Chinese mitten crab (Eriocheir sinensis) SOCS2 and fruit fly (D. melanogaster) SOCS44A, respectively. The MjSTAT and MjSOCS genes are constitutively expressed in the muscle, stomach, brain and gill of kuruma shrimp. In lymphoid organ cells, an enhanced expression of both MjSTAT and MjSOCS genes are observed following stimulation with peptidoglycan and polycytidylic acid. These observations suggest that MjSTAT and MjSOCS might play a major role in the innate immune defense of kuruma shrimp. The discovery of JAK/STAT signaling pathway in shrimp will allow a complete and concrete understanding of shrimp cytokine signaling.

Prospective evaluation of corrected QT intervals and arrhythmias after exposure to epirubicin, cyclophosphamide, and 5-fluorouracil in women with breast cancer.

BACKGROUND: Corrected QT (QTc) interval prolongation can induce fatal arrhythmias such as torsade de pointes. PATIENTS AND METHODS: To assess the characteristics of QTc intervals and arrhythmias in women with early breast cancer who received FEC100 adjuvant chemotherapy, electrocardiograms (ECGs) were recorded before and after each chemotherapy. Associations between QTc interval prolongation and single nucleotide polymorphisms (SNPs) of potassium channel genes were also investigated. RESULTS: A total of 131 ECG records were obtained in 34 patients who received 153 cycles of FEC100. QTc intervals could be measured in 127 records. There was a significant trend toward QTc interval prolongation after each treatment, persisting through four cycles of chemotherapy (P < 0.001). Median QTc interval prolongations were 13, 11, 18, and 14 ms in the first through fourth cycles of chemotherapy, respectively. QTc intervals differed significantly between cycles 1 and 4 before treatment as well as after treatment (P < 0.05). A single supraventricular premature contraction was noted in 3 (2.3%) of the 131 cycles in 2 (5.9%) of the 34 patients. There was no significant association between QTc interval prolongation and SNPs of potassium channel genes. CONCLUSION: This prospective study confirmed that FEC100 is associated with significant QTc interval prolongation in women with early breast cancer.

Deciphering the DNA repair protein, Rad23 from kuruma shrimp Marsupenaeus japonicus: full-length cDNA cloning and characterization.

AIMS: Lesions of DNA are removed by nucleotide excision repair (NER) process in the living systems. NER process-related host factors are believed to aid recovery steps during viral integration. Here, we report identification and characterization of a DNA repair molecule Rad23 from kuruma shrimp Marsupenaeus japonicus. METHODS AND RESULTS: The full-length cDNA of M. japonicus Rad23 gene (MjRad23) has 1149 bp coding for a putative protein of 382 amino acids with a 5' untranslated region (UTR) of 92 bp and 3' UTR region of 1116 bp. Quantitative expression analysis revealed MjRad23 is constitutively expressed in all the organs of healthy shrimp, whereas with high level in muscle tissue. Although MjRad23 expression is observed in every haemolymph samplings to post-white spot syndrome virus infection, high expression is recorded at 2 h post infection (h.p.i.). MjRad23 consists of putative functional domains including one ubiquitin domain (UBQ), two ubiquitin-associated domains (UBA) and one heat-shock chaperonin-binding motif (STI1). Multiple alignment of MjRad23 with Rad23 of other species showed highly significant identity ranging from 37 to 53%; however, high homology is observed with Rad23 of Bombyx mori (BmRad23). UBQ domain region alignment revealed maximum of 66% homology with Rad23 of Apis melifera (AmRad23). MjRad23 clustered with invertebrate sector along with insect species in evolution analysis. Three-dimensional structural analyses demonstrated the highest identity between MjRad23 and human Rad23A (hHR23A). CONCLUSIONS: The present work revealed the presence of MjRad23 gene, which is essential in DNA repair process. Further studies are required to clarify the involvement of MjRad23 in NER process. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report on identification and characterization of DNA repair protein in crustaceans, which will lead to further investigation to explore the molecular mechanisms behind the NER process.

Associations between oxaliplatin-induced peripheral neuropathy and polymorphisms of the ERCC1 and GSTP1 genes.

OBJECTIVE: Oxaliplatin-induced chronic neuropathy is cumulative and dose-limiting; reliable predictors and determination of the mechanism of this toxic effect are needed. METHODS: We retrospectively studied 51 Japanese adults with colorectal cancer who had received oxaliplatin-based chemotherapy to explore the pharmacogenetic association between oxaliplatin-induced neuropathy and polymorphisms of the excision repair cross-complementation Group 1 (ERCC1) and glutathione-S-transferases pi 1 (GSTP1) genes. RESULTS: For the ERCC1 C118T polymorphism, Grade 1 chronic neuropathy developed earlier in patients with C/T and T/T genotypes (median number of treatment cycles at onset = 6) than in those with the reference C/C genotype (7 cycles; p = 0.0162 by the generalized Wilcoxon test). For the GSTP1 Ile105Val polymorphism, chronic neuropathy developed earlier in patients with the reference Ile/Ile genotype (6 cycles) than in those with Ile/Val and Val/Val genotypes (9 cycles; p = 0.0321). ERCC1 C118T and GSTP1 Ile105Val polymorphisms were not significantly associated with an increased risk of developing Grade 2 or more severe chronic neuropathy. CONCLUSIONS: Our results suggest that ERCC1, C118T and GSTP1 Ile105Val polymorphisms are more strongly related to the time until onset of neuropathy than to the grade of neuropathy. Most likely these polymorphisms influence patients' sensitivity to neuropathy.

Factors affecting efficacy in patients with genotype 2 chronic hepatitis C treated by pegylated interferon alpha-2b and ribavirin: reducing drug doses has no impact on rapid and sustained virological responses.

Reducing the dose of drug affects treatment efficacy in pegylated interferon (Peg-IFN) and ribavirin combination therapy for patients with hepatitis C virus (HCV) genotype 1. The aim of this study was to investigate the impact of drug exposure, as well as the baseline factors and the virological response on the treatment efficacy for genotype 2 patients. Two-hundred and fifty patients with genotype 2 HCV who were to undergo combination therapy for 24 weeks were included in the study, and 213 completed the treatment. Significantly more patients who achieved a rapid virological response (RVR), defined as HCV RNA negativity at week 4, achieved a sustained virological response (SVR) (92%, 122/133) compared with patients who failed to achieve RVR (48%, 38/80) (P < 0.0001). Multivariate logistic-regression analysis showed that only platelet counts [odds ratio (OR), 1.68; confidence interval (CI), 1.002-1.139] and RVR (OR, 11.251; CI, 5.184-24.419) were independently associated with SVR, with no correlation being found for the mean dose of Peg-IFN and ribavirin for RVR and SVR. Furthermore, in the stratification analysis of the timing of viral clearance, neither mean dose of Peg-IFN (P = 0.795) nor ribavirin (P = 0.649) affected SVR in each group. Among the patients with RVR, the lowest dose group of Peg-IFN (0.77 +/- 0.10 microg/kg/week) and ribavirin (6.9 +/- 0.90 mg/kg/day) showed 100% and 94% of SVR. Hence, RVR served as an important treatment predictor, and drug exposure had no impact on both SVR and RVR in combination therapy for genotype 2 patients.

Reduced risk of hepatocellular carcinoma after interferon therapy in aged patients with chronic hepatitis C is limited to sustained virological responders.

This study was undertaken to investigate the effect of interferon (IFN) monotherapy on the risk of hepatocellular carcinoma (HCC) in aged-patients with chronic hepatitis C. Seven hundred and twenty-five patients with histologically proven chronic hepatitis C were enrolled in this retrospective cohort study; 531 received IFN monotherapy for 6 months between 1992 and 1995, and 157 were collected as a historical control. The effect of IFN therapy on the development of HCC was compared between the patients with chronic hepatitis C under 60 years old (non-aged group, n = 531) and those 60 and over (aged group, n = 194). A stepwise Cox proportional-hazards regression analysis in the non-aged group revealed that IFN therapy (risk ratio 0.52, 95% CI 0.33-0.81, P = 0.004), older age (P = 0.001), and higher histological stage (P < 0.001) were independent factors associated with the development of HCC. In the aged-group, only higher histological stage (P = 0.002) and male gender (P = 0.011), but not IFN therapy (risk ratio 0.77, 95% CI 0.42-1.40, P = 0.386), were identified as independent risk factors for HCC, although HCC was significantly reduced when sustained virological response (SVR) was obtained (risk ratio 0.23, 95% CI 0.08-0.64, P = 0.005). In conclusion, inhibitory effect of IFN on development of HCC in the patients with chronic hepatitis C aged 60 and over was limited to the patients achieving SVR when treated with 6 months-IFN monotherapy.

Pharmacokinetic modelling of [2-13C]uracil metabolism in normal and DPD-deficient dogs.

A physiologically based pharmacokinetic (PBPK) model to simulate the plasma concentration and 13CO2 exhalation after [2-13C]uracil administration to DPD-suppressed dogs was developed. Simulation using this PBPK model should be useful in clinical situations where DPD-deficient patients at risk are to be detected with [2-13C]uracil as an in vivo probe.

Role of RANKL-induced osteoclast formation and MMP-dependent matrix degradation in bone destruction by breast cancer metastasis.

Bone metastasis of breast cancer induces severe osteolysis with increased bone resorption. Osteoclast differentiation regulated by the receptor activator of NF-kappaB ligand (RANKL) in osteoblasts and matrix degradation induced by matrix metalloproteinases (MMPs) are thought to be involved in the process of bone resorption. When nude mice were inoculated with human breast cancer cells, MDA-MB-231(MDA-231), numerous osteoclasts resorbed bone and the degradation of the bone matrix markedly progressed in the femur and tibia with metastasis of the MDA-231 tumour. The expression of RANKL, MMP-13 and membrane-type 1-MMP mRNA was markedly elevated in bone with metastasis. When MDA-231 cells were cocultured with mouse calvaria, MDA-231 markedly induced bone resorption measured by calcium release from the calvaria, and the expression of RANKL, MMP-2 and MMP-13 was elevated in the calvaria after the coculture. The separation of MDA-231 from the calvaria using filter insert showed decreased bone resorption, suggesting that cell-to-cell interaction is essential for cancer-induced bone resorption. Adding MDA-231 cells to bone marrow cultures markedly induced osteoclast formation, and the expression of RANKL in osteoblasts was enhanced by contact with the cell surface of MDA-231 cells. These results indicate that RANKL-induced osteoclast formation and MMP-dependent matrix degradation are associated with osteolysis because of bone metastasis of breast cancer.

Connection between B lymphocyte and osteoclast differentiation pathways.

Osteoclasts differentiate from the hemopoietic monocyte/macrophage cell lineage in bone marrow through cell-cell interactions between osteoclast progenitors and stromal/osteoblastic cells. Here we show another osteoclast differentiation pathway closely connected with B lymphocyte differentiation. Recently the TNF family molecule osteoclast differentiation factor/receptor activator of NF-kappaB ligand (ODF/RANKL) was identified as a key membrane-associated factor regulating osteoclast differentiation. We demonstrate that B-lymphoid lineage cells are a major source of endogenous ODF/RANKL in bone marrow and support osteoclast differentiation in vitro. In addition, B-lymphoid lineage cells in earlier developmental stages may hold a potential to differentiate into osteoclasts when stimulated with M-CSF and soluble ODF/RANKL in vitro. B-lymphoid lineage cells may participate in osteoclastogenesis in two ways: they 1) express ODF/RANKL to support osteoclast differentiation, and 2) serve themselves as osteoclast progenitors. Consistent with these observations in vitro, a decrease in osteoclasts is associated with a decrease in B-lymphoid cells in klotho mutant mice (KL(-/-)), a mouse model for human aging that exhibits reduced turnover during bone metabolism, rather than a decrease in the differentiation potential of osteoclast progenitors. Taken together, B-lymphoid lineage cells may affect the pathophysiology of bone disorders through regulating osteoclastogenesis.

Intestinal Behçet's disease associated with myelodysplastic syndrome with chromosomal trisomy 8--a report of two cases and a review of the literature.

Two cases of intestinal Behçet's disease, which developed in the state of myelodysplastic syndrome with trisomy 8, are presented. Both cases are included in the incomplete type of Behçet's disease, with recurrent aphthous stomatitis, skin lesions, genital ulcers or vascular involvement and punched-out ulcers in the cecum, without ocular involvement. The chromosomal analyses revealed chromosomal abnormalities, including trisomy 8, in both cases. Chromosomal trisomy 8 was shown in all 6 cases with the intestinal Behçet's disease associated with myelodysplastic syndrome reported previously, including our patients. Their histories indicated that myelodysplastic syndrome might have started before the development of intestinal Beçet's disease. Theses findings suggested that chromosomal trisomy 8 might play an important role in the pathogenesis, at least in some groups, of intestinal Behçet's disease.

Circulating transforming growth factor beta 1 as a predictor of liver metastasis after resection in colorectal cancer.

Plasma transforming growth factor beta1 (TGF-beta1) has been reported to be correlated with the extent of disease in colorectal cancer, but it is not known whether measuring this cytokine can help predict liver metastasis after curative resection. We prospectively studied whether plasma TGF-beta1 levels could predict liver metastasis in 117 patients with colorectal cancer before and after curative resection. Blood samples were drawn before and 2 weeks after surgery to determine the cytokine levels. Abdominal ultrasonography or computed tomography was done every 3 months after surgery. The primary end point for follow-up was recurrence. Seventy-seven of 117 cases (66%) had preoperative levels of the cytokine higher than the borderline limit of 7.5 ng/ml. Postoperative levels were >7.5 ng/ml in 29 of 117 patients (25%). The median follow-up period was 42 months (range, 5--66 months), with follow-up of all 117 patients. No recurrence was observed in 13 patients with Dukes' stage A lesions. Liver metastasis occurred in 18 of 104 patients (17%) with Dukes' stage B or C disease. Fourteen of 18 patients (78%) who developed liver metastasis had shown a postoperative plasma TGF-beta1 level of >7.5 ng/ml. Cox proportional hazards regression analysis showed that the postoperative level was a significant predictive factor for liver metastasis (P < 0.001). A single point measurement of plasma TGF-beta1 levels at 2 weeks after curative resection seems to be able to predict liver metastasis in colorectal cancer. This finding suggests the value of a prospective trial of liver-targeted adjuvant therapy for patients with elevated postoperative plasma TGF-beta1 levels.