Clinical factors that impair health-related quality of life in ulcerative colitis patients vary with the disease duration

BACKGROUND AND AIM: The health-related quality of life (HRQOL) of patients with ulcerative colitis (UC) can be impaired because of the chronic symptoms. Although UC patients suffer from such symptoms over the long term, there have been few reports on the changes of HRQOL with disease duration. The aim of this study was to clarify these changes. METHODS: The HRQOL of 331 Japanese UC patients was examined using the validated Japanese version of the Inflammatory Bowel Disease Questionnaire (J-IBDQ). HRQOL and factors affecting HRQOL identified using multiple linear regression analysis were stratified by disease duration. RESULTS: Of the 15 clinical factors examined, the clinical activity index score was the strongest determinant (P<0.0001) of all the scores of IBDQ regardless of disease duration. HRQOL did not differ significantly among patients with different disease durations. The factors, however, that affected HRQOL varied according to disease duration. In patients with disease duration of less than 5 years, the clinical activity index score was the predominant factor affecting HRQOL. Being 'on sick leave or hospitalized' was a significant factor impairing HRQOL in patients with disease duration of 5-9 years. Moreover, complications due to corticosteroids significantly impaired all of the IBDQ scores in patients with disease duration of 10 years or more. CONCLUSION: Factors that affected the HRQOL of UC patients varied according to the patients' disease duration. Our findings should assist in the development of a long-term strategy for the treatment of UC patients.     

Expression change of Flk-2/Flt-3 on murine hematopoietic stem cells in an activating state

OBJECTIVE: The receptor tyrosine kinase Flk-2/Flt-3 (Flt-3) represents an important molecule involved in early hematopoiesis. Murine hematopoietic stem cells (HSCs) have been shown to be negative for the expression of Flt-3. We now present clear evidence for the expression change of Flt-3(-) HSCs in an activating state, and the reversibility of Flt-3 expression by HSCs in vivo. MATERIALS AND METHODS: Bone marrow cells isolated from Ly5.1 mice were sorted on the basis of Flt-3 expression and transplanted into lethally irradiated Ly5.2 recipients. After 24 weeks, peripheral blood was analyzed for donor contribution by flow cytometry. RESULTS: Although long-term engraftment was predominantly detected in Flt-3(-) populations as previously described, a 6-day cultivation of Lin(-/low)c-kit(+)Sca-1(+) Flt-3(-) bone marrow cells with stem cell factor and interleukin-11 resulted in the generation of Flt-3(+) HSCs with long-term engraftment capabilities. However, the Flt-3 ligand had no significant effect on self-renewal of the Flt-3(+) HSCs. Next, to examine reversible expression of this receptor molecule, Flt-3(+) cells converted in vitro from Ly5.1 Lin(-/low)c-kit(+)Sca-1(+) Flt-3(-) bone marrow cells were isolated and transplanted into Ly5.2 primary recipients. After 24 weeks, Ly5.1 Lin(-/low) bone marrow cells were again separated into Flt-3(-) and Flt-3(+) cells and retransplanted into Ly5.2 secondary recipients. The majority of donor HSCs with long-term engraftment capabilities were detected in the Flt-3(-) populations, indicating the reversion of Flt-3(+) to Flt-3(-) HSCs. CONCLUSIONS: These observations suggest that Flt-3 is a useful cell-surface marker of HSC activation and that this phenotypic change is reversible.     

Carboxylic monolayer formation for observation of intracellular structures in HeLa cells with direct electron beam excitation-assisted fluorescence microscopy

Intracellular structures of HeLa cells are observed using a direct electron beam excitation-assisted fluorescence (D-EXA) microscope. In this microscope, a silicon nitride membrane is used as a culture plate, which typically has a low biocompatibility between the sample and the silicon nitride surface to prevent the HeLa cells from adhering strongly to the surface. In this work, the surface of silicon nitride is modified to allow strong cell attachment, which enables high-resolution observation of intracellular structures and an increased signal-to-noise ratio. In addition, the penetration depth of the electron beam is evaluated using Monte Carlo simulations. We can conclude from the results of the observations and simulations that the surface modification technique is promising for the observation of intracellular structures using the D-EXA microscope.OCIS codes: (170.0170) Medical optics and biotechnology, (170.0180) Microscopy     

Reproducibility of three-dimensional coordinate systems based on craniofacial landmarks

Abstract Objectives: To propose a method for evaluating the reproducibility of anatomical coordinate systems based on craniofacial skeletal landmarks and to tentatively evaluate four systems created on preoperative cone-beam computed tomography (CBCT) data obtained from mandibular prognathism patients in order to confirm the utility for actual patients' data. Materials and Methods: In three-dimensional images of 10 patients obtained by a CBCT with a large field of view, six dentists set four coordinate systems that were created in different ways, twice by plotting some landmarks situated in the superior portion of the maxillofacial skeletons. The 95% confidence ellipse of six objective landmarks related to the jaw and teeth (upper incisor, left upper first molar, lower incisor, left lower first molar, menton, and left gonion) were three-dimensionally drawn for each coordinate system. The ellipsoid volume was calculated to evaluate the reproducibility of the coordinate systems. Results: The reproducibility could be evaluated for each coordinate system using the method proposed. The coordinate systems that were created by landmarks situated at greater distances from each other showed relatively small ellipsoid volume in comparison to those with shorter distances between landmarks. Conclusion: Anatomical coordinate systems with larger distances between the landmarks used were stable when landmarks related to the jaw and teeth were assigned as objective landmarks. The method proposed here was effective in terms of the reproducibility evaluation of a coordinate system.     

Late-onset Leigh syndrome with myoclonic epilepsy with ragged-red fibers

We report the case of a boy with myoclonic epilepsy with ragged-red fibers (MERRF) who had astatic seizures since 2 years of age and later developed ataxia, absence seizures, and myoclonus. Almost homoplasmic A8344G mutation of mitochondrial DNA (m.8344A>G mutation) was detected in lymphocytes. He developed late-onset Leigh syndrome (LS) when he contracted pneumonia at 6 years. He developed bulbar palsy and deep coma. MRI demonstrated lesions in the brainstem, basal ganglia, and cerebral cortex. Three similar cases have been reported; two carried the almost-homoplasmic m.8344A>G mutation in muscle tissue. These suggested that almost homoplastic m.8344A>G mutation developed clinical phenotype of MERRF in the early stage and late-onset Leigh syndrome in the late course of the disease.     

Uterine smooth muscle cells increase invasive ability of endometrial carcinoma cells through tumor–stromal interaction

The incidence of lymph node metastasis by endometrial carcinoma (EMCA) increases with the depth of myometrial invasion, and this depth of invasion has been found to have a major impact on the outcome. In the present study, we assessed the effect of tumor–stromal interactions on the invasive behavior of EMCA cells and examined the involvement of SDF-1alpha/CXCL12-CXCR4 in the interaction of EMCA cells and uterine smooth muscle cells (UtSMCs). We investigated whether SDF-1alpha/CXCL12 produced and secreted from UtSMCs induces EMCA cell migration by using 5 human EMCA cell lines such as AMEC and RL95 cells. The SDF-1alpha/CXCL12 concentration in conditioned medium (CM) of UtSMCs(was 4,120 ± 530 pg/ml. Treatments with CM of UtSMCs and plated UtSMCs significantly induced both AMEC and RL95 cell migration. The induced cell migrations were significantly inhibited by CXCR4 mAb (12G5) and CXCR4 antagonist (AMD3100) pre-treatments. Treatments with UtSMCs CM to AMEC and RL95 cells stimulated Akt phosphorylation in a time-dependent manner. Pre-treatment of AMEC and RL95 cells with wortmannin as a PI3K inhibitor significantly inhibited UtSMCs CM-induced cell migration. The SDF-1alpha/CXCL12-CXCR4 chemokine axis between UtSMCs and EMCA played an important role in the muscular infiltration of endometrial cancer through activation of PI3K-Akt signaling pathway. Suppression of this pathway could be an effective target for the treatment of early uterine body cancer in particular.     

Multiple gastrointestinal stromal tumors in neurofibromatosis type 1 treated with laparoscopic surgery

Gastrointestinal stromal tumors (GISTs) have been reported to occasionally occur in patients with neurofibromatosis type 1 (NF-1), and many cases have had multiple lesions predominantly involving the small intestine. We report herein a case of multiple GISTs associated with NF-1 from whom laparoscopic surgery was beneficial. In a 79-year-old female admitted with anemia and melena, the abdominal computed tomography revealed a tumor arising from the small intestine. Laparoscopic surgery was performed, and another small tumor was revealed during laparoscopic observation. Extracorporeal partial and wedge resection of the small intestine were undertaken. Both lesions were diagnosed as typical GISTs of low risk. Laparoscopic surgery would be useful for examination and a minimally invasive approach to tumors of the small intestine, especially on cases with the possibility of multiple tumors.     

Clinical features and parasite-specific IgM/IgG antibodies of paragonimiasis patients recently found in Japan

Clinical features of a total of 30 paragonimiasis westermani patients referred to and diagnosed in our laboratory in 1999 were analyzed retrospectively. Most patients were middle-aged (average: 48 years, range: 13-72 years) with the male/female ratio of 19/11. Over 70% of the patients had respiratory symptom and over 80% had peripheral blood eosinophilia and high serum IgE level. All but two cases had radiologic abnormalities on the chest X-ray. Only in 3 cases were Paragonimus eggs detected in the sputum smear. We classified the patients into two groups depending on the chest X-ray findings: patients having pleurisy alone and those having nodular/cavitating lesions in the lung parenchyma. We measured parasite specific IgM/IgG antibodies in all patients sera by microplate ELISA. The mean parasite-specific IgM/IgG antibody ratio was significantly higher in the parenchymatous lesion group than in the pleurisy group. While IgM antibody titer had a strong positive correlation with the degree of eosinophilia in peripheral blood, IgG antibody titer had an inverse correlation. Although the degree of eosinophilia in peripheral blood was higher in the pleurisy group than in the parenchymatous lesion group, total IgE level in serum was comparable between the two groups. The present results indicate that pleurisy with eosinophilia and dominant IgM antibody are the characteristic features of the early stage of paragonimiasis, whereas parenchymatous lesions in lungs with low grade eosinophilia and dominant IgG antibody are of the late stage. These results suggest that detection of IgM antibody should always be considered for the immunodiagnosis for paragonimiasis-suspected patients with pleurisy.     

Mac-2 binding protein glycosylation isomer as a novel predictive biomarker for patient survival after hepatitis C virus eradication by DAAs

Background

It is crucial to identify risk factors for life prognosis after hepatitis C virus (HCV) eradication among patients with or without a high risk of liver cancer or complications.

Methods

This is a prospective, multicenter and observational study using the database of 1031 patients after HCV eradication by direct-acting antiviral agents (DAAs) to evaluate the development of hepatocellular carcinoma (HCC) and patients’ survival after a sustained virological response (SVR). The Cox proportional hazards regression model was used to estimate hazard ratios associated with HCC development and survival.

Results

AFP at SVR was significantly associated with HCC recurrence in the adjusted model. Liver fibrosis, Mac-2 binding protein glycosylation isomer (M2BPGi) at SVR and smoking status before treatment were positively associated with the development of HCC and M2BPGi was positively associated with HCC recurrence, although not reaching statistical significance. Among patients without a history of HCC, M2BPGi and estimated glomerular filtration rate (eGFR) at SVR were significantly associated with death after viral eradication [M2BPGi (HR 4.07, 95% CI 1.22, 13.57), eGFR (HR 0.97, 95% CI 0.94, 0.99)]. Strikingly, of 16 patients who died, among participants without a history of HCC, only two died of liver cancer associated with HCV, whereas 11 died of non-HCV- related cancer or cardiovascular diseases.

Conclusion

M2BPGi at SVR is a potential predictor for patients’ survival and a candidate biomarker for detecting individuals who are at greater risk of death due to cancer-related and unrelated to HCV, as well as cardiovascular diseases, after viral eradication.

     

Comparison of respiratory function recovery in the early phase after laparoscopy-assisted gastrectomy and open gastrectomy

Background  

Laparoscopic gastrectomy (LAG) is recognized as a less invasive surgery, but no advantage in terms of respiratory function recovery has been demonstrated. We investigated respiratory function recovery in the early period after LAG compared with open gastrectomy (OG) for measuring the recovery of oxygen saturation level (SaO₂).