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Hemophagocytosis is a phenomenon in which macrophages phagocytose blood cells. There are reports on up-regulated hemophagocytosis in patients with infectious diseases including typhoid fever, tuberculosis, influenza and visceral leishmaniasis (VL). However, mechanisms of infection-associated hemophagocytosis remained elusive due to a lack of appropriate animal models. Here, we have established a mouse model of VL with hemophagocytosis. At 24 weeks after infection with 1 x 10(7) Leishmania donovani promastigotes, BALB/cA mice exhibited splenomegaly with an average tissue weight per body weight of 2.96%. In the tissues, 28.6% of macrophages contained phagocytosed erythrocytes. All of the hemophagocytosing macrophages were parasitized by L. donovani, and higher levels of hemophagocytosis was observed in heavily infected cells. Furthermore, more than half of these hemophagocytes had two or more macrophage-derived nuclei, whereas only 15.0% of splenic macrophages were bi- or multi-nuclear. These results suggest that direct infection by L. donovani causes hyper-activation of host macrophages to engulf blood cells. To our knowledge, this is the first report on hemophagocytosis in experimental Leishmania infections and may be useful for further understanding of the pathogenesis.

Background and study aims: Despite the clinical advantages of colorectal endoscopic submucosal dissection (ESD), an effective training system, especially for Western endoscopists, has been challenging to establish. Herein, we propose a novel training program using ex vivo animal models and evaluate the learning curve of colorectal ESD trainees without gastric ESD experience. Patients and methods: A total of 80 colorectal lesions were prospectively collected and removed by two novice operators. Before human ESD procedures, they received ESD training using an ex vivo porcine “proximal colon” model, which simulates a lumen with many folds and flexions. To assess the validity of our training system, the self-completion and en bloc R0 resection rates, the operation time, and prevalence of complications were compared between the first and latter period. Moreover the factors associated with prolonged operation time were evaluated. Results: The overall rates of self-completion and en bloc R0 resection were 98 % (78/80) and 100 % (80/80), respectively. The operation time during the first period was significantly longer than that during the latter period (86 ± 50 minutes vs. 60 ± 36 minutes, P = 0.01). Regarding complications, only two cases of perforations and delayed hemorrhage were observed during the first period; however, all of the complications were successfully managed endoscopically. The presence of fibrosis was identified as a significant independent predictor of a prolonged operation time during the first period (coefficient, 5.90; 95 %CI, 2.36 – 9.44, P = 0.002). Conclusions: Our trainees achieved high rates of self-completion and R0 resection without severe complications even during the first 20 cases, suggesting that our training programs using ex vivo animal models are useful for trainees without gastric ESD experience. Study registration: UMIN000013566

Abstract: The newly developed assay system using recombinant Leishmania amazonensis expressing enhanced green fluorescent protein (La/egfp) has been applied to the screening of Japanese marine sponges for antileishmanial activity. Bioassay-guided fractionation of an active sponge Neopetrosia sp. afforded an active compound which was identified as renieramycin A by spectroscopic analysis. It inhibited La/egfp with an IC50 value of 0.2 μg/mL.

Canine distemper virus (CDV) vaccination confers long-term protection against CDV reinfection. To investigate the utility of CDV as a polyvalent vaccine vector for Leishmania, we generated recombinant CDVs, based on an avirulent Yanaka strain, that expressed Leishmania antigens: LACK, TSA, or LmSTI1 (rCDV-LACK, rCDV-TSA, and rCDV-LmSTI1, respectively). Dogs immunized with rCDV-LACK were protected against challenge with lethal doses of virulent CDV, in the same way as the parental Yanaka strain. To evaluate the protective effects of the recombinant CDVs against cutaneous leishmaniasis in dogs, dogs were immunized with one recombinant CDV or a cocktail of three recombinant CDVs, before intradermal challenge (in the ears) with infective-stage promastigotes of Leishmania major. Unvaccinated dogs showed increased nodules with ulcer formation after 3 weeks, whereas dogs immunized with rCDV-LACK showed markedly smaller nodules without ulceration. Although the rCDV-TSA- and rCDV-LmSTI1-immunized dogs showed little protection against L. major, the cocktail of three recombinant CDVs more effectively suppressed the progression of nodule formation than immunization with rCDV-LACK alone. These results indicate that recombinant CDV is suitable for use as a polyvalent live attenuated vaccine for protection against both CDV and L. major infections in dogs.

PURPOSE: To study the changes in the outer retinal microstructures during a six month period after the onset of acute zonal occult outer retinopathy (AZOOR)-complex by spectral-domain optical coherence tomography (SD-OCT). METHODS: Seventeen eyes of 17 patients with the AZOOR-complex were studied. The integrity of the external limiting membrane (ELM), ellipsoid zone (EZ; also called the inner/outer segment junction), and interdigitation zone (IDZ; also called the cone outer segment tips) were evaluated in the SD-OCT images obtained at the initial visit and at six months. The three highly reflective bands were divided into three types; continuous, discontinuous, and absent. The integrity of the outer nuclear layer (ONL) was also assessed. RESULTS: Among the three highly reflective bands, the IDZ was most altered at the initial visit and least recovered at six months. Fifteen of 17 eyes (88%) had a recovery of at least one of the three bands at six months in the retinal area where the ONL was intact, and these areas showed an improvement of visual field. Three eyes (18%) had retinal areas where the ONL was absent at the initial visit, and there was no recovery in both the retinal structures and visual fields in these areas. CONCLUSIONS: Our results indicate that more than 85% eyes with AZOOR-complex show some recovery in the microstructures of the outer retina during a six month period if the ONL is intact. We conclude that SD-OCT is a useful method to monitor the changes of the outer retinal microstructure in eyes with the AZOOR-complex.

The malaria vaccine candidate antigen, SE36, is based on the N-terminal 47 kDa domain of Plasmodium falciparum serine repeat antigen 5 (SERA5). In epidemiological studies, we have previously shown the inhibitory effects of SE36 specific antibodies on in vitro parasite growth and the negative correlation between antibody level and malaria symptoms. A phase 1 b trial of the BK-SE36 vaccine in Uganda elicited 72% protective efficacy against symptomatic malaria in children aged 6-20 years during the follow-up period 130-365 days post-second vaccination. Here, we performed epitope mapping with synthetic peptides covering the whole sequence of SE36 to identify and map dominant epitopes in Ugandan adult serum presumed to have clinical immunity to P. falciparum malaria. High titer sera from the Ugandan adults predominantly reacted with peptides corresponding to two successive N-terminal regions of SERA5 containing octamer repeats and serine rich sequences, regions of SERA5 that were previously reported to have limited polymorphism. Affinity purified antibodies specifically recognizing the octamer repeats and serine rich sequences exhibited a high antibody-dependent cellular inhibition (ADCI) activity that inhibited parasite growth. Furthermore, protein structure predictions and structural analysis of SE36 using spectroscopic methods indicated that N-terminal regions possessing inhibitory epitopes are intrinsically unstructured. Collectively, these results suggest that strict tertiary structure of SE36 epitopes is not required to elicit protective antibodies in naturally immune Ugandan adults.

Although thymus-independent type 2 antigens generally do not undergo Ig class switching from IgM to IgG, pneumococcal polysaccharide vaccine (PPV) induces the production of serotype-specific IgG. How this happens remains unclear, however. In the present study, PPV immunization induced production of IgG as well as IgM specific for a serotype 3-pneumococcal polysaccharide in the sera of wild-type (WT) mice, but this phenomenon was significantly reduced in Dectin-2 knockout (KO) mice. Immunization with PPV caused IL-12p40 production in WT mice, but this response was significantly reduced in Dectin-2KO mice. Likewise, immunization with PPV activated natural killer T (NKT) cells in WT mice but not in Dectin-2KO mice. Furthermore, administration of α-galactosylceramide, recombinant (r)IL-12 or rIFN-γ improved the reduced IgG levels in Dectin-2KO mice, and treatment with neutralizing anti-IFN-γ mAb resulted in the reduction of IgG synthesis in PPV-immunized WT mice. Transfer of spleen cells from PPV-immunized WT mice conferred protection against pneumococcal infection on recipient mice, whereas this effect was cancelled when the transferred spleen cells were harvested from PPV-immunized Dectin-2KO mice. These results suggest that the detection of PPV antigens via Dectin-2 triggers IL-12 production, which induces IFN-γ synthesis by NKT cells and subsequently the production of serotype-specific IgG.

Salivary adenoid cystic carcinoma (ACC) is a rare relentlessly progressive malignant tumor. The molecular events associated with ACC tumorigenesis are poorly understood. Variable microRNAs (miRNA) have been correlated with tumorigenesis of several solid tumors but not in ACC. To investigate the association of miRNAs with the development and/or progression of ACC, we performed a comparative analysis of primary ACC specimens and matched normal samples and a pooled salivary gland standard and correlated the results with clinicopathologic factors and validated selected miRNAs in a separate set of 30 tumors.MiRNA array platform was used for the identification of target miRNAs and the data was subjected to informatics and statistical interrelations. The results were also collected with the MYB-NFIB fusion status and the clinicopathologic features.Differentially dysregulated miRNAs in ACC were characterized in comparison to normal expression. No significant differences in miRNA expression were found between the MYB-NFIB fusion positive and -negative ACCs. Of the highly dysregulated miRNA in ACC, overexpression of the miR-17 and miR-20a were significantly associated with poor outcome in the screening and validation sets.Our study indicates that the upregulation of miR-17-92 may play a role in the biology of ACC and could be potentially targeted in future therapeutic studies.

Invasive fungal infections, particularly those considered opportunistic, have become a common and significant complication of procedures performed in advanced contemporary medicine. Among such infections, cryptococcosis, which is usually caused by infection with Cryptococcus neoformans and Cryptococcus gattii, is particularly problematic because this fungal infection occurs in immunocompromised and apparently immunocompetent individuals. It has been largely accepted that Cryptococcus species are recognized by cellular receptors and that Th1-type immune responses play an important role in defense mechanisms against the yeast. However, the interaction between the yeast and host tissue varies depending on the characteristics of the yeast and the immune status of the host. To gain a better understanding of the pathophysiology of cryptococcosis, we wish to emphasize the usefulness of histopathological examinations, because it allowed more detailed information of an extremely complex interaction between the causative yeasts and tissue response. In the present review, we describe the pathophysiology of cryptococcosis as largely revealed in our previous histopathological investigations of the experimental infection.

Since a gesture involves a dynamic and complex motion, multiview observation and recognition are desirable. For the better representation of gestures, one needs to know, in the first place, from which views a gesture should be observed. Furthermore, it becomes increasingly important how the recognition results are integrated when larger numbers of camera views are considered. To investigate these problems, we propose a framework under which multiview recognition is carried out, and an integration scheme by which the recognition results are integrated online and in realtime. For performance evaluation, we use the ViHASi (Virtual Human Action Silhouette) public image database as a benchmark and our Japanese sign language (JSL) image database that contains 18 kinds of hand signs. By examining the recognition rates of each gesture for each view, we found gestures that exhibit view dependency and the gestures that do not. Also, we found that the view dependency itself could vary depending on the target gesture sets. By integrating the recognition results of different views, our swarm-based integration provides more robust and better recognition performance than individual fixed-view recognition agents.

Aim: Aiming at environmental arrangements for pediatric cancer patients and their families to receive appropriate medical care and support with a sense of security, the Japanese Ministry of Health, Labour, and Welfare designated 15 hub hospitals for childhood cancer. These hub hospitals have established networks with approximately 200 centers/hospitals treating pediatric cancer. In order to promote equal access to nursing, we investigated nurses' difficulties and needs at these treatment hospitals with limited experience in pediatric cancer nursing., Methods: In order to examine education on pediatric cancer nursing, we investigated difficulties felt by treatment hospital nurses, their educational experience and their educational needs. A total of 584 nurses (66.51%) from 52 hospitals from which written consent was received completed the questionnaires., Results: Nurses had difficulties regarding nursing care for patients with critical conditions, such as terminal care, and actions to be taken when a patient's physical condition rapidly changes. Nurses most strongly desired education on nursing care for patients with serious problems, such as terminal care, and follow-up provided in the form of in- and hub-hospital lectures., Conclusion: Our study suggested that in order to provide nurses in treatment hospitals with education focusing on nursing care for patients with serious problems, education systems based on cooperation between hub and treatment hospitals are needed., (© 2020 The Authors. Japan Journal of Nursing Science published by John Wiley & Sons Australia, Ltd on behalf of Japan Academy of Nursing Science.)

Background and Objectives: Identification of yeasts provides helpful information for appropriate administration of anti-fungal treatments; however, few reports from the Vietnam have been published. This study has been performed to find the prevalence of Candida blood stream isolates from patients in two hospitals in Vietnam., Materials and Methods: Candida spp. were isolated from blood cultures in two hospitals, Vietnam between May 2013 and May 2015. Participating hospitals were 103 Military Hospital, Ha Noi city (550 beds) and Cho Ray Hospital, Ho Chi Minh city (1800 beds). All the bloodstream isolates were identified to species level by the germ tube test and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In addition, unknown isolates were subjected to PCR sequencing., Results: A total of 93 Candida isolates were isolated from blood cultures during the study period. The results of this study showed that C. tropicalis (n = 47, 50.54%) was the most common agent, followed by Candida albicans/dubliniensis (n = 18, 19.35%), C. parapsilosis (n = 16, 17.20%), C. glabrata (n = 6, 6.45%), C. mesorugosa (n = 5, 5.38%) and C. krusei (n = 1, 1.08%), respectively., Conclusion: The frequency of the non- albicans Candida species in blood is increasing, especially C. tropicalis . Additional investigations should be made to clarify the epidemiological profile of invasive Candida bloodstream in Vietnam.

It is necessary to consider the affinity of prodrugs for metabolic enzymes for efficient activation of the prodrugs in the body. Although many prodrugs have been synthesized with consideration of these chemical properties, there has been little study on the design of a structure with consideration of biological properties such as substrate recognition ability of metabolic enzymes. In this report, chemical synthesis and evaluation of indomethacin prodrugs metabolically activated by human carboxylesterase 1 (hCES1) are described. The synthesized prodrugs were subjected to hydrolysis reactions in solutions of human liver microsomes (HLM), human intestine microsomes (HIM) and hCES1, and the hydrolytic parameters were investigated to evaluate the hydrolytic rates of these prodrugs and to elucidate the substrate recognition ability of hCES1. It was found that the hydrolytic rates greatly change depending on the steric hindrance and stereochemistry of the ester in HLM, HIM and hCES1 solutions. Furthermore, in a hydrolysis reaction catalyzed by hCES1, the V max value of n-butyl thioester with chemically high reactivity was significantly lower than that of n-butyl ester., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims/introduction: To determine the diagnostic potential of plasma lipids and apolipoproteins in gestational diabetes mellitus (GDM), we carried out a retrospective cohort study of 1,161 Japanese women at 20-28 weeks of gestation who underwent a glucose challenge test (GCT)., Materials and Methods: A total of 1,161 Japanese women at 20-28 weeks of gestation underwent a GCT. Participants with a positive test (GCT[+]) underwent a subsequent oral glucose tolerance test. Clinical and biochemical parameters were determined and quantification of apolipoproteins (Apo), including ApoB, ApoB48, ApoA-I and ApoC-III, was carried out., Results: The prevalence of GCT(+; with a 130 mg/dL glucose cut-off) and GDM was 20% and 4%, respectively. There was a trend for increased triglycerides and ApoC-III in GDM(+) participants. However, the difference in plasma triglycerides, ApoC-III or ApoB48 did not reach statistical significance between GDM(+) and GDM(-) women. Values of 1-h glucose (P < 0.001) and fasting glucose (P = 0.002) were significant risk factors for GDM., Conclusions: Prediction of GDM using only the ApoC-III value is not easy, although triglycerides and ApoC-III were higher in the GDM(+) group. The present findings show no significant difference in plasma lipid levels between women diagnosed with GDM and those with normal glucose tolerance.

Aim: To assess the effects of sitagliptin and nateglinide on lipid metabolism., Methods: In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A1c (HbA1c) > 6.5% despite diet and exercise; HbA1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially., Results: Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m(2); the nateglinide group: 21.39 ± 2.24 kg/m(2)). Fasting levels of HbA1c, glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P < 0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P = 0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group., Conclusion: Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.

It is usually assumed that only amino acids located near the retinal chromophore are responsible for color tuning of rhodopsins. However, we recently found that replacement of Ala178 with Arg in the E-F loop of proteorhodopsin (PR), an archaeal-type rhodopsin in marine bacteria, shifts the lambda(max) from 525 to 545 nm at neutral pH [Yoshitsugu, M., Shibata, M., Ikeda, D., Furutani, Y., and Kandori, H. (2008) Angew. Chem., Int. Ed. 47, 3923-3926]. Since the location of Ala178 is distant from the retinal chromophore (approximately 25 A), the molecular mechanism of the unusual mutation effect on color tuning is intriguing. Here we studied this mechanism by using additional mutations and some analytical methods. Introduction of Arg into the corresponding amino acid in bacteriorhodopsin (BR, M163R mutant) does not change the absorption spectra, indicating that the effect is specific to PR. Introduction of Arg into the A-B or C-D loop yields little (3 nm) or no color change, respectively. T177R and P180R mutants exhibited absorption spectra identical to that of the wild type, while N176R and S179R mutants exhibit lambda(max) values of 528 and 535 nm, respectively. Therefore, the observed color change is position-specific, being fully effective at position 178 and half-effective at position 179. Salt affects the absorption spectra of wild-type and A178R PR similarly. FTIR spectroscopy at 77 K indicated similar chromophore structures for wild-type and A178R PR, and A178R PR pumps protons normally. We infer that the E-F loop has a unique structure in PR and the mutation of Ala178 disrupts the structure that includes the transmembrane region, leading to the observed changes in color and pK(a).

Bacteriorhodopsin (BR), a membrane protein found in Halobacterium salinarum, functions as a light-driven proton pump. The Schiff base region has a quadrupolar structure with positive charges located at the protonated Schiff base and Arg82, and the counterbalancing negative charges located at Asp85 and Asp212. The quadropole inside the protein is stabilized by three water molecules, forming a roughly planar pentagonal cluster composed of these waters and two oxygens of Asp85 and Asp212 (one from each carboxylate side chain). It is known that BR lacks proton-pumping activity if Asp85 or Asp212 is neutralized by mutation, but binding of Cl- has different functional effects in mutants at these positions. Binding of Cl- to D85T converts into a chloride ion pump (Sasaki, J., Brown, L. S., Chon, Y.-S., Kandori, H., Maeda, A., Needleman, R., and Lanyi, J. K. (1995) Science 269, 73-75). On the other hand, photovoltage measurements suggested that binding of Cl- to D212N restores the proton-pumping activity at low pH (Moltke, S., Krebs, M. P., Mollaaghababa, R., Khorana, H. G., and Heyn, M. P. (1995) Biophys. J. 69, 2074-2083). In this paper, we studied halide-bound D212N mutant BR in detail. Light-induced pH changes in a suspension of proteoliposomes containing D212N(Cl-) at pH 5 clearly showed that Cl- restores the proton-pumping activity. Spectral blue-shift induced by halide binding to D212N indicates that halides affect the counterion of the protonated Schiff base, whereas much smaller halide dependence of the lambdamax than in D85T suggests that the binding site is distant from the chromophore. In fact, the K minus BR difference Fourier-transform infrared (FTIR) spectra of D212N at 77 K exhibit little halide dependence for vibrational bands of retinal and protein. The only halide-dependent bands were the C=N stretch of Arg82 and some water O-D stretches, suggesting that these groups constitute a halide-binding pocket. A strongly hydrogen-bonded water molecule is observed for halide-bound D212N, but not for halide-free D212N, which is consistent with our hypothesis that such a water molecule is a prerequisite for proton-pumping activity of rhodopsins. We concluded that halide binding near Arg82 in D212N restores the water-containing hydrogen-bonding network in the Schiff base region. In particular, the ion pair formed by the Schiff base and Asp85 through a strongly hydrogen-bonded water is essential for the proton-pumping activity of this mutant and may be controlled by the halide binding to the distant site.

The patient is a 71-year-old woman who underwent splenectomy after the diagnosis of idiopathic portal hypertension (IPH) at the age of 51 years. Thirst and polyuria occurred in December 1995. In April 1996, she was hospitalized for assessment because of elevation of her blood glucose and HbA1c levels to 535 mg/dl and 14.9%, respectively. The GAD antibody level was high (256 units/ml) and tests for ICA and anti-TPO antibody were positive. Since her HLA type was A 24, B 13, B 46, CW 1, CW 3, DRB 1*[0901/0901], DQB 1*[0303/0303], and DPB 1*[0201/0201], this patient was regarded as being susceptible to type 1 diabetes mellitus. There was no evidence of portal hypertension at the time of consultation. Although there was a considerable difference in the time of onset between IPH and type I diabetes mellitus, we reported this patient as a valuable case for investigating the complications of autoimmune disease.

Background: Multicentric development of hepatocellular carcinoma (HCC) is a characteristic feature of hepatitis C virus (HCV)-associated cirrhosis (HCV-LC). In this study, the objective was to determine whether the persistent elevation of the serum alanine aminotransferase (ALT) level, which represents the inflammatory necrosis of hepatocytes, is correlated with the multicentric development of hepatocellular carcinoma (HCC) in patients with early-stage HCV-LC., Methods: Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage A) who had been followed for > 5 years for the development of HCC were studied. They were subdivided into three groups according to their serum ALT level: Group A included 33 patients with annual average serum ALT levels that were persistently high (> or = 80 IU; high ALT group), Group B included 41 patients with annual average serum ALT levels that were persistently low (< 80 IU; low ALT group), and Group C included 19 unclassified patients. The patients had been studied prospectively with frequent ultrasonography and magnetic resonance imaging or computed tomography (CT) scans for > 5 years. When the development of HCC was suspected, angiography, infusion of lipiodol into the hepatic artery, and lipiodol-CT scans were performed in all patients to determine the number of HCC nodules., Results: In Group A, 27 patients (81.8%) developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1 of these 12 patients (8.3%) had multiple nodules. There was a significant difference between Groups A and B in the incidence of developing HCC (P < 0.001) and developing multiple nodules (P = 0.006). In addition, among the male patients, the incidence of developing multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was significantly higher (P < 0.05) compared with the incidence in Group B (0 of 6 patients; 0%). The same tendency was observed among the female patients., Conclusions: These results showed a close correlation between multicentric hepatocarcinogenesis and sustained necroinflammation of the liver in patients with HCV-LC., (Copyright 2002 American Cancer Society.)

A study was made of a 55 years old male, who suffered from emphysematous cystitis with diabetes mellitus. He had multiple complications due to diabetic neuropathy such as foot ulceration, oculomotor nerve palsy, peroneal nerve palsy and a neurogenic bladder. Klebsiella pneumoniae and Pseudomonous aeruginosa were cultured from urine specimens. There have been only 19 reported cases of emphysematous cystitis since 1962. Fourteen of these cases had diabetes mellitus.

Objective: To assess the production of prostaglandin E(2), an important chemical mediator in diarrhea induced by laxative administration, a prostaglandin E-main urinary metabolite (7alpha-hydroxy-5,11-diketotetranor-prosta-1,16-dioic acid, PGE-MUM) was measured in healthy volunteers and compared with the values of patients with ulcerative colitis., Methods: PGE-MUM was determined by a simplified immunoassay of bicyclic PGE-MUM and analyzed for the influence of laxative administration and active/remission phases of ulcerative colitis., Results: Administration of laxatives induced a significant increase in PGE-MUM in healthy volunteers. A significant elevation was also found in the active as compared with the remission phase of ulcerative colitis. The PGE-MUM levels were significantly correlated with our modified Talstad scores, clinical disease activity indices in ulcerative colitis. It was confirmed by time course studies of individual patients that changes in PGE-MUM correlated well with colitis activity., Conclusion: Laxative administration induces production of prostaglandin E(2) as one of the chemical mediators, although its production grade is relatively low as compared with ulcerative colitis in the active phase., (Copyright 2000 S. Karger AG, Basel)

Various endocrine disturbances are often observed in the patients with liver cirrhosis. We focused this paper on the sex hormones. Clinical features of male cirrhotic subjects are feminization(gynecomastia etc) and hypogonadism(testicular atrophy, reduced fertility, loss of libido, impotence etc). Chief abnormalities of sex hormones are a decrease in serum testosterone levels and an increase in serum estrogen levels accompanied by an increase in ratio of estrogen to testosterone in the patients with severe liver cirrhosis associated with the severity of hepatic dysfunction. Hyperestrogenization may be related with feminization of male cirrhotic subjects, whereas hypogonadism is the result of alcohol abuse per se, rather than the indirect consequence of liver cirrhosis.

This study was conducted to investigate the sialylations of glycoproteins in the nasal glands of patients with chronic sinusitis. Sialic acids were detected using lectin histochemistry, and the mRNA of sialyltransferase was evaluated by in situ hybridization histochemistry. Sambucus nigra agglutinin (SNA), which recognizes terminal sialic acids, strongly stained the glandular mucous cells of normal subjects, but not those of patients with chronic sinusitis. In situ hybridization histochemistry showed that the expression of alpha2,6 sialyltransferase mRNA was decreased in the secretory cells of patients with chronic sinusitis. Our present results suggest that a reduction in sialyltransferase activity at the mRNA level in the nasal glands may lead to the persistence of chronic sinusitis.

There are few reports about direct effects of specific oxygen products on ciliary function because of their instability and reactivity. We investigated the direct effects of superoxide anion (O2-) and of hydrogen peroxide (H2O2) on the ciliary function of human respiratory epithelial cells, using monolayer cell cultures, high speed video analysis of frequency (CBF), amplitude (CBA), and coordination of ciliary beats and evaluating the surface structural changes of ciliated cells at the same time. 10(-2) M H2O2 decreased ciliary beat activity. The CBF was 36.5 +/- 4.4% and the CBA was 51.0 +/- 3.8% of the baseline (time = 0) after 5 min (all p < 0.001). Catalase (2 micrograms/ml) abolished the ciliotoxic effect of H2O2. The O2- produced by reaction of xanthine (0.06 mM)-xanthine oxidase (0.04 U/ml) caused a temporary rapid increase of 26.8 +/- 1.7% in CBF and an increase of 42.5 +/- 4.1% in CBA after 15 sec (all p < 0.001). Superoxide dismutase significantly reduced these increases. Results indicated that O2- activated ciliary function with a temporary increase in O2(-)-production. This suggests that the removal of H2O2 from the O2- reaction is important in improving mucociliary clearance in excessive oxygen metabolites.

The effects of exogenous ATP and physical stimulation on ciliary beat depressed by lipopolysaccharide from Pseudomonas aeruginosa were studied in cell culture. Both the ciliary beat frequency (CBF) and the amplitude (CBA) of human respiratory cells in monolayer cell cultures were studied by using a differential interference microscope equipped with a high speed video. Both the ATP and the physiol stimulation stimulated temporarily the depressed CBF and CBA. In both groups the CBF and CBA increased in 1 min to the initial level and then gradually decreased to the level before the stimulation. The duration of the ATP stimulation on the CBF (10.1 +/- 1.8 min) and CBA (10.1 +/- 2.3 min) were significantly better than the duration of physical stimulation on CBF (8.0 +/- 1.8 min) and CBA (6.8 +/- 1.6 min). However, the areas under the CBF/CBA curves (from the beginning of stimulation until the initial level of CBF or CBA was reached again) did not differ significantly. After the removal of the bacterial toxin the CBF was restored to the initial level. In the present study the adenosine receptor antagonist could not prevent the ciliostimulative effect of exogenous ATP combined with the physical stimulation. Both exogenous ATP and physical stimulation have a clear but temporary stimulative effect on the ciliary beat depressed by bacterial toxin, ATP being slightly more effective. It seems that the effects of ATP are not mediated by adenosine receptors.

We used human respiratory epithelial cells in floating culture to study the motility and surface morphology of the cilia during ciliogenesis. Ciliary motility and surface morphology was examined by a high-speed video system and electron microscopy, respectively. On day 8 of floating culture, but rarely before, cells with numerous moving short cilia with mean ciliary beat frequency (CBF) of 17.8 +/- 2.5 Hz (mean +/- SD) were seen. The mean CBF was highest on day 10 (19.6 +/- 3.9 Hz) and reached 17.4 +/- 2.5 Hz on day 14. The ciliary beat amplitude (CBA) was recognized on day 8, abruptly increased on day 9, then continued with aging of the culture. The intracellular coordination of ciliary beats was poor on day 8 with random beat direction but improved up to day 12 when the intracellular uniform beat direction was established. However, intercellular coordination remained absent even on day 14. Results suggest that immature short cilia have a rigid beat pattern. With the elongation of the resulting whip-like movement, the ciliary beat was gradually synchronized. Although a ciliary elongation seems to be required for making intracellular coordination, other factors are involved in intercellular coordination. Also, a high CBF does not always indicate the activity of mature cilia.

To study the detailed effects of exogenous adenosine triphosphate (ATP) on ciliary function, we used the differential interference microscope equipped with high speed video and evaluated ciliated cells from the human sinus mucosa in monolayer culture. With this system it was possible to evaluate all parts of ciliary motility with a minimum of interference from the mucous membrane, secretory cells and the autonomic nervous system. The best direct ciliostimulative effect of exogenous ATP on ciliary beat frequency (CBF) and ciliary beat amplitude (CBA) was observed at concentrations of ATP ranging from 10(-5) M to 10(-3) M. Exogenous ATP appeared to normalize the slightly damaged ciliary motility in groups with an initial CBF of 14 Hz or higher. When the CBF was less than 14 Hz, ATP produced an increase in CBF greater than 40%, an increase in CBA greater than 30%, but these did not reach the normal level in 5 min. The biggest increases: 59.9% in CBF and 40.7% in CBA were seen in the group with an initial CBF less than 9 Hz. In the cells with a low initial CBF and unsynchronized motility exogenous ATP increased the synchrony of ciliary movement together with an increase in CBF and CBA.

We experienced a chronic alcoholic patient in whom a large intake of alcohol led to the development of frank clinical diabetes, and glucose intolerance and insulin deficiency improved perfectly following abstinence from alcohol. The patient was a 31-year-old male with no diabetes among his relatives. He was a heavy drinker since 12 years, and especially had a large intake of alcohol from Dec. 25 '84 to Jan. 3 '85. From the end of Jan. 1985 he complained of thirst, polydipsia, polyuria and body weight loss from 94 to 69 Kg. On June 25 1985 he admitted for the treatment of diabetes and had abstinence from alcohol. The blood glucose and HbA1 levels were 291 mg/dl and 14.7%, respectively on admission. His 75 g OGTT was diabetic in type and serum insulin response to glucose decreased markedly. Liver function tests were normal, and islet cell antibody was negative. Blood adrenaline, noradrenaline, growth hormone, glucagon, cortisol, T3 and T4 levels were normal. FBS, HbA1 and 75 g OGTT recovered to normal by dietary treatment (1800 kcal) with oral hypoglycemic agents for 8 weeks. This case report suggests that the cause of alcohol-induced diabetes is probably due to impairment of insulin secretion by either alcohol itself or alcohol metabolites.

Smoking cessation instruction for individuals using a standardized smoking cessation manual and a handout developed by the authors was studied in a controlled trial among employees who visited a health center for Industrial Safety and Health Law mandated annual health examinations. Smokers in the study group were given 5-10 minutes smoking cessation instruction mainly by public health nurses and nutritionists following the above-mentioned manual and using the handouts. Subjects in both groups were interviewed by telephone to assess changes in smoking habits one month after the first contact. Smoking clients who came on Friday (132) and on Monday (93) were assigned to study and control groups, respectively. One hundred and nineteen members (90.2%) of the study group and 88 (94.6%) of the control group were successfully followed until one month after the initial contact. Seven subjects in the study group were not smoking one month after the instruction, while no one gave up smoking in the control group (p less than 0.05). It was confirmed by telephone survey that 6 of the 7 subjects who were not smoking at one month were still maintaining abstinence from smoking one year after the instruction. Smokers who did not stop smoking reported a reduction in their smoking dose in the study group. Lighter smokers reacted more readily to instruction than did heavier smokers and the knowledge level of subjects was positively associated with the success rate.