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We report a pediatric case of disseminated Bartonella henselae infection accompanied by multiple intracranial lesions. The patient developed multiple intracranial lesions despite treatment with azithromycin and gentamicin. After switching to rifampicin, the clinical symptoms of the patient improved. Given its good penetration into the central nervous system, rifampicin may be recommended for the treatment of B. henselae infection accompanied by intracranial lesions., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Lymphocyte homing is mediated by the interaction between L-selectin on lymphocytes and its glycoprotein ligands modified with 6-sulfo sialyl Lewis x (6-sulfo sLe x ) glycans on high endothelial venules (HEVs) in peripheral lymph nodes (PLNs). However, the lack of specific antibodies reactive with both human and mouse 6-sulfo sLe x has limited our understanding of its function in vivo. Here, we generated a novel monoclonal antibody, termed SF1, that specifically reacts with 6-sulfo sLe x expressed on HEVs in both species in a manner dependent on sulfate, fucose, and sialic acid modifications. Glycan array and biolayer interferometry analyses indicated that SF1 specifically bound to 6-sulfo sLe x with a dissociation constant of 6.09 × 10 -9 M. SF1 specifically bound to four glycoproteins from PLNs corresponding to the molecular sizes of L-selectin ligand glycoproteins. Consistently, SF1 inhibited L-selectin-dependent lymphocyte rolling on 6-sulfo sLe x -expressing cells ex vivo and lymphocyte homing to PLNs and nasal-associated lymphoid tissues in vivo. Furthermore, SF1 significantly attenuated ovalbumin-induced allergic rhinitis in mice in association with significant suppression of Th2 immune responses. Collectively, these results suggest that SF1 can be useful for the functional analysis of 6-sulfo sLe x and may potentially serve as a novel therapeutic agent against immune-related diseases., (© 2023. Springer Nature Limited.)

Background: With the increased use of immune checkpoint inhibitors (ICIs), side effects and toxicity are a great concern. Anaphylaxis has been identified as a potential adverse event induced by ICIs. Anaphylaxis is a life-threatening medical emergency. However, the mechanisms and factors that can potentially influence the incidence and severity of anaphylaxis in patients with cancer remain unclear., Methods: Healthy, murine colon 26, CT26, breast 4T1, EMT6, and renal RENCA tumor-bearing mice were treated with an anti-PD-L1 antibody (clone 10F.9G2). Symptoms of anaphylaxis were evaluated along with body temperature and mortality. The amounts of antidrug antibody and platelet-activating factor (PAF) in the blood were quantified via ELISA and liquid chromatography-mass spectrometry (LC-MS/MS). Immune cells were analyzed and isolated using a flow cytometer and magnetic-activated cell sorting, respectively., Results: Repeated administration of the anti-PD-L1 antibody 10F.9G2 to tumor-bearing mice caused fatal anaphylaxis, depending on the type of tumor model. After administration, antidrug immunoglobulin G (IgG), but not IgE antibodies, were produced, and PAF was released as a chemical mediator during anaphylaxis, indicating that anaphylaxis was caused by an IgG-dependent pathway. Anaphylaxis induced by 10F.9G2 was treated with a PAF receptor antagonist. We identified that neutrophils and macrophages were PAF-producing effector cells during anaphylaxis, and the tumor-bearing models with increased numbers of neutrophils and macrophages showed lethal anaphylaxis after treatment with 10F.9G2. Depletion of both neutrophils and macrophages using clodronate liposomes prevented anaphylaxis in tumor-bearing mice., Conclusions: Thus, increased numbers of neutrophils and macrophages associated with cancer progression may be risk factors for anaphylaxis. These findings may provide useful insights into the mechanism of anaphylaxis following the administration of immune checkpoint inhibitors in human subjects., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Patients in psychiatric care wards face serious problems in terms of declining physical function due to aging and long-term hospitalization. This study aimed to determine the current status of locomotive syndrome (LS) in long-term inpatients in psychiatric care wards and to clarify the factors associated with LS risk severity., Methods: The study included 84 patients admitted to psychiatric care wards who underwent the LS stage test. We investigated the participants' age, length of stay, antipsychotic drug use, body mass index, and activities of daily living were assessed and analyzed the correlations between the LS stage test and each assessment item., Results: The participants' mean age was 60.0 ± 13.6 years, with those aged ≥60 years comprising nearly 60% of the sample. The participants' mean length of stay was 10.5 ± 12.0 years, and over half of the patients stayed >5 years: 17.9% stayed between 5 and 10 years, while 36.9% stayed ≥10 years. Nearly 90% of participants stayed for >1 year. The LS stage test showed that 60.7% of the participants were stage 3, 21.4% were stage 2, 14.3% were stage 1, and 3.6% had no risk. The results of the LS stage indicated significant correlations with age, length of stay, and the Barthel Index scores., Conclusions: Patients who stay in a psychiatric care unit for a long period experience declining physical function, which is associated with aging and long-term hospitalization and might affect their activities of daily living., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2021 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Asthma is an allergic disease that causes severe infiltration of leukocytes into the lungs. Leukocyte infiltration is mediated by the binding of sialyl Lewis X (sLe x ) glycans present on the leukocytes to E-and P-selectins present on the endothelial cells at the sites of inflammation. Here, we found that mouse eosinophils express sLe x glycans, and their infiltration into the lungs and proliferation in the bone marrow were significantly suppressed by an anti-sLe x monoclonal antibody (mAb) F2 in a murine model of ovalbumin-induced asthma. The percentage of eosinophils in the bronchoalveolar lavage fluid and bone marrow and serum IgE levels decreased significantly in the F2-administered mice. Levels of T helper type 2 (Th2) cytokines and chemokines, involved in IgE class switching and eosinophil proliferation and recruitment, were also decreased in the F2-administered mice. An ex vivo cell rolling assay revealed that sLe x glycans mediate the rolling of mouse eosinophils on P-selectin-expressing cells. These results indicate that the mAb F2 exerts therapeutic effects in a murine model of allergen-induced asthma, suggesting that sLe x carbohydrate antigen could serve as a novel therapeutic target for allergic asthma.

Water-soluble paper (WSP), which easily dissolves in water, has been found in criminal gang hideouts as evidence in crimes including bank transfer fraud, phone fraud, and grandparent scams, i.e. identity fraud to steal money. Distinguishing WSP products used in crimes is required in forensic investigations to link fraud groups with paper evidence or prove connections among fraud groups. In this work, we investigate distinguishing WSP products. White sheets of six WSP products available in Japan were analyzed by measuring the grammage and thickness, determining additive compounds by X-ray diffraction (XRD), X-ray fluorescence (XRF), and scanning electron microscopy (SEM)/energy dispersive X-ray spectrometry (EDX), and performing fiber analysis by transmitted light microscopy. The six products were categorized into three groups by grammage and thickness. XRD, XRF, and SEM/EDX analysis provided elemental information about additive compounds and their distribution on the surface. Pulp analysis by Graff "C" stain provided the composition and morphology of the pulp. The six products could be distinguished in a similar way to plain paper by these analyses. Our results demonstrate that conventional analytical methods used for plain paper analysis can also be used to discriminate WSP in forensic investigations., Competing Interests: Conflict of interest The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Accumulating evidence has shown that valproate has the greatest teratogenic potential for increasing the risk of major congenital malformations, such as neural tube defects, cleft palate, and neurodevelopmental disability. Although valproate is a pharmacological option for acute mania and is used as a stabilization drug for patients with bipolar disorder, some global guidelines state that valproate should not be used for girls or women of childbearing age with bipolar disorder. We investigated patterns in psychiatrists' prescription of valproate for bipolar female patients of childbearing age in Japan., Methods: From March to May 2018, we conducted a questionnaire survey among psychiatrists from all prefectures in Japan on psychiatric practice as it relates to major depression and bipolar disorder throughout women's life. The questionnaire had two parts: (1) assessment of participating psychiatrists' backgrounds and attitudes toward patients and (2) their patterns of prescription of psychotropics for female patients with mood disorders across generations and periods of pregnancy. Each question item had four response options: "not at all," "rarely," "sometimes," and "frequently." We examined patterns of prescription for childbearing-aged women (late adolescence/young adulthood aged 18-24 years, childbearing-age, older adults aged 25-49 years) and pregnant women., Results: In total, 571 psychiatrists (427 males, 123 females, and 21 unknowns) responded appropriately to the questionnaire, including 320 who examined at least one or more late adolescence/young adulthood bipolar women. Approximately 70% of psychiatrists answered that they frequently or sometimes prescribed valproate for bipolar women of childbearing age [late adolescence/young adulthood: not at all, n = 23 (7.5%); rarely, n = 69 (22.5%); sometimes, n =116 (37.8%); and frequently, n = 99 (32.2%); childbearing-age, older adults: not at all, n = 13 (2.7%); rarely, n = 67 (13.8%); sometimes, n = 185 (38.1%); and frequently, n = 220 (45.4%)]. The proportion of general hospital psychiatrists who answered "not at all" or "rarely" to the frequency of their valproate prescriptions was higher than that of psychiatrists working in other medical facilities ( χ 2 (3) = 18.2, p < 0.001)., Conclusion: Most psychiatrists frequently or sometimes prescribe valproate for women of childbearing age in Japan., (Copyright © 2020 Tachibana, Hashimoto, Tanaka, Watanabe, Sato, Takeuchi, Terao, Kimura, Koyama, Ebisawa, Shizu, Nagase, Hirakawa, Hatta, Nakazato and Iyo.)

CXC chemokine ligand 10 (CXCL10) is a CXC chemokine family protein that transmits signals by binding to its specific receptor, CXCR3. CXCL10 is also known as an interferon-γ-inducible chemokine involved in various biological phenomena, including chemotaxis of natural killer (NK) cells and cytotoxic T lymphocytes, that suppress tumor growth and inhibition of angiogenesis. In this study, we examined the effects of forced expression of CXCL10 in a murine colon carcinoma cell line (CT26) on growth and metastasis in syngeneic mice. We first established CT26 cells that were stably expressing murine CXCL10 (CT26/CXCL10) and compared their growth with their parental CT26 cells in vitro and in vivo. The in vitro growth of the CT26/CXCL10 and CT26 cells was comparable, whereas the in vivo growth of the CT26/CXCL10 cells in the skin was strongly suppressed. Liver metastasis of the CT26/CXCL10 cells was also significantly suppressed after intra-splenic implantation. Removal of NK cells by the administration of anti-asialo GM1 antibody canceled the suppression of subcutaneous growth and liver metastasis of CT26/CXCL10 cells. Immunofluorescence clearly showed that abundant NKp46-positive NK cells were recruited into the liver metastatic lesions of the CT26/CXCL10 cells, consistent with specific NK cell migration towards the culture supernatant from the CT26/CXCL10 cells in the chemotaxis assay using transwells. These findings indicate that CXCL10 prevents in vivo growth and metastasis of colon carcinoma cells by recruiting NK cells, suggesting that forced expression of CXCL10 in the colon tumors by gene delivery should lead to a favorable clinical outcome.

Ulcerative colitis (UC) is a chronic inflammatory disease histologically characterized by diffuse mononuclear cell infiltrates in colonic mucosa. These inflammatory cells are considered to be recruited via high endothelial venule (HEV)-like vessels displaying mucosal addressin cell adhesion molecule 1 (MAdCAM-1), the ligand for α4β7 integrin, and/or peripheral lymph node addressin (PNAd), an L-selectin ligand. 6- O-sulfation of N-acetylglucosamine in the carbohydrate moiety of PNAd is catalyzed exclusively by N-acetylglucosamine-6- O-sulfotransferase 1 (GlcNAc6ST-1) and GlcNAc6ST-2. To determine the role of 6- O-sulfation of N-acetylglucosamine on HEV-like vessels in UC, we used a chronic dextran sulfate sodium-induced colitis model using mice deficient in both GlcNAc6ST-1 and GlcNAc6ST-2. We found that more inflammatory cells, with expression of tumor necrosis factor α, were infiltrated in double knockout mouse colitis compared with that in wild-type mice. Moreover, the number of MAdCAM-1-positive vessels was increased in double knockout mouse colitis, and these vessels were bound by E-selectin•IgM chimeras that bind to unsulfated sialyl Lewis X (sLeX). These findings suggest that interactions between MAdCAM-1 and α4β7 integrin and/or unsulfated sLeX and L-selectin may become a dominant mechanism for inflammatory cell recruitment in the absence of 6-sulfo sLeX and contribute to more severe colitis phenotypes seen in double knockout mice.

The World Health Organization has warned that substandard and falsified medical products (SFs) can harm patients and fail to treat the diseases for which they were intended, and they affect every region of the world, leading to loss of confidence in medicines, health-care providers, and health systems. Therefore, development of analytical procedures to detect SFs is extremely important. In this study, we investigated the quality of pharmaceutical tablets containing the antihypertensive candesartan cilexetil, collected in China, Indonesia, Japan, and Myanmar, using the Japanese pharmacopeial analytical procedures for quality control, together with principal component analysis (PCA) of Raman spectrum obtained with handheld Raman spectrometer. Some samples showed delayed dissolution and failed to meet the pharmacopeial specification, whereas others failed the assay test. These products appeared to be substandard. Principal component analysis showed that all Raman spectra could be explained in terms of two components: the amount of the active pharmaceutical ingredient and the kinds of excipients. Principal component analysis score plot indicated one substandard, and the falsified tablets have similar principal components in Raman spectra, in contrast to authentic products. The locations of samples within the PCA score plot varied according to the source country, suggesting that manufacturers in different countries use different excipients. Our results indicate that the handheld Raman device will be useful for detection of SFs in the field. Principal component analysis of that Raman data clarify the difference in chemical properties between good quality products and SFs that circulate in the Asian market.

Naive lymphocytes systemically recirculate for immunosurveillance inspecting foreign antigens and pathogens in the body. Trafficking behavior such as the migration pathway and transit time within the gastrointestinal tract, however, remains to be elucidated. Rat thoracic duct lymphocytes (TDLs) were transferred to a congeneic host that had undergone mesenteric lymphadenectomy. The migration pathway was investigated using newly developed four-color immunohistochemistry and immunofluorescence. Donor TDLs showed rapid transition in gut tissues from which they emerged in mesenteric lymph around 4 h after intravenous injection. Immunohistochemistry showed that donor TDLs predominantly transmigrated across high endothelial venules (HEVs) at the interfollicular area of the Peyer's patches (PPs), then exited into the LYVE-1+ efferent lymphatics, that were close to the venules. The rapid recirculation depended largely on the local expression of unsulfated sialyl-Lewis X on these venules where putative dendritic cells (DCs) were associated underneath. Recruited naive T cells briefly made contact with resident DCs before exiting to the lymphatics in the steady state. In some transplant settings, however, the T cells retained contact with DCs and were sensitized and differentiated into activated T cells. In conclusion, we directly demonstrated that lymphocyte recirculation within the gut is a very rapid process. The interfollicular area of PPs functions as a strategically central site for rapid immunosurveillance where HEVs, efferent lymphatics and resident DCs converge. PPs can, however, generate alloreactive T cells, leading to exacerbation of graft-versus-host disease or gut allograft rejection., (© The Author(s) 2018. Published by Oxford University Press on behalf of The Japanese Society for Immunology.)

Sialyl Lewis X (sLe(x)) antigen functions as a common carbohydrate determinant recognized by all three members of the selectin family. However, its expression and function in mice remain undefined due to the poor reactivity of conventional anti-sLe(x) monoclonal antibodies (mAbs) with mouse tissues. Here, we developed novel anti-sLe(x) mAbs, termed F1 and F2, which react well with both human and mouse sLe(x), by immunizing fucosyltransferase (FucT)-IV and FucT-VII doubly deficient mice with 6-sulfo-sLe(x)-expressing cells transiently transfected with an expression vector encoding CMP-N-acetylneuraminic acid hydroxylase. F1 and F2 specifically bound both the N-acetyl and the N-glycolyl forms of sLe(x) as well as 6-sulfo-sLe(x), a major ligand for L-selectin expressed in high endothelial venules, and efficiently blocked physiological lymphocyte homing to lymph nodes in mice. Importantly, both of the mAbs inhibited contact hypersensitivity responses not only when administered in the L-selectin-dependent sensitization phase but also when administered in the elicitation phase in mice. When administered in the latter phase, F1 and F2 efficiently blocked rolling of mouse leukocytes along blood vessels expressing P- and E-selectin in the auricular skin in vivo. Consistent with these findings, the mAbs blocked P- and E-selectin-dependent leukocyte rolling in a flow chamber assay. Taken together, these results indicate that novel anti-sLe(x) mAbs reactive with both human and mouse tissues, with the blocking ability against leukocyte trafficking mediated by all three selectins, have been established. These mAbs should be useful in determining the role of sLe(x) antigen under physiological and pathological conditions., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background: Intercultural differences influence acute inpatient psychiatric care systems., Aims: To evaluate characteristics of acute inpatient care in a German and a Japanese hospital., Method: Based on a sample of 465 admissions to the Psychiatric State Hospital Regensburg (BKR) and 91 admissions to the Hirakawa Hospital (HH) over a six-month period in 2008, data from the psychiatric basic documentation system (BADO) were analysed with regard to socio-demographic characteristics, treatment processes and outcome indicators., Results: Schizophrenia and related psychosis was the most common diagnosis in both hospitals. Cases at the BKR were admitted more quickly after onset of the present episode. Global Assessment of Psychosocial Functioning (GAF) ratings at admission were lower at the HH. Most admissions to both hospitals received psychopharmacological treatment, but more at the HH received psychotherapy. Length of stay was significantly longer at the HH (75 days) than at the BKR (28 days). Admissions to the HH were more improved with regard to GAF and clinical global impression (CGI)., Conclusions: Acute admissions in Germany provide intensive care with short hospitalization as crisis intervention. For acute admissions in Japan, comprehensive care for severe mental illness precedes emergency admissions and achieves greater improvement with longer hospitalization.

Lymphocyte homing to peripheral lymph nodes (PLNs) is mediated by multistep interactions between lymphocytes and high endothelial venules (HEVs). Heparan sulfate (HS) has been implicated in the presentation of chemokines on the surface of HEVs during this process. However, it remains unclear whether this cell surface presentation is a prerequisite for lymphocyte homing. In this study, we generated conditional knockout (cKO) mice lacking Ext1, which encodes a glycosyltransferase essential for HS synthesis, by crossing Ext1(flox/flox) mice with GlcNAc6ST-2-Cre transgenic mice expressing Cre recombinase in HEVs. Immunohistochemical studies indicated that HS expression was specifically eliminated in PLN HEVs but retained in other blood vessels in the cKO mice. The accumulation of a major secondary lymphoid tissue chemokine, CCL21, on HEVs was also abrogated without affecting CCL21 mRNA levels, indicating that HS presents CCL21 on HEVs in vivo. Notably, a short-term lymphocyte homing assay indicated that lymphocyte homing to PLNs was diminished in the cKO mice by 30-40%. Consistent with this result, contact hypersensitivity responses were also diminished in the cKO mice. The residual lymphocyte homing to PLNs in the cKO mice was dependent on pertussis toxin-sensitive Gi protein signaling, in which lysophosphatidic acid-mediated signaling was partly involved. These results suggest that chemokine presentation by HS on the surface of HEVs facilitates but is not absolutely required for lymphocyte homing.

Claudin-4 regulates ion permeability via a paracellular pathway in renal epithelial cells, but its other physiological functions have not been examined. We found that hyperosmotic stress increases claudin-4 expression in Madin-Darby canine kidney cells. Here, we examined whether claudin-4 affects cell motility, cell association, and the intracellular distribution of endogenous junctional proteins. Doxycycline-inducible expression of claudin-4 did not change endogenous levels of claudin-1, claudin-2, claudin-3, occludin, E-cadherin, and ZO-1. Claudin-4 overexpression increased cell association and decreased cell migration without affecting cell proliferation. Doxycycline did not change cell junctional protein levels, cell association or cell migration in mock-transfected cells. The insolubility of claudin-1 and -3 in Triton X-100 was increased by claudin-4 overexpression, but that of claudin-2, occludin, ZO-1, and E-cadherin was unchanged. Immunocytochemistry showed that claudin-4 overexpression increases the accumulation of claudin-1 and -3 in tight junctions (TJs). Furthermore, claudin-4 overexpression increased the association of claudin-4 with claudin-1 and -3. These results suggest that claudin-4 accumulates claudin-1 and -3 in TJs to enhance cell-cell contact in renal tubular epithelial cells., (Copyright © 2011 Wiley Periodicals, Inc.)

Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4(+)CD25(+) regulatory T cells (T(reg) cells). Compared with the homing of CD4(+)CD25(-) conventional T cells, the homing of CD4(+)CD25(+) T(reg) cells to NALT was less dependent on the L-selectin-PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses.

Cell surface glycans play pivotal roles in immune cell trafficking and immunity. Here we present an efficient method for generating anti-carbohydrate monoclonal antibodies (mAbs) using gene-targeted mice and describe critical glycans in lymphocyte homing. We immunized sulfotransferase GlcNAc6ST-1 and GlcNAc6ST-2 doubly deficient mice with sulfotransferase-overexpressing Chinese hamster ovary cells and generated two mAbs, termed S1 and S2. Both S1 and S2 bound high endothelial venules (HEVs) in the lymphoid organs of humans and wild-type mice, but not in those of doubly deficient mice. Glycan array analysis indicated that both S1 and S2 specifically bound 6-sulfo sialyl Lewis X and its defucosylated structure. Interestingly, S2 inhibited lymphocyte homing to peripheral lymph nodes by 95%, whereas S1 inhibited it by only 25%. S2 also significantly inhibited contact hypersensitivity responses and L-selectin-dependent leukocyte adhesion to HEVs. Immunohistochemical and Western blot analyses indicated that S1 preferentially bound sulfated O-glycans, whereas S2 bound both sulfated N- and O-glycans in HEVs. Furthermore, S2 strongly inhibited the N-glycan-dependent residual lymphocyte homing in mutant mice lacking sulfated O-glycans, indicating the importance of both sulfated N- and O-glycans in lymphocyte homing. Thus, the two mAbs generated by a novel method revealed the cooperative function of sulfated N- and O-glycans in lymphocyte homing and immune surveillance.

Introduction: Despite an increasing concern that atypical antipsychotics seem to have a stronger diabetogenic risk than conventional antipsychotics, little information is available on the prevalence of diabetes among schizophrenia patients, and prescription patterns for patients with comorbid schizophrenia and diabetes in Japan., Objectives: To compare the prevalence of diabetes between schizophrenia patients and the general population and to investigate whether diabetes status correlates the prescription patterns of antipsychotics at hospital discharge., Methods: Schizophrenia patients who were discharged between April 2004 and March 2005 and who continued to receive outpatient treatment from 526 hospitals were included in this retrospective open cohort study. We collected information about the doctor diagnosis of diabetes during hospitalization, and drug prescriptions for schizophrenia at hospital discharge using medical charts., Results: The overall prevalence of diabetes was 8.6% among patients with schizophrenia. Compared with the general population, the estimates of diabetes prevalence in the schizophrenia population were 2.6-10.8 percentage point higher among males aged 30-49 years, and 1.9-9.9 percentage point higher among females aged 40-59 years. The odds of being prescribed conventional antipsychotics were about 2 times higher among patients with diabetes than without diabetes, relative to atypical and combination of conventional and atypical antipsychotics. These results were robust across various sensitivity analyses., Conclusion: When treating schizophrenia patients with preexisting diabetes, psychiatrists need to monitor the occurrence of diabetes regularly regardless of antipsychotic class, strike a balance, and provide the most efficacious antipsychotic medication., (Copyright (c) 2010 Elsevier B.V. All rights reserved.)

Objectives: To consider smoke-free policies for the patients with schizophrenia, the present study examined how smoking behavior is related to hospital readmission among patients with schizophrenia., Methods: A retrospective study was conducted in 2007 on 460 discharged patients with schizophrenia who voluntarily admitted in the participating psychiatric hospitals at first time. We reviewed smoking status, readmissions, and other variables including socio-demographic characteristics, process of care, and social functioning at discharge using the Global Assessment of Functioning scale (GAF)., Results: The rate of cigarette smoking in this study was 42.2%. The rate of smoking was significantly higher in males (56.1%) than in females (26.2%). Mean GAF score at discharge was slightly higher in smoking patients than non-smoking patients (g = 0.18). Cox proportional hazard model revealed that hospital readmission rate was significantly higher in smoking patients than non-smoking patients after controlling for all other variables (HR = 1.78)., Conclusions: Non-smoking patients had fewer hospital readmissions than smoking patients. This finding could be a reason to promote cessation of smoking which might provide positive influences on prognosis of schizophrenia.

High endothelial venules (HEVs) are specialized blood vessels of secondary lymphoid organs composed of endothelial cells with a characteristic cuboidal morphology. Lymphocytes selectively adhere to and migrate across HEVs to initiate immune responses. In this study, we established a novel transgenic mouse line expressing Cre recombinase under the transcriptional control of the gene encoding HEV-expressed sulfotransferase, N-acetylglucosamine-6-O-sulfotransferase 2 (GlcNAc6ST-2), using bacterial artificial chromosome recombineering. Crossing these transgenic mice with the ROSA26 reporter strain, which expresses lacZ following Cre-mediated recombination, and staining the resulting progeny with 5-bromo-4-chloro-5-indolyl-beta-D-galactoside indicated that Cre recombinase was specifically expressed in mAb MECA79-reactive HEVs in secondary lymphoid organs but not in any other blood vessels of the transgenic mice. The expression of Cre recombinase correlated with a developmental switch, from immature, mAb MECA367-reactive HEVs to mature, mAb MECA79-reactive HEVs in neonatal lymph nodes. In addition to the HEVs, Cre recombinase was also strongly expressed in the colonic villi, which recapitulated the intrinsic expression of GlcNAc6ST-2 as confirmed in GlcNAc6ST-2(GFP/GFP) knock-in mice and by RT-PCR. Furthermore, treatment with an antimicrobial agent revealed that the colonic expression of Cre recombinase in the transgenic mice was regulated by commensal bacteria in the colon. In addition, Cre recombinase was expressed in a small subset of cells in the brain, testis, stomach, small intestine, and lung. In view of the restricted expression of Cre recombinase, this transgenic mouse line should be useful for elucidating tissue-specific gene functions using the Cre/loxP system.

Alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and P450IIE1 are the primary enzymes that catalyze the conversion of ethanol to acetaldehyde and then to acetate. Genetic polymorphisms have been reported in ADH2, ADH3, ALDH2, and the 5'-flanking region of P450IIEI. In this study, we used multivariate analysis to determine which genetic polymorphisms in alcohol metabolizing enzymes were independently associated with the development of alcoholic cirrhosis. Thirty-four noncirrhotic alcoholic patients, including 27 with fatty liver and 7 with nonspecific changes, and 46 patients with alcoholic liver cirrhosis were studied. Restriction fragment length polymorphisms (RFLPs) in the ADH2 and P450IIE1 genes were detected by digestion of polymerase chain reaction (PCR)-amplified DNA with MaeIII and RsaI, respectively. In the ALDH2 gene, RFLPs were detected by differences in the MboII site after PCR amplification. By multivariate analysis of four significant factors including total alcohol intake, ADH, ALDH, and P450IIE1 using the multiple logistic regression model, genotype ADH2(2)/ADH2(2) (P = .029) and genotype c1/c1 of P450IIE1 (P = .013) were found to be independently associated with alcoholic cirrhosis. The odds ratios for ADH2(2)/ADH2(2) genotype and the type A genotype of P450IIE1 (c1/c1) were 4.600 and 4.006, respectively. These results suggest that ADH2 and P450IIE1 gene polymorphisms may be independently associated with the development of alcoholic liver cirrhosis in Japan.

The urinary levels of L-fucose were measured in 93 alcoholics; 20 of these were without liver disease, 57 with noncirrhotic alcoholic liver disease, and 16 with alcoholic liver cirrhosis. In addition, patients with cirrhosis due to viral infection, and healthy subjects were evaluated. The mean urinary L-fucose concentration showed significantly higher values in patients with alcoholic liver disease and alcoholic liver cirrhosis when compared with the healthy subjects or the chronic alcoholics without liver disease (p < 0.001). The urinary L-fucose level was also significantly higher (p < 0.001) in cases of alcoholic liver cirrhosis than in noncirrhotic alcoholic liver disease (384 +/- 97 vs. 240 +/- 95 mumol/g of creatinine). No difference was observed between the healthy subjects and chronic alcoholics without liver disease (143 +/- 29 vs. 155 +/- 60 mumol/g of creatinine). The urinary level of L-fucose was significantly higher with alcoholic cirrhosis (384 +/- 97 mumol/g of creatinine) than with viral cirrhosis (265 +/- 42 mumol/g of creatinine) (p < 0.001). The measurement of urinary L-fucose may be a useful marker of alcoholic liver disease.

Sixty-three patients with alcoholic cirrhosis were retrospectively studied for the prevalence of antibodies to core (P22) and nonstructural (C100) region of hepatitis C virus (HCV). The prevalence rate of anti-P22 antibodies in patients with alcoholic cirrhosis was higher than that of anti-C100 antibodies (63.5% vs. 54.9%). The positivity rate of anti-C100 and/or anti-P22 antibodies was 73.0% (46/63) in alcoholic cirrhosis. We performed a multivariate analysis on the effects of age, sex, cumulative alcohol intake, anti-HCV antibodies, indocyanine green excretion test, and serum albumin on the development of hepatocellular carcinoma HCC in patients with cirrhosis, using Cox's proportional-hazards model, which revealed that anti-HCV positivity was the only independent prognostic variable for HCC in patients with alcoholic cirrhosis. The probability of HCC was significantly higher in the anti-HCV-positive patients than in the negative patients with alcoholic cirrhosis (p < 0.05). The 3-, 5- and 10-yr cumulative occurrence rate of HCC was, respectively, 13.3%, 41.3%, and 80.7% for anti-HCV-positive patients with alcoholic cirrhosis, compared with 0%, 8.3%, and 18.5% for anti-HCV-negative patients. In nonalcoholic patients with type C cirrhosis, the 3-, 5-, and 10-yr cumulative occurrence rate of HCC was 7.3%, 23.1%, and 56.5%, respectively. The follow-up studies indicate that hepatocarcinogenesis is hastened significantly in patients with alcoholic cirrhosis if they are positive for anti-HCV antibody, and that heavy alcohol consumption also is a risk factor for the development of HCC in patients with type C cirrhosis.

Serum levels of carbohydrate-deficient transferrin (CDT) were assayed in 87 patients with alcoholic liver disease, 25 alcoholics without liver disease, 25 cases with viral liver disease and 37 healthy subjects, by two different methods (Pharmacia CDT RIA kit and Axis % CDT kit). The serum level of Pharmacia-CDT was significantly higher in the patients with alcoholic liver disease (38.9 +/- 2.8 U/l) compared to the normal subjects (18.9 +/- 0.2 U/l), alcoholics without liver disease (21.7 +/- 1.5 U/l) and non-alcoholic liver disease (viral liver disease) (23.4 +/- 1.6 U/l) (P < 0.001). The serum level of Axis-CDT was also significantly higher in the patients with alcoholic liver disease (4.22 +/- 0.48%) compared to the normal subjects (0.84 +/- 0.14%), alcoholics without liver disease (1.14 +/- 0.23%) and non-alcoholic liver disease (1.84 +/- 0.29%) (P < 0.001). A significant correlation was found between serum levels of CDT determined by the two kits (r = 0.718, P < 0.001). The serum level of Axis-CDT was significantly higher in patients with alcoholic hepatitis compared to the normal subjects (P < 0.005), while the serum level of Pharmacia-CDT was not increased in the patients with alcoholic hepatitis. These results indicate that determination of serum CDT levels is a useful marker of alcoholic liver disease, not a marker for alcohol consumption. Axis-CDT is more useful than Pharmacia-CDT for assaying the serum level of CDT in patients with alcoholic liver disease.

The relationship between serum concentration of inorganic fluoride (F(-)) and cytochrome P-450 content after sevoflurane anesthesia was investigated in ethanol treated rats. Twenty male Wistar rats were randomly divided into 2 isocaloric diet groups of 10 rats each: one group receiving a standard diet and the other an ethanol diet. After 28 days on the diets the animals were administered 2.5% sevoflurane for 2 hr with 30% oxygen and 70% nitrous oxide. Cytochrome P-450 and cytochrome b(5) were induced by the ethanol diet. In the ethanol diet group serum concentration of F(-) was significantly higher than that of the standard diet group after sevoflurane anesthesia. These results suggest that cytochrome P-450 and b(5), which were induced by ethanol, enhanced sevoflurane defluorination.

Pooled sera collected from cirrhotic patients was fractionated by affinity chromatography with a fibronectin receptor monoclonal antibody against the beta-subunit of fibronectin receptor. Eluates were assayed using Western immunoblotting. The relative mobility of the protein reactive with fibronectin receptor antibody was nearly identical to that of the beta-subunit of fibronectin receptor, confirming that fibronectin receptor is present in human serum. Serum levels of the beta-subunit of fibronectin receptor were analyzed by sandwich enzyme-linked immunosorbent assay in patients with various liver diseases. The serum level of fibronectin receptor (micrograms/ml) was significantly higher in patients with chronic hepatitis (inactive, 2.59 +/- 0.04; active, 3.45 +/- 0.13), cirrhosis (4.77 +/- 0.30), alcoholic liver disease (2.96 +/- 0.16) and hepatocellular carcinoma (4.71 +/- 0.49) than in normal subjects (2.11 +/- 0.08). Strong positive correlation was observed between serum levels of fibronectin receptor and histological findings, particularly in the degree of hepatic fibrosis. Immunohistochemical studies with fibronectin receptor antibody revealed that the beta-subunit of fibronectin receptor was present on the plasma membrane of hepatocytes and sinusoidal lining cells in the normal liver and was increased in fibrotic areas and on the plasma membrane of hepatocytes and sinusoidal lining cells of fibrotic liver. The serum level of fibronectin receptor in patients with chronic liver diseases may therefore be a useful marker of hepatic fibrosis.