Detection of anti-Borna Disease Virus (BDV) antibodies from patients with schizophrenia and mood disorders in Japan

The relationship between infection with the Borna Disease Virus (BDV) and the clinical symptoms of schizophrenia and mood disorders (DMS-IV) was investigated. Western blotting techniques were used to examine anti-p10-BDV antibodies in serum from 32 patients with schizophrenia and 33 patients with mood disorders in Japan. The results showed that 1 out of 25 controls (4.0%), 7 out of 32 patients with schizophrenia (21.9%) and 9 out of 33 patients with mood disorders (27.3%) were positive for anti-BDV-p10 antibodies. Compared with levels of anti-BDV-p10 antibodies in controls, the production of anti-BDV-p10 antibodies failed to show a statistically significant relationship with schizophrenia but did show a significant relationship with mood disorder. The subgroup of schizophrenia patients with positive syndromes had a non-significantly higher frequency of anti-BDV-p10 antibodies than the subgroup of patients with negative syndromes. Similarly, the production of anti-BDV-p10 antibodies was non-significantly higher among patients with the unipolar subtype of mood disorder than in those with the bipolar subtype.     

Roles of the jejunum and ileum in the first-pass effect as absorptive barriers for orally administered tacrolimus

BACKGROUND: The immunosuppressant tacrolimus shows poor and variable bioavailability following oral administration in clinical use. Recently, the hepatic and intestinal metabolisms, or first-pass effect, of tacrolimus have been suggested to be responsible for its bioavailability. In the present study, we investigated the respective contribution of the jejunum and ileum to the first-pass effect of tacrolimus in rats. METHODS: The metabolism of tacrolimus in everted sacs of the duodenum, jejunum, and ileum was examined. Tacrolimus was administered intravenously or intraintestinally to sham-operated, jejunum-resected, or ileum-resected rats. Blood samples were collected over a 240-min period, and whole-blood tacrolimus concentrations were measured by semiautomated microparticle enzyme immunoassay. The pharmacokinetic parameters of tacrolimus in each group were estimated. RESULTS: The metabolic activity of tacrolimus appeared to be the highest in the everted sacs of the duodenum. The bioavailability of tacrolimus in the jejunum- or ileum-resected rats was higher than that in sham-operated controls. On the other hand, the time to peak concentration in the jejunum-resected rats was about twofold slower than those in ileum-resected and sham-operated rats. CONCLUSIONS: These results suggested that the first-pass effect of tacrolimus in the small intestine shows regional differences and the extraction of tacrolimus in the small intestine consists of the amount of extraction in the jejunum and ileum. In addition, the ileum rather than the jejunum as a graft of segmental small bowel transplantation would be useful to avoid the adverse effects of tacrolimus.     

Serum levels of soluble CD26 and CD30 in patients on hemodialysis

BACKGROUND/AIMS: Various abnormalities of the immune system have been demonstrated in patients on hemodialysis (HD). We hypothesize that the imbalance between type 1 helper T (Th1) cells and type 2 helper T (Th2) cells in patients on HD contributes to these abnormalities. Furthermore, we investigate the relationship between the Th1/Th2 imbalance and HD duration. METHODS: We measured the serum levels of soluble CD26 (sCD26) and soluble CD30 (sCD30) in 47 patients on HD and in 13 patients with chronic renal failure not on HD and analyzed the effect of HD duration on the serum levels of sCD26 and sCD30. RESULTS: The serum level of sCD26 in the HD group was significantly lower than that in the control group. On the other hand, the serum levels of sCD30 in the HD group and in the CRF group were significantly higher than in the control group. In the short-term HD group (<1 year), the serum levels of sCD26 were lower and the sCD30 levels higher than those in middle-term HD group (1-10 years). CONCLUSIONS: In the HD group, the Th1/Th2 balance may shift towards Th2 dominance. It is possible that this imbalance contributes to the abnormality of the immune system in HD patients.     

Comparison of plasma levels of mature adrenomedullin and natriuretic peptide as markers of cardiac function in hemodialysis patients with coronary artery disease

BACKGROUND: It has been suggested that, like ANP and BNP, high plasma levels of mature adrenomedullin (mAM) indirectly reflect the severity of heart failure or renal failure. However, the relationship between mAM levels and hemodynamics and cardiac function has not been examined in hemodialysis (HD) patients with coronary artery disease (CAD). The best marker, among mAM, ANP and BNP, for left-ventricular function in those patients is also unclear. PATIENTS AND METHODS: Plasma levels of mAM, total AM (tAM), ANP and BNP were determined before HD in chronic HD patients with CAD (group 1; n = 17) and were compared with those of HD patients without cardiac disease (group 2; n = 22). We examined their relationship to hemodynamics and cardiac function in group 1 using data obtained by cardiac catheterization. RESULTS: Plasma levels of ANP and BNP were significantly higher in group 1 than in group 2, but there was no significant difference in plasma levels of mAM and tAM between the two patient groups. Plasma levels of both mAM and tAM significantly correlated with right atrial pressure (RAP), and only plasma tAM levels correlated with pulmonary artery pressure (PAP) and pulmonary artery wedge pressure (PAWP). However, no correlations were found between levels of the two forms of AM and ejection fraction (EF). In contrast, plasma ANP and BNP levels significantly correlated with both PAP and PAWP, and also with EF, although they did not correlate with RAP. The correlation of PAP and PAWP with ANP and BNP levels was closer than that with tAM levels. The most significant correlation was between BNP levels and EF (r = -0.756, p < 0.0001). CONCLUSIONS: Our results suggest that the mAM level may be less useful than natriuretic peptide levels as a marker of cardiac function in HD patients with CAD, and that the BNP level might be the best indicator of left-ventricular function. In addition, cardiac disease such as CAD may have a minor impact on mAM levels compared to renal failure.     

Methylenetetrahydrofolate reductase polymorphism in childhood primary focal segmental glomerulosclerosis

AIM: The purpose of this study was to evaluate the association between the methylenetetrahydrofolate reductase (MTHFR) C/T polymorphism and the prevalence and course of focal segmental glomerulosclerosis (FSGS) in our pediatric population. METHODS: Genotypes for MTHFR were determined in 15 primary FSGS patients (male/female, 6/9) and 238 control subjects (male/female, 110/128) by the polymerase chain reaction and restriction fragment length polymorphism method. RESULTS: For the whole group, the genotype frequencies (CC/CT/TT) of MTHFR in FSGS and control subjects were almost comparable. The TT genotype was associated with early onset of the disease as compared with the CC genotype. Furthermore, all the patients with the TT genotype had steroid-resistant FSGS and developed into end-stage renal failure, while those carrying either CC or CT genotype did not. CONCLUSION: We speculate that the TT genotype may be associated with early development and progression of childhood FSGS. Confirmatory studies using larger and ethnically distinct populations are needed to reveal the role of homocysteine in FSGS with consideration of medical interventions.     

Effect of histamine on intercellular adhesion molecule-1 expression and production of interferon-gamma and interleukin-12 in mixed lymphocyte reaction stimulated with interleukin-18

BACKGROUND: Interleukin (IL)-18 was identified as an interferon (IFN)-gamma-inducing factor and was demonstrated to up-regulate the expression of intercellular adhesion molecule (ICAM)-1 on human monocytes. In organ transplantation, elevation of plasma IL-18 levels has been reported during acute rejection. In the present study, we examined the effect of IL-18 on human mixed lymphocyte reaction (MLR), an in vitro model of acute rejection after organ transplantation. We also investigated the modulatory effects of histamine on IL-18 action because histamine has been demonstrated to be a modulator of IL-18 effect and a mediator of inflammation. METHODS: We measured the expression of ICAM-1 on human monocytes in MLR in the presence or absence of IL-18 by flow cytometer and determined the associated production of IFN-gamma and IL-12 by ELISA. The modulatory effects of histamine and the relevant histamine receptor subtypes were characterized pharmacologically. RESULTS: The expression of ICAM-1 on monocytes in MLR was markedly enhanced by the addition of IL-18 in a concentration- and time-dependent manner. In parallel to ICAM-1 up-regulation, IL-18 significantly enhanced the production of IFN-gamma and IL-12 in MLR. Histamine concentration-dependently inhibited ICAM-1 expression and cytokine production in MLR stimulated with IL-18, whereas histamine alone did not show any effects on these responses in the absence of IL-18. The effects of histamine on both ICAM-1 expression and cytokine production were mimicked by the selective H2-receptor agonists 4-methylhistamine and dimaprit and were antagonized by the H2-receptor antagonist famotidine but not by H1- and H3-receptor antagonists. CONCLUSION: IL-18 strongly enhanced human MLR with respect to ICAM-1 expression and cytokine production. The fact that histamine could inhibit the IL-18-stimulated MLR implies that immunomodulation by histamine and selective H2-receptor agonists may have an important role in future immunosuppressive strategies.     

Direct killing of xenograft cells by CD8+ T cells of discordant xenograft recipients

BACKGROUND: Long-term pig xenografts in monkeys demonstrated the infiltration of CD8 T cells into pig cartilage xenografts, transplanted into monkeys. The objective of the present study was to determine in an experimental animal model whether CD8 T cells in pig xenograft recipients exert any direct cytotoxic effect on pig cells. METHODS: The killing of xenograft cells by CD8 T cells, obtained from xenograft recipients, was studied in alpha1,3galactosyltransferase knockout mice that were repeatedly injected intraperitoneally with pig kidney membranes. The pig kidney cell line PK15, which shares many antigens with pig kidney membranes, served as a model for xenograft target cells in cytotoxicity assays. Cell lines from other species were also studied as target cells. RESULTS: Lymphocytes obtained freshly from spleens of mice immunized with pig kidney membranes failed to display significant cytotoxic activity against pig cells. However, incubation of these lymphocytes with irradiated PK15 cells and addition of recombinant interleukin (IL)-2 (100 U/mL), on the third day of incubation, resulted in extensive proliferation and expansion of CD8 cytotoxic T lymphocytes (CTL). These CTL, obtained after 12 days of incubation, killed nonspecifically pig, human, and mouse normal and malignant cells. These CTL were not generated in cultures in the absence of stimulatory pig cells or in the absence of IL-2. These CTL could not be generated in cultures of lymphocytes from naive mice that were incubated with PK15 cells and IL-2. CONCLUSIONS: The data obtained imply that CD8 T cells from xenograft recipients can be stimulated in vitro by xenoantigens and IL-2 to differentiate into highly reactive nonspecific CTL that are capable of killing a large variety of xenogeneic and syngeneic cells. Similar in vivo microenvironmental conditions within the xenograft may induce the local differentiation of infiltrating CD8 T cells into CTL that can destroy nonspecifically adjacent xenograft cells. Such cells may not be active outside the xenograft because of the absence of IL-2 in sufficiently high concentrations.     

Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology

BACKGROUND: Invasion to the visceral pleura is an important component of lung cancer staging and an independent prognostic factor. However, the accuracy of pathologic examination depends on how the sections are made, and the pathologist may miss the most invaded part of the pleura. Therefore, we have designed "touch" cytology in an effort to more accurately diagnose the pleural invasion by lung cancer. METHODS: Immediately after thoracotomy, the surface of the visceral pleura just above the tumor was gently touched by a glass slide without scrubbing in 100 patients who simultaneously underwent pleural lavage cytology or cytology of the subclinical pleural effusion. RESULTS: Seventeen percent of the tumors were diagnosed as invading the visceral pleura by touch cytology. Lavage cytology was found to be positive in 7%. In reference to the pathologic examination of the tumor specimen, touch cytology was found to be positive in all of p3, 5 out of 6 of p2, 5 out of 30 of p1, and 5 out of 62 of p0 cases. Touch cytology correctly diagnosed all the positive cases detected by lavage or effusion cytology. CONCLUSIONS: This study suggests that our method is useful in detecting the visceral pleural invasion and raises a possibility that pathologic p0 and p1 lung cancers include a subset of patients with tumor cells exposed on the pleural surface.     

Subchondral cysts arise in the anterior acetabulum in dysplastic osteoarthritic hips

The distribution of subchondral cysts in 57 dysplastic osteoarthritic hips of 38 patients was assessed by computed tomography and by a new computerized technique. The cyst count in osteoarthritic hips was inversely correlated with the width of the joint space. A greater accumulation of cysts was found in the acetabulum than in the femoral head, and more cysts were found in the anterior part of the hip than in the posterior part. Osteoarthritic change was more predominant in the acetabulum than in the femoral head, and was more predominant in the anterior part of the hip than in the posterior part.