Accumulation of SNAP25 in mouse gustatory and somatosensory cortices in response to food and chemical stimulation.

Food intake stimuli, including taste, somatosensory, and tactile stimuli, are received by receptors in the oral cavity, and this information is then transferred to the cerebral cortex. Signals from recently ingested food during the weaning period can affect synaptic transmission, resulting in biochemical changes in the cerebral cortex that modify gustatory and somatosensory nervous system plasticity. In this study, we investigated the expression patterns of molecular markers in mouse gustatory and somatosensory cortices during the weaning period. The expression of synaptosomal-associated protein 25 (SNAP25), a component of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, was increased in the insular and somatosensory cortices at postnatal week 3 compared to postnatal week 2. Additionally, SNAP25 protein in the cerebral cortex accumulated in weaning mice fed solid food but not in mice fed only mother's milk at the weaning stage. Chemical stimulation by saccharin or capsaicin at the weaning stage also increased SNAP25 immunoreactivity in the insular or somatosensory cortical area, respectively. These results suggest that recently ingested chemical signals in the oral cavity during weaning increase the accumulation of SNAP25 in the gustatory and somatosensory cortices and promote neural plasticity during the development of the gustatory and somatosensory nervous systems.

Preoperative estimation of remnant hepatic function using fusion images obtained by (99m)Tc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography.

BACKGROUND: Assessment of hepatic functional reserve is important in hepatic resection. The aim of this study was to evaluate the role of hepatic asialoglycoprotein receptor (ASGP-R) analysis in the preoperative estimation of remnant liver function in liver surgery. METHODS: One hundred and one patients undergoing hepatic resection for liver tumours were studied. Seventeen patients had preoperative percutaneous transhepatic portal vein embolization (PTPE). Function of the hepatic remnant was estimated before surgery using radioactivity in fusion images of both liver single-photon emission computed tomography and computed tomography scans using (99m)Tc-labelled diethylene triamine penta-acetate-galactosyl-human serum albumin. RESULTS: All three patients with an ASGP-R concentration below 400 nmol/l and preoperative total amount of receptor in the future remnant liver (R0-remnant) of less than 53.0 nmol per liver died. Two patients with chronic hepatitis and R0-remnant values between 53.0 and 65.0 nmol per liver and a receptor concentration lower than 600 nmol/l developed liver dysfunction. The incidence of liver failure decreased inversely with increasing R0-remnant value. CONCLUSION: A combination of receptor concentration and the amount of hepatic receptor in the future liver remnant as detected on fusion images is useful in evaluating the risk of postoperative liver failure.

The association of Pro12Ala polymorphism in PPARgamma2 with lower carotid artery IMT in Japanese.

In this study, the association of the Pro12Ala peroxisome proliferator-activated receptor gamma2 (PPARgamma2) polymorphism with atherosclerosis was examined in a Japanese Type 2 diabetic population. PPARgamma has been identified as a key regulator of adipogenesis. Recently, some studies reported that the Pro12Ala polymorphism was associated with resistance to Type 2 diabetes. It is well-known that Type 2 diabetes is closely related with disorder of lipid metabolism as well as impaired glucose homeostasis, resulting in atherosclerosis. We aimed to evaluate the association between carriers of the Pro12Ala PPARgamma2 mutation and clinical profiles concerning atherosclerosis besides plasma glucose and lipid concentrations. Screening for the mutation was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method among 154 Type 2 diabetic patients. The homozygotes of the Pro12 allele were 143 (93%), the heterozygotes of the Pro12 and Ala12 allele were 11 (7%) and the homozygote of the Ala12 allele was not detected. The group with the Ala12 allele had a significantly lower value of carotid artery intima-media thickness (IMT) than that without it, although there was no difference between two groups in sex, age or other clinical variables we examined. The Pro12Ala PPARgamma2 polymorphism may be associated with carotid artery IMT values in Type 2 diabetes mellitus.

Uterine NK cells produce epidermal growth factor in the murine pregnant uterus.

Uterine natural killer (uNK) cells belong to the large granular lymphocytes in the murine pregnant uterus and play essential roles in pregnancy success. We defined whether uNK cells can produce epidermal growth factor (EGF) important for implantation and embryo growth. The uNK cells were immunohistochemically positive for anti-EGF antibody especially during days 6 to 9 and at day 15 of pregnancy. Immunoreaction for EGF receptor was observed on the stromal cells in the metrial gland and trophoblasts in the placental labyrinth. EGF secretion (72.1 +/- 2.25 ng/10(40 cells) was noted in cultured uNK cells isolated from the metrial gland at day 15 of pregnancy. Treatment of anti-asialo-GM I antibody raised the level of EGF (129 +/- 21.5 ng/10(4) cells). These results suggest uNK cell can produce and release EGF for placental development.

Accumulation of multiple T-cell clonotypes in the liver of primary biliary cirrhosis.

The histological hallmark of primary biliary cirrhosis (PBC) is the destruction of the interlobular and septal bile ducts accompanied by a dense accumulation of lymphocytes; this constellation of features is termed chronic nonsuppurative destructive cholangitis. To analyze the T cells responsible for bile duct destruction, the T-cell receptor (TCR) Vbeta repertoire was studied in liver biopsy specimens, and also in peripheral blood lymphocytes (PBL) obtained from seven patients with PBC in the early stage (Scheuer's stage I or II). The complementary DNA (cDNA) of each TCR Vbeta1-20 chain was amplified by reverse-transcription polymerase chain reaction (RT-PCR), and the PCR products were examined by single-strand conformation polymorphism (SSCP) analysis. On the RT-PCR/SSCP analysis, a leukemic cell line, HPB-ALL, showed bands in TCR Vbeta 5.2 and Vbeta 6, indicating clonal expansion with distinct TCR. In the PBL from healthy subjects, the PCR products were amplified from many TCR Vbeta and were shown as smears on SSCP, suggesting that PBL consist of diverse T-cell clones. In PBC, many TCR Vbeta products were amplified by RT-PCR in both liver tissues and PBL, and no biased expression of a particular Vbeta was observed. SSCP analysis revealed multiple bands in most Vbeta chains, suggesting the presence of selected but multiple T-cell clones. Both the number and types of Vbeta showing clonal expansion were heterogeneous in the PBC patients. A comparative RT-PCR SSCP analysis of each TCR Vbeta between tissue lymphocytes and PBL revealed the presence of some identical T-cell clones in both the PBC liver and the PBL. These results suggest that T cells infiltrating the liver in PBC consist of multiple clonotypes and that T-cell clones accumulated in the liver are also present in PBL.

Activated liver macrophages in human liver diseases.

Immunohistochemical analysis using monoclonal antibodies specific for cells of monocyte/macrophage lineage reveals that resident liver macrophages have a phenotype distinct from that of monocytes or activated liver macrophages. Liver macrophages consist of heterogeneous cell populations in maturation (matured 25F9-positive and immature 25F9-negative) but the ratio of two populations is constant in normal and diseased livers. The expression of CD14 is down-regulated in resident liver macrophages as compared to that in monocytes, while the expression of 25F9 is up-regulated. On the other hand, the expressions of CD14 and Fc gamma RI are up-regulated in activated liver macrophages in viral and autoimmune hepatitis. In vitro culture of monocytes in medium without cytokines induces the phenotype similar to that of resident liver macrophages. Addition of macrophage-colony stimulating factor or interferon-gamma into the culture medium induces the expression of Fc gamma RI, the phenotype of which resembles that of activated liver macrophages. These results suggest that liver macrophages consist of heterogeneous cell populations and that both phenotype and function are affected by the local milieu of cytokines.

Immunohistochemical phenotyping of liver macrophages in normal and diseased human liver.

The phenotypical heterogeneity of human liver macrophages was analyzed with monoclonal antibodies that recognize antigens specific for the monocyte-macrophage lineage. Most liver macrophages in normal and diseased liver were positive for CD68, whereas fewer matured macrophages were detected by 25-F9. Comparative staining of mirror sections revealed some to be doubly positive and others to be singly CD68 positive. Quantitative analysis confirmed the difference, suggesting heterogeneity of maturation in liver macrophages. Most liver macrophages in the normal liver were negative for CD14, a receptor for lipopolysaccharide and lipopolysaccharide-binding protein complexes. Liver macrophages in liver diseases were activated to express CD14 at varying degrees and were involved in the clearance of lipopolysaccharide-lipopolysaccharide-binding protein complexes. Fc gamma RI, a receptor for monomeric IgG that is involved in antibody-mediated cell cytotoxicity, was negative in the normal liver, but was expressed in liver macrophages at inflammatory sites (e.g., in piecemeal and focal necrosis) in diseased livers. Fc gamma RII was expressed in most liver macrophages, as well as in sinusoidal endothelial cells; Fc gamma RIII was expressed in a smaller number of liver macrophages. Expression of Fc gamma RII and Fc gamma RIII was increased in chronic active hepatitis. These results suggest that liver macrophages are heterogeneous in maturation and function and that they are activated in liver diseases as shown by the novel expression of CD14 and Fc gamma RI. The restricted expression of Fc gamma RI indicates that Fc gamma RI-positive macrophages, in cooperation with cytotoxic T lymphocytes, may play an important role in liver cell injury through antibody-mediated cell cytotoxicity.

Anxiety among Canadian, Japanese, and American children.

The What I Think and Feel, a revised children's manifest anxiety scale, was administered to 660 children in grades 1 through 6 in the U.S., Japan, and Canada. Both cultural and grade differences were found on the Lie and Anxiety scales. Males did not differ significantly from females on either anxiety or social desirability. Canadian and American children were generally higher on the Lie score (social desirability) and children from the U.S. reported a higher level of anxiety than did children from the other two nations.