Histamine downregulates CD14 expression via H2 receptors on human monocytes

Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.     

Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.     

Establishment and characterization of cell lines from human adenovirus type 12-induced murine tumors producing endogenous virus particles.

Two cell lines designated IC-KMS and D-KMS were established from human adenovirus type 12-induced tumors of C3Hf/OK mouse. The cell lines retained the characteristics of the original tumor i.e., production of numerous C-type and intracisternal A-type particles, integration of Ad12 E1 region DNA and amplification of the myc gene family. Chromosomal analysis revealed chromosome aberrations in both IC-KMS and D-KMS cells. The modal chromosome number of IC-KMS cells was 54 and that of D-KMS cells was 48. Metacentric chromosomes and minichromosomes were found. Trisomy of chromosome 3, 7 and 12 was seen frequently in D-KMS cells. Although DNA aneuploidy was revealed by flow cytometry, the DNA indices of these cells showed no relation to the copy number of integrated Ad12 DNA. These cells have been propagated by serial culture during the past 17 months. Production of endogenous virus particles is a unique characteristic of IC-KMS and D-KMS cells. These cell lines would be useful materials for examining the contribution of Ad12 carcinogenesis to activation of endogenous virus particles, and also the correlation between Ad12 carcinogenesis and cancer-related genes.     

A simple and rapid method for the determination of macrophage activating factor involving a new type of apparatus suitable for the measurement of macrophage chemiluminescence

A simple and rapid method for the determination of macrophage activating factor is described. A new type of apparatus suitable for the measurement of macrophage chemiluminescence was devised, and the effect of lymphokines on macrophage activities was studied by measuring phorbol myristate acetate-induced luminol-dependent chemiluminescence. An outstanding feature of the new apparatus is that the plastic dish used for the cell culture can be used as the vessel for the chemiluminescence reaction. When thioglycollate-elicited ICR mouse peritoneal macrophages were incubated with lymphokines, their ability to generate chemiluminescence increased rapidly, reaching a maximal level at about 4 h, and then it progressively decreased to the control level at 8 h. Although this increasing effect of lymphokines on macrophage chemiluminescence was short-lived, it could be seen at a relatively low concentration, at which lymphokine-mediated cytotoxic activity of macrophages was not observed.     

Appearance of prolactin-releasing peptide-producing neurons in the area postrema of adrenalectomized rats

Prolactin-releasing peptide (PrRP) was found to be a novel hypothalamic peptide that stimulates prolactin release in vitro and in vivo. In the normal adult rat brain, PrRP neurons are known to be located in only three areas, i.e. the dorsomedial hypothalamic nucleus, ventrolateral reticular formation; and nucleus of the tractus solitarius in the medulla oblongata. These PrRP neurons project neurites into various brain areas, including regions such as the paraventricular nucleus, supraoptic nucleus, and bed nucleus of the stria terminalis. Both PrRP nerve fibers and a high level of PrRP receptor, UHR-1, mRNA are observed in the area postrema (AP),but no PrRP neurons are detected in the AP of normal rats. In this study, we clearly demonstrated that PrRP-producing cells newly appeared in the AP of adrenalectomized rats by in situ hybridization and immunocytochemistry. Our results suggest that PrRP may have some important roles in the AP of adrenalectomized rats. This is the first report demonstrating the appearance of PrRP-positive cells in the AP.     

Genetic verification of the role of CCK-AR in pancreatic proliferation and blood glucose and insulin regulation using a congenic rat carrying CCK-AR null allele

A number of studies have indicated that cholecystokinin type A receptor (CCK-AR) plays a crucial role in postnatal pancreatic proliferation and blood glucose regulation through stimulating insulin secretion. The Otsuka Long-Evans Tokushima Fatty (OLETF) rat has been shown to possess poor pancreatic proliferation (PPP) capability after pancreatectomy (Px). Here we have constructed a congenic strain which introgressed an OLETF-derived 18.5 cM genomic fragment identified in our previous quantitative trait locus (QTL) analysis as a locus responsible for PPP into normoglycemic F344 genetic background The introgressed region includes CCK-AR null mutation. After Px, the congenic rat showed weak pancreatic proliferation equivalent to that of the OLETF rat. Furthermore, post-surgery non-fasting blood glucose levels for the congenic rats are significantly higher in comparison with the F344 rats. At 28 days after Px, the congenic rats also showed lower blood insulin levels than the F344 rats. These results further provide the genetic evidence that 1) CCK-AR is essential for pancreatic regeneration; 2) impaired pancreatic proliferation mediates the development of hyperglycemia.     

Villous capillary lesions of the placenta: distinctions between chorangioma, chorangiomatosis, and chorangiosis

Chorangioma (CA), chorangiosis (CH), and chorangiomatosis (CM) are incompletely understood and overlapping villous capillary (VC) lesions believed by some to be related to hypoxia. In this study, we reviewed all cases of CA (n = 36, 0.51%) and CM (n = 39, 0.55%) diagnosed in 7,062 placentas examined at our institution between 1990 and 1999. CH was evaluated in a subsample of 689 cases (n = 46, 6.67%). Controls were derived from cases in the subsample (n = 639) without any VC lesions. Most CA were incidental findings measuring less than 0.5 cm. Nodular and multinodular morphologic variants were otherwise similar. CA were most frequently located under the chorionic plate and at the placental margins and occasionally showed nonspecific trophoblast hyperplasia (Ki-67-positive) similar to that seen in partial moles. CA and CM shared associations with preeclampia, multiple gestation, and premature delivery at 32 to 26 weeks and had a significant co-occurrence rate. Cases of CM were separated into focal, segmental, and diffuse multifocal subgroups. Diffuse multifocal CM (n = 16) showed associations with extreme prematurity (<32 weeks), congenital malformations, IUGR, delayed villous maturation, avascular villi, and placentomegaly, which were not seen in the other 2 localized subgroups. CH lacked the associations noted for CA and CM, was not increased in placentas with CA or CM, and was most frequent at greater than 37 weeks. CH was positively associated with maternal diabetes, placentomegaly, delayed villous maturation, and chronic villitis. Finally, CH lacked the continuous perivascular layer of muscle-specific actin (MSA)-positive pericytes and the multifibrillar lattice-like reticulin pattern seen in both CA and CM. In conclusion, CA and localized CM are clinically and morphologically similar lesions distinct from CH. Diffuse multifocal CM is morphologically similar to CA and localized CM, but has a distinct clinicopathologic profile.     

ENCEPHALOMYELONEURITIS WITH MEDIASTINAL GERM CELL TUMOR A Paraneoplastic Condition ?

An unusual case of encephalomyeloneuritis associated with germ cell tumor with mature and immature teratoma arising in the mediastinum is presented. There was an unusually long interval from the onset of neurologic symptoms to the development of malignancy. The histopathology, characterized by limbic encephalitis, brain stem encephalitis, cortical cerebellar degeneration and myeloneuritis, was similar to that of paraneoplastic encephalomyeloneuritis previously described in the literature. Virological and immunological studies failed to demonstrate any causative agents or autoantibodies reacting with brain tissue. The causal relationship between the malignant neoplasm and encephalomyeloneuritis thus seems to be very complex.     

Synthesis and side-chain crystallization of comb-like polymers obtained from isopropenyl-1,3,5-triazines carrying two,three, and four long alkyl groups

Monomers containing several octadecyl groups, e.g., 2-isopropenyl-4,6-bis(octadecylamino)-1,3,5-triazine ( 2 ), 2-dioctadecylamino-4-isopropenyl-6-octadecylamino-1,3,5-triazine ( 3 ) and 2,4-bis(dioctadecylamino)-6-isopropenly-1,3,5-triazine ( 4 ) were prepared by the alkylation reaction of 2,4-diamino-6-isopropenyl-1,3,5-triazine ( 1 ) with 1-bromooctadecane in the presence of sodium hydride. In the free-radical homopolymerization of these monomers, the polymer yield of 3 was lower than that of 2 due to a decrease in the ceiling temperature, and the polymerization of 4 did not proceed. Copolymerizations of these monomers with styrene or methyl methacrylate were carried out and the monomer reactivity ratios (r₁ and r₂) were determined. The monomer reactivity decreased with increasing the number of octadecyl groups in the monomers. Crystallinity of the octadecyl side chains in the resulting comb-like polymers was evaluated by differential scanning calorimetry.     

Effects of drug adherence on patient outcomes to early treatment for Japanese cedar pollinosis]

Drug adherence is one of the important aspects in caring for patients with allergic rhinitis. To improve clinical efficacy of early treatment for Japanese cedar pollinosis (JCP), we evaluated the effect of drug adherence on patients' outcomes. Patients were randomly selected from 16 ENT clinical sites in Osaka and Wakayama between February 24 and March 8, 2003 (peak pollen season). Efficacy was assessed using patients' ratings of nasal and ocular symptoms and overall assessment in their condition compared with previous season ones. Costs include direct costs of the drugs used for treatment to JCP from January to February. Five hundred one patients taking early treatment were enrolled. Compared to low adherence patients, those who reported higher level of adherence significantly improved overall health condition, and achieved better symptom relief of rhinorrhea and nasal congestion. In multiple logistic regression analysis, the following factors were independent risk factors for low adherence: student (p=0.002), using OTC medications (p=0.006), and short-duration of medication (p=0.001). Low costs were also risk factor for low adherence. We conclude that taking medications for JCP for 22-28 days is the best way to enhance patients' outcomes.