Biomedical subjects

Takeshi Watanabe

Publications and source records attributed to Takeshi Watanabe.

At least 55 records · Page 3Linked to original sources

PubMed2004

Growth retardation and dyslymphopoiesis accompanied by G2/M arrest in APEX2-null mice.

APEX2/APE2 is a secondary mammalian apurinic/apyrimidinic endonuclease that associates with proliferating cell nuclear antigen (PCNA), and the progression of S phase of the cell cycle is accompanied by its expression. To determine the biologic significance of APEX2, we established APEX2-null mice. These mice were about 80% the size of their wild-type littermates and exhibited a moderate dyshematopoiesis and a relatively severe defect in lymphopoiesis. A significant accumulation of both thymocytes and mitogen-stimulated splenocytes in G(2)/M phase was seen in APEX2-null mice compared with the wild type, indicating that APEX2 is required for proper cell cycle progression of proliferating lymphocytes. Although APEX2-null mice exhibited an attenuated immune response against ovalbumin in comparison with wild-type mice, they produced both antiovalbumin immunoglobulin M (IgM) and IgG, indicating that class switch recombination can occur even in the absence of APEX2.

Animals↗

PubMed2004

PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism.

The amino boronic dipeptide, PT-100 (Val-boro-Pro), a dipeptidyl peptidase (DPP) inhibitor, has been shown to up-regulate gene expression of certain cytokines in hematopoietic tissue via a high-affinity interaction, which appears to involve fibroblast activation protein. Because fibroblast activation protein is also expressed in stroma of lymphoid tissue and tumors, the effect of PT-100 on tumor growth was studied in mice in vivo. PT-100 has no direct cytotoxic effect on tumors in vitro. Oral administration of PT-100 to mice slowed growth of syngeneic tumors derived from fibrosarcoma, lymphoma, melanoma, and mastocytoma cell lines. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 caused regression and rejection of tumors. The antitumor effect appeared to involve tumor-specific CTL and protective immunological memory. PT-100 treatment of WEHI 164-inoculated mice increased mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells. The role of innate activity was further implicated by observation of significant, although reduced, inhibition of WEHI 164 and A20/2J tumors in immunodeficient mice. PT-100 also demonstrated ability to augment antitumor activity of rituximab and trastuzumab in xenograft models of human CD20(+) B-cell lymphoma and HER-2(+) colon carcinoma where antibody-dependent cytotoxicity can be mediated by innate effector cells responsive to the cytokines and chemokines up-regulated by PT-100. Although CD26/DPP-IV is a potential target for PT-100 in the immune system, it appeared not to be involved because antitumor activity and stimulation of cytokine and chemokine production was undiminished in CD26(-/-) mice.

Administration, Oral↗

PubMed2004

DGGE method for analyzing 16S rDNA of methanogenic archaeal community in paddy field soil.

A denaturing gradient gel electrophoresis (DGGE) method for analyzing 16S rDNA of methanogenic archaeal community in paddy field soil is presented. Five specific primers for 16S rDNA of methanogenic archaea, which were modified from the primers for archaea, were first evaluated by polymerase chain reaction and DGGE using genomic DNAs of 13 pure culture strains of methanogenic archaea. The DGGE analysis was possible with two primer pairs (0348aF-GC and 0691R; 0357F-GC and 0691R) of the five pairs tested although 16S rDNA of some non-methanogenic archaea was amplified with 0348aF-GC and 0691R. These two primer pairs were further evaluated for use in analysis of methanogenic archaeal community in Japanese paddy field soil. Good separation and quality of patterns were obtained in DGGE analysis with both primer pairs. A total of 41 DNA fragments were excised from the DGGE gels and their sequences were determined. All fragments belonged to methanogenic archaea. These results indicate that the procedure of DGGE analysis with the primer pair 0357F-GC and 0691R is suitable for investigating methanogenic archaeal community in paddy field soil.

Archaea↗

PubMed2004

Association of a four-amino acid residue insertion polymorphism of the HS1 gene with systemic lupus erythematosus: molecular and functional analysis.

OBJECTIVE: To investigate whether polymorphism(s) or mutation(s) in the hematopoietic cell-specific Lyn substrate 1 (HS1) gene are involved in the pathogenesis of systemic lupus erythematosus (SLE). METHODS: The entire coding region of the HS1 gene was analyzed by reverse transcriptase-polymerase chain reaction/single-strand conformational polymorphism analysis. HS1-transfected WEHI-231 cells or B lymphocytes from patients with SLE were studied for apoptosis, activation, and proliferation by flow cytometric analysis and MTT assay. RESULTS: We identified a glutamic acid-proline-glutamic acid-proline insertion between codons 366 and 367 (EPEP366-367ins) and 2 amino acid substitutions (A235T and E361K). The genotype frequency among individuals homozygous for the EPEP+ allele was 0.184 in 201 patients with SLE but only 0.098 in 184 healthy individuals (P = 0.016). The allele frequency of EPEP366-367ins was 0.408 in patients with SLE; this frequency was significantly higher than that in healthy controls (0.312) (P = 0.006). WEHI-231 cells transfected with EPEP+ HS1 were 100-fold more sensitive to B cell receptor (BCR)-mediated apoptosis than were those transfected with HS1 without EPEP. B lymphocytes from SLE patients with the EPEP+ allele were significantly more apoptotic without BCR stimulation and less activated after BCR stimulation than were those from SLE patients without the EPEP allele. CONCLUSION: These results suggest that HS1 with the EPEP insertion polymorphism transmits accelerated signals from BCR and is involved in the pathogenesis of SLE.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Impaired lymphocyte development and function in Clast5/Stra13/DEC1-transgenic mice.

Clast5/Stra13/DEC1 is a member of the helix-loop-helix family of transcriptional repressors. We have previously shown that Clast5 is rapidly down-regulated upon B cell activation and its overexpression inhibits cell cycle progression in B lymphoma cells. In the present study, we show that Clast5 expression is developmentally regulated during B cell differentiation, being expressed at the progenitor B cells, down-regulated at the precursor B cells, elevated in immature and mature resting B lymphocytes, and down-regulated again in germinal center B cells. To investigate the function of Clast5 in regulating lymphocyte development, we have generated transgenic mice expressing Clast5 in B- and T-lineage cells (Clast5-Tg). Clast5-Tg mice grew and bred normally but their spleen and thymus cellularity was reduced compared with control littermates. The development of B cells in the bone marrow and T cells in the thymus was impaired, with the expansion of progenitor B and T cells most strongly affected. The frequency of IL-7-responsive cells in the bone marrow of Clast5-Tg mice was reduced by >80% and their proliferative response to IL-7 was also compromised. Mature B cells from Clast5-Tg mice were hyporesponsive to antigen receptor cross-linking and exhibited mild reduction in the proliferative response to CD40 ligation or lipopolysaccharide stimulation. Moreover, the development of germinal center B cells and antibody production against a T-dependent antigen were reduced in Clast5-Tg mice. These results reveal a critical role for Clast5/Stra13/DEC1 in negatively regulating lymphocyte development and function in vivo.

Animals↗

PubMed2004

Opsonophagocytic dysfunction in patients with liver cirrhosis and low responses to tumor necrosis factor-alpha and lipopolysaccharide in patients' blood.

To evaluate their defense level against bacterial infection of patients with liver cirrhosis, we compared the luminol-dependent chemiluminescence (CL) response of peripheral blood from 40 patients with that from 40 healthy volunteers. Small quantities of heparinized whole blood (100 microl; final dilution, 1:10) were used for phagocytes, and CL was measured on addition of nonopsonized zymosan or Escherichia coli without special opsonization. Whole blood CL in cirrhotic patients was significantly lower than that in the healthy controls. The incidence of lower CL response in patients increased as disease stage advanced. Polymorphonuclear leukocytes (PMN) from cirrhotic patients exhibited a slightly lower CL response than those from controls, but this was not statistically significant. In contrast, the CL response of monocytes in patients was significantly lower than that of controls. The opsonizing capacity of the patients' sera and ascitic fluid was also decreased. In fact, the levels of opsonins such as complement in the patients' sera and both immunoglobulins and complement in the ascitic fluids were found to be lower in cirrhotic patients. On the basis of these findings, defect of opsonophagocytic function seems to participate in the increased susceptibility to infection in cirrhotic patients. Furthermore, whole blood CL induced by nonopsonized zymosan at the onset of relatively severe bacterial infections such as sepsis, pneumonia, or spontaneous bacterial infection was less augmented in the blood of cirrhotic patients than that in noncirrhotic patients. To clarify the reason why whole blood exhibits a lower CL response in the acute phase of bacterial infections, we investigated the priming effects of lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-alpha), well-known CL activators, on the CL response of whole blood obtained from cirrhotic patients in comparison with that from healthy persons. The priming effects were significantly decreased in patients' blood when compared with that of healthy persons. These low responses of patients' blood to LPS or TNF-alpha support our finding that phagocytes are not fully activated when gram-negative bacterial infections occur.

Adult↗

PubMed2004

Opsonic activity assessment of human intravenous immunoglobulin preparations against drug-resistant bacteria.

We have used the ability of opsonized bacteria to stimulate luminol-enhanced chemiluminescence (CL) of human polymorphonuclear leukocytes (PMN) to examine the opsonic capabilities of commercially available human intravenous immunoglobulin (i.v.Ig) preparations. The method was tested against 14 strains of drug-resistant gram-positive bacteria (including methicillin-resistant Staphylococcus aureus, hetero-vancomycin-resistant S. aureus, vancomycin-resistant enterococci, penicillin-resistant Streptococcus pneumoniae), and 23 strains of gram-negative bacteria (including extended-spectrum beta-lactamase-producing bacteria, metallo-beta-lactamase-producing bacteria, beta-lactamase-negative ampicillin-resistant Haemophilus influenzae). An Fc-intact i.v.Ig preparation treated with polyethylene glycol (PEG) was evaluated for opsonization effectiveness against these bacteria in vitro. The opsonization of these organisms was enhanced by an Fc-intact i.v.Ig, and the opsonic activity was dose dependent. A pepsin-treated i.v.Ig preparation exhibited poor opsonic activity for all bacteria tested. These results suggest that Fc-intact i.v.Ig, which augments opsonic activity against various drug-resistant bacteria, will be a useful addition to the treatment of severe bacterial infections in immunocompromised patients with impaired serum opsonic capacity.

Anti-Bacterial Agents↗

PubMed2004

Attenuation of Th1 effector cell responses and susceptibility to experimental allergic encephalomyelitis in histamine H2 receptor knockout mice is due to dysregulation of cytokine production by antigen-presenting cells.

Histamine, a biogenic amine with both neurotransmitter and vasoactive properties, is well recognized as an immunomodulatory agent in allergic and inflammatory reactions. It also plays a regulatory role in the development of antigen-specific immune responses. CD4+ T-cells from histamine H1 receptor (H1R)-deficient (H1RKO) mice produce significantly less interferon-gamma and more interleukin (IL)-4 in in vitro recall assays compared to wild-type controls. H1RKO mice are also less susceptible to acute early-phase experimental allergic encephalomyelitis indicating that H1R signaling in CD4+ T cells plays a central role in regulating pathogenic T-cell responses. In this study, we show that mice lacking histamine H2 receptor (H2RKO) are similar to H1RKO mice in that they develop encephalitogen-specific T-cell responses as assessed by proliferation and IL-2 production and present with less severe acute early-phase experimental allergic encephalomyelitis. However, unlike T cells from H1RKO mice, which exhibit a strong Th2 bias, T cells from H2RKO mice do not. Rather, they are uniquely characterized by a significant inhibition of Th1 effector cell responses. Given that both histamine and adjuvants such as pertussis toxin modulate antigen-presenting cell (APC) maturation and function, including T-cell-polarizing activity, we analyzed the cytokines/chemokines secreted by APCs from wild-type, H1RKO, and H2RKO mice. Significant differences in cytokine/chemokine production by APCs from unimmunized and immunized mice were delineated. APCs from H2RKO mice produce significantly less IL-12 and IL-6 and markedly greater amounts of MCP-1 compared to wild-type and H1RKO mice. Because MCP-1 is known to inhibit IL-12 production, the failure of H2RKO mice to generate encephalitogenic Th1 effector cell responses is consistent with inhibition of negative regulation of MCP-1 secretion by H2R signaling in APCs.

Animals↗

PubMed2004

Inducible histamine protects mice from P. acnes-primed and LPS-induced hepatitis through H2-receptor stimulation.

BACKGROUND & AIMS: Inducible histamine and histamine H2-receptors have been suggested to be involved in innate immune response. METHODS: We examined a functional role of inducible histamine in the protection against hepatic injury and lethality in Propionibacterium acnes -primed and lipopolysaccharide-induced hepatitis, using histidine decarboxylase knockout and H2-receptor knockout mice. RESULTS: Lipopolysaccharide challenge after Propionibacterium acnes priming increased histidine decarboxylase activity in the liver of wild-type mice, associated with a marked elevation of histamine turnover. Histidine decarboxylase-like immunoreactivity was observed in CD68-positive Kupffer cells/macrophages. Treatment of wild-type mice with famotidine or ranitidine but not d -chlorpheniramine augmented hepatic injury and inhibited the survival rate significantly. The same dose of Propionibacterium acnes and lipopolysaccharide induced severe hepatitis and high lethality in histidine decarboxylase knockout and H2-receptor knockout mice; the former were rescued by the subcutaneous injection of histamine. Immunohistochemical study supported the protective role of histamine against the apoptosis of hepatocytes. Histamine suppressed the expression of IL-18 and tumor necrosis factor alpha in the liver, leading to the reduced plasma levels of cytokines including IL-18, TNF-alpha, IL-12, IFN-gamma, and IL-6. CONCLUSIONS: These findings as a whole indicated that endogenously produced histamine in Kupffer cells/macrophages plays a very important role in preventing excessive innate immune response in endotoxin-induced fulminant hepatitis through the stimulation of H2-receptors.

Animals↗

PubMed2004

Importance of exposed aromatic residues in chitinase B from Serratia marcescens 2170 for crystalline chitin hydrolysis.

Chitinase B (ChiB) of S. marcescens has five exposed aromatic residues linearly aligned toward the catalytic cleft, Tyr481 and Trp479 in the C-terminal domain, and Trp252, Tyr240 and Phe190 in the catalytic domain. To determine the contribution of these residues to the hydrolysis of crystalline beta-chitin, site-directed mutagenesis, to replace them by alanine, was carried out. The Y481A, W479A, W252A, and Y240A mutations all decreased the binding activity and hydrolyzing activity toward beta-chitin microfibrils. Substitution of Trp residues affected the binding activity more severely than that of Tyr residues. The F190A mutation decreased neither the binding activity nor the hydrolyzing activity. None of the mutations decreased the hydrolyzing activity toward soluble substrates. These results suggest that ChiB hydrolyzes crystalline beta-chitin via a mechanism in which four exposed aromatic residues play important roles, similar to the mechanism of hydrolysis by ChiA of this bacterium, although the directions of hydrolysis of the two chitinases are opposite.

Catalysis↗

PubMed2004

Development of amygdaloid kindling in histidine decarboxylase-deficient and histamine H1 receptor-deficient mice.

PURPOSE: This study attempted to clarify the role of histamine or histamine H1 receptors in the development of amygdaloid kindling by using histidine decarboxylase (HDC)-deficient and histamine H1 receptor (H1R)-deficient mice. METHODS: Under pentobarbital anesthesia, mice were fixed to a stereotaxic apparatus, and bipolar electrodes were implanted into the right amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. A bipolar electroencephalogram was recorded; bipolar stimulation of the amygdala was applied every day with a constant-current stimulator and continued until a generalized convulsion was obtained. RESULTS: The development of amygdaloid kindling in HDC-deficient and H1R-deficient mice was significantly accelerated compared with that in their respective wild-type mice. In addition, the afterdischarge (AD) duration and generalized seizure duration in HDC-deficient and H1R-deficient mice were prolonged. Intraperitoneal injection of histidine resulted in an inhibition of amygdaloid kindled seizures in wild-type mice at doses that caused an increase in the histamine contents of the brain. However, no significant effect was observed with histidine in H1R-deficient mice at the same dose. CONCLUSIONS: These findings suggest that histaminergic mechanisms through H1 receptors play a crucial role not only in amygdaloid kindled seizures but also in the development of amygdaloid kindling.

Amygdala↗

PubMed2004

Expression of RCAS1 in human gastric carcinoma: a potential mechanism of immune escape.

RCAS1 (receptor-binding cancer antigen expressed on SiSo cells) inhibits the in vitro growth of receptor-expressing cells and induces apoptosis, which may contribute to the ability of tumor cells to evade host immune surveillance. In this study, we investigated RCAS1 expression in gastric cancer and precancerous lesions by immunohistochemical means. We then analyzed the relationship between RCAS1 expression and clinicopathological variables, and examined whether RCAS1 expression is associated with infiltration of tumor-infiltrating lymphocytes (TILs) and apoptosis of TILs. Of 54 gastric cancers analyzed, RCAS1 expression was positive in 52 (96%) of them. The expression pattern of RCAS1 in gastric cancer cells could be classified as granular staining either enriched in the glandular side of the cytoplasm with polarity (P pattern) or scattered diffusely in the cytoplasm and on the cell membranes (D pattern). Nineteen of 39 intestinal-type carcinomas (49%) showed the P pattern, and all of 13 diffuse type carcinomas (100%) showed the D pattern. In contrast, all RCAS1-positive specimens of gastric adenoma and metaplastic mucosa were of the P pattern. The D pattern of gastric cancers was more frequently recognized in carcinomas with large size (P < 0.01), in those with regional lymph node metastasis (P < 0.05) and in those that had invaded beyond the submucosa (P < 0.01), compared with the P pattern. On the same sections, significantly less TILs were identified in RCAS1-positive areas than RCAS1-negative areas. Furthermore, the rate of apoptosis of TILs was significantly higher in RCAS1-positive areas than in RCAS1-negative areas. The expression and distribution of RCAS1 may be involved in malignant transformation, tumor progression, histological type and tumor escape from host immune surveillance in gastric cancer.

Aged↗

PubMed2004

Urodynamic effects and safety of modified intravesical oxybutynin chloride in patients with neurogenic detrusor overactivity: 3 years experience.

BACKGROUND: Intravesical oxybutynin chloride with hydroxypropylcellulose (HPC) (modified intravesical oxybutynin) has been reported to be effective for treatment of overactive bladder. We reported the short-term effects of modified intravesical oxybutynin previously. In the present article, we detail the results of a 3-year follow-up study of patients from our previous analysis and report the efficacy and side-effects of modified intravesical oxybutynin. METHODS: Modified intravesical oxybutynin (5 mg/10 mL, twice a day) was applied for more than 3 years to six neurogenic overactive detrusor patients (three men and three women, average age 53.3 years) who were not satisfied with oral anticholinergic agents or the other therapy. A cystometogram (CMG) was performed before, 1 week after and 3 years after the start of modified intravesical oxybutynin treatment. We evaluated the patient's satisfaction of this treatment after 4 weeks and again after 3 years. We compared the patients' answers before and after the therapy (excellent, good, fair, unchanged and worse). We also monitored systemic and topical side-effects in these patients during this period. RESULTS: CMG studies showed that two of six patients no longer exhibited uninhibited contraction 1 week after the treatment and that the cystocapacity of patients before, 1 week after and 3 years after the initial modified intravesical oxybutynin was 129.7 +/- 19.4, 283.5 +/- 40.4 and 286.8 +/- 38.1 mL, respectively. For the evaluation of patients' satisfaction with this treatment, four patients considered the therapy excellent and one patient described it as good after both 4 weeks and after 3 years. Two patients dropped out of the study; one developed left ureteral cancer (2.25 years) and the other developed ileus (1.5 years). Dry mouth and acute cystitis were observed in both patients. CONCLUSION: Modified intravesical oxybutynin is an effective and relatively safe option of therapy for overactive bladder patients. However, this therapy requires careful observation for emergent side-effects.

Administration, Intravesical↗

PubMed2004

Serum levels of soluble molecules associated with evasion of immune surveillance: a study in biliary disease.

BACKGROUND: Biliary carcinoma cells produce the transmembrane proteins, Fas, FasL, and RCAS1. It has been demonstrated that the Fas/FasL and RCAS1 systems induce apoptosis of activated immune cells and that the soluble isoforms of these proteins (sFas, sFasL, and sRCAS1) also exhibit this function. METHODS: We measured serum levels of these soluble-types in patients with biliary disease by ELISA and investigated their clinical significance. RESULTS: In some cases of cholangitis and autoimmune biliary disease, serum sFasL values were over 0.1 ng/ml but the protein was undetectable in any patients with biliary carcinoma. sFas levels were significantly higher in the autoimmune disease (mean, 6.83 ng/ml) and cancer (mean, 6.42 ng/ml) groups than in the cholangitis group (mean, 4.23 ng/ml) and normal controls (mean, 2.93 ng/ml). However, the sFas values in malignancy did not correlate with the progression of clinical stage. The percentage positive for serum sRCAS1 was 9.7% in benign disease but was 63.4% in cancer. CONCLUSIONS: Our data suggest that serum sFasL in biliary disease may be derived predominantly from activated immune cells and not from cancer cells and that autoimmune biliary disease may be mediated by the Fas/FasL apoptotic system. sRCAS1 is highly tumor-specific and may be of value in the diagnosis of malignancy.

Adolescent↗

PubMed2004

[Transferability of vanA gene from vancomycin-resistant Enterococcus faecalis in the digestive tract of specific pathogen-free mice].

We evaluated the transferability of vanA gene from vancomycin-resistant Enterococcus faecalis (VREF) to vancomycin-sensitive E. faecalis (VSEF) in vitro and in vivo. In vitro conjugal transfer experiment by filter mating, the vanA gene of VREF was transferable at the high frequency to VSEF and a mutant strain which cured vanA gene of VREF. In vivo studies in the digestive tract of specific pathogen-free mice pretreated with oral antibiotics, transconjugants were also detected from the feces of a mouse at the lower frequency. However, the colonization of transconjugants was transient. The vanA gene in the donor and the transconjugant strain was confirmed by using a polymerase chain reaction method. These results suggest that VSEF colonizing in the human digestive tract might be developed to VREF by transferring of the vanA gene.

Animals↗

PubMed2004

Distribution and phylogenetic analysis of family 19 chitinases in Actinobacteria.

In organisms other than higher plants, family 19 chitinase was first discovered in Streptomyces griseus HUT6037, and later, the general occurrence of this enzyme in Streptomyces species was demonstrated. In the present study, the distribution of family 19 chitinases in the class Actinobacteria and the phylogenetic relationship of Actinobacteria family 19 chitinases with family 19 chitinases of other organisms were investigated. Forty-nine strains were chosen to cover almost all the suborders of the class Actinobacteria, and chitinase production was examined. Of the 49 strains, 22 formed cleared zones on agar plates containing colloidal chitin and thus appeared to produce chitinases. These 22 chitinase-positive strains were subjected to Southern hybridization analysis by using a labeled DNA fragment corresponding to the catalytic domain of ChiC, and the presence of genes similar to chiC of S. griseus HUT6037 in at least 13 strains was suggested by the results. PCR amplification and sequencing of the DNA fragments corresponding to the major part of the catalytic domains of the family 19 chitinase genes confirmed the presence of family 19 chitinase genes in these 13 strains. The strains possessing family 19 chitinase genes belong to 6 of the 10 suborders in the order Actinomycetales, which account for the greatest part of the Actinobacteria: Phylogenetic analysis suggested that there is a close evolutionary relationship between family 19 chitinases found in Actinobacteria and plant class IV chitinases. The general occurrence of family 19 chitinase genes in Streptomycineae and the high sequence similarity among the genes found in Actinobacteria suggest that the family 19 chitinase gene was first acquired by an ancestor of the Streptomycineae and spread among the Actinobacteria through horizontal gene transfer.

Actinobacteria↗

PubMed2004

Methamphetamine and brain histamine: a study using histamine-related gene knockout mice.

The central histamine (HA) neurons that originate from the posterior hypothalamus modulate a variety of physiological functions. In order to investigate the roles of brain histaminergic neuron system in the behavioral effects of methamphetamine (METH), we administrated METH repeatedly to L-histidine decarboxylase (HDC)-, histamine H1 receptor-, H2 receptor-gene knockout (KO) mice, H1/H2 receptor-gene double KO mice, and wild type (WT) mice corresponding to each of them, and we measured locomotor activities. We also measured the contents of monoamines and amino acids in the brain of HDC-gene KO and WT mice after a single administration of METH. METH-induced locomotor hyperactivity and the development of behavioral sensitization were facilitated more in the HDC-gene KO mice and H1/H2 gene double KO mice than the WT mice, suggesting that brain histamine has an inhibitory effect on the METH action through both H1 and H2 receptors. In addition, neurochemical study suggested the involvement of the GABAergic neuron system in the inhibitory effect of brain histamine.

Animals↗

PubMed2004

Expression of human tumor-associated antigen RCAS1 in adult T-cell leukemia/lymphoma.

In human cancer, RCAS1 (the receptor-binding cancer antigen expressed on SiSo cells) on the surface of various kinds of tumor cells reportedly induces the apoptosis of T-cells and natural killer cells, resulting in evasion of the immune system. In the present study, an immunohistochemical analysis of RCAS1 expression was performed with lymph node specimens obtained from patients with adult T-cell leukemia/lymphoma (ATLL). Positive staining was seen in 15 (75%) of 20 cases and in all cases of patients with short survival times. In the cases of B-cell lymphomas, positive staining was seen in only 1 (13%) of 8 cases. These findings indicate that expression of RCAS1 may be associated with the evasion from immune surveillance of cells infected with human T-lymphotropic virus type I, resulting in the development of overt leukemia/lymphoma. Determination of RCAS1 expression may be useful for predicting the prognosis of patients with ATLL.

Adult↗