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Biomedical subjects

Tetsuya Nakamura

Publications and source records attributed to Tetsuya Nakamura.

At least 91 records · Page 5Linked to original sources
PubMed2003

Therapeutic approaches to chronic intestinal inflammation by specific targeting of mucosal IL-7/IL-7R signal pathway.

Inflammatory bowel disease is thought to result from inappropriate activation of mucosal immune responses. Intestinal epithelial cells produce interleukin (IL)-7 that serves as a regulatory factor for IL-7 receptor (IL-7R)(+) mucosal lymphocytes. The pivotal role of mucosal IL-7/IL-7R dependent signals in the activation of mucosal immune responses that lead to the development of chronic intestinal inflammation are demonstrated. Therapeutic approaches targeting IL-7/IL-7R signal pathway may be feasible in the treatment of inflammatory bowel disease.

Animals↗
PubMed2003

[A clinical results of TS-1 in advanced and recurrent gastric cancer in our hospital].

A total of 40 patients with advanced and recurrent gastric cancer in our hospital were treated with TS-1 alone, and the efficacy of treatment, survival time, and adverse effects were examined. TS-1 was administered with the usual dosage and dose regimen. Response to treatment included a complete response (CR) in 3 cases, partial response (PR) in 8 cases, no change (NC) in 10 cases, and progressive disease (PD) in 7 cases. The response rate was 39.3%, and among the 28 patients with evaluable lesions TS-1 produced a high response rate of 56.3% in 16 patients who had undergone prior therapy. The median survival time (MST) was 478 days in the 28 patients with evaluable lesions, excluding patients with peritoneal dissemination, and 283 days in the 12 patients with peritoneal dissemination. The outcome was markedly poorer in the patients with peritoneal dissemination than in the patients with evaluable lesions. The incidence of grade 3 or higher adverse effects was 20%, including two cases in which decreased dihydropyrimidine dehydrogenase (DPD) activity was suspected, and one case in which decreased dihydropyrimidinase (DHP) was suspected. Although the effect of TS-1 alone on gastric cancer is significantly superior to that of any conventional cancer drugs, the results of this study suggest that the antitumor effect varies with the site of the target lesions and according to whether the lesion is a remnant or recurrence.

Adenocarcinoma↗
PubMed2002

The first isolation of Nocardia nova from an HIV-1 infected individual in Japan.

Nocardia species are opportunistic pathogens of immunocompromised patients. We report a case of Nocardia nova infection complicating Pneumocystis carinii pneumonia (PCP) in an HIV-1 infected individual. A 27-year-old man with hemophilia A was admitted on October 17, 2000, with fever and dyspnea. CD4 cell counts were 5/microl on admission. Prophylaxis against PCP was administered by inhalation of pentamidine isethionate because he was allergic to sulfamethoxazole-trimethoprim (SMZ-TMP). He was diagnosed with PCP from chest X-ray and bronchoalveolar lavage. The sputum obtained for culture on admission was positive for Gram-positive branching rods; the organism was later identified as Nocardia nova. He died from respiratory failure on November 7, 2000. Although PCP might be a principal factor in respiratory failure, this case shows the need to consider pulmonary nocardiosis as a cause of respiratory illness in patients with advanced HIV-1 infection.

Acquired Immunodeficiency Syndrome↗
PubMed2002

Acute disseminated encephalomyelitis following dengue fever.

A58-year-old man suffered from acute disseminated encephalomyelitis (ADEM) after dengue fever. ADEM has not been described as the cause of neurological complications in dengue fever. However, the increasing use of magnetic resonance imaging in endemic areas may help to identify ADEM as being responsible for neurological complications in dengue fever.

Dengue↗
PubMed2002

Disseminated coccidioidomycosis with intra- and paravertebral abscesses.

We report a case of paravertebral and intravertebral abscesses caused by Coccidioides immitis in a Japanese man. The patient had lived in Arizona, United States, for 5 years, and suffered from overt disease after coming back to Japan. Culture of pus from the paravertebral abscess revealed Coccidioides immitis, and a diagnosis of disseminated coccidioidomycosis was made. Fluconazole (600 mg/day), taken orally, was started, and the abscesses surrounding the vertebral bodies disappeared after 2 years of treatment. The abscess in the vertebral bodies also responded to treatment, but a small lesion was still left in the 10th vertebral body after 2 years of treatment. Coccidioidomycosis is a fungal infection that is endemic in the southwestern United States and in Central and South America. Although coccidioidomycosis causes self-limiting flu-like illness or pneumonia, a small proportion of the infections progress to disseminated diseases. Because the incidence of coccidioidomycosis is increasing year by year, physicians not only in endemic but also in nonendemic areas have to consider coccidioidomycosis as one of the differential diagnoses when they examine patients from endemic areas.

Abscess↗
PubMed2002

Human GM-CSF induces HIV-1 LTR by multiple signalling pathways.

Human immunodeficiency virus type-1 (HIV-1) gene expression is known to be affected by numerous cytokines or growth factors. However, the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on long terminal repeat (LTR)-mediated transcription of HIV-1 still remains unknown. By transient transfection experiments with HIV-1 LTR reporter constructs, we showed that strong LTR-mediated activation was induced by GM-CSF in mouse Ba/F3 cells expressing human GM-CSF receptors (GM-CSFR). Mutational analysis of the HIV-1 LTR reporters revealed that both NF-kappaB and Sp1 binding sites play important roles as positive regulatory elements. Analysis of various mutants of the cytoplasmic region of GM-CSFR indicated that both the conserved membrane proximal region and tyrosine residues located in the distal part of the beta subunit were required for HIV-1 LTR activation. Possible involvement of MAPK and PI3-K signalling pathways was suggested by the partial inhibition by wortmannin, a specific inhibitor of the PI3-K pathway, and enhancement by constitutively active MEK1, of HIV-1 LTR activation. However, the MEK1 pathway is not essential since MEK1 inhibitor PD98059 did not suppress GM-CSF-induced HIV-1-LTR activation. Further analyses of GM-CSFR mutants suggested that some other unknown signalling pathway also participates in GM-CSF-induced HIV-1 LTR activation. Taken together, the data suggest that GM-CSF could upregulate the LTR-driven transcription of HIV-1 through modulation of NF-kappaB and SP1 by multiple signalling pathways.

Animals↗
PubMed2002

Dihydrofolate reductase gene polymorphisms in Pneumocystis carinii f. sp. hominis in Japan.

This study examined polymorphisms in the dihydrofolate reductase (DHFR) gene of Pneumocystis carinii isolates from 27 patients with P. carinii pneumonia (PCP) in Japan. Four substitution sites with two synonymous and two non-synonymous changes were found. Two synonymous substitutions at nucleotide positions 540 and 312 were identified in one and 13 patients, respectively. Two amino acid substitutions (Ala67Val, Cysl66Tyr) were found in two different patients. No linkage of amino acid substitutions in DHFR to those in dihydropteroate synthase was observed. The two patients whose isolates showed non-synonymous DHFR mutations were not exposed to DHFR inhibitors before they developed PCP and were treated successfully with co-trimoxazole.

Amino Acid Sequence↗
PubMed2002

Pneumocystis carinii carriage in immunocompromised patients with and without human immunodeficiency virus infection.

Eighty-one bronchoalveolar lavage (BAL) specimens obtained from 26 HIV-infected, 45 non-HIV immunosuppressed and 10 immunocompetent patients with primary pulmonary diseases were analysed for the presence of Pneumocystis carinii by staining and by P. carinii 5S rDNA determined by PCR. P. carinii was observed by staining of BAL specimens from HIV-infected patients significantly more frequently than those from immunocompromised hosts without HIV infection (57.7% versus 20.0%, respectively). P. carinii 5S rDNA was detected by PCR assay in seven (26.9%) HIV-infected individuals, which was significantly more frequent than for four (8.9%) immunosuppressed patients without HIV infection, for whom staining was negative. None of these patients developed P. carinii pneumonia (PCP) within the follow-up period. BAL specimens from 10 immunocompetent patients with pulmonary disorders were negative for PCP by both staining and PCR assay.

AIDS-Related Opportunistic Infections↗
PubMed2002

An efficient and versatile mammalian viral vector system for major histocompatibility complex class I/peptide complexes.

We report a Sendai virus (SeV) vector system for expression of major histocompatibility complex (MHC) class I/peptide complexes. We cloned the extracellular domain of a human MHC class I heavy chain, HLA-A*2402, and human beta-2 microglobulin (beta2m) fused with HLA-A*2402-restricted human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte (CTL) epitopes (e-beta2m) in separate SeV vectors. When we coinfected nonhuman mammalian cells with the SeVs, naturally folded human MHC class I/peptide complexes were secreted in the culture supernatants. Biotin binding peptide sequences on the C terminus of the heavy chain were used to tetramerize the complexes. These tetramers made in the SeV system recognized specific CD8-positive T cells in peripheral blood mononuclear cells of HIV-1-positive patients with a specificity and sensitivity similar to those of MHC class I tetramers made in an Escherichia coli system. Solo infection of e-beta2m/SeV produced soluble e-beta2m in the culture supernatant, and cells pulsed with the soluble protein were recognized by specific CTLs. Furthermore, when cells were infected with e-beta2m/SeV, these cells were recognized by the specific CTLs more efficiently than the protein pulse per se. SeV is nonpathogenic for humans, can transduce foreign genes into nondividing cells, and may be useful for immunotherapy to enhance antigen-specific immune responses. Our system can be used not only to detect but also to stimulate antigen-specific cellular immune responses.

Animals↗
PubMed2002

Reciprocal expression of vascular endothelial growth factor and nitric oxide synthase by coronary arterial wall cells during chronic inhibition of nitric oxide synthesis in rats.

Chronic inhibition of nitric oxide (NO) synthesis by oral administration of N(G)-nitro-L-arginine methyl ester (L-NAME) causes hypertension and produces arteriosclerosis in rats. Balloon injury induces upregulation of vascular endothelial growth factor (VEGF) in medial smooth muscle cells of the rat arterial wall, and NO secreted by a restored endothelium acts as the negative feedback mechanism that downregulates VEGF expression to basal levels. In this study, we tested the hypothesis that a reciprocal relation between VEGF and NO would be established in a rat model of chronic NO blockade. Male Wister rats received plain drinking water (n = 10) or L-NAME (0.5 mg/ml) in the drinking water (n = 11) for 6 weeks. After 6 weeks, the wall-to-lumen ratios and perivascular fibrosis in the coronary arteries were greater in the L-NAME group than in the control group. NO synthase-positive cells in the intima were abundantly observed in the control group, whereas no such cells were seen in the L-NAME group. In contrast, the number of VEGF-positive smooth muscle cells in the media was greater in the L-NAME group than in the control group. These findings strongly suggest a reciprocal relation between VEGF and NO even in a rat model of chronic NO blockade.

Animals↗
PubMed2002

Successful treatment of renovascular hypertension due to fibromuscular dysplasia by intravascular ultrasound-guided atherectomy.

A 22-year-old man presented with renovascular hypertension, based on a stenosis of the distal portion of the right renal artery with a "string of beads"-like appearance. An intravascular ultrasound image at the renal artery lesion revealed irregularity of the vascular wall. Directional atherectomy was performed and histopathology of atherectomised tissues showed medial fibroplasia, a common type of fibromuscular dysplasia. After atherectomy his hypertension was markedly improved. We report here a case of renovascular hypertension due to fibromuscular dysplasia, successfully diagnosed and treated with IVUS-guided renal atherectomy.

Adult↗
PubMed2002

Production of nitric oxide, but not prostacyclin, is reduced in klotho mice.

A novel murine model of aging (kl/kl mice) has been developed by in vivo mutagenesis. We analyzed endothelial function in this strain. Ring preparations of the thoracic aorta were obtained from 6- to 9-week old wild-type (+/+) and heterozygous (kl/+) klotho mice. The aortas of kl/+ mice showed an exaggerated contractile response to norepinephrine and attenuated vasodilator responses to acetylcholine and lecithinized superoxide dismutase (SOD) compared to +/+ mice. The response to sodium nitroprusside was unaltered in kl/+ mice. The contraction in response to norepinephrine was augmented by treatment with N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) to a greater extent in +/+ mice than in kl/+ mice. Treatment with L-NAME abolished the vasodilator responses to both acetylcholine and lecithinized SOD. NO metabolites (NO2- and NO3-) and cGMP concentrations in the urine were significantly reduced in kl/+ mice compared to +/+ mice. However, the urinary excretion of 6-keto-prostaglandin F1alpha was unaltered. There was little immunostaining for NO synthase and vascular endothelial growth factor (VEGF) in the aorta of kl/+ mice. No immunostaining for NO synthase was noted in the aorta of kl/kl mice. The expression of the klotho gene product may have a role in the regulation of VEGF expression and is tightly linked to endothelial release of NO.

Animals↗
PubMed2002

Effects of hormone replacement therapy on left ventricular hypertrophy and growth-promoting factors in hypertensive postmenopausal women.

We investigated the effects of hormone replacement therapy (HRT) on left ventricular hypertrophy (LVH) and growth-promoting factors in hypertensive postmenopausal women (PMW) with LVH. Twenty-one Japanese hypertensive PMW (age 55.3+/-0.8 years) with LVH who had never received HRT volunteered to participate in this study. Eleven subjects received a daily dose of HRT (0.625 mg conjugated equine estrogen, 2.5 mg medroxyprogesterone acetate) orally for 12 months. Ten PMW who refused HRT were enrolled as controls. Blood pressure and serum angiotensin-converting enzyme (ACE) activity, plasma aldosterone, and insulin resistance were measured. M-mode echocardiography and blood pressure measurements were performed in all patients. Data obtained before and after 12 months of HRT were compared. No significant differences in blood pressure were observed between the two groups after 12 months of HRT. In the HRT group, the LV mass index (p<0.01), serum ACE activity (p<0.01), and plasma aldosterone (p<0.01) levels were reduced after 12 months of treatment. The changes in serum ACE activity and plasma aldosterone were not correlated with the change in LV mass index in the HRT group. No significant changes in blood pressure, LV mass index, serum ACE activity, plasma aldosterone, or insulin resistance were observed in the control group. HRT contributed to the reduction of LV mass in hypertensive PMW. However, the effect of HRT on LVH did not appear to be associated with changes in growth-promoting factors, such as blood pressure, serum ACE activity, plasma aldosterone, and insulin resistance.

Aldosterone↗
PubMed2002

Prospective examination of adrenocortical function in advanced AIDS patients.

In human immunodeficiency virus infected individuals, human cytomegalovirus (CMV) remains a significant pathogen. The adrenal gland is a preferential site of CMV disease in acquired immunodeficiency syndrome (AIDS) patients. However, glucocorticoid replacement is often not selected because of the risk of exacerbating underlying infection. To evaluate the need for glucocorticoid replacement in these patients, we performed a prospective study to investigate the adrenal function in 60 advanced AIDS patients. Their adrenal function including rapid ACTH test (RAT), basal plasma ACTH level, and daily urinary free cortisol level was evaluated. Approximately 25% of the patients turned out to be abnormal in this evaluation. Almost 60% of the patients could be followed up for one year or until their death. Using the follow-up data, we calculated sensitivity, specificity, positive predictive value and negative predictive value. Excretion of urinary free cortisol with normal RAT was comparable to normal controls, whereas patients with abnormal RAT excreted significantly lower urinary free cortisol. During hospitalization, 14 patients with normal RAT had febrile episode. During the febrile period the concentration of the urinary free cortisol level increased by 2.2 times. This study suggests that glucocorticoid replacement is necessary for AIDS patients suspected as clinically adrenal insufficiency, and that the dose of glucocorticoid replacement might be increased during sick days in AIDS patients with abnormal adrenal function.

Acquired Immunodeficiency Syndrome↗