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Biomedical subjects

M Kubo

Publications and source records attributed to M Kubo.

At least 127 records · Page 7Linked to original sources
PubMed2000

Myositis and interstitial lung disease associated with autoantibody to a transfer RNA-related protein Wa.

We describe 2 patients with myositis and interstitial lung disease with the autoantibody to Wa antigen, a 48-kDa transfer RNA-related protein. In contrast to the previous description of anti-Wa antibody, our patients lacked systemic sclerosis-related features, but had clinical features consistent with those associated with antibodies to aminoacyl-transfer RNA synthetases. The difference in clinical presentation between our patients and patients with systemic sclerosis may be explained by recognition of different epitopes on the Wa antigen.

Aged↗
PubMed2000

Optimal hematocrit for the maximum oxygen delivery to the brain with recombinant human erythropoietin in hemodialysis patients.

AIM: Although hematocrit (Ht) around 33 to 36% has been recommended, Ht of 30% is usually achieved as a target level during recombinant human erythropoietin (rHuEPO) therapy in the majority of hemodialysis (HD) patients. The present study aimed at estimating an optimal hematocrit (Ht) for the maximum oxygen delivery to the brain with rHuEPO. PATIENTS AND METHODS: Oxygen delivery was defined as a product of cerebral blood flow and arterial oxygen content (CaO2). The regional cerebral blood flow (rCBF) in each region of interest was measured by positron emission tomography and CaO2 was calculated from hemoglobin concentration, arterial oxygen saturation, and arterial oxygen tension before and after rHuEPO therapy (1,500 units, 3 times a week) in 5 HD patients (the mean age of 52 +/- 2 (SEM) years old and the mean HD duration of 98 +/- 21 months). RESULTS: Ht rose significantly from 21 +/- 1 to 31 +/- 1% (p < 0.001) after the 3-month rHuEPO treatment in association with a significant increase in CaO2 from 7.7 +/- 0.4 to 11.6 +/- 0.3 ml O2/100 ml (p < 0.01). Hemispheric rCBF decreased significantly from 40 +/- 3 to 32 +/- 1 ml/100 g/min (p < 0.02). In all data both before and after rHuEPO treatment, Ht inversely correlated with the hemispheric rCBF (y = 55.7 - 0.76x, where y is rCBF and x is Ht, r = 0.80, p < 0.01), and positively with CaO2 (y = 0.85 + 0.34x, where y is CaO2 and x is Ht, r = 0.95, p < 0.01). By using these correlations, the hemispheric oxygen delivery was expressed as a function of Ht, being y = 47.3 + 18.3x - 0.3 x2, where y is cerebral oxygen delivery and x is Ht. From this curve, Ht at the highest cerebral oxygen delivery in the hemisphere, i.e. an optimal Ht was found to be 35.2%. Above this level of Ht, the hemispheric cerebral oxygen delivery would rather decline. CONCLUSION: The present study indicated that Ht of about 35% is required for a better oxygen delivery to the brain metabolism during anemia correction with rHuEPO.

Anemia↗
PubMed1999

CD28 costimulation accelerates IL-4 receptor sensitivity and IL-4-mediated Th2 differentiation.

The development of Th1 and Th2 cells is determined by the type of antigenic stimulation involved in the initial cell activation step. Evidence indicates that costimulatory signals, such as those delivered by CD28, play an important role in Th2 development, but little is known about how CD28 costimulation contributes to Th2 development. In this study, TCR cross-linking was insufficient for Th2 development, while the addition of CD28 costimulation drastically increased Th2 generation through the IL-4-mediated pathway. Th2 generation following CD28 costimulation was not simply explained by the enhancement of IL-4 production in naive T cells. To generate Th2 cells after TCR cross-linking only, it was necessary to add a 20- to 200-fold excess of IL-4 generated after TCR and CD28 stimulation. TCR cross-linking increased the expression level and binding property of the IL-4R, but enhanced the sensitivity to IL-4 only slightly. In contrast, as evidenced by the enhanced phosphorylation of Jak3, the IL-4Ralpha-chain, and STAT6 following IL-4 stimulation, CD28 costimulation increased IL-4R sensitivity without affecting its expression and binding property. This evidence of the enhancement of IL-4R sensitivity increases our understanding of how CD28 costimulation accelerates Th2 development.

Adjuvants, Immunologic↗
PubMed1999

A novel approach toward bacteriochlorophylls-e and f.

Methyl bacteriopheophorbide-f was prepared from methyl bacteriopheophorbide-d with retention of the 3(1)-chirality. The transformation of the methyl to the formyl group at the 7-position of the chlorin moiety will provide an alternative route for the synthesis of bacteriochlorophylls-e and f.

Bacteriochlorophylls↗
PubMed1999

Molecular cloning, chromosome mapping and characterization of the mouse CRTH2 gene, a putative member of the leukocyte chemoattractant receptor family.

We have cloned the mouse CRTH2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) gene encoding a putative leukocyte chemoattractant receptor, of which human homologue is expressed selectively in Th2 but not in Th1 clones among T cell clones. The deduced amino-acid sequence of mouse CRTH2 bears 77% identity with its human homologue. Phylogenetic analysis suggested that both mouse and human CRTH2 are closely related to the N-formyl peptide receptor and the C5a receptor among leukocyte chemoattractant receptors. The mouse CRTH2 gene was mapped on chromosome 19c with FISH, where no other genes for leukocyte chemoattractant receptors are mapped. RT-PCR analysis revealed that mouse CRTH2 mRNA is expressed in various cell lineages, including both hematopoietic and non-hematopoietic cell lines. Expression was also observed in liver, lung, kidney, brain, heart, thymus, and spleen. These results suggest that mouse CRTH2 functions in a variety of cells, making the effects of CRTH2 pleiotropic.

Amino Acid Sequence↗
PubMed1999

T cell antigen receptor-mediated activation of the Ras/mitogen-activated protein kinase pathway controls interleukin 4 receptor function and type-2 helper T cell differentiation.

The central role of type-2 helper T (Th2) cells in the development of allergic responses and immune responses against helminthic parasites is well documented. The differentiation of Th2 cells from naive T cells requires both the recognition of antigen by T cell antigen receptors (TCR) and the activation of downstream signal-transduction molecules of the interleukin 4 receptor (IL-4R) pathway, including Jak1, Jak3, and STAT6. Little is known, however, about how these two distinct pathways cooperate with each other to induce Th2 cells. Here, we use a T cell-specific H-Ras-dominant-negative transgenic mouse to show that TCR-mediated activation of the Ras/mitogen-activated protein kinase pathway alters IL-4R function and is required for Th2 cell differentiation. The enhancement of IL-4R signaling seems to be a consequence of both direct "crosstalk" with the TCR signaling pathway and increased protein expression of downstream signaling molecules of the IL-4R pathway. Therefore, successful Th2 differentiation depends on the effectiveness of the TCR-mediated activation of the Ras/mitogen-activated protein kinase pathway in modifying the IL-4R-mediated signaling pathway.

Animals↗
PubMed1999

Risk of non-Hodgkin's lymphoma in patients with hepatitis C virus infection.

Hepatitis C virus (HCV) has been suggested to play an etiological role in the development of B-cell non-Hodgkin's lymphoma (NHL) in Italy. However, another study in Scotland questioned increased risk of development of NHL in patients with chronic HCV infection. A total of 2,162 patients admitted to 3 hospitals in Osaka, where the incidence of HCV-related hepatitis is highest in Japan, during the period from 1957 to 1997 were followed up from the date of diagnosis of chronic HCV-related hepatitis until 30 October 1997. Overall, 12,404.5 person-years of observation were accrued with a follow-up period ranging from 0.25 to 40.4 (average 5.74) years. NHL of the B-cell type developed in 4 patients. The interval between onset of chronic HCV and NHL ranged from 6 to 36 (median 13) years. Expected number of cases of NHL in the sex-, age- and calendar year-matched general population was 1.90, which gave a relative risk (RR) of 2.10 (95% confidence interval 0.57-5.38; p = 0.247). Taking the much higher RR for hepatocellular carcinoma among patients with HCV infection into account, chronic HCV infection was considered to be moderately associated with increased risk of NHL.

Adolescent↗
PubMed1999

Hypersensitivity reactions to intraperitoneal administration of carboplatin in ovarian cancer: the first report of a case.

Hypersensitivity reactions to intravenous administration of carboplatin (CP) have been previously reported. However, hypersensitivity reaction to intraperitoneal administration of CP has not yet been reported. A 66-year-old woman diagnosed with ovarian carcinoma underwent six courses of intraperitoneal administration of carboplatin. During the seventh course of chemotherapy, delivered intraperitoneally, she developed hypersensitivity reactions with hypotension to carboplatin. Etoposide was used for the further chemotherapy. To the best of our knowledge, this is the first case report of hypersensitivity reactions to intraperitoneal administration of carboplatin.

Aged↗
PubMed1999

A rare case of acromegaly associated with pachydermoperiostosis.

Pachydermoperiostosis (PDP) is a rare syndrome manifested clinically by finger clubbing, extremity enlargement, hypertrophic skin changes, and periosteal bone formation. The pathogenesis of the disorder has not been clarified and few endocrine abnormalities were apparent. We report here a 58-year-old man with acromegaly associated with PDP, the features of clubbed fingers, coarse skin, and cutis verticis gyrata. Acromegaly due to GH-producing pituitary adenoma was confirmed in endocrinological and pathological studies.

Acromegaly↗
PubMed1999

Hemodialysis causes severe orthostatic reduction in cerebral blood flow velocity in diabetic patients.

Orthostatic hypotension is a serious problem in patients with diabetes mellitus (DM) undergoing hemodialysis (HD). To evaluate cerebral circulation during orthostasis in patients with DM, we examined changes in mean blood flow velocity in the middle cerebral artery (VMCA) during 60 degrees head-up tilt for 5 minutes in patients with DM (six men, two women; age, 57 +/- 3 years [mean +/- SEM]; HD duration, 47 +/- 27 months) before and after bicarbonate HD by using transcranial Doppler sonography. The findings were compared with those in HD patients without diabetes (non-DM; 12 men, 5 women; age, 47 +/- 3 years; HD duration, 82 +/- 23 months). Mean blood pressure (MBP) in the supine position, hematocrit (Hct), plasma fibrinogen, and volume of fluid removed by HD were not significantly different between the two groups (MBP, 106 +/- 6 versus 103 +/- 4 mm Hg; Hct, 26% +/- 1% versus 28% +/- 1%; fibrinogen, 355 +/- 37 versus 357 +/- 27 mg/dL; fluid, 2.5 +/- 0.2 versus 2.3 +/- 0.2 L). Percentage of change in VMCA (% VMCA) during tilt was compared between the groups before and after HD. Before HD, MBP decreased significantly to 93 +/- 5 mm Hg during tilt only in patients with DM. The degree of MBP reduction was -13 +/- 2 mm Hg in DM and -2 +/- 2 mm Hg in non-DM patients (P < 0.01). % VMCA equally decreased during tilt; DM, -12% +/- 3%, and non-DM, -12% +/- 2%. After HD; MBP decreased by 36 +/- 7 mm Hg in patients with DM, which was significantly greater than before HD. VMCA also decreased in both groups after HD, and % VMCA in DM (-32% +/- 5%) was significantly greater than before HD (P < 0.01) and in non-DM patients (-13% +/- 2%; P < 0.01). % VMCA positively correlated with the percentage of change ratio of MBP during tilt in both groups after HD (DM, r = 0. 87, P < 0.01; non-DM, r = 0.61, P < 0.01). Our results showed a significant decrease in cerebral blood flow velocity during tilt of equal magnitude in both groups before HD despite differences in the level of hypotension, whereas reduction in cerebral blood flow velocity and decrease in MBP were more marked in DM after HD. Orthostasis could thus cause hemodynamically mediated brain damage after HD, especially in patients with DM.

Aged↗
PubMed1999

Quantitative analysis of aristolochic acids, toxic compounds, contained in some medicinal plants.

The amounts of aristolochic acid I and II in four groups of medicinal plants from the Aristolochiaceae and some related plants were determined by high-pressure liquid chromatography, for Aristolochia was reported to produce interstitial nephritis caused by aristolochic acids during chronic use for the treatment of rheumatism, diuretic and analgesic. They were detected in all the plants that originated from the genus Aristolochia (Aristolochiaceae) and in some of the plants from the genus Asarum (Aristolochiaceae). The present results suggest that these medicinal plants should be prohibited to use for remedy due to the harmful effects attributed to aristolochic acids.

Aristolochic Acids↗
PubMed1999

Effect on locomotion of indole alkaloids from the hooks of uncaria plants.

Three predominant Uncariae plants, Uncaria rhynchophylla U. sinensis and U. macrophylla and their indole and oxindole alkaloid constituents were studied for their effect on locomotor response. Water extracts of U. macrophylla and U. sinensis and four indole alkaloids, corynoxine, corynoxine B, isorhynchophylline and geissoschizine methyl ether, significantly decreased locomotor activity after oral administration to mice. The depression of locomotor activity upon administration of these alkaloids appears to be due to mediating of the central dopaminergic system.

Alkaloids↗
PubMed1999

Functional and electrophysiological effects of a novel imidazoline-based K(ATP) channel blocker, IMID-4F.

1. The functional and electrophysiological effects of IMID-4F (2-[N-(2, 6-dichlorophenyl)-N-(4-flurorobenzyl)amino]imidazoline), a fluoro-benzyl derivative of clonidine, on vascular K(ATP) channels were investigated. In pig coronary artery, IMID-4F inhibited the vasorelaxation response to the K(ATP) channel opener levcromakalim with a pK(B) value of approximately 7.1. IMID-4F (30 microM) did not affect the vasorelaxation response to sodium nitroprusside (SNP). 2. In rat mesenteric artery smooth muscle cells IMID-4F (1 - 10 microM) caused a concentration-dependent depolarization of membrane potential. IMID-4F (10 microM) abolished the hyperpolarizing effects of levcromakalim (10 microM). 3. In patch clamp experiments using rat mesenteric artery smooth muscle cells, K(ATP) channel currents induced by levcromakalim (10 microM) were inhibited by IMID-4F (0.3 - 3 microM) in a concentration-dependent manner. The calculated IC(50) for IMID-4F inhibiting K(ATP) channel current was approximately 0.8 microM. 4. Radioligand binding studies using bovine aortic smooth muscle cell membranes showed that IMID-4F (30 microM) did not displace binding to the K(ATP) channel opener [(3)H]-P1075. However, both levcromakalim (10 microM) and glibenclamide (10 microM) caused significant displacement of [(3)H]-P1075. 5. These studies show that the imidazoline compound IMID-4F is one of the most potent antagonists of arterial K(ATP) channels identified. Vasorelaxation, hyperpolarization and K(+) currents through K(ATP) channels were all inhibited by IMID-4F at micromolar concentrations. Radioligand binding studies indicate that IMID-4F does not bind to the same site as levcromakalim or as glibenclamide. Considering other evidence, it is likely that IMID-4F acts by interacting directly with the pore of the K(IR) channel, rather than through the sulphonylurea subunit of the K(ATP) channel complex.

Aniline Compounds↗
PubMed1999

Liver metastases after curative resection in patients with distal bile duct cancer.

BACKGROUND: Curative resection cannot ensure long-term survival for patients with distal bile duct cancer. The aim of this study was to determine the most frequent mode of recurrence after curative resection and to analyse its risk factors. METHODS: Clinical details for 64 consecutive patients with distal bile duct cancer who underwent surgical resection between 1980 and 1997 were reviewed. Modes of recurrence and clinicopathological findings were analysed based on the residual tumour (R) classification. RESULTS: The overall actuarial 5-year survival rate was 32 per cent. Of 42 patients undergoing R0 resection 10 were alive at 5 years, of 17 having R1 resection one was alive at 5 years, and none of the five patients having R2 resection survived for 5 years (R0 versus R1, P = 0.02). In the R0 group, the incidence of liver recurrence (14 of 42 patients) was similar to that in the R1 resection group (six of 17), although there were fewer lymph node and peritoneal recurrences than in patients who had R1 resection (P < 0.05). The high-risk factor for liver metastasis was microscopic vascular involvement. Important factors for survival were lymph node metastasis, microscopic vascular involvement and age. In addition, microscopic vascular involvement was the only independent factor for survival in the R0 group. CONCLUSION: R0 resection provided significant survival benefit but had no effect on liver recurrence. Therefore, new agents or strategies to prevent liver metastasis are necessary for improvement of survival.

Adult↗
PubMed1999

Dermatomyositis with elevated serum hyaluronate.

We report two Japanese patients with dermatomyositis whose serum hyaluronate levels were correlated with their disease activities. The diagnosis of one patient was primary idiopathic dermatomyositis, and that of the second patient was dermatomyositis associated with neoplasia. The serum hyaluronate level of the former patient was decreased by systemic corticosteroid therapy, and that of the latter patient decreased following the surgical resection of mammary carcinoma and subsequent chemotherapy. The disease activity of each patient was greatly improved after these therapies. The longitudinal measurement of serum hyaluronate concentration may be useful to estimate the disease activity of patients with dermatomyositis whose initial serum levels of hyaluronate are elevated.

Adult↗
PubMed1999

Distribution and antigen specificity of anti-U1RNP antibodies in patients with systemic sclerosis.

Systemic sclerosis (SSc) is a generalized connective tissue disease which is characterized by the presence of several autoantibodies. To determine the prevalence and antigen specificity of anti-U1RNP antibodies (anti-U1RNP) in patients with SSc, serum samples from 223 patients with SSc, 117 patients with systemic lupus erythematosus (SLE), 18 patients with mixed connective tissue disease (MCTD) and 40 healthy control subjects were examined by indirect immunofluorescent analysis (IIF), double immunodiffusion, and immunoblotting using nuclear extract of HeLa cells. Eighteen of the 223 (8%) serum samples from patients with SSc were shown to be positive for anti-U1RNP. The frequency of anti-U1RNP positivity in limited cutaneous SSc (14%) was significantly higher than that in those with diffuse cutaneous SSc (3%). Anti-Sm antibodies were detected in patients with SLE positive for anti-U1RNP, but not in those with SSc positive for anti-U1RNP or those with MCTD. Immunoblotting demonstrated that anti-70-kD antibodies were detected more often in patients with SSc positive for anti-U1RNP and in those with MCTD than in those with SLE. Furthermore, anti-U1RNP was closely correlated with pulmonary fibrosis and joint involvement in patients with SSc. These results suggest that anti-70-kD antibodies are useful in the classification of patients with anti-U1RNP.

Antibodies, Antinuclear↗