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Biomedical subjects

H Tamura

Publications and source records attributed to H Tamura.

At least 235 records · Page 13Linked to original sources

Different modulation of protein kinase C isozymes in dibutyryl cyclic AMP-differentiated PC12h cells.

PC12h cells can be differentiated into sympathetic neuron-like cells by various agents, including nerve growth factor, basic fibroblast growth factor, cyclic AMP analogues, and protein kinase C (PKC) activators. To study the involvement of PKC in the process of PC12h cell differentiation by cyclic AMP treatment, PKC isozymes (alpha, beta I, beta II, and gamma) were analyzed using column chromatography and immunoblotting. Two PKC isozymes, PKC(alpha) and PKC(beta II), were predominantly detected in PC12h cells. When stimulated by dibutyryl cyclic AMP, PKC(alpha) levels declined in the cytosolic fraction of the cells, whereas PKC(beta II) levels increased. Increased PKC(beta II) levels were also detected in the particulate fraction, whereas particulate PKC(alpha) levels did not change. The total PKC activity decreased in the cytosolic fraction following cyclic AMP stimulation of PC12h cells, whereas it stayed constant in the particulate fraction. Fractionation on a hydroxyapatite column showed a decreased level of PKC(alpha) activity and a transient increase followed by a decreased level of PKC(beta II) activity. This discrepancy between increased PKC(beta II) immunoreactivity and reduced PKC(beta II) activity suggested the presence of nonactivatable PKC(beta II) in cyclic AMP-treated PC12h extract. These findings indicate that PKC(alpha) and PKC(beta II) are differentially regulated during the differentiation of PC12h cells. In addition, the differentiation of PC12h cells triggered by cyclic AMP seems to involve characteristic alterations of PKC isozymes.

Animals↗

Congenital biliary dilatation with pancreatico-biliary maljunction: a comparative study between children and adults.

A comparative study of congenital biliary dilatation with pancreatico-biliary maljunction in 15 children and 16 adults was undertaken. Cystic and fusiform dilatation of the common bile duct was seen in 9 and 6 cases respectively in the child group, with 8 and 8 cases respectively in the adult group. Cholangiographically, neither the length of the common channel nor the type of pancreatico-ductal union varied significantly between groups. Furthermore the incidence of higher amylase levels of bile showed no apparent variance from group to group. This was also true when looking histologically at the number and distribution of periductal glands surrounding the intra-hepatic bile duct. Therefore, we concluded that there was no essential etiological difference between the two groups.

Adult↗

Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator, in male F-344 rats.

The characteristics of the hepatocarcinogenesis induced by dehydroepiandrosterone (DHEA) were compared with that induced by other peroxisome proliferators such as [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14,643) and di(2-ethylhexyl)phthalate (DEHP). Male F-344 rats were given a diet containing DHEA at 0.5 or 1%, Wy-14,643 at 0.1% and DEHP at 2% for up to 78 weeks. In rats fed 0.5 or 1% DHEA the incidence of neoplasias was 20% after 52 weeks. At 78 weeks all rats treated with 1% DHEA had numerous grossly visible nodules and the incidence of hepatic neoplasia was dose-dependent. The magnitude of hepatocellular tumorigenicity after DHEA treatment was less potent than that after Wy-14,643, but more than that after DEHP treatment. Peroxisomal beta-oxidation activity increased three- or six-fold after a 10 week course of 0.5 or 1% DHEA respectively and this was significantly lower than that induced in Wy-14,643- or DEHP-fed rats. From 52 to 78 weeks these activities increased 3-9 times over that in controls. In both the group of rats treated with Wy-14,643 and those treated with DEHP, peroxisomal beta-oxidation constantly increased 11- to 15-fold during the experiment. Catalase activity increased 1.3- to 1.5-fold for the first 10 weeks of DHEA treatment and then recovered to the control level. The activities of glutathione peroxidase and glutathione S-transferase decreased markedly after 30 weeks in DHEA-treated rats and the decreases were sustained for up to 78 weeks. The profile of changes in enzyme activities in the rats fed DHEA was not significantly different from that of those fed Wy-14,643 or DEHP. There were no increases in 8-hydroxydeoxyguanosine, oxidative DNA damage or lipid peroxide level in the liver in any of the treated rats at 10 or 30 weeks. Since these results showed that the characteristics of hepatocarcinogenesis caused by DHEA were basically similar to those caused by Wy-14,643 and DEHP, typical peroxisome proliferators, hepatocarcinogenesis induced by DHEA is probably due to the same mechanisms as that induced by general peroxisome proliferators.

8-Hydroxy-2'-Deoxyguanosine↗

Assessment of therapeutic potential of interleukin 2 for myelodysplastic syndromes.

The therapeutic potential of interleukin 2 (IL-2) for myelodsplastic syndromes (MDS) was evaluated in vitro. IL-2-induced lymphokine-activated killer (LAK) cells were prepared from 38 MDS patients and 20 normal subjects. The cytotoxicity of LAK cells against K562 and Raji cell lines and MDS blasts was significantly reduced in high-risk MDS (refractory anaemia with excess blasts (RAEB), RAEB in transformation, and leukaemic transformation of MDS), but was relatively well-preserved in low-risk MDS (refractory anaemia (RA) and RA with ringed sideroblasts). Examination of the immunophenotypes of freshly-isolated lymphocytes showed that the percentage of CD4+ cells in low-risk MDS and the percentage of CD3+, CD4+ and CD8+ cell populations in high-risk MDS was significantly reduced compared with these populations in normal subjects. After cultivation with IL-2, these three cell populations were still reduced in the corresponding MDS groups and the percentage of CD3-CD56+ cells were significantly reduced in high-risk MDS. There was a positive correlation between the percentage of K562 cells lysed by MDS LAK cells and the percentage of CD3-CD56+ lymphocytes in MDS LAK cells. These aberrant lymphocyte subpopulations appeared to explain, at least in part, the reduced LAK cell cytotoxicity in MDS. These results present a possibility that IL-2 and LAK therapies are ineffective for most high-risk MDS patients, whereas they have potential value for low-risk MDS patients whose lymphocyte cytotoxicity is usually preserved.

Adult↗

Defective natural killer (NK) cell-mediated cytotoxicity does not imply clonal involvement of NK cells in myelodysplastic syndromes.

The clonality of purified cells was examined in 10 myelodysplastic syndromes (MDS) patients by analysing the restriction fragment length polymorphism and methylation pattern of the phosphoglycerate-kinase gene. Natural killer (NK) cell-mediated cytotoxicity was also examined. The granulocytes and monocytes were monoclonal or oligoclonal in all cases, except for the monocytes in one case. Conversely, the NK and T cells had a polyclonal pattern in most cases, including all cases who had defective NK cell-mediated cytotoxicity. The hypothesis that reduced NK cell-mediated cytotoxicity in MDS is caused by a clonal involvement of NK cells was not supported by the present study.

Adult↗

Broad-tuned chromatic inputs to color-selective neurons in the monkey visual cortex.

1. Input mechanisms of 21 color-selective cells in cytochrome oxidase-rich blobs in layer II/III of the anesthetized and paralyzed monkey primary visual cortex were studied by an iontophoretic administration of the GABAergic receptor antagonist bicuculline methiodide (BMI). 2. Color-selective blob cells become responsive to originally nonresponsive colors of stimuli or brightness contrast stimuli during removal of intracortical inhibition. 3. The magnitudes of the cells' responses to color stimuli during BMI administration were larger than the expected value of response calculated from the previously reported color tuning of color-selective geniculate cells and emission spectra of color stimulus. 4. These results suggest that color-selective blob cells receive a convergence of different types of chromatic inputs and that intracortical inhibition confers selectivity for a given color on them.

Animals↗

Quantitative assay of (1-3)-beta-D-glucan in culture media of Candida albicans using the G-test.

The diagnosis of invasive candidiasis is often difficult. The limulus test, which has been used for the assay of endotoxin in blood, was also found to react with (1-3)-beta-D-glucan, a component of the fungal cell wall. The factor in the limulus test that is activated by glucan, but not by endotoxin, is called factor G. The G-test utilizes the activation pathway starting with factor G, and sensitivity reacts with trace amounts of glucan. In this study, we investigated in vitro proliferation of Candida albicans and changes in the glucan concentration of RPMI-1640 media in the presence and absence of neutrophils and antifungal agents, as a pilot evaluation to possible clinical applications of the G-test. The proliferation of C. albicans and the glucan level measured in the culture media showed parallel changes. The glucan level in the culture media also increased when C. albicans was phagocytosed and digested by neutrophils, but not with administration of amphotericin B. The G-test closely reflected quantitative changes of C. albicans in vitro, and should be considered for future clinical studies in the diagnosis and evaluation of therapeutics in invasive candidiasis.

Amphotericin B↗

Cardiopulmonary effects of medetomidine-midazolam and medetomidine-midazolam- atipamezole in laboratory pigs.

The cardiopulmonary effects of medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg) and medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg)-atipamezole (160 micrograms/kg) were evaluated in laboratory pigs. The intramuscular administration of medetomidine-midazolam caused a pressor response, characterized by a rapid increase in arterial and pulmonary arterial pressure mediated mainly through systemic and pulmonary vasoconstriction. These pressures decreased after reaching a peak 5 to 10 min after the administration of sedatives, but maintained higher values than the base-line. However, all these changes caused by medetomidine-midazolam were within the physiological fluctuation. In addition, this combination did not induce bradycardia, subsequent hypotension or a significant decrease in cardiac output, which were generally observed with alpha 2-adrenoceptor agonists, and caused fewer changes in the respiratory system. The administration of atipamezole resulted in a marked transient decrease in vascular resistance, and caused a decrease in blood pressure and increases in cardiac output and heart rate. However, these changes were relatively small and sustained for a short time. Thus the combination of medetomidine-midazolam and atipamezole have minimal cardiopulmonary effects and might be used safely in laboratory pigs.

Adrenergic alpha-Agonists↗

Effects of medetomidine-midazolam on plasma glucose and insulin concentrations in laboratory pigs.

Effects of medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg) on plasma glucose and insulin concentrations were evaluated in laboratory pigs. Intramuscular injection of medetomidine-midazolam induced a gradual hyperglycemic response associated with hypoinsulinemia which was much smaller than that by 80 micrograms/kg of medetomidine alone and was almost within a physiological fluctuation. These mild responses induced by medetomidine-midazolam were antagonized by use of an alpha 2-adrenoreceptor antagonist atipamezole (160 micrograms/kg), therefore those changes were thought to be mainly attributed to the effect of medetomidine on alpha 2-adrenoreceptors. A combination of medetomidine at a low dose and midazolam reduces undesirable effects, while providing more profound sedation than medetomidine alone in laboratory pigs.

Adrenergic alpha-Agonists↗

[Mutagenicity studies of lactitol (NS-4)].

Lactitol (NS-4), a hepatic encephalopathy drug, was examined for mutagenicity in the reverse mutation test in bacteria, the chromosome aberration test with cultured mammalian cells, and the micronucleus test in mice. 1. In the reverse mutation test using Salmonella typhimurium (TA1535, TA100, TA1537, and TA98) and Escherichia coli (WP2uvrA), the drug did not significantly increase revertant colonies in any of the test strains with or without metabolic activation system (S-9mix). 2. In the chromosome aberration test with cultured Chinese hamster lung cells (CHL/IU), the drug did not significantly increase aberrant cells in the direct method or in the metabolic activation method. 3. In the micronucleus test with Slc:ddY male mice, the drug did not significantly increase micronucleated polychromatic erythrocytes in the bone marrows. These results suggest that lactitol has no mutagenicity in vitro or in vivo.

Animals↗

An autopsy case of light chain deposition disease.

This report describes a case of light chain deposition disease (LCDD) with unusual findings of fibrillar structures in the deposits and marked calcification in several organs. A forty-year-old man was initially diagnosed with LCDD in 1987, and died of sepsis three and one-half-years later. Histological examination of autopsy specimens demonstrated eosinophilic amorphous materials, which differed from amyloid, in vessel walls or around parenchymal cells in almost every organ examined. Ultrastructurally, in addition to granular deposits, fibrillar structures were also seen in the deposits. Marked calcification was present in the myocardium, skeletal muscles, adrenal glands and arteries.

Adrenal Glands↗

[Problems and solutions of home care for a terminal cancer patient--cooperation as a team approach].

In order to have a terminal cancer patient spending fulfilling remaining of his life, the role of home care is important. Caremark clinical team, consists of nurses, pharmacists and clinical coordinators (CC), provides home care service for patients. We have faced many problems regarding providing care for our cancer patients, especially terminal patients, and solved the problems in cooperation with the physicians. The main problems which we have faced with care for terminal cancer patients are as follows: (1) For emergency case, such as sudden changes in patient condition, if a hospital where the patient used to stay can not accept his return, our clinical coordinator makes a contact with closer hospital and asks them to hospitalize the patient. (2) Concerns of a patient and his family increase when his pain is getting severe. For this case, our nurse gives his caregiver training on treatment method, and normal pain management care for the patient. Also our pharmacist talks with the patient and his family and try to reduce the pain by using more suitable drugs at each conditions. (3) A patient with serious conditions which requires long term home care, his family and caregivers have more burdens. For this problem we suggests them to use high touch home care providers, and also our nurse provides psychological care (counseling). We have solved other problems in cooperation with each specialists, and we are confident that we are able to provide better home care service for our patients.

Female↗

An adult case of polycystic kidney disease associated with congenital hepatic fibrosis.

Congenital hepatic fibrosis is often associated with infantile, but not with adult polycystic kidney disease. We report the unusual case of an adult patient with polycystic kidney disease complicated by congenital hepatic fibrosis. A 27-year-old women was admitted to our hospital because of gross hematuria due to hemorrhage from renal cysts. She presented hematemesis from ruptured esophageal varices at the age of 14 years. She was diagnosed as having end-stage renal disease due to polycystic kidney disease at the age of 23 years, and maintenance hemodialysis was initiated the following year. Gross hematuria was managed with supportive therapy. However, the patient developed cholangitis and died of sepsis. Postmortem examinations as well as the patient's clinical course suggested that she had an autosomal dominant type of polycystic kidney disease. Histological findings of the liver were compatible with congenital hepatic fibrosis.

Adult↗

[T cell selection and tolerance induction in the thymus].

T cells play a major role in the immune system. While developing in the thymus, useful T cells are selected for expansion and harmful ones are deleted or inactivated. During this process, it is the T cells themselves which are doing the learning as opposed to the thymus doing the teaching. Both clonal deletion and clonal anergy are mechanisms of tolerance, the former being thymic, and thus central, while the latter is peripheral. Following a signal from the T cell receptor, anergy or deletion is triggered, if there are no co-stimulatory factors. Here, the outcome is determined by binding intensity. However, if the signal from the T cell receptor is accompanied by the required additional co-stimulatory signals, then the T cell is rescued from apoptosis and proliferates.

Animals↗

Hyperhomocysteinemia as a possible role for atherosclerosis in CAPD patients.

It has been shown that hyperhomocysteinemia is a risk factor for atherosclerotic vascular disease. In this study, we measured total plasma homocysteine in continuous ambulatory peritoneal dialysis (CAPD) patients and evaluated its correlation with atherosclerosis. Subjects consisted of healthy volunteers, and hemodialysis (HD) and CAPD patients. Fluoro-HPLC was employed to estimate plasma levels of total homocysteine (Hcy). Plasma levels of total Hcy were significantly higher in the CAPD patients compared with the HD patients and controls. Atherosclerotic score (ASS) was calculated, and the correspondence with plasma levels of total Hcy was analyzed. There was a significant correlation between plasma levels of total Hcy and ASS in CAPD patients. However, plasma levels of total Hcy did not correlate with age, plasma vitamin B6 level, residual renal function, protein catabolic rate (PCR), or KT/V. Our present study suggests that elevated concentrations of total plasma Hcy might play a role in the development of atherosclerosis in CAPD patients.

Arteriosclerosis↗

Studies on the GPI-anchored enzyme, hepatic 5'-nucleotidase. Microheterogeneity of the anchor, processing and localization.

Hepatic 5'-nucleotidases of vertebrates were investigated for localization in the lysosomes and the plasma membrane, microheterogeneity of the glycosylphosphatidylinositol (GPI)-anchor moiety and minimal requirement of the C-terminal signal peptide for GPI attachment. Using PIPLC of Bacillus thuringiensis and subcellular fractionation by Percoll gradient centrifugation, we found that chicken liver 5'-nucleotidase can be transferred from plasma membrane to lysosomes in the GPI-anchored or soluble form. Bovine liver ecto 5'-nucleotidase was solubilized by PIPLC, purified to a homogeneous state, and analyzed for the structures of GPI-anchor isoforms by HPLC and ESI-MS in combination with glycosidase treatments, after peptide-bond cleavage by CNBr or trypsin. Several isomers of the GPI anchor were thus characterized; major components contained two phosphorylethanolamine residues, whereas the component containing three phosphorylethanolamine residues was present only as a small percentage of the total. The cleavage/attachment site of the GPI anchor in the C-terminal of 5'-nucleotidase was shown to be Ser523. The peptide region cleaved off at the posttranslational processing has a length of 25 amino acid residues which contains a hydrophobic stretch of 17 amino acids. By site-directed mutagenesis, we determined the minimal length of the hydrophobic peptide to be 13 amino acids for expression of 5'-nucleotidase as a GPI-anchored form on the COS cell surface. When peptide length was shortened to less than 13 amino acids, the expressed enzyme was not sorted to the cell surface but present within, or secreted out of the cells.

5'-Nucleotidase↗

[An adult case of glomerulocystic kidney disease].

A 56-year-old female presented with end-stage renal disease. A CT scan of her kidneys demonstrated that the density of the renal parenchyma was quite low as compared with normal kidneys, and that corticomedullary demarcation was obscured. Magnetic resonance imaging (MRI) disclosed low intensity of the kidneys in T1-weighed images, and high intensity in T2-weighed images. In order to elucidate the etiology of her kidney disease, open renal biopsy was performed. The kidney surface was covered with numerous cysts with a diameter of less than 3 mm. Biopsy specimens from the cortical surface showed multiple cystic lesions. Serial sections of more than 200 slices of the biopsy material demonstrated that traces of collapsed glomeruli were present in most of the cysts. On electron microscopy, some epithelial cells lining the cysts were found to be round-shaped and contained a substantial amount of mitochondria, suggesting proximal tubules. These histological findings were compatible with glomerulocystic kidney disease (GCKD). An adult case of GCKD has rarely been reported, but the CT scan as well as MRI of the kidneys appeared to complement the diagnosis of GCKD. Although the cysts of GCKD have been considered to be dilatations of the Bowman's capsules, our observation suggested that part of the cells lining the cysts consisted of proximal tubular epithelium.

Female↗