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Biomedical subjects

H Tamura

Publications and source records attributed to H Tamura.

At least 109 records · Page 6Linked to original sources
PubMed1998

Ovarian immune cells express granulocyte-macrophage colony-stimulating factor (GM-CSF) during follicular growth and luteinization in gonadotropin-primed immature rodents.

To obtain clues as to whether granulocyte-macrophage colony-stimulating factor (GM-CSF) is related to ovarian physiology, the sites, the gene expression and the production of GM-CSF in the ovary during follicular development and luteinization were studied in equine CG (eCG)-primed immature mice and rats. During follicular development, the expression of GM-CSF mRNA was localized in theca-interstitial tissues, oocytes and granulosa cells of small developing follicles in mice. In the mouse ovary after ovulation, luteal tissues as well as the above components had intense signals for GM-CSF mRNA. Mast cells, which were present mainly in the ovarian medulla, also expressed mRNA for GM-CSF in rats. Immunohistochemical analyses with two different antibodies against murine GM-CSF revealed that GM-CSF-like immunoreactivity was detectable mainly in theca-interstitial, luteal tissues, oocytes and mast cells. Intense GM-CSF positive cells in theca-interstitial and luteal tissues were stained with anti-CD11b antibody in mice. Messenger RNAs for GM-CSF receptor subunits were expressed in mast cells of the medulla and in luteal tissues in rat ovary. The levels of GM-CSF released into the culture media by rat ovarian dispersed cells 1-2 days after eCG treatment were higher than those before the treatment, although no significant change in the levels of ovarian GM-CSF mRNA was detected by reverse transcription-polymerase chain reaction analysis. The secretion of GM-CSF was also increased by treatment of the cells with immune stimulators such as phorbol ester, interleukin-1 and lipopolysaccharide. These data indicate that ovarian macrophages and mast cells in addition to theca-interstitial cells, synthesize and release GM-CSF during ovarian cycles, and that ovarian GM-CSF secreting capacity is enhanced during early stages of follicular development in rodents.

Animals↗
PubMed1998

Comparison of ipsilateral activation between right and left handers: a functional MR imaging study.

We used fMRI to compare the ipsilateral activation in the sensorimotor region (SMR) during dominant and non-dominant hand motor tasks between right and left handers. In right handers, the ipsilateral activation was significantly greater during non-dominant (left) hand task than dominant (right) hand task, while in left handers, it showed no significant difference. The ipsilateral activation was most pronounced in the precentral subregion (presumably corresponding to the premotor area) during either hand task in both groups. We conclude that the different patterns of ipsilateral activation might be mainly explained by the hemispheric dominance. The skill of the hand and complexity of tasks may be related to the predominant activation of the premotor area.

Adult↗
PubMed1998

Induction of hepatic poly(ADP-ribose) polymerase by peroxisome proliferators, non-genotoxic hepatocarcinogens.

Two peroxisome proliferators, [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio] acetic acid (Wy-14,643) or di(2-ethylhexyl) phthalate (DEHP), were given orally to male F-344 rats for up to 78 or 97 weeks. At 1 week, the activity of poly(ADP-ribose) polymerase (pADPRP) was increased 2- and 1.8-fold in the liver of rats treated with Wy-14,643 and DEHP, respectively. The induction of the activity was maintained at 2.5- or 2-fold for up to 52 weeks. The immunoblot and Northern blot analyses revealed that the induction of pADPRP activity would be responsible for the increase in the amount of mRNA. In addition, in the liver tumor induced by Wy-14,643 and DEHP, the pADPRP mRNA level increased 3.6- or 3.7-fold. The magnitude of the increase in the mRNA level was higher than that in the non-tumor portion. These findings suggest that the induction of pADPRP may play an important role in the hepatocarcinogenesis induced by peroxisome proliferators.

Administration, Oral↗
PubMed1998

On the nature of rat hepatic and mouse olfactory sulfotransferases.

Rat hydroxysteroid sulfotransferase (HS-SULT) cDNAs, ST-40 and ST-20 are 90% identical in amino acid sequences and show different substrate specificities toward dehydroepiandrosterone (DHEA), androsterone (AD) and cortisol (CS). ST-40 enzyme is active toward the three substrates, whereas ST-20 enzyme is preferentially active for CS. First we prepared mutants of well conserved histidine, lysine and asparagine by site-directed mutagenesis. Secondly we constructed 20 chimeric HS-SULTs by reciprocal exchange of five protein domains between ST-20 and ST-40 enzymes. The studies on the expressed mutant and chimeric enzymes indicate the importance of the C-terminal region for the substrate specificity and the involvement of multiple regions for the enzyme activities. Next we determined the genetic loci of ST-40 and ST-20 by fluorescence in situ hybridization. Biotinylated ST-20 and ST-40 probes gave a pair of fluorescent spots on the same region of rat chromosome 1 and the loci of these genes were localized to the same chromosomal region of 1q21.3 --> q22.1. Finally we studied mouse olfactory phenol SULT (P-SULT). It was immunolocalized in the cytoplasm of mouse olfactory sustentacular cells and mouse nasal cytosols show high SULT activities toward phenolic aromatic odorants. We subsequently isolated a mouse P-SULT cDNA from mouse olfactory cDNA library. It encodes 304 amino acid polypeptide and is 94% identical with rat ST1C1 in amino acid sequences.

Amino Acid Sequence↗
PubMed1998

Repeated cycles of G-CSF-combined postremission chemotherapy for acute myeloid leukemia in a first complete remission: a pilot study.

The cure rate of acute myeloid leukemia might increase if G-CSF were given concurrently with repeated postremission chemotherapy. However, this therapy might cause severe complications, including depletion of normal hematopoietic progenitors as a long-term toxicity. Thus, we conducted a pilot study of this strategy. Twenty-six acute myeloid leukemia patients in a first complete remission (CR) were treated with two courses of consolidation chemotherapy (10-day BHAC-DMP, consisting of behenoyl cytosine arabinoside, daunorubicin, 6-mercaptopurine and prednisolone) and repeated maintenance-intensification therapy including eight cycles of six-day BHAC-DMP. G-CSF (filgrastim) was administered concurrently with these BHAC-DMP therapies. Toxicity during the therapeutic period was not significant in the study group compared with the historical control, treated with the same regimen without G-CSF. Neutrophil recovery after the consolidation therapy was more rapid in the study group than in the historical control (p = 0.066 and 0.024 for the first and second consolidation courses, respectively). Long-term toxicity, such as cytopenia, has not been seen in eight patients who have remained in CR for a long period (range: 39-58 months). At a median follow-up of 39 months, the predicted rate of 42-month CR duration for these 26 patients was 50% (95% confidence limits: 30% to 71%). We conclude that G-CSF-combined repeated BHAC-DMP postremission therapy is feasible. Full elucidation of the clinical benefit of this strategy will require further study.

Acute Disease↗
PubMed1998

Hemorrhage in pituitary adenoma: correlation of MR imaging with operative findings.

The aim of this study was to correlate MR imaging and operative findings of hemorrhage in pituitary macroadenomas. We retrospectively reviewed MR images of 113 surgically proven pituitary adenomas. All patients were examined on a 1.5-T MR system. The intensity of intratumoral cystic cavities was correlated with operative findings. In 15 patients with pituitary apoplexy, we determined relationship between interval of MR examination after apoplectic event and MR signal intensity. In 8 patients with repeated preoperative MR examination, we evaluated sequential changes of intratumoral hemorrhage. There were 54 cavities at surgery: 52 were hemorrhagic and 2 were nonhemorrhagic. Twenty-nine of 52 hemorrhagic cysts demonstrated high/low signal (H/L) fluid-fluid levels on T2-weighted image (T2WI). In 19 of them, two components could be separately seen at operation: the supernatant high-intensity area represented xanthochromic fluid, and the dependent low-intensity area represented liquefied hematoma. The H/L fluid-fluid level was observed predominantly in hematomas on MR images obtained after longer intervals. In patients with repeated MR examination, follow-up MR imaging revealed additional hemorrhage or new formation of fluid-fluid levels. It was surprising that 12 of 14 cysts preoperatively judged as nonhemorrhagic in fact contained hemorrhagic components. The preoperative MR images are well correlated to the operative findings in hemorrhagic pituitary macroadenomas. It proved that 52 of 54 cystic cavities had hemorrhagic component.

Adenoma↗
PubMed1998

Fulminant hepatitis complicated by small intestine infection and massive hemorrhage.

A 34-year-old man diagnosed with fulminant hepatitis, caused by hepatitis B virus, and acute renal failure was referred to our hospital. After admission to the intensive care unit, the liver and renal failure were ameliorated. Melena requiring transfusion occurred during the course of his illness. Endoscopic examination demonstrated pseudomembranes, erosions, ulcers, and hemorrhage in the duodenum, the upper jejunum, and the terminal ileum, suggesting widespread lesions throughout the small intestine. Pseudomonas putida, Xanthomonas maltophilia, and Candida glabrata were cultured from ileal fluid. Candida glabrata was also detected in sputum, feces, and on an intravenous catheter tip. The patient was treated with amphotericin B and miconazole. The melena was ameliorated, but inflammation of the small intestine persisted. Although we had difficulty in treating the enteritis, the patient survived, and 1 year later colonoscopic examination demonstrated no abnormalities. The small intestine is a difficult site to examine, but endoscopic examination of this site is important when massive hemorrhage develops.

Adult↗
PubMed1998

Pulmonary toxicity after granulocyte colony-stimulating factor-combined chemotherapy for non-Hodgkin's lymphoma.

Sporadic cases have developed pulmonary toxicity after receiving chemotherapy and granulocyte colony-stimulating factor (G-CSF). However, because such cases received chemotherapy that alone frequently causes pulmonary toxicity, the role of G-CSF in this toxicity has been unclear. CHOP therapy (cyclophosphamide, doxorubicin, vincristine and prednisolone) only slightly induces pulmonary toxicity. However, we observed a considerable incidence of this toxicity in non-Hodgkin's lymphoma subjects receiving CHOP therapy and G-CSF (6 out of 52 subjects, 11.5%). In this cohort, among various characteristics, including the dose and interval of CHOP therapy, only the mean peak leucocyte count (MPLC) with each therapy cycle was associated with development of this toxicity (MPLC > or = 23.0 x 10(9) l(-1), 6 out of 29 cases; MPLC < 23.0 x 10(9) l(-1), 0 out of 23 cases; P = 0.020). These findings suggest that the effect of G-CSF is the main determinant of the pulmonary toxicity in these cases. Because the toxicity was associated with a large MPLC and did not recur in cases readministered G-CSF, an idiosyncratic reaction to G-CSF is unlikely to be the pathogenesis of this toxicity. Thus, lowering the G-CSF dose seems to be useful in the prevention of this toxicity. In all six cases, the time course of manifestation of the toxicity was the same, and early application of high-dose corticosteroid led to cure. This knowledge will be helpful in the care of similar cases.

Adult↗
PubMed1998

Plasma thrombopoietin (TPO) levels and expression of TPO receptor on platelets in patients with myelodysplastic syndromes.

Data on endogenous thrombopoietin (TPO) levels and their regulation in myelodysplastic syndromes (MDS) are sparse. We examined the plasma TPO level of 85 MDS patients by a sensitive enzyme immunoassay and the platelet expression of TPO receptor (TPO-R) protein, which metabolizes endogenous TPO, in 19 MDS patients with an equilibrium binding assay using 125I-TPO. The MDS patients had higher plasma TPO levels (7.0 +/- 9.3 fmol/ml) than 52 normal subjects (P < 0.0001). Refractory anaemia (RA) patients (n = 39) had higher plasma TPO levels than patients (n = 28) with RA with excess blasts (RAEB) or RAEB in transformation (RAEB-t) (P = 0.0002), irrespective of similar platelet counts in these groups. The plasma TPO level correlated inversely with the platelet count in RA patients (P = 0.0027) but not in RAEB and RAEB-t patients (P = 0.7865). These data suggest that the physiological pathway for TPO production and metabolism is conserved, at least partially, in RA, but deranged in RAEB/RAEB-t. The number of TPO-R per platelet was significantly smaller in 19 MDS patients (17.5 +/- 13.3) than in normals (P = 0.0014), but similar between RA patients and patients with RAEB and RAEB-t. Further, the bone marrow megakaryocyte count, determined in 31 MDS patients, was quite similar between RA patients and patients with RAEB or RAEB-t. Thus, in addition to thrombocytopenia, a reduced platelet TPO-R number may contribute to elevated plasma TPO levels in MDS, and a regulatory pathway for circulating TPO other than platelet TPO-R and marrow megakaryocytes, such as blasts expressing TPO-R, may operate in RAEB/RAEB-t.

Blood Platelets↗
PubMed1998

Gradual solubilization of Candida cell wall beta-glucan by oxidative degradation in mice.

Candida spp. is a medically important fungi which induces disseminated candidiasis and candidemia in hospitalized immunocompromised patients. The cell wall of Candida is mainly composed of two polysaccharides, mannan and beta-glucan, and at least part of beta-glucan is basically insoluble in H2O or NaOH. We became interested in when and how particulate beta-glucan changes to the soluble form. However, the fate of wall components has not been examined in detail. In this study, modification and solubilization of the cell wall beta-glucan were analyzed in vivo and in vitro. Cells of Candida, intravenously administered to mice (1 mg/mouse), were immediately deposited mainly in liver as determined by 3H-labeled cells. Beta-Glucans were detected in these mice for at least for 6 months by the beta-glucan specific assay. During this period, the insoluble cell wall beta-glucan was gradually solubilized in these organs, probably by oxidative stress of macrophages. Candida cells and particulate beta-glucans were also gradually solubilized in vitro using sodium hypochlorite solution, but part of the cell wall beta-glucan was still insoluble even after treatment with concentrated hypochlorite solution for one day at room temperature. These findings strongly suggested that the fungal cell wall beta-glucans were quite resistant to oxidative metabolism in vivo and in vitro, and thus deposited for quite long period in the host.

Animals↗
PubMed1998

Melatonin directly suppresses steroid production by preovulatory follicles in the cyclic hamster.

The purpose of these studies was to investigate the effects of melatonin on the production of steroids (progesterone, testosterone, and estradiol) and cAMP by preovulatory follicles and to examine changes in melatonin concentrations in the ovary during the estrous cycle. Adult cyclic hamsters were used in this study. Melatonin concentrations in the ovary, pineal gland, and serum were measured at mid-light and mid-dark during the estrous cycle. Effects of melatonin on steroidogenesis by preovulatory follicles, thecae, and granulosa cells were examined, and its effect on cAMP production by preovulatory follicles was also investigated. Melatonin (0.1-10 ng/ml) had no effect on steroid production in the absence of hCG, but melatonin decreased progesterone and estradiol production by preovulatory follicles in a dose-dependent and time-dependent manner in the presence of hCG (100 mIU/ml). The target of melatonin was thecae but not granulosa cells, and melatonin significantly reduced cAMP production by preovulatory follicles. Melatonin concentrations in the ovary showed a similar phasic variation with high levels during mid-dark and low during mid-light, as in the pineal gland and serum. These results show that the ovarian melatonin levels also exhibit a circadian rhythm and suggest that the high melatonin milieu in the ovary may induce gonadal regression in the cyclic hamster.

Animals↗
PubMed1998

[Pathological changes by the imbalance of host T helper lymphocyte subsets in Mycoplasma pulmonis pneumonia of mice].

To evaluate the contribution of the subsets of T helper lymphocyte (Th) to the development of pulmonary lesion in mycoplasma pneumonia, we compared the pathological findings between Th1 dominant mice (C57BL/6) and Th2 dominant mice (BALB/c) in experimental Mycoplasma pulmonis (M. pulmonis) pneumonia. Mice (ICR, C57BL/6, and BALB/c) were intranasally inoculated with 0.03 ml of a solution containing M. pulmonis (1 x 10(8)) colony forming units per ml. Another M. pulmonis inoculated ICR mice were treated with interleukin-2 (IL2; 4.8 micrograms/day), days 3-9, intracutaneously). All mice were sacrificed at day 14, and the lung specimens were examined. Peribronchial lymphocyte cuffing was more prominent in C57BL/6 mice than that of ICR mice, and intra-alveolar inflammatory-cell infiltration in BALB/c mice was more prominent than in ICR mice. Pathological patterns of the lung in IL-2 treated ICR mice were mimicking those of C57BL/6 mice. These results suggested that pathological patterns of mycoplasma pneumonia in mice might be altered by the imbalance of host T helper lymphocyte subset.

Animals↗
PubMed1998

Biological characterization of endotoxins released from antibiotic-treated Pseudomonas aeruginosa and Escherichia coli.

The supernatants taken from Pseudomonas aeruginosa and Escherichia coli cultures in human sera or chemically defined M9 medium in the presence of ceftazidime (CAZ) contained high levels of endotoxin, while those taken from the same cultures in the presence of imipenem (IPM) yielded a very low level of endotoxin. The biological activities of endotoxin in the supernatants were compared with those of phenol water-extracted lipopolysaccharide (LPS). The endotoxin released from the organisms as a result of CAZ treatment (CAZ-released endotoxin) contained a large amount of protein. The protein, however, lacked endotoxic activity, since the endotoxin did not show any in vivo toxic effects in LPS-hyporesponsive C3H/HeJ mice sensitized with D-(+)-galactosamine (GalN) or any activation of C3H/HeJ mouse macrophages in vitro. The activities of CAZ- and IPM-released endotoxin (as assessed by a chromogenic Limulus test) were fundamentally the same as those of P. aeruginosa LPS, since their regression lines were parallel. The CAZ-released endotoxin was similar to purified LPS with respect to the following biological activities in LPS-responsive C3H/HeN mice and LPS-hyporesponsive C3H/HeJ mice: lethal toxicity in GalN-sensitized mice, in vitro induction of tumor necrosis factor- and NO production by macrophages, and mitogen-activated protein kinase activation in macrophages. The macrophage activation by CAZ-released endotoxin as well as LPS was mainly dependent on the presence of serum factor and CD14 antigen. Polymyxin B blocked the activity. These findings indicate that the endotoxic activity of CAZ-released endotoxin is due primarily to LPS (lipid A).

Animals↗
PubMed1998

Protective effects of a human 18-kilodalton cationic antimicrobial protein (CAP18)-derived peptide against murine endotoxemia.

CAP18 (an 18-kDa cationic antimicrobial protein) is a granulocyte-derived protein that can bind lipopolysaccharide (LPS) and inhibit various activities of LPS in vitro. The present study examined the protective effect of a synthetic 27-amino-acid peptide (CAP18(109-135)) from the LPS-binding domain of CAP18 against antibiotic-induced endotoxin shock, using highly LPS-sensitive D-(+)-galactosamine (D-GalN)-sensitized C3H/HeN mice. The antibiotic-induced endotoxin (CAZ-endotoxin) was prepared from the culture filtrate of Pseudomonas aeruginosa PAO1 exposed to ceftazidime (CAZ). Injection of CAP18(109-135) protected the mice injected with LPS or CAZ-endotoxin from death and lowered their tumor necrosis factor (TNF) levels in serum in a dose-dependent manner. Treatment with CAZ caused death of the D-GalN-sensitized P. aeruginosa PAO-infected mice within 48 h, while injection with CAP18(109-135) rescued the mice from death. In the mice rescued from death by injection with CAP18(109-135), endotoxin levels in plasma and TNF production by liver tissues were decreased but the numbers of viable infecting bacteria in their blood were not decreased significantly and remained at the levels in CAZ-treated mice. These results indicate that CAP18(109-135) is capable of preventing antibiotic-induced endotoxic shock in mice with septicemia and that the effect is due to its LPS-neutralizing activity rather than to its antibacterial activity.

Animals↗
PubMed1998

Measurement of (1-->3)-beta-D-glucan in an experimental model of systemic candidiasis.

To investigate the utility of measuring blood concentrations of (1-->3)-beta-D-glucan, a component of the fungal cell wall, as an auxiliary diagnostic method for systemic candidiasis, rats were inoculated with Candida albicans and the number of C. albicans in the viscera and glucan in the blood were quantitated. The concentration of blood glucan and the number of C. albicans in the viscera were also measured both under leukopenia and with deteriorated reticuloendothelial system cell function, and when the liver and spleen had been excised. As a result, systemic candidiasis appeared in the group with leukopenia, and the number of living C. albicans increased in the kidney and liver. Together with this increase in the number of C. albicans, there was an increase in blood (1--> 3)-beta-D-glucan. Measurements of blood (1--> 3)-beta-D-glucan well reflect a proliferation of C. albicans in vivo, which would make this a useful auxiliary for the clinical diagnosis of systemic mycosis.

Animals↗
PubMed1998

Identification of three hydroxysteroid sulfotransferase isoenzymes in the rat liver.

Isolation of several hydroxysteroid sulfotransferase (HS-ST) cDNAs from the rat liver cDNA library has demonstrated the possible expression of these HS-ST isoforms in rat liver. We devised a method to detect unequivocally ST-20 and ST-40 mRNAs by a reverse transcription-polymerase chain reaction, using specific primers. ST-40 mRNA was expressed only in liver, but ST-20 mRNA was present predominantly in the liver and slightly in extrahepatic tissues. On chromatofocusing, expressed ST-20 or ST-40 enzymes were eluted at approx. pH 8.2 and 5.7-4.7 or at pH 6.4-5.4, respectively. Chromatofocusing of adult female rat liver cytosols resolved HS-ST isoenzymes in a broad range of pH, and ST fractions A, B, C, D and E were eluted at approx. pH 8.2, 7.6, 7.5-6.8, 6.2 and 6.1-5.5, respectively. After PAP-agarose affinity column chromatography and SDS-polyacrylamide gel electrophoresis (PAGE), their N-terminal amino acid sequences were determined. ST isoenzymes present in fractions B and E showed identical N-terminal amino acid sequences with those of ST-21 and ST-20, respectively, whereas the ST isoenzymes present in fractions C and D had the same N-terminal amino acid sequence as those of ST-40 (and/or ST-41). The results demonstrated the presence of at least three HS-ST isoenzymes in adult female rat liver.

Amino Acid Sequence↗
PubMed1998

Suppression of apoptotic cell death progressed in vitro with incubation of the chorion laeve tissues of human fetal membrane by glucocorticoid.

In the trophoblast layer of the chorion laeve of human fetal membranes obtained by cesarean section at the month of normal parturition, cells with condensed nuclei could be observed by histochemical examination. Incubating fetal membranes at 37 degrees C in vitro in cultivation medium, the frequency of cells with condensed nuclei increased in the chorion laeve, associating with an increase in DNA fragmentation and the population of in situ TUNEL (terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-X nick end labeling) staining-positive cells. The progressed apoptotic cell death in the chorion laeve in vitro was suppressed by incubation of the tissue in the presence of glucocorticoids, cortisone or hydrocortisone, which was also demonstrated by DNA fragmentation analysis and in situ TUNEL staining. These results reveal that a substantial proportion of trophoblast cells in the chorion laeve of human fetal membranes are induced to undergo apoptosis at the end of pregnancy, and that the apoptosis progresses rapidly in vitro as the incubation period increases. It is suggested that certain hormones such as glucocorticoid, may be related to the regulation of the apoptosis in human fetal membranes.

Amnion↗