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Biomedical subjects

H Tamura

Publications and source records attributed to H Tamura.

At least 37 records · Page 2Linked to original sources

B7-H1 costimulation preferentially enhances CD28-independent T-helper cell function.

B7-H1 is a recently described B7-like molecule that costimulates T-cell growth and cytokine secretion without binding to CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and inducible costimulator (ICOS). In this report, a mouse homologue of human B7-H1 is identified, and its immunologic functions are studied in vitro and in vivo. Mouse B7-H1 shares 69% amino acid homology to the human counterpart. Similar to human B7-H1, mouse B7-H1 can be induced to express on macrophages, T cells, and B cells and to enhance T-cell proliferation and secretion of interleukin-10 (IL-10), interferon-gamma, and granulocyte-macrophage colony-stimulating factor but not IL-2 and IL-4. Furthermore, B7-H1 preferentially costimulates CD4+ T cells independently of CD28 and enhances mixed lymphocyte responses to allogeneic antigens. In contrast to B7-1, expression of B7-H1 on murine P815 tumor cells by transfection fails to increase allogeneic and syngeneic cytolytic T-cell responses in vitro and in vivo. Administration of B7-H1Ig fusion protein, however, enhances keyhole limpet hemocyanin- specific T-cell proliferation and 2,4,6-trinitrophenyl-specific immunoglobulin G2a antibody production. The study thus identifies a unique costimulatory pathway that preferentially affects T-helper cell functions.

Amino Acid Sequence↗

Measurement of the B(e2) of (7)(lambda)Li and shrinkage of the hypernuclear size.

We report on the first measurement of a hypernuclear gamma-transition probability. gamma rays emitted in the E2(5/2(+)-->1/2(+)) transition of (7)(Lambda)Li were detected by a large-acceptance germanium detector array (Hyperball), and the lifetime of the parent state ( 5/2(+)) was determined by the Doppler shift attenuation method. The obtained result, 5.8(+0.9)(-0.7)+/-0.7 ps, was then converted into the reduced transition probability [ B(E2)] to be B(E2;5/2(+)-->1/2(+)) = 3.6+/-0.5(+0.5)(-0.4) e(2) fm(4). Compared with the B(E2) of the corresponding E2(3(+)-->1(+)) transition in the 6Li nucleus, our result gives evidence that the size of the 6Li core in (7)(Lambda)Li is smaller than the 6Li nucleus in the free space.

Journal Article↗

Evaluation of the rodent micronucleus assay by a 28-day treatment protocol: Summary of the 13th Collaborative Study by the Collaborative Study Group for the Micronucleus Test (CSGMT)/Environmental Mutagen Society of Japan (JEMS)-Mammalian Mutagenicity Study Group (MMS).

To examine whether micronucleus tests can be incorporated into general toxicology assays, we performed micronucleus tests applying the treatment protocols typically used in such assays. In this 13th Collaborative Study of the CSGMT, both rats and mice were tested, although rats were used in the majority of the studies. Fifteen mutagens were tested in rats, mainly by oral (p.o.) administration. Micronucleus induction was evaluated 2, 3, and 4 days, and 1, 2, 3, and 28 days after the beginning of the treatment in the peripheral blood, and at 28 days in the bone marrow. Of the 15 chemicals that induced micronuclei in rats in short-term assays, two chemicals (1,2-dimethylhydrazine.2HCl and mitomycin C) were negative in all our experiments, possibly because of insufficient dose levels. The remaining 13 were positive within the estimated dose range of a general toxicology assay, suggesting the possibility of integrating the micronucleus assay into general toxicology assays. Three patterns were observed in micronucleus induction during the period of repeated treatment: (1) gradual increases in micronucleus frequency with sequential doses, (2) a peak at 3-5 days followed by gradual decreases in micronucleus frequency with sequential doses, and (3) a rapid increase in micronucleus frequency followed by a plateau. We evaluated factors that might have been involved in those patterns, such as the spleen function, target organ exposure, extramedullary hematopoiesis, hypothermia, and hypoxia. Another factor we considered was dosage. Because the dosages employed in a general toxicity assay are usually lower than those used in short-term micronucleus assays, this discrepancy was considered the greatest potential problem for integrating the micronucleus assay into general toxicology assays. Our results indicate that the integration of the micronucleus assay into a 28-day toxicological assay is feasible. To serve this purpose, blood samples collected 4 days after the beginning of treatment and blood and bone marrow samples collected at autopsy should be examined. Furthermore, although it is recognized that mice may be suitable for performing independent micronucleus assays, we propose that rats can provide biologically important and relevant information regarding potential chemical mutagens that can be evaluated under conditions used in the conduct of general toxicology studies.

Animals↗

Arterial fraction of cerebral blood volume in humans measured by positron emission tomography.

In quantitative functional neuroimaging with positron emission tomography (PET) and magnetic resonance imaging (MRI), cerebral blood volume (CBV) and its three components, arterial, capillary, and venous blood volumes are important factors. The arterial fraction for systemic circulation of the whole body has been reported to be 20-30%, but there is no report of this fraction in the brain. In the present study, we estimated the arterial fraction of CBV with PET in the living human brain. C(15)O and dynamic H2(15)O PET studies were performed in each of seven healthy subjects to determine the CBV and arterial blood volume (Va), respectively. A two-compartment model (influx: K1, efflux: k2) that takes Va into account was applied to describe the regional time-activity curve of dynamic H2(15)O PET. K1, k2 and Va were calculated by a non-linear least squares fitting procedure. The Va and CBV values were 0.011 +/- 0.004 ml/ml and 0.031 +/- 0.003 ml/ml (mean +/- SD), respectively, for cerebral cortices. The arterial fraction of CBV was 37%. Considering the limited first-pass extraction fraction of H2(15)O, the true arterial fraction of CBV is estimated to be about 30%. The estimated arterial fraction of CBV was quite similar to that of the systemic circulation, whereas it was greater than that (16%) widely used for the measurement of cerebral metabolic rate of oxygen (CMRO2) using PET. The venous plus capillary fraction of CBV was 63-70% which is a important factor for the measurement of CMRO2 with MRI.

Adult↗

O-carboxymethyl-chitin concentration in granulocytes during bone repair.

Peroral and intravenous administrations of (14)C-labeled carboxymethyl-chitin (CM-chitin) revealed that CM-chitin accumulated in bone marrow. Thus, a composite of CM-chitin with hydroxyapatite (HA) was prepared to examine the bone repairing properties by animal and cell line experiments. The new bone formation of CM-chitin.HA composite was superior to that of CM-chitin, HA, and blank. A porous CM-chitin.HA composite is a functional material which could act as a scaffolding of osteoblast-like cells, a barrier to ingrowth of fibrous connective tissues. The cytotoxicity of CM-chitin was evaluated using the MC3T3-E1 cell line, and we found that control of degree of deacetylation is a very important factor in using CM-chitin as bone repairing material.

Administration, Oral↗

Evidence for surfactant solubilization of plant epicuticular wax.

The solubilization of isolated, reconstituted tomato (Lycopersicon esculentum Mill.) fruit and broccoli (Brassica oleracaea var. botrytis L.) leaf epicuticular waxes (ECW) by nonionic octylphenoxypolyethoxy ethanol surfactant (Triton X-100) was demonstrated in a model system by TLC and fluorescence analysis using pyrene as a fluorescent probe. ECW was solubilized at or above the surfactant critical micelle concentration; solubilization increased with an increase in micelle concentration. As shown by the fluorescence quenching of pyrene, surfactant solubilization of the ECW increased rapidly for the first 12 h, then approached a plateau, increased linearly with an increase in temperature (22--32 degrees C), and decreased linearly with the log of the polyoxyethylene chain length (range 5--40 oxyethylenes). These data are discussed in relation to surfactant effects on phytotoxicity and performance of foliar spray application of agrochemicals.

Brassica↗

Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy.

Serum melatonin concentrations were studied in normal pregnant women and in women with several types of pathologic pregnancies, e.g., twins, preeclampsia or intrauterine growth retardation (IUGR). Blood samples were collected from the maternal antecubital vein at 14:00 hr (daytime) and 02:00 hr (nighttime) during pregnancy, and also from the umbilical vein and artery immediately after delivery. Serum melatonin concentrations were measured by radioimmunoassay. Daytime serum melatonin levels in normal (single fetus; singleton) pregnancies were low. While the levels showed an increasing tendency toward the end of pregnancy, no statistically significant changes occurred. On the other hand, the nighttime serum melatonin levels increased after 24 weeks of gestation, with significantly (P < 0.01) high levels after 32 weeks; these values decreased to non-pregnant levels on the 2nd day of puerperium. Nighttime serum melatonin levels were significantly (P < 0.05) higher in twin pregnancies after 28 weeks of gestation than in singleton pregnancies, whereas the patients with severe preeclampsia showed significantly (P < 0.05) lower serum melatonin levels than the mild preeclampsia or the normal pregnant women after 32 weeks of gestation. Melatonin concentrations in umbilical vessels showed a higher tendency in neonates who were born during at night compared with the other neonates; moreover, those in the umbilical artery were generally higher than those in the umbilical vein. The present results indicate that in humans, the maternal serum melatonin levels show a diurnal rhythm, which increases until the end of pregnancy, reflecting some pathologic states of the feto-placental unit. Fetuses may produce melatonin with a circadian rhythm.

Adult↗

Evaluation of pulse sequences used for magnetic resonance sialography.

OBJECTIVES: To determine the most appropriate sequences for the visualization of small parotid ducts in MR sialography. METHODS: MR images of a phantom consisting of distilled water in polyethylene tubes were obtained with turbo-spin echo (TSE), single-shot turbo-spin echo (SSTSE), half-fourier acquisition, single-shot turbo-spin echo (HASTE) and turbo gradient-spin echo (TGSE) pulse sequences and compared visually and quantitatively. MR sialograms obtained from healthy volunteers and patients with Sjögren's syndrome (SS) were obtained using the same four sequences. RESULTS: In the phantom, TSE images were best and the contrast-noise ratio (CNR) highest. In the volunteers, the main ducts were especially clearly visualized with TSE and in SSTSE; however, the majority of secondary and/or tertiary parotid ducts were not depicted by any of the sequences used. In SS patients, images of small main ducts and small pseudocysts were clearer using TSE. However, TSE could not depict the narrow main ducts or peripheral ducts or very small pseudocysts. CONCLUSIONS: TSE is considered the most suitable MR sequence for assessing small parotid gland ducts. However, further improvement is needed since it does not always visualize them sufficiently.

Adult↗

Thyroid hormones regulate pituitary growth hormone secretagogue receptor gene expression.

Thyroid hormones regulate growth hormone (GH) secretion by actions both at the hypothalamus and at the pituitary gland. At the level of the pituitary, thyroid hormones increase GH and GH-releasing hormone receptor (GHRH-R) mRNA expression. To test if thyroid hormones might also regulate the pituitary expression of mRNA for the recently identified GH secretagogue (GHS) receptor, GHS-R, primary pituitary cell cultures from adult male rats were treated with triiodothyronine (T3) and GHS-R mRNA levels were assessed by reverse transcriptase-polymerase chain reaction. T3 increased pituitary GHS-R mRNA levels in a dose- and time-dependent manner. The stimulatory action of T3 on GHS-R mRNA levels was also observed in the presence of the RNA synthesis inhibitor, actinomycin D, indicating that gene transcription is not required. Closer examination of the decay rates of GHS-R mRNA in the presence of actinomycin D revealed T3 extended the half-life of the GHS-R mRNA from 8 h (basal) to15 h, demonstrating that T3 increases GHS-R mRNA levels in vitro by increasing message stability.

Animals↗

Visual response properties of cells in the ventral and dorsal parts of the macaque inferotemporal cortex.

We recorded from cells in the anterio-ventral (TEav) and anterio- dorsal (TEad) parts of area TE of the inferotemporal cortex and examined their responses to a set of 100 visual stimuli in awake, fixating monkeys. In both TEav and TEad we found that, depending on the stimulus, the time course of responses varied considerably within individual cells and that there were three main factors in the variation. One factor is variance in the balance between the initial transient part of responses around 130 ms after stimulus onset and the later part after 240 ms from stimulus onset. The later parts of responses were more stimulus selective. The second factor is variance in the latency of response onset and peak and the third is variance in the speed of decay from the peak within the initial part of the responses. Stronger responses had shorter onset and peak latencies and longer decay times. The results suggest that stimulus images can be discriminated very rapidly in TEav and TEad by detecting differences in response onset. TEav cells differed from TEad cells in that they were more difficult to activate than TEad cells: the proportion of responsive TEav cells was smaller, the maximal responses of individual cells were smaller than in TEad and the number of stimuli that evoked significant responses in individual responsive cells was also smaller than in TEad. Moreover, TEav cells, overall, responded more strongly to more colorful object images than less colorful ones, while TEad cells did not show such a tendency. However, the minimum onset latency of individual cells and the sharpness of stimulus selectivity did not differ significantly between TEav and TEad. Responses of TEav cells are as selective as those of TEad cells, although there remains a possibility that the domain of selectivity differs between the two areas. These results support an earlier anatomical finding that TEav and TEad are located at the same hierarchical level of separate serial pathways rather than at successive stages of a single pathway.

Algorithms↗

Androgen receptor antagonism by the organophosphate insecticide fenitrothion.

Organophosphate insecticides represent one of the most widely used classes of pesticides with high potential for human exposure in both rural and residential environments. We investigated the interaction of the organophosphothioate pesticide fenitrothion (O,O-dimethyl O-(4-nitro-m-tolyl) phosphorothioate) with the human androgen receptor (AR). Fenitrothion blocked dihydrotestosterone-dependent AR activity in a concentration-dependent and competitive manner in HepG2 human hepatoma liver cells transiently transfected with human AR and an AR-dependent luciferase reporter gene. Schild regression analysis yielded an equilibrium dissociation constant value of 2.18 x 10(-8) M. To determine the antiandrogenic potential of fenitrothion in vivo, 7-week-old castrated Sprague-Dawley rats were dosed once a day for 7 days with testosterone propionate (50 microg/day, sc) plus gavage doses of either corn oil vehicle or fenitrothion (15 or 30 mg/kg/day). An additional group of rats was given testosterone propionate and flutamide (50 mg/kg/day). Motor activity and acetylcholinesterase activity in whole blood and brain were also assessed. Both fenitrothion and the reference antiandrogen flutamide caused significant decreases in the ventral prostate, seminal vesicle, and levator ani plus bulbocavernosus muscles tissue weights. In contrast, blood acetylcholinesterase activity, a standard biomarker of organophosphate poisoning, was only inhibited at the higher dose of fenitrothion (30 mg/kg). Our results demonstrate that fenitrothion is a competitive AR antagonist, comparable in potency to the pharmaceutical antiandrogen flutamide and more potent, based on in vitro assays, than the known environmental antiandrogens linuron and p,p'-, 2,2-bis(p-hydroxyphenyl)-1,1-dichloroethylene ( p,p'-DDE).

Acetylcholinesterase↗

The influence of the laryngeal mask airway on the shape of the submandibular gland.

UNLABELLED: Although transient sialadenopathy of the submandibular gland associated with insertion of the laryngeal mask airway (LMA) has been described, the influence of the LMA on the submandibular gland is unknown. We measured the width and length of the submandibular glands by using ultrasonography in patients in whom the LMA was used. An increased intracuff pressure of the LMA, up to 150 cm H2O, was used in a prospective study of adult patients scheduled for elective surgery. The width of the gland increased with an increasing intracuff pressure from 50 to 100 cm H2O (P < 0.01) and 100 to 150 cm H2O (P < 0.01) but did not change from 0 to 50 cm H2O. There was no change in the length of the gland. We conclude that the submandibular gland was deformed by the insertion of the LMA. IMPLICATIONS: The findings in our study show that the submandibular triangle can be easily compressed by the insertion of the laryngeal mask airway (LMA). When inserting the LMA, it is important to consider that the LMA cuff may alter these tissues, which are situated between the lingual root and the submandibular triangle.

Adult↗

Clonal analysis of esophageal squamous cell carcinoma with intraepithelial components.

OBJECTIVE: In tumors of the upper aerodigestive tract, field carcinogenesis is a prevailing concept which suggests that such tumors are commonly of multiclonal origin. METHODS: To test this possibility, we applied a PCR-based clonality assay utilizing the polymorphic locus of the human androgen receptor gene (HUMARA) in female patients with esophageal squamous cell carcinomas (SCCs). DNA was extracted from small pieces of tissues microdissected from multiple points of intraepithelial and invasive parts of each tumor and the adjacent epithelia in 12 cases. The HUMARA locus was PCR amplified with or without prior digestion with Hpa II. PCR products were analyzed by a genetic analyzer and polyacrylamide gel electrophoresis followed by silver staining. RESULTS: In each of 8 informative cases, the pattern of X chromosome inactivation of the major cell population in each sample was common among the samples from the invasive part and among those samples, if any, from the intraepithelial part, and was concordant between the intraepithelial and invasive parts in 5 cases and discordant in 1 case. Out of the samples of adjacent epithelia, a monoclonal pattern was demonstrated in 8 basal cell hyperplasias and 3 dysplasias, of which 2 and 1, respectively, showed inactivation patterns discordant with those of the concomitant cancers. CONCLUSION: Esophageal SCCs may often be preceded or accompanied by multiclonal precancerous lesions, and may develop through the outgrowth of single or less commonly multiple dominant clones.

Aged↗

Estrogen receptor (ER)alpha, but not ERbeta, gene is expressed in growth hormone-releasing hormone neurons of the male rat hypothalamus.

GH synthesis and release from pituitary somatotropes is controlled by the opposing actions of the hypothalamic neuropeptides, GH-releasing hormone (GHRH), and somatostatin (SS). There is a striking sex difference in the pattern of GH secretion in rats. Early reports indicate that gonadal steroids have important imprinting effects during the neonatal period. Recently, our laboratory and others have reported that the GH secretory pattern is altered by short-term gonadal steroid treatment in adult rat, suggesting that gonadal steroids are also important determinants of the pattern of GH secretion during adult life. However, the site of action of gonadal steroids in the adult rat hypothalamus is still unknown. In this study, we used in situ hybridization in the adult male rat brain to determine whether GHRH neurons and/or SS neurons coexpress estrogen receptor alpha (ERalpha) and ERss genes. In the medial basal hypothalamus of adult male rat, the ERalpha messenger RNA (mRNA) was located in medial preoptic area (MPA) and arcuate nucleus (ARC), whereas ERss mRNA was detected in MPA, supraoptic nucleus, and paraventricular nucleus. From studies using adjacent sections, the distribution of ERalpha mRNA-containing cells appeared to overlap in part with those of GHRH and SS expressing cells only in the ARC. On the other hand, the distribution of ERss mRNA-containing cells does not appear to overlap with GHRH cells or SS cells. The double label in situ hybridization studies showed that in the ARC, 70% of GHRH neurons contain ERalpha mRNA, whereas less than 5% of SS neurons expressed the ERalpha gene. These results indicated that GHRH neurons are direct target cells for estrogens, and estrogens may act directly on GHRH neurons through ERalpha during adult life to modify GH secretory patterns.

Animals↗

Regulation of the ghrelin gene: growth hormone-releasing hormone upregulates ghrelin mRNA in the pituitary.

Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHS-R), was originally purified from the rat stomach. Ghrelin specifically releases GH following intravenous administration, and its GH-releasing activity in vivo is dependent on growth hormone-releasing hormone (GHRH). We previously reported that the expression of the GHS-R gene in the pituitary is developmentally regulated and GHRH infusion increases pituitary levels of GHS-R mRNA. Ghrelin mRNA and peptide have recently been detected in rat and human pituitaries. However, the regulation of the ghrelin gene in the pituitary is unknown. In this study, pituitary levels of ghrelin mRNA were measured with the reverse transcriptase-polymerase chain reaction in male rats at embryonic day (e)18 and postnatal days 1, 10, 30, and 75. The highest concentrations of ghrelin mRNA in the pituitary were observed at e18 and then they declined with age. The infusion of GHRH (10 microg/h, 4h) in freely-moving adult male rats resulted in a 1.9-fold increase in ghrelin mRNA levels relative to control rats (P < 0.05). These data indicated that the expression of the ghrelin gene in the pituitary is developmentally regulated and the pituitary ghrelin/GHS-R signaling system could modulate the regulation of GH secretion by GHRH.

Aging↗

Epigallocatechin gallate (EGCG) inhibits the sulfation of 1-naphthol in a human colon carcinoma cell line, Caco-2.

We have previously reported that epigallocatechin gallate (EGCG) strongly inhibits the in vitro phenol sulfotransferase (P-ST) activity of a human colon carcinoma cell line, Caco-2. In the present study, we examined the ability of EGCG to inhibit the sulfation of 1-naphthol in intact Caco-2 cells. Sulfation of 1-naphthol was detected in Caco-2 cells after 2 h of incubation, and was observed to continue for 24 h, resulting in an accumulation of sulfated 1-naphthol. Sulfation was strongly inhibited by the addition of EGCG to the culture medium. The IC50 of EGCG was calculated to be 20 microM; this value is similar to that obtained from in vitro assays (14 microM) [Ref. Tamura et al., Biol. Pharm. Bull., 23, 695, (2000)]. These results indicate that catechins are capable of inhibiting P-ST activity in intact cells as well as in vitro. We believe that the inhibitory activity of catechins might be the mechanism by which catechins (and green tea) exert anti-carcinogenic activity against procarcinogenic compounds that require P-ST activation in vivo.

Antineoplastic Agents↗

Isolation of antidiabetic components from white-skinned sweet potato (Ipomoea batatas L.).

We have already reported that white-skinned sweet potato (Ipomoea batatas L.) (WSSP) shows antidiabetic activity in streptozotocin (STZ) induced diabetic rats and genetically diabetic models (yellow KK, db/db mice and Zucker fatty rats). In this study, isolation and purification of the antidiabetic component of WSSP were attempted. Almost all antidiabetic activity was found in the cortex of WSSP. The fractionation of the antidiabetic component in the WSSP cortex was done by the following methods: dialysis of the water extract, 85% ethanol precipitation, 15% trichloroacetic acid (TCA) treatment, butyl-, phenyl-hydrophobic column chromatography, and ultrafiltration treatment. The antidiabetic component was not eliminated during dialysis and was soluble in 85% ethanol and 15% TCA, but it passed through a filter that allows the passage of substances of a molescular weight of 30,000. The uniformity of this isolated active component was analyzed using HPLC. A single peak was seen with three different columns (C8 reverse-phase column, anion exchange QA column, and gel filtration column (GFC)), indicating that the component is a uniform substance. The molecular weight of this antidiabetic component was estimated to be 22,000 by GFC analysis. This active component was presumed to be an acidic glycoprotein because it contained protein and sugar and was adsorbed onto the QA column at pH 7.0.

Animals↗

Glomerulonephritis after methicillin-resistant Staphylococcus aureus infection resulting in end-stage renal failure.

A 58-year-old man developed proteinuria and renal dysfunction following pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin was administered, and prednisolone pulse therapy and plasmapheresis were performed. Subsequently, serum creatinine was decreased. Eight months later, creatinine and CRP were again elevated, and MRSA was detected. Vancomycin was again administered and plasmapheresis was performed. However, renal function was not improved and continuous hemodialysis was initiated. This case indicates that complete eradication of MRSA is necessary to treat MRSA-associated glomerulonephritis, and if this is not attained, a permanent loss of renal function occurs.

Anti-Bacterial Agents↗