Biomedical subjects

T Uemura

Publications and source records attributed to T Uemura.

At least 19 recordsLinked to original sources

PubMed2000

Pharmacokinetics and biodisposition of fluorescein-labeled arabinogalactan in rats.

Fluorescein-labeled arabinogalactan (FA) was prepared by the reaction with FITC in methyl sulphoxide according to the method of deBelder and Granath. A systemic kinetic analysis of FA in rats was carried out by using a specific high-performance size-exclusion chromatography. Intravenously administered FA was rapidly eliminated from the blood circulation followed by an appreciable distribution to the liver and kidney. FA was accumulated in these organs over a long period whereas negligible levels of FA were detected in the other organs. A marked dose-dependency was seen in the hepatic uptake of FA which was markedly reduced by coinjected asialofetuin whereas the renal uptake of FA was not altered. Measurement of the hepatocellular localization demonstrated the overwhelming distribution of FA in the parenchymal liver cell fraction. Furthermore, the microscopic examination revealed FA that was effectively endocytosed by the parenchymal liver cells. These results suggested that FA which is bound to the asialoglycoprotein receptor with a high affinity is subsequently internalized to the hepatocyte via receptor-mediated endocytosis. FA was partially activated by periodate oxidation in order to acquire aldehyde groups to which guest molecules can be bound. A 12.5% oxidized arabinogalactan keeping a hepatocellular targetability showed a good conjugating reactivity to guest molecules via Schiff-base formation or by reductive amination. It was suggested that arabinogalactan can serve as a potential carrier for the delivery of enzymes and drugs to the parenchymal liver cells via the asialoglycoprotein receptor.

Animals↗

PubMed2000

Effects of naloxone on the serum luteinizing hormone level and the number of Fos-positive gonadotropin-releasing hormone neurons in immature female rats.

To examine developmental changes in the number of gonadotropin-releasing hormone (GnRH) neurons activated by an opioid receptor antagonist in female rats, blood sampling and double-labeled immunocytochemistry for Fos and GnRH were performed after the injection of naloxone (NAL) in immature (postnatal d16 and d30) and mature female rats. Three age groups of rats were perfused with 4% paraformaldehyde-PB 90 min after the subcutaneous injection of NAL (2.5 mg/kg) or saline. All tissue incubation and staining for double-labeled immunocytochemistry were simultaneously performed. Although no significant developmental change was observed in the total number of GnRH neurons (p0.05), NAL-induced increases in serum luteinizing hormone (LH) concentrations were much greater in the d16 group than those in the d30 and mature groups (p<0.01). Conversely, Fos-positive GnRH neurons were rarely observed in d16, and some Fos-positive GnRH neurons were observed in the d30 group (p<0.05 vs. saline) and the mature group (p<0.01 vs. saline). These results suggest that opiatergic inhibitory system on GnRH neuron in immature female rats is different from that in mature female rats.

Age Factors↗

PubMed2000

Transplantation of highly differentiated immortalized human hepatocytes to treat acute liver failure.

BACKGROUND: Temporary support of a damaged liver by a bioartificial liver (BAL) devise is a promising approach for the treatment of acute liver failure. Although human primary hepatocytes are an ideal source of hepatic function in BAL, shortage of human livers available for hepatocyte isolation is the limiting factor for the use of this modality. A clonal human hepatocyte cell line that can grow economically in culture and exhibit liver-specific functions should be an attractive solution to this problem. METHODS: To test this alternative, primary human fetal hepatocytes were immortalized using Simian virus 40 large T antigen. To investigate the potential of the immortalized cells for BAL, we transplanted the cells into the spleen of adult rats and performed a 90% hepatectomy 12 hr later. RESULTS: One of the cloned human liver cell lines, OUMS-29, showed highly differentiated liver functions. Intrasplenic transplanting of 20x10(6) OUMS-29 cells protected the animals from hyperammonemia and the associated hepatic encephalopathy. Survival was significantly prolonged in 90% of hepatectomized rats receiving OUMS-29 cells. CONCLUSIONS: A highly differentiated immortalized human hepatocyte cell line, OUMS-29, was able to provide metabolic support during acute liver failure induced by 90% hepatectomy in rats. Essentially unlimited availability of OUMS-29 cells may be clinically useful for BAL treatment.

Ammonia↗

PubMed2000

Medicinal foodstuffs. XVIII. Phytoestrogens from the aerial part of Petroselinum crispum MIll. (Parsley) and structures of 6"-acetylapiin and a new monoterpene glycoside, petroside.

In the course of our screening for natural estrogenic compounds from Occidental medicinal herbs, the extracts of several herbs were found to show proliferative activity in MCF-7 (an estrogen-sensitive breast cancer cell line). Among these active herbs, the methanolic extract from the aerial parts of Petroselinum crispum (parsley) showed potent estrogenic activity, which was equal to that of isoflavone glycosides from soybean. Through bioassay-guided separation, we isolated several flavone glycosides and a new flavone glycoside, 6"-acetylapiin, with estrogenic activity together with a new monoterpene glucoside, petroside. The structures of 6"-acetylapiin and petroside were characterized by the chemical and physicochemical evidence. Estrogenic activities of these flavone glycosides were found to be enhanced by removal of their glycoside moieties. The EC50 values (concentration needed to enhance the MCF-7 proliferation 50% compared to non-estrogen treated cell) of their aglycones are as follows, apigenin (1.0 microM), diosmetin (2.9 microM), and kaempferol (0.56 microM). The estrogenic activities of these flavones are nearly equal to those of the isoflavones, daidzein (0.61 microM) and genistein (0.60 microM). The methanolic extract of parsley, apiin, and apigenin restored the uterus weight in ovariectomized mice when orally administered for consecutive 7 days.

Animals↗

PubMed2000

Atypical aortic coarctation with resistant hypertension treated with axilloiliac artery bypass.

A 68-year-old woman was found to have atypical coarctation of the aorta, accompanied by systolic hypertension of the upper extremities despite administration of five types of antihypertensive drugs. Since the systolic hypertension was resistant to the conventional antihypertensive therapy, axilloiliac artery bypass grafting with a subcutaneous tunnel was performed to alleviate the pressure gradient. Systolic blood pressure was successfully reduced and hypertension was controlled after surgery.

Aged↗

PubMed2000

Different expression of positive and negative regulators of hepatocyte growth in growing and shrinking hepatic lobes after portal vein branch ligation in rats.

Portal vein branch embolization is often performed before hepatectomy to prevent postoperative liver failure. It is, however, still not clear how the embolized lobe shrinks and the non-embolized lobe proliferates in counterbalance. We investigated the expression of positive and negative regulators of hepatocyte growth to clarify the mechanisms of liver growth and atrophy in a rat portal vein ligation (PVL) model compared with partial hepatectomy (PH). A significant increase in DNA synthesis within the non-ligated lobe reached a peak at 36 h, a delay of 12 h as compared with PH, while no increase occurred in the ligated lobe. Expression of hepatocyte growth factor mRNA remarkably increased in the non-ligated growing lobe between 6 and 24 h, but was only slightly elevated in the ligated shrinking lobe. Contrarily, negative regulators of hepatocyte proliferation, such as TGF-beta1 and IL-1beta, were strongly expressed in the ligated shrinking lobe. Thus, the changes of portal venous flow and/or pressure caused by PVL may contribute to induction of different kinds of growth factors between the ischemic and non-ischemic lobes; these factors possibly regulate liver regeneration and atrophy after PVL.

Animals↗

PubMed2000

Preservation of fish cutlet (Pangasius pangasius) at ambient temperature by irradiation.

Development of gamma irradiation preservation of ready-to-eat, commercially prepared fish cutlet and improvement of microbiological quality were studied. Studies on the shelf life extension by a combination of irradiation and ascorbic acid treatments of fish cutlets prepared at the laboratory and commercial scale have also been conducted. Cutlets prepared at the laboratory scale according to selected formulation and irradiated at a dose of 5 kGy could extend the shelf life up to 5 weeks at room temperature. In commercially prepared fish cutlets, maximum shelf life extension observed was 14 days for samples treated with 5 kGy of irradiation and stored at ambient temperature on the basis of combined microbiological, chemical, and organoleptic evaluation. The microbiological quality of the commercially prepared fish cutlets revealed the unhygienic conditions of the place where the fish was prepared and the unhygienic storage conditions and temperatures. As a result, the chemical and irradiation treatments were not effective in extending the shelf life of the cutlets under the storage condition used in this study compared with that of the laboratory scale-prepared cutlets.

Animals↗

PubMed1999

Flamingo controls the planar polarity of sensory bristles and asymmetric division of sensory organ precursors in Drosophila.

The sensory bristles of the fruit fly Drosophila are organized in a polarized fashion such that bristles on the thorax point posteriorly. These bristles are derived from asymmetric division of sensory organ precursors (SOPs). The Numb protein, which is localized asymmetrically in a cortical crescent in each SOP, segregates into only one of the two daughter cells during cell division, thereby conferring distinct fates to the daughter cells [1] [2]. In neuroblasts, establishment of apical-basal polarity by the protein Inscuteable is crucial for orienting asymmetric division, but this is not the case for division of SOPs [3]. Instead, the Frizzled (Fz) protein mediates a planar polarity signal that controls the anteroposteriorly oriented first division (pl) of SOPs [4]. Here, we report that Flamingo (Fmi), a seven-transmembrane cadherin [5], controls the planar polarity of sensory bristles and the orientation of the SOP pl division. Both the loss of function and overexpression of fmi disrupted bristle polarity. During mitosis of the SOP, the axis of the pl division and the positioning of the Numb crescent were randomized in the absence of Fmi activity. Overexpression of Fmi and Fz caused similar effects. The dependence of proper Fmi localization on Fz activity suggests that Fmi functions downstream of Fz in controlling planar polarity. We also present evidence suggesting that Fz also functions in the Wingless pathway to pattern sensory organs.

Animals↗

PubMed1999

Preventive effect of sesquiterpenes from bay leaf on blood ethanol elevation in ethanol-loaded rat: structure requirement and suppression of gastric emptying.

The methanolic extract from the leaves of Laurus nobilis (bay leaf, laurel) potently inhibited the elevation of blood ethanol level in ethanol-loaded rat. Through bioassay-guided separation, costunolide, dehydrocostus lactone, and santamarine were isolated as the active constituents and the alpha-methylene-gamma-butyrolactone structure was found to be essential for the preventive effect on ethanol absorption. In addition, the retardation of gastric emptying seemed to be partially involved in the preventive effects.

Animals↗

PubMed1999

Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity under the control of Frizzled.

We identified a seven-pass transmembrane receptor of the cadherin superfamily, designated Flamingo (Fmi), localized at cell-cell boundaries in the Drosophila wing. In the absence of Fmi, planar polarity was distorted. Before morphological polarization of wing cells along the proximal-distal (P-D) axis, Fmi was redistributed predominantly to proximal and distal cell edges. This biased localization of Fmi appears to be driven by an imbalance of the activity of Frizzled (Fz) across the proximal/distal cell boundary. These results, together with phenotypes caused by ectopic expression of fz and fmi, suggest that cells acquire the P-D polarity by way of the Fz-dependent boundary localization of Fmi.

Amino Acid Sequence↗

PubMed1999

Effects of glucose and related substrates on the recovery of the electrical activity of gonadotropin-releasing hormone pulse generator which is decreased by insulin-induced hypoglycemia in the estrogen-primed ovariectomized rat.

We investigated the effect of glucose and its related substrates on the recovery of pulsatile luteinizing hormone (LH) secretion which was suppressed by insulin in estrogen-primed ovariectomized rats. We also examined the effect of glucose on the electrical activity of the gonadotropin-releasing hormone (GnRH) pulse generator which was suppressed by insulin. The intravenous (i.v.) injection of insulin (5 units/rat) suppressed the pulsatile LH secretion for 3 h in estrogen-primed ovariectomized rats. This suppressive effect of insulin on the LH secretion was rapidly reversed by the i.v. injection of glucose and mannose but not by the injection of lactate and saline. Fructose could recover the LH secretion suppressed by insulin, but took a longer time than glucose did. By monitoring the electrical activity of the GnRH pulse generator, we found that i.v. injection of insulin suppressed the pulsatile LH secretion by decreasing the activity of the GnRH pulse generator. Again, the i.v. injection of glucose, but not saline, immediately recovered the decrease in the electrical activity of the GnRH pulse generator. Fructose could recover the activity of the GnRH pulse generator, but it took a longer time than glucose did. We suggest that glucose availability, but not simply a metabolic state such as the ATP level, is an essential factor for maintaining the electrical activity of the GnRH pulse generator which is responsible for pulsatile LH secretion.

Animals↗

PubMed1999

Purification of L-kynurenine 3-monooxygenase from mitochondrial outer membrane of pig liver.

The aim of the present work is to obtain the homogeneous L-kynurenine 3-monooxygenase (Fpk) enzyme preparation by a simple and rapid immunoaffinity purification method. Fpk was purified by monoclonal antibody (mAb) immunoabsorbent column. The column was prepared using hydrazide-activated agarose beads (Affi-Gel Hz) to which IgG molecules were coupled via carbohydrate moieties located on the Fc region and peroxidized with periodate. Partially purified Fpk was charged on the column and after washing the column with buffer containing 0.5 M NaCl and 0.5% Triton-X-100 and then with buffer alone, the enzyme was eluted with acidic elution buffer. Despite the loss of the catalytic activity due to the acidic elution, the immunoaffinity preparation may be useful for the analysis of the chemical structure of Fpk and for the production of the polyclonal antibody toward Fpk.

Animals↗

PubMed1999

Experimental evaluation of the effects of the intraportal administration of cyclic guanosine monophosphate on ischemia/reperfusion in the porcine liver.

This study was done to examine the protective effects of cyclic guanosine monophosphate (cGMP), a second messenger of nitric oxide, for ischemia/reperfusion injury of the liver, since it is known to induce vasodilatation and to inhibit platelet aggregation. Using an experimental model of porcine liver ischemia, 8-bromoguanosine 3',5' monophosphate, a cGMP analog, was continuously administered into the portal vein before ischemia and after reperfusion 30 min for each in the cGMP group (n = 6). Saline water was administered in the same way in the control group (n = 6). The cardiac output (CO), mean arterial blood pressure (MAP), portal venous flow (PVF), hepatic arterial flow (HAF), hepatic tissue blood flow (HTBF), and hepatic tissue cGMP level were determined. Hepatic enzymes and the bile discharge were also assessed as indicators of hepatic function. The hepatic tissue cGMP level was significantly higher, and PVF, HTBF, and the bile discharge were significantly greater in the cGMP group, while there were no remarkable differences between the groups with CO, MAP, HAF, and hepatic enzymes. In conclusion, the continuous supplementation of cGMP into the portal vein was found to be beneficial for preserving both the hepatic circulation and, consequently, the hepatic function after warm ischemia of porcine liver.

Analysis of Variance↗

PubMed1999

Early and late postmenopausal bone loss is associated with BsmI vitamin D receptor gene polymorphism in Japanese women.

To determine whether vitamin D receptor (VDR) gene polymorphisms are associated with bone mineral density (BMD) and bone loss in the Japanese population, VDR BsmI RFLPs were analyzed in 191 postmenopausal Japanese women by comparing B allele and b allele DNA sequences, and a point mutation was confirmed. We examined VDR BsmI restriction fragment length polymorphism (RFLP) with an amplification refractory mutation system (ARMS) using this point of mutation. The frequency of VDR BsmI alleles in the Japanese population was significantly different from that in whites. The bb genotype was identified in 79.6%, of the subjects, the Bb genotype in 19.3%, and the BB genotype was in only 1.1%. We find no significant differences in lumbar spine baseline BMD between the bb genotype and the Bb genotype. In both early and late postmenopausal periods, serial measurements of vertebral BMD revealed that subjects with the Bb genotype lost BMD faster than those with the bb genotype (P = 0.001). We conclude that there is a significant relationship between RFLPs of BsmI VDR and the annual rates of bone loss during early and late postmenopausal periods in the Japanese population.

Aged↗

PubMed1999

Classification of polycystic ovary syndrome into three types according to response to human corticotropin-releasing hormone.

OBJECTIVE: To evaluate disturbances of the hypothalamic-pituitary-adrenal axis in women with polycystic ovary syndrome (PCOS). DESIGN: Retrospective cohort study. SETTING: Yokohama City University, Yokohama, Japan. PATIENT(S): Sixty women with PCOS and 19 women with normal menstruation. INTERVENTION(S): Administration of human corticotropin-releasing hormone (hCRH), dexamethasone suppression testing, and stimulation of ovulation with clomiphene citrate. MAIN OUTCOME MEASURE(S): Plasma cortisol and ACTH levels, plasma androstenedione and DHEAS levels, and ovulation rates. RESULT(S): In women with PCOS, plasma ACTH and cortisol levels were significantly higher and the plasma ACTH level after the administration of hCRH was higher than in controls. Based on the response to hCRH, patients with PCOS could be classified into three categories: those with a normal response to hCRH (group 1), those with an exaggerated response of ACTH to hCRH (group 2), and those with a high basal level of cortisol and a poor response to hCRH (group 3). In groups 2 and 3, DHEAS levels were significantly higher, suppression of androstenedione by dexamethasone was significantly greater, and ovulation rates with clomiphene citrate were significantly lower than in group 1. CONCLUSION(S): This classification provides insight into the underlying cause of PCOS and thus is useful in selecting appropriate treatment.

17-alpha-Hydroxyprogesterone↗

PubMed1999

Rates of endometriosis recurrence and pregnancy 1 year after treatment with intranasal buserelin acetate (Suprecur) (a prospective study).

OBJECTIVES: This multicenter prospective study of buserelin acetate (Suprecur) therapy for endometriosis was performed in order to examine pregnancy rates and the recurrence of endometriosis 1 year after the end of intranasal administration. METHODS: This study was conducted at 349 institutions, including university hospitals and major hospitals in Japan, and 1,284 patients were recruited as participants. Recurrence of symptoms was followed for 1 year after the end of administration of buserelin acetate in patients whose condition as a whole was evaluated as "improved" or better at the end of administration. Furthermore, the pregnancy rate was similarly followed in patients who complained of sterility at the commencement of the administration. Recurrence was defined as either a case in which all of the main symptoms observed before administration returned to the pretreatment state, or a case in which at least one symptom deteriorated compared to the pretreatment state. Kaplan-Meier's method was used for statistical analysis. RESULTS: Among 459 patients who could be evaluated for recurrence of symptoms, the cumulative recurrence rate was 17.8% 1 year after the end of administration. Among 156 patients who could be evaluated for pregnancy, the pregnancy rate was 23.3% 1 year after the end of administration. CONCLUSION: Intranasal buserelin acetate therapy exhibited not only transient clinical effects during administration or immediately after the end of administration, but also exhibited specific continuing effects after the end of administration.

Administration, Intranasal↗

PubMed1999

Low-dose GnRH agonist therapy for the management of endometriosis.

OBJECTIVE: In order to examine whether treatment with a GnRH agonist alone can maintain estrogen levels within the "estrogen window" that inhibits endometriosis without influencing bone-mineral density, we studied the effects of GnRH agonist therapy and changes in bone-mineral density. METHODS: Buserelin acetate nasal spray was administered 3 times a day for 8 weeks (daily dose, 900 micrograms) to 21 women with endometriosis. The drug was then given twice a day for 16 weeks (daily dose, 600 micrograms). The total duration of treatment was 24 weeks. The bone-mineral density of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry before treatment (baseline), at the end of treatment, and 24 weeks after the end of treatment. RESULTS: The bone-mineral density of the lumbar vertebrae at the end of treatment was 2.44% +/- 0.46% (mean +/- standard error) lower than the baseline value. The value at 24 weeks after the end of treatment was 1.10% +/- 0.64% lower than the baseline value. More than 80% of the patients had serum-estradiol levels of 45 pg/ml or less. During treatment, more than 90% of the patients had serum-estradiol levels of 60 pg/ml or less. Genital bleeding was inhibited in 90% of the patients. After 8 weeks of treatment, the clinical symptoms improved in 75% of the patients; such improvement persisted for the duration of the treatment. CONCLUSION: Decreasing the dose of GnRH agonist during treatment can minimize the loss of bone-mineral density without lessening the beneficial effects on endometriosis. This technique might be useful in the management of endometriosis.

Abdominal Pain↗

PubMed1999

Chemical constituents from the leaves of Hydrangea macrophylla var. thunbergii (III): Absolute stereostructures of hydramacrosides A and B, secoiridoid glucoside complexes with inhibitory activity on histamine release.

Following the characterization of dihydroisocoumarin constituents, two secoiridoid glucoside complexes, called hydramacrosides A and B, were isolated from the leaves of Hydrangea macrophylla Seringe var. thunbergii Makino. The absolute stereostructures of hydramacrosides A and B were elucidated on the basis of chemical and physicochemical evidence, which included the application of the 13C-NMR glycosylation shift rule of 1,1'-disaccharides and the modified Mosher's method. Hydramacrosides A and B exhibited an inhibitory effect on histamine release from rat mast cells induced by an antigen-antibody reaction.

Acetylation↗