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Biomedical subjects

T Hirakawa

Publications and source records attributed to T Hirakawa.

At least 19 recordsLinked to original sources
PubMed1998

Angiogenesis in adenocarcinoma of the uterine cervix.

BACKGROUND: Angiogenesis is essential for tumor growth, progression, and metastases. Microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance in many tumor types for predicting metastasis and survival. METHODS: Between 1979-1989, 56 cases of FIGO Clinical Stage I and II adenocarcinoma of the uterine cervix treated by hysterectomy were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. MVD and several other prognostic parameters were examined for correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: In early adenocarcinoma of the uterine cervix, MVD was increased significantly in invasive areas compared with adjacent nonneoplastic areas (median: 62.5 [range, 30-105] vs. median: 36.5 [range, 23-47]; P=0.0003). MVD also was significantly correlated with ascites cytology (P=0.0377). There was no correlation between microvessel count and lymph node status, depth of invasion, disease stage, lymph-vascular space invasion, grade, or parametrial involvement. Patients with high MVD (> or=75) had significantly worse PFS and OS than those with low MVD (< 75) (log rank test, P=0.0180 and 0.0199, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In adenocarcinoma of the cervix, MVD is an independent prognostic factor for PFS and OS.

Adenocarcinoma↗
PubMed1998

Glutamatergic synaptic inputs to mouse supraoptic neurons in calcium-free medium in vitro.

The effects of Ca2+-free perfusion medium on excitatory postsynaptic currents (EPSCs) and potentials (EPSPs) were studied by whole-cell recordings from neurons of the supraoptic nucleus (SON) in trimmed slice preparations of mouse hypothalamus. EPSCs evoked with either focal stimulation to the SON or perfusion of slices with high K+-medium, spontaneous EPSCs (sEPSCs) and miniature EPSCs (mEPSCs) recorded from neurons of the SON were blocked by the glutamate receptor antagonist kynurenic acid (1 mM). While EPSCs evoked by focal stimulation were abolished in the presence of Ca2+-free perfusion medium; sEPSCs and mEPSCs remained. Neither the frequency nor the amplitude of the sEPSCs and mEPSCs significantly changed during the application of Ca2+-free perfusion medium. Perfusion of slices with high K+-medium increased the mEPSC frequency compared with that recorded in normal Ca2+-containing perfusion medium. In contrast, mEPSC frequency did not change during perfusion with Ca2+-free high K+-medium. In current-clamp mode sEPSPs were observed during the perfusion with Ca2+-free medium. Some sEPSPs recorded in Ca2+-free medium were sufficiently large to evoke action potentials. These results imply that spontaneous glutamatergic synaptic inputs to the hypothalamic neurosecretory cells exist in Ca2+-free perfusion medium. Thus, the present study suggests that Ca2+-free medium does not always block the synaptic transmission in hypothalamic slice preparations.

Action Potentials↗
PubMed1998

Expression and effect of adrenomedullin on rat granulosa cell.

Adrenomedullin (AM) is a potent hypotensive peptide recently discovered in extracts of human pheochromocytoma. To elucidate the regulation of AM production in the ovary, the effect of gonadotropin on the production of AM was studied in the cultured rat granulosa cells. A Northern blot analysis of the LH receptor and adrenomedullin yielded a major hybridizing band at 5.4 kb and 1.6 kb, respectively. In our culture system of rat granulosa cells, without any stimulus, the LH receptor mRNA was undetectable and the AM mRNA level was stably expressed for 6 days. FSH significantly induced LH receptor mRNA and suppressed AM mRNA for 4 days of culture and with the addition of hCG after 2 days of pretreatment with FSH, AM mRNA levels were markedly suppressed. FSH and 8-Br-cAMP significantly increase LH receptor mRNA and suppress AM mRNA in a dose-dependent manner. These data indicated that the differentiation of granulosa cells mediated by gonadotropins were associated by suppression in AM expression through a cAMP-dependent mechanism. On the other hand, AM stimulated a rapid rise in intracellular cAMP levels, which peaked within 15 min of addition, in a dose-dependent manner with a maximal response seen at 100 nM. Additionally, AM enhanced the effects of FSH, acting additionally to produce cAMP in the cells. AM may play a role in the process of granulosa cell differentiation as a local regulator through an autocrine/paracrine mechanism.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1998

Implications of heat shock/stress proteins for medicine and disease.

Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced.

Animals↗
PubMed1997

Adult T cell leukemia (ATL)-derived factor/human thioredoxin prevents apoptosis of lymphoid cells induced by L-cystine and glutathione depletion: possible involvement of thiol-mediated redox regulation in apoptosis caused by pro-oxidant state.

Thiol compounds, such as L-cysteine and glutathione (GSH), play crucial roles in the regulation of lymphocyte proliferation. In this study, we analyzed the effect of L-cystine and GSH depletion on lymphocyte survival and investigated the regulatory roles of adult T cell leukemia (ATL)-derived factor (ADF)/human thioredoxin (hTRX) in relation to these low m.w. thiols. MT-1, MT-2, and Jurkat cells underwent apoptosis when cultured in the L-cystine- and GSH-free medium within 18 to 24 h. Dichlorofluorescin oxidation assay indicated that the apoptosis in MT-1 and MT-2 cells was preceded by an increase in the level of intracellular hydrogen peroxide (H2O2). The addition of catalase and recombinant ADF/hTRX (rADF) partially blocked the apoptosis in a dose-dependent manner. rADF has been also shown to enhance the internalization of L-cystine into MT-2 cells in a dose-dependent manner, whereas oxidized rADF or mutated rADF that has no insulin-reducing activity failed to do so. Furthermore, culture in the L-cystine- and GSH-free medium lowered the cellular GSH content of PHA blasts, which was restored dose-dependently by rADF. These data suggest that the inability to neutralize oxidative stress results in the apoptosis of lymphoid cells under L-cystine- and GSH-depleted conditions. The protective effects of rADF may be explained by direct scavenging action on H2O2 (catalase-like activity) or by indirect neutralizing effects on the pro-oxidant status through enhancing the L-cystine internalization and elevating the intracellular GSH content.

Apoptosis↗
PubMed1997

Relationship between pelvic lymph node involvement and other disease sites in patients with ovarian cancer.

In 109 patients with epithelial ovarian cancer, 25 (23%) had pelvic lymph node (PLN) metastasis. Positive rates of PLN metastasis according to the clinical stage based on disease distribution except retroperitoneal lymph node were 2% for stage I, 6% for stage II, 44% for stage III, and 64% for stage IV. The nine disease sites, such as subdiaphragmatic surface, liver and spleen capsule, intestine and mesentery, omentum, pelvic peritoneum, sigmoid colon and rectum, uterus and tubes, peritoneal cytology, and paraaortic lymph node (PAN), were found to have a statistically significant relationship with PLN metastasis by univariate analysis. Multivariate analysis using a logistic regression model selected the omentum and PAN as independent factors with a statistical significance. The incidence of PLN metastasis in epithelial ovarian cancer with the above two parameters can be assumed to be greater than that without the two parameters by 42.6 times. The present data suggested that for the disease with PAN and/or omental metastasis, removal of the PLN may be mandatory from the standpoint of cytoreduction.

Adolescent↗
PubMed1997

Inhibition of cerebral metabolic and circulatory responses to nitrous oxide by 6-hydroxydopamine in dogs.

PURPOSE: To determine whether cerebral metabolic and circulatory consequences of N2O result from activation of the sympathoadrenal system. The effects of pretreatment with intracisternal injection of 6-OHDA, which produces chemical sympathectomy, were studied in dogs. METHOD: Seven days before measurement dogs were pretreated with intracisternal injection of either saline vehicle (sham-group) or 100 micrograms.kg-1 6-hydroxydopamine (6-OHDA, group). Cerebral blood flow (CBF) was measured using an electromagnetic flow-meter probe and cerebral metabolic rate for oxygen (CMRO2) was calculated as the product of CBF and arterial-sagittal sinus blood oxygen content difference [C(a-v)O2]. RESULTS: In the sham group, N2O (60%) increased CMRO2 from 6.11 +/- 0.21 ml.100 g-1.min-1 to 7.10 +/- 0.39 ml.100 g-1.min-1 and CBF from 63 +/- 5 ml.100 g-1.min-1 to 173 +/- 26 ml.100 g-1.min-1. In the 6-OHDA group, CMRO2, did not change during N2O exposure, whereas CBF increased from 61 +/- 3 ml.100 g-1.min-1 to 135 +/- 19 ml.100 g-1.min-1 but less then in the sham group. The 6-OHDA group displayed a reduction in cortical noradrenaline (NA) concentration from 263.2 +/- 35.6 ng.g-1 to 102.7 +/- 16.5 ng.g-1. Cortical dopamine (DA) concentration was not affected by 6-OHDA administration. CONCLUSION: These results suggest that most of the increase in CMRO2 and at least a part of the increase in CBF during N2O exposure in the sham-group are related to sympathoadrenal-stimulating effects of N2O.

Adrenergic Agents↗
PubMed1997

The effects of idazoxan combined with 30% nitrous oxide on the jaw-opening reflex in the rat.

In rats, the jaw-opening reflex is elicited by activation of a nociceptive receptor by the electric stimulation of the tooth pulp. This study was undertaken to assess the effects of 30% nitrous oxide and 30% nitrous oxide with idazoxan, an alpha 2-adrenergic antagonist, on this reflex. Each rat received electric stimulation for the jaw-opening reflex at 3, 5, 7, 10, 15, and 20 min after both the start of inhalation and the withdrawal of 100% oxygen or 30% nitrous oxide in oxygen. Idazoxan, 400 micrograms/ kg, was administered intravenously at the start of the inhalation period. Amplitudes significantly decreased during inhalation of nitrous oxide, but they returned gradually to control levels after cessation of nitrous oxide inhalation. In the cases of 100% oxygen, 100% oxygen with idazoxan, and 30% nitrous oxide in oxygen with idazoxan, amplitudes did not change from controls during and after 30% nitrous oxide inhalation. The latency remained unchanged irrespective of the treatment. Since in rats the degree of inhibition by 30% nitrous oxide in oxygen is partially diminished by administration of idazoxan, we conclude that nitrous oxide affects an alpha 2-adrenergic receptor in the central nervous system.

Administration, Inhalation↗
PubMed1996

Glutathione depletion impairs transcriptional activation of heat shock genes in primary cultures of guinea pig gastric mucosal cells.

When primary cultures of guinea pig gastric mucosal cells were exposed to heat (43 degree C), ethanol, hydrogen peroxide (H2O2), or diamide, heat shock proteins (HSP90, HSP70, HSP60, and HSC73) were rapidly synthesized. The extent of each HSP induction varied with the type of stress. Ethanol, H2O2, and diamide increased the syntheses of several other undefined proteins besides the HSPs. However, none of these proteins were induced by exposure to heat or the reagents, when intracellular glutathione was depleted to <10% of the control level by pretreatment with DL-buthionine-[S,R]-sulfoximine. Gel mobility shift assay using a synthetic oligonucleotide coding HSP70 heat shock element showed that glutathione depletion inhibited the heat- and the reagent-initiated activation of the heat shock factor 1 (HSF1) and did not promote the expression of HSP70 mRNA. Immunoblot analysis with antiserum against HSF1 demonstrated that the steady-state level of HSF1 was not changed in glutathione-depleted cells, but glutathione depletion inhibited the nuclear translocation of HSF1 after exposure to heat stress. These results suggest that intracellular glutathione may support early and important biochemical events in the acquisition by gastric mucosal cells of an adaptive response to irritants.

Animals↗
PubMed1996

Endometrial carcinoma associated with hyperplasia.

The aim of this study was to clarify the relationship of endometrial hyperplasia to endometrial carcinoma. From 1979 through 1990, 115 cases of stage I-IV endometrial carcinomas treated initially by hysterectomy were reviewed histologically. Forty-two of 115 (36.3%) patients had hyperplasia in the endometrium adjacent to the carcinoma. Women with both endometrial carcinoma and hyperplasia were significantly younger than those with carcinoma without hyperplasia (P < 0.05). In a comparison of patients with carcinoma without hyperplasia, those with hyperplasia were better differentiated (P = 0.0072), and lacked deep myometrial invasion (P < 0.0001), cervical involvement (P = 0.0192), lymph-vascular space invasion (P = 0.0102), and para-aortic lymph node metastases (P = 0.0434). The presence of endometrial metaplasia (P = 0.0001). The estimated 5-year survival rates for patients with carcinoma with hyperplasia and those with carcinoma without hyperplasia were 96.55 and 73.33%, respectively (P = 0.0016). In endometrial carcinomas, the presence of endometrial hyperplasia may demonstrate a more favorable prognosis.

Adult↗
PubMed1996

Regulation of pyridoxal-5'-phosphate level by biogenic amines in mouse brain.

We investigated the relationship between the concentration of pyridoxal-5'-phosphate (PLP) and biogenic amine in mouse brain. The production of PLP from pyridoxal (PL) by pyridoxal kinase (PLK) was inhibited by the addition of dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT), but not by that of epinephrine and N-acetyl-serotonin. DA and NE were combined with PLP by a non-enzymatic reaction, whereas 5-HT was bound only slightly with PLP. The conjugated product of PLP with DA was also detected by HPLC analysis when PLK activity was assayed using PL as a substrate in the presence of DA. In an in vivo investigation, the depletion of DA and 5-HT in mouse brain after an intraperitoneal injection of 5 mg/kg reserpine, led to slight elevation of the PLP level to 120% of the control level. By contrast, the increase in DA in the brain caused by intraperitoneal administration of 150 mg/kg L-DOPA caused the PLP concentration to decrease to 70% of the control level. However, no change in PLK activity in the brain was observed when the mice were treated with either reserpine or L-DOPA. These results suggested that the level of PLP in mouse brain was partly regulated by the concentration of biogenic amines, such as DA, NE and 5-HT, without apparent induction of PLK.

Animals↗
PubMed1996

Geranylgeranylacetone induces heat shock proteins in cultured guinea pig gastric mucosal cells and rat gastric mucosa.

BACKGROUND & AIMS: An antiulcer drug, geranylgeranylacetone (GGA), rapidly induces resistance of gastric mucosal cells to irritants in vivo and in vitro. The aim of this study was to elucidate the mechanism of this action. METHODS: Heat shock proteins (HSPs) were detected by immunoblotting with antibody against HSP90, HSP70, heat shock cognate protein 70, or HSP60. HSP70 messenger RNA level was measured by Northern hybridization with an HSP70 complementary DNA probe. Activation of the heat shock factor was detected by gel mobility shift assay with the heat shock element oligonucleotide. RESULTS: GGA induced resistance of cultured guinea pig gastric mucosal cells against ethanol-induced exfoliation and damage within 30 minutes, proportionally to the induction of the HSPs. This protection was blocked by cycloheximide but not by indomethacin. GGA caused rapid activation of heat shock factor 1 and expression of HSP70 messenger RNA in the cells. Intragastric administration of GGA to rats induced HSPs in gastric mucosa. The administration of GGA additionally enhanced the heat shock response and reduced ulcer formation in rats subjected to restraint and water-immersion stress. CONCLUSIONS: GGA may induce transcriptional activation of HSP genes, and this novel action may increase gastric mucosal defense at conditions of stress.

Animals↗
PubMed1996

A new cleft palate repair.

Cleft palate can be repaired by a palatal mucoperiosteal flap, but we have devised a new technique for cleft palate repair using a wide mucoperiosteal flap with an alveolar ridge mucosa and a cleft margin flap. This technique leaves the mucosa of the nasal cavity and vomer intact. The results include (1) good velopharyngeal competence and normal articulation, (2) few cases of fistula formation, and (3) minimal maxillary retardation.

Age Factors↗
PubMed1995

The human interleukin-10 receptor gene maps to chromosome 11q23.3.

The human interleukin-10 receptor (IL-10R) gene has previously been mapped to chromosome 11. Here, we have determined the precise location of the human IL-10R gene by the fluorescence in situ hybridization method, and have found that the IL-10R gene maps to chromosome 11q23.3.

Chromosome Mapping↗
PubMed1995

Assessment of working skeletal muscle oxygenation in patients with chronic heart failure.

Patients with chronic heart failure (CHF) are frequently limited by muscle fatigue resulting from impaired skeletal muscle blood flow. Accordingly, we assessed working skeletal muscle oxygenation in such patients using near-infrared (NIR) spectroscopy. Nine normal subjects (mean age 52 years) and 12 patients with CHF (mean age 60 years) were studied. NIR spectroscopy was used to monitor relative changes in oxygenated hemoglobin (Hb) and myoglobin (Mb) (oxy Hb/Mb), deoxygenated Hb and Mb (deoxy Hb/Mb), and total (oxy + deoxy) Hb and Mb (total Hb/Mb) contents in the vastus lateralis muscle at rest, during warm-up (0 W, 30 cycles/min for 3 min), incremental maximal supine bicycle exercise (ramp protocol, 15 W/min, 50 cycles/min), and recovery. At peak exercise the patients exhibited reduced heart rate, systolic blood pressure, peak exercise oxygen consumption (VO2; 15 +/- 3.0 ml/kg/min vs 32 +/- 8.5 ml/kg/min), and workload (99 +/- 23.4 W vs 183 +/- 68.4 W) as compared with the normal subjects. The respiratory quotient was comparable in both groups. In the normal subjects, oxy Hb/Mb was increased from the warm-up period to the early phase of exercise, followed by a progressive decrease to peak exercise. In the recovery phase, oxy Hb/Mb was increased abruptly. For these patients, change in oxy Hb/Mb followed a pattern similar to that seen in normal subjects, and oxy Hb/Mb was decreased earlier in contrast to that in the normal subjects. There was a significant difference in the change of oxy Hb/Mb during warm-up, early phase exercise, and recovery between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise Test↗