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Biomedical subjects

T Ishiguro

Publications and source records attributed to T Ishiguro.

At least 145 records · Page 8Linked to original sources

Reciprocal changes of plasma glucose and ketone bodies in fasted and acutely diabetic rats after CNS stimulation.

To assess the effect of chemical stimulation of the central nervous system (CNS) on ketogenesis, we injected neostigmine (5 x 10(-8)mol) into the third cerebral ventricle in normal rats fasted for 48 h and fed rats with diabetes induced by streptozotocin (STZ, 80 mg/kg). The hepatic venous plasma levels of ketone bodies (3-hydroxybutyrate and acetoacetate), free fatty acids (FFA), and glucose were measured for 120 min after the injection of neostigmine under pentobarbital anesthesia. In the normal rats, plasma glucose levels were significantly increased but neither ketone bodies nor FFA were affected by CNS stimulation with neostigmine. In contrast the plasma levels of ketone bodies and FFA were significantly increased in STZ-diabetic rats, while glucose levels remained unchanged. The intravenous infusion of somatostatin (1.0 microgram/kg/min) suppressed the increase in plasma ketone bodies following CNS stimulation in STZ-diabetic rats. These findings suggest that CNS stimulation with neostigmine may accelerate ketogenesis by promoting the lipolysis, which may be induced by glucagon, in fed diabetic rats but not in normal fasted rats.

Animals↗

Hyperglycemia induced by hippocampal administration of neostigmine is suppressed by intrahypothalamic atropine.

We investigated the relationship between the hyperglycemia induced by the administration of neostigmine into the hippocampus and the hypothalamus. Prior to the injection of neostigmine (5 x 10(-8) mol) into the hippocampus, 1 microliter each of atropine or hexamethonium (5 x 10(-11)-5 x 10(-8) mol) was injected into the bilateral ventromedial hypothalamus (VMH). Atropine suppressed in a dose-dependent manner the hyperglycemia induced by hippocampal administration of neostigmine, whereas hexamethonium had no significant effect. These observations suggest that the pathway for this experimental hyperglycemia involves, at least in part, the muscarinic cholinergic neurons in the VMH.

Animals↗

Dissociation of hyperthermic and hyperglycemic effects of central prostaglandin F2 alpha.

We previously reported that intraventricular prostaglandins (PGs) produced hyperthermia and hyperglycemia in anesthetized rats. However, the relationship of them is little known. We examined the relationship between hyperthermia and hyperglycemia induced by intraventricular PGF2 alpha using curarized and adrenal demedullated rats. Iv curare completely prevented the PGF2 alpha-induced hyperthermia, but enhanced the hyperglycemic effect of PGF2 alpha. Adrenal demedullation completely prevented the hyperglycemia, but did not affect the hyperthermic effect of PGF2 alpha. To further assess the site of action concerned with PGF2 alpha-induced thermoregulation and glucoregulation in the central nervous system (CNS), we injected saline or PGF2 alpha into the preoptic area of the anterior hypothalamus (POA) in intact rats. After microinjection of PGF2 alpha into the POA, the rectal temperature rose, but the plasma glucose level did not increase significantly, as compared with saline-treated control rats. These results suggest that PGF2 alpha causes the central nervous system to produce hyperthermia via shivering, stimulated the somatic motor system, and to produce hyperglycemia by stimulating central sympathetic outflow to the adrenal medulla, but these operate independently under different neural regulation, and these sensitive sites are organically dissociated in the CNS.

Adrenal Medulla↗

Absolute structure-cytotoxic activity relationships of steganacin congeners and analogues.

The cytotoxic activities of optically pure and racemic steganacin congeners and analogues against KB cells in culture and the inhibitor activity of cilia regeneration in Tetrahymena were studied with regard to absolute and relative configurations. The stereochemical requirements of dibenzocyclooctadiene lignan lactones for activity were clarified.

4-Butyrolactone↗

Flow cytometric DNA analysis with use of normal lymph node cells as an internal reference standard in ovarian cancer.

Fresh frozen and paraffin-embedded tumor specimens of 21 patients with ovarian cancer were investigated by means of flow cytometry. In 4 patients, the fresh frozen tumor specimens (fresh tumor specimens) of ovarian tumors were measured for the DNA ploidy and index. We used the paraffin-embedded normal lymph node tissue specimens which were acquired from retroperitoneal lymphadenectomy as the internal reference standard (IS). In all 21 patients, the paraffin-embedded tumor specimens mixed with a lymph node specimen as an IS (tumor specimen with IS) were measured. In addition, all 21 paraffin-embedded tumor specimens without a lymph node tissue specimen (tumor specimens without IS) were measured. In 4 cases which were measured with the fresh tumor specimens, all 4 tumor specimens with IS had the same patterns of DNA ploidy as the fresh tumor specimens. Of 21 patients, 6 patients showed different DNA ploidy patterns between the tumor specimens with and without IS. Furthermore, all of these 6 patients showed diploidy in the tumor specimens without IS while showing aneuploidy in the tumor specimens with IS. Fourteen (66.7%) of 21 tumor specimens with IS were aneuploidy despite aneuploidy of only 8 (38.1%) tumor specimens without IS. All 4 patients with stage I had diploidy in the tumor specimens with IS, and 13 (81.3%) of 16 patients with stage III or IV had aneuploidy. All 8 patients with diploidy in the tumor specimens with IS had survived for 1-2 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Aneuploidy↗

Analysis of cell cycle kinetics using flow cytometry from paraffin-embedded tissues in endometrial adenocarcinoma.

Flow cytometric analysis of cell cycle kinetics from paraffin-embedded tissues was performed to evaluate the DNA heterogeneity and risk factor of endometrial adenocarcinoma. We studied 54 tumor samples and 6 controls with normal endometrium, and all samples were measured for S-phase fraction (SPF) and proliferative index (PI). Intratumor variations of SPF and PI values were evaluated at 3 different sites of the tumor; (1) primary endometrial lesion, (2) the site of myometrial invasion, and (3) metastatic lesions. SPF and PI values of endometrial adenocarcinoma were significantly higher than those of normal endometrium. There was a significant correlation between the PI value and the histological grade. SPF and PI values at the primary endometrial lesion had a significant correlation with the prognosis of this cancer at stage III or IV. SPF and PI values which were measured at the site of myometrial invasion tended to be lower than those from other sites. Our results indicate that the SPF and PI values of endometrial lesions are one of the important prognostic factors of endometrial adenocarcinoma at stage III or IV. In addition, DNA syntheses of endometrial adenocarcinoma cells display intratumor heterogeneity.

Adenocarcinoma↗

Relative contribution of nervous system and hormones to hyperglycemia induced by thyrotropin-releasing hormone in fed rats.

In a continuation of our studies on the mechanism of central nervous system induced hyperglycemia in the rat, we evaluated the relative contribution of a direct neural effect on the liver and of certain hormones to the hyperglycemia induced by administration of thyrotropin-releasing hormone (TRH). The findings were compared with those of a previous investigation using neostigmine or 2-deoxy-D-glucose. In the present study TRH was injected into the third cerebral ventricle of rats, and the concentrations of hepatic venous plasma glucose, immunoreactive glucagon, immunoreactive insulin, epinephrine, and norepinephrine, were measured. Four groups of animals were evaluated: (1) intact rats; (2) rats receiving an infusion of somatostatin with insulin via the femoral vein to inhibit glucagon secretion and to maintain the basal insulin level; (3) rats bilaterally adrenalectomized (ADX) to prevent epinephrine secretion, and (4) ADX rats administered an infusion of somatostatin and insulin. Evaluation of the areas under the glucose curves for the rats receiving somatostatin with insulin, ADX rats, and ADX rats receiving somatostatin with insulin showed values 202, 50, and 79% of those observed in intact animals. These observations suggest that TRH-induced hyperglycemia results from at least two effects: a direct neural effect on the liver including a suppressive effect of epinephrine on insulin secretion (contributing about 79% to the total hyperglycemic effect) and a direct effect of epinephrine on the liver (contributing about 21% to the total hyperglycemic effect).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

[Detection of human papillomavirus types 16, 18 and 33 in exfoliated cervical cells by polymerase chain reaction].

Human papillomavirus (HPV) types 16, 18 and 33 were identified by means of the polymerase chain reaction using exfoliated cells from the uterine cervix in 361 patients. Of 261 patients without cervical lesions, 10(3.8%) patients had HPV DNA whereas 7(70.0%) of 10 patients with invasive cervical carcinomas had HPV DNA. The younger patients' group (29 year-old or less) without cervical lesions had a 6.5% HPV positive rate which was distinctly higher than the older patients' groups. No menopausal patient without cervical lesions had HPV DNA. In the cervical dysplasia group, the HPV DNA positive rate tended to be higher in the older patients. Type 16 was detected more often than types 18 or 33. However, the detectable incidence of type 16 in the follow up group was lower than in the cervical carcinoma groups. The younger patients without cervical lesions had a higher incidence of type 16 than the older patients. The younger patients with cervical neoplastic lesions had a lower incidence of type 16 than the older patients. These results suggest that type 16 has a higher frequency of cervical HPV infections than types 18 and 33. In addition, human papillomavirus is not the only causative factor in cervical carcinomas.

Adult↗

[Microheterogeneity of alpha-fetoprotein in the amniotic fluid--developmental changes in the molecular structure of carbohydrate chain].

By means of lectin affinity crossed-line immunoelectrophoresis, microheterogeneity of alpha-fetoprotein (AFP) was studied in 41 amniotic fluid samples between 41 to 287 days of gestation. Microheterogeneity was assessed by the structural differences in the carbohydrate chain identified by the specific binding between oligosaccharide molecule(s) and certain lectins such as concanavalin A, Lens culinaris hemagglutinin, phytohemagglutinin E or Ricinus communis agglutinin I. It was found that four carbohydrate chains were identifiable at an early stage of gestation; (1) mannose (Man).core type, (2) bisecting N-acetylglucosamine (GlcNAc) type, (3) fucose (Fuc) type, and fucosyl-bisecting GlcNAc type. A carbohydrate chain with both bisecting GlcNAc and Fuc was found only at an early stage of of gestation. A carbohydrate chain with either bisecting GlcNAc or Fuc also decreased with fetal growth, and AFP at the end stage of gestation was composed mainly of Man.core type carbohydrate chain. The addition or removal of the oligosaccharide molecule takes place at the Goldi complex subjected to various modifications by the glycosylation enzyme, and the present findings indicate that a certain enzyme (s) for the processing of oligosaccharide differs according to the developmental change in AFP-producing sites or the maturation of AFP-producing cells, and such is responsible for the different AFP carbohydrate chains in the amniotic fluid at different gestational stages.

Amniotic Fluid↗

[Molecular heterogeneity of alpha-fetoprotein in ovarian or extragonadal yolk sac tumor].

The molecular heterogeneity of alpha-fetoprotein (AFP) in yolk sac tumor (YST) was investigated. The study included 14 sera from YST, 78 sera from primary hepatocellular carcinoma (PHC), 5 fetal yolk sac (YS) culture fluids and 4 fetal liver culture fluids. The microheterogeneity of AFP was assessed by differences in reaction with AFP carbohydrate chain and lectins, and concanavalin A (Con A), Lens culinaris hemagglutinin (LCH) and phytohemagglutinin E (PHA-E) affinity crossed-line immunoelectrophoresis was used to fractionate AFP. It was found that AFP in YST or YS had similar subfraction patterns and differed clearly from AFP in PHC or fetal liver. Characteristic features of AFP subfraction in YST or YS were the presence of a LCH weakly-reactive subfraction and a high proportion of both Con A non-reactive and PHA-E strongly-reactive subfractions. The LCH weakly-reactive subfraction was specifically found in YST or YS, but was not found at all in PHC or in fetal liver. This variant is known to exist in amniotic fluid at an early stage of gestation, and is assumed to have a carbohydrate chain with both fucose and bisecting N-acetyl-glucosamine. The present findings therefore suggest that glycosylation of AFP in YST takes place by retro-genetic differentiation toward fetal yolk sac, but not toward fetal liver, and these studies confirm the suggested yolk sac origin of ovarian, as well as extragonadal, yolk sac tumor.

Carbohydrate Sequence↗

Isolation of a urinary digitalis-like factor indistinguishable from digoxin.

A digitalis-like factor has been purified to apparent homogeneity from human urine based on the inhibitory effect on [3H] ouabain binding to intact human erythrocytes. The purification scheme involved large scale adsorption followed by preparative, semipreparative and analytical high-performance liquid chromatography. The purified material showed a prominent digoxin-like immunoreactivity. The behaviour of the isolated substance was identical to that of authentic digoxin in three high-performance liquid chromatography and three thin-layer chromatography systems. Moreover, fast atom bombardment mass spectrum and proton nuclear magnetic resonance spectrum suggested that the purified material may be indistinguishable from digoxin.

Blood Proteins↗

Neuroleptic malignant syndrome: a study of CSF monoamine metabolism.

In 8 cases of typical neuroleptic malignant syndrome (NMS), homovanillic acid (HVA), 5-hydroxyindole acetic acid (5-HIAA), noradrenaline (NA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) levels in the cerebrospinal fluid (CSF) were assayed during both the active phase of NMS and after recovery. Compared with levels in normal control subjects the levels of HVA were significantly lower in patients with active NMS. This finding supports the central dopamine blockade theory of NMS pathophysiology. In addition, the levels of HVA were significantly decreased after recovery, suggesting that there may be a decreased dopamine metabolism in patients susceptible to NMS. The levels of 5-HIAA in patients with active NMS and after recovery were also significantly lower than those in normal control group, suggesting a relationship between the development of NMS and a disturbance of serotonin metabolism. The levels of NA in patients with active NMS were significantly higher than in normal subjects, and were within normal range after recovery. The levels of MHPG had a tendency to increase in patients with active NMS, compared with levels during recovery. These findings are a result of increased sympathetic nervous system activity in patients with active NMS; however, they are also observed in other disorders and may well reflect the physical stress caused by NMS.

Adult↗

[Antianaphylactic components of Asarum forbsii Maxin].

From the ethyl acetate extract of Asarum forbesii Maxin, four new constituents, asarumin A(I), B(II), C(III) and D(IV), were isolated along with elemicin (V), trans-asarone(VI) and linoleic acid(VII). The structures of the new compounds were elucidated as methyl 3 S-benzoyloxy-2 S-hydroxy-2-isopropylbutyrate for I, methyl 2 R-benzoyloxyisopentanoate for II, methyl 2 R-trans-cinnamoyloxyisopentanoate for III and methyl 2 R-piperonyloyloxyisopentanoate for IV. Compounds I, II, III and VII showed weak inhibition of PCA in rats, but the other compounds were inactive.

Animals↗

[Clinico-pathologic evaluation of retroperitoneal lymph node metastasis in ovarian carcinoma].

Retroperitoneal lymph node dissection was performed in 18 cases of ovarian carcinoma. Of 18 patients, 8 (44.4%) patients had lymph node metastasis. It was found that 50.0% of patients with stage III and 100% of patients with stage IV had lymph node metastasis. Serous cystadenocarcinoma and poorly differentiated carcinoma were demonstrated to be the risk factors in lymph node metastasis. Lymph node metastasis was found to be significantly correlated with the volume of ascites, peritoneal cytology, or peritoneal dissemination. Patients without peritoneal dissemination or positive peritoneal cytology had no lymph node metastasis. Patients with bilateral ovarian tumors tended to have a higher incidence of lymph node metastasis than those with a unilateral ovarian tumor. The incidence of para-aortic lymph node metastasis was found to be higher than that of pelvic or inguinal lymph node metastasis. We concluded that in the clinical stage, serous cystadenocarcinoma, poorly differentiated epithelial carcinoma, ascites, peritoneal cytology, peritoneal dissemination and bilateral ovarian tumors were assumed to affect the incidence of retroperitoneal lymph node metastasis of ovarian carcinoma. It was suspected that the lymphatic spread of ovarian carcinoma had two routes: via ascites and peritoneal dissemination.

Ascitic Fluid↗

Existence of a polar digitalis-like factor in mammalian hypothalamus.

We were able to partially purify a polar digitalis-like factor from rat and bovine hypothalami based on the capacity to inhibit [3H]ouabain binding to intact human erythrocytes. This factor was characterized in reference to the digitalis-like factor that we have isolated and reported on. Hypothalamic factor shared digitalis-like activities and physicochemical properties with the one derived from human urine and mammalian plasma. These findings strongly suggest that a polar digitalis-like factor identical to the circulatory factor does exist in mammalian hypothalamus.

Animals↗

The ratio of fucosylation of alpha-fetoprotein in hepatoblastoma.

Hepatoblastoma differs from the adult type of hepatoma in clinical and pathologic features. The ratio of fucosylation of serum alpha-fetoprotein (AFP) was determined in seven patients with hepatoblastoma and in 21 infants and children with otherwise elevated serum AFP, using the improved technique of lentil agglutinin-affinity immunoelectrophoresis. The clinical data for the seven patients with hepatoblastoma were also reviewed. The ratio of fucosylation of AFP was significantly higher in all seven patients with hepatoblastoma, whereas it was minimal in all other cases of benign hepatic conditions such as neonatal hepatitis or biliary atresia, as well as in normal newborns. The ratio of fucosylation in hepatoblastoma, however, definitely decreased with the age of the patient at presentation. This finding suggests a correlation between fucosylation and a rapid rate of tumor growth, because all hepatoblastomas are believed to originate early in fetal life.

Carcinoma, Hepatocellular↗

[Response of human lymphocytes to phytohemagglutinin (PHA) as measured by fluorescence polarization technique--differences between malignant conditions and benign or healthy conditions].

Percoll gradient (density: 1.081 g/cm3) centrifugation of peripheral venous blood yielded two layers of mononuclear cells. Preliminary study using lower lymphocyte layer revealed that there were significant differences in lymphocyte fluorescence polarization changes after PHA stimulation between malignant conditions and benign or healthy conditions, while such differences were not apparent by use of upper lymphocyte layer. According to these preliminary results, we studied fluorescence polarization changes after PHA stimulation in lower lymphocyte layer obtained from 242 individuals, including 49 apparently healthy women, 93 patients with benign gynecological tumor, 17 patients with severe dysplasia of the uterine cervix and 83 patients with malignant gynecological tumor. Stimulation index (R) was defined as the ratio between the degree of polarization before PHA stimulation (P CONTROL) and the degree of polarization after PHA stimulation (PPHA): R = PPHA/PCONTROL. R values of less than unity (R less than 1) indicate stimulation with PHA, and R values of greater than unity (R greater than or equal to 1), non-stimulation with PHA, respectively. R values of less than unity (R less than 1) was found in 118 of 142 (83.1%) healthy women or patients with benign tumor, 5 of 17 (29.4%) patients with cervical dysplasia, and 13 of 83 (15.7%) patients with malignant tumor, respectively. Preoperative R values of greater than unity decreased to R values of less than unity in 17 of 20 (85.0%) patients who received complete resection of the malignant lesion, while decline of R values was noted only in 8 of 22 (36.4%) patients who received incomplete resection of the lesion and/or chemotherapy or radiation. Present findings indicate that fluorescence polarization changes after PHA stimulation in lymphocytes isolated by Percoll gradient facilitate feasible detection of various malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytoplasm↗