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Biomedical subjects

N Takayanagi

Publications and source records attributed to N Takayanagi.

At least 73 records · Page 4Linked to original sources
PubMed1988

Simultaneous detection of epidermal growth factor receptor (EGF-R), epidermal growth factor (EGF) and ras p21 in cholangiocarcinoma by an immunocytochemical method.

Expression of the epidermal growth factor (EGF), EGF receptor (EGF-R) and ras oncogene product p21 was simultaneously examined in 37 cases with intrahepatic cholangiocarcinoma (CC) by means of an immunocytochemical method. While normal livers were all negative for any of the antigens at the concentration of the antibodies used, EGF-R was positive in 12 (32.4%) CCs, EGF in 22 (59.5%), and ras p21 in 33 (89.2%). The positive incidence of the three antigens was not different among the histologic subtypes of the tumor. However, the number of EGF-R- and ras p21-positive tumor cells decreased with progressing histologic tumor grade, but the expression of EGF was not associated with the tumor grade. Expression of the three antigens was not related to the degree of metastatic spread of the tumor. Simultaneous expression of the three antigens was seen only in 4 CCs, and that of EGF-R and EGF in 4, EGF-R and ras p21 in 12, and EGF and ras p21 in 20. These data suggest that the expression of EGF, EGF-R and ras p21 on CC cells is not related to the tumor aggressiveness, and the activation of each respective gene is independent. Furthermore, the data also indicate that an autocrine model for tumor growth, as suggested by a combination of EGF and EGF-R, may be applicable only to very limited cases of CCs.

Adenoma, Bile Duct↗
PubMed1988

Remarkable changes in the plasma levels of pituitary protein "7B2" during childhood.

We measured plasma immunoreactive (IR)-7B2 concentrations in 96 children (57 males and 39 females) from the newborn period to 20 yr of age. Plasma IR-7B2 concentrations in infants less than 2 yr of age (range 175-580 pg/ml, n = 19) were much higher than those in adults (range 20-138 pg/ml). Plasma levels of IR-7B2 decreased with age during childhood to reach the adult level at 15-20 yr. Significant negative correlations were found between plasma levels of IR-7B2 and dehydroepiandrosterone sulfate (r = -0.4154, p less than 0.05, n = 27), luteinizing hormone (r = -0.4948, p less than 0.05, n = 20) and follicle-stimulating hormone (r = -0.4682, p less than 0.05, n = 20). The possibility of a relationship between the reduction of plasma IR-7B2 levels and pubertal development warrants attention.

Adolescent↗
PubMed1987

Brain nicotine cholinoceptor binding in spontaneous hypertension.

To study the role of central cholinergic mechanisms in hypertension, we have determined nicotinic and muscarinic agonist binding sites in the brain regions of stroke-prone spontaneously hypertensive rats (SHRSP), using [3H]nicotine and [3H]cismethyldioxolane (CD). There was a significant decrease in specific [3H]nicotine binding in the cerebral cortex, thalamus, midbrain, cerebellum and medulla oblongata of SHRSP at 16-24 weeks of age compared to that of age-matched Wistar Kyoto rats (WKY). Scatchard analysis revealed 35% decrease in the Bmax value for [3H]nicotine binding in the SHRSP medulla oblongata without a change in the Kd value, suggesting a change in the receptor density. Similar reduction of nicotinic cholinoceptor binding sites was also observed in the discrete brain regions of young (5-week-old) SHRSP. In contrast, there was no alteration in specific [3H]CD binding in the SHRSP brains regions, except the hypothalamus which showed a significant increase. The SHRSP medulla oblongata showed no change in the ChAT activity. Thus, the present study suggests an important role for medullary nicotinic cholinoceptors in the pathogenesis of spontaneous hypertension.

Animals↗
PubMed1987

Immunohistochemical localization of ras p21 and carcinoembryonic antigens (CEA) in cholangiocarcinoma.

An expression of ras p21 proteins on cholangiocarcinoma (CC) (intrahepatic bile duct carcinoma) cells was examined by an immunoperoxidase method using an appropriate dilution of mouse monoclonal antibody RAP-5, with which no positive staining was obtained in livers with normal histology. Of 44 CCs examined 39 were positive for the antigens; well-differentiated adenocarcinoma usually showed a diffuse weak, cytoplasmic staining in nearly all tumor cells with the same staining intensity, while in moderately and poorly differentiated adenocarcinoma the expression of p21 varied markedly in intensity from cell to cell in the same cell nest. The number of positive cells decreased with the grade of tumor, and no or little staining was observed in undifferentiated areas. These findings indicate that the expression of ras p21 antigens was lost with increasing dedifferentiation of tumor cells. Carcinoembryonic antigens (CEA) were positive in 42 of 44 CCS. Well-differentiated adenocarcinoma expressed CEA along the apical surfaces of the tumor glands. With the dedifferentiation of tumor cells, the expression of CEA became prominent not only at the apical surfaces but also on the basolateral surfaces and in the cytoplasms, and further in the surrounding stromal tissue. There was no clear-cut correlation between the expression of p21 antigens and the production of CEA in CCs.

Adenoma, Bile Duct↗
PubMed1987

Immunoenzymatic studies of ornithine transcarbamylase (OTC) in liver of patients with OTC deficiency by enzyme linked immunosorbent assay (ELISA).

Antigen contents of ornithine transcarbamylase (OTC) protein in the liver of 5 patients with OTC deficiency and mutant mice were studied by ELISA. OTC activities in the liver tissues of 2 patients were 13.1% and 5.2% of the controls, respectively. The 2 patients' antigen contents of OTC protein were decreased in parallel with the enzyme activities. OTC antigen contents were not detected in the liver tissues of remaining 3 patients who had the complete type of OTC deficiency. Enzyme activities, kinetic properties and antigen contents of the OTC deficient mutant mice were the same as the results reported previously (Briand et al. 1982). The ELISA method for the assay of OTC antigen contents used in this study is more sensitive as compared with the radial immunodiffusion technique.

Animals↗
PubMed1987

Comparison of antinicotinic activity by neosurugatoxin and the structurally related compounds.

Neosurugatoxin (NSTX) which contains two sugars (myoinositol and xylopyranose) and bromine in the chemical structure, has been shown previously to be a selective antagonist of nicotinic receptors in guinea pig ileum and in murine brain. To study the role of sugar moiety and bromine in the antinicotinic activity by NSTX, we have examined the action of NSTX (compound I) and the structurally related compounds (compound II, III and IV) on the nicotine-induced contraction of guinea pig isolated ileum and on specific [3H]nicotine binding in rat forebrain membranes. Among four compounds examined, compound I was the most potent in inhibiting the nicotine-induced contraction of guinea pig isolated ileum (pA2 = 9.1 +/- 0.1, pD2' = 8.0 +/- 0.1) and also in inhibiting specific [3H]nicotine binding in rat forebrain (IC50 = 83 +/- 9 9 nM). Compared to compound I, compound II and III which are devoid of one and two sugars, respectively, in the chemical structure of compound I were 2 or 3 times less potent in the antinicotinic activity in both tissues, and compound IV which lacks bromine in addition to two sugars was two orders of magnitude less potent. Thus, the present study demonstrates that bromine rather than sugar moiety in the chemical structure of compound I (NSTX) is an important determinate of its high affinity for nicotinic receptors.

Animals↗
PubMed1987

Immunohistochemical detection of ras oncogene p21 product in liver cirrhosis and hepatocellular carcinoma.

Expression of the ras oncogene p21 product by hepatocytes of cirrhotic liver with hepatocellular carcinoma (HCC) was examined immunohistochemically using mouse monoclonal antibody RAP-5. At the concentration of antibody used, histologically normal liver tissues were negative for p21 antigen, whereas hepatocytes of cirrhotic nodules from 80 of 92 HCC patients (87.4%), and 10 of 32 patients without HCC (59.4%) were positive. This difference was statistically significant (p less than 0.05). The incidence of p21 expression by hepatocytes was significantly higher in macronodular cirrhotic patients than in those with micronodular cirrhosis (p less than 0.05) and tended to be higher in those positive for hepatic hepatitis B virus markers than in those that were negative (p less than 0.1). All 16 patients with liver cell dysplasia, and 17 of 18 with adenomatous hyperplasias showed increased expression of p21 antigen. In HCC it was detected on tumor cells of 63 of 101 patients (62.4%). Characteristically, its expression in well-differentiated HCC was mild and uniformly diffuse, and in moderately differentiated tumors was markedly heterogeneous in both intensity and distribution, whereas no expression was observed in cells of poorly differentiated HCC. These observations suggest that elevated ras p21 antigen expression is important in the development of both cirrhotic nodules and HCC, but that after tumor development, its sustained elevation is no longer necessary for cell proliferation and progression through the grades of anaplasia.

Antibodies, Monoclonal↗
PubMed1987

[The neuromuscular blocking activity of isepamicin sulfate (HAPA-B) compared with other aminoglycoside antibiotics].

Effects of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, on the neuromuscular transmission were studied in rats and compared with those of amikacin (AMK) or other aminoglycoside antibiotics. The HAPA-B, as well as other aminoglycoside antibiotics, depressed the twitch response of diaphragm to phrenic nerve stimulation in vitro. The depression effects of different drugs were compared and graded in the order of strengths of blocking action as: netilmicin (NTL) greater than gentamicin (GM) greater than streptomycin (SM) greater than kanamycin (KM) greater than AMK greater than HAPA-B. The IC50 (concentration which inhibited the response by 50%) of HAPA-B was 3.6 X 10(-3) g/ml. The neuromuscular blockade produced by HAPA-B was reversed by CaCl2, KCl or caffeine but not by neostigmine. D-Tubocurarine or MgCl2 augmented the neuromuscular effects of HAPA-B. Intramuscular (400 mg/kg) and intravenous (100 mg/kg) injections of HAPA-B did not affect the twitch response of gastrocnemius muscle to sciatic nerve stimulation in situ. Intravenous injection of 200 mg/kg caused death in some rats and depression of the twitch response in others. Intravenous AMK produced no significant effect on the twitch response at 50 mg/kg and caused death at 100 mg/kg. GM and SM caused death or significant degree of depression of the twitch response at intravenous doses of 50 mg/kg. In experiments of intravenous drug infusion for 60 minutes, the twitch response was depressed by HAPA-B at 400 mg/kg/hr and by AMK at 200 and 400 mg/kg/hr. In conclusion, HAPA-B has a neuromuscular blocking action presumably at the nerve terminal. However, its action was the weakest among the aminoglycoside antibiotics tested.

Amikacin↗
PubMed1987

[General pharmacological studies on isepamicin sulfate (HAPA-B)].

General pharmacological properties of isepamicin sulfate (HAPA-B), a new aminoglycoside antibiotic, were studied in animals and the results obtained were summarized below. Intramuscular injections of HAPA-B at doses of 500 mg/kg inhibited the writing response induced by acetic acid, and at doses of 1,000 mg/kg, caused muscle relaxation, respiratory depression, suppression of spontaneous motor activity and prolongation of thiopental anesthesia. Anticonvulsive action and the effect on the rectal temperature were not observed. Intravenous Intravenous HAPA-B showed no significant effect on the general behavior and the function of the central nervous system at doses of 100 mg/kg. Intravenous injections of HAPA-B to anesthetized dogs resulted increases in the femoral arterial blood flow at doses of 12.5 mg/kg, decrease in the blood pressure and increase in the respiratory rate at doses of 25 mg/kg, and increase in the carotid arterial blood flow at doses of 50 mg/kg. Apparent changes were not recognized in the heart rate and electrocardiograms. In conscious rabbits, intravenous HAPA-B produced increases in the heart rate without significant changes of the blood pressure and electrocardiograms at doses of 100 mg/kg. Spontaneous beatings of isolated atria were depressed by HAPA-B in concentrations of 3 X 10(-4) to 10(-3) g/ml. The HAPA-B inhibited the gastric secretion at intramuscular doses of 500 mg/kg or intravenous doses of 100 mg/kg, and depressed charcoal transport through small intestine and the spontaneous movement of isolated ileum at intramuscular doses of 1,000 mg/kg and at concentrations of 3 X 10(-4) to 10(-3) g/ml, respectively. No irritative effect was found on the gastric mucous membrane. Intravenous HAPA-B inhibited the response of nictitating membrane to pre and post ganglionic stimulations of cervical sympathetic nerve at doses of 100 mg/kg. In in vitro test, HAPA-B inhibited nonspecifically the constrictive responses of trachea, aorta, stomach, ileum and vas deferens to various agonists in concentrations of 3 X 10(-4) to 10(-3) g/ml. Spontaneous movements of uteri of estrous or pregnant animals were depressed by HAPA-B at intravenous doses of 50 to 100 mg/kg and in in vitro at concentrations of 10(-4) to 3 X 10(-4) g/ml. Antidiuretic effect was also observed at intramuscular doses of 250 mg/kg. HAPA-B increased the length of the whole blood clotting time and raised the plasma glucose level at intramuscular doses of 1,000 mg/kg and inhibited the platelet aggregation induced by ADP in vitro at concentrations of 10(-3) g/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

Aminoglycosides↗
PubMed1986

Inhibition by neosurugatoxin of nicotine-induced antinociception.

We have found a selective inhibition of nicotine-induced antinociception in mice by neosurugatoxin (NSTX, 0.4-3.8 nmol/kg), a neurotoxin with a high affinity for ganglionic nicotinic receptors (ED50 = 0.65 nmol/kg). The toxin also reduced specific [3H]nicotine binding in mouse brain membranes (IC50 = 95 nM). The anti-nicotinic activity of NSTX was markedly greater than that of mecamylamine and pempidine. These data indicate that NSTX may block functional nicotinic cholinoceptors possibly in the central nervous system.

Animals↗
PubMed1986

Ontogenesis of nicotinic acetylcholine receptors and presynaptic cholinergic neurons in mammalian brain.

We find a significantly lower level of specific [3H]nicotine binding in the fetal rat forebrain of 20 day gestational age as compared to adult rat tissue, and a progressive increase in the [3H]nicotine binding in the early neonatal forebrain, reaching adult level at 14-28 days of age. The maximal binding sites (Bmax) for the brain [3H]-nicotine binding at the ages of 3, 14 and 28 days were 36%, 74% and 98% respectively of the adult value. Neosurugatoxin (NSTX) was a potent inhibitor of [3H]nicotine binding in the neonatal forebrain (IC50 = 205, 81 and 103 nM at the 3, 14 and 28 days of age) as well as in the adult tissue (IC50 = 79 nM). Both the choline acetyltransferase (ChAT) activity and high affinity uptake of [14C]choline were not detectable or extremely low in the 1 week neonatal forebrain, and then increased progressively with age to reach the adult level at about 6 weeks of age. These data indicate that central nicotinic receptors may mature prior to the development of presynaptic cholinergic elements.

Animals↗
PubMed1986

Correlation of morphologic subtypes of liver cirrhosis with excess alcohol intake, HBV infections, age at death, and hepatocellular carcinoma. A study on 234 autopsy cases in Japan.

Two hundred thirty-four autopsy cases of liver cirrhosis were examined to correlate the tissue HBV markers and excess alcohol intake with the type of liver cirrhosis, and the incidence of hepatocellular carcinoma (HCC). The following four groups were classified as follows: (1) HBV marker-positive alcoholic group A, (2) HBV marker-negative alcoholic group B, (3) HBV marker-positive non-alcoholic group C, and (4) HBV marker-negative non-alcoholic group D. Macronodular cirrhosis predominated in groups, A, C, and D, while in group B macronodular and micronodular cirrhosis were almost of the same frequency. The mean age at death of the patients with macronodular cirrhosis of HBV-positive alcoholic group A was similar to that of HBV-positive non-alcoholic group C but lower than that of HBV-negative alcoholic group B, suggesting a longer survival of alcoholics without HBV infection than that with HBV infection, when patients had macronodular cirrhosis at autopsy. In HBV-negative alcoholic group B, patients with macronodular cirrhosis had a higher mean age than those with micronodular cirrhosis, while in HBV-positive alcoholic group A, the mean age of patients with either cirrhosis was similar. This suggested that in the absence of HBV infection, macronodular cirrhosis in alcoholics may be related to the increased life span that allows a conversion of micronodular cirrhosis into macronodular one, and in HBV-positive alcoholics it may arise in relation to HBV infection. HCC was frequently associated with macronodular cirrhosis, regardless of the presence or absence of alcohol abuse or HBV infection, but rare in micronodular cirrhosis.

Age Factors↗
PubMed1986

Studies on the pathogenesis of hepatocellular carcinoma in HBV-negative alcoholic cirrhotics.

Ninety five cases of HBV marker-negative cirrhosis with excess alcohol intake were examined clinicopathologically to obtain some clues and insights into the pathogenesis of hepatocellular carcinoma (HCC). The following data were obtained: cases were divided morphologically into 37 cases of macronodular cirrhosis (MacCir), 16 mixed cirrhosis (MixCir), and 42 micronodular cirrhosis (MicCir), the mean age at death was the oldest in MacCir (61 yrs), the youngest in MicCir (51 yrs), and intermediate in MixCir (59 yrs), association of HCC was common both in MacCir and MixCir (78 and 63%, respectively) but infrequent in MicCir (17%), all livers of MicCir with HCC had broad collapse and a small number of macronodules in non-cancerous areas and the mean age of them was older than that of MicCir without both the collapse and macronodules (56 vs 48 yrs), in total cases, the mean age at death of patients with HCC was 7 years older than that without HCC (60 vs 53 yrs), the mean liver weight was the largest in MicCir (1,211 g), the smallest in MacCir (829 g), and intermediate in MixCir (1,022 g), the incidence of MacCir was significantly higher in patients who had given up alcohol for more than one year before death than those without abstinence, and neither the subtypes of cirrhosis nor the incidence of HCC was significantly related to the total amount of alcohol intake. These data indicate that the development of HCC in HBV-negative alcoholics with cirrhosis occurs in relation to the development of macronodules and loss of liver weight, most likely along with the prolongation of the life span.

Adult↗
PubMed1986

Effect of piperidine and related alicyclic amines on nicotinic and muscarinic agonist binding sites in the mammalian brain.

The effect of piperidine and related alicyclic amines on central nicotinic and muscarinic cholinoceptors was investigated by measuring specific binding of [3H]nicotine and [3H]cismethyldioxolane (CD) in rat cerebral cortical membranes. Piperidine, pyrrolidine, 4-hydroxypiperidine and piperazine at concentrations of 1 microM-30 mM completed dose-dependently with [3H]nicotine and [3H]CD for the binding sites. Among these compounds, piperidine was the most potent competitor of brain [3H]nicotine binding sites. Piperidine and pyrrolidine showed a greater affinity for [3H]nicotine binding sites in the rat cerebral cortex than of [3H]CD binding sites. In contrast, 4-hydroxypiperidine and piperazine displayed approximately 10 times greater affinity for [3H]CD binding sites. Pipecolic acid had little effect on these cholinoceptor agonist binding sites. The inhibitory effect of brain [3H]nicotine binding by piperidine did not differ between brain regions or during development. In addition, there was little difference in the piperidine-induced inhibition of brain [3H]nicotine binding between species such as rat, mouse, guinea-pig and rabbit. Thus, the present study demonstrates a high affinity of piperidine for nicotinic cholinoceptors in the mammalian brain.

Amines↗
PubMed1985

Effect of elcatonin on experimental gastric and duodenal ulcers.

The antiulcer action of elcatonin, an analogue of natural eel calcitonin, was compared with that of cimetidine, secretin and solcoseryl. Elcatonin (3 to 10 mu/kg, s.c.) inhibited the development of gastric ulcers induced by pylorus ligation, water-immersion stress, aspirin and reserpine and duodenal ulcers induced by cysteamine in rats. Moreover, once daily injections of elcatonin (1 to 10 mu/kg/day, s.c.) promoted the healing of acetic acid-induced chronic gastric ulcers not only in rats but in dogs. The healing effect persisted after the cessation of administrations. Cimetidine (30 to 100 mg/kg, p.o.) inhibited the development of gastric ulcers induced by water-immersion stress, aspirin and reserpine and duodenal ulcers induced by cysteamine in rats. However, once daily administrations of cimetidine (30 to 100 mg/kg/day, p.o.) did not show significant effect on acetic acid-induced chronic gastric ulcers in rats. Secretin (30 to 100 mu/kg, s.c.) inhibited the development of gastric ulcers induced by pylorus ligation, water-immersion stress, aspirin and reserpine in rats, but was not effective on cysteamine-induced duodenal ulcers and acetic acid-induced chronic gastric ulcers in rats. Solcoseryl (2 ml/kg, s.c.) inhibited only the development of water-immersion stress-induced gastric ulcers in rats. These results suggest that elcatonin is different from these reference drugs in its properties of action on experimental ulcers. Mechanisms of the antiulcer action of elcatonin which has a superior effect on experimental ulcers are discussed.

Acetates↗
PubMed1985

Brain nicotinic acetylcholine receptors. Biochemical characterization by neosurugatoxin.

Specific [3H]nicotine binding to rat forebrain membranes was saturable and of high affinity, and it exhibited pharmacological specificity as well as stereoselectivity for nicotinic agents. There was a regional variation of specific [3H]nicotine binding in rat brain. Low concentrations of neosurugatoxin markedly inhibited specific [3H]nicotine binding in rat forebrain (IC50 = 78 nM) and the competition curve by the toxin was biphasic (pseudo-Hill slope, 0.44). Approximately 50% of [3H]nicotine binding in rat forebrain was inhibited by low concentrations (0.3-100 nM) of neosurugatoxin and the residual binding was inhibited by higher concentrations (0.3-10 microM). In the presence of 3 nM, 100 nM, and 1 microM neosurugatoxin, there was a concentration-dependent (28, 54, and 71%, respectively) loss of [3H]nicotine-binding sites (Bmax) in rat forebrain with little change in the dissociation constant (Kd). The blockade of brain [3H]nicotine-binding sites induced by neosurugatoxin was not reversed by washing. Further, the toxin (10 microM) considerably accelerated the dissociation of [3H]nicotine from its receptor sites initiated by nonlabeled (-)nicotine. These observations suggest that neosurugatoxin may allosterically regulate [3H]nicotine binding rather than competing directly. In contrast to a marked inhibition of [3H]nicotine binding, neosurugatoxin (100 nM-10 microM) had no effect on brain [3H]quinuclidinyl benzilate binding. In conclusion, the present study has shown that [3H]nicotine selectively labels nicotinic cholinergic receptors in rat brain and that neosurugatoxin is a potent noncompetitive antagonist of these receptors.

Animals↗