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N Inaba

Publications and source records attributed to N Inaba.

At least 37 records · Page 2Linked to original sources

Modulation of the inspiratory-related activity of hypoglossal premotor neurons during ingestion and rejection in the decerebrate cat.

Single-unit activities of the bulbar reticular inspiratory neurons directly projecting to hypoglossal motoneurons were studied during fictive ingestion (e.g., swallowing) and rejection elicited by repetitive stimulation of the superior laryngeal nerve and by application of water to the pharynx in immobilized decerebrated cats. The single-unit activity was recorded during 113 episodes of fictive ingestion from 25 inspiratory neurons directly projecting to hypoglossal motoneurons (single projection neurons) and 7 inspiratory neurons directly projecting to both hypoglossal and phrenic motoneurons (dual projection neurons) in the regions ventrolateral to the nucleus tractus solitarii and dorsomedial to the nucleus ambiguus. All of single projection neurons ceased inspiratory-related rhythmical discharges coincidentally with the onset of repetitive stimulation of the superior laryngeal nerve. The majority of them (19/25, 76%, type A) showed a spike burst during ingestion, whereas the minority (6/25, 24%, type B) kept silent until the end of repetitive stimulation of the superior laryngeal nerve. During fictive ingestion elicited by application of water to the pharynx, the type-A neurons showed a spike burst activity, whereas the type-B neurons kept silent. All dual projection neurons (7/7, 100%, type C) ceased inspiratory-related rhythmical discharges at the onset of repetitive stimulation of the superior laryngeal nerve and showed no activity during fictive ingestion. Likewise, the type-C neurons kept silent during fictive ingestion elicited by application of water to the pharynx. A spike burst was induced during 33 episodes of fictive rejection in all of 5 tested type-A, 3 tested type-B, and 6 tested type-C neurons. It is concluded that the premotor neurons involved in the respiratory-related rhythmical activity of hypoglossal motoneurons is responsible for switching from respiration to ingestion and rejection.

Animals↗

Maternal-infant transmission of hepatitis G virus.

By a reverse transcriptase-polymerase chain reaction assay, we studied the risk of hepatitis G virus vertical infection in seven infants born to women positive for hepatitis G virus ribonucleic acid and hepatitis C virus antibody. Of these, three (42.9%) tested positive for hepatitis G virus ribonucleic acid and two (28.6%) had a carrier state. Intrauterine or birth canal infection seemed much more significant than the infection by breast-feeding.

Breast Feeding↗

Effects of several denervation procedures on distribution of calcitonin gene-related peptide and substance P immunoreactive in rat stomach.

The effect of chemical deafferentation, vagotomy (VGX), and gangliosympathectomy (GSX) on the density of fibers containing calcitonin gene-related peptide (CGRP) and substance P (Sub.P) in the rat gastric wall was studied. Chemical deafferentation by capsaicin abolished the density of CGRP-immunoreactive (IR) fibers, not Sub.P-IR fibers. Ten days after VGX, the density of CGRP-IR or Sub.P-IR fibers in the mucosa was largely reduced, while no reduction of CGRP-IR and Sub.P-IR fibers was seen in submucosal and muscular layers. GSX significantly reduced the density of CGRP-IR fibers in the mucosa and caused a moderate decrease in the fibers in submucosal and muscular layers. Pretreatment with 6-hydroxydopamine, a neurotoxin for noradrenergic nerves, did not affect the density of CGRP-IR fibers in the gastric wall. The density of Sub.P-IR fibers in the gastric wall was not affected by GSX. These studies indicate that the CGRP-IR and Sub.P-IR fibers in the mucosa are susceptible to extrinsic nerve denervation compared with those in the submucosa and muscle layers, that a major portion of the CGRP-IR fibers in the mucosa is of both vagal and spinal origin, and that a major portion of the Sub.P-IR fibers in the mucosa is of vagal origin. Furthermore, the present results support that CGRP-IR fibers, not Sub.P-IR fibers, in the rat stomach are capsaicin-sensitive.

Animals↗

[Effect of a novel antiulcer drug, lafutidine, on experimental chronic gastritis in rats].

Oral administration of an ammonia solution (0.01%) or a sodium taurocholate solution (TCA solution, 5 mM) as drinking water for 4 weeks or 13 weeks, respectively, resulted in gastric mucosal thinning and decreased parietal cell numbers. Oral administration of TCA solution also caused cell infiltration in the lamina propria of the mucosa and mucosal fibrosis. When lafutidine (3, 10 mg/kg) was administered orally once daily for one week after the withdrawal of ammonia or TCA solution, the recovery of the mucosal thickness in the fundic gland area and the parietal cell number were significantly accelerated, and the recovery of mucosal thickness in the pyloric gland area also tended to be accelerated. Lafutidine at 10 mg/kg for 1 week had no influence on normal mucosal thickness and parietal cell numbers. At the doses that produce equal or greater acid antisecretory effect than lafutidine, oral administration of cimetidine (30 mg/kg) and famotidine (1 mg/kg) had no effect on either of these atrophy indexes. These results demonstrate that lafutidine, unlike cimetidine and famotidine, can accelerate the healing of mucosal injuries in ammonia- and TCA-induced chronic gastritis models.

Acetamides↗

Increased susceptibility of rat gastric mucosa to ulcerogenic stimulation with aging. Role of capsaicin-sensitive sensory neurons.

We examined the influences of aging on gastric damage and gastric mucosal blood flow (GMBF) responses induced by acid back-diffusion, following the barrier disruption, and investigated the relation of capsaicin-sensitive sensory nerves to these changes. Male Fischer rats 3, 13, and 24 months old were used. Under urethane anesthesia, a rat stomach was mounted on a chamber, and gastric potential difference (PD), luminal H+ loss, and GMBF were measured before, during, and after exposure to 20 mM sodium taurocholate (TC) for 30 min, in the presence of 50 mM HCl. Mucosal exposure to TC caused surface cell damage, PD reduction, and acid back-diffusion (luminal H+ loss) in all groups of rats; delta PD reduction and the amount of H+ loss were not significantly different between young and aged rats. In young rats, a marked increase of GMBF was observed with luminal acid loss following TC treatment, yet it resulted in less damage in the gastric mucosa. In aged rats, however, such GMBF responses were apparently mitigated, leading to a significant worsening of gastric mucosal lesions induced by TC. Mucosal application of capsaicin (0.1 mg/ml) caused an increase of GMBF in young rats, but this response was significantly attenuated in aged rats. In addition, the amount of calcitonin gene-related peptide (CGRP) released in the isolated stomach in response to capsaicin (1 X 10(-5) M) was significantly lower in aged animals when compared to young rats. These findings suggest that the gastric mucosa of aged rats is more vulnerable to acid back-diffusion following the barrier disruption, partly because of dysfunction of GMBF responses mediated by capsaicin-sensitive sensory neurons in the acidic conditions.

Aging↗

Capsaicin-induced calcitonin gene-related peptide release from isolated rat stomach measured with a new chemiluminescent enzyme immunoassay.

The peripheral capsaicin-sensitive afferent nerve has been reported to play an important role in gastroprotection and to release a calcitonin gene-related peptide (CGRP). We developed a new chemiluminescent enzyme immunoassay (CLEIA) for CGRP and measured capsaicin-induced CGRP release from the isolated and inverted rat stomach. The basal CGRP release from the stomach was 0.40 +/- 0.02 pg/mg wet weight in a 30-min incubation. Capsaicin (1 x 10(-8)-1 x 10(-5) M) stimulated CGRP release in a concentration-dependent manner. In the stomach from rats with defunctionalization of afferent neurons, the levels of the basal and capsaicin-induced CGRP release were below the limit of detection. On the other hand, the capsaicin-induced CGRP release was not blocked by tetrodotoxin treatment. The gangliosym-pathectomy abolished the increase in the CGRP levels. However, the capsaicin-induced CGRP release was not affected by pretreatment with 6-hydroxydopamine, a neurotoxin that causes a complete degeneration of adrenergic nerve terminals. In conclusion, the CLEIA system may be useful for detecting the released CGRP and studying the activity of capsaicin-sensitive nerves, particularly the CGRP-containing nerves. Our results also confirmed that although the CGRP-containing nerve runs in the sympathetic nerve trunk, the activity of the nerve is not affected by adrenergic nerves, and the capsaicin-induced CGRP release may be attributable to the tetrodotoxin-resistant component.

Adrenergic Agents↗

Regional comparison of prolactin gene expression in the human decidualized endometrium in early and term pregnancy.

Prolactin (PRL) is known to be expressed in the decidualized human endometrium and secreted into amniotic fluid. Although the site of synthesis of endometrial PRL is known to be the decidual cells, the difference in PRL gene expression within each area of decidua, i.e. decidua basalis, decidua parietalis and decidua capsularis, during pregnancy is not clear. We have applied an in situ hybridization histochemistry technique using a radiolabeled RNA probe to compare the difference in expression of PRL gene within each area of the decidualized endometrium. Specific hybridization signals were distributed over the decidual cells in early and term pregnancy. More intense hybridization signals were always detected in the tissues of early pregnancy than in those of term pregnancy. In the decidua capsularis of early pregnancy, labeled cells were concentrated close to the amniotic cavity, whereas cells were concentrated close to the maternal surface of the fetal membrane in term pregnancy. In the decidua parietalis, almost all decidual cells were labeled, but no specific labeling was seen in the endometrial glands or capillary endothelium in both groups. In the decidua basalis, most decidual cells showed hybridization signals whereas no hybridization signal was seen over the trophoblast cells. These results show that there are regional and periodic differences in PRL gene expression in the decidual cells during pregnancy.

Decidua↗

[Measurement of serum tissue polypeptide antigen (TPA) in patients with malignant tumor using prolifigen TPA-M "Daiichi" kit].

Serum tissue polypeptide antigen (TPA) was measured using a newly developed Prolifigen TPA-M "Daiichi" kit in 1,236 healthy subjects, 2,867 patients with malignant tumors, and 901 with benign diseases. Because 94.0% of healthy subjects had serum TPA under 70 U/l, the cut-off value was set at 70 U/l. Serum TPA was elevated in more than 50% of patients with head and neck cancer, lung cancer, liver cancer, gallbladder or bile duct cancer, pancreatic cancer, colorectal cancer, ovarian cancer, and prostate cancer. The overall positive rate in malignant tumors was 55.5%. Serum TPA was higher in advanced cancer than in earlier stage cancer, and decreased after the resection of the tumor. The false positive rate in benign diseases was 31.3%. ROC analysis revealed the usefulness of TPA as a tumor marker in many cancers. The correlation coefficient between TPA and CYFRA 21-1, and between TPA and TPSA, was 0.747 and 0.694, respectively. In conclusion, measurement of serum TPA using the new kit is useful in the management of patients with various malignant tumors.

Antigens, Neoplasm↗

[The combination assay of tumor markers by multivariate analysis for improvements of the diagnostic precision in malignancies].

Since 1987, we have been trying to develop a computer-aided multivariate pattern analysis system (CAMPAS) with the focus on ovarian tumors using a discriminant analysis, which is one of multivariate analysis, to raise specificity while retaining sensitivity of combination assay as high as possible. We applied this CAMPAS which was developed in collaboration with SRL (Tokyo, Japan) under the guidance of Prof. Em. Terashima, Y.(The Jikei University School of Medicine, Tokyo, Japan). CAMPAS OV-2, which is the newest one, based on 2 discriminant formulas with 6 tumor markers, ie, cancer antigen 125 (CA125), immunosuppressive acidic protein (IAP), tissue polypeptide antigen (TPA), alkaline phosphatase (ALP), albumin and iron (Fe), was developed and practised prospectively as a pretherapeutic serological diagnostic means to distinguish epithelial ovarian carcinomas from benign ones tumors. The sensitivity and specificity reached 87.1% and 82.9%, respectively in CAMPAS OV-2.

Biomarkers, Tumor↗

[Expression of prolactin receptor gene in human decidua of early pregnancy].

UNLABELLED: This study was designed to examine the expression of the prolactin receptor (PRL-R) gene in the human decidualized endometrium and to determine the localization of endometrial cells expressing the PRL-R gene. METHOD: Decidua and trophoblast tissues of normal and ectopic pregnancy were obtained by curettage from patients undergoing artificial abortion at 8 -10 weeks of gestation. Total RNA was extracted to perform northern blot hybridization with a radiolabeled human PRL-R cDNA probe. Some tissues were cut and processed for in situ hybridization histochemistry with a radiolabeled RNA probe. RESULTS: 1. Northern blot hybridization: Approximately 9.0, 3.6 and 2.8kb size bands were detected in decidua in normal and ectopic pregnancy. No hybridization signal was detected in the chorionic villi. 2. In situ hybridization: Hybridization signals were detected in the cytoplasm of the decidual cells not only in normal pregnancy but also in ectopic pregnancy. No hybridization signal was detected in the trophoblast cells or endometrial glands. CONCLUSION: The human PRL-R gene is expressed in the decidual cells in early pregnancy not only in normal pregnancy but also in ectopic pregnancy. And it has been reported that the decidual cells produce PRL. These results suggest that PRL may act directly on the decidual cells by paracrine and/or autocrine mechanisms.

Blotting, Northern↗

Cytokeratin fragment 21-1 in gynecologic malignancy: comparison with cancer antigen 125 and squamous cell carcinoma-related antigen.

We measured serum cytokeratin fragment 21-1 (CYFRA 21-1) levels by a solid-phase immunoradiometric assay in 102 healthy Japanese women, and set the reference value at 1.9 ng/ml (mean +2 SD of the serum levels based on a linear distribution). Pretreatment serum CYFRA 21-1 levels were also analyzed in 235 women with benign (n = 94) or malignant (n = 141) gynecologic disease, and were compared with the serum levels of CA 125 and SCC. The respective positivity rates for CYFRA 21-1 and CA 125 were 64.0 and 77.2% in ovarian malignancy, while they were 4.2 and 30.8% in benign ovarian masses. CYFRA 21-1 had an accuracy of 61.3% in diagnosing ovarian malignancy, which was higher than that of CA 125 (53.4%). The positive predictive value of CYFRA 21-1 for ovarian malignancy reached 94.1%, which was significantly (p < 0.005) higher than that of CA 125 (68.8%). These findings indicate the potential usefulness of CYFRA 21-1 as a tumor marker for ovarian malignancy. In addition, the positivity rates fo CYFRA 21-1 in cervical cancer (51.2%) and endometrial cancer (52.2%) were also similar to the respective rates for SCC and CA 125, which suggests that CYFRA 21-1 seems to be a general tumor marker for gynecologic malignancy.

Adolescent↗

[Studies on histamine H2-receptor antagonistic property of FRG-8813, a novel anti-ulcer drug].

The present study was conducted to investigate the histamine H2-receptor antagonistic property of FRG-8813 by using isolated guinea pig right atria, gastric cells and cerebral cortex preparations. FRG-8813 inhibited the histamine-induced positive chronotropic response of the right atria and shifted the concentration-response curve of histamine to the right with suppression of the maximal response. Although the inhibitory effect of FRG-8813 was enhanced in a time-dependent manner and long-lasting, the antagonism was reversible. The potency of FRG-8813 was 2 times and 50 times greater than those of famotidine and cimetidine, respectively. FRG-8813 decreased the histamine-induced [14C]aminopyrine accumulation in gastric cells. Schild plot analysis showed that the slopes of FRG-8813, famotidine and cimetidine were 1.56, 1.40 and 1.07, respectively, suggesting that the mode of the antagonism of FRG-8813 is also unsurmountable in gastric cells. The lack of effect on dbcAMP- and bethanechol-induced [14C]aminopyrine accumulations indicated the selectivity of FRG-8813 for histamine H2-receptor. As in the right atria, the potency of H2-antagonism was 1.5 times and 40 times greater than those of famotidine and cimetidine, respectively. In the [3H]tiotidine binding study of the cerebral cortex preparation, the Ki values showed that the affinity of FRG-8813 was 2 times and 80 times more potent than those of famotidine and cimetidine, respectively. In conclusion, FRG-8813 is an unsurmountable and selective histamine H2-receptor antagonist with 2 times greater potency than famotidine. The antagonistic activity is reversible in spite of the time-dependent increase of the antagonism.

Acetamides↗

Gastroprotective activity of FRG-8813, a novel histamine H2-receptor antagonist, in rats.

FRG-8813 ((+/-)-2-(furfurylsulfinyl)-N-[4-[4-(piperidinomethyl)-2- pyridyl]oxy-(Z)-2-butenyl]acetamide) is a novel histamine H2-receptor antagonist with gastric antisecretory and gastroprotective activities. The present study was designed to investigate the property of gastroprotective action. The oral ED50 values for inhibition of mucosal lesions against 1% NH3-, 60% ethanol in 0.15 N HCl-, 100% ethanol-, 0.6 N HCl- and sodium taurocholate in 0.4 N HCl-induced damage were 3.3, 11.1, 14.9, 23.3 and 23.1 mg/kg, respectively. FRG-8813 was gastroprotective despite pretreatment with omeprazole, suggesting that the protective effect is independent of its antisecretory activity. It is unlikely that FRG-8813 works as a mild irritant because it showed a gastroprotective effect after intraperitoneal injection, but oral administration itself did not influence the rat gastric mucosa. Although pretreatment with indomethacin or N-ethylmaleimide did not affect the gastroprotection of FRG-8813, chemical deafferentation induced by capsaicin abolished the gastroprotection. Furthermore, prior administration of tetrodotoxin, the calcitonin gene-related peptide (CGRP) antagonist hCGRP or NG-nitro-L-arginine attenuated the gastroprotection of FRG-8813 as well as that of capsaicin. In contrast to capsaicin, repeated administration of FRG-8813 neither enhanced the susceptibility of the mucosa to damage nor affected the gastroprotective action of short-term treatment. In conclusion, these results suggest that FRG-8813 has gastroprotective activity independently of acid antisecretory activity and that capsaicin-sensitive nerves may be partially or fully involved in the gastroprotective mechanisms of FRG-8813.

Acetamides↗

Human cell clones, RSa and UVr-1, differing in their capability for UV-induced virus reactivation and phenotypic mutation.

UVr-1 is a human cell clone established as a variant with increased resistance to cell killing by ultraviolet light (UV, principally 254 nm wavelength) from a UV-sensitive cell clone, RSa. Both cells have been characterized to have much the same capacity of UV-induced DNA repair synthesis in whole cells, and the parent RSa cells were recently found to be hypermutable. In the present study UVr-1 cells were characterized in comparison RSa cells with respect to UV-induced virus reactivation and phenotypic mutation. Survival levels of UV-irradiated vaccinia virus and herpes simplex virus type 1 (HSV-1) were much the same in logarithmically proliferating UVr-1 and RSa cells. Correlated with these host cell reactivation levels, the same extent of UV-induced DNA repair replication synthesis was observed in isolated nuclei of the two cell clones. Enhancement of survival levels of UV-irradiated HSV-1 was detected when proliferating RSa cells were irradiated with UV prior to the virus infection. In contrast, this enhanced virus reactivation (EVR) was not detected in similarly irradiated and infected UVr-1 cells. As for phenotypic mutation frequencies assessed by the cloning efficiency of cells with increased resistance to ouabain cell killing (OuaR), OuaR mutants were not obtained from UVr-1 cells either with or without UV irradiation. When the proliferation of cells was synchronized, both EVR and OuaR mutations were detected in RSa cells irradiated with UV at any cell cycle phase, being greatest in the later half of the G1 phase. However, there was no detectable EVR or mutation in any phase of synchronous UVr-1 cells. The hypomutability of UVr-1 cells and hypermutability of RSa cells in a G1 cell cycle phase was also found even if 4-nitroquinoline 1-oxide was used as a mutagen or mutant cells with increased resistance to 6-thioguanine cell killing were estimated.

Cell Cycle↗

Hypoglossal premotor neurons with rhythmical inspiratory-related activity in the cat: localization and projection to the phrenic nucleus.

Localization and projection to the phrenic (PH) nucleus were studied in a sample of premotor neurons that directly projected to hypoglossal motoneurons (XII Mns) and showed respiratory-related patterns of activity. The experiments were carried out in cats, under pentobarbital anesthesia. In the first part of the study, the retrograde double-labeling technique was used to reveal the existence of neurons projecting to both the XII and the PH nuclei. Injection of a fluorescent dye (fast blue, FB) into the XII nucleus and another (nuclear yellow, NY) into the PH nucleus retrogradely labeled, with either FB or NY, medullary reticular neurons mainly in the regions ventrolateral to the nucleus of the tractus solitarius (vl-NTS), ventrolateral to the hypoglossal nucleus (vl-XII), and dorsomedial to the nucleus ambiguus (dm-AMB) bilaterally. In addition, some neurons in these regions were labeled with both FB and NY. In the second part of the study, unitary activity was recorded extracellularly from medullary respiratory neurons. In the regions vl-NTS, vl-XII, and dm-AMB, inspiratory neurons were found which antidromically responded to stimulation of the XII nucleus. Some of them also responded antidromically to stimulation of the PH nucleus. Averaging of rectified and integrated XII and PH nerve discharges by spontaneous spikes of single inspiratory neurons in the vl-NTS and dm-AMB regions revealed a facilitation in either XII nerve discharge or both XII and PH nerve discharges after a short latency of monosynaptic range. It is concluded that in the vl-NTS and dm-AMB regions there are inspiratory neurons that are excitatory premotor neurons projecting to XII Mns showing the respiratory-related activity. Some of them have excitatory synaptic connections to XII and PH Mns via bifurcating axons.

Animals↗