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Biomedical subjects

N Inaba

Publications and source records attributed to N Inaba.

At least 19 recordsLinked to original sources

Placenta accreta/increta. Review of 10 cases and a case report.

A review of the patients seen at the Department of Obstetrics at Dokkyo University Hospital who had suffered placenta accreta/increta in the past 18 years, was performed. There were 10 such cases out of 9,716 deliveries during this period. This incidence is higher than that which has been reported in other Western countries. Forty percent of the patients in our study had placenta accreta/increta accompanied by placenta previa or low lying; 30% had had a prior cesarean section (C/S); 70% had previously experienced dilatation and curettage (D & C); 80% had previously undergone a C/S and/or D & C: and 40% had a history of miscarriage. Three of the ten patients with placenta accreta/increta required a hysterectomy; 2 patients were successfully treated with hemostatic stitches on the endometrium; and the remaining 5 mild cases were treated with removal of the placenta, either manually or with the use of forceps. There was no case of maternal death. In 2 cases, neonatal asphyxia was noted, but the neonate immediately recovered.

Adult↗

Gastroprotective mechanism of lafutidine, a novel anti-ulcer drug with histamine H2-receptor antagonistic activity.

Lafutidine (CAS 118288-08-7, FRG-8813) is a novel histamine H2-receptor antagonist with gastroprotective activity. The aim of this study was to investigate the property of the gastro-protective activity of lafutidine by examining the effect on ammonia-induced change in transmucosal potential difference (PD), basal gastric mucosal blood flow (GMBF) and noxious agent-induced cell damage. Intragastrical application of lafutidine accelerated the recovery of the PD reduction after exposure of the mucosa to 0.25% ammonia solution and the accelerating effect was abolished by chemical deafferentation, but not with indometacin, a cyclooxygenase inhibitor. The application of capsaicin, as a reference compound, significantly promoted the recovery of the ammonia-induced PD reduction and this effect was not altered with indometacin. Lafutidine given intragastrically caused a sustained increase in GMBF in a dose-dependent fashion, which was also completely inhibited in the deafferentated rats. In vitro studies revealed that, in contrast to 16,16-dimethyl prostaglandin E2, lafutidine did not protect isolated gastric superficial epithelial cells from ethanol- or ammonia-induced damage. In conclusion, the gastroprotection of lafutidine is induced by promoting the restitution of the damaged mucosa after a noxious agent, not by directly protecting the epithelial cells and this effect may be caused through the mechanism of capsaicin-sensitive afferent nerves.

16,16-Dimethylprostaglandin E2↗

Antiulcer effect of lafutidine on indomethacin-induced gastric antral ulcers in refed rats.

Lafutidine is a new type antiulcer agent with antisecretory and gastroprotective activities. We investigated the effect of lafutidine on indomethacin-induced antral ulcer in refed rats. Subcutaneous indomethacin injection resulted in the formation of gastric antral ulcer. Lafutidine (1-10 mg/kg, p.o.) reduced the area of ulcer in a dose-dependent manner when administered immediately after the indomethacin injection. Capsaicin at 3 mg/kg, p.o. and 16,16-dimethyl prostaglandin E2 at 3 microg/kg, p.o. also reduced the ulcer area. Chemical deafferentation of capsaicin-sensitive neurons or N(G)-nitro-L-arginine treatment aggravated the ulcer formation and abolished the preventive effect of lafutidine and capsaicin. After the induction of gastric ulcer, lafutidine given twice daily for 2.5 days reduced the area of ulcer in a dose-dependent manner with a significant effect at 10 mg/kg, p.o., as compared with that of the control group. In chemically-deafferentated rats, lafutidine did not show any healing effect. Cimetidine (30 mg/kg, p.o.) and famotidine (1 mg/kg, p.o.) had no significant effect on indomethacin-induced antral ulcer. These results may suggest that lafutidine, unlike cimetidine and famotidine, can prevent the indomethacin-induced antral ulcer formation and accelerate the healing of the ulcer in refed rats through mechanisms involving the capsaicin-sensitive afferent neurons and nitric oxide.

16,16-Dimethylprostaglandin E2↗

[TTV materno-infantile infection--a study on the TTV frequency in Japanese pregnant women and the natural history of TTV mother-to-infant infection].

We preliminarily describe the frequency of TTV in Japanese pregnant women, non-parenteral, postnatal materno-infantile transmission of TTV, and 2 cases in which infantile development of the TTV carrier-state seemed to have occurred by vertical infection. The sera of 85 hepatitis B, C and G-positive and 36 non-pathological pregnant Japanese women were screened for the presence of TTV DNA with a use of semi-nested PCR. The positive rates were 25.9 and 27.8%, respectively. No significant differences were gained between these two groups. Twenty-one infants were born to the TTV carrier women. Of them, 9 infants (42.9%) sero-converted to TTV DNA-positive after their age of 4 months. Among the infants who were breast-fed, the positive sero-conversion rate of TTV DNA tended to increase as the length of the breast feeding period increased. Serum AST/ALT levels stayed within normal upper limits in the 9 infants. This study indicates the frequent, and furthermore, certain possibility of non-parenteral (i.e., via breast milk), postnatal vertical infection of TTV.

Biomarkers↗

Nasal absorption kinetic behavior of azetirelin and its enhancement by acylcarnitines in rats.

PURPOSE: The long-term stability and nasal absorption characteristics of a basic nasal formulation of azetirelin, a thyrotropin-releasing hormone analog and its absorption enhancement by incorporation of acylcarnitines in the formulation were investigated. METHODS: The long-term stability of basic nasal azetirelin formulations at 25 degrees C was predicted by calculation from the Arrhenius plot of the data on 6 months' storage at 40, 50 and 60 degrees C. Nasal azetirelin absorption characteristics were kinetically examined by intranasal administration to rats, determination of plasma azetirelin level by radioimmunoassay, and fitting the data to a two-compartment model including absorption rate. RESULTS: Basic nasal azetirelin formulations of pH 4.0 and pH 5.1 were predicted to be highly stable. Residual azetirelin after 2 years storage at 25 degrees C was greater than 95%. Nasal absorption characteristics of this formulation in the pH 4.0-6.3 range showed pH-dependency, with pH 4.0 showing the highest absolute bioavailability (Bioav) of 17.1%. This nasal Bioav was 21 times greater than that of oral administration (0.8%). Acylcarnitines with 12 or more carbon atoms in the acyl chain greatly enhanced nasal absorption of azetirelin: Bioavs with lauroylcarnitine chloride (LCC) and palmitoylcarnitine chloride were 96.9% and 72.9%, respectively. This enhancement by LCC plateaued at the low concentration of 0.1%. CONCLUSIONS: The basic nasal azetirelin formulation at pH 4.0 is stable and shows adequate absorption, with nasal absorption having greater Bioav than oral absorption. The 12-carbon acylate LCC was the strongest enhancer among acylcarnitines and provided near-total delivery of the administered dose to the blood.

Absorption↗

Vertical transmission of hepatitis C virus: risk factors and infantile prognosis.

OBJECTIVES: To clarify the incidence and risk factors of the vertical transmission of hepatitis C virus (HCV) and to determine the prognosis of the carrier infants. METHODS: At our hospital, 1,941 non-pathological (non-HIV carriers) Japanese pregnant women were screened for anti-HCV antibodies. Sera of the antibody-positive women were examined by the reverse transcription polymerase chain reaction (RT-PCR) method, and the positive women and their infants were followed by testing HCV-related markers. RESULTS: The HCV carrier rate among the pregnant women was 3.5% (68/1,941). Four among the 65 infants (6.2%) who were successfully followed for more than 6 months developed the HCV carrier-state. Of all the risk factors examined, only the elevation (> or = 110 IU/l) of maternal serum alanine aminotransferase (ALT) was found to be significant for HCV vertical transmission. Seventy-five and 50% of the carrier infants manifested chemical hepatitis and seroconverted to an HCV-RNA-negative status, respectively, during the follow-up period. CONCLUSIONS: The frequency of HCV vertical transmission was 6.2%. Half of the carrier infants became seronegative for HCV-RNA. HCV vertical transmission was significantly affected by the maternal serum ALT level prior to delivery.

Adolescent↗

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↗