Biomedical subjects

N Haga

Publications and source records attributed to N Haga.

At least 37 records · Page 2Linked to original sources

PubMed1999

Postprandial normal saline intake delays gastric emptying of solids in conscious dogs: partial involvement of CCK in its mechanism.

Although it is known that a caloric liquid meal given after food intake delays solid gastric emptying, the effect of a noncaloric liquid is not known. The aims of this study were to determine the effect of normal saline given at 3 hr after feeding on gastric antral motor activity and gastric emptying and to evaluate the role of endogenous cholecystokinin in the changes in gastric function induced by postprandial saline intake in conscious dogs. Two cannulas were implanted in each of five mongrel dogs for infusion of phenolsulfonphthalein into the proximal duodenum and for aspiration of luminal samples from the distal duodenum. Gastric contractile and emptying activity were measured by the force transducer method and a freeze-drying method newly developed by our group, respectively. Postprandial pancreaticobiliary secretion was assessed from amylase and bile acid outputs into the duodenum. One hundred grams of freeze-dried dog food was given as a solid meal after mixing it with 100 ml of normal saline. The dogs were given 100 ml of normal saline per os at 3 hr after feeding. In another study, intravenous administration of devazepide, a specific cholecystokinin-A receptor antagonist, at a dose of 0.1 mg/kg/hr was begun 15 min before postprandial saline intake and continued for 1 hr. Gastric antral motility was significantly (P < 0.01) inhibited for 30 min after the dogs had drunk saline at 3 hr after feeding. The mean fractional emptying rate of gastric solids in percentage per 30 min after postprandial saline intake was significantly (P < 0.05) slower than that in the control study without saline intake at 3 hr after feeding. Amylase output into the duodenum after postprandial saline intake showed a gradual increase lasting for about 1 hr, whereas that of bile acid increased transiently but markedly 15 min after saline intake, in comparison with the control study. Pretreatment with devazepide partially ameliorated the suppression of gastric antral motility. Postprandial intake of saline inhibited gastric motor activity and delayed solid gastric emptying, whereas it increased the outputs of amylase and bile acid. Endogenous cholecystokinin may be partially involved in these phenomena caused by saline intake at 3 hr after feeding.

Administration, Oral↗

PubMed1999

Spondylo-epi-metaphyseal dysplasia with normal stature: a case followed from infancy to skeletal maturity.

Spondylo-epi-metaphyseal dysplasia is a rare skeletal dysplasia showing radiographic abnormalities in the epiphyses and metaphyses of the long and short tubular bones, and in the spine. There are very few reports of a case followed throughout the entire growth period. Here we report the case of a Japanese girl followed from 1 month old to skeletal maturity at 16 years old. She developed progressive kyphoscoliosis at 7 years old, and underwent a surgical correction of the spine at 14 years old. The diagnosis of spondylo-epi-metaphyseal dysplasia was made from examining all the follow-up radiographs showing abnormalities in the spine, long bones and hands involving epiphyses and metaphyses. She had normal stature--a rare finding in this condition.

Adolescent↗

PubMed1998

2-Deoxyglucose inhibits chemotherapeutic drug-induced apoptosis in human monocytic leukemia U937 cells with inhibition of c-Jun N-terminal kinase 1/stress-activated protein kinase activation.

Human monocytic leukemia U937 cells undergo apoptosis when treated with antitumor drugs, such as etoposide, camptothecin and mitomycin C. The molecular mechanism of the drug-induced apoptosis is not well understood. In this study, we found that 2-deoxyglucose (2DG), an analog of D-glucose and an inducer of glucose-regulated stress, inhibited anticancer drug-induced but not tumor necrosis factor-alpha-induced apoptosis of U937 cells. 2DG did not reduce initial cellular damage caused by etoposide, an inhibitor of topoisomerase II, suggesting that 2DG affected subsequent cellular responses involved in apoptosis. 2DG inhibited the etoposide-induced activation of c-Jun N-terminal kinase 1/stress-activated protein kinase (JNK1/SAPK) and the subsequent activation of CPP32, both of which are positive regulators for etoposide-induced apoptosis of U937 cells. Our results indicate that 2DG inhibits apoptosis by blocking the signals from cellular DNA damage for JNK1/SAPK activation.

Antineoplastic Agents, Phytogenic↗

PubMed1998

An evaluation of motor function in transverse colon transplants after total gastrectomy.

The motor activity of the isolated colon is understood less than that of any other part of the gastrointestinal viscus. Thus, the aim of the present study was to evaluate the motor activity of the interposed transverse colon following total gastrectomy through a study of 21 patients. Manometric studies were carried out with a 5-lumen, open-tipped catheter in the resting state, in response to dry swallows, and swallowing distilled water and a liquid meal. Contractile waves in the interposed colon grafts were divided into three types, namely, high-amplitude propagated contractions (HAPCs), low-amplitude propagated contractions (LAPCs), and low-amplitude nonpropagated contractions (LANPCs). No retrograde contractions were observed during the entire recording. Motor activity in the interposed colon increased to a greater extent after swallowing distilled water or liquid meals than during the resting period or after dry swallows; however, there was no significant difference between the effect of distilled water and liquid meals. The motor activity of the interposed colon was lower in patients with symptoms than in asymptomatic patients. These results suggest that the volume, rather than the composition, of the lumen contents is an important factor for inducing interposed colon graft contractions, and that contractions of the interposed colon can help to propel the contents of the colon into the duodenum and clear any duodenal juice if reflux should occur.

Anastomosis, Surgical↗

PubMed1998

Risk factors of myelopathy at the atlantoaxial level in spondyloepiphyseal dysplasia congenita.

Spondyloepiphyseal dysplasia congenita (SEDC) can be accompanied by hypoplasia of the odontoid and/or lax ligaments which may lead to spinal cord compression. Since an early diagnosis of myelopathy is essential for rational treatment, identification of the high-risk factors is imperative. Sixteen patients were retrospectively reviewed, 10 male and 6 female, and their average age at the time of examination was 18 (range 3-37) years. Myelopathy was seen in 6 individuals. Five were associated with atlantoaxial subluxation, and the critical value of space available for the spinal cord at the level of the atlas was 10 mm or less. Their height was less than -7SD of average Japanese of the same age, and all were associated with severe coxa vara. Although SEDC itself is a risk factor, marked short stature of less than -7SD and severe coxa vara are particularly high-risk factors for cord compression at the level of the atlas.

Adolescent↗

PubMed1998

An exocytotic mutant of Paramecium caudatum: membrane fusion without secretory contents release.

This is a detailed characterization of a secretory mutant incapable of releasing secretory contents despite normal exocytotic membrane fusion performance. Trichocyst non-discharge strain tnd1 of Paramecium caudatum and its wildtype (wt) both show a transient cortical [Ca2+]i increase and exocytotic membrane fusion in response to the polyamine secretagogue, aminoethyldextran (AED), or to caffeine. tnd1 cells frequently display spontaneous Ca2+ signals parallelled by spontaneous exocytotic membrane fusion. This remains undetected, unless the trichocyst matrix is shown to be freely accessible to the inert, non-membrane permeable fluorochrome, F2FITC, from the outside. In these tnd1 cells, spontaneous and AED- or caffeine-induced membrane fusion, always without contents expulsion by decondensation (i.e. several-fold stretching), is ascertained by electron microscopy. Exocytotic openings, with condensed trichocysts retained, may persist for hours without impairing cells. Trichocyst decondensation normally requires micromolar [Ca2+]e, but an increase to 10 mM has no effect on tnd1 trichocyst expansion in vivo or in vitro (when isolated and exposed to ionophore A23187 + Ca2+). Paracrystalline packing of the major secretory components (trichynins) does occur, despite incomplete proteolytic precursor processing (according to SDS-PAGE). However, 45Ca(2+)-binding by secretory components is considerably reduced--the likely cause of the non-discharge phenotype. Our findings imply significant untriggered membrane fusion in a system normally following the triggered pathway and clear separation of exocytotic membrane fusion from any later Ca(2+)-dependent steps of the secretory cycle.

Animals↗

PubMed1998

Effect of TKS159, a novel 5-hydroxytryptamine4 agonist, on gastric contractile activity in conscious dogs.

A novel 5-hydroxytryptamine (5-HT)4 receptor agonist, TKS159, ¿4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2- hydroxymethyl-4-pyrrolidinyl] benzamide), has recently been developed as a gastroprokinetic drug. Cisapride is already used clinically to increase gastric contractions. The stimulatory effects of TKS159 and cisapride on gastric contractions were examined using force transducers chronically implanted on the vagally denervated pouch (Heidenhain pouch) and the vagally innervated main stomach in conscious dogs. Contractile activity was analysed by computer and expressed as a motor index. Intravenous administration of TKS159 or cisapride significantly increased the motor index in both the main stomach and the Heidenhain pouch during the fed and fasted states. Pharmacological characterization in the fasted state revealed that the contraction-stimulating activity of TKS159 and cisapride on the stomach was significantly inhibited by atropine, hexamethonium and a 5-HT4 receptor antagonist, SDZ 205-557. Granisetron (a 5-HT3 receptor antagonist) significantly inhibited cisapride-induced, but not TKS159-induced gastric contractions. The plasma motilin concentration was significantly increased after cisapride, but not after TKS159 injection. In conclusion, TKS159 has a contractile-stimulating effect on both the innervated and the denervated stomach. It is likely that a cholinergic pathway and 5-HT4 receptors are involved in producing the contractions, although other mechanisms cannot be excluded. Cisapride has almost the same characteristics, but the present findings suggest the involvement of motilin and 5-HT3 receptors in the effects of cisapride.

Animals↗

PubMed1998

Motilin controls cyclic release of insulin through vagal cholinergic muscarinic pathways in fasted dogs.

The effect of motilin on insulin release has not been studied in the interdigestive state. Adult mongrel dogs were chronically implanted with force transducers in the stomach and duodenum to monitor contractile activity, and the plasma motilin and insulin concentrations were measured by a specific radioimmunoassay and enzyme immunoassay, respectively. The concentration of insulin in plasma was found to fluctuate in close association with that of motilin and phase III of the interdigestive migrating contractions in the stomach. This spontaneous release of insulin was mimicked by intravenous infusion of motilin at a dose of 0.3 microgram.kg-1.h-1. Exogenous motilin (0.01-0.3 microgram/kg) dose dependently stimulated insulin release, which was abolished by atropine, hexamethonium, ondansetron, and truncal vagotomy. Phentolamine significantly enhanced, whereas propranolol inhibited, motilin-induced insulin release. In a perifusion system using islet cells from the canine pancreas, motilin did not affect insulin release. In conclusion, motilin stimulates insulin release through vagal cholinergic, muscarinic receptors on pancreatic beta-cells, and the effect appears to be modulated by adrenergic nerves.

Activity Cycles↗

PubMed1998

Benign form of congenital angulation of long bones associated with shortening of soft tissues.

We report a benign form of congenital angulation of long bones associated with shortening of soft tissues. The patients were three males and four females including two siblings. The average age at first examination was 6 months (range, 1-17 months) and that at the time of follow-up was 7 years (range, 13 months-11 years). The characteristics were short-limb type short stature, congenital multiple angulation deformities of the long bones of both upper and lower extremities, with almost the same angulation directions for all the patients and improvement of the deformities with age. There was also accelerated skeletal maturation, lack of epi-metaphyseal lesions, skin dimples, limitation of the ankle joint dorsiflexion, and inconspicuousness of skin creases on the flexor side of the elbow and knee. This phenotype is not consistent with any of the bent bone dysplasia group. Caffey's report [Caffey J (1947). Am J Dis Child 74:543-5621 included two different subtypes of bent bones, round bowing and sharp angulation, and the latter are similar to this report. However, Caffey's cases lack limitation of ankle dorsiflexion and reduced skin creases. An autosomal recessive mode of inheritance could be present in this subtype.

Bone and Bones↗

PubMed1998

Enchondromatosis with features of dysspondyloenchondromatosis and Maffucci syndrome.

We report a girl with multiple enchondromatosis, unequal leg length, short stature, congenital scoliosis, lymphangioma, and cutaneous hemangiomata. The skeletal findings were consistent with the clinical and radiological features of dysspondyloenchondromatosis except that short stature was not apparent in the neonatal period. Dysspondyloenchondromatosis is a rare disorder, one of the several types of multiple enchondromatosis with spinal abnormalities. In previous reports of this condition the association of vascular lesions usually found in Maffucci syndrome has not been described.

Child↗

PubMed1998

[A case of neutropenic enterocolitis in high dose chemotherapy with peripheral blood stem cell transplantation for relapsed testicular tumor].

High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) is safe and useful for the treatment of refractory or relapsed testicular tumors, but is sometimes accompanied by serious complications. We report a case of relapsed testicular tumor complicated by neutropenic enterocolitis during high dose chemotherapy with PBSCT.

Adult↗

PubMed1997

Mutations in the N-terminal globular domain of the type X collagen gene (COL10A1) in patients with Schmid metaphyseal chondrodysplasia.

Schmid metaphyseal chondrodysplasia (SMCD) is a relatively common, heritable osteochondrodysplasia characterized by short-limbed short stature with normal facies, and generalized metaphyseal dysplasias of the long and short tubular bones. Several mutations of the type X collagen gene (COL10A1) have been reported in patients with SMCD, all in the C-terminal globular domain. To address whether mutations in other domains can cause SMCD, we examined the coding region of the COL10A1 gene in DNA samples from six Japanese families affected with SMCD, by direct sequencing. We detected novel mutations in three unrelated SMCD patients; one was a one-base deletion in the C-terminal globular domain and others were de novo missense mutations in the N-terminal globular domain. All three cases revealed a typical clinical phenotype for SMCD. Thus, we have demonstrated that mutations of COL10A1 in regions other than the C-terminal globular domain can cause SMCD, and the results suggest that the N-terminal globular domain also plays an important role in formation of type X collagen.

Asian People↗

PubMed1997

Muscarinic control of phase III contractions and motilin release in dogs.

The role of muscarinic receptor subtype(s) in the control of gastric phase III contractions and motilin release was determined in dogs. Pirenzepine (226 nmol/kg/h) shortened the phase III cycle, causing an early increase in plasma motilin concentrations. Both AF-DX116BS and 4-DAMP inhibited the occurrence of spontaneous and motilin-induced phase III contractions, and 4-DAMP also inhibited the spontaneous increase in plasma motilin concentration. Only 4-DAMP inhibited carbachol-induced motilin release in perifused duodenal mucosal cells. In conclusion, M1 receptors are involved in the indirect inhibition of motilin release. Motilin-induced contractions are mediated mainly by M3 receptors and partly by M2 receptors, and M3 receptors are present in motilin-producing cells.

Animals↗

PubMed1997

Potent and subtype-selective CCK-B/gastrin receptor antagonists: 2,4-dioxo-1,5-benzodiazepines with a plane of symmetry.

A series of CCK-B/gastrin receptor antagonists, 2,4-dioxo-1,5-benzodiazepine derivatives with a plane of symmetry, were designed, synthesized, and evaluated for antagonistic activity. Structure-activity relationship studies revealed that carbonylmethyl groups at both N-1 and N-5 positions and hydrophilic groups, such as the carboxyl group on the benzene ring attached to the ureido group at the C-3 position, brought about potent affinity and subtype selectivity for CCK-B/gastrin receptors. Several compounds showed excellent in vivo inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats.

Animals↗

PubMed1997

Synthesis and pharmacological properties of ureidomethylcarbamoylphenylketone derivatives. A new potent and subtype-selective nonpeptide CCK-B/gastrin receptor antagonist, S-0509.

A novel series of CCK-B/gastrin receptor antagonists-ureidomethylcarbamoylphenylketone derivatives-were designed, synthesized, and evaluated for activity. Structure-activity relationship studies revealed the importance of a carboxylic acid at substituent R2 and tert-butoxycarbonyl group at R1 in structure A. Compound 7a (S-0509) showed remarkable affinity for the CCK-B/gastrin receptor and a subtype selectivity profile in vitro. Administration (id) of 7a led to excellent inhibition of gastric acid secretion induced by pentagastrin in anesthetized rats with an ED50 value of 0.014 mg/kg. Furthermore, 7a proved to have poor blood-brain permeability by its small effect on enhancement of morphine analgesia. Thus, S-0509 has an increase in selectivity for the peripheral effects of gastrin antagonism from the central effects of CCK-B antagonism.

Animals↗

PubMed1997

Long-term observations of uterine contractions in nonpregnant dogs.

Uterine contractile activity in nonpregnant conscious dogs was investigated based on 2- to 6-mo-long continuous recording by means of a chronically implanted force transducer. We found that nonpregnant uterine contractile activity could be classified into six major patterns: sporadic contractions, weak and strong tonic contractions, weak and strong phasic contractions, and phasic contraction bursts. The contractile patterns during proestrus and estrus were the most active, with strong phasic and tonic contractions and phasic contraction bursts. The phasic and tonic contractions were inhibited dose-dependently by a beta 2 adrenergic agonist, ritodrine, and reproduced by an alpha 2 adrenergic agonist, clonidine. In contrast, the cholinergic inhibitors atropine and hexamethonium did not affect the spontaneous occurrence of these contractions, although bethanechol evoked uterine contractions. Oxytocin and prostaglandin F2 alpha-induced contractions were phasic during estrus, whereas they showed tonic increases with phasic contractions during proestrus, diestrus, and anestrus, and these contractions did not resemble the spontaneous contractions. In conclusion, the nonpregnant uterus contracts continuously in harmony with the estrous cycle phases, and its contractile activity is enhanced by alpha adrenergic receptors and inhibited by beta 2 adrenergic receptors.

Adrenergic Agonists↗

PubMed1997

A new method to measure gastric emptying in conscious dogs: a validity study and effects of EM523 and L-NNA.

A new method for measurement of gastric emptying without the use of radioisotope markers has been developed in dogs. A test meal was given after measurement of its freeze-dried weight, and 1-ml duodenal samples were collected through an indwelling tube at 15-min intervals, and their absolute weight was measured. The duodenum was continuously perfused with phenolsulfonphthalein to determine the recovery of each sample. Three different calorie or fat-enriched meals were administered with 100 ml saline containing polyethylene glycol as a liquid marker. The results showed that increasing the calorie load of, and adding fat to, the test meal proportionally delayed gastric emptying of the solid phase. Utilizing this method, it was found that EM523, an erythromycin derivative, accelerated the gastric emptying of solids, whereas N(omega)-nitro-L-arginine (L-NNA) markedly delayed the gastric emptying of both solids and liquids. In conclusion, this freeze-drying method is a reliable technique for measuring the gastric emptying of the solid phase in dogs.

Animals↗

PubMed1997

Congenital deficiency of the fibula with ipsilateral iliac horn and absence of the kidney.

Congenital deficiency of the fibula is sometimes accompanied by femoral hypoplasia, genu valgum, patellar a/hypoplasia or dislocation, tibial bowing, foot deformity, and toe deficiency in the affected limb. 'Iliac horns' are bony projections extending posterolaterally from the ilium and considered to be pathognomonic of nail-patella syndrome. We report a 5-year-old Japanese girl with congenital complete deficiency of the left fibula, ipsilateral iliac horn and absence of the left kidney.

Female↗