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Biomedical subjects

M Ohtsuka

Publications and source records attributed to M Ohtsuka.

At least 127 records · Page 7Linked to original sources
PubMed1995

Luminal dilution caused by certain mild irritants and capsaicin contributes to their gastric mucosal protection.

We have recently shown that certain mild irritants caused the increase in fluid volume in the rat stomach. The present study was conducted to investigate 1) whether standing fluid in the gastric cavity can prevent gastric mucosal injury caused by 0.6 N HCl and 2) the mechanisms by which certain mild irritants increase the gastric fluid volume. One milliliter of water administered immediately before irritants greatly inhibited gastric lesion formation. Sodium chloride and capsaicin induced a profound enhancement of gastric fluid volume, as acid mild irritants did also. Sensory denervation completely abolished the volume increase caused by capsaicin but hardly influenced that caused by mild irritants. Capsaicin increased the amount of Evans blue in the gastric fluid, but mild irritants did not. On the other hand, HCl and capsaicin significantly inhibited the emptying of phenol red. From these results, we conclude that mild irritants and capsaicin can induce volume increase that by itself is enough to afford protection through luminal dilution. Capsaicin but not mild irritants requires sensory neurons to increase the gastric fluid volume. Certain mild irritants may provide a fluid pooling effect partly by inhibiting gastric emptying.

Animals↗
PubMed1995

A compartmentalized bias for T-cell receptor V beta usage in summer-type hypersensitivity pneumonitis.

Several monoclonal antibodies specific to the human T-cell receptor (TCR) variable (V) region were used to examine whether T-cell oligoclonality plays a key role in the development of the T-cell-mediated lung disease, summer-type hypersensitivity pneumonitis (SHP). The usage of TCR V-regions was examined using bronchoalveolar lavage (BAL) and matched peripheral blood lymphocytes (PBL) in patients with SHP. In 18 SHP patients, the majority of lymphocytes in both BAL and PBL was CD3+ cells (94.2 vs. 63.9%, respectively), which was similar to that in normals (n = 7). Of CD3+ lymphocytes in a SHP patient, the percentage of CD4+ cells in BAL was reduced compared to those in paired PBL, whereas the percentage of CD8+ cells was significantly elevated. In contrast, the percentage of CD4+ cells was much higher than that of CD8+ cells in both BAL and PBL of normal subjects. While a majority of CD3+ T cells expressed TCR alpha/beta+ in BAL and PBL from both SHP patients and normal controls, a marked increase of the expression of TCR gamma/delta+ was observed in PBL in 4 out of 18 SHP patients. A markedly increased prevalence (> 3 SD) of specific TCR alpha/beta+ V-region families in BAL was detected in 5 of 18 patients with SHP as compared to normal controls, whereas no specific increase was found in PBL. Increased V beta 8 was detected in 3 cases; V beta 6 was observed in 1 patient, and V beta 5 in another patient.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Reddish Escherichia coli cells caused by overproduction of Bacillus stearothermophilus uroporphyrinogen III methylase: cloning, sequencing, and expression of the gene.

During shotgun cloning of an amylase gene, we found a transformant of Escherichia coli with a reddish color. The transformant produced highly water-soluble red pigments the molecular masses of which were less than 3000. The plasmid harbored by the transformant contained a DNA fragment derived from a strain of Bacillus stearothermophilus. Truncation of the insert DNA showed that an 1.1-kbp Sau 3A-SalI fragment was responsible for the reddish colony. An open reading frame was found in the nucleotide sequence of the 1.1-kbp DNA fragment. The production of the red pigment was accompanied by a colorless 28-kDa protein. The sequence of the 28-kDa protein was highly homologous to bacterial uroporphyrinogen III methylases participating in corrinoid biosynthesis. The 28-kDa protein was found to be a thermostable uroporphyrinogen III methylase.

Amino Acid Sequence↗
PubMed1995

Increase in length of experimental skin flaps that survive with dibutyryl cyclic AMP.

One of the most important research topics in plastic surgery is the extension of the length of skin flaps that survive. We have investigated the increase in the length of skin flaps that can be achieved by giving dibutyryl cyclic AMP (DB-cAMP) to rabbits with experimental skin flaps and compared the results with those in animals not given DB-cAMP. Three variables, the arrival of DB-cAMP in the critical area of circulation of the flap (n = 6), changes in the blood flow in the flap (n = 10), and increase in the length of skin flap that survived (n = 30) were investigated by high performance liquid chromatography and laser Doppler flowmetry. DB-cAMP reached the critical area of circulation in the skin flap (dye distance), increased the blood flow within this area (mean (SEM) peak value 30 minutes after operation 1.24 (0.06) ml/min/kg compared with 1.06 (0.02) in control flaps), and extended the length of the flap that survived (mean (SEM) length seven days after operation 66.1 (3.0) mm compared with 60.8 (1.8) mm in the control group). We conclude that DB-cAMP improved the blood flow in skin flaps in rabbits with a consequent increase in the length of skin flap that survived.

Animals↗
PubMed1995

Effects of vamicamide on urinary bladder functions in conscious dog and rat models of urinary frequency.

PURPOSE: To investigate the usefulness of vamicamide, (+/-)-(2R*, 4R*)-4-dimethylamino-2-phenyl-2-(2-pyridyl)valeramide, as a novel drug for the treatment of urinary frequency and incontinence. MATERIALS AND METHODS: Urinary frequency was evaluated in specially devised conscious dog and rat models by investigating the effects of the drug on urinary bladder function of these animals by cystometrography. RESULTS: In the dog model with transected hypogastric nerves, the bladder volume at micturition (bladder capacity) was less than 50% that of the sham-operated dog, and in the rat model with bilateral lesioning of nuclei basalis, a part of the brain, by ibotenic acid injection, bladder capacity was about 50% that of the sham-operated rat. Other bladder functions in both models were unchanged. In the dog model, orally administered vamicamide at 0.32 and 1.0 mg./kg. significantly increased bladder capacity and did not change residual urine volume or micturition pressure. Oxybutynin 0.10 mg./kg., one of the most popular drugs for the treatment of urinary frequency and incontinence, or atropine 0.10 mg./kg. induced significant increases in bladder capacity similarly to vamicamide at 0.32 mg./kg. In the rat model, oral vamicamide 0.32 mg./kg. also significantly increased bladder capacity and did not change micturition pressure or threshold pressure. Again, oxybutynin 0.10 mg./kg. or atropine 0.32 mg./kg. had almost the same effects as vamicamide 0.32 mg./kg. CONCLUSIONS: These findings suggest that vamicamide should be useful for the treatment of urinary frequency.

Animals↗
PubMed1995

General pharmacology of the new antimuscarinic compound vamicamide.

The general pharmacology of the new antimuscarinic compound vamicamide (FK176, (+/-)-(2R*, 4R*)-4-dimethylamino-2-phenyl-2- (2-pyridyl)valeramide, CAS 132373-81-0) was investigated using mice, rats, guinea pigs and dogs, and was in part compared with that of oxybutynin hydrochloride (oxybutynin, CAS 1508-65-2), a similar type of compound. 1. Vamicamide induced mydriasis after oral administration (p.o.) of 10 mg/kg or more, and suppressed defecation after 32 mg/kg or more in the general activity and behavior test with rats. 2. Vamicamide increased spontaneous locomotor activity in mice at 32 mg/kg or more (p.o.) and suppressed tonic convulsions in the electroconvulsive shock test with mice at 100 mg/kg. The compound at 10-100 mg/kg (p.o) did not show significant effects on hexobarbital-induced anesthesia, pentetrazole-induced convulsions and pain response by Haffner's method in mice, body temperature in rats or spontaneous electroencephalogram (EEG) in rabbits. On the other hand, oxybutynin increased high voltage slow waves of spontaneous EEG in rabbits at 32 mg/kg or more (p.o.) and prolonged hexobarbital-induced anesthesia time in mice at 100 mg/kg. 3. Vamicamide in concentrations of 0.001-1% (1 x 10(-4)-1 x 10(-1) g/ml) did not show local anesthetic effect on the corneal reflex test with guinea pigs. The compound in concentrations of 1 x 10(-5) and 1 x 10(-4) g/ml also had no effects on contractions of the isolated rat diaphragm caused by electrical stimulation of the phrenic nerve. 4. Vamicamide on the highest concentration of 1 x 10(-4) g/ml augmented contractions of isolated rat vas deferens induced by noradrenaline, resting tonus of the isolated guinea pig trachea, and contractile force of spontaneous movement of the isolated rat nonpregnant uterus. The compound at 1 x 10(-4) g/ml had no significant effects on KCl-induced contraction of the isolated rat thoracic aorta. 5. Vamicamide elevated systemic blood pressure and increased heart rate but had no effects on respiratory movement of the chest in conscious dogs at an oral dose of 10 mg/kg or more. The compound in intraduodenal (i.d.) doses of 3.2-32 mg/kg had no effect on femoral blood flow in anesthetized dogs. Vamicamide augmented contractile force and reduced beating rate in isolated guinea pig atria at a concentration of 1 x 10(-5) g/ml or more. Oxybutynin increased heart rate at 3.2 mg/kg or more (p.o.), and elevated blood pressure at 10 mg/kg or more in conscious dogs. 6. Vamicamide slightly inhibited small intestinal transit in rats at 3.2 mg/kg or more (p.o.). On the other hand, oxybutynin inhibited the transit in rats at 0.32 mg/kg or more. 7. Vamicamide had no effects on urine volume, urinary excretion of Na+, K+, Cl- and uric acid in rats at an oral dose of 100 mg/kg or less, or on renal function in anesthetized dogs at an i.d. dose of 32 mg/kg or less. 8. Vamicamide showed no effects on bleeding time in mice at 100 mg/kg p.o., rabbit platelet aggregation induced by adenosine diphosphate or collagen at 1 x 10(-4) g/ml, blood coagulation systems in rats at 100 mg/kg p.o., or hemolysis on rabbit blood at a concentration of 1% or less. Thus, vamicamide in the doses used inhibited gastrointestinal motility, and caused mydriasis as effects possibly due to its anticholinergic action. The compound had no effects on the central nervous system, cardiovascular system, renal functions, or blood system.

Animals↗
PubMed1994

Tolerance to the vascular effect of a novel nitric oxide-donating vasodilator, FK409.

We investigated whether tolerance develops to the vasorelaxant effects of a new vasodilator, (+-)-(E)-4-ethyl-2-[(E)-hydroxy-imino]-5-nitro-3-hexenamide (FK409), in isolated canine coronary artery strips and to its hypotensive effect in rats, and whether FK409 activates soluble guanylate cyclase isolated from vascular tissues in the absence of L-cysteine. No tolerance to FK409 (0.46 nM to 0.46 microM or 1-1000 micrograms/kg, i.v.) or cross-tolerance between FK409 and glyceryl trinitrate was demonstrated in in vitro and in vivo experiments, whereas the tolerance to glyceryl trinitrate (0.44 nM to 4.4 microM or 1-1000 micrograms/kg, i.v.) was marked in both conditions. In addition, FK409 (0.1-10 microM) activated soluble guanylate cyclase without L-cysteine, but glyceryl trinitrate (1-100 microM) required the addition of L-cysteine (5 mM) for the activation of the enzyme. The results suggest that FK409 may be advantageous compared to tolerance-producing nitrates currently in clinical use, and that this property of FK409 is probably due to its independence of a sulfhydryl group donor.

Animals↗
PubMed1994

Sequential evaluation of clinical and immunological findings in hypersensitivity pneumonitis: serial subclass distribution of antibodies.

The long-term outcome of hypersensitivity pneumonitis (HP) is variable depending upon the individual. To evaluate the mechanisms involved in the progression or regression of HP, the longitudinal changes in pulmonary function test results, bronchoalveolar lavage (BAL) cells and the subclass distribution of IgA and IgG antibodies were investigated in 14 patients with HP, including 5 cases with bird fancier's lung (BFL). The present study has shown that: (1) All patients with bird fancier's lung (BFL) demonstrated either a restrictive pattern or a reduced diffusing capacity for carbon monoxide (DLco), or both; one BFL patient showed deterioration in %VC and %DLco after avoidance of direct exposure. (2) All three patients with summer type HP who demonstrated reduced VC and DLco at the initial test improved, (3) T cells, especially CD8 cells, were predominant in the BAL fluids of the summer type HP patients, whereas either CD8 or CD4 cells were less common, but showed an increase in the BAL fluids of the BFL patients, depending upon individuals, (4) The number of CD8 cells in the summer type HP patients decreased gradually, but at slower rate than in the BFL patients; (5) Antibody activities of IgG1, G2, G3, G4, and A1 subclasses in the sera and BAL fluids were detected during the 5-year observation period; (6) IgA2 subclass was abundant in the BAL fluids of both BFL and summer type HP patients, in contrast to very minute amounts in sera; (7) The level of IgG2 antibody in the BAL fluids of the summer type HP patients was low (0.15 +/- 0.05) as compared to that in BFL (0.82 +/- 0.29); (8) The level of IgG3 antibody in the BAL fluids of summer type HP patients was lower (0.18 +/- 0.05) than in BFL (1.01 +/- 0.1); and (9) The antibody activities in most immunoglobulin subclasses fluctuated, but declined gradually in the BAL fluids, although they were well beyond the normal ranges. We were unable to predict the progression or the disappearance of hypersensitivity pneumonitis based merely upon the results of the present study.

Adult↗
PubMed1994

Monoclonal antibody HML-1 reactivity with adult T-cell leukaemia/lymphoma and other lymphomas.

Human T-cell leukaemia/lymphoma virus type 1 (HTLV-1), a causative virus of adult T-cell leukaemia/lymphoma (ATLL), is known to be transmitted by breast-feeding. Using a monoclonal antibody HML-1 which labels human intestinal intra-epithelial T lymphocytes, we have immunohistochemically examined ATLL tissues in order to evaluate the possibility that HTLV-1 infected intestinal T cells are the origin of ATLL cells. Previously this antibody was reported to react with intestinal T-cell malignant lymphomas but not with peripheral tumours, or any B-cell lymphomas. We investigated 181 patients with malignant lymphomas and found that 19 out of 113 ATLLs were positive for HML-1. T-cell malignant lymphomas excluding ATLL also reacted with HML-1 (7/24), but all the B-cell lymphomas 0/33) and non-neoplastic lymph node and skin lesions (0/10) were negative for HML-1. In patients with ATLL and other T-cell malignant lymphomas, the positivity level of HML-1 was relatively higher in stomach (3/7) and tonsil (2/6) than that in lymph nodes (15/100) and skin (8/47). We observed one HML-1 positive ATLL patient with tumour formation in the skin and lymphadenopathy and marked infiltration of the large intestine but minimal involvement of other organs. Although HML-1 was frequently expressed in gastric infiltration of ATLL, the level of positivity was too low in lymph nodes to support the hypothesis that HTLV-1 infected intestinal T cells are the origin of ATLL cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Antianginal effects of FK409, a new spontaneous NO releaser.

1. The aim of this study was to compare antianginal effects of (+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide (FK409), a new spontaneous nitric oxide releaser, with those of isosorbide dinitrate (ISDN). We used two types of rat angina model; methacholine- and arginine vasopressin (AVP)-induced coronary vasospasm models. 2. In the in vitro study, FK409 showed 80 times more potent vasorelaxant effect in dog isolated coronary artery than ISDN (EC50 = 16.7 +/- 4.8 and 1340 +/- 320 nM, respectively). 3. In the rat methacholine-induced coronary vasospasm model, FK409 suppressed the elevation of ST segment dose-dependently and significantly at 0.1 mg kg-1, i.d. On the other hand, ISDN suppressed it significantly at 3.2 mg kg-1, i.d. In addition, the efficacy of 3.2 mg kg-1 ISDN in the model was almost the same as that of 0.1 mg kg-1 FK409. 4. In the above experiments, FK409 and ISDN decreased mean blood pressure significantly at the maximum dose tested (1.0 mg kg-1, i.d. and 3.2 mg kg-1, i.d., respectively) but did not change heart rate at these doses. Therefore, the hypotensive effect of FK409 was 10 times weaker than the antianginal effect of the compound, while those of ISDN were almost the same. 5. In the rat AVP-induced coronary vasospasm model, 32 mg kg-1 FK409 significantly inhibited the depression of ST segment 60 min after oral administration. On the other hand, 32 mg kg-1 ISDN did not inhibit it at 60 and 120 min after oral administration. 6. In conclusion, FK409 inhibits coronary vasospasm more potently in two types of rat angina models than ISDN. In addition, FK409 shows an antianginal effect more selectively that a hypotensive effect,compared with ISDN.

Angina Pectoris, Variant↗
PubMed1994

The motility of lung lymphocytes in hypersensitivity pneumonitis and sarcoidosis.

Lymphocytes obtained by bronchoalveolar lavage (BAL) in hypersensitivity pneumonitis (HP) and pulmonary sarcoidosis (PS) are believed to be derived from interstitial inflammatory lesions of the lung in which lymphocytes have migrated from the blood. Because cellular motility is one of the important factors in lymphocyte migration, we investigated the motility of BAL lymphocytes from 12 patients with HP and 12 with PS, as well as their responsiveness to chemoattractants in vitro by modified Boyden chamber method. Motility was evaluated by the number of migrated cells and the migration distance. The numbers of migrated BAL lymphocytes from patients with HP and PS in albumin-containing medium were 318.3 +/- 93.0 (mean +/- SD) and 207.6 +/- 35.5, respectively, and were greater than those of BAL lymphocytes from normal control subjects (133.3 +/- 40.9) and blood lymphocytes, and comparable with those of mitogen-activated blood lymphocytes. The motility of BAL lymphocytes in these diseases compared with blood lymphocytes was also increased in protein-free medium. In addition, the culture supernatants of alveolar macrophages (AM) enhanced the motility of BAL, mitogen-activated, and blood lymphocytes. These results suggest that BAL lymphocytes in these diseases are functionally motile, and their enhanced motility, as well as mediators from AM, may facilitate the accumulation of lymphocytes at the epithelial surface.

Alveolitis, Extrinsic Allergic↗
PubMed1994

[A case of life-threatening acute asthma with marked elevation of serum theophylline level during inhalational anesthesia].

A 21-year-old man was admitted to our hospital because of life-threatening acute asthma. His condition deteriorated while he was receiving aminophylline and high-dose corticosterolids, and complicated by pneumomediaststinum. He was intubated and ventilated mechanically. Since peak inspiratory pressure was very high and arterial blood gases were not improving, he was treated with inhaled haltohane and enflurane, and bronchial lavage was done via a bronchoscope. Anesthesia continued for 114 hours before his condition improved. The serum theophylline levels were elevated during anesthesia. Since the dose of aminophylline was not very high, this elevation may have been related to the inhalation of halothane and enflurane.

Acute Disease↗
PubMed1994

Cold agglutinin disease following allogeneic bone marrow transplantation.

We describe a case of cold agglutinin disease (CAD) following allogeneic bone marrow transplantation. This 36-year-old male developed CAD 3 weeks after allogeneic bone marrow transplantation for chronic myelogenous leukemia. Cyclosporin A and methotrexate had been administered to prevent graft-versus-host disease. Other agents administered included cytomegalovirus hyperimmune globulin and recombinant human G-CSF. Pericarditis preceded the development of CAD. The characterization of cold agglutinin (CA) was monoclonal IgM-kappa with anti-Pr antigen specificity, probably derived from the engrafted donor lymphocytes. The administration of prednisolone led to transient improvement. The CA titer decreased without further treatment 12 weeks after transplant.

Adult↗
PubMed1993

Activin enhances osteoclast-like cell formation in vitro.

The effect of activin (activin A/EDF) on osteoclast formation was investigated. In mouse bone marrow cell cultures, activin enhanced the formation of tartrate-resistant acid phosphatase (TRACP)-positive multinucleated cells (MNC) in a dose-dependent manner, either in the presence or absence of 1,25-(OH)2D3 or PTH. In organ cultures of neonatal mouse calvaria, activin also enhanced the generation of TRACP-positive giant cells in the endosteal periosteum and increased the TRACP staining of whole calvaria, but did not exhibit bone resorbing activity. These results indicate that activin stimulates the formation of osteoclasts, but not osteoclast activation. Activin is produced by bone marrow cells and might be involved in the local process of osteoclast differentiation.

Acid Phosphatase↗
PubMed1993

Vasorelaxant mechanism of the new vasodilator, FK409.

To define the vasorelaxation mechanism of FK409, we examined the effect of the compound on vascular tension and cyclic nucleotide levels in isolated rat thoracic aorta contracted with norepinephrine, and on activities of guanylate cyclase and cyclic GMP phosphodiesterase prepared from rat or rabbit thoracic aorta. FK409 (1 x 10(-9) to 1 x 10(-6) M), like nitroglycerin (1 x 10(-9) to 1 x 10(-6) M), produced a potent vasorelaxant effect associated with an increase in cyclic GMP content of the tissue. There was no change in cyclic AMP levels. The vasorelaxant effect of FK409 was independent of the integrity of the endothelium, and was unaffected by L-NG-monomethylarginine (0.1 mM) or oxyhemoglobin (1 microM). On the other hand, FK409 (3.2 x 10(-7) M) activated soluble guanylate cyclase, and the activating effect was completely inhibited by oxyhemoglobin (10 nM). Cyclic GMP phosphodiesterase was unaffected by FK409 (1 x 10(-7) to 1 x 10(-5) M). Furthermore, in rat aortic soluble fraction FK409 (3 mM) was found to liberate nitric oxide (NO) which was evaluated spectrophotometrically after diazotization of sulfanilic acid and coupling with N-(1-naphthyl)-ethylenediamine. The liberation occurred even in the absence of L-cysteine (5 mM), in contrast to the case with nitroglycerin (3 mM). These results suggest that the vasorelaxant effect of FK409 is associated with an increase in intracellular cyclic GMP, and that the cyclic GMP accumulation is due to activation of soluble guanylate cyclase. The enzyme activation is probably due to NO released from the compound molecule in the vascular smooth muscle cells.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1993

Pulmonary alveolar proteinosis. Xe-133 scintigraphic findings before and after bronchopulmonary lavage.

A 44-year-old woman with pulmonary alveolar proteinosis was treated by repeated unilateral bronchopulmonary lavages over 6.5 years. The effectiveness of the treatment was assessed by Xe-133 scintigraphy as well as lung function tests and chest roentgenograms. Xe-133 scintigraphy clearly demonstrated improvement of regional ventilation and perfusion, and equalization of the ventilation and perfusion ratio. Therefore, Xe-133 scintigraphy was found to be useful in the analysis of changes in regional aeration, ventilation, and perfusion before and after bronchopulmonary lavage in pulmonary alveolar proteinosis.

Adult↗