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Biomedical subjects

T Azuma

Publications and source records attributed to T Azuma.

At least 91 records · Page 5Linked to original sources

Alterations in gastric mucosal microvascular endothelium in a stressed condition--relevance to gastric ulcerogenesis.

The present paper describes the morphological and functional alterations of the gastric mucosal microvascular endothelium under restraint-stressed condition. On the basis of the direct cholinergic innervation of capillaries and non-muscular venules in the gastric mucosa, these endothelial changes would be caused by the stress-induced overstimulation of the cholinergic nerves and modified by the degranulation of mast cells, contributing to the stress-induced ulcer formation as schematically illustrated in Fig. 10.

Aged

The aortic alpha 1-adrenergic receptor in familial amyloidotic polyneuropathy.

To assess the pathophysiology of the sympathetic nervous system in familial amyloidotic polyneuropathy (FAP), we used 3H-bunazosin to identify and characterize the alpha 1-adrenergic receptor in human aortic membranes. The binding of 3H-bunazosin was rapid, readily reversible, stereospecific, and saturable. The Scatchard analysis described a single class of binding sites with a dissociation constant (KD) of 0.370 +/- 0.035 nM and a maximal binding capacity (Bmax) of 11.8 +/- 1.30 fmol/mg protein in control patients. Competition analysis demonstrated the alpha 1-adrenergic specificity of the 3H-bunazosin binding sites in human aortic membranes. The KD and Bmax of 3H-bunazosin binding in four FAP patients was 0.274 +/- 0.052 nM and 7.79 +/- 0.15 fmol/mg protein, respectively; these values did not differ significantly from those in 14 control patients. An increase in Bmax or affinity of alpha 1-adrenergic receptors may not be the cause for denervation supersensitivity in FAP.

Adrenergic alpha-Antagonists

Involvement of autonomic nervous system in gastric mucosal defense mechanism.

This article describes the histochemical, immunohistochemical, radioautographic, and ultrastructural localizations of aminergic and peptidergic nerves, neurotransmitter receptors, and their binding sites in the stomach wall. Cholinergic and vasoactive intestinal polypeptide (VIP)-ergic nerve fibers are distributed along the gastric microvasculature, within the myenteric and submucosal plexuses, and in the muscularis mucosae and circular muscle layer. In the mucosa, both nerve fibers evenly extend along the capillaries in association with the epithelial cells up to the mucosal surface. In particular, cholinergic nerves are proved to doubly innervate the mucosal capillaries and nonmuscular venules as well as the parietal cells. Adrenergic and neuropeptide Y (NPY)-containing nerves are distributed primarily along the arterioles of the gastric microvasculature, within the myenteric plexuses, and in the circular muscle layer. These nerve fibers extend up to the basal portion of the mucosa in close association with small arterioles, capillaries, and epithelial cells. Some of the adrenergic nerve axons are coexistent with the cholinergic nerve axons within the Schwann cell. Histamine H1 receptors are widely located on the walls of arterioles, capillaries and venules, while H2 receptors are evident not only on the parietal cells but also on the walls of the collecting venules and surrounding capillaries in the mucosa. Dopamine D1 receptors are predominantly located on the smooth muscle cells of the arterioles near the muscularis mucosae, while D2 receptors are present on the walls of postcapillary venules and collecting venules. Functional coordination of both intramural peptidergic nerves as intrinsic origin and aminergic nerves as extrinsic origin is considered to be essential for maintaining the gastric mucosal defense mechanism against a variety of aggressive factors.

Animals

Monoclonal antibodies to O4 antigen of Vibrio parahaemolyticus.

Four monoclonal antibodies were prepared against O4 antigen of Vibrio parahaemolyticus. All the antibodies were shown to be specific for O4 antigen by agglutination with heat-killed O-cells of the organism and precipitation with LPS preparations. The inhibition experiments of the precipitations with various sugars and oligosaccharides suggested that the combining sites of these hybridoma antibodies were directed to an antigenic determinant structure containing----3 and----6 linked D-glucose, D-galactose, and N-acetyl-D-galactosamine.

Agglutination

Studies of neurocirculatory effects of long-term L-threo-3,4-dihydroxyphenylserine administration in a patient with familial amyloidotic polyneuropathy.

The case is reported of a 57-year-old woman with familial amyloidotic polyneuropathy and concomitant orthostatic hypotension for which L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) was clinically effective. Testing of autonomic function under telemetric intra-arterial pressure monitoring before and during L-threo-DOPS treatment clearly demonstrated the pathophysiology of the sympathetic nervous system and its modification by L-threo-DOPS.

Amyloidosis

Vortex generation in pulsatile flow through arterial bifurcation models including the human carotid artery.

Visualization experiments were performed to elucidate the complicated flow pattern in pulsatile flow through arterial bifurcations. Human common carotid arteries, which were made transparent, and glass-models simulating Y- and T-shaped bifurcations were used. Pulsatile flow with wave forms similar to those of arterial flow was generated with a piston pump, elastic tube, airchamber, and valves controlling the outflow resistance. Helically recirculating flow with a pattern similar to that of the horseshoe vortex produced around wall-based protuberances in circular tubes was observed in pulsatile flow through all the bifurcations used in the present study. This flow type, which we shall refer to as the horseshoe vortex, has also been demonstrated to occur at the human common carotid bifurcation in steady flow with Reynolds numbers above 100. Time-varying flows also produced the horseshoe vortex mostly during the decelerating phase. Fluid particles of dye solution approaching the bifurcation apex diverged, divided into two directions perpendicularly, and then showed helical motion representing the horseshoe vortex formation. While this helical flow was produced, the stagnation points appeared on the wall upstream of the apex. Their position was dependent upon the flow distribution ratio between the branches in the individual arteries. The region affected by the horseshoe vortex was smaller during pulsatile flow than during steady flow. Lowering the Reynolds number together with the Womersley number weakened the intensity of helical flow. A separation bubble, resulting from the divergence or wall roughness, was observed at the outer or inner wall of the branch vessels and made the flow more complicated.

Adult

[Multidisciplinary, intra-arterial chemotherapy (IAC) with CDDP and 5-FU against cervical cancer].

As one method of multidisciplinary treatment for cancer of the uterine cervix, a combination IAC using CDDP and 5-FU was applied. Six operable and three inoperable, advanced patients were treated with a single 100-120 mg/body IAC bolus of CDDP followed by a continuous IA infusion of 2,500 mg/body of 5-FU. This was combined with surgical therapy in the former group and radiotherapy in the latter group. In operable cases, the extirpated tissues were examined histopathologically for effects of the combination IAC. Microscopic findings included atrophy and swelling of the cancer cell nucleus, plus variable diffused reduction of the cancer cell nest accompanied by vacuolation of the cytoplasm. In inoperable cases, observations carried out by graphical scintigram, and clinical investigation at 10 days after the IAC, indicated improved conditions. Among the adverse reactions, renal dysfunction recovered two weeks after IAC. No evidence of severe myelosuppression was observed. Therefore, IAC with CDDP and 5-FU, plus surgery or radiotherapy, against carcinoma of the cervix had favorable laboratory and clinical results.

Adult

Secretion and biosynthesis of COOH-terminal glycine extended progastrin (gastrin-G) in rat gastric antrum.

The effects of serotonin (5-HT) on gastrin and COOH-terminal glycine extended progastrin (gastrin-G) secretion, biosynthesis of gastrin and gastrin-G, and the effects of gastrin-G on gastric acid secretion were examined in rats. 5-HT 10(-5) M significantly stimulated gastrin and gastrin-G secretion. Atropine 10(-6) M, which abolished the effects of cholinergic agent to stimulate gastrin secretion, blocked the 5-HT-stimulated gastrin and gastrin-G secretion. In biosynthesis of gastrin and gastrin-G the peak of 35S radioactivity appeared in gastrin-G immunoreactive peak at 30 minutes incubation, however, 35S radioactivity did not appear in the gastrin immunoreactive peak until 1 hour chase incubation. The peak of 35S radioactivity transferred from the gastrin-G immunoreactive peak to the gastrin immunoreactive peak. Concerning the bioactivity of gastrin-G, it did not stimulate gastric acid secretion. From these findings we may conclude that serotoninergic neurons act as interneurons which themselves stimulate a second neuron stimulatory to gastrin and gastrin-G secretion, the posttranslational processing of gastrin occurs sequentially through the proteolytic processing of progastrin to glycin extended processing intermediates, gastrin-G, followed by activation via alpha-amidation in secretory granules, gastrin-G co-secreted with gastrin does not have biological activity, PAM activity in serum does not play a functional role under physiological conditions.

Animals

Immunocytochemical characterization of monoclonal antibody A2B5 in the rat gastric antrum.

Immunocytochemical characterization of monoclonal antibody A2B5 was carried out in the rat gastric antrum, in which immunoreactive cells were found mainly around the middle of the pyloric glands. In serial sections, most cells were identified as gastrin cells, but only 60.6 + 5.9% (mean + SD, n = 5) of them reacted with the antibody. Somatostatin cells did not react with antibody A2B5. The different reaction of antibody A2B5 to gastrin cells indicated that gastrin cells may have a variety of cell surface receptors and have different physiological functions. From these findings, it was concluded that antibody A2B5 did not satisfy the requirements for the cell surface marker of gastrointestinal endocrine cells, though it could be useful in studies of cell surface receptors, concerning which little is known about gastrointestinal endocrine cells.

Animals

Effects of bombesin on the release of glycine-extended progastrin (gastrin G) in rat antral tissue culture.

Recently, glycine-extended processing intermediates of progastrin were identified in porcine stomach using a radioimmunoassay with conventional polyclonal antisera developed against a synthetic peptide analogue for progastrin processing intermediates, gastrin 6-G(Tyr-Gly-Trp-Met-Asp-Phe-Gly). We developed monoclonal antibodies specific for glycine-extended processing intermediates of progastrin (gastrin G). Monoclonal antibody 109-21 appeared to require the carboxyl-terminal pentapeptide structure of gastrin 6-G for maximal binding. Cross-reactivities of 109-21 against gastrin 17 I, gastrin 17 II, cholecystokinin-octapeptide, des(SO3) cholecystokinin-octapeptide, and gastrin 6-G-R-R were respectively 1%, less than 0.1%, less than 0.1%, 0.1%, and 0.5%. With this monoclonal antibody and a polyclonal gastrin antibody we examined the concentrations of gastrin and gastrin G in tissue and the effects of bombesin on the release of gastrin and gastrin G from rat antral mucosa in tissue culture. The gastrin G to gastrin ratio was 2.2 in rat antral mucosa and 0.66 in rat duodenal mucosa. In tissue culture, bombesin significantly stimulated gastrin and gastrin-G secretion at doses of 10(-8) and 3 X 10(-8) M. Atropine (10(-6) M) abolished the actions of carbachol to stimulate gastrin and gastrin-G secretion but had no effect on bombesin-stimulated gastrin and gastrin-G secretion. These results suggest that gastrin G is cosecreted with gastrin in response to carbachol and bombesin, and the stimulation of gastrin and gastrin-G secretion by bombesin does not involve cholinergic neural pathways and may reflect a direct action on gastrin cells.

Animals

Alpha 2-adrenergic receptor in familial amyloidotic polyneuropathy.

alpha 2-Adrenergic receptor binding has been studied in platelet membranes from 16 patients with type 1 familial amyloidotic polyneuropathy (FAP) at various clinical stages and 15 normal subjects. Binding of the radioligand [3H]yohimbine to platelet membranes was used to examine alpha 2-adrenergic receptors. The number of alpha 2-adrenergic receptors were significantly lower in patients of the early stage than in normal subjects. Then, the numbers tended to be higher than those of normal subjects in the intermediate stage, and they were higher in the single advanced-stage patient studied. The reduction in alpha 2-adrenergic receptor numbers in platelet membranes from patients of the early stage might be explained by the down-regulation of the receptors in vascular smooth muscle, but it remains uncertain whether a high number of alpha 2-adrenergic receptors observed in the single advanced-stage patient might be explained by the up-regulation of the receptors.

Adult

Maturation of the immune response to (4-hydroxy-3-nitrophenyl)-acetyl (NP) haptens in C57BL/6 mice.

Changes with time in specificity and affinity of anti-NP antibodies in C57BL/6 mice after immunization with NP22-chicken gamma-globulin (CGG) were studied by comparing the abilities of the antibodies to bind to NP3-bovine serum albumin (NP3-BSA) at pH 5 and 8. Early anti-NP antibodies (on day 14 after immunization) bound to NP3-BSA at pH 8, but not pH 5. This pH-dependence of binding was explained in terms of the low affinity of the antibody to the phenolic form of NP on the basis of results of fluorescence quenching titration of a monoclonal anti-NP antibody that showed similar specificity to that of the early anti-NP antibodies. Since NP on the CGG molecule ionized with an apparent pK of about 7.4, more than half the NP should be in the unionized (phenolic) form under the immunization conditions. However, early anti-NP antibodies bound preferentially to the ionized (phenolate) form of NP, which was a minor form at neutral pH, whereas later anti-NP antibodies showed ability to bind to both the phenolate and phenolic forms of NP. This change in specificity with time was observed on immunization with T cell-dependent (TD) antigens such as NP-CGG and NP keyhole limpet hemocyanin (KLH), but not with a T cell-independent (TI) antigen such as NP-Ficoll. The heavy (H) chains from the two monoclonal antibodies 3G6 and 3C6, which bound to the phenolate form and both the phenolate and phenolic forms, respectively, were recombined with lambda 1 chains (L3G6 and L3C6) from these antibodies as well as a lambda 1 chain (LHOPC-1) with the amino acid sequence of the germline. Ability to bind to the phenolate form of NP was recovered in all the reconstituted IgGs, while ability to bind to both the phenolate and phenolic form of NP was observed only with IgG reconstituted from H3C6 and L3C6. These results suggest that the specificity corresponding to early anti-NP antibodies were generated even by lambda 1 chains of a germline sequence, but that of late anti-NP antibodies was expressed only by an appropriate pair of H and L chains. The contribution of amino acid substitution by somatic point mutation to the change of specificity with time was discussed.

Animals

Biliary penetration of cefbuperazone in the presence and absence of obstructive jaundice.

In thirteen patients with normal liver function, the mean concentrations of cefbuperazone in hepatic bile, gall bladder bile and gallbladder tissue 30 min after injection were 1134.8 +/- 36.8 (mean +/- S.E.M.) mg/l, 6.6 +/- 3.0 mg/l and 26.1 +/- 7.6 mg/l, respectively. In patients with obstructive jaundice, cefbuperazone concentrations in bile were 99 +/- 29.2 mg/l (mean +/- S.E.M.) 1 h post-dose and decreased to 13.9 +/- 5.1 mg/l 6 h post-dose. In both groups of patients biliary concentrations of cefbuperazone were higher than the MICs of most organisms causing biliary infection.

Bile