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Biomedical subjects

S Hashimoto

Publications and source records attributed to S Hashimoto.

At least 991 records · Page 55Linked to original sources
PubMed1988

The Ins(1,4,5)P3-sensitive Ca2+ store of non-muscle cells: endoplasmic reticulum or calciosomes?

The binding of a number of extracellular ligands (hormones, growth factors, neurotransmitters etc.) to their plasma membrane receptors causes hydrolysis of phosphatidylinositol bisphosphate to initiate the formation of two second messengers, inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] and diacylglycerol, DAG. DAG has been shown to activate protein kinase C, whereas Ins(1,4,5)P3 induces the release of Ca2+ from an intracellular pool. This rapidly mobilizable, Ins(1,4,5)P3-sensitive Ca2+ store has until now been identified as the endoplasmic reticulum, ER. We demonstrate that this is untenable and provide evidence for the existence of an unrecognized organelle, the 'calciosome'. This conclusion is based on the following experimental evidence. (1) There is no correlation between the abundance of ER and the amount Ins(1,4,5)P3-sensitive Ca2+ release. (2) There is no correlation between ER markers and those for the Ca2+ store [Ins(1,4,5)P3 binding and sensitivity, Ca2+ uptake]. (3) A protein similar to striated muscle calsequestrin, CS, has been identified in microsomal fractions from a number of tissues; it copurifies with markers of the Ca2+ store, but not with those of ER. (4) Subcellular localization of the CS-like protein by electron microscopy reveals that in all cells so far analysed this protein is localized in small, membrane-enclosed structures, calciosomes, which are also stained by an anti-Ca2+-ATPase antibody. Calciosomes appear to be morphologically distinct from any other known cell organelle. (5) Although they stain different portions of the calciosomes (membrane and lumen, respectively), anti-Ca2+-ATPase and anti-CS antibodies do not recognize any antigen in ER cysternae; antibodies directed against known components of ER do not bind to calciosomes.

Animals↗
PubMed1988

[Effects of (+/-)-4'-ethyl-2-methyl-3-(l-pyrrolidinyl) propiophenone hydrochloride (HY-770) on the bladder function].

The effects of HY-770 on micturition reflexes in rats, dogs and cats and urethral pressure in dogs were compared with those of flavoxate.HC1 (flavoxate), terodiline.HCl (terodiline) and oxybutynin.HCl (oxybutynin). 1) HY-770, in intravenous (2 and 4 mg/kg) and intraduodenal (12.5 and 25 mg/kg) administrations, dose-dependently abolished the rhythmic bladder contractions in anesthetized rats. The activity of HY-770, in intravenous administration (i.v.), was almost equal to those of flavoxate, terodiline and oxybutynin; and the activity of HY-770, like terodiline, was more potent than that of flavoxate in intraduodenal administration (i.d.). 2) In the cystometrograms, HY-770 (3, 4 or 8 mg/kg, i.v.) dose-dependently increased the time to micturition (capacity of bladder) without decreasing the amplitude of micturition contraction in anesthetized rats, dogs and cats, and HY-770 (25 mg/kg, i.d.) also increased the capacity in anesthetized cats. 3) HY-770 (4 and 8 mg/kg, i.v.) dose-dependently increased the capacity of the bladder in the cystometrograms of pollakiuria induced by either transection of both the hypogastric nerves or chronic cannulation to the bladder in anesthetized or conscious rats, respectively. 4) HY-770 (25 mg/kg, i.d.) slightly decreased the urethral pressure in anesthetized dogs. These results suggest that HY-770 is a promising drug for the treatment of pollakiuria induced by a neurogenic bladder or unstable bladder, etc.

Animals↗
PubMed1988

Pharmacological studies on the selectivity of HV-723, a new alpha-1 adrenoceptor antagonist.

The pharmacological profile of a new alpha-1 adrenoceptor antagonist, alpha-ethyl-3,4,5-trimethoxy-alpha-(3-((2-(2-methoxyphenoxy)ethyl)amino) propyl) benzene-acetonitrile fumarate (HV-723), was studied in vitro. In dog mesenteric arteries, HV-723, prazosin and yohimbine competitively inhibited noradrenaline-induced contraction: the pA2 value of HV-723 (9.37) was apparently larger than that of prazosin (8.22) and yohimbine (7.18). However, HV-723 showed no or only a slight inhibition on the contractile responses to 5-HT, KCl and prostaglandin F2 alpha. HV-723 also showed potent alpha-1 adrenoceptor antagonist activity in the dog mesenteric and saphenous veins. However, HV-723 showed little antagonist activity on the pre- and postsynaptic alpha-2 adrenoceptors, beta-1 and beta-2 adrenoceptors and muscarinic receptors. HV-723 also inhibited the sympathetic contraction induced by electrical transmural stimulation in the dog mesenteric arteries, and the inhibition of HV-723 was about 10 times more potent than that of prazosin. However, 3H-noradrenaline release evoked by electrical stimulation was not influenced by HV-723. These results clearly show that HV-723 is a potent and selective alpha-1 adrenoceptor antagonist.

Acetonitriles↗
PubMed1988

Role of protein kinase C in the vesicular release of acetylcholine and norepinephrine from enteric neurons of the guinea pig small intestine.

The involvement of protein kinase C in the release of [3H]acetylcholine (ACh) and [3H]norepinephrine (NE) was studied in strips of guinea pig small intestine. 12-O-tetradecanoyl phorbol 13-acetate (TPA), but not 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD) potentiated the A23187-evoked release of [3H]ACh and [3H]NE from the strips of small intestine preloaded with [3H]choline and [3H]NE, and the potentiating effect of TPA was inhibited by polymyxin B. High K+-evoked releases of [3H]ACh and [3H]NE in the presence of tetrodotoxin were also potentiated by TPA. These TPA-induced potentiations of the evoked release were greater at a low concentration of external Ca2+ (0.5 mM) than at a high concentration (2 mM). Ouabain induced the release of these neurotransmitters both in the absence and presence of the low concentration of external Ca2+. The ouabain-evoked release was not altered by TPA. These results indicate that the activation of protein kinase C potentiates the vesicular release of ACh and NE at low Ca2+ concentration from the nerve terminals of enteric neurons in the guinea pig small intestine.

Acetylcholine↗
PubMed1988

Blood vascular organization of the human appendix: a scanning electron microscopic study of corrosion casts.

Blood vascular beds of the human appendix were reproduced with a methacrylate casting medium and observed with a scanning electron microscope. The appendix received some small afferent arterial branches of the appendicular artery. These small arterial branches pierced the muscular layer and reached the submucosal plexus. Small arterioles arising from this plexus, climbed the mucosa and formed honeycomb-like capillary meshes at the luminal surface level. These capillaries were drained by the collecting veins, which descended the mucosa and joined the submucosal plexus. The large efferent veins arising from the submucosal plexus passed through the muscular layer and continued with the appendicular vein. In the mucosal and submucosal layers, several spherical basket-like casts of the germinal center (lymphoid follicle) were seen. In the parafollicular region (primary follicle), casts of postcapillary venules with prominent surface undulations were relatively frequently observed.

Adult↗
PubMed1988

Intraventricular arachnoid cyst. Report of two cases.

Two patients with intraventricular arachnoid cysts are reported and a brief review of the relevant literature is presented. Arachnoid cysts are usually extracerebral or extraventricular. Intraventricular arachnoid cysts are rare: including the two cases reported here, only five cases have been described. The following characteristics were noted in these five patients: all were young; headache was the initial symptom in four; the cyst was in the trigone of a lateral ventricle in four; and there was dilatation of the inferior horn in three.

Adult↗
PubMed1988

Effect of adenosine triphosphate on canine renal circulation.

The effect of adenosine triphosphate (ATP) on systemic and renal hemodynamics was studied in seven dogs anesthetized with pentobarbital and enflurane. Adenosine triphosphate was given via the vena cava, the left atrium, and the abdominal aorta close to the left renal artery. Bolus injection of ATP in the vena cava showed a dose-dependent decrease of mean arterial pressure and renal blood flow, while cardiac output showed only a slight change. Continuous infusion of ATP in the vena cava or the left atrium showed stable hypotension, decrease of renal blood flow, with slight change of cardiac output. Despite the decrease of total peripheral resistance (TRP), renal vascular resistance (RVR) increased significantly in all cases. However, the continuous infusion of ATP into the abdominal aorta close to the left renal artery caused variable responses of systemic arterial pressure and a significant decrease of the RVR. These results suggest that ATP has a renal vasodilator effect only when given directly into the renal artery, and that a renal vasoconstriction occurs responding to the systemic effect of ATP when ATP is given intravenously or into the left atrium.

Adenosine Triphosphate↗
PubMed1988

[Recent advances in tumor-seeking agents--radioimmunoimaging of cancers using monoclonal antibodies].

Development of biotechnology has made it possible to produce monoclonal antibodies (MoAbs) which associate with tumors. Injected RN-labeled MoAbs would be expected to accumulate in specific tumors. This concept can be evaluated not only from the point of diagnosis but also the therapy of cancers. Before applying RN-labeled MoAbs to patients with cancers, certain factors influencing radioimmunodetection should be investigated, such as (1) Labeling nuclides:RN should be selected by considering its physical properties. Biodistributions of RN-labeled MoAbs differ from one RN to another. (2) Labeling method: labeling techniques and optimum conditions should be established for each MoAb, in order to retain the immunoreactivity and stability of RN-labeled MoAb in vivo. (3) Circulating antigen:RN-labeled MoAb, once injected, may be challenged by the circulating antigen in the blood. We found that uptake of MoAbs against tumor markers (AFP, DU-PAN II) into tumors (hepatoma or pancreatic tumor) was decreased, and that the background activity was increased when the concentration of AFP or DU-PAN II in the blood was high. In addition to this fundamental information with respect to each MoAb, some clinical considerations are necessary for the application of RN-MoAbs to humans, mainly possible side effects. Clinical applications of immunoscintigraphy have not been well developed in Japan, although more than 2,000 cases utilizing this technique have been reported in Europe. In Europe and the U.S.A., tumors were detected with about 70% positivity without any serious side effects. General concerns regarding MoAb products, which have been proposed by the FDA, are also discussed in this paper.

Antibodies, Monoclonal↗
PubMed1988

Experimental in vivo regeneration of peripheral nerve axons and perineurium guided by resorbable collagen film.

In our previous paper, we reported a marked advantage in using collagen gel matrix available for cell culture in combination with a silicone tube as an effective environment for axonal sprouting during peripheral nerve regeneration. In the present experiment, collagen film was substituted for the silicone tube because of its non-toxicity, biocompatibility and better availability. Also, the surgical procedure was simplified, using a fibrin adhesive system instead of suturing. In the second postoperative week, severed proximal and distal stumps became joined together concomitantly with absorption of the collagen matrix and film. On size-frequency histograms, the diameters of both myelinated and unmyelinated axons at 8 weeks after surgery had recovered to their normal ranges. These findings demonstrate that this procedure of enveloping a collagen matrix and severed nerve stumps in bioresorbable collagen film would be an ideal way of forming a perfect perineurium. The regeneration of peripheral nerve axons resulted in normal thickness of the original nerve bundle without exception, unlike the axons on the control side.

Animals↗
PubMed1988

Immunocytological identification of the microsomal calcium store of nonmuscle cells.

The biochemical and functional similarities between skeletal muscle sarcoplasmic reticulum and the microsomal Ca2+ store of nonmuscle cells are discussed. It is shown that antibodies raised against two characteristic proteins of sarcoplasmic reticulum, Ca2+ ATPase and calsequestrin, recognize similar proteins in nonmuscle cells. The subcellular distribution of these two antigens was studied at the subcellular levels in ultrathin cryosections. In a variety of cell types these two proteins were found to be localized in small membrane enclosed vesicles, apparently distinct from other known organelles. We propose that these newly recognized structures (calciosomes) represent the functional equivalent of sarcoplasmic reticulum in nonmuscle cells.

Animals↗
PubMed1988

Benzodiazepines and barbiturate potentiate the pre- and postsynaptic gamma-aminobutyric acid (GABA)A receptor-mediated response in the enteric nervous system of guinea pig small intestine.

To determine whether or not presynaptic gamma-aminobutyric acid (GABA) receptors regulate the release of GABA, we examined properties of the presynaptic GABA receptor and compared the findings within the case of the postsynaptic GABA receptor, using the longitudinal muscle with myenteric plexus (L-M) preparation of guinea pig small intestine. Muscimol, but not baclofen, reduced the Ca++-dependent release of [3H]GABA evoked by high K+ in the presence of tetrodotoxin from L-M preparation of the small intestine preloaded with [3H]GABA. Bicuculline, picrotoxin and furosemide antagonized the effect of muscimol. Diazepam, clonazepam and pentobarbital potentiated the muscimol-induced inhibition of high K+-evoked release of [3H]GABA. The potentiating effect of clonazepam was antagonized by Ro 15-1788. Muscimol induced a Ca++-dependent and tetrodotoxin-sensitive release of [3H]acetylcholine from L-M preparation preloaded with [3H]choline. The effect of muscimol was antagonized by bicuculline, picrotoxin and furosemide. Diazepam, clonazepam and pentobarbital potentiated the muscimol-evoked release of [3H]ACh. The potentiation of muscimol effect by clonazepam was inhibited by Ro 15-1788. These results indicate that both the GABA autoreceptor and postsynaptic receptor may possess the same property which is related to benzodiazepine and barbiturate binding sites in the enteric nervous system of the guinea pig small intestine. The benzodiazepine binding site seems to be of central type.

Acetylcholine↗
PubMed1988

[Mechanism of production of pulse deficit in atrial fibrillation: assessment by blood flow dynamics].

Pulse deficit in patients with atrial fibrillation is caused by the reduction of preload. The purpose of this study was to visualize the mechanism in view of blood flow dynamics using pulsed Doppler echocardiography. The subjects were 15 cases with atrial fibrillation and pulse deficit, and the results were as follows: 1. Simultaneous recordings of the carotid pulse wave (CPW) and blood flow at the left ventricular inflow tract indicated that, in nine of the total 15 cases, CPW disappeared from the cardiac cycle even with sufficient preceding RF in the other six cases (Group B). 2. In Group A, %RF correlated well with %CPW; however, there was poor correlation between them in Group B. Moreover, CPW was always greater than 26% if RF was greater than 50% of each mean value in Group A, but less than 25% in Group B, suggesting poor left ventricular ejection in the latter group. 3. The left ventricular ejection fraction (EF) and %fractional shortening (%FS) decreased significantly in Group B compared to those in Group A (EF; 59 +- 7 vs 41 +- 12%, p less than 0.01, %FS; 31 +- 5 vs 20 +- 6, p less than 0.01). These findings indicate that left ventricular contractility was significantly reduced in the cases with pulse deficit in Group B. 4. Systolic backward flow in the mid-ventricle caused by left ventricular asynchrony due to localized apical wall motion abnormalities was observed in all 15 cases. The heart rate during pulsed Doppler echocardiography was significantly increased in Group A as compared to that in Group B.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗