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Biomedical subjects

M Ohmura

Publications and source records attributed to M Ohmura.

At least 37 records · Page 2Linked to original sources

Assessment of right artrial mapping and P wave-triggered signal-average in patients with paroxysmal atrial fibrillation.

To assess right atrial mapping and P wave-triggered signal-averaged electrocardiogram (ECG) in patients with paroxysmal atrial fibrillation (PAF), this study examined right atrial electrograms using atrial mapping and parameters by P wave-triggered signal-averaged ECG in 39 patients without sick sinus syndrome. Subjects were divided into those with PAF (n = 13; 60+/-13 years old) and a control group (n = 26; 49+/-19 years old). The total number of abnormal right atrial electrograms per patient was significantly greater in the PAF group (3.2+/-1.9) than in the control group (1.1+/-0.9; P < .001). The longest duration of right atrial electrogram in the PAF group tended to be greater than that in the control group (P = .06). The filtered P wave duration was significantly longer in the PAF group than in the control group (144+/-21 vs 125+/-14 ms [P < .002]). The values of the root mean square of P wave-triggered signal-averaged ECG 15 ms from the onset (RMSi 15) and 20 ms from the offset (RMSe 20) were significantly lower in the PAF group (1.1+/-0.4 microV, 1.4+/-0.5 microV) than in the control group (1.9+/-1.1 microV [P < .02], 2.1+/-0.9 microV [P < .01]). The total number of right atrial electrograms in patients with RMSi 15 of < or =1.5 microV was significantly greater than in patients with RMSi 15 of >1.5 microV (2.2+/-1.8 vs 1.3+/-1.3 [P < .05]). Thus, the total number of abnormal right atrial electrograms per patient, the total filtered P wave duration, RMSi 15, and RMSe 20 may be good indices of PAF in patients without sick sinus syndrome. RMSi 15 may reflect the total number of the abnormal right atrial electrograms per patient.

Atrial Fibrillation↗

A nontoxic adjuvant for mucosal immunity to pneumococcal surface protein A.

In this study, we demonstrated that pneumococcal surface protein A (PspA) nasally administered with a nontoxic A subunit mutant of cholera toxin (mCT) S61F elicited a protective immune response. Immunization with PspA and mCT elicited higher levels of PspA-specific IgG and IgA Abs in serum and of IgG and IgA anti-PspA Ab-forming cells in spleens, cervical lymph nodes (CLN), and lung tissue when compared to nonimmunized mice. Furthermore, significant PspA-specific IgA Abs were induced in saliva and nasal secretions. These responses were dependent on the use of mCT as a mucosal adjuvant. The PspA-specific Ab responses induced by mCT S61F were comparable with those induced by native CT (nCT). Analysis of cytokine responses showed that nasal PspA plus mCT S61F enhanced the induction of PspA-specific CD4+ T cells producing IL-4 but not IFN-gamma in CLN at both the protein and mRNA levels. Importantly, significant numbers of mice intranasally immunized with PspA plus mCT S61F were protected from lethal challenge with capsular serotype 3 Streptococcus pneumoniae A66. These results show that intranasal administration of PspA together with mCT S61F is an effective mucosal vaccine against pneumococcal infection and induces CD4+ Th2-type cells, which provide help for both mucosal and systemic Ab responses.

Adjuvants, Immunologic↗

Induction of fertile estrus in bitches using a sustained-release formulation of a GnRH agonist (leuprolide acetate).

A single subcutaneous injection of a sustained-release formulation of a potent GnRH agonist, leuprolide acetate (LA; [D-Leu6, Pro9NEt]-GnRH), was evaluated as a method of inducing fertile estrus in 12 mature anestrous and 6 prepubertal beagle bitches. The bitches were treated with microencapsulated LA (100 micrograms/kg, s.c.) at 120 or 150 d post partum, or at 1 yr of age, followed by a GnRH-analogue (fertirelin; [Pro9NEt]-GnRH, 3 micrograms/kg, i.m.) on the first day of induced estrus. Signs of estrus were seen within 10.3 +/- 0.9 d after LA administration in all bitches. The interestrous interval in 120- and 150-d post-partum bitches was shortened (P < 0.05) to 191 +/- 3 and 222 +/- 3 d, respectively, compared with 264 +/- 11 d in control bitches. All LA treated dogs demonstrated behavioral estrus and mated. Three of 6 (50%) at 120 d post partum, 6 of 6 (100%) at 150 d post partum and 5 of 6 (83%) of prepubertal (1-yr old) bitches then became pregnant and produced a mean litter size of 4.1 +/- 0.8 pups. A normal circulating estrogen and progesterone response pattern was observed in mature anestrous bitches. A prepubertal bitch that failed to become pregnant had a similar estrogen response pattern but an insufficient progesterone profile. The results suggest that microencapsulated LA can be useful in inducing fertile estrus in the domestic dogs.

Anestrus↗

Effects of ligation of the internal iliac artery on blood flow to the bladder and detrusor function in rat.

Ischaemia induced by atherosclerosis is a common cause of disorders in the elderly, including impairment of bladder function. To evaluate experimentally the effects of ischaemia on detrusor function, we performed infusion cystometry and evaluated the morphologic findings in the bladder of the rat. Blood flow to the bladder of the rat was evaluated with a Doppler flowmeter before and after the unilateral or bilateral ligation of the internal iliac arteries. Reevaluation was done at one and two weeks after surgery. Bladder function was studied by infusion cystometry performed in vivo under urethane anaesthesia. Finally, histological examination was performed. Blood flow at mid-dorsal wall of the control bladder was inversely related to intravesical volume. Unilateral or bilateral ligation of the internal iliac arteries decreased blood flow to the bladder, which showed a complete recovery two weeks postoperatively. Infusion cystometry of the ischaemic bladder with bilateral ligation of the internal iliac arteries demonstrated a decrease in voiding pressure, an increase in bladder capacity, and an increase in pressure at which micturition was initiated vs. the control. The bladder with unilateral ligation of the artery showed a decrease in voiding pressure, with no change in the other parameters. Histological examination indicated that the bilateral ischaemia and ischaemic side of unilateral ischaemia led to a degeneration of the mucosa, and severe oedema in submucosal and muscle layers one week postoperatively. Degeneration of smooth muscle was predominant at 2 weeks. Contralateral side of the unilaterally ischaemic bladder showed oedema and congestion of the submucosa and smooth muscle. Ligation of the internal iliac artery decreased blood flow to the bladder significantly, which resulted in smooth muscle degeneration. Consequently, in vivo voiding pressure was impaired in the ischaemic bladder.

Animals↗

Does potassium induce the release of nitric oxide in the rabbit corpus cavernosum?

We investigated the effects of increases in the extracellular potassium concentration on the function of the rabbit corpus cavernosum. The resting tissue tension increased as the potassium concentration was increased from 4.7 mM to 20 mM or 30 mM. The maximum contraction induced by 200 microM phenylephrine was significantly decreased in the presence of 30 mM potassium compared with 4.7 mM potassium. After precontraction was induced with 200 microM phenylephrine, the magnitude of field-stimulated relaxation increased significantly as the potassium concentration was increased from 4.7 mM to 10 or 20 mM, but was almost completely abolished at 30 mM potassium. There was no difference in the suppressive effect of L-NAME on field-stimulated relaxation between specimens treated with 4.7 mM or 20 mM potassium. ATP- and bethanechol-induced relaxation was not affected by increases in the extracellular potassium concentration. A high-dose potassium solution (124 mM) induced contraction of the corpus cavernosum. In tissue precontracted with phenylephrine, a high-dose potassium solution that contained phenylephrine induced relaxation of corpus cavernosum; this relaxation was completely suppressed by L-NAME. These findings suggest that small increases in the extracellular potassium concentration increase field-stimulated relaxation of the corpus cavernosum and that this relaxation is not related to the effects of nitric oxide. Relaxation induced by high-dose potassium in tissue precontracted with phenylephrine is probably the result of release of nitric oxide.

Animals↗

[Novel mechanisms for increasing Ca2+ sensitivity of contractile apparatus in smooth muscle].

Smooth muscle contraction is primarily regulated not only by changes in cytosolic Ca2+ concentrations ([Ca2+]i) but also by changes in the force/[Ca2+]i ratio. The use of membrane-permeabilization technique facilitated demonstration of an increase in the level of force at constant [Ca2+]i (Ca2+ sensitization). It was clarified that Rho-associated kinase (Rho-kinase) is a novel mediator of Ca2+ sensitization of the smooth muscle contraction, by introducing the recombinant catalytic domain of Rho-kinase into the cytosol of vascular smooth muscle permeabilized with beta-escin. This review article focuses on novel mechanisms, by which activation of receptor-coupled G-protein(s) increases Ca2+ sensitivity of the contractile apparatus in smooth muscle: Rho-kinase and protein kinase C.

Animals↗

Ca2+-dependent interaction of the growth-associated protein GAP-43 with the synaptic core complex.

The synaptic vesicle exocytosis occurs by a highly regulated mechanism: syntaxin and 25 kDa synaptosome-associated protein (SNAP-25) are assembled with vesicle-associated membrane protein (VAMP) to form a synaptic core complex and then synaptotagmin participates as a Ca2+ sensor in the final step of membrane fusion. The 43 kDa growth-associated protein GAP-43 is a nerve-specific protein that is predominantly localized in the axonal growth cones and presynaptic terminal membrane. In the present study we have examined a possible interaction of GAP-43 with components involved in the exocytosis. GAP-43 was found to interact with syntaxin, SNAP-25 and VAMP in rat brain tissues and nerve growth factor-dependently differentiated PC12 cells, but not in undifferentiated PC12 cells. GAP-43 also interacted with synaptotagmin and calmodulin. These interactions of GAP-43 could be detected only when chemical cross-linking of proteins was performed before they were solubilized from the membranes with detergents, in contrast with the interaction of the synaptic core complex, which was detected without cross-linking. Experiments in vitro showed that the interaction of GAP-43 with these proteins occurred Ca2+-dependently; its maximum binding with the core complex was observed at 100 microM Ca2+, whereas that of syntaxin with synaptotagmin was at 200 microM Ca2+. These values of Ca2+ concentration are close to that required for the Ca2+-dependent release of neurotransmitters. Furthermore we observed that the interaction in vitro of GAP-43 with the synaptic core complex was coupled with protein kinase C-mediated phosphorylation of GAP-43. Taken together, our results suggest a novel function of GAP-43 that is involved in the Ca2+-dependent fusion of synaptic vesicles.

Amino Acid Sequence↗

Baculovirus-insect cell production of bioactive porcine FSH.

The in vitro and in vivo bioactivity of recombinant porcine FSH (rpFSH) produced from insect cells through use of a baculovirus expression system were studied and compared with those of natural FSH preparations. Determination of in vitro bioactivity, using the rat Sertoli cell aromatase bioassay, indicated that rpFSH is as active as purified pituitary FSH. Determination of in vivo bioactivity, using the mouse uterine weight bioassay, indicated that rpFSH is as active as purified pituitary FSH. Using the mouse Leydig cell testosterone bioassay, it was demonstrated that the intrinsic LH bioactivity of rpFSH is negligible. The increases in ovarian and uterine weight, and the stimulation in follicular growth in immature hypophysectomized rats induced by rpFSH supplemented with hCG were comparable to those induced by natural FSH preparations. Furthermore, rpFSH alone in hypophysectomized mice stimulated preantral follicular growth to preovulatory stages, and the subsequent injection of hCG caused ovulation. These results demonstrate that in vitro and in vivo biological characteristics of rpFSH produced from baculovirus-insect cells are indistinguishable from those of FSH isolated from natural sources.

Journal Article↗

Simple technique for pancreatogastrostomy and the histological findings of pancreatogastric anastomosis.

The leakage of pancreatic juice is the most serious complication after pancreatoduodenectomy. In an attempt to lessen the incidence of this complication, we have developed a simple technique for the anastomosis of pancreatogastrostomy. Since March 14, 1995, we have already performed surgical procedures on 8 cases of pancreatogastrostomy using this technique and as yet have never experienced fatal complications. We report the autopsy findings of pancreatogastric anastomosis histologically. The specimen taken from the anastomosis reveals good mucosal continuity. This result suggests the importance of reliable sutures between the pancreatic parenchyma and the full thickness of the gastric wall for the anastomosis of pancreatogastrostomy.

Adenocarcinoma↗

Elevated concentrations of the small stress protein HSP27 in rat renal tumors.

The expression of two small stress proteins, alpha B crystallin and the 27-kDa heat shock protein (HSP27), was studied quantitatively and immunohistochemically in normal kidney and renal tumors in rats. Levels of alpha B crystallin in renal cell tumors tended to be higher than in normal kidney (P = 0.07), but with a wide range of values, whereas they were significantly lower in mesenchymal tumors (P < 0.0001). In contrast, HSP27 concentrations in both renal cell (mean +/- SD: 1790 +/- 940 ng/mg protein, n = 15) and mesenchymal (1260 +/- 1080 ng/mg protein, n = 10) tumors were significantly higher than the normal kidney value (142 +/- 30 ng/mg protein, n = 10, P < 0.0001). A positive correlation was found between alpha B crystallin and HSP27 levels limited to the renal cell tumor case (Pearson's correlation coefficient, r = 0.68, P < 0.01). Immunohistochemistry revealed the loops of Henle to be positive for alpha B crystallin, whereas HSP27 staining was positive in glomerular and interstitial vascular walls and epithelial cells of proximal and distal tubules. Positive immunostaining for alpha B crystallin was demonstrated in six of nine renal cell tumors (67%) studied and for HSP27 in all of the nine cases (100%).

Animals↗

Restoration of rat bladder function following release of short- and long-term partial outflow obstruction.

Detrusor dysfunction does not recover in some patients with benign prostatic hyperplasia (BPH) even after prostate resection. 'We studied the functional restoration of the rat bladder after release of short- or long-term outflow obstruction. Bladder function was assessed by in vivo infusion cystometry and an in vitro organ bath technique. There were no significant differences in bladder weight and contractile strength induced by stimuli in detrusor muscle strips from obstructed rats and age-matched control rats. After short-term obstruction the whole bladder pressure generated in vitro by field stimulation, bethanechol, ATP, and KCl completely recovered to control levels. In contrast, after long-term obstruction, the whole bladder pressure in response to field stimulation remained significantly lower than in controls. Infusion cystometry variables, including the pressure at which micturition was induced, maximal voiding pressure, capacity, and residual urine volume, were similar between controls and rats subjected to short-term obstruction. However, the maximal voiding pressure after long-term obstruction was significantly less than that of controls.

Adenosine Triphosphate↗

Effect of ischemia and partial outflow obstruction on rat bladder function.

We investigated the effects of ischemia induced by ligation of the bilateral internal iliac arteries following partial outlet obstruction on changes in detrusor function in rat. Rats were divided into three groups: sham-operated control rats, rats with partial outlet obstruction, and rats with obstruction+ischemia. Bladder function was studied by the in vitro organ bath technique 7 days after surgery. The weight of the bladder was significantly increased in both the obstruction and obstruction+ischemia groups. The obstruction+ischemia group exhibited a greater increase in weight. The passive length-tension relationship of detrusor muscle strips showed that tissue elasticity was decreased and the active length-tension relationship demonstrated that the peak response was observed at a shorter tissue length in the obstruction+ischemia group compared with the other two groups. There was no difference in the passive and active length-tension relationships between the control group and the obstruction group. The contractile response to various kinds of stimulation (field stimulation, bethanechol, ATP, and KCl) increased in the obstruction group and decreased in the obstruction+ischemia group. These findings suggest that partial outflow obstruction alone increased bladder contractility in response to stimuli. However, ischemia reduced the contractility and elasticity of the bladder wall.

Animals↗

Effects of ethanol on responses of isolated rabbit urinary bladder and urethra.

BACKGROUND: Acute ethanol ingestion increases the risk of urinary retention in patients with benign prostatic hyperplasia (BPH). To elucidate the mechanism of this effect, we investigated the in vitro effects of ethanol on lower urinary tract function in rabbits. METHODS: The responses to various stimuli of muscle strips isolated from male rabbit bladder and urethra were determined in the presence of 0%, 0.5%, 1.0%, and 3.0% ethanol. RESULTS: Basal tension of tissue strips taken from the bladder and the urethra was reduced by ethanol in a dose-dependent manner, as were bladder contractions induced by field stimulation, bethanechol, and ATP. Ethanol also reduced phenylephrine-induced contractions of the prostatic urethra. A high (3%) concentration of ethanol significantly reduced KCl-induced contraction of both the bladder and urethra, as well as urethral relaxation induced by field stimulation following contraction with 200 mumol/L phenylephrine. CONCLUSION: Responsiveness of the rabbit lower urinary tract was significantly reduced by exposure to ethanol. A similar decrease in tonus and contractility of the detrusor and inhibition of relaxation in the prostatic urethra may lead to urinary retention in men following acute ingestion of ethanol.

Adenosine Triphosphate↗

Renal fossa recurrence of a renal cell carcinoma 13 years after nephrectomy: a case report.

Between 1980 and 1995, we performed a nephrectomy with curative intent on 183 patients with renal cell carcinoma at Nagoya University Hospital. Among these patients, 5 (2.7%) developed renal fossa recurrence (median follow-up, 65 months). We report a case of such a recurrence found 13 years after a nephrectomy for renal cell carcinoma (stage pT3a, pN0, M0). A 62-year-old female presented with a nodule on her back. Computed tomography and magnetic resonance imaging revealed a mass in the right back and retroperitoneum, and a biopsy revealed the tumor to be a renal cell carcinoma. Complete resection was performed, followed by administration of alpha-interferon. The patient is doing well 16 months after the operation. The case illustrates that very long-term follow-up after a nephrectomy is mandatory for patients with perinephric invasion of a renal cell carcinoma due to the risk of renal fossa recurrence.

Biopsy↗

Effect of mucosal resection on detrusor function in the disused rabbit bladder.

A new rabbit model of disused bladder was developed. Disused bladders were created by sagittal splitting of the bladders along the midline and closure of one side (reservoir side), leaving the remaining side unclosed (disused). The mucosa was dissected from some of the disused sides. Tissue elasticity and the weight of the detrusor muscle were decreased by bladder disuse. The responsiveness to field stimulation, bethanechol, ATP, KCl, or isoproterenol, was decreased by disuse. Tissue elasticity and responsiveness to stimuli were decreased to a lesser extent in disused tissue with intact mucosa. Results suggest that the bladder mucosa helps to preserve the function of the disused bladder.

Animals↗

Response of isolated human neurogenic bladders to tachykinins.

Tachykinins act as stimulants of the isolated urinary bladder. However, the efferent role of tachykinins on detrusor function is controversial. We investigated the contractility of isolated human neurogenic bladders taken from patients with myelomeningocele or sacral agenesis, and tested the response to neurokinin A (NKA), neuromedin K (NKB), and substance P (SP). The contractile strengths were compared with normal controls. All tachykinins investigated induced significant contractions in both neurogenic and control bladders. The rank order of contractile potency was the same in both groups, namely, NKA > NKB > SP. The contraction induced by SP was not affected by atropine, but was completely blocked by [Sar9,Met(O2)11]-SP (a SP antagonist). Responses to electrical field stimulation were not changed by the SP antagonist. The contractile magnitude to field stimulation was also not altered by administration of 10(-6) M tachykinins. Responses of the neurogenic bladder to NKA and SP were significantly greater than the control. There were no differences in the response to KCl administration between the 2 groups. We conclude that hypersensitivity to NKA and SP in neurogenic bladders may contribute to bladder dysfunction in patients with sacral cord lesions.

Adolescent↗

Effects of partial outflow obstruction on bladder contractility and blood flow to the detrusor: comparison between mild and severe obstruction.

Detrusor dysfunction secondary to partial outflow obstruction is caused in part by decreased blood flow to the detrusor. We investigated changes in blood flow to the bladder and in bladder function after inducing partial outflow obstruction. The urethras of male Sprague-Dawley rats were constricted by sutures to degrees representing either mild and severe obstruction. Blood flow to the bladder was measured by a Doppler flowmeter prior to and 7 days after obstruction. In vivo and in vitro experiments were performed 7 days after surgery. After cystometry was used to determine bladder capacity, the pressure at which micturition was induced, and maximum voiding pressure, the bladder was removed and placed in an organ bath where increases in intravesical pressure in response to field stimulation were evaluated. Finally, volume-pressure studies were performed in order to determine passive detrusor compliance and response to field stimulation at each specific capacity in vitro. Although blood flow to the bladder was significantly decreased by severe obstruction, no differences in blood flow between control and mildly obstructed bladders was observed. While maximum voiding pressure decreased in severely obstructed bladders, both the pressure at which micturition was induced and bladder capacity were increased. The response to field stimulation was increased by mild obstruction but decreased by severe obstruction, although bladder compliance was increased by both. The peak response to filled stimulation was observed at a larger capacity in severely obstructed bladders than the others. In conclusion, when outflow obstruction was mild, blood flow to the bladder remained unchanged and detrusor contractility increased. On the other hand, severe obstruction decreased bladder blood flow and induced deterioration of detrusor function.

Animals↗