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Biomedical subjects

K Munakata

Publications and source records attributed to K Munakata.

At least 37 records · Page 2Linked to original sources

Role of non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with ulcerative colitis.

The cause of impaired colonic motility in patients with ulcerative colitis (UC) is unknown. The non-adrenergic non-cholinergic (NANC) inhibitory nervous system is one of the most important factors in the enteric nervous system of human gut. To assess the physiological significance of NANC inhibitory nerves in the colon of patients with UC, we investigated the enteric nerve responses of colonic tissues from patients with this disease. Colonic tissues were obtained from the lesional sigmoid colons of six patients with UC. Normal sigmoid colonic tissues obtained from ten patients with colonic cancer were used as controls. A mechanographic technique was used to evaluate in-vitro muscle responses to the electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. NANC inhibitory nerves were found to act on both normal colon and the lesional colon of patients with UC, but colon with UC was more strongly innervated by NANC inhibitory nerves than was the normal colon. These findings suggest that NANC inhibitory nerves play an important role in the impaired motility observed in the colon of patients with UC.

Adult↗

[Therapeutic effect of cefluprenam on polymicrobial urinary tract infection associated with Enterococcus faecalis, using the infectious urolithiasis model in rats].

We examined the therapeutic effect of cefluprenam (CFLP) on the polymicrobial urinary tract infection associated with infectious stones as compared to that of ceftazidime (CAZ), using the experimental polymicrobial urinary tract infection caused by Proteus mirabilis (P. mirabilis), Pseudomonas aeruginosa (P. aeruginosa) and Enterococcus faecalis (E. faecalis). In order to form bladder stones in rats, a sterile zinc ring was implanted as a foreign body, followed by inoculating P. mirabilis E05106 transurethrelly. Thereafter, P. aeruginosa E030033 and E. faecalis 966 were inoculated according to the same way. CFLP or CAZ was administered intravenously twice a day for 5 days. The therapeutic effect was evaluated by the eradication of these bacteria from the urine, the kidney and stones, inhibition of growth of stones, and also a value of BUN. The urinary excretion rates of CFLP and CAZ was also determined (20 mg/kg). In result, CFLP significantly more effective in the eradication of P. mirabilitis, P. aeruginosa and E. faecalis from the urine, the kidney and stones than the control than the control (p < 0.05). Furthermore, CFLP significantly more effective in the eradication of P. aeruginosa from the urine and also E. facalis from the urine and stones (p < 0.05). Meanwhile, CAZ significantly more effective in the eradication of P. mirabilis from the urine, the kidney and stones and also P. aeraginosa from the kidney and stones than the control. However, CAZ did not show eradicative effect on E. faecalis. The urinary excretion rates of CFLP and CAZ at rats were 59.3% and 59.4%, respectively, within 8 hrs after administration, showing a similar excretion pattern. CFLP exhibited the prominent therapeutic effect on polymicrobial urinary tract infection associated with infectious stones caused by P. mirabilis, P. aeruginosa and E. faecalls. On the basis of these results, it has been strongly suggested that CFLP is highly beneficial in the management of intractable polymicrobial urinary tract infectious in clinic.

Animals↗

Relationship between nitric oxide and non-adrenergic non-cholinergic inhibitory nerves in human lower esophageal sphincter.

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the non-adrenergic non-cholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the the role of NO in the human lower esophageal sphincter (LES), enteric nerve responses in lower esophageal tissue specimens obtained from patients with esophageal cancer (n = 7) and patients with gastric cancer (n = 6) were investigated. A mechanographic technique was used to evaluate in vitro LES muscle responses to electrical field stimulation (EFS) of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, including NG-nitro-L-arginine (L-NNA) and L-arginine. Findings were: (1) Cholinergic nerves were those mainly involved in the regulation of enteric- nerve responses to EFS in the steady state, and NANC inhibitory nerves acted on the LES; (2) L-NNA concentration-dependently inhibited the relaxation in response to EFS in the LES; and (3) this inhibitory effect in the LES was reversed by L-arginine. These findings suggest that cholinergic and NANC inhibitory nerves play important roles in regulating contraction and relaxation of the human LES, and that NO plays an important role as a neurotransmitter in NANC inhibitory nerves of the human LES.

Electric Stimulation↗

The role of motilin and cisapride in the enteric nervous system of the lower esophageal sphincter in humans.

To assess the pharmacophysiological significance of the enteric nervous system and the responses of the human lower esophageal sphincter (LES) to motilin and cisapride, the mechanical responses of esophageal tissues from six patients with esophageal cancer and seven patients with gastric cancer were investigated. Circular muscle reactions were recorded to evaluate the in vitro esophageal responses to electrical field stimulation (EFS), motilin, and cisapride, evoking the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. The findings of this study revealed that: cholinergic nerves are mainly involved in the regulation of enteric nerves in the steady state, while non-adrenergic non-cholinergic (NANC) inhibitory nerves also exist; motilin may act both via nerves and also directly on the LES smooth muscle; and cisapride releases acetylcholine from the end of the postganglionic fiber of the cholinergic nerve in human LES thereby inducing contraction of the LES. These results suggest that cholinergic and NANC inhibitory nerves play an important role in human LES, and that motilin and cisapride is clinically useful for improving the impaired LES of patients with gastroesophageal reflux.

Aged↗

Anti-atherogenicity in women does not prevent restenosis after balloon angioplasty.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

Adult↗

Increased accumulation of acidic fibroblast growth factor in left ventricular myocytes of patients with idiopathic cardiomyopathy.

To clarify the pathophysiologic role of fibroblast growth factors in idiopathic cardiomyopathy, we evaluated endomyocardial biopsy specimens obtained from 24 patients (nine with hypertrophic cardiomyopathy [HCM], 12 with dilated cardiomyopathy [DCM], and three with hypertensive hypertrophy) and six controls. All the specimens were stained for acidic fibroblast growth factor (aFGF) and basic FGF (bFGF) with immunohistochemistry. In situ hybridization was carried out for detection of aFGF mRNA. The average diameter of the myocytes, the percent area of interstitial fibrosis, and capillary vessel density were assessed in each biopsy specimen with morphometric methods. Positive staining of aFGF was observed in the myocytes of the biopsy specimens taken from 15 of 21 (71%) patients with cardiomyopathy (six of nine HCM, nine of 12 DCM) and all hypertensive hypertrophy patients but in none of the controls (p < 0.01). The average diameter of the myocytes was significantly larger in the patients with positive aFGF staining than in those with negative staining (23.1 +/- 1.5 versus 18.3 +/- 1.2 microm, p < 0.05). The percent area of fibrosis and the density of capillaries did not differ between the two groups. Intense expression of aFGF mRNA was observed in the myocytes from the patients with positive aFGF protein. In conclusion, the expression of FGF was significantly increased in myocytes obtained from the left ventricle of patients with cardiomyopathy. Acidic FGF may contribute to the hypertrophy of myocytes as the repair response to myocardial injury in patients with idiopathic cardiomyopathy.

Adult↗

Preliminary immunohistochemical new findings in the myenteric plexus of patients with intestinal neuronal dysplasia type B.

In order to investigate the causes of abnormal peristalsis of the colon in intestinal neuronal dysplasia (IND), we studied the structure of the myenteric plexus of IND colon using silver-impregnation (Suzuki's method) as well as the innervation of both IND colons and normal colons using immunofluorescence technique with monoclonal antibodies to synaptic vesicles, and antisera to vasoactive intestinal polypeptide (VIP), substance P (SP), methionine-enkephalin (Met-Enk), and gastrin-releasing peptide (GRP). The following results were obtained. 1) In the IND colon, the number of identifiable myenteric ganglia was decreased. In a few cases of IND, irreversible neuron degeneration can be involved in the pathogenesis of IND. 2) In the IND colon, the distribution and fluorescence intensity of synaptic vesicles coincided with those of peptidergic nerve fibers. In the normal colon, synaptic vesicles were much more numerous in the circular muscle layers than in the longitudinal muscle layers, and the fluorescence intensity of those in the circular muscle layers was stronger than that of those in the longitudinal muscle layers. On the other hand, in IND colon, there were fewer synaptic vesicles in the circular muscle layers, and their fluorescence intensity was weak, while there were many synaptic vesicles in the longitudinal muscle layers, and their fluorescence intensity was strong. 3) Morphological abnormalities may exist in synaptic vesicles in the circular muscle layers of the IND colon. 4) Regarding the peptidergic nerve fibers, in the IND colon, innervation of circular muscle layers by Met-Enk-, GRP- and SP-immunoreactive fibers was reduced, and longitudinal muscles were more strongly innervated by immunoreactive fibers than those in the normal colon. 5) Disturbed innervation of non-adrenergic non-cholinergic excitatory nerves may cause the disturbance of muscle contractions in the IND colon. In addition, an imbalance of peptidergic and synaptic vesicle's innervations in both muscle layers may be related to the abnormal peristalsis of IND colon. Also, morphological abnormalities of synaptic vesicles may be concerned with its abnormal peristalsis.

Adolescent↗

Mitral insufficiency as a complication of acute myocardial infarction and left ventricular remodeling.

The presence of mitral insufficiency after acute myocardial infarction (AMI) often leads to hemodynamic impairment and heart failure. This study was designed to examine the relationship between mitral regurgitation (MR), an indicator of mitral insufficiency, and the course of recovery from AMI. We evaluated the course of MR after AMI in 223 patients by color Doppler echocardiography. MR was detected in 21% (47/223) of patients at the onset of AMI, and developed in 18% (40/223) of patients during follow-up. Patients were grouped according to the course of MR as well as the success of acute recanalization therapy. No correlation was observed between the presence or course of MR and the site of infarction. The incidence of successful recanalization was higher in patients with MR that improved during follow-up than in patients with MR that was unchanged or that worsened during follow-up. Although no significant differences in hemodynamic variables were noted among the groups at admission, the group with unsuccessful recanalization and unimproved MR (BS-) showed a significantly greater left ventricular end-diastolic diameter (LVDd), left ventricular end-systolic diameter, and left ventricular end-diastolic volume (LVEDV) as well as a lower left ventricular ejection fraction than patients with successful recanalization and no MR (CS+) during the convalescent period. The extent of change in LVDd and LVEDV between admission and convalescence was significantly greater in the BS(-) group than in the CS(+) group. The results suggest that successful recanalization after AMI reduces the incidence of MR. Acute recanalization therapy after AMI may prevent left ventricular remodeling, resulting in a secondary improvement of MR.

Aged↗

[Drug-induced laryngospasm].

We report a case of drug-induced laryngospasm due to Chlorpromazine. A drug-induced laryngospasm has not been previously reported in the literature. A 70-year-old male with the proximal end fracture of the femur was scheduled for the operative fixation. He had a past history of alcoholism and had underwent a long-term chlorpromazine therapy for 45 years until admission to our hospital. There have been a few reports on unexplained sudden deaths of patients receiving long-term treatment with chlorpromazine. Caution was therefore needed in general anesthesia, which was thought to be safer than epidural or spinal anesthesia in this case. Accordingly for the preparation of an emergency operation, the central venous catheterization via the internal jugular vein was performed under subcutaneous injection of lidocaine. Severe dyspnea and cyanosis occurred a few minutes after the administration of lidocaine. The specific diagnosis of laryngospasm was made by inspection of the vocal cords. Immediate oral intubation was performed and no complications ensued during and after the operation. This episode strongly suggests that one reason of the unexplained sudden deaths of patients receiving long term treatment with chlorpromazine could be laryngospasm. In conclusion, anesthesiologists should be aware of the possibility of laryngospasm under similar conditions.

Aged↗

[Assessment of left ventricular systolic function derived from ECG-gated myocardial SPECT with 99mTc-tetrofosmin: automatic determination of LV epi- and endocardial surface].

Non-invasive assessment of ischemic heart disease requires information of both LV function and myocardial perfusion. Recently, ECG-gated myocardial SPECT with technetium-labeled radiopharma-ceuticals can provide both of them. Gated myocardial SPECT were performed in thirty-three patients with cardiac disease using a two-headed rotating gamma camera system (ADAC; VERTEX), 30-60 minutes after resting injection of 555-740 MBq of 99mTc-Tetrofosmin. Then, the SPECT data were used to determine the LV epi- and endocardial surface, and LV volume for measurement of LVEF was calculated automatically. This entire computational process required only 210 seconds per 16 frame study. Interobserver agreement of EF values obtained from gated SPECT was excellent (r = 0.996, n = 10, p < 0.01). LVEFs obtained from gated SPECT showed good correlation to those calculated from radionuclide ventriculography (MUGA) (r = 0.91, p < 0.01). In conclusion, this automatic method using gated myocardial SPECT data was considered to be useful for assessment of LV function with reproducibility.

Aged↗

[Prediction of the myocardial contractility improvement on early stage after the revascularization using low-dose dobutamine stress 99mTc-MIBI gated SPECT].

For prediction of recovery of LV contractility, 99mTc-MIBI gated SPECT at rest and that with dobutamine (DOB) loading were performed in 15 patients with myocardial infarction (MI). Regional % uptake (regionalx100/maximal count), % wall thickening [%WT; (ES-ED)x100/ED maximal count], and delta %WT (%WT at DOB stress-%WT at rest) were calculated for each of 8 segments (seg.), including 34 MI out of total 120 seg., which derived from short axis LV count profile. These 34 seg. were divided into two groups, recontractile (18 seg.) and non-recontractile (16 seg.), whether improvement of the wall motion following the intervention (3-5 months) was observed by echocardiography. In the result, there were 7 recontractile seg. in 8 seg. with mildly reduced perfusion (> or = normal mean % uptake-2 S.D.), and there were 11 recontractile seg. in 26 seg. with severe reduced perfusion (< normal mean % uptake-2 S.D.). Moreover, in segments with severely reduced perfusion, there was no significant % uptake difference between recontractile and non-recontractile seg. However, delta %WT of recontractile group (11.1 +/- 4.8%) was significantly higher than that of non-recontractile group (5.7 +/- 2.9%) (p < 0.01). In conclusion, although the improvement of contractility on early stage after the revascularization was sometimes underestimated with only perfusion (% uptake), myocardial DOB response of %WT which were obtained by gated SPECT with MIBI would avoid the underestimation.

Angioplasty, Balloon, Coronary↗

Developmental abnormalities and epimutations associated with DNA hypomethylation mutations.

A number of aberrant morphological phenotypes were noted during propagation of the Arabidopsis thaliana DNA hypomethylation mutant, ddm1, by repeated self-pollination. Onset of a spectrum of morphological abnormalities, including defects in leaf structure, flowering time, and flower structure, was strictly associated with the ddm1 mutations. The morphological phenotypes arose at a high frequency in selfed ddm1 mutant lines and some phenotypes became progressively more severe in advancing generations. The transmission of two common morphological trait syndromes in genetic crosses demonstrated that the phenotypes are caused by heritable lesions that develop in ddm1 mutant backgrounds. Loss of cytosine methylation in specific genomic sequences during the selfing regime was noted in the ddm1 mutants. Potential mechanisms for formation of the lesions underlying the morphological abnormalities are discussed.

Arabidopsis↗

Electrophysiologic assessments in pudendal and sacral motor nerves after ileal J-pouch-anal anastomosis for patients with ulcerative colitis and adenomatosis coli.

PURPOSE: To clarify neurologic function with respect to external anal sphincter and puborectalis muscles after J configuration ileal J-pouch-anal anastomosis for patients with ulcerative colitis and adenomatosis coli, we examined the terminal motor latency in the pudendal and sacral motor nerve (S2-4). METHODS: Latency of the response in the external anal sphincter muscle following digitally directed transrectal pudendal nerve stimulation (PNTML) and in the puborectalis muscle following transcutaneous magnetic stimulation of the cauda equina at the levels S2-4 (SMNLTSS) were measured in 12 patients with ileal J-pouch-anal anastomosis; they were divided into a group with continence (7 cases) and a group with soiling (5 cases). Results were compared with data obtained from 12 patients before operation and 15 controls. RESULTS: Conduction delay of PNTML and SMNLTSS in patients with soiling was longest, followed by delay in those without any soiling, then delay in patients before operation, and then controls. In addition, significant differences were also noted between conduction delay of PNTML in controls and those who are incontinent and experience soiling (P < 0.05 and P < 0.01, respectively), and there were significant differences also noted between conduction delay of PNTML in patients before operation and those who are incontinent and experiencing soiling (P < 0.05 and P < 0.01, respectively). Conduction delay of PNTML and SMNLTSS were found in patients before operation rather than in controls. No significant differences were noted between conduction delay of PNTML and SMNLTSS in patients before operation and controls. Significant differences were also noted between conduction delay of PNTML and SMNLTSS in patients who are incontinent and experiencing soiling (P < 0.01, respectively). CONCLUSION: These findings support the hypothesis that soiling after this procedure may be partially caused by damage to pudendal and sacral motor nerves (S2-4).

Adenomatous Polyposis Coli↗

[ECG-gated myocardial SPECT with 99mTc-MIBI in patients with right ventricular infarction].

Although 99mTc-pyrophosphate (PYP) myocardial scintigraphy has so far been widely used for the diagnosis of right ventricular infarction, PYP accumulation disappears within one week or so. To evaluate the myocardial condition of the right ventricle alternatively, myocardial SPECT with 99mTc-MIBI was performed in 16 patients with acute inferior left ventricular infarction, and ECG-gated myocardial SPECT data acquisition was accompanied in 14 of 16 patients. Right ventricular perfusion defect was observed in 4 of 16 patients (RVI (+) group), and the remains were negative (RVI (-) group). Then, right ventricular count increase rate (RV %WT) of MIBI from end-diastole to end-systole was calculated using an automated method which was developed for quantification of wall thickening in our laboratory. The RV %WT was conceived to be an objective index representing right ventricular contractility. RVI (+) group (n = 3) as compared with RVI (-) group (n = 11) had significant lower RV %WT (26.7 +/- 3.2 vs. 49.6 +/- 14.2; p < 0.01). In conclusion, ECG-gated myocardial SPECT with MIBI was considered to be useful for assessment of myocardial perfusion and contractility of right ventricle.

Aged↗

[ECG-gated dual-isotope myocardial SPECT with 201Tl and 99mTc-tetrofosmin: simultaneous assessment of stress/rest myocardial perfusion and left ventricular function].

ECG-gated dual-isotope acquisition protocol involving rest imaging with 201Tl and stress 99mTc-tetrofosmin (TF) SPECT was designed for the simultaneous assessment of rest/stress myocardial perfusion and rest ventricular systolic function. This study assessed the feasibility and diagnostic accuracy of this protocol. Forty-five patients underwent the dual-isotope SPECT protocol. Twenty minutes after resting injection of 111 MBq of 201Tl, 370 MBq of 99mTc-TF was administered at a peak exercise. The dual-isotope gated SPECT acquisition was performed 1 hour later. Then, the regional count increase rate (%WT) of 99mTc-TF from end-diastole end-systole was calculated using an automated method which was developed for quantification of regional wall thickening based on circumferential profile analysis in our laboratory. Myocardial perfusion and contractility analysis was carried out using 8 segments of left ventricle with comparison of coronary angiographical findings. The sensitivity and specificity for the detection of diseased coronary vessels (> = or 75% stenosis) were 76% and 94%, respectively. Infarcted regions showing reversible defect had significantly greater %WT as compared with those with fixed defects (63 seg; 12.7 +/- 6.1% vs. 36 seg; 8.9 +/- 7.2%, p < 0.01). In conclusion, this dual-isotope protocol has some advantages; i.e., shortening an examination time, having the exact registration of stress/rest perfusion, and simultaneous evaluation of resting regional wall thickening.

Coronary Angiography↗

Terminal motor latency in the pudendal nerves after colectomy with mucosal proctectomy and ileal J pouch-anal anastomosis for ulcerative colitis.

Pudendal nerve terminal motor latencies (PNTML) were measured in eight patients with ulcerative colitis who underwent colectomy with mucosal proctectomy and ileal J pouch-anal anastomosis, using a new digitally directed transrectal stimulation and recording technique, and the results were compared with data obtained from 15 control subjects. The conduction delay of PNTML in the patients with some degree of fecal incontinence was the longest, followed by those without any incontinence, and then the control subjects. These findings support the hypothesis that fecal incontinence after this procedure may be partially caused by damage to the pudendal nerve.

Adolescent↗

Sacral nerve terminal motor latency after ileal J pouch-anal anastomosis for ulcerative colitis.

Using a new transcutaneous magnetic stimulation technique, sacral nerve terminal motor latencies (SNTML) were measured after ileal J pouch-anal anastomosis in eight patients with ulcerative colitis, and the results were compared with those obtained from 15 normal subjects. The conduction delay of the SNTML in patients with soiling was significantly longer than that of the continent group as well as that of normal subjects (P < 0.01). There were no significant differences in the conduction delay between the continent group and the control subjects. These findings therefore support the hypothesis that such soiling, which is sometimes seen after ileal J pouch-anal anastomosis, is partly due to damage to the sacral nerves.

Adolescent↗

A role of nitric oxide in Hirschsprung's disease.

Nitric oxide (NO) has recently been shown to be a neurotransmitter in the nonadrenergic noncholinergic (NANC) inhibitory nerves in the gastrointestinal tract. To clarify the significance of NO in Hirschsprung's disease (HD), enteric nerve responses in colonic tissue obtained from HD patients were investigated. Colonic tissue specimens were obtained from four patients with HD and from 11 patients without constipation who were used as controls. A mechanograph was used to evaluate in vitro colonic responses to electrical field stimulation (EFS) of the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers, and NG-nitro-L-arginine (L-NNA) and L-arginine with the following results: (1) NANC inhibitory nerves were found to act on normal human colon, but had no effect on aganglionic colon; (2) L-NNA concentration dependently inhibited the relaxation in response to EFS in the normal colon, but had no effect on aganglionic colon; and (3) this inhibitory effect was reversed by L-arginine in the normal colon, but had no effect on the aganglionic colon. Nitric oxide mediates the relaxation reaction of NANC inhibitory nerves in the human colon, but the effect of NO was absent in aganglionic colon. The loss of action by NO may be implicated in the impaired motility observed in aganglionic colon.

Adolescent↗