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Biomedical subjects

M Hongo

Publications and source records attributed to M Hongo.

At least 55 records · Page 3Linked to original sources

Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome.

BACKGROUND: Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals. AIMS: To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with irritable bowel syndrome (IBS) have an exaggerated response to CRH. SUBJECTS: Ten IBS patients diagnosed by Rome criteria and 10 healthy controls. METHODS: CRH (2 micrograms/kg) was intravenously administered during duodenal and colonic manometry and plasma adrenocorticotropic hormone (ACTH) was measured by radioimmunoassay. RESULTS: CRH induced motility of the descending colon in both groups (p < 0.001) and induced greater motility indexes in IBS patients than in controls (p < 0.05). CRH produced duodenal phase III motor activity in 80% of the subjects and duodenal dysmotility in 40% of IBS patients. Abdominal symptoms evoked by CRH in IBS patients lasted significantly longer than those in controls (p < 0.05). CRH induced significant increases in plasma ACTH levels in both groups (p < 0.001) and produced significantly higher plasma ACTH levels in IBS patients than in controls (p < 0.001). CONCLUSION: Human intestinal motility is probably modulated by exogenous CRH. The brain-gut in IBS patients may have an exaggerated response to CRH.

Adrenocorticotropic Hormone↗

Effects of growth hormone and IGF-I on cardiac hypertrophy and gene expression in mice.

Cardiac hypertrophic and contractile responses were studied in mice administered growth hormone (GH) and insulin-like growth factor (IGF-I) (8 mg . kg-1 . day-1), alone or in combination (IGF-I/GH), for 2 wk. Also, changes in expression of selected left ventricular (LV) genes in response to IGF-I/GH were compared with those in other forms of cardiac hypertrophy. GH or IGF-I alone at three to four times the usual dose in rats failed to produce increases in heart and LV weights and hemodynamic effects; however, IGF-I/GH was synergistic, increasing body weight and LV weights by 39 and 35%, respectively. A measure of myocardial contractility (maximal first derivative of LV pressure, catheter-tip micromanometry) was increased by 34% in the IGF/GH group, related in part to a force-frequency effect, since the heart rate increased by 21%. Other mice were treated surgically to produce pressure overload (transverse aortic constriction) or volume overload (arteriovenous fistula) for 2 wk; LV weights were then matched to those in the IGF-I/GH group, and mRNA levels of selected markers were assessed. In contrast to the increased mRNA levels of atrial natriuretic factor, alpha-skeletal actin, and collagen III generally observed in overloaded hearts, changes in IGF-I/GH-treated mice were not significant. Thus high-dose IGF-I/GH produce cardiac hypertrophy and a positive inotropic effect without causing significant changes in expression of fetal and other selected myocardial genes, suggesting that this hypertrophy may be of a more physiological type than that due to mechanical overload.

Actins↗

Effect of rabeprazole (E3810), a novel proton pump inhibitor, on intragastric pH in healthy volunteers.

In this study, we examined the effect of rabeprazole (E3810), a novel proton pump inhibitor, on gastric acidity under physiological conditions in healthy volunteers using 24-hour intragastric pH monitoring. Twenty-four-hour intragastric pH monitoring was performed three times to seven subjects randomly assigned in a cross over fashion to one of the following groups; without drug administration (basal), and with 10 mg or 20 mg of rabeprazole for four days. The median pH for 24 hours was 2.15 in the basal study, while the corresponding median pH were 5.05 and 5.90 after treatment with 10 mg and 20 mg of rabeprazole, respectively. Significant differences in the median pH were observed between the basal study and that after administration of the 10 mg and 20 mg doses of rabeprazole. The cumulative percentage of pH readings above the threshold pH 4 value, was 34.1% in the basal study, and 72.6% and 78.3% after treatment with 10 mg and 20 mg doses of rabeprazole, respectively. This result indicates that the efficacy of rabeprazole allows for substantial control of gastric acidity with once-daily dosing, and that both the 10 mg and 20 mg doses result in potent inhibition of gastric acid secretion.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Brain-gut induction of heat shock protein (HSP) 70 mRNA by psychophysiological stress in rats.

Restraint water-immersion stress-induced expression of heat shock protein (HSP)70 mRNA in the cerebral cortex and stomach of rats was evaluated by Northern blotting. Cerebral and gastric HSP70 mRNA significantly increased in the 6 h-stressed rats and the amount of mRNA measured as optical densities was highest in the 12 h-stressed rats. These data confirmed our previous observations and suggest that families of HSPs play a salient cytoprotective role in stress-vulnerable organs.

Animals↗

MLP-deficient mice exhibit a disruption of cardiac cytoarchitectural organization, dilated cardiomyopathy, and heart failure.

MLP is a LIM-only protein of terminally differentiated striated muscle cells, where it accumulates at actin-based structures involved in cytoarchitecture organization. To assess its role in muscle differentiation, we disrupted the MLP gene in mice. MLP (-/-) mice developed dilated cardiomyopathy with hypertrophy and heart failure after birth. Ultrastructural analysis revealed dramatic disruption of cardiomyocyte cytoarchitecture. At birth, these hearts were not hypertrophic, but already abnormally soft, with cell-autonomous and MLP-sensitive alterations in cytoarchitecture. Thus, MLP promotes proper cardiomyocyte cytoarchitecture, whose perturbation can lead to dilated cardiomyopathy. In vivo analysis revealed that MLP-deficient mice reproduce the morphological and clinical picture of dilated cardiomyopathy and heart failure in humans, providing the first model for this condition in a genetically manipulatable organism.

Animals↗

Iodine-123 metaiodobenzylguanidine scintigraphic assessment of myocardial sympathetic innervation in patients with familial amyloid polyneuropathy.

OBJECTIVES: This study attempted to assess myocardial sympathetic innervation using iodine-123 (I-123) metaidobenzylguanidine (MIBG) imaging in patients with familial amyloid polyneuropathy. BACKGROUND: Signs and symptoms of cardiac autonomic dysfunction are commonly seen in patients with cardiac amyloidosis. However, the incidence and magnitude of abnormalities in myocardial sympathetic nerve function by means of I-123 MIBG imaging and their relation to clinical findings, cardiac function and the results of thallium-201 (Tl-201) and technetium-99m pyrophosphate (Tc-99m PYP) myocardial scanning have not yet been clarified. METHODS: We performed M-mode, two-dimensional and Doppler echocardiography and I-123 MIBG, Tl-201 and Tc-99m PYP imaging of the heart in 12 patients with familial amyloid polyneuropathy and biopsy-proved cardiac amyloidosis. RESULTS: Ten of 12 patients had no clinical evidence of overt heart disease, but left ventricular (LV) wall thickening was observed in 4 of these 10. Left ventricular percent fractional shortening and Doppler transmitral flow velocity patterns were found to be normal in all 12 patients. Eight of 12 patients showed no myocardial MIBG accumulation, with limited uptake in the remaining 4 demonstrated only in the LV anterior wall. Diffuse but mild myocardial uptake of Tc-99m PYP occurred in only 4 of 12 patients, and all 12 had normal results on Tl-201 myocardial scanning. Complete defects on myocardial MIBG scans were found in five of eight patients with negative findings on Tc-99m PYP myocardial scanning. The incidence and magnitude of myocardial uptake of MIBG were independent of clinical findings, extent of endomyocardial amyloid deposition, electrocardiographic QRS voltage and ventricular wall thickness. CONCLUSIONS: Patients with familial amyloid polyneuropathy show a high incidence of myocardial adrenergic denervation with viable myocardium that can be identified very early in cardiac amyloidosis, before the development of clinically apparent heart disease, ventricular wall thickening, significant LV systolic and diastolic dysfunction and positive findings on Tc-99m PYP myocardial scanning.

3-Iodobenzylguanidine↗

Echocardiographic diagnosis of subepicardial aneurysm ruptured into the right ventricle after inferior myocardial infarction.

A subepicardial aneurysm is a rare complication of myocardial infarction that sometimes causes a left to right shunt at the ventricular level. We report on echocardiographic observations in two recent cases of inferior myocardial infarction complicated by rupture of a subepicardial aneurysm into the right ventricle (RV). Two-dimensional and color flow Doppler images in several planes offered diagnostic characteristics of the lesion, including discontinuity of the myocardium at the neck of the aneurysm, a narrow neck relative to the diameter of the aneurysm, and a back and forth flow at the neck of the aneurysm. These techniques also provided new findings, such as a two-chambered structure of the aneurysm and a circular flow pattern within the inner aneurysmal cavity. In addition, color flow Doppler imaging showed multiple shunt flows from the aneurysm to the RV. Echocardiographically diagnosed abnormalities were verified by and successfully treated with surgery in both cases. In conclusion, echocardiography with color flow Doppler imaging may have the potential to diagnose the anatomic and hemodynamic condition of a subepicardial aneurysm.

Aneurysm, Ruptured↗

Heart rate variability in patients with familial amyloid polyneuropathy.

The purpose of this study was to evaluate heart rate variability (HRV) in patients with familial amyloid polyneuropathy (FAP) using the time- and frequency-domain analysis. The study population consisted of 19 patients with FAP, and 19 age and sex matched normal volunteers. The 24-hour Holter recordings of all subjects in sinus rhythm and off medication were analyzed. Five time-domain indices of HRV were computed. The frequency component of HRV was calculated by fast Fourier transform analysis of the RR intervals. The power spectrum of the low frequency (LF) between 0.04-0.15 Hz and high frequency (HF) between 0.15-0.40 Hz and the LF/HF ratio was calculated. Global measures of HRV including the standard deviation of the mean of RR intervals (SDNN) and the standard deviation of 5-minute mean RR intervals (SDANN) were decreased in patients with FAP. Specific vagal influences on HRV including the proportion of RR intervals more than 50 milliseconds different (pNN50) and the HF power on spectral analysis were less in patients with FAP. LF power and LF/HF ratio were more decreased in patients with FAP at the advanced stage than at the early stage. In conclusion, HRV was significantly decreased in patients with FAP at the early stage, and sympathetic activity was more decreased in patients at the advanced stage. These findings suggest that the decrease of the HRV is an indicator of this disease and the power spectral analysis of the HRV is beneficial in assessing the severity of the autonomic dysfunction.

Adult↗

Force-frequency effect is a powerful determinant of myocardial contractility in the mouse.

The effects of heart rate (HR) on myocardial contractility in the mouse heart in situ were first investigated in open-chest mice (n = 7) by left ventricular (LV) catheter-tip micromanometry. HR was first slowed with a sinus node inhibitor (zatebradine), and atrial pacing to progressively increase the HR caused a positive inotropic response (assessed by maximum positive first derivative of LV pressure, LV dP/dtmax) up to a HR of 282 beats/min with the onset of a descending limb of the force-frequency relation (FFR) at 332 beats/min. beta-Adrenergic receptor stimulation (dobutamine) shifted upward and significantly steepened the positive FFR and increased HR at the onset of the descending limb to 402 beats/min. HR and LV dP/dtmax were then studied in closed-chest mice without pacing during recovery from anesthesia (n = 7), and during rest and intermittent physical activity the FFR was linear and positive up to 600 beats/min. HR was then progressively slowed with zatebradine, and the points at rest and during activity fell on the same linear relation. Thus we conclude the following: 1) in the open-chest anesthetized mouse, a positive FFR was amplified by beta-adrenergic receptor stimulation, and 20 in the mouse recovering from anesthesia the sinus node rate remained a critical determinant of myocardial contractility, without a descending limb of the FFR.

Anesthesia, General↗

[A case of sarcoidosis with proliferative retinopathy].

A 19-year-old female manifested severe bilateral panuveitis with neovascularization in the iris, optic disc, and retina. Fluorescein fundus angiography showed dye leakage from the optic disc and retinal blood vessels, and a large non-perfused area was present in the peripheral retina of the right eye. Sarcoidosis was diagnosed histologically by conjunctival and skin biopsy. Although the patient was given a large dose of a corticosteroid systemically and received panretinal photocoagulation, a dense vitreous hemorrhage and cataract were apparent in the right eye. The right visual acuity decreased to hand motions. A pars plana lensectomy and vitrectomy were performed. After vitrectomy, inflammation and neovascularization regressed and the visual acuity improved to 20/100. Proliferative membrane obtained during vitrectomy was histopathologically studied by light and electron microscopy. Many new vessels containing neutrophils were observed. A direct effect of inflammation as well as ischemia in the retina may have been the stimulus for the proliferative changes.

Adult↗

[Myocardial scintigraphic studies with 123I-MIBG, 201Tl and 99mTc-PYP in patients with cardiac amyloidosis].

Myocardial scintigraphic studies, using 123I-metaiodobenzylguanidine (MIBG), 99mTc-pyrophosphate (PYP) and 201Tl were performed in 4 patients with cardiac amyloidosis. In MIBG myocardial images, 2 patients with familial amyloid polyneuropathy (FAP) showed complete or partial defect and the other 2 with primary amyloidosis had normal myocardial uptake of MIBG. In PYP myocardial images, diffuse myocardial uptake of PYP was mild in 2 patients with FAP and moderate in the other 2. 201Tl myocardial images revealed normal myocardial uptake of 201Tl in 2 patients with FAP and 1 with primary amyloidosis, and intense myocardial uptake in the other one with primary amyloidosis. These results suggest that myocardial scintigraphies with PYP and 201Tl may be useful for the detection of cardiac amyloidosis and estimation of its pathophysiology. And MIBG myocardial scintigraphy may provide useful information about sympathetic nerve abnormalities which vary with type of the fibril protein, clinical syndromes and disease process of cardiac amyloidosis.

3-Iodobenzylguanidine↗

[New trends in diagnosis of reflux esophagitis].

Reflux esophagitis is acid peptic disorder at the lower part of the esophageal mucosa. Acid reflux into the esophagus also induces typical and atypical reflux symptoms. Endoscopy is the definitive diagnostic procedure for reflux esophagitis, the consequence of acid reflux. Evaluation of pathophysiology of acid reflux is also important for the diagnosis of gastroesophageal reflux disease. 24hr esophageal pH monitoring measures acid reflux semiquantitatively. Fluoroscopic and ultrasonographic observation of reflux, esophageal manometery and gastric emptying study are useful for evaluation of pathophysiological state of gastroesophageal reflux disease, particularly in patients lacking evident endoscopic esophagitis. Symptom evaluation, either by acid suppression or acid load, shows relationship analysis is also the important diagnostic approach to acid reflux. Changes in symptoms by acid suppression and acid perfusion of the esophagus suggest the link between acid irritation and symptomatogenesis. Health-related quality of life evaluation seems to be another important diagnostic toll in near future.

Esophagitis, Peptic↗

The role of hypertrophy and growth factors in heart failure.

The physiologic trophic factors growth hormone (GH) and insulin-like growth factor 1 (IGF-1) generally increase body weight and cardiac mass proportionately, and several studies suggest that both growth factors cause vasodilation and increased myocardial contractility. Established clinical benefits of ACE inhibitors can be explained, at least in part, by inhibition of cell hypertrophy, lowered systemic vascular resistance (SVR) and afterload, leading to reduction of progressive left-ventricular (LV) enlargement. An alternative approach would be to administer IGF-1 or GH to stimulate compensatory hypertrophy and reduce afterload by their vasodilator action, as well as through potential favorable effects on myocardial contractility. In our initial study in the rat myocardial infarction (MI) model, when IGF-1 was administered early (at 2 days) post-MI and continued for 2 weeks, body weight (BW) increased and LV weight/BW remained unchanged, the LV end-diastolic volume (EDV) and stroke volume increased (but not when normalized to BW), and the LV ejection fraction increased in rats with large infarctions. These findings suggested a beneficial rather than detrimental effect of such treatment, and we then studied the action of combined IGF-1 and GH starting after infarct healing at 4-weeks' post-MI. BW increased substantially and LVEDV/BW was lower in treated rats than in control rats, suggesting relatively less LV dilation with little remodeling in this setting; IGF-1/GH increased the cardiac output by 46%, systemic vascular resistance (SVR) fell and the cardiac index (CI) was significantly elevated in treated rats with a large MI. Recently, others have used the rat MI model to study the effects of 2-weeks' of GH started at 4-weeks' post-MI, as well as IGF/GH for 2-weeks in rats treated with an ACE inhibitor for 3-month's post-MI. In both studies, in conscious treated rats the BW increased, LV/BW was not different compared to the control rats, but the CI increased, SVR fell, and estimated LV dP/dtmax was significantly augmented. Preliminary data in our laboratory suggest that beneficial effects may also occur with GH administration in the setting of chronic angiotensin II receptor blockade (losartan) after MI in the rat. Thus, growth factor therapy appears to have favorable effects in heart failure early and late after MI in the rat. Additional cardiac hypertrophy occurs early after MI, but the later beneficial effects appear to relate primarily to systemic vasodilation, improved cardiac output, and enhanced myocardial contractility.

Angiotensin Receptor Antagonists↗

Effect of aging on the esophageal motor functions.

To clarify the changes of esophageal motility along with age, we performed esophageal manometry on 47 healthy volunteers, and compared the values of four groups under 49 years old (n = 11), 50 to 59 (n = 15), 60 to 69 (n = 11), and over 70 years old (n = 10). Resting lower esophageal sphincter (LES) pressure in the group over 70 years old showed the tendency of decrease, but not statistically significant. Nadir LES pressure on swallow-induced relaxation was not statistically different among 4 groups. On esophageal body testing, percentage of non-conduction sequence in the group 60 to 69 and over 70 years old was statistically higher compared with that of the group under 49 years old (p < 0.05) but spared in some elderly subjects. Percentage of simultaneous contractions was not statistically different among 4 groups. Peristaltic contraction amplitude in the group over 70 years old was significantly lower than that of the group under 49 years old both at the level of 5 cm above (p < 0.01) and 10 cm above LES (p < 0.05). We speculate that the influence of aging on esophageal motility is the reduced transmission sequence of peristalsis and contractility of esophageal body. This alteration along with age may differ from the pathological condition of scleroderma or diffuse esophageal spasm.

Adult↗