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Biomedical subjects

M Hongo

Publications and source records attributed to M Hongo.

At least 19 recordsLinked to original sources

Primary care in the treatment of functional gastrointestinal symptoms in Japan: prescription preferences and impression of results.

BACKGROUND: Functional gastrointestinal (GI) disorders are common in primary care. However, proper pharmacological approaches have not yet been established. The reason for a lack of proper approaches may be attributable to the lack in clarity of their pathogenesis and pathophysiology. Meta-analysis of pharmacological approaches to functional GI disorders failed to identify the solid cluster of patients' symptoms. AIM: The aim of this study is to assess the perspective of primary care doctors concerning prescriptions for functional GI symptoms, evaluate the efficacy of the drugs prescribed, and the need for medication for these symptoms. METHOD: Questionnaires were sent to primary care doctors, and a total of 149 responses were obtained. Efficacy of each medication was evaluated by the number of doctors favouring the category, and the respective impressions of prescriptions given. RESULTS: Symptoms of heartburn were well controlled by anti-secretory drugs (H2RAs and PPIs), while appetite loss and abdominal gurgling were not controlled by any medications. CONCLUSIONS: This survey reveals differences in need for various prescription drugs in functional GI symptoms.

Abdominal Pain↗

Review article: Barrett's oesophagus and carcinoma in Japan.

In Asia, oesophageal diseases, such as Barrett's oesophagus and oesophageal carcinoma, have traditionally been less common than in America and Europe. In recent years, however, the number of reported cases of these conditions in Japan has increased. Two large prospective studies, the Sendai Barrett's Esophagus Study (S-BEST) and the Far East Study (FEST), on the geographic prevalence of Barrett's oesophagus, have recently investigated the epidemiology of Barrett's oesophagus in Japan. Results from both studies showed that overall prevalence of the condition is lower than in the West: 0.9-1.2% in Japan compared with 1-4% in Europe and 5-12% in USA. Similar to the situation in the West, the condition was shown to be most prevalent in elderly male patients and least prevalent in patients with Helicobacter pylori. Adenocarcinoma of the oesophagus is still rare in this region, although there has been an increase in the annual death rate from 3.7 (1960) to 6.9 (1995) per 100,000 population. Risk factors for oesophageal carcinoma include a strong association with the prevalence of gastro-oesophageal reflux disease (GERD). With the increasing prevalence of GERD in the Japanese population, continued surveillance of changes in the epidemiology of columnar-lined oesophagus (a precursor of Barrett's oesophagus), Barrett's oesophagus and adenocarcinoma of the oesophagus is strongly recommended.

Adenocarcinoma↗

Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome.

BACKGROUND AND AIMS: Corticotropin releasing hormone (CRH) is a major mediator of the stress response in the brain-gut axis. Irritable bowel syndrome (IBS) is presumed to be a disorder of the brain-gut link associated with an exaggerated response to stress. We hypothesised that peripheral administration of alpha-helical CRH (alphahCRH), a non-selective CRH receptor antagonist, would improve gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation in IBS patients. METHODS: Ten normal healthy subjects and 10 IBS patients, diagnosed according to the Rome II criteria, were studied. The tone of the descending colon and intraluminal pressure of the sigmoid colon were measured at baseline, during rectal electrical stimulation (ES), and at recovery after administration of saline. Visceral perception after colonic distension or rectal ES was evaluated as threshold values on an ordinate scale. The same measurements were repeated after administration of alphahCRH (10 micro g/kg). RESULTS: ES induced significantly higher motility indices of the colon in IBS patients compared with controls. This response was significantly suppressed in IBS patients but not in controls after administration of alphahCRH. Administration of alphahCRH induced a significant increase in the barostat bag volume of controls but not in that of IBS patients. alphahCRH significantly reduced the ordinate scale of abdominal pain and anxiety evoked by ES in IBS patients. Plasma adrenocorticotropic hormone and serum cortisol levels were generally not suppressed by alphahCRH. CONCLUSION: Peripheral administration of alphahCRH improves gastrointestinal motility, visceral perception, and negative mood in response to gut stimulation, without affecting the hypothalamo-pituitary-adrenal axis in IBS patients.

Abdominal Pain↗

Food-deprived activity stress decreased the activity of the histaminergic neuron system in rats.

The hypothalamus, which is rich in histaminergic neurons, is highly sensitive to aversive stimuli such as stress. Histamine H3 receptors, which regulate histamine release from the presynaptic site, are associated with stress-induced brain activity. In this study, we investigated the changes of histamine content and histamine H1 and H3 receptors in the brains of rats subjected to stress induced through food deprivation and physical activity on a running wheel (food-deprived activity stress). For purposes of comparison, we also examined the stressful effects of forced swimming on the histaminergic neuron system of rats. The H3 receptor density rapidly declined in the acute phase of stress but gradually returned to the control level in the chronic phase. On the other hand, the H1 receptor slowly decreased and remained at a low level during the chronic phase. These results reveal that there is a discrepancy between the levels of H1 and H3 receptors in the acute and chronic phases of stress. Brain histamine content gradually increased during the late phase of both food-deprived activity stress and forced swimming stress. These changes presumably resulted in the inhibition of histaminergic neuronal activity in the chronic stress condition. In accordance with this hypothesis, the intraventricular administration of histamine significantly reduced the hyperactivity caused by food-deprived activity stress. Since extensive exercise and restricted feeding are thought to be associated with anorexia nervosa, the abnormalities in the histaminergic neuron system might contribute to trait status in anorexia nervosa.

Animals↗

Effects of growth hormone following chronic angiotensin-converting enzyme inhibition in chronic heart failure: their relation to infarct size.

Growth hormone (GH) has been attracted as a possible adjunctive treatment for severe heart failure. However, its treatment effects have been still controversial. To assess severity of basal cardiac disease states in which GH might be effective, we analyzed the relation of treatment effects of GH following chronic angiotensin-converting enzyme (ACE) inhibition on cardiac function and structures to infarct size in rat model of chronic heart failure after myocardial infarction. One day after coronary occlusion, rats were randomized to either an ACE inhibitor, temocapril (T) (80 mg/L in drinking water) or placebo for 12 weeks. The animals received concomitant recombinant human (rh) GH (2 mg/kg/day, SC) (T + GH) or vehicle during the final 2 weeks. Compared with the T group, the T + GH group with large MI had smaller increments of left ventricular (LV) dP/dt(max) (0 vs 17%) and cardiac output (9 vs 49%), less improvement of LV relaxation (tau) (-3 vs 29%) and systemic vascular resistance (8 vs 29%), and a greater increase in LV end-diastolic pressure (123 vs -5%) than did the T+GH group with moderate MI. In the T + GH group when compared with the T group, these functional alterations were associated with a 12% reduction in the LV capillary density and a 21% increase in hydroxyproline contents in rats with large MI, whereas a 12% increase in the density and similar collagen contents were found in rats with moderate MI. Thus, prominent beneficial cardiovascular effects of the additive short-term, high-dose GH to chronic high-dose ACE inhibition were obtained in rats with moderate MI, whereas little additional benefit or even detrimental effects of GH were found in rats with large MI. The present study may provide an insight into the therapeutic strategy of GH given late after MI in the presence of chronic ACE inhibition in congestive heart failure.

Angiotensin-Converting Enzyme Inhibitors↗

Simulation studies of the ischemic vulnerability of the subendocardium.

Changes in the subendo-subepi flow ratio were studied by using a simple electronic circuit model of the coronary vessel consisting of a resistor, capacitor and field effect transistor in order to provide a better understanding of the ischemic vulnerability of the subendocardium. The simulated subendo-subepi flow ratio was found to be approximately 1.2 under normal condition. Changes in the flow ratio were observed while varying the main arterial resistance, mean arterial pressure and intramyocardial pressure individually. The mean flow in the subendocardium was found to decrease at a rate faster than that in the subepicardium with the increase in the septal arterial resistance and the intramyocardial pressure. The same tendency was also observed while the arterial pressure was lowered. This decrease in the mean subendocardial flow is considered to be the effect of higher end-systolic resistance in the subendocardial venule compared to that in the subepicardial venule. These results would be helpful in understanding the vulnerability of the subendocardium to ischemia and in providing clinical treatment to patients with that disease.

Animals↗

Pulmonary arterial aneurysm with CATCH 22 syndrome--a case report.

An adult case of CATCH 22 syndrome with a pulmonary arterial aneurysm is presented. The chest radiograph showed a large massive lesion, which should be differentiated from lung cancer, mediastinal tumor, or aortic aneurysm. CATCH 22 syndrome is a developmental malformation caused by hemizygous deletion of 22q11 chromosome, which usually presents with cardiac malformation including tetralogy of Fallot, truncus arteriosus, patent arterial duct, and ventricular septal defect. Most patients with this syndrome usually die early in life.

Adult↗

Urocortin and corticotropin-releasing factor receptor expression in normal cycling human ovaries.

Urocortin is a member of the CRF neuropeptide family and has a 43% homology to CRF in amino acid sequence. Urocortin has been found to bind with high affinity to CRF receptors. CRF has been detected in the human ovary and has been demonstrated to suppress ovarian steroidogenesis in vitro. In this study we examined urocortin and CRF receptor expression in normal cycling human ovaries, using immunohistochemistry and RT-PCR. Normal cycling human ovaries were obtained at oophorectomy and hysterectomy from patients who underwent surgery for cervical cancer or myoma uteri. Intense urocortin immunoreactivity was detected in luteinized thecal cells of regressing corpora lutea, in which only luteinized thecal cells have the capacity for steroidogenesis. Immunoreactive urocortin was also detected in luteinized granulosa and thecal cells of functioning corpora lutea, in which both cell components are capable of producing steroids. RT-PCR analyses revealed that messenger ribonucleic acid levels for urocortin, CRF, and CRF receptor type 1 and type 2alpha were significantly higher in the regressing corpus luteum than in the functioning corpus luteum. The spatial and temporal immunolocalization patterns of CRF receptor were similar to those of urocortin. These results suggest that urocortin is locally synthesized in steroidogenic luteal cells and acts on them as an autocrine and/or paracrine regulator of ovarian steroidogenesis, especially during luteal regression.

Adult↗

Biventricular hypertrophic cardiomyopathy with right ventricular outflow tract obstruction associated with Noonan syndrome in an adult.

This report describes an adult patient with Noonan syndrome accompanied by biventricular hypertrophic cardiomyopathy causing isolated right ventricular outflow tract obstruction. Biventricular hypertrophic cardiomyopathy causing right- and/or left-side outflow tract obstruction, as well as valvular pulmonary stenosis, is relatively common in infants with Noonan syndrome. However, this condition without a dysplastic pulmonary valve, or indeed any polyvalvular dysplasia, is rare in adults with Noonan syndrome. Treatment with a beta-adrenergic receptor blocking agent improved the patient's symptoms. Because neither the etiologic and prognostic relationship nor the genetic linkage between hypertrophic cardiomyopathy associated with Noonan syndrome and non-syndromic hypertrophic cardiomyopathy is clearly defined, clinicopathological findings and further follow-up may provide important evidence for the pathogenesis of hypertrophic cardiomyopathy.

Adult↗

Comparison of electrocardiographic findings in patients with AL (primary) amyloidosis and in familial amyloid polyneuropathy and anginal pain and their relation to histopathologic findings.

To assess the prevalence of chest pain and ischemic electrocardiographic (ECG) changes and relate them to histopathologic findings of coronary arteries in cardiac amyloidosis, 33 patients with AL (primary) amyloidosis and 60 patients with familial amyloid polyneuropathy (FAP) were examined. Five patients (15%) with AL amyloidosis had recurrent anginal pain with exertion and 2 of them also experienced anginal pain after orthostatic hypotension. The chest pain was associated with transient downsloping or horizontal ST-segment depression with or without T-wave inversion in right precordial leads, whereas the remaining patients with AL amyloidosis and all patients with FAP did not show anginal pain or ischemic ST-T changes. Histologic sections of coronary arteries were obtained in 12 patients with AL amyloidosis, including 4 of the 5 patients who had angina pectaris and in 25 patients with FAP. Three patients with anginal pain had variable degrees of stenoses of the intramural coronary arteries by amyloid deposition predominantly in the media with normal or nearly normal epicardial arteries. One patient with AL amyloidosis who had effort angina showed marked stenosis and complete occlusion of the small coronary vessels by transmural amyloid deposition. The remaining 8 patients with AL amyloidosis and 25 with FAP without chest pain did not exhibit any stenosis or occlusion of both the epicardial and intramural vessels. These findings suggest that ischemic ST-T changes with chest pain are not so rare in patients with AL amyloidosis, and that markedly decreased myocardial oxygen supply due to diffuse stenotic or occlusive disease of the small coronary vessels by amyloid deposition contributes to the development of clinically significant ischemic heart disease in these patients.

Aged↗

Increased sinusoidal pressure is associated with early liver weight gain in ischemia-reperfusion injury in isolated perfused rat liver.

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation. This could be caused by an increase in sinusoidal pressure, a determinant of hepatic transvascular fluid movement. We determined the role of sinusoidal pressure, assessed by triple vascular occlusion pressure (P(to)), in the I/R injury in isolated rat livers perfused with leukocyte-free diluted blood bivascularly via the portal vein and hepatic artery. MATERIALS AND METHODS: Ischemia was induced at room temperature by occlusion of either the inflow lines of the hepatic artery and portal vein (the open outflow group, n = 10) or both the inflow and the outflow (hepatic venous) lines (the closed outflow group, n = 10) for 1 h, followed by 1-h reperfusion in a recirculating manner. RESULTS: Liver weight in both groups increased biphasically after reperfusion; the initial peak occurred at 3 min and the second peak at 60 min. Immediately after reperfusion, P(to) peaked, followed by a gradual decline. The initial weight increase in groups combined was significantly and positively correlated with an increase in P(to) (r = 0.716, P = 0.0002), but the second peak was independent of P(to). Liver injury, assessed by perfusate levels of hepatic enzymes and reduced bile flow rate, was observed at 60 min after reperfusion in both groups. CONCLUSIONS: These findings suggest that increased sinusoidal pressure contributes to only the early liver weight gain after reperfusion in isolated perfused rat livers. The late weight gain may be presumably due to liver injury.

Animals↗

Effects of growth hormone on cardiac dysfunction and gene expression in genetic murine dilated cardiomyopathy.

Beneficial cardiac effects of growth hormone (GH) have been shown in heart failure in several settings, but studies are lacking on this and other forms of treatment in the cardiomyopathic (CM) mouse heart. In mice with dilated cardiomyopathy due to disruption of the muscle LIM protein (MLP) gene [MLP null mice (MLP-/-)], natural history was first assessed by an initial echocardiogram at 8 weeks and a later follow-up study (n = 31). In most mice, left ventricular (LV) dilation increased and/or function decreased by 5 months, and 3 of 12 mice followed for 9 months died. At the end of follow-up, 22 MLP-/- mice (average age 10.2 months) had both LV dilation and reduced LV function and were selected for studies of GH effects on cardiac function and gene expression; mice were randomized to vehicle (controls) or recombinant human (rh) GH and restudied after 2 weeks. In the GH-treated group compared to the control group, LV % fractional shortening and LV wall thickness (echocardiography) were increased, the LV dP/dtmax (catheter-tip micromanometry) was enhanced, and LV relaxation (tau) improved; however, the LV weight was not significantly increased. The LV expression of many genes was altered in MLP-/- mice, and several were influenced by GH. Thus, short-term RhGH treatment improved LV function in a setting of chronic cardiac deterioration and significantly reduced elevated LV mRNA expression of some (ANP, BNP) but not other members of the embryonic gene program. The MLP null cardiomyopathic mouse can be useful for exploring altered signaling and therapeutic interventions in heart failure.

Animals↗

Urocortin and corticotropin-releasing factor receptor expression in the human colonic mucosa.

Urocortin is a newly identified member of the CRF neuropeptide family. Urocortin has been found to bind with high affinity to CRF receptors. The present study investigated urocortin and CRF receptor expression in human colonic mucosa. Non-pathologic sections of adult colorectal tissues were obtained from patients with colorectal cancer at surgery. Urocortin expression was examined using immunohistochemistry and messenger (m) RNA in situ hybridization. Isolated lamina propria mononuclear cells (LPMC) and epithelial cells were also analyzed by flow cytometry for the characterization of urocortin-positive cells, and by RT-PCR for detection of urocortin, CRF, and CRF receptor mRNA. Urocortin peptide distribution at various stages of human development (n = 35, from 11 weeks of gestation to 6 years of age) was examined by immunohistochemistry using surgical and autopsy specimens. Immunoreactive urocortin and urocortin mRNA were predominantly detected in lamina propria macrophages. Urocortin peptide expression was detected from as early as three months of age, but not before birth or in neonates. Urocortin, CRF receptor type 1 and type 2 alpha mRNA were detected in LPMC. CRF receptor type 2 beta mRNA, a minor isoform in human tissues, was also detected in LPMC, but at lower levels. Urocortin is locally synthesized in lamina propria macrophages and may act on lamina propria inflammatory cells as an autocrine/paracrine regulator of the mucosal immune system. The appearance of urocortin after birth indicates that the exposure to dietary intake and/or luminal bacteria after birth may contribute to the initiation of urocortin expression in human gastrointestinal tract mucosa.

Adult↗

Expression and activity of dehydroepiandrosterone sulfotransferase in human gastric mucosa.

Dehydroepiandrosterone sulfotransferase (DHEA-ST) is a key enzyme in the formation of Dehydroepiandrosterone sulfate (DHEAS) and is thought to be involved in the conversion of various substances such as bile acids and cholesterol. The existence of DHEA-ST in the small intestine in addition to the adrenal gland and liver in adult humans was recently reported. As the sulfotransferases can act on toxic or potentially toxic substances to reduce their biological activity, we attempted to clarify the significance of DHEA-ST in gastrointestinal tract. We examined surgically resected human stomach for the presence of DHEA-ST and attempted to determine its possible biological significance. DHEA-ST activity ranged widely from 6 to 84 pmoles/mg protein/90 min in 7 cases. Immunoblotting revealed one single band of a 35-kDa protein corresponding to the moleculr weight of DHEA-ST. Both DHEA-ST immunoreactivity and mRNA hybridization signals were localized in parietal cells of the gastric glands. The results of our present study demonstrated that the sulfation of DHEA by DHEA-ST occurs in the gastric glands. The localization of DHEA-ST in parietal cells suggests that this enzyme is correlated to mucosal function in the human stomach in addition to detoxification of exogenous substances.

Adult↗

Abnormal visceral perception in patients with functional dyspepsia: use of cerebral potentials evoked by electrical stimulation of the oesophagus.

Altered visceral perception is thought to be included in the pathogenesis of functional dyspepsia. However, in previous studies, the assessment of visceral perception has been based solely on patients self-reported symptoms. Cerebral evoked potential (EP), either by mechanical or electrical stimulation (ES) of the visceral organ, is used to evaluate visceral perception via afferent neural pathways. In this study, we investigated the visceral perception in patients with functional dyspepsia by EP to eliminate the possibility of self-reported bias. EP responses were recorded by oesophageal ES at 37 cm from the nostril in 14 patients with functional dyspepsia and 14 normal healthy control subjects. Threshold levels of perception, peak latencies and peak-to-peak amplitudes of EP were evaluated. There was no difference in the sensory threshold between the dyspeptic patients and the control subjects (median 6 mA, range 2-12 mA, vs. 8 mA, range 6-14 mA; P= 0.09). There was a strong trend towards a decreased discomfort threshold in the patients when compared to the control subjects (median 14 mA, range 6-24 mA vs. 20 mA, range 14-26 mA; P = 0.05). The latency of the later EP peak (N2) among the patients (154 ¿ 4 ms) was significantly shorter than that of the control subjects (171 ¿ 3 ms, P < 0.01) although there was no difference between the earlier peaks (Ni and P1). There was also no difference in the amplitudes (Ni/Pi and P1/N2) of EP between the patients and the control subjects. Half of the patients (seven out of 14) complained of nausea during ES but the control subjects were unaffected. The latency of the first EP peak (Ni) in the patients with nausea was significantly shorter (66 ¿ 3 ms) than that of the patients without nausea (79 ¿ 4 ms, P 0.05) or among the control subjects (80 ¿ 3 ms, P < 0.05). These results suggest that dyspeptic patients may recruit a greater number of fast conducting myelinated nerve fibres that convey visceral afferent impulses to the brain and/or that dyspeptic patients may have an altered central processing of the visceral perception. We conclude that EP recording by oesophageal ES provides an objective measurement of altered visceral perception in patients with functional dyspepsia.

Adolescent↗