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Biomedical subjects

H Masuyama

Publications and source records attributed to H Masuyama.

At least 37 records · Page 2Linked to original sources

Evidence for ligand-dependent intramolecular folding of the AF-2 domain in vitamin D receptor-activated transcription and coactivator interaction.

A ligand-dependent transcriptional activation domain (AF-2) exists in region E of the nuclear receptors. This highly conserved domain may contact several coactivators that are putatively involved in nuclear receptor-mediated transcription. In this study, a panel of vitamin D receptor (VDR) AF-2 mutants was created to examine the importance of several conserved residues in VDR-activated transcription. Two AF-2 mutants (L417S and E420Q) exhibited normal ligand binding, heterodimerization with retinoid X receptor, and vitamin D-responsive element interaction, but they were transcriptionally inactive in a VDR-responsive reporter gene assay. All AF-2 mutations that abolished VDR-mediated transactivation also eliminated interactions between VDR and several putative coactivator proteins including suppressor of gal1 (SUG1), steroid hormone receptor coactivator-1 (SRC-1), or receptor interacting protein (RIP140), suggesting that coactivator interaction is important for AF-2-mediated transcription. In support of this concept, the minimal AF-2 domain [VDR(408-427)] fused to the gal4 DNA binding domain was sufficient to mediate transactivation as well as interaction with putative coactivators. Introducing the L417S and E420Q mutations into the minimal AF-2 domain abolished this autonomous transactivation and coactivator interactions. Finally, we demonstrate that the minimal AF-2 domain interacted with an AF-2 deletion mutant of the VDR in a 1,25-(OH)2D3-dependent manner, suggesting a ligand-induced intramolecular folding of the VDR AF-2 domain. The L417S mutant of this domain disrupted the interaction with VDR ligand-binding domain, while the E420Q mutant did not affect this interaction. These studies suggest that the conserved AF-2 motif may mediate transactivation through ligand-dependent intermolecular interaction with coactivators and through ligand-induced intramolecular contacts with the VDR ligand-binding domain itself.

Adaptor Proteins, Signal Transducing↗

The N-terminal domain of transcription factor IIB is required for direct interaction with the vitamin D receptor and participates in vitamin D-mediated transcription.

The interaction of the vitamin D receptor (VDR) with transcription factor IIB (TFIIB) represents a potential physical link between the VDR-DNA complex and the transcription preinitiation complex. However, the functional relevance of the VDR-TFIIB interaction in vitamin D-mediated transcription is not well understood. In the present study, we used site-directed mutagenesis to demonstrate that the structural integrity of the amino-terminal zinc finger of TFIIB is essential for VDR-TFIIB complex formation. Altering the putative zinc-coordinating residues (C15, C34, C37, or H18) to serines abolished TFIIB interaction with the VDR as assessed in a yeast two-hybrid system and by in vitro protein interaction assays. This N-terminal, VDR-interactive domain functioned as a selective, dominant-negative inhibitor of vitamin D-mediated transcription. Expressing amino acids 1-124 of human TFIIB (N-TFIIB) in COS-7 cells or in osteoblastic ROS17/2.8 cells effectively suppressed 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3)-induced transcription, but had no effect on basal or glucocorticoid-activated transcription. A mutant N-terminal domain [N-TFIIB(C34S:C37S)] that does not interact with VDR had no impact on 1,25-(OH)2D3-induced transcription. Interestingly, both in vitro and in vivo protein interaction assays showed that the VDR-TFIIB protein complex was disrupted by the 1,25-(OH)2D3 ligand. Mechanistically, these data establish a functional role for the N terminus of TFIIB in VDR-mediated transcription, and they allude to a role for unliganded VDR in targeting TFIIB to the promoter regions of vitamin D-responsive target genes.

Amino Acid Sequence↗

Motor activity of refashioned colorectoanus in patients with total colonic aganglionosis.

An ano-recto-sigmoid colon pressure study was designed to evaluate the characteristics of the motor activity of refashioned colorectoanus in patients with total colonic aganglionosis (TCA) in comparison to patients with rectosigmoid Hirschsprung's disease (HD) and healthy children (HC), and to elucidate the pathophysiology of the pulled-through ileum, with aganglionic colon as an onlay patch, in coordination with the anal sphincter. The study group consisted of six patients with TCA, six with HD who underwent endorectal colonic pull-through, and six HC. Pressure studies were performed using a triple-lumen catheter; recording sites were 15 and 9 cm from the anal verge, and at the anal canal. The following were measured and compared: (1) anal canal pressure profile, (2) resting pattern of activity at the refashioned colorectum and anal canal, and (3) changes in motor activity after stimulation with cold water and glycerin. The motor activities of the refashioned colorectoanus of TCA and HD patients differed greatly from those of HC. All six HC had no isolated high-amplitude contraction (IHAC) in the colorectum during the 45-minute study period; they complained of a strong urge to defecate after glycerin enema and actually did so. In contrast, IHAC appeared 2.0 +/- 1.3 times per 10 minutes, with maximal amplitude of 60.3 +/- 24.9 cm H2O in TCA, and 5.6 +/- 3.7 per 10 minutes with maximal amplitude of 79.5 +/- 11.7 cm H2O in HD. After glycerin enema, IHAC increased to 0.5 +/- 0.2 per minute and 69.3 +/- 44.6 cm H2O in TCA and to 0.8 +/- 0.4 per minute and 93.0 +/- 12.8 cm H2O in HD. Defecation was postponed for more than 10 minutes in two HD and all TCA patients. The mean motility index per minute was least for TCA patients (76.9 +/- 98.2); it was 406.5 +/- 197.1 (P < .05) for HD patients and 159.2 +/- 84.2 (P < .01) for HC. TCA patients had the lowest amplitude of maximal resting anal pressure, and hypoactivity of the colorectum during rest and after stimulation; this suggests that motor dysfunction involves even the ganglionic ileum, concomitant with suppressed signals to the higher integrating center for defecation.

Adolescent↗

Effect of epidermal growth factor on placental amino acid transport and regulation of epidermal growth factor receptor expression of hepatocyte in rat.

We investigated the effect of epidermal growth factor (EGF) on amino acid transport in the rat placenta and the hormonal and nutritional regulation of hepatic expression of epidermal growth factor receptor (EGFR). Fetuses born to maternal rats administered EGF were larger than control fetuses, while fetuses born to mothers administered EGF antibody were smaller than controls. The fetomaternal amino acid concentration ratio (fetal blood/maternal blood) was higher in the EGF-treated group than in the control group, and was lower in the EGF antibody-treated group. EGF treatment stimulated 14C-aminoisobutyric acid, isoleucine and alanine uptake by placental explants as did treatment with insulin-like growth factor-1 and insulin, which have been reported to stimulate the active amino acid transport. Thus, EGF promoted amino acid transport in the rat placenta and influenced fetal growth as a result. In addition, retinol induced a 170% increase of EGF binding to rat hepatocytes and insulin induced a 120% increase of EGF binding, while amino acids (isoleucine and serine) had no effect on EGF binding. This result indicated that there is hormonal regulation of EGF binding to hepatocytes and that changes of some hormone levels may affect hepatic EGFR expression.

Alanine↗

[Gastric mucosal congestion following endoscopic variceal ligation--analysis using reflectance spectrophotometry].

UNLABELLED: Endoscopic variceal ligation (EVL) has been accepted as a new treatment for esophageal varices in cirrhotic patients, and evaluated to have a lower incidence of complications compared to sclerotherapy. Sclerotherapy may increase the risk of portal hypertensive gastropathy (PHG), which is recognized to be gastric mucosal congestion due to portal hypertension in cirrhotics. However, the gastric mucosal hemodynamics after EVL has not been established yet. The aim of this study is to assess whether EVL could affect the hemodynamics of the gastric mucosa. PATIENTS AND METHODS: Eleven cirrhotic patients with severe esophageal varices, who underwent prophylactic EVL were enrolled in the trial. Age and sex-matched non-cirrhotic patients who had only gastric mucosal atrophy were entered as control to compare the mucosal hemodynamics to that of cirrhotic patient. EVL was performed as described by Stiegmann et al. The gastric mucosal hemodynamics was evaluated with both gastric mucosal blood volume (IHB) and hemoglobin O2 saturation (ISO2), which were measured by reflectance spectrophotometry during endoscopy. These parameters were measured in the three points of the stomach (gastric antrum, lower corpus and upper corpus) just before and after EVL. RESULT: In all patients with cirrhosis, mild PHG was observed endoscopically. ISO2 in cirrhotic patients was significantly lower in all points of the stomach compared with control. IHB in cirrhotic patients was not significantly different from control. ISO2 of post-EVL was significantly lower than that of pre-EVL, whereas IHB of post-EVL revealed significantly higher than that of pre-EVL. However, endoscopic grade of PHG remained mild. The hemodynamics of the mucosa two weeks after the initial EVL showed improvement of the congestion. CONCLUSIONS: The gastric mucosal hemodynamics showed increment of the gastric blood volume and decreased hemoglobin O2 saturation in cirrhotic patients, indicating that cirrhotic gastric mucosa is in congestive condition. EVL for esophageal varices makes the gastric mucosa more congestive soon after the procedure in spite of the same grade of endoscopic PHG. However, the worsened congestion improves within a few weeks.

Aged↗

Calculation of biliary atresia prognostic index using a multivariate linear model.

The purpose of this study was to determine the relative value of liver function markers in predicting the magnitude of morbidity and to develop a quantitative estimate of the prognostic risk using a multivariate regression model in patients who have been operated on for biliary atresia. The study sample consisted of 37 patients who had undergone a Kasai portoenterostomy; the jaundice disappeared in 32 and persisted in five. A computer-based stepwise regression procedure produced the linear predictive models by the equation: biliary atresia prognostic index (BAPI) = 9.2 Cu:Zn + 1.0 ZTT + 3.2 TB - 0.05 ChE + 9.9 for infants under 1 year of age, and BAPI = 10.3 Cu:Zn + 0.8 ZTT + 0.03 GGTP - 0.12 ChE + 25.6 for children over 1 year of age. In validation of these models, the indexes fluctuated from -17 to 122, and the degree of morbidity increased linearly with the increase in BAPI. Postoperatively the patients were classified into four categories according to the dynamics of their postoperative course: A (BAPI < 25), successful cases that should not require liver transplantation (40.5%); B (25 < or = BAPI < or = 50), improved cases that have extended survival with their native liver (29.7%); C (50 < BAPI < or = 75), cases that improved in terms of disappearance of jaundice but ultimately will require liver transplantation (8.1%); and D (BAPI > 75), cases that require early referral for transplantation (21.6%). (The percentages indicate the distribution rate of patients at the time of final follow-up evaluation.) These models allow quantification of the risk of morbidity from progressive liver cirrhosis in the individual patient, permitting the clinician to consider whether such patients should be considered for liver transplantation.

Biliary Atresia↗

Effect of retinoids on fetal lung development in the rat.

We investigated the effect of retinoids on fetal lung development in the rat. The concentration of retinyl palmitate increased rapidly to a peak on day 17 of gestation and decreased to a minimum on day 21 of gestation; there was a slight increase after birth. Retinoid acid receptor (RAR)-alpha and -beta mRNA were detected in all samples obtained from perinatal and adult rat lung, and only a trace of RAR-gamma mRNA was detected in the fetuses on days 15, 17 and 19 of gestation and in the adults by reverse transcriptase-polymerase chain reaction. After a maternal retinol deficiency of 28 days' duration, fetal body and lung weights were significantly lower than those of controls; the concentrations of retinyl palmitate and phosphatidylcholine (PC) in the lung after a maternal retinol deficiency of 14, 21, or 28 days were significantly lower than those of controls. Expression of RAR-beta mRNA in the group with 28-day retinol deficiency was lower than in controls, that of RAR-alpha mRNA was increased and that of RAR-gamma mRNA was not influenced by retinol deficiency. The rate of choline incorporation into PC in fetal lung explants was significantly higher in the group treated with retinoic acid (RA) than in controls. RA enhanced the effect of epidermal growth factor on choline incorporation and prevented that of dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of long surviving inflammatory breast cancer with bone metastasis, treated by intra-arterial infusion chemotherapy followed by extended mastectomy].

Since there is no established therapeutic strategy in the treatment of stage IV breast cancers and there are cases with bone metastases from the breast showing long survival, the authors usually perform due local control in cases with bone metastases. The present case is an inflammatory carcinoma of the breast with bone metastasis for which doxorubicin hydrochloride was administered via the subclavian and internal thoracic arteries followed by extended mastectomy. The patient is being treated with tamoxifen citrate and doxifluridine and shows no other metastasis at this writing, four years and seven months after the mastectomy. Bone scintigraphy of the patient indicated disappearance of the bone metastases. Since there are long surviving cases among those with a poor prognosis involving inflammatory breast cancer with concomitant bone metastasis, it is necessary to treat cases with locally advanced breast cancer by preoperative intraarterial infusion together with mastectomy, ie, sufficient local control.

Bone Neoplasms↗

[A study of ambulatory treatment for pulmonary tuberculosis in foreigners residing in Japan].

We studied 130 cases of pulmonary tuberculosis in foreigners residing in Japan to obtain the results as follows; 1. Of the cases of pulmonary tuberculosis in foreigners who are registered and receiving treatment in Japan, 20.3% were treated at three dispensaries of the Japan Antituberculosis Association in Tokyo. 2. The nationality of the cases treated was China in more than half of them, followed by the Republic of Korea. 3. The number of days taken from entry into Japan to the start of treatment was about 11.4 months; 0.9% of the total number of cases examined by chest radiophotography required medical treatment. 4. Their living conditions in Japan according to questionnairing are: 56.2% have jobs in Japan; working hour, 4.99 +/- 1.19 hours a day; 64.4% take night work; 57.6% work in food/drink service industry; living space is 12.5 m2; 52.4% share the same house with other persons, living together with 1.6 persons. 5. As for the type of illness at the start of treatment, GAKKAI classification type III accounted for 90% and spread 1 83.8%. GAKKAI classification type II accounted for 10%, consisting of many relatively mild cases. 6. The defaulter rate was high at 40.8%. The reason for defaulting was broken down to discontinuation on his own 68%, repatriation 15% and side-effects 19%. The time to default was average 3.2 +/- 3.1 months after the start of treatment. They defaulted 1.2 +/- 0.4 times on the average. 7. To reduce the defaulter rate to the minimum in treating the foreigners residing in Japan, the following may be needed. a. To give guidance on the regimen including the need of treatment and risk associated with discontinuation of treatment at the first visit. b. Measures to reduce the amount to be born by the individual in the medical expenses. c. Preparation of a pamphlet for therapeutic guidance in foreign languages.

Adult↗

A prognostic evaluation of endoscopic intravariceal injection sclerotherapy for esophageal varices.

Eighty cases of endoscopic injection sclerotherapy for esophageal varices were retrospectively studied to evaluate their prognoses. These cases were evaluated in terms of post-therapeutic bleeding, survival rates and causes of death. Post-therapeutic bleeding occurred in 50% of the emergency cases (26 cases), 25% of the elective cases (16 cases) and 23.7% of the prophylactic cases (38 cases). The frequency of post-therapeutic bleeding was significantly lower in cases with variceal obliteration than in cases without obliteration. An evaluation of the survival rates by the Kaplan-Meier method revealed that poor prognostic factors in sclerotherapy cases were emergency cases, Child's C group, post-therapeutic cases with unsuccessfully obliterated varices, and cases with post-therapeutic bleeding. Concerning early death within 7 days after sclerotherapy, 4 emergency cases died from initial variceal bleeding despite sclerotherapy. Three of these 4 were hepatocellular carcinoma cases, and all 3 cases had tumor thrombi of the portal vein. We recommend prophylactic sclerotherapy from the standpoint of the prognosis after sclerotherapy. However, in the bleeding cases of hepatocellular carcinoma in Child's C group complicated by tumor thrombi of the portal vein, overly enthusiastic application of the therapy should be avoided.

Actuarial Analysis↗

[Hemostatic effect of local intramural injection of dehydrated ethanol in the canine gastrointestinal tract].

The relative value of a subserosal injection of 98% ethanol (0.2 ml x 4) in controlling acute and chronic bleeding from serosal vessels was assessed in dogs. Blood flow was measured from gastric serosal vessels (average diameter 1.6 mm) severed immediately after, 24 hours after, and 48 hours after ethanol injection. Blood flow from severed colonic serosal vessels (averaging diameter 1.0 mm) was measured prior to and immediately after ethanol injection. The safety of ethanol injection was tested by endoscopically guided submucosal injection which were sequentially observed endoscopy at one hour, 24 hours, and weekly for weeks after injection. Ethanol injection had no effect on bleeding from larger gastric vessels unless the injection was made 24 or 48 hours prior to vessel severence. Ethanol injection was effective in reducing bleeding from the smaller colonic vessels when done immediately prior to vessel severence. Gastric submucosal injections led to ulcers which extended into the muscle layer at on week and healed completely by three weeks; none perforated or bleed. These data support the potential efficacy of therapeutic ethanol injection for the control of small vessel (1.0 mm diameter) bleeding and the potential prophylactic value against rebleeding from larger vessels. Further studies are needed to determine if these findings are organ related as opposed to being diameter specific.

Animals↗

Comparison of ventilatory response between dead space and CO2 breathing in humans.

Ventilatory response during external dead space (tube) breathing and CO2 inhalation for given increase in PETCO2 were compared at different levels of PETO2 (hyperoxia, normoxia, and hypoxia) in human subjects. At all the PETO2 levels studied, magnitude of increment in minute ventilation (VE) and tidal volume were larger in the dead space breathing than in the CO2 inhalation. The slope of CO2-ventilation response line was significantly steeper in the dead space breathing only in the hypoxic condition. There was no significant difference in frequency response to CO2 between the two methods. These results suggested that augmented ventilatory response to CO2 in the dead space breathing occurs in the condition of peripheral chemoreceptor activation.

Administration, Inhalation↗

Differences in ventilatory responses to hypoxia and hypercapnia between normal and judo athletes with moderate obesity.

Hypercapnic and hypoxic ventilatory sensitivities were compared in twenty-one judoists and 24 control subjects with similar degrees of moderate obesity. Data from ten non-obese control subjects were also included as a reference. Mean body weight (BW) and % of ideal body weight in the judoists and the obese and non-obese controls were 100 +/- 14.8, 94.4 +/- 5.3 and 63.4 +/- 6.1 (mean +/- SD) kg, and 142.3 +/- 16.7, 142.2 +/- 12.9 and 98.4 +/- 10.7%, respectively. Mean body fat in the judoists was 16.2 +/- 13.9%, being 25.3 +/- 7.7% in the obese control group, the difference being significant (p less than 0.01). Hypercapnic sensitivities in terms of the CO2 ventilatory response slope (S) and its normalized value for 70 kg BW (SN) of the obese controls were higher than the judoists. These findings were also verified by the CO2-occlusion pressure responses. S and SN in the obese controls were significantly correlated with BW and % body fat. However, no positive correlation was found between BW and S or SN in the judoists as well as between lean body mass and S or SN in the obese control. Hypoxic sensitivity in terms of the PETO2-ventilation hyperbola slope (A) and its normalized value (AN) in the obese control was significantly higher than the non-obese control, but the difference from the judoists was not significant. A and AN were found to increase with increasing % body fat in both judoists and obese controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

Pancreas divisum: is it a normal anatomic variant?

One thousand five hundred twenty-nine pancreatograms were obtained between 1973 and 1985. Complete pancreas divisum was demonstrated in 41 patients, for an incidence of 2.7 percent, and incomplete pancreas divisum in 14 cases, for an incidence of 0.9 percent. No increased incidence of pancreas divisum was found in any of four groups: an incidental group, a group with alcoholic pancreatitis, a group with unexplained upper abdominal pain, and an idiopathic pancreatitis group. The majority of patients (80 percent) were found to have pancreas divisum as an incidental finding or in association with alcoholic pancreatitis. Of 82 patients with idiopathic pancreatitis, only 2 had pancreas divisum. The three patients with pancreas divisum who had sphincteroplasty of the minor papilla were not helped by the procedure. We conclude that pancreas divisum is a normal anatomic variant and is very seldom a cause of pancreatic pain.

Abdomen↗