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Biomedical subjects

A Moriya

Publications and source records attributed to A Moriya.

At least 19 recordsLinked to original sources
PubMed2003

Validation of microdialysis probes for studying nitrosative chemistry within localized regions of the human upper gastrointestinal tract.

BACKGROUND: We have examined the suitability of microdialysis probes for examining nitrosative chemistry within localized regions of the lumen of the gastrointestinal tract. Chemical nitrosation occurs maximally at pH 2.5 in the presence of nitrite and thiocyanate and absence of ascorbic acid. Nitrite and thiocyanate are delivered into the stomach in saliva and ascorbic acid is secreted in gastric juice. METHODS: We used a benchtop model to reproduce the nitrosative chemistry occurring in the human upper GI tract and assessed the ability of the microdialysis probes to measure it. RESULTS: The microdialysis probes were reliable at measuring nitrite ascorbic acid, total vitamin C and thiocyanate in both aqueous solutions and human gastric juice over the full range of intragastric pH, i.e. 1.5, 2.5, 3.5, 5.0 and 7.0. The probes were also reliable at measuring these chemicals under conditions simulating the active interaction between nitrite and ascorbic acid. Under such conditions with ascorbic acid in excess the probes gave a more accurate assessment of the nitrite level than that obtained by directly sampling the gastric juice. This was due to the probes not being subject to artefactual measurement of nitric oxide as nitrite. This was prevented by the rapid diffusion of nitric oxide through the probe collecting tube. CONCLUSION: Microdialysis probes provide a reliable means of examining nitrosative chemistry within the lumen of the upper GI tract. In addition, they have the advantage of measuring this chemistry in very local regions and of simultaneously comparing the chemistry in different regions of the upper GI tract.

Ascorbic Acid↗
PubMed2003

Conditions for acid catalysed luminal nitrosation are maximal at the gastric cardia.

BACKGROUND: Saliva has a high nitrite concentration, derived from the enterosalivary recirculation of dietary nitrate, and is the main source of nitrite entering the acidic stomach. Acidification of nitrite in the presence of secondary amines or amides generates potentially carcinogenic N-nitroso compounds. The reaction is inhibited by ascorbic acid and catalysed by thiocyanate. AIM: To determine whether there is intragastric regional variation in the chemical conditions promoting luminal nitrosation following nitrate ingestion. METHODS: Using microdialysis probes, we measured concentrations of nitrite, ascorbic acid, total vitamin C, and thiocyanate simultaneously in saliva, the distal oesophagus, cardia, and the proximal and distal stomach of 17 healthy volunteers before and following intragastric nitrate (2 mmol) administration. RESULTS: The median pH in the distal oesophagus, cardia, and proximal and distal stomach were 7, 2.6, 1.9, and 1.7, respectively, before, and were similar following nitrate administration. Mean nitrite concentration in the distal oesophagus was similar to that of saliva, being 29.1 micro M and 36.7 micro M, respectively, before nitrate and increasing to 181.6 micro M and 203.3 micro M after nitrate ingestion. Within the stomach, mean (SEM) nitrite concentration following nitrate was higher in the cardia (45.5 (12.7) micro M) than in the mid (7.8 (3.1)) (p<0.01) or distal (0.8 (0.6)) (p<0.1) stomach, and ascorbic acid concentration was lower at the cardia (13.0 (6.1)) than in the mid (51 (19.2)) (p<0.02) or distal (86 (29)) (p<0.01) stomach. Consequently, the median ascorbic acid to nitrite ratio was lowest at the cardia (0.3) (p<0.01) versus the mid (7.8) or distal (40) stomach. Thiocyanate concentration was similar throughout the stomach. CONCLUSIONS: The conditions favouring luminal generation of N-nitroso compounds from dietary nitrate are maximal at the most proximal cardia region of the acidic stomach and may contribute to the high incidence of mutagenesis at this site.

Adolescent↗
PubMed2002

Dietary nitrate generates potentially mutagenic concentrations of nitric oxide at the gastroesophageal junction.

BACKGROUND & AIMS: Twenty-five percent of absorbed dietary nitrate is re-secreted in saliva, and 30% of this is reduced to nitrite by buccal bacteria. When saliva is swallowed, the acidic gastric juice reduces the nitrite to nitric oxide. The aim of this study was to examine the anatomic distribution of nitric oxide generation within the lumen of the upper gastrointestinal tract under basal conditions and after ingesting nitrate equivalent to that in salad portion. METHODS: Using custom-made sensors, the dissolved luminal nitric oxide concentration and pH were measured at 1-cm increments for 2 minutes throughout the length of the stomach and distal esophagus in 15 Helicobacter pylori-negative healthy volunteers with and without ingestion of 2 mmol potassium nitrate. Serum nitrate and saliva nitrite concentrations were also monitored. RESULTS: The nitrate ingestion increased mean (range) serum nitrate from 30 micromol/L (18-49) to 95 micromol/L (32-152), mean salivary nitrite from 36 micromol/L (19-153) to 252 micromol/L (32-600), and mean peak luminal nitric oxide concentration from 4.7 micromol/L (1.4-7.8) to 23.2 micromol/L (2.1-50) (P < 0.05 for each). After nitrate, the peak nitric oxide concentration occurred in 11 of the 15 (73%) subjects within 1 cm distal to the gastroesophageal pH step-up point. The mean nitric oxide concentration over the 1-cm segment immediately distal to the gastroesophageal pH step-up after nitrate was 7.5 micromol/L (range, 0.5-30.7) and was significantly higher than at all other sites. Nitric oxide concentrations greater than 50 micromol/L were observed at the precise location where neutral esophageal pH fell to acidic gastric pH. CONCLUSIONS: Luminal generation of nitric oxide from dietary nitrate via salivary nitrite is maximal at the gastroesophageal junction and cardia. The high concentrations of nitric oxide generated may contribute to the high incidence of mutagenesis and neoplasia at this site.

Adult↗
PubMed2002

In vitro studies indicate that acid catalysed generation of N-nitrosocompounds from dietary nitrate will be maximal at the gastro-oesophageal junction and cardia.

BACKGROUND: Dietary nitrate increases saliva nitrite levels and swallowed saliva is the main source of nitrite entering the acidic stomach. In acidic gastric juice, this nitrite can generate potentially carcinogenic N-nitrosocompounds. However, ascorbic acid secreted by the gastric mucosa can prevent nitrosation by converting the nitrite to nitric oxide. METHODS: To study the potential for N-nitrosocompound formation in a model simulating salivary nitrite entering the acidic stomach and the ability of ascorbic acid to inhibit the process. Concentrations of ascorbic acid, total vitamin C, nitrite, nitrosomorpholine, oxygen and nitric oxide were monitored during the experiments. RESULTS: The delivery of nitrite into HCl containing thiocyanate resulted in nitrosation of morpholine, with the rate of nitrosation being greatest at pH 2.5. Under anaerobic conditions, ascorbic acid converted the nitrite to nitric oxide and prevented nitrosation. However, in the presence of dissolved air, the ascorbic acid was ineffective at preventing nitrosation. This was due to the nitric oxide combining with oxygen to reform nitrite and this recycling of nitrite depleting the available ascorbic acid. Further studies indicated that the rate of consumption of ascorbic acid by nitrite added to natural human gastric juice (pH 1.5) was extremely rapid with 200 micromol/l nitrite consumed 500 micromol/l ascorbic acid within 10 s. CONCLUSIONS: The rapid consumption of ascorbic acid in acidic gastric juice by nitrite in swallowed saliva indicates that the potential for acid nitrosation will be maximal at the GO junction and cardia where nitrite first encounters acidic gastric juice. The high incidence of mutagenesis and neoplasia at this anatomical location may be due to acid nitrosation arising from dietary nitrate.

Ascorbic Acid↗
PubMed2001

Serum levels of fluconazole in patients after cytotoxic chemotherapy for hematological malignancy.

We performed a prospective evaluation of pharmacokinetics of fluconazole administered for prophylactic purposes to 19 patients after cytotoxic chemotherapy for hematological malignancies. On days 7 and 15, we obtained 5 ml of blood from each patient. If fluconazole was administered orally, blood samples were drawn 2, 8, and 24 hr after ingestion of the drug. If it was administered intravenously, blood samples were drawn 1, 8, and 24 hr post-injection. Serum fluconazole levels were analyzed by HPLC with ultraviolet light detection. In patients receiving 200 or 400 mg of fluconazole per day, maximal serum levels were 7.9 and 15.6 mg/l and minimum levels were 5.0 and 10.3 mg/l, respectively. There was no significant difference in serum fluconazole levels comparing the levels after oral and intravenous administration, and pharmacokinetic parameters of fluconazole were comparable at each time point within one dose level. However, considerable variation in serum fluconazole levels was noted in this study, as the maximal serum levels ranged from 4.0 to 13.3 mg/l and from 8.7 to 26.9 mg/l in patients receiving 200 and 400 mg of fluconazole orally, respectively. These variations may be associated with prophylactic failures for patients with insufficient fluconazole concentrations. Multiple regression analysis showed significant correlation between serum fluconazole levels and some variables including dose of fluconazole, age, serum aspartate aminotransferase levels and blood urea nitrogen levels. These variations may be associated with disturbance of body water balance, such as massive hemorrhage and dehydration.

Adult↗
PubMed2001

Octreotide for severe acute bleeding from portal hypertensive colopathy: a case report.

A 56-year-old man developed severe lower gastrointestinal bleeding. He was classified as Child-Pugh grade C. Colonoscopy revealed multiple angiodysplasia-like lesions and mucosal friability throughout the entire colon (portal hypertensive colopathy, PHC). Haemostasis was immediately achieved with octreotide treatment, although melaena recurred after discontinuation of the infusion. Propranolol treatment before discontinuation of octreotide infusin prevented the recurrence of bleeding from PHC. Octreotide is a safe and effective treatment for severe acute bleeding from PHC, especially if the patient is not a candidate for transjugular intrahepatic portosystemic shunt (TIPS) or treatment with a beta-blocker due to the severity of liver disease or haemodynamic instability. However, a sufficient reduction of portal pressure by propranolol or other medical treatment may be needed in order to discontinue octreotide infusion without the recurrence of bleeding.

Acute Disease↗
PubMed2000

A prospective randomized multicenter study of chlormadinone acetate versus flutamide in total androgen blockade for prostate cancer.

BACKGROUND: A randomized multicenter study was conducted to investigate the efficacy of total androgen blockade (TAB) for patients with previously untreated prostate cancer using the steroidal anti-androgen chlormadinone acetate (CMA) and the non-steroidal anti-androgen flutamide. We also compared the liver dysfunction in these two arms. METHODS: From November 1995 to October 1997, 71 patients were registered into this study and 70 of them were eligible. RESULTS: There was no significant difference in the efficacy of TAB between CMA and flutamide at 24 weeks. The testosterone and prostate-specific antigen (PSA) levels in patients administered flutamide (Group II) increased significantly 3 days after the first dose of LH-RH analog, whereas no such increase was observed in patients administered CMA (Group I), indicating that CMA prevented the flare-up. Parameters of liver function, serum GOT and GPT levels, which were normal at the baseline, became abnormal in 30.0% and 35.3%, respectively, of patients in Group II. These figures were significantly higher than the corresponding figures of 6.3% and 12.5%, respectively, in Group I. When the degree of change in each of these parameters was analyzed, both GOT and GPT levels showed a significantly greater increase in Group II than in Group I. CONCLUSION: These results indicate that attention must be paid to changes in liver function during the administration of flutamide in patients with prostate cancer even if their baseline liver function is normal. It is also suggested that CMA may be better tolerated from the viewpoint of the drug effects on liver function.

Adenocarcinoma↗
PubMed2000

[A retrospective study of the length of hospitalization following allogeneic bone marrow transplantation].

To estimate the length of hospitalization following bone marrow transplantation(BMT), we conducted a retrospective study of 190 patients who had received allogeneic BMTs at our institution. By our criteria, patients were considered ready for discharge if they were afebrile, did not need intravenous chemotherapy or blood transfusions more than 2 times per week, had maintained these conditions for 1 week or more, and also had no medical history of hepatic veno-occlusive disease, grade-II-or-higher graft-versus-host disease, interstitial pneumonitis, or severe hepato-renal dysfunction. The median length of hospitalization was 108.5 days. Of 82 patients who satisfied our discharge criteria by their 70th hospital day, 10 experienced mild complications during the next 30 hospital days. Of 89 patients who were considered ready for discharge by the 40th hospital day, 30 and 38 experienced complications during the next 30 and 60 hospital days, respectively, and 16 required emergency treatment. No significant baseline characteristics distinguished the patients who experienced complications from those who did not, either after 40 or 70 hospital days. This compounded the difficulty of predicting the development of complications in patients who satisfied our discharge criteria. Although management on an outpatient basis should be safe and feasible for BMT patients who meet our discharge criteria by the 70th day of hospitalization, caution is advised for early discharges after only 40 hospital days.

Adolescent↗
PubMed1999

Molecular remission in adult T cell leukemia after autologous CD34+ peripheral blood stem cell transplantation.

This report describes a patient with acute-type adult T cell leukemia/lymphoma (ATLL) successfully treated by autologous CD34+ peripheral blood stem cell transplantation after fractionated total body irradiation and high-dose cytarabine and cyclophosphamide. A newly established inverse polymerase chain reaction method was used to demonstrate the disappearance of ATLL clonal cells. The patient achieved a sustained molecular remission after transplantation, but died from opportunistic infection 4 months after transplantation. Thus, autologous CD34+ peripheral blood stem cell transplantation is promising for this type of malignancy. However, a prudent clinical attitude toward immunological fragility after transplantation is needed for better outcome.

Antigens, CD34↗
PubMed1999

Primary smooth muscle tumor of the liver encasing hepatobiliary cystadenoma without mesenchymal stroma.

We describe a 59-year-old Japanese woman with a large mass of her liver encasing cystic components. Radiologic imaging showed the mass to be hypervascular, and surgical resection disclosed a white tumor. The solid portion was immunohistochemically characterized as a smooth muscle tumor. The cystic components were multilocular and lined with columnar epithelium, consistent with a hepatobiliary cystadenoma. The epithelium strongly stained for CA19-9. The subepithelial space was occupied by collagenous connective tissue interspersed with a small number of spindle-shaped cells. The cystic lesions lacked the mesenchymal stroma between the epithelium and connective tissue layer. There have been no previous reports of a hepatic smooth muscle tumor encasing a hepatobiliary cystadenoma. Because of the pathogenesis of the cystadenoma, it is possible to assume that the smooth muscle tumor also arose from the cells composing the biliary duct in association with the development of the cystadenoma.

Biliary Tract Neoplasms↗
PubMed1998

Control of expression by the cellulose synthase (bcsA) promoter region from Acetobacter xylinum BPR 2001.

The 5' upstream region (about 3.1kb) of the cellulose synthase operon (bcs operon) has been isolated by cloning from Acetobacter xylinum strain BPR 2001. The expression level of the upstream region was determined using sucrose synthase cDNA as a reporter gene in the shuttle vector pSA19. The expression occurred with the 1.1-kb upstream sequence from the ATG start codon of the bcs operon but not with the 241-bp upstream sequence in A. xylinum, although neither the 1.1-kb nor the 241-bp upstream sequence caused any expression as a promoter in Escherichia coli. The level of expression with the 1. 1-kb upstream sequence in A. aceti was 75% of that in A. xylinum. These results suggest that the upstream region functions as a specific promoter for the Acetobacter genus. The expression was reduced by the introduction of the 241-bp upstream region between the lac promoter and the reporter gene in E. coli and was not detected in A. xylinum. This suggests that the short upstream region composed of 241bp contains the site(s) which causes a negative regulation on the transcription for bcs operon. The production of recombinant protein with the ribosome-binding site (RBS) of A. xylinum obtained from the bcs operon, was reduced to about half in E. coli, and that with the site of the lac promoter was also reduced to about half in A. xylinum. This shows that a species-specific predominance occurs during interaction between mRNA and 16S rRNA in the RBS between A. xylinum and E. coli.

Amino Acid Sequence↗
PubMed1998

Responses of trabecular and cortical bone turnover and bone mass and strength to bisphosphonate YH529 in ovariohysterectomized beagles with calcium restriction.

Thirty-six beagles, 18 months of age, underwent ovariohysterectomy (OHX) or a sham operation. Sham-operated animals were given a diet with standard calcium (1.4%) (group 1, n = 6) or a restricted calcium diet (0.14%) (group 2, n = 6). The OHX animals were given the restricted calcium diet and YH529 orally with respective daily doses of 0, 0.02, 0.1, and 0.5 mg/kg of body weight (groups 3-6, n = 6 each) for 12 months. At the end of this period, the lumbar bone mineral densities (BMDs) in groups 2 and 3 and the load values for group 3 were significantly smaller than those for group 1. The midfemur BMD did not differ among the groups. The urinary deoxypyridinoline (U-Dpy) and bone formation rates (BFR/BS, BFR/BV) in groups 2 and 3 and the osteonal BFR/BS and trabecular osteoclast number (Oc.N/BS) in group 3 were significantly larger than the respective values for group 1. However, these parameters did not significantly differ between groups 2 and 3. The serum osteocalcin (OC) level, wall thickness (W.Th), and mineral apposition rate values for group 3 were significantly larger than those for group 2. In group 2, the trabecular activation frequency (Ac.F) increased by 3.11 times, and the percent values of the number of labeled osteons (L-Ot.N/T-Ot.N, %) in the tibia by 3.28 times over those for group 1. In group 3, the Ac.F increased by 3.20 times and the number of labeled osteons by 3.77 times over those for group 1. In groups 4-6, the U-Dpy and Oc.N/BS values were smaller, but their OC levels did not significantly differ from the level for group 3. The lumbar BMD, the load, and W.Th were dose-dependently significantly larger than those for group 3. The Ac.F values were significantly smaller, and the respective value in groups 4-6 was 67.9, 25.5, and 10.2% of that in group 3. The BMDs of the midfemur in groups 4-6 were significantly larger than those in group 3, but the ultimate load values did not significantly differ. The L-Ot.N/T-Ot.N values were also significantly smaller, and the respective value in groups 4-6 was 82.0, 48.5, and 55.2% of that in group 3. The tibial endocortical and periosteal BFR/BSs did not differ significantly. These data demonstrate that the effects of OHX on bone mass and turnover were small in the beagles fed a restricted calcium diet. YH529 maintained the mass and strength of the lumbar bone by reducing the bone resorption. The cortical bone appeared to be less sensitive to the agent than the trabecular bone in this animal model.

Administration, Oral↗
PubMed1997

Percutaneous transluminal mitral valvuloplasty normalizes baroreflex sensitivity and sympathetic activity in patients with mitral stenosis.

BACKGROUND: In patients with mitral stenosis, reduced cardiac output or altered pulmonary hemodynamics may increase sympathetic nerve activity. However, the magnitude of the increase in sympathetic activity in such patients and the effect of valvuloplasty on this activity are unknown. METHODS AND RESULTS: We microneurographically measured muscle sympathetic nerve activity before and after mitral valvuloplasty in 10 patients (mean+/-SEM age, 48+/-2 years) with mitral stenosis and in 10 healthy volunteers (47+/-4 years); hemodynamic variables were also measured. Baroreflex sensitivity was assessed on the basis of the ratio of the change in heart rate or muscle sympathetic activity to the change in mean arterial pressure during intravenous infusion of sodium nitroprusside or phenylephrine. At baseline, muscle sympathetic activity was significantly higher in the patients with mitral stenosis than in the control subjects (42.1+/-3.2 versus 26.1+/-3.7 bursts/min, P<.05). However, there was no significant difference between the groups in sympathetic activity at 1 week after valvuloplasty. The reduction in sympathetic activity after valvuloplasty was maintained for > or = 6 months and correlated with the increase in cardiac index (r=.74, P<.05). Baroreflex sensitivity was significantly lower in the patients than in the control subjects, but after valvuloplasty there was no significant difference in baroreflex sensitivity between the groups. CONCLUSIONS: Sympathetic activity is increased in patients with mitral stenosis. Mitral valvuloplasty in such patients results in early and long-lasting normalization of sympathetic nerve activity, possibly because of an improvement in arterial baroreflex sensitivity.

Adult↗
PubMed1997

Relationship between hepatic angiotensinogen mRNA expression and plasma angiotensinogen in patients with chronic hepatitis.

Recent association and linkage studies suggested that angiotensinogen may play an important role in the pathogenasis of essential hypertension. However, there is little information in human concerning a relationship between plasma angiotensinogen levels and the angiotensinogen mRNA expression in the liver, which is the main production site of angiotensinogen. Therefore, the aim of this study was to examine whether hepatic angiotensinogen gene expression determines the level of circulating angiotensinogen and the activity of the renin-angiotensin system in humans. The subjects were 36 patients with chronic hepatitis. Blood was collected from each patients for estimation of plasma renin activity, plasma angiotensinogen and angiotensin II concentrations and several parameters of liver function. In addition, total RNA was isolated from liver biopsy specimens, which were then used to measure angiotensinogen mRNA with Northern blot analysis. Levels of angiotensinogen mRNA were detected easily in the liver biopsy specimens in all of the patients. Hepatic angiotensinogen mRNA levels were positively correlated with plasma angiotensinogen levels (r=0.41, P=0.013). In contrast, hepatic angiotensinogen mRNA levels did not show any significant relationship with plasma renin activity, plasma angiotensin II concentration, histological subgroup of hepatitis, histological activity index and parameters of liver function tests. The present study demonstrated, for the first time, that hepatic angiotensinogen mRNA levels correlated with plasma angiotensinogen concentration in humans.

Adult↗
PubMed1997

[Clinical studies on lower urinary tract injury].

A total of 61 patients with lower urinary tract injuries were treated at Nara Medical University and its affiliated hospitals, between January 1985 and June 1995. There were 9 patients with bladder injuries and 52 patients with urethral injuries. The main cause of bladder injury was a traffic accident sustained in 4 patients (44.5%) and that of urethral injury was an occupational accident sustained in 27 cases (51.9%). The major associated injuries were a bone fracture seen in 45 patients (73.8%) and an intrascrotal hematoma seen in 28 patients (45.9%). Posterior urethral injuries associated with pelvic bone fractures were classified into 3 types according to the classification reported by Colapinto et al.; 8 patients (32.0%) into Type I, 8 (32.0%) into Type II and 9 (36.0%) into Type III. Of the 25 patients with posterior urethral injuries, 8 (32.0%) underwent immediate surgical treatment, 12 (48.0%) underwent initial cystostomies and delayed surgical treatment and 5 (20.0%) received indwelling of urethral catheters. Postoperative complications of urethral injury included urethral stricture in 30 patients (57.7%), incontinence in 3 (5.8%) and impotence in 3 (5.8%). A significant relationship between the duration of cystostomy and the incidence of postoperative urethral stricture was observed in our patients. Therefore at least three weeks of cystostomy will be necessary in the management of patients with complicated urethral injuries.

Accidents, Occupational↗
PubMed1995

What is the difference of bone growth in SHR and SD rats?

1. Both sexes of spontaneously hypertensive rats (SHR) and Sprague-Dawley (SD) rats were used in this study. 2. At 6, 12, 18, 24, 30, 36, 42, 48, 54 and 60 weeks old, tibia length (L), volume (V), dry weight (DW), bone mineral density (BMD) in tibia and serum biochemical parameters (Ca2+, Ca, iP, ALP, TRAP) were measured. 3. At the 18 and 48 weeks old, bone morphometry was performed (mineral apposition rate, trabecular bone volume and trabecular thickness). Serum PTH and osteocalcin level were determined in 18 week old rats. 4. The time course change of DW, L and V were almost the same as the trends of bodyweight in each group, namely, male SD had the highest value, female SD and male SHR showed the same value and the lowest figures were obtained in female SHR. 5. BMD of the middle area showed almost the same trends with the time course change of bodyweight. On the other hand, both sexes of SHR had lower BMD than that of SD in the proximal area. 6. Serum biochemical parameters showed the same trends in both sexes of SD and SHR except for ALP (a marker of bone formation) which was higher in male than in female rats. 7. Mineral apposition rate, trabecular bone volume and trabecular thickness were not different between the same sex of SD and SHR. 8. These findings suggest that trabecular bone in SHR had a lower mineral status than that of SD rats not only in the adult but also in the young. This alteration may due to the abnormal mineralization mechanisms.

Aging↗