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Biomedical subjects

T Iwata

Publications and source records attributed to T Iwata.

At least 289 records · Page 16Linked to original sources

Atrial natriuretic factor effects on cyclic nucleotides in a human renal cell line.

The natriuretic effects of atrial peptide hormones have been attributed, at least in part, to their stimulation of guanylate cyclase activity in renal cell membranes. The effects of atrial natriuretic factor (ANF) on stimulation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) accumulation were investigated in cloned human kidney tumor (hKT) cells and parent cells from a human renal tumor epithelial cell line (SK-NEP-1). Human ANF-(99-126) (10(-6)M) stimulated (p less than 0.001) cellular cGMP accumulation in a dose-dependent manner from a basal level of 0.26 +/- 0.04 to 3.73 +/- 0.81 pmol/mg protein/5 mi (mean +/- SEM, n = 13). ANF stimulation of cGMP accumulation was specific, in that high concentrations (10(-6)M) of atriopeptin I [rat ANF-(103-123)], angiotensin II, arginine vasopressin, and amiloride (10(-4)M) did not increase basal cGMP. Amiloride (10(-4)M) enhanced (p less than 0.01, n = 6) the ANF stimulation of cGMP accumulation (1.24 +/- 0.39 pmol/mg protein/5 min), particularly at low doses of ANF (10(-10)M) where stimulation by ANF without amiloride (0.34 +/- 0.08 pmol/mg protein/5 min) was barely distinguishable from a basal level (0.19 +/- 0.02 pmol/mg protein/5 min) of cGMP accumulation. The stimulatory effect of ANF (1.59 +/- 0.07 pmol/mg protein/5 min) was attenuated (0.75 +/- 0.06 pmol/mg protein/5 min, p less than 0.01, n = 6) by preincubation of the cells with pertussis toxin but not by cholera toxin. ANF (4.56 +/- 0.93 pmol/mg protein/5 min, n = 8) did not affect cAMP accumulation (4.32 +/- 0.98 pmol/mg protein/5 min) in hKT cells. This is the first report of an ANF responsive human renal cell line, and its use should facilitate investigation of ANF-receptor interactions.

Atrial Natriuretic Factor↗

[Pharmacokinetics of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoate (Y-20811), a new thromboxane synthetase inhibitor. II. Pharmacokinetics of intact drug and main metabolite in dog].

The pharmacokinetics of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoat e (I-Na) in the beagle dog was investigated after p.o. and i.v. administration. After the administration of I-Na at 3 mg/kg (p.o.), 70.9% of the dose was absorbed, and the maximum plasma concentration of free acid (I) was observed at 0.33 h. After p.o. administration, the area under the plasma concentration-time curve of I increased almost linearly in proportion to the dose. The metabolite, 4-[alpha-hydroxy-2-hydroxymethyl-5-(1-imidazolyl)benzyl]-3,5-dimethyl benzoic acid (II) was also detected in the plasma, but the concentration of II was lower than that of I. After the administration at 3 mg/kg (p.o.), 27.7% and 3.8% of the dose were recovered as I and II, respectively, in the urine, and 32.2% and 30.1% recovered as I and II in the feces. Therefore, 93.8% of the dose was totally recovered within five days. The inhibitory effect of II on the aggregation of rabbit platelets was studied in vitro. This metabolite showed only one sixth activity of I-Na. Thus, the inhibitory effect on the platelet aggregation of II is considered to be almost negligible in the beagle dog administered with I-Na.

Animals↗

[Pharmacokinetics of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoate (Y-20811), a new thromboxane synthetase inhibitor. I. Isolation and structure elucidation of urinary metabolite in dog].

The urinary metabolites of sodium 4-[alpha-hydroxy-5-(1-imidazolyl)-2-methylbenzyl]-3,5-dimethylbenzoat e (Y-20811) in dog were investigated. The main metabolite was isolated by high performance liquid chromatography and subsequent preparative thin layer chromatography. The structure of this metabolite was established as 4-[alpha-hydroxy-2-hydroxymethyl-5-(1-imidazolyl)benzyl]-3,5- dimethylbenzoic acid on the basis of spectral analyses and confirmed by its total synthesis.

Animals↗

Liver function in congestive heart failure: abnormal elevation of serum hepatic enzyme and hepatic venous flow velocity.

Fifty one patients (pts) with various heart diseases and 6 normal subjects (N) were studied. Four of the 51 pts showed unusually high GOT values (greater than 3000 IU) without preceding evidence of acute heart failure, myocardial infarction, or hepatitis. Of these 4 pts, either ventricular tachyarrhythmias, marked bradycardia, or rapid ventricular response with atrial fibrillation (af) were evident a few days prior to the GOT elevation. GOT values returned to below 100 IU within a few days, but hypotension and frequent arrhythmias were sustained in 3 of the 4 pts and these 3 pts died about one month later. The symptoms of the remaining one improved but he too died 9 months later of ventricular fibrillation. A postmortem histological examination revealed centrilobular necrosis of the liver cells. Thus, abnormal GOT elevation may result from hepatic cell necrosis, which is probably due to tissue hypoperfusion caused by severe arrhythmias. Hepatic venous flow velocity (HFV) was measured in the remaining 47 pts and 6N using a pulsed doppler echocardiogram. The HFV curve was biphasic, with the first curve corresponding to the forward flow velocity during ventricular systole (s-HFV) and the second corresponding to ventricular diastole (d-HFV). The ratio of the area under s-HFV curve to the sum of areas under s-HFV and d-HFV curves was defined as the VI ratio. In N, the VI ratio was 0.7 +/- 0.06 whereas the VI ratio in pts in sinus rhythm tended to be above 0.7. This indicated that s-HFV is greater than d-HFV in N while s-HFV is less than d-HFV in pts in sinus rhythm. There was a good negative correlation (n = 15: r = -0.70) between VI ratio and cardiac index (CI) in these pts, suggesting that the contribution of s-HFV to the venous return becomes greater as the cardiac function becomes more impaired. In pts with af, the VI ratio was below 0.5 and there was a good positive correlation (n = 14: r = 0.82) between the VI ratio and CI. This suggested that the s-HFV may be reduced due to a lack of atrial contribution in af so that contribution of d-HFV to venous return becomes greater as the cardiac function becomes more impaired. Thus, the HFV pattern may reflect the abnormality of the cardiac pump function in human beings.

Adult↗

[Chronic trismus in the severe skeletal Class III cases].

In general, patients who have trismus as chief complaint often have acute symptoms, but limited number of these patients have chronic trismus. We studied 51 patients (mean age; 18y 4n) with severe skeletal class III (less than ANB less than or equal to O), who need surgical treatment. Three types were classified according to the movement of the mandibular head at the maximum mouth opening at their first visit. A-type; the mandibular head hardly move. B-type; it dose not move beyond articular eminence. C-type; it moves beyond articular eminence. These classifications were applied to the both sides of the mandibular head in the 51 patients to divide into 5 types (Type AA, Type AB, Type BB, Type BC, Type CC). Those patients were analyzed according to these five types. The results obtained were as follows; 1) Seventy-three percent of all the cases were female in this study. Sixty-five percent of both the sexes had chronic trismus without having subjective symptoms on the mandibular joints in their daily lives. Type AA, AB, BB, and BC accounted for 12%, 6%, 31%, and 16% respectively. 2) There were fewer contacts in the upper posterior antagonist teeth in AA and AB; particularly at 5. In all the cases of Type CC, contacts with the antagonist tooth 5 were seen. 3) As a conclusion, movement of the mandibular head in the patients with trismus are found to have a characteristic limitation at the maximum mouth opening and the stress points in the occlusal contacts at the centric occlusion to be the posterior area.

Adolescent↗

[A clinical study of terminal pneumonia].

A total of 210 cases of terminal pneumonia were studied out of 1183 autopsied cases at Tenri Yorozu Hospital from 1978 to 1985. Underlying diseases included lung cancer (77 patients), gastric cancer (26 patients), leukemia (24 patients). There was no statistical significance between the time from death until autopsy and the bacterial examination of autopsied lung and blood. P. aeruginosa and Klebsiella sp. were the most frequently isolated organisms. Seventy percent of isolated organisms were gram negative bacilli. In spite of administration of antibiotics, bacteria isolated from specimens before death were sometimes the same as the one isolated from specimens after death. In addition it was recognized that multiple intensive examinations of sputum are necessary for rapid diagnosis of pneumonia. It was also noted that the longer the duration of antibiotic administration, the more frequently P. aeruginosa was isolated. Finally the possibility of pneumonia should be kept in mind in compromised hosts.

Humans↗

[Studies on initiation and progression of focal glomerular sclerosis in rats].

In order to clarify the mechanisms of the initiation and progression of focal glomerular sclerosis (FGS), we investigated changes in the mesangial function or qualitative changes in the extracellular matrix of mesangium in puromycin aminonucleoside (PAN)-induced FGS in rats. At first, we investigated that the relationship between the progression of FGS and mesangial function. In order to evaluate the mesangial function, rats received the i.v. injection of colloidal carbon (C. C.) (20 or 30 mg/100 g). Results obtained from this experiment suggest that the progression of glomerular sclerosis may be related to changes in mesangial function. Furthermore, results suggest that the abnormality of the extracellular matrix may lead to changes in mesangial function and the progression of glomerular sclerosis. Therefore, in the next experiment, the proteoglycans (PGs), one of the components of extracellular matrix, were analyzed by the column chromatography to clarify qualitative changes in the PGs such as the molecular size and charge density. Results obtained from this experiment indicate that the sclerotic glomeruli synthesize the PGs with different molecular size and charge density from normal glomeruli. It is concluded from these experiments that the abnormality of the mesangial function and the synthesis of PGs, the components of the extracellular matrix, may lead to the progression of FGS. Namely, the qualitatively altered PGs may cause abnormal interactions with other components of matrix, which lead to changes in mesangial function, death of mesangial cell and the progression of FGS.

Animals↗

Effects of zopiclone on sleep spindles studied with an improved waveform recognition method.

The effects of zopiclone on sleep spindles were analyzed in six normal volunteers by using an improved waveform recognition method. The appearance rate of spindles during stage 2 of NREM sleep showed a significant increase on the drug night, which returned to the baseline on the withdrawal night. The mean duration of spindles was significantly prolonged on the drug night. No definite changes were observed in the average spindle frequency. The mean amplitude of spindles had a tendency to decrease on the drug night. On the withdrawal night, the mean amplitude decreased significantly compared with that of the baseline. Our results indicate that zopiclone is one of the spindle enhancing drugs, and that its property resembles that of benzodiazepines.

Adult↗

[Traumatic ophthalmic artery-superior ophthalmic vein fistula: a case report].

Traumatic intraorbital arteriovenous fistula is rare and only 2 cases have been reported. The authors report the case of a 70-year-old man with consciousness disturbance after non-penetrating head injury. CT scan showed diffuse subarachnoid hemorrhage in the basal cistern, and angiography on the next day revealed ophthalmic artery-superior ophthalmic vein fistula in the right orbit. During the clinical course of this lesion, there was mild chemosis of the right eye, without palsy of extraocular muscles. Both papilledema and bruit were absent. Conservative treatment was chosen. On the 26th day after the head injury, repeated angiography showed complete disappearance of the fistula. The patient was discharged on the 39th day without neurological deficit. In the other two reported cases, intraorbital A-V fistulae were caused by direct-penetrating injury. But, in the present case the head injury was non-penetrating and blunt type. The pathogenesis was considered to be indirect injury of the intraorbital vessels at the retrobulbar portion, approximately where the artery and the vein crossed. As regards to treatment, simple observation may be the first choice, and spontaneous obliteration can be expected. If this does not occur, either embolization or ligation of the ophthalmic artery is suggested as the second choice as proposed by Freitas MAL et al.

Aged↗

[A case report of atypical coarctation of the aortic arch with thoracic aortic aneurysm].

A 30-year-old woman was admitted to our hospital because of the abnormal shadow on chest X ray film and paralysis of right fingers. The preoperative aortogram and DSA showed atypical coarctation of the aortic arch with thoracic aortic aneurysm. We successfully performed extra-anatomical bypass with a 14 mm Cooley low porosity Ducron graft between ascending aorta and discending aorta. Her postoperative course was uneventful and discharged one month after the operation.

Adult↗

[A probable case of adult Williams-Campbell syndrome incidentally detected by an episode of atypical mycobacterial infection].

A 39-year-old woman was admitted to our hospital because of dry cough. She had been quite well until 1 month before admission. She had no history of chronic sinusitis. Chest X-ray film showed a thin-walled cavity in the superior segment of the left lower lobe of the lung. Curettage biopsy of the cavity wall revealed granulomatous change. Mycobacterium intracellulare-avium complex was identified on sputum culture. Anti-tuberculous therapy was given and the cavity disappeared in 3 months. Since atypical mycobacterial infection is quite unusual for a healthy woman to contract, we performed high-resolution CT (HRCT) in search for occult abnormalities of the lung. HRCT detected a lot of thin-walled cystic lesions, and bronchography showed that they were consistent with cystic dilatation of relatively large bronchi, which ballooned up during inspiration, and collapsed during expiration. Airways peripheral to these dilatations were also visible, and were quite different from usual cystic bronchiectasis formed by acquired recurrent infections. Her bronchiectasis is most likely congenital in its etiology, and might be considered as an adult case of Williams-Campbell syndrome.

Adult↗

Synthesis of p-nitrophenyl 6(5)-O-benzyl-alpha-maltopentaoside, a substrate for alpha amylases.

p-Nitrophenyl alpha-maltopentaoside, having a benzyl group on O-6 of the terminal (nonreducing) D-glucosyl group was prepared by use of a reductive ring-opening reaction. Highly regioselective reduction of p-nitrophenyl O-(2,3-di-O-benzoyl-4,6-O-benzylidene-alpha-D-glucopyranosyl)-(1----4)- tris[O-(2,3,6-tri-O-benzoyl-alpha-D-glucopyranosyl)-(1----4)]-2,3,6-tri- O- benzoyl-alpha-D-glucopyranoside by dimethylamine-borane and p-toluenesulfonic acid, followed by debenzoylation, gave p-nitrophenyl O-(6-O-benzyl-alpha-D-glucopyranosyl)-(1----4)-tris[O-alpha-D-glucopyran osyl- (1----4)]-alpha-D-glucopyranoside. An experiment was done on the mode of action of human pancreatic and salivary alpha amylases on this derivative. The compound is suitable as a substrate for the assay of alpha amylase when used with glucoamylase and alpha-D-glucosidase as coupling enzymes.

Carbohydrate Conformation↗

Type-specific efficacy of acellular pertussis vaccine.

Two types of acellular pertussis vaccine have been used in Japan since their introduction in 1981. They are different in their antigen content and immunogenicity. To assess the type-specific efficacy of acellular pertussis vaccine commercially available in Japan, 442 households of patients with pertussis were surveyed from 1981 to 1987. The secondary attack rates in children 2 through 8 years of age were 61.3% (46/75) in unimmunized children, 7.5% (4/53) in children fully immunized by the filamentous hemagglutinin predominant type acellular pertussis vaccine, 14.3% (1/7) in children fully immunized by the pertussis toxin-filamentous hemagglutinin type vaccine, and 13.5% (7/52) in children given whole-cell pertussis vaccine. The estimated efficacy was 87.7% for the filamentous hemagglutinin predominant type vaccine and 76.7% for the pertussis toxin-filamentous hemagglutinin type vaccine in children aged 2 through 8 years. Both types of acellular pertussis vaccine were similarly effective, without any statistically significant differences, and their efficacy was not different from that of whole-cell vaccines. This survey also indicated that adults are a major source of infection, with a high secondary attack rate of 7.8%.

Adult↗

Aminoglycoside-induced alterations in apical membranes of kidney epithelial cell line (LLC-PK1).

Aminoglycoside-induced renal cell injury was investigated using the LLC-PK1 pig kidney epithelial cell line. The development of aminopeptidase and gamma-glutamyltransferase, marker enzymes for apical membranes, was inhibited in the LLC-PK1 cells cultured with gentamicin. The inhibitory effect of gentamicin on the enzyme activities was dose dependent and was related to its accumulation within the cells. The development of Na+ -dependent active transport of alpha-methyl-D-glucoside, a nonmetabolizable hexose, was also inhibited by treatment with gentamicin. Inhibitions in apical membrane enzyme activities and Na+ -dependent transport of alpha-methyl-D-glucoside were associated with the elevation of cytosolic free calcium, determined with a fluorescent indicator fura-2. The correlation between the alterations in apical membrane functions and the increase in cytosolic free calcium concentration was also supported by the study using the calcium ionophore A23187. The present data suggest that aminoglycoside-induced alterations in apical membranes of the LLC-PK1 cells are related to the increase in cytosolic free calcium levels.

Aminoglycosides↗

Body temperature monitoring in subjects with delayed sleep phase syndrome.

To clarify the circadian aspects of delayed sleep phase syndrome (DSPS) in 4 patients with DSPS, we recorded polysomnograms and rectal temperature before and after chronotherapy. The time interval (2.7 h) between sleep onset and rectal temperature minimum before chronotherapy was shorter than the time interval after chronotherapy (5.3 h). Before chronotherapy, the period of rectal temperature rhythm was 24.7 h. After chronotherapy, the period of rectal temperature rhythm was 24.0 h. These findings lead to the conclusion that in DSPS there is a weakened mechanism of entrainment similar to that in non-24-hour sleep-wake syndrome.

Adult↗