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Biomedical subjects

M Ohta

Publications and source records attributed to M Ohta.

At least 757 records · Page 42Linked to original sources

Genomic DNA fingerprinting by pulsed-field gel electrophoresis as an epidemiological marker for study of nosocomial infections caused by methicillin-resistant Staphylococcus aureus.

In this study, we have compared genomic DNA fingerprintings among isolates of methicillin-resistant Staphylococcus aureus (MRSA) by using pulsed-field gel electrophoresis (PFGE). Chromosomal fragments digested with SmaI were most suitable for the PFGE separation. SmaI cut genomic DNA into 15 to 20 fragments whose sizes ranged from about 30 to 1,500 kb. Thirty-one distinctive fragment patterns were identified in 111 infecting and colonizing MRSA isolates from six different hospitals in Japan. On the basis of the genomic typing by PFGE, we performed an epidemiological investigation of an outbreak of nosocomial MRSA infections among inpatients in Nagoya University Hospital. Ten types of chromosomal digestion were identified in the 20 strains isolated from 18 infected patients and 1 from colonized hospital personnel. According to the restriction patterns, we found that four types of these strains had caused epidemic infections among 13 patients in the outbreak. Two types (types 1 and 4) of the strains were involved in the death of five patients. The other infections were sporadic. The clarity and polymorphism of the chromosomal digestion patterns enabled us to discriminate between isolates which could not be differentiated by antibiogram or plasmid analysis. Classification of the genomic DNA fingerprinting patterns by PFGE is therefore proposed as a useful method for investigating the source, transmission, and spread of nosocomial MRSA infections.

Biomarkers↗

Effects of calmodulin antagonists on hydrogen-translocating shuttles in perfused rat liver.

The effects of calmodulin antagonists on the capacity of hydrogen-translocating shuttles were studied in the perfused rat liver. The capacity was estimated by measuring the changes in the rate of production of glucose from sorbitol during the oxidation of ethanol [T. Sugano, T. Ohta, A. Tarui, and Y. Miyamae. Am. J. Physiol. 251 (Endocrinol. Metab. 14): E385-E392, 1986]. Thyroxine given to intact rats increased the activity of alpha-glycerophosphate dehydrogenase (alpha-GPD). Glucocorticoid replacement in adrenalectomized rats decreased the activity of the alpha-GPD to values obtained after treatment with PTU. In either thyroxine-treated or steroid-replaced rats, the capacity of hydrogen-translocating shuttles increased markedly. However, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), trifluoperazine, and chlorpromazine inhibited the increased capacity in steroid-replaced rats and had no effect on the increased capacity in thyroxine-treated rats. W-7 inhibited the stimulatory effects of norepinephrine on the capacity of the malate-aspartate shuttle without inhibition of efflux of intracellular Ca2+. The stimulatory effects of vasopressin on the malate-aspartate shuttle were also inhibited by W-7, trifluoperazine, and chlorpromazine. The results suggest that the malate-aspartate shuttle may be regulated by Ca(2+)-calmodulin.

Adrenalectomy↗

Effect of cyproterone acetate on active and inactive renin secretion in patients with precocious puberty and genetic short stature.

To evaluate the effect of cyproterone acetate (CA) on the renin-angiotensin-aldosterone axis, we measured the plasma active, inactive and total renin concentrations (PARC, PIRC and PTRC) during and after CA treatment in patients with precocious puberty and genetic short stature. CA was administered at a daily dose of 150-170 mg/m2 in all subjects. PARC and PTRC were measured by immunoradiometric assays. During CA treatment, PARC, PIRC, PTRC and the PARC/PTRC ratio were significantly decreased. The plasma renin activity, measured by enzymatic assay, and the plasma aldosterone concentration were also decreased. After CA discontinuation, all of these were increased immediately along normal ranges. PARC closely correlated with plasma renin activity. These results suggest that CA produces mineralocorticoid action and suppresses the production and activation of renin.

Androgen Antagonists↗

Determination of leukocyte elastase concentration in plasma and serum by a simple method using a specific synthetic substrate.

The concentration of leukocyte elastase (ELP) in plasma and serum was determined by an amidolysis method using a specific synthetic substrate for ELP, Suc-Ala-Tyr-Leu-Val-pNA. Results were compared with those using ELISA. ELP levels in plasma from healthy donors were similar to those determined by ELISA; however, the levels in serum were lower than those determined by ELISA. Correlation coefficients of ELP levels in plasma and serum as measured by the two methods were 0.75 (amidolysis) and 0.90 (ELISA). On the other hand, the correlation coefficient between serum ELP by the two methods was 0.83. Half of the ELP levels in plasma from 150 patients and serum from 400 patients were significantly elevated when compared with those from healthy donors, and the ELP elevation determined by amidolytic assay correlated with some variables in blood, namely fibrin(ogen)-degraded products, fibrinogen, GOT, GPT, gamma-GTP, LDH and leucine aminopeptidase. Despite the fact that the amidolysis method detects the alpha 2-macroglobulin-ELP complex while ELISA detects the alpha 1-antitrypsin-ELP complex, a comparative study showed amidolysis to provide sufficiently sensitive measurement of both plasma and serum ELP.

Adult↗

Long-term survivors in resected and nonresected small cell lung cancer.

Long-term survival (greater than or equal to 3 years) was evaluated in 164 patients with small cell lung cancer (SCLC). Thirty-seven patients underwent surgical resection, and 127 did not. All but one resected patient received combination chemotherapy. Of the 20 (12%) long-term survivors, 13 (35%) were resected, and 7 (6%) were not. Eleven of these resected patients had pathologically confirmed stage I disease. All of the 7 nonresected patients achieved complete remission by treatment, 6 of these having presented with limited disease. In addition, all patients received thoracic irradiation combined with chemotherapy. Two of the 20 patients who survived beyond 3 years developed a second malignancy 11.3 and 12 years, respectively, after initial treatment for SCLC. In conclusion, surgical resection for stage I, and probably stage II SCLC followed by chemotherapy may be an appropriate therapeutic approach. For advanced limited disease, thoracic irradiation, in addition to chemotherapy, seems to improve long-term survival.

Adult↗

Late enhancement of the left ventricular wall in hypertrophic cardiomyopathy by ultrafast computed tomography: a comparison with regional myocardial thickening.

Eight patients with hypertrophic cardiomyopathy (HCM) were examined by ultrafast computed tomography (UFCT) to investigate the relationship between late enhancement (LE) of the left ventricular (LV) wall after injection of contrast medium and the variations between minimum and maximum wall thickness of the LV. Late enhancement was usually found as a patchy, stained area in the myocardium on delayed phase volume mode images of UFCT. Out of 48 LV segments of the patients with HCM, 21 had LE. Normalized percentage regional wall thickening in the segments that had LE was significantly less than that in the segments that did not have LE (63.6 +/- 44.5% and 137.6 +/- 54.6%, respectively; p less than 0.001). This may reflect abnormal myocardial architecture.

Adolescent↗

Appearance of thrombosis-inducing activity in the plasma of patients undergoing pulmonary resection.

Thrombosis-inducing activity (TIA) was detected in the peripheral blood of patients with lung cancer who had undergone pulmonary resection. TIA was examined by intravenously injecting plasma from the patients into BALB/c mice. The plasma containing TIA induced multiple thromboses in the lung and caused the mice to die 3 to 30 minutes after injection. The subjects were 19 patients whose plasma contained no TIA before operation. TIA was detected in 5.3 percent (1/19) on the first postoperative day (POD), 47.4 percent (9/19) on the seventh POD, 47.1 percent (8/17) on the 14th POD, 26.7 percent (4/15) on the 21st POD, and 20 percent (2/10) on the 28th POD. Plasma fibrinogen levels and peripheral platelet counts increased postoperatively and reached a maximum on the seventh and 14th POD, respectively. Peripheral blood with TIA had a significant elevation of plasma fibrinogen levels and platelet counts as compared to that without TIA. These observations suggest that TIA is present in blood in a hypercoagulable state in patients after pulmonary resection. Since tumor necrosis factor and interleukin 1 are known to induce hypercoagulable states both in vitro and in vivo, we tried to determine whether it was possible to detect both cytokines in blood indicated as hypercoagulable state by the presence of TIA. They did not, however, reach detectable levels in the blood.

Aged↗

Cyclical edema in a patient with hypothalamic disorders and chronic glomerulonephritis: arginine vasopressin-dependent atrial natriuretic hormone release.

A 28-year-old woman had hypothalamic disorders (amenorrhea, obesity, psychiatric abnormalities, polydipsia and fever) and chronic glomerulonephritis. She also suffered from general edema associated with cyclical oliguria and polyuria. Her body weight and plasma osmolality increased during the oliguria phase lasting 2 to 8 days and decreased after paroxysmal polyuria accompanied by the natriuresis. These episodes occurred repeatedly, regardless of the treatment with or without diuretics. The release of arginine vasopressin in response to increased plasma osmolality was exaggerated, but changes in plasma volume did not affect arginine vasopressin release. Plasma atrial natriuretic hormone increased in response to a rise in plasma arginine vasopressin and plasma volume during the oliguria phase, thereby resulting in the diuresis and natriuresis. The renin-angiotensin-aldosterone system was secondarily activated by body fluid depletion and diuretics, and this might play an additive role in general swelling. Plasma gonadal hormones did not change to explain the edema. The mechanism of this cyclical edema remains unknown, but it is likely that hypothalamic dysfunction related to psychiatric abnormalities may exaggerate arginine vasopressin release, and enhanced renal sympathetic activity may cause retention of Na and water, and the increase in atrial natriuretic hormone release responding to the plasma volume expansion may bring about the diuresis and natriuresis.

Adult↗

A case of syndrome of inappropriate secretion of antidiuretic hormone associated with diabetes mellitus.

A 46-year-old man, presenting with headache, nausea, and lassitude, was diagnosed as having diabetes mellitus and hyponatremia, and admitted to Tohoku University Hospital. Insulin treatment improved the hyperglycemia but aggravated hyponatremia, which was proved to be elicited by the inappropriate secretion of antidiuretic hormone (SIADH). An acute water load failed to suppress ADH release in the supine posture but slightly increased plasma atrial natriuretic peptide (ANP). On the other hand, plasma ADH markedly increased in response to an upright posture, accompanied by a fall in blood pressure and a rise in heart rate. After treatment with droxidopa "a sympathomimetic drug", ambulatory blood pressure gradually increased and hyponatremia disappeared. However, blood pressure and ADH responses to upright posture were not improved by treatment with the drug. Moreover, plasma ADH was still not sufficiently suppressed by acute water loading in the supine position, but plasma ANP markedly increased, thereby resulting in urinary dilution and natriuresis. These results suggest that exaggerated ADH release (SIADH) was brought about by the baroreceptor reflex stimulated by the postural hypotension, and also by the impaired osmoregulation associated with diabetic neuropathy, and that droxidopa improved cardiovascular function and increased ANP release with resultant urinary dilution and natriuresis in spite of slightly increased ADH release.

Blood Pressure↗

Responses of atrial natriuretic peptide, vasopressin, aldosterone and renal function to intracerebroventricular infusion of angiotensin II in dogs.

To assess the mechanisms how angiotensin II (Ang II) given intracerebroventricularly (i.c.v.) induces natriuresis, the effects of Ang II (10 ng/kg/min, for 30 min) on the renin-angiotensin-aldosterone system, the release of vasopressin (AVP) and atrial natriuretic peptide (ANP) and on cardiovascular and renal functions were investigated in anesthetized dogs. In control dogs, vehicle alone (artificial cerebrospinal fluid) was infused at a rate of 10 microliters/min. Ang II given i.c.v. produced a gradual increase in urine flow, urinary sodium and potassium excretion and osmolar clearance, but had no effect on plasma ANP, aldosterone, arterial blood pressure, and renal blood flow. However, i.c.v. Ang II increased plasma AVP and decreased heart rate, plasma renin activity, inulin clearance and filtration fraction. In the cotrol group, vehicle treatment had no effect on these parameters except for decreases in inulin clearance and filtration fraction. These results suggest that circulating ANP and blood pressure may not play an important role in i.c.v. Ang II-induced natriuresis, but increased AVP release and decreased renal sympathetic nervous activity may contribute to the natriuresis.

Aldosterone↗

Glucocorticoid-induced central diabetes insipidus in a case of malignant lymphoma.

A 37-year-old man was diagnosed as malignant lymphoma infiltrating in the central nervous system with hypopituitrism and secondary glucocorticoid deficiency. In this case, plasma arginine vasopressin (AVP) increased, but glucocorticoid administration decreased plasma AVP and increased urine volume with a reduction in urinary osmolality, indicative of the presence of glucocorticoid-induced diabetes insipidus. At the terminal stage, plasma AVP did not increase in response to the withdrawal of glucocorticoid and urine volume remained decreased, suggesting the presence of masked diabetes insipidus. Autopsy showed an infiltration of lymphoid cells around the cerebral ventricles and necrosis in the hypothalamo-hypophyseal system. These findings suggested that glucocorticoid might centrally play an important role in the regulation of AVP release, and its deficiency potentiated AVP release.

Adult↗

Effect of vasopressin on cardiovascular and renal functions and ANP release under plasma volume expansion.

To assess the mechanisms whereby arginine vasopressin (AVP) increases atrial natriuretic peptide (ANP) release and to examine whether AVP-mediated ANP release affects the effect of AVP on the cardiovascular and renal function, AVP was infused continuously at a rate of 20 ng.kg-1.min-1 for 75 min following 200 ng/kg bolus injection under stepwise increases in plasma volume in anesthetized dogs. Moreover, the effect of an AVP antagonist, a V1 blocker, 1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid)-2-(o-methyl)tyrosine AVP (TMeAVP), on these parameters was also investigated. In the control study, saline alone was infused. AVP infusion increased total peripheral resistance (TPR), pulmonary capillary wedge pressure (PCWP), and plasma ANP, but decreased cardiac index (CI) and heart rate (HR) without increases in mean arterial blood pressure (MABP). Stepwise rises in plasma volume further increased plasma ANP, CVP, CI and PCWP, but gradually decreased TPR. TMeAVP curtailed AVP-induced increases in TPR and plasma ANP as well as decreases in CI and HR. The replacement of ANP to prevent a fall in plasma ANP following TMeAVP never affected cardiovascular function. AVP infusion increased plasma volume accompanied by a fall in urinary Na excretion (UNaV) and urine flow (UF) under the stepwise plasma volume expansion compared to the control group, but did not affect mean circulatory filling pressure (MCFP). ANP administration enhanced UNaV and UF and decreased MCFP. These results indicate that AVP may preferentially increases ANP release via the increased cardiac afterload, not preload, but increased plasma ANP per se may not be involved directly in the AVP-induced cardiac suppression.

Animals↗

[Study on recurrence of hypertensive intracerebral hemorrhage].

Recurrence of hypertensive intracerebral hemorrhage confirmed by computed tomography scan has rarely been reported. The authors have experienced nine cases of recurrent hemorrhage among 494 cases of hypertensive intracerebral hemorrhage. Recurrence rate was 1.8%. There were eight males and one female with an average age of 60.5 years. Six cases had their first and second attacks in ganglionic regions. Among them, three cases had the second attack in the ipsilateral side, and the other three cases had the second attack in the contralateral side. Two cases had the first attack in the thalamic and the second in the cerebellar regions. One case had the first attack in the pontine and the second in the putaminal regions. Intervals between the first and second attacks were within 6 months for ipsilateral ganglionic attacks and over 4 years for contralateral ganglionic attacks. In all cases systemic blood pressure was normalized or well controlled by antihypertensive agents after the first attack. The mechanism of rebleeding has not been clarified.

Activities of Daily Living↗

Comparison of 1,5-anhydroglucitol, HbA1c, and fructosamine for detection of diabetes mellitus.

To evaluate the use of serum 1,5-anhydroglucitol (AG) levels in screening for diabetes mellitus, we compared the sensitivity and specificity of HbA1c, fructosamine (FA), and AG in 1620 randomly selected subjects in 11 institutions throughout Japan. Most individuals were receiving diet and/or drug therapy for diabetes. Subjects were separated into four groups based on World Health Organization criteria: nondiabetic control subjects, subjects with impaired glucose tolerance (IGT), patients with diabetes, and patients with other disorders without IGT. The overlap of AG values between each group was less than that of HbA1c or FA values. AG levels were significantly correlated with fasting plasma glucose (r = -0.627), HbA1c (r = -0.629), and FA (r = -0.590) levels. If we took 14 micrograms/ml as the normal lower limit, AG level was highly specific (93.1%), and a decreased AG level indicated diabetes mellitus (84.2% sensitivity). According to the selectivity index (sensitivity value times specificity value), AG determinations were superior to both HbA1c and FA measurements for diabetes screening. When combinations of these tests were used, only AG and HbA1c together were slightly better than AG alone. Thus, together with other advantages of AG, e.g., its wide variance with relatively fair glycemic control and the negligible influence of the sampling conditions, AG level has more potential than HbA1c or FA level as a screening criterion for diabetes.

Biomarkers↗

[Epidemiologic background and changes in patients infected with human papilloma virus].

Contagion with certain types of HPV was supposed to have a causal relationship with cervical neoplasia of the uterus. The rate of prevalence of HPV was investigated in pre-cancer and cancer patients with uterine cervical smear using virapap or viratype. According to the cytologic classification, among those whose cytology was diagnosed as class I or II, were found a few positive HPV, however, in cases in classes cytology IIIa, III and IIIb, the positive rate turned out to be 22.5, 41 and 72.4%, respectively. About 65% of patients whose post-operative diagnosis was cervical carcinoma, had been found positive in the pre-operative HPV.DNA check up. The statistical profiles of virally infected subjects were regarded as slightly younger females with early onset of menarche. A higher positive rate was found in such groups such as unmarried single and divorced single women, career employees with special skills, housewives and dwellers in residential and commercial sections. The follow up study of HPV infection was checked with subjects with dysplasia, and no case was recognized in which initially HPV negative dysplasia turned to positive during the observation period. But, in about 50% of those checked, initially HPV positive dysplasia turned to negative, during the follow up period. In the cases with long term (more than 8 years) dysplasia which was followed up, only one out of 10 was found to be HPV positive, while in middle term (more than 2 years but less than 8 years) followed up dysplasia, the positive rate was calculated as 47.8%.

Female↗

[Assessment of a phase III trial of adjuvant chemotherapy in resected lung cancer: an imbalance of surgical results among cooperative institutions].

Many investigators have studied the benefit of adjuvant chemotherapy (AC) in resected lung cancer. However, its benefit is still controversial, except for small cell lung cancer. In the present study, we discussed problems in the preparation of a phase III trial of AC in resected lung cancer. Since a phase III trial requires generally large sample sizes for a short period, a multicenter approach is frequently necessary. However, there are several problems in the preparation of such trial. Firstly, we found that survival for resected lung cancer was considerably different among institutions. Overall 5-year survival for 279 resected N2 disease collected from 7 major institutions was 23%. The 5-year survival for each institution, however, ranged from 7 to 41%. This difference is probably caused by the fact that surgical indication, an ability in operation and postoperative care are different among institutions. Secondly, the number of patients enrolled in the trial spread widely among cooperative institutions. In a phase III trial of AC for resected stage III A patients, 209 patients were collected from 25 institutions. The number of patients enrolled from individual institutions ranged from 0 to 25. Only 5 institutions were possible to enter more than 10 evaluable patients on the trial. Recently, a phase III trial of neoadjuvant therapy was carried out in stage III A (T1-2N2) patients at 5 major institutions. Patients were treated initially with 2 cycles of chemotherapy (CDDP + VDS + MMC), followed by surgical resection. Of 22 resected patients, 4 who underwent extended pneumonectomy, happened to die postoperatively only in one institution. This also shows an imbalance of surgical results among cooperative institutions. In conclusion, we consider that it is particularly important to select institutions without an imbalance of surgical results in a phase III trial.

Antineoplastic Combined Chemotherapy Protocols↗

Synchronous lung cancers defined by deoxyribonucleic acid flow cytometry.

When two pulmonary tumors are seen simultaneously in patients with lung cancer, it always raises a question as to whether the lesions are synchronous lung cancers or lung cancer with intrapulmonary metastasis. To settle this issue, we used deoxyribonucleic acid flow cytometry. Deoxyribonucleic acid ploidy patterns of tumors were able to be analyzed in 14 patients with two simultaneous pulmonary tumors resected by operation. These two tumors, with completely different patterns of deoxyribonucleic acid ploidy, were defined as synchronous lung cancers. Tumors were defined as lung cancer with intrapulmonary metastasis when both tumors showed diploidy or when at least one deoxyribonucleic acid index of abnormal clones between two aneuploid tumors was the same or almost identical. Tumors of the five patients with stage I disease were classified as synchronous lung cancers according to the criteria involving deoxyribonucleic acid flow cytometry. Both tumors were adenocarcinomas in four patients and large-cell and squamous cell carcinomas in one. Both tumors in four patients were located in the same lobe but different segments. All but one patient with different histologic types are alive without recurrence from 24 to 100 months after operation. Tumors of the nine patients with stage III disease in whom intrapulmonary metastasis was clinically suspected were classified as lung cancer with intrapulmonary metastasis according to the criteria. These data suggest that deoxyribonucleic acid flow cytometry of tumors may have diagnostic value in determining synchronous lung cancers.

Adult↗

Pharmacologic profile of (R)-5-[(1-methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H- benzimidazole hydrochloride (YM060), a potent and selective 5-hydroxytryptamine3 receptor antagonist, and its enantiomer in the isolated tissue.

(R)-5-[(1-Methyl-3-indolyl)carbonyl]-4,5,6,7-tetrahydro-1H-benzimidazole hydrochloride (YM060) is a structurally novel, extremely potent, and highly selective serotonin (5HT)3 receptor antagonist. Its 5HT3 receptor blocking properties were compared with those of its enantiomer (S-form), granisetron and ondansetron, in the isolated distal colon of the guinea pig. YM060 competitively antagonized 5HT- and 2-methyl-5HT-induced contraction of the colon, with pA2 values of 8.71 +/- 0.09 (n = 12) and 8.69 +/- 0.06 (n = 9), respectively. Its antagonistic activity was approximately 200, 5 and 50 times more potent than those of the S-form (pA2 = 6.33 +/- 0.06, n = 9 against 5HT; 6.47 +/- 0.1, n = 9 against 2-methyl-5HT), granisetron (pA2 = 8.03 +/- 0.07, n = 9; 8.02 +/- 0.04, n = 9), and ondansetron (pA2 = 7.02 +/- 0.08, n = 9; 6.98 +/- 0.02, n = 9), respectively. Each pA2 value was constant and the isomeric activity ratio (R-form/S-form) was constant irrespective of the agonist used, suggesting that each drug acted on the same 5HT3 receptor. YM060 failed to antagonize contractions induced by 5HT in the saphenous vein of the dog (5HT1-like receptor) or in the aorta of the rabbit (5HT2 receptor. YM060 has a low affinity for alpha-1 (rabbit aorta; pA2 = 5.08 +/- 0.07, n = 8) and alpha-2 (guinea pig ileum; pA2 = 5.61 +/- 0.09, n = 11) adrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗