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Biomedical subjects

M Mino

Publications and source records attributed to M Mino.

At least 55 records · Page 3Linked to original sources

Beneficial effect of fructose-1,6-bisphosphate on mitochondrial function during ischemia-reperfusion of rat liver.

BACKGROUND/AIMS: Several groups have reported that administration of fructose-1,6-bisphosphate (FBP) reduces ischemic injury. The aim of this study was to determine the protective effect of FBP on the impairment of mitochondrial oxidative phosphorylation by ischemia-reperfusion injury in the rat liver. METHODS: The respiratory control ratio (RCR) and the adenine nucleotide content of mitochondria isolated from ischemic and reperfused livers with or without FBP treatment were measured. RESULTS: In FBP-treated livers, the cellular adenosine triphosphate level was restored to more than 50% of normal after 120 minutes of reperfusion following 120 minutes of ischemia, whereas that of control livers only reached 15% of normal. The RCR and the adenine nucleotide content of mitochondria isolated from FBP-treated livers were significantly higher than those of mitochondria from control livers after ischemia and reperfusion. FBP strongly suppressed the formation of lipid peroxides during reperfusion. In vitamin E-deficient rats, the RCR decreased markedly during reperfusion, but FBP protected the mitochondria against reperfusion injury. CONCLUSIONS: FBP has a protective effect against ischemia-reperfusion injury on the liver and especially preserves the oxidative phosphorylation capacity of hepatic mitochondria.

Adenosine Triphosphate↗

Serial changes of cystic air spaces in fibrosing alveolitis: a CT-pathological study.

In patients with cryptogenic fibrosing alveolitis (CFA), subpleural large cysts are sometimes seen within honeycombing on computed tomography (CT). These cysts may be interpreted as bullae and the coexistence of emphysema with CFA might be assumed. We evaluated whether cystic spaces in honeycombing become larger in patients with CFA on serial CT scans. CT scans were obtained in 16 patients with CFA, who had undergone two CT examinations (6 to 43 months, mean 25.1 months apart), were reviewed focusing on the changes in size of the cystic spaces in honeycombing. The mechanism of enlargement of cystic spaces was investigated using microscopic serial sections of autopsied specimens. In 15 of 16 patients, the cystic spaces in honeycombing were larger on the second examination. Histologically, stenosis of bronchioles and slit-like structures between cysts and bronchioles were detected in addition to alveolar septal dissolution and bronchiolectasis. Both the bronchiolar stenosis and the slit-like gaps have the potential to work as check-valves and increase the volume of cystic spaces. Therefore, in the evaluation of CFA, large cysts should be interpreted with caution to avoid misinterpretation of the cysts as bullae associated with emphysema. From the results of this correlative study, we suggest that a check-valve effect is an important mechanism in the formation of large cysts in honeycomb lung.

Aged↗

Pharmacokinetics of all-trans retinoic acid in pediatric patients with leukemia.

Since all-trans retinoic acid (ATRA) induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), and its effectiveness appears to be related to the plasma or serum level, a pharmacokinetic study of ATRA was undertaken in nine patients with various leukemias. After oral administration at a dose of 30 mg/m2, the time required to reach the peak plasma level of ATRA (20-1198 ng/ml) was between 120 and 240 min and the apparent plasma elimination half life was 21-51 min. In addition, 13-cis retinoic acid was detected in the plasma of seven patients, indicating the occurrence of ATRA isomerization in vivo. ATRA therapy did not induce complete remission in all patients, even when high plasma levels were achieved. Among the six APL patients given ATRA therapy, one who failed to respond had a very low plasma ATRA level. These findings suggest that it may be useful to monitor plasma levels during oral ATRA therapy in order to achieve an appropriate treatment regimen.

Adolescent↗

Plasma copper and antioxidant status in Wilson's disease.

It has been demonstrated that the level of serum copper unbound to ceruloplasmin (loosely bound copper) is increased in Wilson's disease, although the total serum copper concentration is usually low, reflecting a low ceruloplasmin level. To assess the contribution of free radical reactions catalyzed by nonceruloplasmin copper to the development of complications in this disease, we investigated copper and antioxidant status in four untreated patients who had hepatic dysfunction with or without hemolytic anemia and made a comparison with five patients controlled on penicillamine therapy and 19 age-matched healthy children. We found that loosely bound copper in plasma measured by the phenanthroline assay was detectable in three of four untreated patients with Wilson's disease, but was not detectable in the patients during therapy or in the healthy controls. Among the various antioxidants, the ascorbate and urate levels were markedly reduced before treatment (mean +/- SD, 23 +/- 16 microM for ascorbate and 90 +/- 59 microM for urate) compared with the values in the patients during treatment with penicillamine (67 +/- 19 and 302 +/- 78 microM, p < 0.05) and in control children (60 +/- 8 and 254 +/- 48 microM, p < 0.05). We also demonstrated that the plasma concentration of allantoin, an oxidation product of uric acid and a possible marker of radical generation in vivo, was markedly elevated in the untreated patients (11.0 +/- 1.8 versus 4.3 +/- 0.5 microM in patients on therapy and 6.5 +/- 0.8 microM in controls, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Allantoin↗

4-oxo retinoic acid for refractory acute promyelocytic leukemia in children with all-trans retinoic acid therapy.

Therapy with all-trans retinoic acid (ATRA) achieves complete remission in a high proportion of patients with acute promyelocytic leukemia (APL), but the efficacy is reported to relate to plasma ATRA level after oral administration. The pharmacokinetics of ATRA and 4-oxo all-trans retinoic acid (4-oxo ATRA), a metabolite of ATRA, were studied in four children with APL at the time of initial oral administration. After administration of ATRA at a dose of 30 mg/m2, the peak plasma ATRA level was 20-741 ng/ml and was reached at 60-120 min. The patient with the lowest peak plasma level did not achieve complete remission and had a very high 4-oxo ATRA level compared to the patients with complete remission. These findings suggest that accelerated metabolism of ATRA plays a role in the failure of this agent in the patients without remission.

Administration, Oral↗

Plasma levels of retinol, retinol-binding protein, all-trans beta-carotene and cryptoxanthin in low birth weight infants.

In neonatal medicine, it is thought that retinol is useful for preventing CLD and for fetal development. However, beta-carotene had other vitamin A precursors have not been studied in neonates with CLD or others disorders. Cord blood of neonates including ELBW and VLBW infants was assayed for plasma levels of retinol, RBP, beta-carotene and cryptoxanthin. Plasma beta-carotene levels in ELBW and VLBW were lower than that in term infants, but plasma cryptoxanthin levels in ELBW and VLBW were about the same as in term infants. Plasma retinol and RBP levels showed almost same levels during 23-41 gestational weeks. Maternal smoking reduced plasma beta-carotene but not cryptoxanthin, retinol, or RBP levels. IUGR was associated with increased cryptoxanthin levels in cord blood. Serious neonatal diseases, including CLD and ROP manifested no significant effects on the cord blood vitamin levels. Thus, the occurrence of these diseases at birth could not be predicted by examination of vitamin levels in cord blood.

Cryptoxanthins↗

Developmental changes of tetrahydrobiopterin in rat and human erythrocytes.

In the present study, we investigated the developmental changes of (1) plasma and erythrocyte tetrahydrobiopterin (BH4); (2) erythrocyte GTP cyclohydrolase (the rate-limiting enzyme of BH4 biosynthesis); (3) the permeability of erythrocyte membrane to BH4; and (4) plasma phenylalanine, both in healthy human subjects and Wistar rats. In vitro experiments demonstrated passive transport of BH4 into erythrocytes. In humans, BH4 levels as well as the other parameters were fairly consistent across all age groups. In contrast, Wistar rats showed significant developmental changes in erythrocyte BH4, which were not simply correlated to either GTP cyclohydrolase, permeability to BH4 or plasma phenylalanine levels. This may suggest the existence of other factors regulating the homeostasis of BH4, such as BH4-binding capacity in plasma and/or erythrocytes. These species/age differences in erythrocyte characteristics may influence the pharmacological behavior and clinical efficacy of BH4 in humans and experimental animals.

Adolescent↗

[A case of lung cancer with choroidal metastasis].

A 72-year-old woman was admitted to our hospital because of a mass shadow in the left upper lobe on chest roentgenograms. She had noticed floaters in both visual fields 2 months before admission. Percutaneous aspiration of the lung lesion was done, and revealed poorly differentiated squamous cell carcinoma. Metastatic tumors were noted in the choroid of both eyes and in both kidneys. These lesions responded partially to systemic chemotherapy and the floaters disappeared. There have been few reports of metastatic choroidal tumors, but most cite the lung and the breast as the primary sites. We should pay attention to ophthalmologic findings because lung cancer may metastasize to the choroid.

Aged↗

[Induction and maintenance therapy in all-trans retinoic acid with relapsed acute promyelocytic leukemia].

We reported a 17-year-old girl with relapsed acute promyelocytic leukemia (APL) who achieved complete remission and has been received maintenance therapy with all-trans retinoic acid (ATRA). The patient was diagnosed as APL in 1986. The ANLL 861 protocol of the Children's Cancer and Leukemia Study Group induced complete remission, and the chemotherapy was discontinued in 1989. However, she suffered a relapse with APL in 1991 and begun receiving ATRA (30 mg/m2/day) therapy because of disseminated intravascular coagulation. Bleeding tendency was discontinued by day 5. During the treatment, the white blood cell count increased markedly to 35,510 per microliters on 15th day, however she achieved complete remission morphologically on day 18. After informed consent was obtained from the family, she has been given ATRA orally for more than three years at the time of this report. The pharmacokinetics examination (ATRA 20 mg/m2 single per os) was performed 12 and 22 months after the induction therapy. The each peak plasma level of ATRA was 89 and 149 ng/ml. The concentration of ATRA has yet reached a level despite the continuous ATRA therapy. We considered that it may be useful to monitor plasma levels of ATRA during the treatment.

Adolescent↗

A new method of quantitating serum and urinary levels of 1,5-anhydroglucitol in insulin-dependent diabetes mellitus.

A new method was developed for quantitating the serum and urinary levels of 1,5-anhydroglucitol (AG), a sensitive and informative marker of glycemic control. This method utilized a combination of ODS and pyranose oxidase-immobilized columns for HPLC, and monitored hydrogen peroxide production with an electrochemical detector. We applied this method to determine the serum and urinary AG levels in 15 patients with insulin-dependent diabetes mellitus (IDDM) as well as in control subjects. Baseline separation of AG from other sugars such as glucose and myoinositol was achieved. Quantitation of AG was achieved over the range from 0.2 ng to 0.3 micrograms based upon peak heights. The serum and urinary AG levels in the IDDM patients were 4.4 +/- 8.3 mg/l and 5.1 +/- 4.3 mg/day, respectively. We found that the urinary AG to serum AG ratio showed a linear correlation with the urinary glucose level in the IDDM patients (urinary glucose (y) vs. urinary AG to serum AG ratio (x): y = 9.071x-0.991; r = 0.968, P < 0.001). This method proved efficient and reliable for quantitating urinary AG. Since determination of both the AG and glucose levels in urine gives equivalent clinical information to the serum AG level, urinary monitoring could provide a valuable addition to the available methods for assessing the glycemic status of IDDM patients.

Adolescent↗

Regional distribution of 14C-zonisamide in rat brain.

Zonisamide (1,2-benzisoxazole-3-methane sulfonamide) is a new antiepileptic drug developed in Japan. This compound was proven to possess a strong inhibitory effect on convulsions of cortical origin, whether induced by electric or chemical stimuli. Regional distribution of 14C-zonisamide was investigated in rat brain using autoradiography. A high uptake of 14C activity was observed in the cerebral cortex and the midbrain. A pair-match analysis of primary motor cortex versus primary sensory cortex revealed a slightly higher uptake in primary motor cortex. In the cerebellum, a higher uptake was observed in the cortex than medulla. Sagittal section analyses revealed that a high uptake of 14C activity was observed in the cerebral cortex and colliculus, and a moderate uptake was seen in the cerebellum, thalamus, hypothalamus, and striatal body, thus suggesting the distribution of 14C-zonisamide is similar to that of flunitrazepam and phenytoin.

Animals↗

Ultrasonographic diagnosis of juvenile colonic polyps.

To reduce the risks of air-contrast barium enemas and colonoscopy, we studied the use of saline enemas for ultrasonographic examination of children with rectal bleeding. Thirty-nine children, from 2 years 8 months to 8 years 3 months of age, were examined. Juvenile colonic polyps were ultrasonographically demonstrated and histologically confirmed in 25 children; all the polyps were solitary and pedunculated, and were located in the splenic flexure in 3 children, the descending colon in 6, the sigmoid colon in 12, and the rectum in 4. Ultrasonographic findings by hydrocolonic ultrasonography were identical to those obtained by immersion ultrasonography of removed specimens. Hypoechoic areas within more hyperechoic polyps were shown histologically to be dilated glandular canals. The 14 children in whom no abnormal ultrasonographic findings were shown had no further rectal bleeding after resuming regular defecation, and 5 of these 14 had negative colonoscopic findings. No adverse reactions were noted in any child during or after the saline enema examination. We conclude that ultrasonographic examination with a saline enema is a safe and accurate method of assessing children with rectal bleeding, especially for the diagnosis of juvenile colonic polyps.

Child↗

Effect of long-term administration of beta-carotene on lymphocyte subsets in humans.

To examine whether or not beta-carotene alters immune indexes, we performed a single-blind trial in healthy male nonsmokers. Lymphocyte subsets were assessed by double labeling with monoclonal antibodies before and after 44 wk of administration of either beta-carotene (60 mg/d; n = 10) or placebo (n = 10). In addition, we measured the beta-carotene concentrations in plasma, mononuclear cells (MNC), platelets, and red blood cells (RBCs), as well as the plasma alpha-tocopherol concentration. An increase of plasma and MNC beta-carotene concentrations to four and three times the baseline value was noted after 2 and 4 wk, respectively. The CD4-CD8 ratio increased after 9 mo of beta-carotene administration whereas natural killer cells, virgin T cells, memory T cells, and cytotoxic T cells remained unaltered throughout the study. No side effects or toxicities were detected by a questionnaire survey and routine laboratory tests.

Adult↗

Blood pressure responses in Japanese and Swedish children in the supine and standing position.

We investigated the cardiovascular responses to active standing in Swedish and Japanese pre-pubertal children using non-invasive continuous beat-to-beat finger blood pressure (BP) monitoring. Seventy-eight Swedish (7-12 years) and 53 Japanese children (6-12 years) were examined. There were no significant differences in body weight or height between the two groups (total group). Finger blood pressure and heart rate were continuously recorded in the supine position and during standing. Supine BP was significantly higher in Swedish compared to Japanese children (115/65 vs 98/50 mmHg, P < 0.001), and Swedish children showed a significantly larger initial BP drop upon rising (-28/15 vs - 14/ -10 mmHg, P < 0.05) and a larger increment of heart rate (39 +/- 10 vs 29 +/- 8 beats. min-1, P < 0.05). There were, however, no differences in the blood pressure and heart rate changes in the following steady state period (2-3 min) between the two groups. These results suggest that Swedish pre-pubertal children have a higher basal blood pressure and enhanced cardiovascular autonomic responses, such as pronounced baroreflex receptor sensitivity and vasoconstrictor mechanisms. These differences in the two cohorts were not related to body dimensions or degree of maturation, indicating that autonomic functions in the cardiovascular system largely depend on genetic factors and environmental variables.

Anthropometry↗

Pharmacokinetics and pharmacodynamics of famotidine in children with gastroduodenal ulcers.

We treated 14 boys, six with gastric ulcers and eight with duodenal ulcers, to determine famotidine pharmacokinetics and its inhibition of gastric acid secretion (pharmacodynamics). Famotidine (1 mg/kg/day) was administered either intravenously or orally at a dose of 0.5 mg/kg twice a day (maximum: 40 mg/day). Blood samples were collected from all subjects and the intragastric pH monitored in eight. Pharmacokinetic parameters were calculated assuming a one-compartment model. Volume of distribution, elimination half-life, and area under the serum concentration-time curve were 1.52 +/- 0.37 l/kg, 2.29 +/- 0.38 h, and 1.14 +/- 0.32 ng.h/ml, respectively. The mean oral bioavailability of famotidine was 50.6%. Both intravenously and orally administered famotidine neutralized gastric acidity during sleep but failed to continuously maintain the intragastric pH > 5.0. All subjects' ulcers healed within 8 weeks. There were no side effects noted during famotidine treatment. Twice daily administration of 0.5 mg/kg famotidine for 8 weeks appears to be a tolerated and effective treatment of children with gastroduodenal ulcers.

Administration, Oral↗

Red blood cell sorbitol in diabetic children.

When red blood cells (RBC) were incubated with various concentrations of glucose, the RBC sorbitol level increased in a concentration-dependent manner. The elevated RBC sorbitol level was not reduced by further incubation in a glucose-free medium. In both diabetic and non-diabetic children, an increase of RBC sorbitol levels occurred in the oral glucose tolerance test and the return to baseline was delayed in diabetics compared with non-diabetics. In the majority of diabetics (87%), RBC sorbitol levels exceeded the upper limit of the normal range, which was arbitrarily determined as the mean + 2 s.d., in healthy non-diabetic children and adults. A good correlation was observed between RBC sorbitol levels and plasma glucose levels (r = 0.644). In both diabetics and non-diabetics, no correlation was observed between RBC sorbitol levels and age, and in diabetics the RBC sorbitol level was not related to the duration of disease. A good correlation was observed between RBC sorbitol levels, and hemoglobin Alc (HbAlc) or fructosamine levels in diabetic children.

Adolescent↗