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Biomedical subjects

T Goda

Publications and source records attributed to T Goda.

At least 19 recordsLinked to original sources

Molecular cloning and sequence analysis of guinea-pig NADPH-cytochrome P-450 oxidoreductase [corrected].

A cDNA clone coding for cytochrome P-450 oxidoreductase was isolated from a guinea-pig liver cDNA library. The cDNA, MSr2, contained a complete coding region of 678 amino acids. The amino acid sequence of the guinea-pig cytochrome P-450 oxidoreductase showed approx. 90% identities with those of rat, human, rabbit, pig enzymes indicating conservation of primary structure of the enzyme during evolutionary divergence of species. The high conservation of acidic residues of the enzyme sustained the importance of them to maintain its function [corrected].

Amino Acid Sequence

Changes in vitamin A status following prolonged immobilization (simulated weightlessness).

A study was conducted to investigate the effects of a simulated weightlessness induced by chronic immobilization on vitamin A status. To simulate the stress condition of weightlessness, rats were suspended for 10 days in a special jacket to which metal chains were attached. Animals received a commercial stock diet. Control rats were pair-fed in reference to the suspended rats. As compared with the control, prolonged immobilization resulted in a decrease in body weight gain and an increase in adrenal weight occurred. In the suspended rats, serum concentrations of retinol and retinol-binding protein (RBP) declined. Hepatic retinyl palmitate content increased, and the hepatic retinol level was decreased. The prolonged immobilization led to significantly reduced retinyl palmitate levels in the testis and lung as well as lowered testicular retinol levels. The results suggest that the stress state induced by prolonged immobilization caused accumulation of hepatic retinyl palmitate, decreasing the serum retinol concentration and retinyl ester content in the extrahepatic tissues.

Adrenal Glands

Dietary-induced increases of disaccharidase activities in rat jejunum.

A study was carried out to examine whether the responsiveness of small intestinal epithelial cells to dietary carbohydrate varied during the daily 24 h cycle. The effect of sucrose on disaccharidase activities was compared during a period of decreasing disaccharidase activities, i.e. between 22.00 and 10.00 hours, and increasing disaccharidase activities, i.e. between 10.00 and 22.00 hours, in the jejunum of 7-week-old-rats. Rats were fed on a low-starch, high-fat diet (Lst; starch 5 and fat 73% of gross energy), or a high-starch, low-fat diet (Hst; starch 70 and fat 7% of gross energy). Both dietary groups exhibited typical diurnal variations in jejunal sucrase (EC 3.2.1.48), maltase (EC 3.2.1.20) and lactase (EC 3.2.1.23) activities, exhibiting a peak around 22.00 hours and a trough at approximately 10.00 hours. When rats were fed on diet Lst for 7 d and then force-fed on an isoenergetic sucrose diet (S; sucrose 40 and fat 37% of gross energy) for 6 or 12 h they exhibited increased sucrase, maltase and lactase activities compared with rats fed on diet Lst. The absolute increase in disaccharidase activities was similar regardless of the time diet S was given or whether rats were killed at 10.00 hours or at 22.00 hours. Analyses of sucrase and lactase activities along the villus-crypt columns showed that the distribution of cell cohorts that responded to diet S was not influenced by the time of introduction of diet S. These findings suggest that small intestinal epithelial cells possess the ability to respond to dietary carbohydrate throughout the daily 24 h cycle.

Animals

Effect of maltitol intake on intestinal calcium absorption in the rat.

To examine whether sugar alcohol affects intestinal calcium absorption, 5-week-old male Wistar rats were fed a basal diet (66% starch) or the diets containing either 10% maltitol, 10% sorbitol or 10% lactose. At 2 and 6 weeks after the start of feeding, the animals were subjected to 5-day-period calcium balance study. Feeding maltitol diets as well as sorbitol diet led to a significantly elevated intestinal calcium absorption and calcium retention. Lactose diet did not produce an increased intestinal calcium absorption in the condition used in the present study. To explore whether maltitol can exert its effect in a short period of time, the rats were starved for 16h and were fed by a polyethylene tube the diet containing 0.44% calcium together with either 10% maltitol or 10% glucose. The total calcium remaining in the gastrointestinal tract at 6h after feeding was significantly decreased in the rats given maltitol diet as compared to the rats given glucose diet. When 10 microCi of 45CaCl2 was given orally with the diets containing maltitol or glucose, the amount of 45Ca remaining in the gastrointestinal tract at 6h after its administration was smaller in the rats fed maltitol diet than in the rats fed glucose diet. These results suggest that both di- and monosaccharide alcohols might affect intestinal epithelium, resulting in an enhanced intestinal calcium absorption.

Algorithms

Decrease of lactase activity in the small intestine of jejunum-bypassed rats.

The effect of jejunum-bypass operation on lactase in rat small intestine was examined. Three groups of four or five rats were designated as jejunum-bypassed, sham-operated and normal rats. All animals including normal rats received by pair-feeding 5% glucose/1% NaCl for 5 days following the operation; thereafter they were fed ad libitum the laboratory chow diet. Three weeks after the jejunal bypass operation, the proximal ileum exhibited a hyperplasia as evidenced by a concomitant increase in mucosal contents of both total proteins and DNA. The specific activity of lactase in this segment was significantly lower in the operated rats than sham-operated controls, whereas the specific activity of sucrase in this segment was significantly elevated. The reduction of lactase activity was also evident in the proximal jejunal segment as well as in the distal jejunum which was deprived of luminal nutrition, suggesting that some hormonal factor(s) might be involved in the decrease of lactase activity in jejunum-bypassed animals. Electroimmunoassay revealed that the amount of immunoreactive lactase also declined in the operated rats relative to the sham-operated controls. Our results thus suggest that lactase activity in residual ileum is not only unable to compensate for the loss of digestive-absorptive surface of jejunum, but lactase activity even decreases following jejunum-bypass operation.

Animals

[Repair of two cases of partial anomalous pulmonary venous return by draining total right pulmonary venous blood to the left atrium through dilated atrial septal defect].

Two cases of partial anomalous pulmonary venous return were reported in whom right pulmonary veins were totally drained to the coronary sinus and to the right atrium respectively. Re-routing of pulmonary veins was done by dilated atrial septal defect and making intra-atrial tunnel using equine pericardial patch. Postoperative courses were uneventful. MRI was useful to identify the pathway from right pulmonary veins to the left atrium.

Adult

[Effect of aortic valve replacement on left ventricular function in adult patients with aortic stenosis].

Echocardiographic and hemodynamic studies were obtained in 16 consecutive adult patients who underwent aortic valve replacement (AVR) with St. Jude Medical valve for aortic stenosis (AS). Three cases of congenital AS was included and two of them had undergone aortic valvotomy in childhood. One of 16 patients died due to late cardiac tamponade six weeks after AVR. Postoperative studies showed improved left ventricular (LV) functions. LV end diastolic and end systolic diameter (LVDs and LVDs) fell from 50.3 and 38.2 to 44.6 and 31.6 mm respectively (p less than 0.05). Fractional shortening (%FS) rose from 26.5 to 32.2% (p less than 0.05). End systolic wall stress (ESWS) fell from 126.2 to 69.6 k dynes/cm2 (p less than 0.01). Cardiac index and pulmonary arterial wedge pressure improved from 3.4 and 14.4 to 3.6 l/min/m2 and 10.5 mmHg respectively (ns). Preoperatively, six were functional class II, eight were class III and one was class IV (New York Heart Association classification). Postoperative improvement was as follows, eight: class I, seven: class II. In four cases, preoperative echocardiography revealed most depressed LV function in %FS (smaller than 21%) and ESWS (greater than 140). Postoperatively they improved from 18.3 and 164 to 26.0% and 72.8 k dynes/cm2 respectively. These results suggested that depressed LV function in the patients with longstanding AS was largely related to limited preload reserve due to LV enlargement and mechanical unloading of LV (correction of afterload mismatch) resulted in improvement of LV function. In conclusion, LV dysfunction owing to AS alone is reversible and AVR results in great clinical improvement.

Adolescent

Degradation of sucrase-isomaltase in the ileum of jejunum-bypassed rats.

At 3 weeks after jejunal-bypass operation in the rat, the proximal ileum exhibited a greater sucrase specific activity than did sham-operated controls, whereas isomaltase activity was unaffected. Electroimmunoassay of sucrase-isomaltase and a degradation product, isomaltase monomer, revealed an elevated molar ratio of sucrase subunit to isomaltase subunit in operated rats, suggesting a decrease in the extent of degradation of ileal sucrase-isomaltase after the jejunal-bypass operation.

Anastomosis, Surgical

Apparent response of subacute sclerosing panencephalitis to intrathecal interferon alpha.

An 8-year-old boy with subacute sclerosing panencephalitis (SSPE) was treated with 1.0 to 3.0 x 10(6) IU human interferon alpha (IFN) by the intrathecal route weekly or fortnightly. Pronounced improvement of clinical and electroencephalographic findings were observed in a dose-dependent manner. Our patient raises hope that IFN can induce sustained remission in patients with SSPE.

Child

Changes in hepatic metabolism through simulated weightlessness: decrease of glycogen and increase of lipids following prolonged immobilization in the rat.

The effect of simulated weightlessness on hepatic metabolisms of carbohydrates and lipids was investigated in rats that were chronically immobilized by means of a suspension harness. During the 10-day period of the suspension, the animals showed a substantial decrease in the hepatic glycogen content, whereas the content of hepatic total lipids was markedly elevated. Similar results were obtained when the "suspended" animals were provided with a regular amount of nutrients by a force-feeding procedure. In the suspended animals, hepatic parenchymal cells were filled with large fat droplets, and hepatic triglyceride contents were elevated. The prolonged immobilization led to a slight, but significant, increase in glucose-6-phosphatase activity in the liver, suggesting that an increased glycogen breakdown might have occurred in the suspended animals. However, it was unlikely that the increased amount of glucose produced by the glycogen breakdown was utilized as a substrate for the lipogenesis in the liver, because hepatic lipogenic enzyme activities were unaffected by the suspension. The results suggest that the hepatic lipids accumulate in animals exposed to a prolonged immobilization state, presumably due to a decreased lipolysis and/or a suppressed lipoprotein mobilization from the liver into the blood stream.

Adrenal Glands

Effects of various dietary protein contents on vitamin A status of rats exposed to prolonged immobilization through suspension.

The investigation was carried out to clarify the effects of various dietary protein contents on vitamin A status of rats exposed to prolonged immobilization through suspension. A rat wearing a special jacket to which metal chains were attached, was suspended for 10 days as an analogy of simulated weightlessness. Five groups of suspended rats were fed on the diets containing various amounts of casein (5, 10, 20, 40 and 60, w/w%), while control group received the 20% casein diet. Through suspending animals, a decrease in body weight gain and increase in adrenal weights occurred. Serum albumin concentration of the suspended rats fed on the 10, 20, 40 and 60% diets were the same as that of the control rats. The suspended rats showed lowered serum retinol concentrations and elevated hepatic retinyl palmitate contents without noticeable differences between the diets. The hepatic retinol levels were not clearly affected. In the suspended rats, testicular levels of retinyl palmitate and retinol significantly decreased as compared with the control. These parameters' alterations did not relate to serum albumin concentration and were independent of dietary protein levels. The results suggest that stress state may cause suppression of releasing hepatic vitamin A, resulting in a lowered serum retinol concentration, being independent of nutritional status of protein.

Adrenal Glands

Developmental changes in vitamin A level and lack of retinyl palmitate in chick lungs.

1. Developmental changes in retinol and retinyl palmitate contents in lungs of chick embryos and posthatch chicks were investigated. 2. Remarkable changes in the lung retinol levels were found during development of chicks. Embryonic lungs 5 days prior to hatching contained the highest content of retinol. The level then declined rapidly and was lowest on 1 day before hatching. 3. Its level then rose substantially within 7 days after hatching. 4. No retinyl palmitate in chick lungs was detectable at any of the developmental stages examined, nor even in adult hen. 5. Serum retinol level changed in parallel with the lung retinol. 6. The patterns of changes in liver retinol and retinyl palmitate were remarkably different from that occurring in the lung retinol. In chick embryonic livers, the levels of them were low, followed by a rapid increase after hatching. 7. The high level and its rapid decrease of lung retinol content during development of chick embryos may be functionally connected with retinol action in embryonic lungs for cellular differentiation and maturation.

Aging

Age-related changes in sucrase and lactase activity in the small intestine of 3- and 10-week-old obese mice (C57BL/6Jobob).

The relationship between obesity and the digestion of carbohydrates is poorly understood. Data in humans have provided conflicting results. Studies using the obese mouse (C57BL/6Jobob) suggest that obesity is associated with increased activity of intestinal alpha-disaccharidases. To evaluate the developmental pattern of these enzyme activities in obesity, we determined the activity of sucrase and lactase in the small intestine of genetically obese mice (C57BL/6Jobob) and lean littermates at 3 and 10 weeks of age. Sucrase and lactase activities were measured on intestinal homogenates from segments of the small intestine in mice maintained on standard laboratory diets during the postweaning period. Results were expressed as specific activity and total activity per intestinal segment. Obese mice did not differ from lean littermates in body weight at 3 weeks of age, but exhibited increased protein content in the proximal small intestine. Sucrase specific activity was significantly higher in the obese mice at 3 weeks of age in all intestinal segments. Sucrase total activity showed a similar pattern. At 10 weeks of age, body weights of obese mice were substantially greater than the lean littermates. Sucrase specific and total activities were also greater in the obese mice at 10 weeks of age. Lactase specific activity, however, was similar in both obese and lean mice at both ages studied. Lactase total activity was greater in the obese mice, consistent with their greater intestinal mass. These observations demonstrate that changes in the intestinal sucrase activity of the obese mouse precede the development of excessive body weight.

Age Factors

Effects of medium-chain triglycerides on brush border membrane-bound enzyme activity in rat small intestine.

The effects of various types of dietary fat on brush border membrane-bound enzymes in rat intestinal mucosa were examined. Four groups of five rats were pair-fed defined diets for 10 d. The control group was fed a diet containing 57% sucrose and 2% corn oil as a fixed carbohydrate reference; the three experimental groups received diets containing 57% sucrose and 2% corn oil plus 13% fat in the form of medium-chain triglycerides (MCT) or long-chain triglycerides (LCT) (either lard as a highly saturated fat or corn oil as a highly unsaturated fat). Feeding LCT compared to the control diet, decreased sucrase activity in mucosal brush borders of the duodenum and jejunum. In these segments of MCT-fed rats, sucrase activity was similar to that in the control animals. In another experiment, measuring immunoreactive sucrase-isomaltase in jejunal brush border membranes revealed that feeding a high corn oil diet, but not a high MCT diet, led to a reduction in the sucrase catalytic activity per unit weight of enzyme protein, suggesting that the degradation status of sucrase-isomaltase might be altered by the different types of dietary fats. With MCT feeding, jejunal alkaline phosphatase activity was enhanced to a large extent compared to the activity in other groups. Feeding MCT, compared to lard or corn oil, also increased microvillus phospholipids of the jejunal mucosa. These results suggest that MCT, unlike LCT, do not suppress the activity of mucosal microvillus membrane enzymes in rat small intestine.

Alkaline Phosphatase

Gastric acidity-dependent bioavailability of commercial sustained release preparations of indomethacin, evaluated by gastric acidity-controlled beagle dogs.

The relationship between gastric acidity and the bioavailability of two kinds of sustained-release indomethacin (IM) formulations was investigated in gastric acidity-controlled beagle dogs, and compared with that of rapid-release IM formulations. All test dosage forms were more rapidly dissolved in simulated intestinal fluid than in simulated gastric fluid. Gastric acidity did not affect the bioavailability of IM from the rapid-release formulation. However, the bioavailability of IM from the two kinds of sustained-release formulations were markedly influenced by gastric acidity. The rates of IM bioavailability from both of the sustained-release formulations were faster under low acidity conditions than under high acidity conditions (p less than 0.01). In addition, Tmax and mean residence time (MRT) were approximately the same for the rapid-release and sustained-release formulations under low acidity conditions. These results suggest that the IM sustained-release formulations showed a rapid-release profile under low acidity conditions.

Animals

[Application of gastric acidity-controlled beagle dog to bioavailability study of cinnarizine].

The relationship between gastric acidity and bioavailability of a weakly basic drug, cinnarizine (CN) was investigated in the gastric acidity-controlled beagle dogs. The dissolution of CN from capsules was very fast at pH 1.2 but it decreased with an increase in pH. The capsules containing CN were orally administered to the beagle dogs of the following three groups: 1) the dogs whose gastric acidity were not controlled; 2) the dogs whose gastric acidity were controlled to high levels (less than pH 2) with pentagastrin; 3) the dogs whose gastric acidity were controlled to low levels (more than pH 6) with omeprazole. The peak plasma concentration (Cmax) and the area under the plasma concentration-time curve (AUC0-8h) of CN were most variable in the first group. On the other hand, the variations of these parameters were small in the second and third groups. The Cmax and AUC0-8h of CN in the high acidity group were about 20 times larger than those in the low acidity group (p less than 0.01). The bioavailability of CN was markedly influenced by the gastric acidity. This finding was similar to that in human subjects. The gastric acidity-controlled beagle dogs are useful animal models to evaluate the bioavailability of weakly basic drugs such as CN, exhibiting pH-dependent dissolution behavior.

Animals

Gastric pH profile and its control in fasting beagle dogs.

The gastric pH of fasting beagle dogs was measured by using an ion-selective field effect transistor pH sensor. In addition, a novel procedure to control the gastric pH in fasting beagle dogs was investigated. Inter- and intra-day variations in the gastric pH of the dogs were observed. The gastric pH of the dogs could be controlled by a single intravenous administration of omeprazole, an H+, K+-adenosine triphosphatase (ATPase) inhibitor (1 mg/0.25 ml/kg). The pH in the stomach was 6.6 +/- 0.2 (mean +/- S.D., n = 6) at 1 h after the omeprazole treatment, and this level of pH was maintained for a period of at least 3 h. Beagle dogs in which the gastric pH has been controlled by omeprazole are considered to be useful as an animal model to be used for the pharmaceutical evaluation of drugs in subjects with a low acidity level.

Animals