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Biomedical subjects

M Ohtsuki

Publications and source records attributed to M Ohtsuki.

At least 55 records · Page 3Linked to original sources

Dietary fructooligosaccharides change the concentration of calbindin-D9k differently in the mucosa of the small and large intestine of rats.

Previously, we confirmed that dietary fructooligosaccharides (FOS) increase calcium absorption in rats. In this study, we examined the influence of FOS feeding on the concentration of calbindin-D9k of several intestinal segments in rats. Rats in the control group were fed a diet without FOS. Rats in the other two groups were fed the diet containing FOS at either 50 or 100 g/kg for 10 d and subjected to a calcium absorption study. On the final day of feeding, the rats were killed and the entire intestine was removed. The intestinal mucosa was collected from four segments, i.e., the proximal and distal segments of the small intestine, the cecum and the colorectum, respectively. The apparent absorption of calcium increased dose dependently (r = 0.9256, P < 0.0001). Significant positive correlations between apparent calcium absorption and the relative amounts of calbindin in both large intestinal segments were observed (cecum, r = 0.8956, P = 0.0011; colorectum, r = 0.8828, P = 0.0016). Also, significant negative correlations between apparent calcium absorption and the relative amounts of calbindin-D9k in both small intestinal segments were observed (proximal, r = -0.7149, P = 0. 0304; distal, r = -0.8740, P = 0.0021). In conclusion, FOS feeding increases levels of calbindin-D9k in the large intestine, but decreases those in the small intestine. Moreover, these results suggest that part of the stimulatory effect of fructooligosaccharides relates to the transcellular route of calcium absorption in the large intestine of rats.

Absorption↗

Nitric oxide donor NOR 3 inhibits ketogenesis from oleate in isolated rat hepatocytes by a cyclic GMP-independent mechanism.

Studies were conducted to clarify the effects of nitric oxide donors NOR 3 ((+/-)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide, FK409), SIN-1 (3-morpholinosydnonimine) and SNAP (S-nitroso-N-acetylpenicillamine) on the accumulation of cGMP and cAMP and Ca2+ mobilization as well as ketogenesis from oleate in isolated rat hepatocytes. NOR 3 caused inhibition of ketogenesis from oleate along with stimulation of cGMP accumulation in rat hepatocytes, whereas SIN-1 and SNAP exerted no effect on ketogenesis despite their marked stimulation of cGMP accumulation. Although the nitric oxide trapping agent, carboxy-PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide), antagonized the stimulation by NOR 3 of cGMP accumulation, it failed to modulate the anti-ketogenic action of NOR 3. Furthermore, neither 8-bromoguanosine-3',5'-cyclic monophosphate nor N2,2'-O-dibutyrylguanosine-3',5'-cyclic monophosphate mimicked the anti-ketogenic action of NOR 3. It is concluded in the present study that NOR 3-induced inhibition of ketogenesis in rat hepatocytes is not mediated by cGMP. The present study revealed that the remaining structure of NOR 3 from which nitric oxide had been spontaneously released had no anti-ketogenic action. We first and clearly demonstrated that nitrite production was dramatically enhanced when NOR 3 was incubated in the presence of rat hepatocytes. The mechanism whereby NOR 3 inhibits ketogenesis in rat hepatocytes will be discussed.

Adenosine Triphosphate↗

In vivo absorption of calcium carbonate and magnesium oxide from the large intestine in rats.

This study was conducted to evaluate the ability of the large intestine to absorb calcium (Ca) and magnesium (Mg) from their sparingly water-soluble salts, and also to determine whether fructooligosaccharides (FOS) stimulate the absorption of these minerals in rat large intestine in vivo. Rats were fed Ca- and Mg-free diets with and without 5% FOS. An aqueous suspension of CaCO3 and MgO was infused into the stomach via a gastric tube or into the cecum via an implanted catheter. Coprophagy was prevented by using wire-mesh anal cups throughout the experiment so as to exclude the re-ingestion of feces as an oral mineral source. In rats fed an FOS-free diet, the absorption degrees of Ca and Mg infused into the cecum were the same as those infused into the stomach. The absorption degree of phosphorus (P) was slightly but significantly higher in rats with the infusion of Ca and Mg into the cecum than in rats with the infusion of Ca and Mg into the stomach. FOS-feeding increased the absorption of Mg to a similar extent in either case of infusion via cecal and oral routes, while FOS-feeding did not increase the absorption of Ca in rats with infusion of Ca and Mg into the cecum. We concluded that both CaCO3 and MgO are absorbed in the large intestine, and we ascertained that the increasing effect of FOS on the absorption of Mg took place mainly in the large intestine.

Analysis of Variance↗

[Analysis of sudden death caused by intestinal obstruction].

Five autopsy cases of sudden death caused by intestinal obstruction are reported. The causes of death of the cases were duodenal obstruction of impacted food stuff, ileocaecal obstruction caused by Crohn's disease, incarceration of inguinal hernia, intestinal obstruction caused by heterotopic pancreas and paralytic ileus. In three cases, the patient was in cardiopulmonary arrest on arrival at hospital, and in the remaining cases the patient died within 12 hours from the beginning of treatment; therefore, a correct clinical diagnosis was not made before the death in all cases. All the patients had from one to three days history of nausea and abdominal pain, major complications of intestinal obstruction. Among all cases, the duration from the onset to death was the shortest in the case of a patient complicated with schizophrenia. It is characteristic that the patients of all cases died suddenly and resuscitation was not successful. Regarding the laboratory data of a hospitalized patient, marked hemoconcentration and an increased level of BUN/Cr ratio and blood sugar were shown. The patient who died from duodenal obstruction caused by impacted food-stuff had suffered from depression for six years, and the patient who died from paralytic ileus had suffered from schizophrenia for about 23 years. In both cases, it is characteristic that the complaints of the patient were poorer than what would be expected. Furthermore, these patients had been taking medication of psychotic, anti-depressant and anti-parkinsonism drugs; therefore the combination of these drugs was thought to be reflected in the bowel movement.

Adult↗

Analysis of an alternative promoter that regulates tissue-specific expression of the human aromatic L-amino acid decarboxylase gene in cultured cell lines.

The human aromatic L-amino acid decarboxylase (AADC) gene is transcribed in a tissue-specific manner by an alternative promoter. In this study using human cultured cell lines, we analyzed the alternative promoter that regulates tissue-specific expression of AADC. Neither neuronal nor nonneuronal-type mRNA of AADC was detected in HeLa cells, nonneuronal-type mRNA of AADC was expressed in HepG2 cells, and the neuronal-type was expressed in the SK-N-SH cell line. We examined the promoter activities located in 5'- and 3'-flanking regions of exon N1 and exon L1 by transfection experiments. Plasmids containing 5'-flanking regions of exon L1, the shortest of which was 0.3 kb, could promote specifically high expression of the reporter gene HepG2 cells. On the other hand, plasmids containing 5'-flanking regions of exon N1 (3.6 kb to 0.5 kb) could promote the reporter gene expression not only in SK-N-SH cells but also in HeLa and HepG2. More enhanced expression were observed by transfection of plasmids containing parts of the first intron in these cell lines. Thus, these results suggest that the basal liver-specific promoter activity is located in the 5'-flanking region of exon L1 and that the first intron may also be needed for enhanced expression rather than determination of cell-specificity.

Aromatic-L-Amino-Acid Decarboxylases↗

Prevention of coprophagy modifies magnesium absorption in rats fed with fructo-oligosaccharides.

We developed a new type of anal cup for prevention of coprophagy and determined whether the absorption of Ca and Mg and the stimulatory effects of feeding fructo-oligosaccharides (FO) on the absorption of Ca and Mg were altered by prevention of coprophagy in rats. Rats were fed on a FO-free diet or a diet containing 50 g FO/kg for 2 weeks with or without prevention of coprophagy. FO-feeding increased the apparent absorptive ratio of Ca and Mg in rats with or without prevention of coprophagy. However, in the FO-fed groups the absorptive ratio of Mg in rats with prevention of coprophagy was higher than in rats without prevention of coprophagy. The Ca content of the femur was higher in rats fed on the FO-diet than in rats fed on the FO-free diet both with and without coprophagy. In conclusion, FO-feeding increased the absorption of Ca and Mg in rats both with and without coprophagy. Moreover, prevention of coprophagy enhanced the absorption of Mg in rats fed with FO. Coprophagy has to be considered when the effects of luminal fermentation or mineral absorption are examined in rats.

Animals↗

[Emergency coronary artery bypass grafting (CABG) in a case of coronary occlusion secondary to long segmental dissection of left anterior descending artery after percutaneous transluminal coronary angioplasty (PTCA)].

A 60-year-old man with unstable angina underwent PTCA at left anterior descending artery (LAD) #6, which had stenosis of 90%. Subsequently, a long segmental dissection formed from #6 to #7 and the patients was scheduled for CABG. On the day before the expected date of CABG, he had an angina attack and a 12 lead electrocardiogram (ECG) showed ST segment and T wave elevation in V1-3. Coronary angiograms revealed 99% stenosis in LAD #6 and immediately rePTCA was performed at the site. RePTCA improved the stenosis to 50%, but ECG showed an inverted T wave in V3,4 and emergency CABG was performed, with the saphenous vein at LAD #8 and high lateral artery. Some authors have stated that CABG is not useful for long segmental coronary dissection, but we conclude that CABG should be definitely considered in such a case, because this procedure resolves pressure gradients at before-and-after entry and the bypass grafts will be never occluded whenever anastomosis (intima-adventitia-graft) is performed.

Angioplasty, Balloon, Coronary↗

[Methamphetamine-like substance detected only in stomach contents from autopsied cadavers].

In this paper we show that a methamphetamine-like substance was detected in the stomach contents of deceased patients who had never taken methamphetamine (MA). MA was assayed by using gas chromatography/mass spectrometry. Blood, urine and stomach content samples were collected from 65 patients not suspected of taking MA. In seven victims, MA-like substance was detected in the stomach contents. Concentration of MA-like substance ranged from 0.03 to 0.38 microgram/ml. Though MA and amphetamine, a metabolite of MA, were detected in forensic samples of patients who had used MA, amphetamine could not be identified in the stomach contents of these seven cases. There was no correlation between MA concentration and interval of time from death to autopsy. The mechanism of the production of MA-like substance is not clear. This phenomenon should be paid attention to in the course of forensic drug analysis because of the possibility of misjudgement.

Adolescent↗

TGF-beta enhances macrophage ability to produce IL-10 in normal and tumor-bearing mice.

In the present study, we demonstrate that TGF-beta is capable of enhancing macrophage ability to produce IL-10 in normal and EL4 tumor-bearing mice. We found the increase in IL-10 in ascitic fluid and IL-10 mRNA expression in macrophages in parallel with the TGF-beta level and tumor progression. The macrophage production of IL-10 in the tumor-bearing mice was significantly enhanced without LPS stimulation in vitro, compared with normal controls. To clarify the mechanism wherein increased IL-10 production was induced, anti-TGF-beta or anti-IL-10 Abs were administered to EL4-bearing mice. Administration of anti-TGF-beta Ab led to a reduction in the IL-10 contents in ascitic fluid of tumor-bearing mice; however, anti-IL-10 Ab administration did not prevent the increase in TGF-beta contents. Enhanced IL-10 production and mRNA expression of macrophages from the tumor-bearing mice were also reduced by anti-TGF-beta Ab administration. Both anti-TGF-beta and anti-IL-10 Ab administration restored the TNF-alpha production by macrophages in EL4-bearing mice. In normal macrophages, in vitro pretreatment with TGF-beta 1 potentiated IL-10 production, and when natural TGF-beta 1 was administered to normal mice, the recovered peritoneal macrophages showed enhanced IL-10 production. Based on the above findings it can be concluded that TGF-beta enhances macrophage ability to produce IL-10, which sheds a new light on the role of TGF-beta in the immune system.

Animals↗

Isolation of a full-length cDNA clone for human GTP cyclohydrolase I type 1 from pheochromocytoma.

Although the existence of three different cDNA forms of human GTP cyclohydrolase I (GCH I) have been reported (Togari et al., 1992), the full-length sequence of any human GCH I cDNA involving poly (A) tail has not yet been documented. In the present study, we first isolated a full-length cDNA clone encoding human GCH I type 1 from human pheochromocytoma cDNA library. The length of the cDNA insert was 2,921 base pairs including poly (A) tail. RNA blot analysis showed a single mRNA species of 4.0 kb in human pheochromocytoma tissue.

Amino Acid Sequence↗

Calcium and magnesium absorption from the colon and rectum are increased in rats fed fructooligosaccharides.

We investigated the effects of fructooligosaccharides on the absorption of calcium, magnesium and water from the colon and rectum of rats fed a control diet or the control diet containing 50 g fructooligosaccharides/kg. Chromium-mordanted cellulose was used as an unabsorbable marker to calculate apparent absorption of calcium and magnesium. There was a positive correlation (r = 0.982, P < 0.001 in rats fed the control diet and r = 0.975, P < 0.001 in rats fed the fructooligosaccharides-containing diet) between the amount of chromium and the dry weight of each fecal pellet in the colon and rectum. Ratios of calcium to chromium and magnesium to chromium in fecal pellets in the colon and rectum were calibrated from the Ca:Cr and Mg:Cr ratios of cecal contents. In rats fed the fructooligosaccharides-containing diet, but not in rats fed the control diet, these ratios were correlated with the fractional length of transit along the colon and rectum, indicating linear disappearance of calcium and magnesium during the colorectal passage. Total apparent absorption of calcium and magnesium, predicted from regression equations with the Ca:Cr and Mg:Cr ratios of cecal contents, agreed well with those calculated from the Ca:Cr and Mg:Cr ratios of feces. The consumption of fructooligosaccharides did not affect net water absorption from the colon and rectum. These results indicated that fructooligosaccharides significantly increased calcium and magnesium absorption and that indigestible and fermentable carbohydrate facilitates colorectal absorption of calcium and magnesium.

Animals↗

Metabolic effects of glibenclamide in isolated rat hepatocytes in the absence of extracellular Ca2+.

We examined the metabolic effects of glibenclamide, a potent second-generation sulfonylurea, in isolated rat hepatocytes incubated in the absence of extracellular Ca2+. We first demonstrated in the present study that glibenclamide caused a significant increase in basal glucose release and lactate production without any modification of intracellular Ca2+ concentration or cAMP levels in isolated rat hepatocytes. Furthermore, glibenclamide inhibited the noradrenaline-induced increase in cAMP accumulation, while activation of glycogenolysis by noradrenaline was not suppressed by this agent. Our data indicate that glibenclamide exerts its metabolic effects independent of intracellular Ca2+ mobilization and cAMP accumulation.

Animals↗

Effects of fructooligosaccharides on the absorption of iron, calcium and magnesium in iron-deficient anemic rats.

We investigated the effects of fructooligosaccharides (FO)-feeding on the absorption of iron (Fe), calcium (Ca) and magnesium (Mg) and on the biochemical parameters in Fe-deficient anemic rats. Fe-deficient anemic rats were made by feeding an Fe-deficient diet for 3 weeks. Then these Fe-deficient rats were fed an experimental diet that contained one of two levels of Fe (15 or 30 mg/kg diet), in the form of ferric pyrophosphate, and one of two levels of FO (0 or 50 g/kg diet) for 2 weeks. After the rats were fed these experimental diets, FO-feeding increased the hematocrit ratio, the concentration of hemoglobin and the hemoglobin regeneration efficiency during the first week. Also, the apparent absorption of Fe was increased by FO-feeding. The levels of Fe in the diet did not affect the absorption of Ca and Mg. However, FO-feeding increased the absorption of Ca and Mg. FO-feeding lowered the pH and raised the solubility of Fe, Ca and Mg in the cecal contents, suggesting that those increasing effects of FO-feeding on absorption of these minerals is correlated with fermentation of FO in the large intestine, namely, the cecum and colon. We concluded that FO-feeding improved recovery from anemia and increased the absorption of Fe, Ca and Mg in Fe-deficient anemic rats.

Absorption↗