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Biomedical subjects

T Sakata

Publications and source records attributed to T Sakata.

At least 235 records · Page 13Linked to original sources

Local stimulatory effect of short-chain fatty acids on the mucus release from the hindgut mucosa of rats (Rattus norvegicus).

Short chain fatty acids such as acetic, propionic and butyric acids produced by hindgut bacteria affect various intestinal functions. However, the effect of short-chain fatty acids on mucus release from the hindgut mucosa was not clear. This study tested if these acids stimulate mucus release from hindgut mucosa and if the effect of these acids is local or requires a systemic mediation. Approximately 2 ml of either a physiologic mixture of acetic, propionic and butyric acids (100, 20 and 60 mmol/l, pH adjusted to 6.1) or 180 mmol/l sodium chloride (control solution, pH adjusted to 6.1) was infused into each permanently isolated cecum of anesthetized rats (Rattus norvegicus) through the ileal stoma by hydrostatic pressure. The cecum and distal colon were removed 1 hr after the infusion. The number of mucin containing cells per crypt section was counted on histological sections of these segments. The number of mucin containing cells was smaller in the cecum (but not in the distal colon) of rats infused in short-chain fatty acids compared with that of control rats. These results indicated that short-chain fatty acids locally stimulated mucus release from hindgut mucosa.

Animals↗

Antiviral action of oligodeoxyguanylic acids against human immunodeficiency virus type 1.

Deoxyguanylic acids, but not other deoxynucleotides, as short as 3- to 4-mer, were effective in preventing HIV-1-induced cytopathicity. In addition, they prevented giant cell formation of infected Sup-T1 cells, and p24 production in HIV-1 infected H9 cells. Phosphorylation at either the 5'- or 3'-end enhanced these activities. Furthermore, 5'-phosphorylated phosphorothioate tetradeoxyguanylic acid was effective in reducing HIV production in chronically infected cells (H9/IIIB). The search for the target steps of this compound revealed that it inhibits at least 3 steps in the life cycle of HIV: interaction with CD4 (measured by inhibitory effect on the syncytia formation between Sup-T1 and H9/IIIB cells), reverse transcriptase, and step(s) after integration. These results suggest that phosphorylated phosphorothioate tetradeoxyguanylic acid may be a novel candidate for a therapeutic agent of AIDS.

Antiviral Agents↗

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↗

Physiological, morphological and anatomical responses of Fraxinus mandshurica seedlings to flooding.

Two-year-old Fraxinus mandshurica Rupr. var. japonica Maxim. seedlings were flooded to 8 cm above soil level for 70 days. The flooding treatment altered the growth, morphology, stem anatomy and ethylene production of the seedlings. Although flooding did not affect height growth, it stimulated diameter growth of the submerged stems by increasing both the number and size of wood fibers produced; however, the thickness of the cell walls of the wood fibers was reduced by flooding. In response to the flooding treatment, the seedlings formed abundant hyperhydric tissues, originating from the vicinity of lenticels on the surface of the flooded stems, and adventitious roots, which grew through the hyperhydric tissues. Aerenchyma tissues were observed in the bark of the adventitious roots. The flooding treatment did not affect dry weight increment of leaves and stems, but it reduced the total dry weight increment of the root system even though it promoted adventitious root formation. Flooding also enhanced ethylene production in the submerged portions of stems. The potential roles of flood-induced ethylene in cambial growth and adventitious root formation in flooded plants are discussed.

Journal Article↗

Anti-human immunodeficiency virus (HIV) activities of halogenated gomisin J derivatives, new nonnucleoside inhibitors of HIV type 1 reverse transcriptase.

Halogenated gomisin J (a derivative of lignan compound), represented by the bromine derivative 1506 [(6R, 7S, S-biar)-4,9-dibromo-3,10-dihydroxy-1,2,11,12-tetramethoxy-6, 7-dimethyl-5,6,7,8- tetrahydrodibenzo[a,c]cyclo-octene], was found to be a potent inhibitor of the cytopathic effects of human immunodeficiency virus type 1 (HIV-1) on MT-4 human T cells (50% effective dose, 0.1 to 0.5 microM). Gomisin J derivatives were active in preventing p24 production from acutely HIV-1-infected H9 cells. The selective indices (toxic dose/effective dose) of these compounds were as high as > 300 in some systems. 1506 was active against 3'-azido-3'-deoxythymidine-resistant HIV-1 and acted synergistically with AZT and 2',3'-ddC. 1506 inhibited HIV-1 reverse transcriptase (RT) in vitro but not HIV-1 protease. From the time-of-addition experiment, 1506 was found to inhibit the early phase of the HIV life cycle. A 1506-resistant HIV mutant was selected and shown to possess a mutation within the RT-coding region (at position 188 [Tyr to Leu]). The mutant RT expressed in Escherichia coli was resistant to 1506 in the in vitro RT assay. Some of the HIV strains resistant to other nonnucleoside HIV-1 RT inhibitors were also resistant to 1506. Comparison of various gomisin J derivatives with gomisin J showed that iodine, bromine, and chlorine in the fourth and ninth positions increased RT inhibitory activity as well as cytoprotective activity.

Antiviral Agents↗

Hypothalamic neuronal histamine modulates physiological responses induced by interleukin-1 beta.

Dynamic involvement of hypothalamic histamine in ingestive behavior and thermogenesis induced by interleukin-1 beta (IL-1 beta) was examined in rats. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta decreased food and water intake and elevated body temperature. However, depletion of neuronal histamine induced by intraperitoneal injection of 160 mumol/rat alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase (HDC), attenuated the suppressive effect of IL-1 beta on food intake, facilitated the suppressive effect on drinking, and enhanced the elevating effect on rectal temperature. Intraperitoneal injection of 0.12 nmol/rat IL-1 beta increased hypothalamic histamine turnover rate. The same dose of IL-1 beta also increased activity of HDC and histamine-N-methyltransferase (HMT). These results suggest that IL-1 beta may stimulate synthesis and release of hypothalamic histamine in presynaptic terminals by activation of HDC and facilitate degradation of extracellular histamine by activation of MHT. These changes in the dynamics of hypothalamic histamine modulate IL-1 beta-induced ingestive behavior and body temperature.

Animals↗

Plasma plasminogen activator inhibitor-1, tissue plasminogen activator and serum lipoprotein(a) after reperfusion therapy in acute myocardial infarction: comparison between sequential and direct percutaneous transluminal coronary angioplasty.

To determine which reperfusion therapy for acute myocardial infarction (AMI) is advantageous to avoid subsequent thrombotic coronary occlusion, 8 patients with AMI were studied. Four of them (group S) underwent sequential PTCA following unsuccessful intracoronary thrombolysis and the others (group D) direct PTCA. Serial changes in plasma plasminogen activator inhibitor-1 (PAI-1), plasma tissue plasminogen activator (t-PA) antigen and serum lipoprotein(a) levels were compared between the two groups. In group S, plasma PAI-1 levels showed no significant serial change after PTCA. However, in group D, plasma PAI-1 levels increased significantly 4-24 h after PTCA. We suggest that more attention should be focused on the prevention of thrombotic coronary closure as well as mechanical abrupt occlusion after direct PTCA.

Angioplasty, Balloon, Coronary↗

Suppression of plasma-activated factor VII levels by warfarin therapy.

To investigate the effect of warfarin treatment on the early phase of tissue factor-induced coagulation, we measured plasma-activated factor VII (factor VIIa) levels by a direct fluorogenic assay in 74 cardiovascular disease patients on long-term oral anticoagulation. We divided the patients into three groups based on the international normalized ratio (INR). In the patients with INR ranges of < 1.7 and 1.7 to 2.5, factor VIIa levels were 42% and 61% lower, respectively, than in age- and sex-matched controls. Factor VII coagulant activity (factor VIIc), factor VII antigen (factor VIIag), protein C, and factor X levels were also reduced to a similar extent in both groups. However, in patients with an INR > 2.5, the factor VIIa level was not decreased compared with that at an INR of 1.7 to 2.5, although the factor VIIc, factor VIIag, factor X, and protein C levels were all decreased further. Although the precise relation between the reduction of factor VIIa levels and the increase of INR requires appropriately designed long-term clinical trials, our data suggest that an INR range of 1.7 to 2.5 is sufficient for the suppression of factor VIIa. During the long-term follow-up of three patients with congenital antithrombin III or protein C deficiency, the factor VIIa level was more responsive to changes in the warfarin dose than the INR, and there were generally no corresponding changes of the thrombin-antithrombin III complex (TAT) level. However, one patient showed a transient marked increase of factor VIIa during the discontinuation of warfarin that was accompanied by an increase in TAT. Based on these findings, factor VIIa could be useful for monitoring both hypercoagulable and hypocoagulable states.

Adult↗

Activation of tissue factor-induced coagulation and endothelial cell dysfunction in non-insulin-dependent diabetic patients with microalbuminuria.

We studied the relationships between albuminuria, tissue factor-induced coagulation, and endothelial cell dysfunction in 67 patients with non-insulin-dependent diabetes mellitus (NIDDM) who were divided into three groups on the basis of their urinary albumin excretion rate (AER). To assess the early phase of tissue factor-induced coagulation, activated factor VII (FVIIa) levels in plasma were measured by a direct fluorogenic assay. As markers of endothelial cell dysfunction, levels of von Willebrand factor (vWF), tissue-type plasminogen activator-plasminogen activator inhibitor-1 (TPA-PAI-1) complex, PAI-1, and tissue factor pathway inhibitor (TFPI) were measured. FVIIa levels were increased in normoalbuminuric NIDDM patients (AER < 15 micrograms/min) when compared with normal control subjects. This FVIIa increase was accompanied by an increase in thrombin-antithrombin III complex (TAT) levels, indicating increased activation of coagulation even in normoalbuminuric patients. In NIDDM patients with microalbuminuria (AER = 15-200 micrograms/min), the FVIIa level, the FVIIa-FVII antigen (Ag) ratio (an indicator of activation of FVII zymogen to FVIIa), and the TAT level were further increased. This group also had higher levels of endothelial cell-derived factors (vWF, TPA-PAI-1 complex, and PAI-1) than the control group. The levels of endothelial cell-derived factors (including TFPI) were highest in the NIDDM patients with overt albuminuria (AER > 200 micrograms/min). In all 67 diabetic patients, AER showed a strong positive correlation with FVIIa (r = .574, P < .0001) and a weakly but still significant correlation with FVIIa-FVII:Ag (r = .365, P = .01), vWF (r = .315, P < .01), and TAT (r = .323, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of specific binding of high density lipoprotein to eel hepatocytes on their secretion of lipoprotein.

Specific binding of eel serum high-density lipoprotein (HDL) to eel hepatocytes was demonstrated by using a synthesized fluorescent lipophilic dye. HDL binding was inhibited by the addition of unlabeled HDL. The binding of HDL to the hepatocytes was saturated at concentrations over 100 micrograms HDL protein/ml and Kd value was 20 micrograms HDL protein/ml. A fluorescent photomicrograph of the cultured eel hepatocytes which were incubated with the dye showed the bright, circumferential plasma membranes stained with the dye. 125I-HDL was incorporated into the acid insoluble- and soluble-fractions of the cultured hepatocytes during incubation at 28 degrees C for 1 h. There are three remarkable characteristics of the effect of HDL on the cultured hepatocytes. One is that the addition of HDL to the hepatocytes induced the efflux of cholesterol, triacylglycerol, and phospholipid from the hepatocytes. The second characteristic is that the efflux of the intracellular lipids was carried out with very-low-density-like or chylomicron-like lipoprotein secreted by the hepatocytes. The third characteristic is that HDL specifically stimulated the synthesis of the lipoprotein and had no effect on the synthesis of intracellular proteins and the secreted proteins except for the lipoprotein.

Anguilla↗

Electrocardiographic abnormalities in patients with Cushing's syndrome.

The electrocardiograms in 8 patients with Cushing's syndrome and 4 with Cushing's disease were studied. The patients were divided into group A with electrocardiographic abnormalities and group B without. The mean age was significantly higher in group B than in group A. However, blood pressure, mean heart rate and the plasma adrenocorticotropic hormone level showed no significant differences between the two groups. In group A, the plasma concentration of cortisol had a tendency to be higher than in group B (A vs. B: 281 +/- 100 ng/ml, 188 +/- 9 ng/ml, respectively). Echocardiography performed on three of four patients in group A revealed cardiac hypertrophy. While, in group B, echocardiography performed on two patients showed no hypertrophic findings. As a result, it seems that the electrocardiographic changes are correlated with the plasma level of cortisol via myocardial hypertrophy.

Adrenocorticotropic Hormone↗

Secondary amyloidosis associated with Castleman's disease.

A rare case of secondary amyloidosis associated with Castleman's disease is reported. A 53-year-old woman was referred for investigation of proteinuria. Biopsy specimens from kidney and gastric mucosa revealed numerous amyloid deposits, defined as AA amyloidosis by immunohistological staining. Castleman's disease was found in the abdomen as the primary disease for the amyloidosis. Although the urinary protein was somewhat reduced and the inflammatory findings were improved after removal of the lymphoma, renal insufficiency progressed and hemodialysis was begun.

Amyloidosis↗

Poor fermentability of "mekabu" (sporophyll of Undaria pinnatifida) alginic acid in batch culture using pig cecal bacteria.

Sodium alginate, mannuronic acid-rich and guluronic acid-rich fractions were prepared from "Mekabu" (sporophyll of Undaria pinnatifida). The production of short-chain fatty acids such as acetic, propionic and n-butyric acids from these fractions in mini-scale batch culture using pig cecal bacteria was studied, and the gas released from the culture was monitored. The volume of released gas corrected for blank value decreased in the order: glucose (a reference substrate) > guluronic acid-rich fraction > sodium alginate = mannuronic acid-rich fraction. The amounts of short-chain fatty acids produced from three fractions of alginic acid were smaller than that of glucose. These results suggested that alginic acid was poorly fermentable for hindgut bacteria and that its contribution to the host energy pool via microbial metabolism is small.

Acetates↗

Histamine effect on ornithine decarboxylase of rat intestine in cases of ischemia-reperfusion compared with refeeding.

Our previous study suggested that histamine might enhance the increase of ornithine decarboxylase activity in injured intestinal mucosa. To test this hypothesis, we measured histamine content in mesenteric lymph and ornithine decarboxylase activity in intestinal mucosa after ischemia-reperfusion in the rat. We examined the effect of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase, on ornithine decarboxylase activity after ischemia-reperfusion and compared this with its effect on the rat after refeeding. Ischemia-reperfusion was performed by 15-min occlusion of the superior mesenteric artery. After ischemia-reperfusion, histamine content in mesenteric lymph increased, and this increase was completely suppressed by alpha-fluoromethylhistidine pretreatment. In contrast to ischemia-reperfusion, histamine content in mesenteric lymph did not change after refeeding. Ornithine decarboxylase activity increased markedly 3 and 6 hr after ischemia-reperfusion and refeeding, whereas alpha-fluoromethylhistidine attenuated the increase in ornithine decarboxylase activity only in the ischemia-reperfusion group. These results indicate that increase in histamine synthesis in the intestinal mucosa plays an important role in the increase of ornithine decarboxylase activity after ischemia-reperfusion but that histamine is not related to the increase in ornithine decarboxylase activity after refeeding.

Animals↗

Marked increase of activated factor VII in uremic patients.

We investigated plasma activated factor VII (FVIIa) levels in uremic patients (nondialysis group: n = 38; dialysis group: n = 36) and healthy controls (n = 32). We also measured the plasma levels of thrombomodulin (an indicator of endothelial cell injury) and tissue factor. Plasma FVIIa showed a marked increase in the nondialysis group (mean [95% confidence interval]: 4.6 [4.1-5.1] ng/ml, p < 0.0001) with the progressive impairment of renal function, as indicated by the serum creatinine level, when compared with the 32 controls (2.8 [2.5-3.1] ng/ml), and was further increased in the dialysis group (6.1 [5.5-6.8] ng/ml, p < 0.001 vs. nondialysis group). Plasma levels of thrombomodulin and tissue factor were also higher in the nondialysis group than the control group, and were further increased in the dialysis group. Plasma tissue factor levels did not show any correlation with FVIIa or thrombomodulin in both the nondialysis and dialysis groups. Thus, circulating tissue factor appears to be released by a different mechanism from thrombomodulin and may not contribute to the direct activation of factor VII in uremic patients. On the other hand, the plasma level of thrombomodulin was positively correlated with that of FVIIa in the nondialysis group, and this correlation was independent of renal function. Thus, enhanced conversion of factor VII zymogen to FVIIa, probably related to endothelial cell injury, may be a risk factor for cardiovascular events in uremic patients.

Aged↗

Effect of n-butyric acid on epithelial cell proliferation of pig colonic mucosa in short-term culture.

Short-chain fatty acids (SCFA) such as acetic, propionic and n-butyric acids produced by hindgut bacteria stimulate gut epithelial cell proliferation through afferent neural and efferent non-neural systemic transmissions beside a probable local mechanism. In the present study, we developed an experimental system using pig hindgut mucosa in short term culture to clarify the mechanism of the local trophic effect of SCFA. Pig mucosal tissue pieces of the distal colon were cultured in RPMI 1640 medium containing glutamine, 20% (v/v) newborn calf serum and n-butyric acid (0, 0.5, 1.0 or 5.0 mmol/L). Crypt cell production rate from 0.5 to 3.5 and from 21 to 24 hours of culture was measured. Butyric acid increased crypt cell production rate of pit distal colon only at 5 mmol/L. The effect of butyric acid did not differ between samples of different length of n-butyric acid exposure. The effect of n-butyric acid in this study resembled to that found in human biopsied specimens of the colon. The present results also indicated that epithelial cells of pig colonic mucosa in short-term culture presented here retained the proliferative activity and the responsiveness to n-butyric acid.

Animals↗