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Biomedical subjects

S Saeki

Publications and source records attributed to S Saeki.

At least 55 records · Page 3Linked to original sources

Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis.

Spontaneous regression of hepatocellular carcinoma is a rare phenomenon. Abscopal regression of tumours resulting from the effect of irradiation of a tissue on a remote non-irradiated tissue is also rare. The case of a 76 year old Japanese man with hepatocellular carcinoma that regressed after radiotherapy for thoracic vertebral bone metastasis is described. Serum levels of tumour necrosis factor-alpha increased after radiotherapy. The findings suggests that such abscopal related regression may be associated with host immune response, involving cytokines such as tumour necrosis factor-alpha.

Aged↗

Circadian rhythms in the incorporation and secretion of 3H-proline by odontoblasts in relation to incremental lines in rat dentin.

Circadian incremental lines are universally found in the dentin of animals. They are believed to be caused by functional changes in odontoblasts over 24 hrs. However, the mechanism of rhythmic dentin formation has not yet been elucidated. In the present study, we investigated whether there is a 24-hour rhythm in the collagen-synthetic and secretory activities of odontoblasts by radioautography with 3H-proline as a tracer. Six different groups of rats were injected with 3H-proline at 0000, 0400, 0800, 1200, 1600, or 2000 after the animals had become acclimated to a 12/12-hour light-dark illumination cycle for 2 wks. One hour after the injection, the maxillary incisors were removed and processed for radioautographic study. The silver grains of 3H-proline were most intense over odontoblasts and predentin during the environmental light period, while the nadir occurred during the dark period. The peak value was approximately two-fold higher than the minimum value. Moreover, in the dentin from rats that had been infused with 3H-proline continuously for 10 days by means of osmotic minipumps, silver grains of 3H-proline were heavily distributed over the dark hematoxylin-stained incremental lines. Thus, we demonstrated that odontoblasts show circadian rhythm with regard to collagen synthesis and secretion. These rhythms in odontoblastic function may be responsible for circadian incremental lines in dentin.

Analysis of Variance↗

Green tea suppresses D-galactosamine-induced liver injury in rats.

Dietary supplementation with powder of a green tea extract suppressed the enhancement of plasma alanine aminotransferase and aspartate aminotransferase activities induced by D-galactosamine, but not by carbon tetrachloride, in a dose-dependent manner in rats. The minimum dose to cause a significant effect was 1 to 2%. Drinking green tea also suppressed plasma enzyme activities. These results indicate that green tea had a liver injury-preventive effect.

Alanine Transaminase↗

[A study of post-operative delirium in elderly patients].

We investigated the post-operative delirium in elderly patients of over 65 years of age. This investigation consisted of two studies, a prospective study and a retrospective study. In the prospective study, we evaluated the incidence of post-operative delirium and the incidence of post-operative delirium was estimated pre-operatively using State-Trait Anxiety Inventory (STAI) and Mini Mental State Examination (MMSE) in 24 patients scheduled for elective surgery under general anesthesia in the period from Nov. 1995 to Oct. 1996. In the retrospective study, we selected patients with post-operative delirium from 1600 patients who had undergone scheduled and emergency operation under general anesthesia in the same period as in the prospective study and analyzed the incidence of post-operative delirium and background of these patients. Twenty four patients in the prospective study were excluded from the retrospective study. In the prospective study, although post-operative delirium was observed in 2 cases (8.3%), no specific changes were observed in anxiety state and the ability of recognition. In the retrospective study, post-operative delirium was observed in 22 cases (1.37%). In these patients, several factors such as blood transfusion, emergency operation, dehydration, thrombosis of the superior mesenteric artery, history of ischemic heart disease, brain infarction and atrial fibrillation were thought to be major risk factors triggering post-operative delirium. In this study we could not conclude that STAI or MMSE are useful to estimate the incidence of post-operative delirium preoperatively. However, our result suggests that we should be careful about the incidence of post-operative delirium in elderly patients with pre-operative risk factors as mentioned above.

Aged↗

[Suppressive effect of isoflurane on somato-sympathetic reflexes in cats].

Effects of isoflurane on the reflex activity of the sympathetic nervous system were investigated in 35 cats by observing alteration of the amplitudes of somato-sympathetic medullary reflex potentials. A and C-reflex potentials, which are induced from lumbar sympathetic trunk by electric stimulation of ipsilateral femoral nerve are known to arise from A-fiber group and C-fiber group, respectively. One or two percent isoflurane in oxygen was administered for 30 minutes, because it is known that I MAC of isoflurane in cats is 1.61%. The amplitude and latency of the potentials were measured during and after inhalation of the test drug, and the results were presented as percentage change from that at prior levels of inhalation as control. The results were as follows. (1) The amplitudes of A- and C-reflex potentials were suppressed dose-dependently in rats with intact brain. (2) The amplitudes of both potentials increased by decerebration at midbrain level. (3) In decerebrate cats, the amplitudes of both potentials at each inhaled concentration were suppressed to the similar levels at inhalation of 2% isoflurane in intact cats, although a slight difference between intact and decerebrated cats was observed with A-potentials during inhalation of 1% isoflurane. (4) The latencies were prolonged slightly in A-reflex potentials, only in intact cats at both concentrations. (5) Blood pressure decreased during inhalation of the test drug in every condition, but their dose-dependencies were evident only in intact cats. (6) Selective suppression of C-reflex potential by inhalation of isoflurane could not be demonstrated. These results suggest that isoflurane has a strong suppressive effect on sympathetic reflex center in medulla oblongata with was demonstrated by greater degree of suppression of the reflex responses in decerebrate cats than that in intact animals. It was concluded that the effect of isoflurane on sympathetic nervous system is similar to that of halothane.

Anesthetics, Inhalation↗

[A clinical and portal hemodynamic analysis for obliteration of gastric-renal shunt communicated with gastric fundic varices].

To clear the efficacy of treatment for large porto-systemic shunts, changes of liver function and portal hemodynamics after obliteration of gastric-renal shunt (GRS) or gastric-inferior phrenic vein shunt (GIS) communicated with gastric fundic varies in 24 patients treated with balloon-occluded retrograde transvenous obliteration (B-RTO) were studied. 1) The wedged hepatic venous pressure and the hepatic venous pressure gradient were statistically not significant changed after obliteration of GRS or GIS. 2) Serum albumin value was significantly increased (p < 0.005) and ICGR15 was significantly improved (p < 0.005) at one year after treatment in patients that, not only whose GRS or GIS were larger than 10mm in diameter, but also whose superior mesenteric arterial venography before treatment showed hepatofugal flow. 3) At a mean follow-up abdominal angiography of 23.3 months in 20 cases, GRS or GIS was yet obliterated respectively. And more, superior mesenteric arterial venography revealed hepatopetal flow alone in 43% of patients that, whose superior mesenteric arterial venography before treatment showed hepatofugal flow. 4) During a mean follow-up of 32.5 months, gastric fundic varies were not recurrent in all patients, but the other hand, cumulative red color sign positive esophageal varies apparent rates were high (16.7% at before treatment, 38.4% at 2-years, 54.4% at 4-years). According to their hemodynamic characteristics, cumulative red color sign positive esophageal varies apparent rates in patients with another collaterals besides GRS or GIS before treatment (26.7% at before treatment, 61.1% at 2-years, 74.1% at 4-years) were significantly higher (p < 0.05) than those in patients without another collateral except GRS or GIS (0% at 2-years, 16.7% at 4-years). We conclude that, 1) Increment of portal flom and improvement of liver function can be expected by obliteration of GRS or GIS in patients that, whose superior mesenteric venous blood flow into large GRS or GIS. 2) After obliteration of GRS or GIS, the incidence of aggravation of esophageal varies in patients with another collaterals besides GRS or GIS before treatment is high, while that in cases without another collateral is low.

Adult↗

Iontophoretic application of prostaglandin E1 for improvement in peripheral microcirculation.

OBJECTIVE: The pharmacological effects of iontophoretically applied prostaglandin E1 (PGE1) on the peripheral microcirculation were investigated. MATERIAL AND METHOD: PGE1 concentrations permeated through hairless mouse skin iontophoretically were measured by HPLC at hourly intervals. 19 patients with arteriosclerosis obliterans were given PGE1 (20 microg) iontophoretically on the dorsum of the foot. As a control, normal saline was applied iontophoretically on another day. The increase rate in cutaneous blood flow as measured by laser Doppler flux (LDF) level was investigated. 5 of these 19 patients received PGE1 (20 microg) solution intravenously on another day. The increase rate in cutaneous blood flow as measured by laser Doppler flux (LDF) level was compared between iontophoresis and intravenous drip infusion. RESULT: PGE1 was transported across hairless mouse skin with iontophoresis in a time-dependent manner, while it did not permeate by passive transport. The percent increase in LDF level was significantly higher in the PGE1 group than in the control group(32.7+/-20.2% vs. 10.3+/-15.5%, p.001). The percentual increase in LDF level was significantly higher with iontophoresis than with intravenous drip infusion (43.7+/-19.5% vs. 11.7+/-28.3%, p < 0.05). CONCLUSION: The results indicated that iontophoretically applied PGE1 was effective in improving the impaired microcirculation due to peripheral arterial occlusive disease. This technique may be useful in managing severely ischemic legs.

Alprostadil↗

Exon/intron organization, chromosome localization, alternative splicing, and transcription units of the human apolipoprotein E receptor 2 gene.

Apolipoprotein E receptor 2 is a recently identified receptor that resembles low and very low density lipoprotein receptors. Isolation and characterization of genomic clones encoding human apolipoprotein E receptor 2 revealed that the gene spans approximately 60 kilobases and contains 19 exons. The positions of the exon/intron boundaries of the gene are almost identical to those of low and very low density lipoprotein receptors. Fluorescent in situ hybridization of human chromosomes revealed that the gene is located on chromosome 1p34. Isolation of a cDNA encoding a variant receptor and reverse transcription-polymerase chain reaction indicate the presence of multiple variants with different numbers of cysteine-rich repeats in the binding domain of the receptor. We also found a variant receptor lacking a 59-amino acid insertion in the cytoplasmic domain. The transcription start site was mapped to the position 236 base pairs upstream of the AUG translation initiator codon by primer extension analysis. Sequence inspection of the 5'-flanking region revealed potential DNA elements: AP-2, GC factor, PEA3, and Sp1. The minimal promoter region and a region required for nerve growth factor inducibility in PC12 cells were also determined.

Alternative Splicing↗

Correlation of suppressed linoleic acid metabolism with the hypocholesterolemic action of eritadenine in rats.

The dose-dependent effects of dietary eritadenine on the metabolism of linoleic acid and on the plasma cholesterol concentration were investigated to clarify the mechanism of the hypocholesterolemic action of eritadenine in rats. Rats were fed control or eritadenine-supplemented (2 to 20 mg/kg) diets for 14 d. Eritadenine supplementation significantly decreased both the plasma cholesterol concentration and the 20:4n-6/18:2n-6 ratio of liver microsomal and plasma phosphatidylcholine (PC) in a dose-dependent manner. Eritadenine was also found to decrease the activity of delta 6 desaturase in liver microsomes; there was significant correlation between the delta 6-desaturase activity and the 20:4n-6/18:2n-6 ratio in the PC of liver microsomes (r = 0.989, P < 0.001) or plasma (r = 0.986, P < 0.001). Certain plasma PC molecular species, as represented by 16:0-18.2, were increased by eritadenine in a dose-dependent manner, and certain plasma PC molecular species, as represented by 18:0-20:4, were conversely decreased by eritadenine. There was a significant correlation between the plasma total cholesterol concentration and the proportion of the sum of plasma PC molecular species which contain 18:1 or 18:2 in the sn-2 position. These results support the idea that the suppression of linoleic acid metabolism by eritadenine might be associated with the hypocholesterolemic action of eritadenine.

Adenine↗

Dietary eritadenine modifies plasma phosphatidylcholine molecular species profile in rats fed different types of fat.

The effect of dietary eritadenine on plasma phosphatidylcholine (PC) molecular species composition was investigated in relation to its hypocholesterolemic action in rats fed different types of fats (olive oil, corn oil and linseed oil; 100 g/kg diet). Eritadenine supplementation (50 mg/kg diet) significantly decreased the plasma total cholesterol concentration, irrespective of dietary fat sources, and without change in the order of plasma cholesterol concentration among the fat groups (corn oil > olive oil > linseed oil). Eritadenine significantly decreased the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver microsomes of all the fat groups, while the PC:PE ratio was unaffected by dietary fat type. The fatty acid and molecular species composition of plasma PC was affected either directly or indirectly by the fatty acid composition of dietary fats. The proportion of linoleic acid and linoleic acid-containing molecular species (16:0-18:2 and 18:0-18:2) in plasma PC was the highest in rats fed linseed oil, despite the fact that linoleic acid concentration of linseed oil was only 1/3 that of corn oil. Eritadenine supplementation significantly increased the proportion of linoleic acid and linoleic acid-containing molecular species, especially 16:0-18:2, in plasma PC, irrespective of dietary fat source. Altered plasma PC molecular species composition, as represented by an increase in 16:0-18:2 PC, might contribute to the hypocholesterolemic action of eritadenine.

Adenine↗

Methionine content of dietary proteins affects the molecular species composition of plasma phosphatidylcholine in rats fed a cholesterol-free diet.

The effects of dietary protein types and methionine supplementation on phospholipid metabolism were investigated to clarify the mechanism of the hypocholesterolemic action of soybean protein in rats fed a cholesterol-free diet. The effect of switching from a casein diet to a soybean protein diet was also investigated. Rats were fed casein, soybean protein or soybean protein + methionine diet for 14 d. Compared with casein diet, feeding of soybean protein diet led to significantly higher proportions of linoleic acid and linoleic acid-containing molecular species, especially 16:0-18:2, in plasma and liver microsomal phosphatidylcholine (PC). In addition, significantly lower plasma cholesterol concentration, hepatic S-adenosylmethionine concentration and liver microsomal PC:phosphatidylethanolamine ratio resulted. These alterations caused by the soybean protein diet were significantly suppressed by supplementing methionine to the level of the casein diet (3.4 g/kg diet). The proportion of the sum of certain plasma PC molecular species, which contain 18:1 or 18:2 in the sn-2 position, increased in response to the switch from the casein diet to the soybean protein diet at a rate similar to the decrease in plasma cholesterol concentration; there was a significant correlation between the two variables (r = -0.992, P < 0.001). These results indicate that about 40% of the hypocholesterolemic action of soybean protein is due to the low methionine content of the protein and might be associated with alterations of the plasma phospholipid molecular species profile.

Animals↗

Human apolipoprotein E receptor 2. A novel lipoprotein receptor of the low density lipoprotein receptor family predominantly expressed in brain.

Isolation and characterization of a human cDNA demonstrated a novel lipoprotein receptor designated apolipoprotein E receptor 2 (apoER2). The new receptor consists of five functional domains resembling the low density lipoprotein (LDL) and very low density lipoprotein (VLDL) receptors. LDL receptor deficient Chinese hamster ovary cells expressing human apoER2 bound apoE rich beta-migrating VLDL with high affinity and internalized. LDL was bound with much lower affinity to these cells. The 4.5- and 8.5-kb mRNAs for the receptor were most highly expressed in human brain and placenta. In rabbit tissues, multiple species of the mRNA with 4, 4.5, 5.5, 8.5, and 11 kb were detected most intensely in brain and testis and, to a much lesser extent, in ovary, but were undetectable in other tissues. In rat adrenal pheochromocytoma PC12 cells, the receptor mRNA was induced by treatment of the cells with nerve growth factor. The receptor transcripts were detectable most intensely in the cerebellar cortex, choroid plexus, ependyma, hippocampus, olfactory bulb and, to a much lesser extent, in the cerebral cortex as revealed by in situ hybridization histochemistry. In the cerebellar cortex, the receptor transcripts were densely deposited in Purkinje cell somata.

Amino Acid Sequence↗

Involvement of several protein kinases in the phosphorylation of p47-phox.

Protein kinases are stimulated during the microbicidal responses of neutrophils. In particular, the activation of protein kinase C causes the phosphorylation of p47-phox, one of the cytosolic components of NADPH oxidase. Phosphorylated p47-phox was accumulated not only by PMA treatment, but also by calyculin A treatment. However, p47-phox phosphorylated by calyculin A treatment lost its ability to activate NADPH oxidase. Several protein kinases were activated by calyculin A treatment. Furthermore the phosphorylation sites of p47-phox by calyculin A treatment were different from those by PMA treatment. These results indicated that calyculin A-activated kinases phosphorylated p47-phox at the site different from that phosphorylate by protein kinase C, resulting in suppression of NADPH oxidase activation.

Amino Acid Sequence↗

Functional contribution of preoperative portal vein occlusion to hepatectomy. With special reference to hepatic energy charge and DNA synthesis after hepatectomy in rats.

OBJECTIVE: To examine possible functional contributions of preoperative portal branch ligation before hepatectomy (PBL-Hx). DESIGN: Rats were randomly divided into 3 groups. In the PBL-Hx group, the portal branch supplying the left lateral and median lobes of the liver was ligated and the corresponding lobes (48% of the whole liver) were excised 2 days later. In the sham groups (one 68% Hx; the other 47% [hereafter, sham-67% Hx, and sham-47% Hx]), originally ligated lobes and left lateral and caudate lobes, similar to the excised liver volume in the PBL-Hx group, respectively, were excised 2 days after sham operation without PBL. MAIN OUTCOME MEASURES: Hepatic adenine nucleotides and energy charge, which are essential for vital function of hepatocytes, and liver regeneration were assessed by the DNA synthesis rate and weight before Hx and on days 1, 2, 3, and 7 after Hx. RESULTS: The remaining liver weight was restored similarly in the PBL-Hx and sham-47% Hx groups and more rapidly than in the sham-68% Hx group. Further enhancement of DNA synthesis did not occur after Hx in the PBL-Hx group, and hepatic energy charge did not decrease. In contrast, hepatic DNA synthesis was significantly activated depending on the excised liver volume in both the sham-Hx groups and was accompanied by corresponding decreases in hepatic energy charge. CONCLUSION: Preoperative PBL has a functional advantage because the recovery of the remaining liver volume is not impaired and hepatic energy charge is preserved with no further enhancement of DNA synthesis after Hx.

Adenine Nucleotides↗

Sphingosine inhibition of NADPH oxidase activation in a cell-free system.

The effects of sphingoid bases, sphingosine and dihydrosphingosine, which are protein kinase C (PKC) inhibitors, on NADPH oxidase were examined in a cell-free system. The bases inhibited cell-free activation of NADPH oxidase by arachidonic acid at lower concentration than N-acetylsphingosine. Thus, positive charge in the molecules may play a critical role in inhibition of the oxidase. Sphingosine did not change the Km value for NADPH, but shifted the optimum concentration of arachidonic acid for activation of the oxidase. Moreover, sphingosine suppressed the translocation of p47-phox, one of the cytosolic components of the oxidase, to the membrane fraction, suggesting that the base inhibits the assembly of the components.

Animals↗

[Polymyositis followed by myasthenia gravis].

A 63-year-old woman was admitted to the hospital because of swelling of both forearms and muscle weakness in the limbs. Laboratory examination revealed abnormally high levels of serum creatine kinase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, and lactate dehydrogenase. Polymyositis was diagnosed, and prednisolone was administered. Her condition had been well controlled on prednisolone until several months before admission, when bilateral blepharoptosis and diplopia developed. An edrophonium test was positive: muscle weakness was transiently alleviated. High titers of anti-acetylcholine receptor antibodies were found. A chest CT scan showed a mass in the anterior part of the mediastinum. We diagnosed myasthenia gravis associated with thymoma. After an extended thymectomy, the patient's condition improved. When muscle weakness recurs after remission of polymyositis, myasthenia gravis should be considered.

Anti-Inflammatory Agents↗

[Analgesic effect of dextromethorphan for postherpetic neuralgia].

We investigated the analgesic effect of dextromethorphan (DM), a non-selective NMDA receptor antagonist, in 25 patients with postherpetic neuralgia (PHN). We administered DM 45mg.day-1 orally for 14 days and then 90mg.day-1 for next 14 days. Decrease in pain intensity and alleviation of allodynia were observed in 9 patients (36%). Side effects with no severe cases occurred in 8 patients (32%) and these were mainly digestive symptoms. We concluded that DM might be useful to treat PHN with allodynia probably due to central sensitization.

Aged↗