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Biomedical subjects

M Shiomi

Publications and source records attributed to M Shiomi.

At least 73 records · Page 4Linked to original sources
PubMed1994

Potent cholesterol-lowering effect by human granulocyte-macrophage colony-stimulating factor in rabbits. Possible implications of enhancement of macrophage functions and an increase in mRNA for VLDL receptor.

The mechanism by which granulocyte-macrophage colony-stimulating factor (GM-CSF) lowers plasma cholesterol levels is not well understood. We tested recombinant human GM-CSF (rhGM-CSF) on plasma cholesterol and triglycerides in rabbits and attempted to determine the mechanisms of the cholesterol-lowering effect. rhGM-CSF (20 micrograms.kg-1.d-1) was administered to normal and cholesterol-fed rabbits for 2 weeks and to Watanabe heritable hyperlipidemic (WHHL) rabbits for 1 week. The administration of rhGM-CSF markedly lowered cholesterol and triglycerides, an effect that persisted in normal and cholesterol-fed rabbits even after termination of treatment. The cholesterol-lowering effect of rhGM-CSF was also observed in WHHL rabbits. rhGM-CSF was capable of stimulating granulocyte-macrophage colony formation in vitro in rabbits with an effect comparable to that in humans. Northern blot analysis with rabbit very-low-density-lipoprotein (VLDL) receptor cDNA revealed that rhGM-CSF increased the levels of VLDL receptor mRNA in muscle of rabbits after only 1.5 hours of treatment compared with control (2.6-fold), with the 1.5-fold increase following a 5-day administration. No changes in the levels of LDL receptor mRNA in liver, spleen, and bone marrow were observed in the treated rabbits. These findings suggest that the cholesterol-lowering effect of rhGM-CSF may be mediated by enhancement of macrophage functions in lipid metabolism and the increase in mRNA for VLDL receptor in rabbits.

Animals↗
PubMed1994

Cell compositions of coronary and aortic atherosclerotic lesions in WHHL rabbits differ. An immunohistochemical study.

This study investigated whether coronary atherosclerosis was different from aortic atherosclerosis in Watanabe heritable hyperlipidemic rabbits. Atherosclerotic lesions were immunohistochemically stained by using a monoclonal antibody for rabbit macrophages (RAM-11) and a monoclonal antibody for muscle actin (HHF35) and were also subjected to conventional staining. The areas of the major lesional components, ie, macrophages, smooth muscle cells, collagen fibers, and extracellular lipid deposits, were measured with a color image analyzer. The percent macrophage area in coronary lesions was significantly lower compared with aortic lesions at all stages (early fatty streak, transitional, and advanced), while the percent smooth muscle cell area and collagen area were significantly higher in early fatty streak lesions of the coronary arteries. In addition, the macrophage area/smooth muscle cell area ratio was significantly lower in coronary lesions compared with aortic lesions at all stages. In conclusion, coronary atherosclerosis had a small number of macrophages and was rich in smooth muscle cells, whereas aortic atherosclerosis showed the opposite features. These results suggested that the role of macrophages and smooth muscle cells in the initiation and/or progression of coronary atherosclerosis differs from the role of these cells in aortic atherosclerosis.

Aging↗
PubMed1994

Immunohistochemical and quantitative analysis of cellular and extracellular components of aortic atherosclerosis in WHHL rabbits.

To investigate changes in the major components of atherosclerotic lesions during the progression of this disease, we measured the lesional areas of macrophages, smooth muscle cells, collagen fibers, and extracellular lipid deposits in the aortas of WHHL rabbits. Aortic segments with lesions of various stages were stained for histological and immunohistochemical examination, and the area of each lesional component was measured by a color image analyzer. In the early fatty streaks observed in 3-month-old rabbits, macrophages were predominant in the intima and were also observed in the inner layer of the media. In the transitional lesions (fibro-fatty streaks) found in rabbits at 11 to 15 months of age, an increase in the lesional area of macrophages was prominent compared to other lesional components. Thus, macrophages may play an important role in the progression of aortic atherosclerosis at this stage. In advanced complicated lesions observed in rabbits at 20 to 24 months of age, the area of macrophages and smooth muscle cells did not increase, whereas the area of collagen fibers and extracellular lipid deposits increased. Therefore, both the disruption of foam cells and fibrosis may play an important role in the progression of atherosclerosis at this stage.

Animals↗
PubMed1994

Effect of fluvastatin sodium on secretion of very low density lipoprotein and serum cholesterol levels. In vivo study using low density lipoprotein receptor deficient watanabe heritable hyperlipidemic rabbits.

The hypolipidemic effects of fluvastatin sodium (XU 62-320, CAS 93957-55-2), a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, were examined. Fluvastatin sodium was administered to Watanabe heritable hyperlipidemic (WHHL) rabbits, a low density lipoprotein (LDL) receptor deficient animal model, for 6 weeks at doses of 12.5 mg/kg, 25 mg/kg, and 50 mg/kg. Total cholesterol levels in serum, in very low density lipoproteins (VLDL), in intermediate density lipoprotein, and in LDL decreased dose-dependently. In the 50 mg/kg group, cholesterol reduction in each of the aforementioned segments was 50%, 91%, 94% and 33%, respectively. The secretion rate of VLDL-cholesterol, as determined by intravenous injection of Triton WR-1339, also decreased in a dose-dependent manner, showing a reduction of 16% (p < 0.05) in the 50 mg/kg group. In addition, the cholesterol content of newly-secreted VLDL also decreased dose-dependently. These results indicate that fluvastatin sodium has a potent hypolipidemic effect, and suggest that one of the mechanisms responsible for the reduction of serum cholesterol may be the suppression of VLDL-cholesterol secretion.

Animals↗
PubMed1993

In vivo kinetics of oxidatively modified HDL.

The kinetics of oxidatively modified high-density lipoprotein (HDL) in vivo were investigated. 125I-labeled oxidized (Ox) HDL and 131I-labeled native (N) HDL were injected simultaneously into control and WHHL rabbits. The fractional catabolic rates of 125I-labeled Ox-HDL were significantly greater than those of 131I-labeled N-HDL in both control (2.52 +/- 0.36/day vs 0.94 +/- 0.02/day) and WHHL rabbits (4.07/day vs 1.32/day). Oxidized HDL was catabolized faster than native HDL and was taken up primarily by the liver, spleen, and kidney.

Animals↗
PubMed1993

99mTc-DTPA activity in the azygos vein before and after sclerotherapy in patients with cirrhosis.

We determined the radioactivity of 99mTc-diethylene-triamine pentaacetic acid (99mTc-DTPA) from the azygos vein in 20 patients with cirrhosis to evaluate the hemodynamic relationship between esophageal varices and azygos venous blood flow before and after sclerotherapy. 99mTc-DTPA was injected into the splenic artery before and after sclerotherapy through a catheter in the right femoral artery. The patients were classified into three types. Type I consisted of nine patients who showed maximum levels of 99mTc-DTPA which were significantly lower (P < 0.01) than those determined before sclerotherapy. The Type II was composed of six patients who had far lower radioactivity levels than those of Type I, but also showed significantly lower maximum activity after sclerotherapy than before (P < 0.01). The five patients in Type III had significantly higher radioactivity after sclerotherapy than before (P < 0.05). Rupture of the esophageal varices occurred in one of the Type I (11.1%), none of the Type II, and four of Type III (80%) cases, among all of the patients followed for 40 months after sclerotherapy. The radioactivity in the azygos vein appeared later in Type I (P < 0.05) and Type II after sclerotherapy than before sclerotherapy, but in Type III there was no difference between pre- and post-sclerotherapy values. Type III patients in whom portography was performed showed short gastric and paraesophageal veins, whereas Type I and Type II patients did not. These data suggest that radioactivity in the azygos vein before and after sclerotherapy reflect the grade of shunting and estimate the recurrence of bleeding in patients with cirrhosis associated with esophageal varices.

Aged↗
PubMed1993

In vivo kinetics of lipoprotein(a) in homozygous Watanabe heritable hyperlipidaemic rabbits.

In vivo kinetics of lipoprotein(a) [Lp(a)] were investigated in homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits (an animal model of familial hypercholesterolemia (FH)), and in normolipidemic Japanese White rabbits (controls). 125I-labelled Lp(a) and 131I-labelled LDL were simultaneously injected intravenously. Blood samples were then taken periodically. Kinetic parameters were calculated from the plasma radioactivity decay curves. The fractional catabolic rates (FCRs) of both Lp(a) and LDL (1.355 +/- 0.189 pools per day and 1.278 +/- 0.397 pools per day, respectively) in the WHHL rabbits were significantly (P < 0.005) smaller than those in the control rabbits (2.008 +/- 0.083 pools per day and 2.855 +/- 0.759 pools per day, respectively). In WHHL rabbits, the FCRs of Lp(a) and LDL were similar. However, in control rabbits, the FCR of Lp(a) was significantly (P < 0.01) smaller than that of LDL. In WHHL rabbit organs, the mean ratio of 125I-Lp(a): 131I-LDL, 48 h after injection, normalized to the corresponding isotope ratio in plasma, were 1.525, 1.020, 1.819 and 1.967, in liver, kidney, spleen and bile, respectively. These values were significantly higher than the corresponding values in control rabbits (0.590, 0.677, 0.862 and 0.766, respectively). Our data strongly suggest that Lp(a) clearance is not entirely dependent upon LDL receptors and may be mediated by some other mechanisms.

Animals↗
PubMed1993

[An outbreak of Pseudomonas sepsis associated with nosocomial infection in a pediatric ward].

A five-year old girl, diagnosed with fever of unknown origin (FUO), was transferred to our hospital due to a deterioration in her general condition. Pseudomonas cepacia (P. cepacia) was detected in her blood culture and she soon recovered after imipenem cilastatin (IPM/CS) administration. When the former hospital was informed of the results of her blood cultures, we learned that five other cases of FUO had occurred there within the previous two weeks in noncompromised children. Except for one case, Pseudomonas species was detected in their blood cultures. P. cepacia was found in one case, Pseudomonas aeruginosa (P. aeruginosa) was detected in two other cases, and both P. cepacia and P. aeruginosa were demonstrated in the other patient. Although the origin of the bacteria is unknown, it may have spread to the children through a contaminated liquid reservoir or medical devices.

Bacteremia↗
PubMed1993

[Application of DNA fingerprinting to investigation of genetic relationships between laboratory rabbit strains].

It is well known that laboratory rabbits are not controlled genetically like laboratory mice and rats. In order to test the usefulness of DNA fingerprinting in investigation of genetic uniformity of the laboratory rabbits strains and their relationships, we applied DNA fingerprinting using bacteriophage M13 probe to five strains (2 inbreds (JWY-NIBS and DuY-NIBS) and 3 outbreds (JW-NIBS, Icl:JW and WHHL)). DNA fingerprints of 2 inbred strains showed the same banding patterns within each strain but the strain-specific patterns. Although there were no rabbits showing the same banding patterns in 3 outbred strains, average percent differences (APD) were 13.7 to 18.6. A dendrogram based on APD of DNA fingerprints was constructed by 2 large clusters, JW group and DuY. The dendrogram was essentially similar to that based on rabbit mandible measurements. These results suggest that DNA fingerprinting is available not only for the genetic monitoring of the laboratory rabbit strains but also for the investigation of their genetic relationships.

Animals↗
PubMed1992

Inheritability of atherosclerosis and the role of lipoproteins as risk factors in the development of atherosclerosis in WHHL rabbits: risk factors related to coronary atherosclerosis are different from those related to aortic atherosclerosis.

Inheritability of atherosclerosis and the influences of serum lipids on atherosclerosis were examined by following its progression in selectively bred WHHL rabbits. Our studies indicate (1) coronary atherosclerosis is clearly inherited from parents by offspring whereas inheritability of aortic atherosclerosis is uncertain; (2) coronary stenosis is positively correlated to serum cholesterol level, although the correlation coefficient is markedly low: in contrast, no relationship between serum lipid levels and aortic atherosclerosis was observed; (3) cholesterol-rich VLDL showed atherogenicity in aorta, but not in coronary arteries; (4) an unknown lipoprotein detected by 3.6% polyacrylamide gel electrophoresis was related to coronary atherosclerosis, although no relationship between the unknown lipoprotein and aortic atherosclerosis was observed. These findings suggest that there are two types of genetic factors involved in atherosclerosis, one of which is unique to coronary atherosclerosis whereas the other is related to only aortic atherosclerosis.

Animals↗
PubMed1992

Macrophage colony stimulating factor prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

The early atherosclerotic lesion is characterized by the presence of macrophage-derived foam cells. Macrophage colony stimulating factor (M-CSF) specifically stimulates the functions of the monocyte-macrophages. To elucidate the effects of M-CSF in the atherogenic process in vivo, we administered human recombinant M-CSF into Watanabe heritable hyperlipidemic (WHHL) rabbits, an animal model for familial hypercholesterolemia. Three hundred micrograms of M-CSF were intravenously injected into WHHL rabbits aged 2.5 months, three times a week for 8.5 months. After the M-CSF treatment, we found very retarded progression of atherosclerosis. The accumulation of cholesterol ester was remarkably decreased in the aortae of M-CSF-treated animals (0.60 +/- 0.32 mg/g tissue), as compared to those of controls (4.32 +/- 0.61 mg/g tissue). Furthermore, the percentage of the surface area of the aorta with macroscopic plaque in animals treated with M-CSF was 14.3 +/- 6.2%, much less than that in controls receiving saline injection (38.8 +/- 8.0%). Thus, M-CSF definitely prevented the progression of atherosclerosis in WHHL rabbits by influencing macrophage functions.

Animals↗
PubMed1992

Effects of pravastatin sodium alone and in combination with cholestyramine on hepatic, intestinal and adrenal low density lipoprotein receptors in homozygous Watanabe heritable hyperlipidemic rabbits.

Pravastatin sodium (pravastatin), a tissue-selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, was administered alone (50 mg/kg) or in combination with cholestyramine, a bile acid sequestrant resin, at the level of 2% in the diet to homozygous Watanabe heritable hyperlipidemic (WHHL) rabbits for 4 weeks. The low density lipoprotein (LDL)-cholesterol levels were reduced by 29% and 56% with pravastatin alone and the combination treatment, respectively. Hepatic LDL receptor activity was increased by 11.2- and 13.9-fold with pravastatin alone and the combination treatment, respectively. The LDL receptor activity in the untreated homozygous WHHL rabbits was only 2.5% of that in the normal rabbits. mRNA for the LDL receptor in the liver was also increased by 2.1- and 3.4-fold with pravastatin alone and the combination treatment, respectively. On the other hand, mRNA for the LDL receptor in the adrenal gland was not affected by pravastatin and the combination treatment, whereas the mRNA in the intestine was increased in both groups. These results suggest the following: 1) the induction of hepatic LDL receptor activity by the treatment of pravastatin alone or in combination with cholestyramine is the main cause of the reduction of serum cholesterol levels by these treatments even in LDL receptor-deficient animals. 2) The induction of the mRNA for the LDL receptor in the liver and intestine, but not that in the adrenal gland, might be a reflection of the tissue-selective inhibition of cholesterol synthesis by pravastatin.

Adrenal Glands↗
PubMed1992

Alterations in acetyl coenzyme A carboxylase activities in voles and mice treated with monosodium aspartate.

Changes of body weights and hepatic acetyl-CoA carboxylase activities were measured in voles and mice treated with monosodium-L-aspartate (MSA). MSA was administrated subcutaneously to neonates at 4 mg/g. The MSA-treated mice showed remarkable obesity, associated with the increase in the plasma insulin concentrations and acetyl-CoA carboxylase activities. The activity of acetyl-CoA carboxylase of control voles was very low; under half that of mice. In the MSA-treated voles, although the plasma insulin concentrations also increased, acetyl-CoA carboxylase activities were not elevated and signs of obesity were not observed.

Acetyl-CoA Carboxylase↗
PubMed1992

Effects of atherosclerosis on mean and daily variation of arterial pressure in conscious WHHL rabbits.

Effects of atherosclerosis on the mean value and daily variation of arterial pressure were studied in 12 Watanabe-heritable hyperlipidemic (WHHL) rabbits aged 12 to 35 months and 25 normal Japanese white rabbits aged 6 to 30 months. A pressure catheter was inserted through the left subclavian artery under pentobarbital anesthesia. A few days after the catheterization, the mean arterial pressure (MAP) of the rabbits, which were active and in a good state of appetite, was recorded by an analogue-to-digital converter every second for about 6 hrs and stored in a computer. The mean (M) and standard deviation (SD) in the WHHL rabbit, calculated from each successive MAP record, ranged widely from 85.8 to 131.4 mmHg and 5.6 to 12.6 mmHg, respectively. There was no significant correlation between M and SD in the WHHL rabbit. M and variance (V) of MAP in the WHHL rabbit were significantly higher than those in the normal rabbit. M did not show any significant change with increasing ages, whereas SD increased significantly with aging in the WHHL rabbit. Concentrations of serum total cholesterol and triglyceride in the WHHL rabbit were 475 and 328 mg/dl, which were about nine and seven times as high as those in the normal rabbit, respectively. Macroscopic and histopathological examinations of the aorta revealed development and spread of sclerotic lesions with aging in the WHHL rabbit. We can conclude that development of atherosclerosis with aging in the WHHL rabbit causes malfunction of the baroreceptors, which contributes to hypertension and lability of arterial pressure.

Aging↗
PubMed1992

Impaired baroreflex control of arterial pressure in WHHL rabbits.

The present study was designed to investigate baroreflex control capacity of arterial pressure (AP) in the conscious Watanabe heritable hyperlipidemic (WHHL) rabbit. The control capacity of the baroreflex system was assessed with overall open-loop gain (G). Seven WHHL and 14 normal Japanese white rabbits were chronically implanted two catheters in the aortic arch through the left subclavian and common carotid arteries. A small amount of blood (2 ml/kg, body weight) was rapidly extracted into a syringe via the left common carotid artery in the conscious state. Mean arterial pressure (MAP) was monitored with a catheter-transducer system through the left subclavian artery. The MAP responses to the rapid hemorrhage were averaged 8 times by a computer. G was calculated as G = delta API/delta APS-1, where delta API was an immediate MAP fall after the hemorrhage and delta APS was a steady-state error 1-2 min after the hemorrhage. The values of G in the conscious normal and WHHL rabbits were 7.35 +/- 0.24 and 1.91 +/- 0.29 (mean +/- SE, p < 0.01), respectively. To investigate effects of pentobarbital anesthesia on baroreflex system, the hemorrhage experiment was repeated several times under pentobarbital anesthesia (20 mg/kg, i.v.). The values of G in the anesthetized normal and WHHL rabbits were 6.69 +/- 0.23 and 1.68 +/- 0.34 (mean +/- SE, p < 0.01), respectively. G in the normal and WHHL rabbits did not show any significant change in the presence and absence of pentobarbital anesthesia (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1992

Role of monocyte colony-stimulating factor in foam cell generation.

Recently, we reported that human monocyte colony-stimulating factor (M-CSF) stimulates the clearance of lipoproteins containing apoB100 via both low density lipoprotein receptor-dependent and -independent pathways in target cells of M-CSF, and reduces plasma cholesterol level (Journal of Biological Chemistry, 265:12869-12875, 1990). This suggests a linkage of cytokines to the metabolic regulation of plasma cholesterol. Furthermore, we found a significant role of M-CSF in cholesterol metabolism of human monocyte-derived macrophages. M-CSF enhanced not only the uptake of acetylated low density lipoprotein and oxidized low density lipoprotein in macrophages, but also the efflux of cholesterol from cholesterol-loaded macrophages. To elucidate in vivo effects of M-CSF on cholesterol efflux from tissues, we administered an intravenous injection of 3H-cholesterol (150 microCi) into WHHL rabbits 1 month before starting M-CSF treatment. We observed an increased cholesterol efflux from tissues to plasma high density lipoprotein after M-CSF treatment when cholesterol efflux was estimated as the change in specific radioactivity of plasma high density lipoprotein-cholesterol. This result suggests that M-CSF can enhance the excretion of cholesterol from target cells of M-CSF, such as cholesterol-loaded macrophages in the arterial wall, and reduce the rate of atherogenesis.

Cells, Cultured↗
PubMed1991

Endoscopic bipolar electrocoagulation in upper gastrointestinal bleeding.

A total of 213 cases of upper gastrointestinal bleeding treated by bipolar electrocoagulation (BPEC) were reviewed and its efficacy in the management of massive bleeding was evaluated. Initial hemostasis was achieved by BPEC in 97.6% cases with an overall rebleeding rate of 17.1%. The majority of rebleeding occurred in patients with acute mucosal lesions who had serious underlying medical problems. There were no complications related to the procedure. Endoscopic BPEC safely arrested oozing to spurting bleeding and contributed greatly to the control of upper gastrointestinal bleeding.

Adolescent↗