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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 19 recordsLinked to original sources
PubMed1992

Platelet-derived growth factor BB-dimer suppresses the expression of macrophage colony-stimulating factor in human vascular smooth muscle cells.

Vascular smooth muscle cell is a major cell component involved in the process of atherosclerosis. In the present study, we investigated the effects of platelet-derived growth factor (PDGF)-BB dimer on the expression of macrophage-colony stimulating factor (M-CSF) in vascular smooth muscle cells isolated from human umbilical artery. On Northern blot analysis of total RNAs isolated from smooth muscle cells, with human cDNA for M-CSF, a marked dose-dependent reduction of mRNA level was found in PDGF-BB-treated smooth muscle cells. Cellular production of M-CSF was estimated by immunoblot analysis of cell lysate with specific polyclonal antibody against recombinant human M-CSF. A concentration of 10 ng/ml PDGF-BB significantly reduced M-CSF mass in smooth muscle cells compared with that in the absence of PDGF-BB. These results suggest that PDGF-BB plays an important role in the cellular metabolism of vascular wall by regulating the rate of M-CSF production in vascular smooth muscle cells.

Antibodies↗
PubMed1992

Platelet-derived growth factor induces c-fms and scavenger receptor genes in vascular smooth muscle cells.

Vascular smooth muscle cells proliferate and transform to foam cells in the process of atherosclerosis. In the present study, we demonstrated that platelet-derived growth factor (PDGF)-BB induced expression of proto-oncogene c-fms in vascular smooth muscle cells, which normally do not express c-fms, isolated from either human umbilical artery or rabbit aorta. No effect of the protein kinase C activator, phorbol ester, was demonstrated on mRNA expression of c-fms. In contrast, the scavenger receptor activity was induced by both PDGF-BB and phorbol ester. These results indicate that two characteristic genes of monocyte-macrophages were induced by PDGF-BB via the different pathways, and suggest that PDGF-BB plays an important role in initiating phenotypic conversion of smooth muscle cells to macrophage-like cells.

Animals↗
PubMed1992

A newly identified null allelic mutation in the human lipoprotein lipase (LPL) gene of a compound heterozygote with familial LPL deficiency.

In a Japanese patient with familial LPL deficiency, a new null allelic mutation, one base pair deletion at nucleotide position 916 was identified in exon 5 of one allele. In exon 3 of the other allele, we found the same nonsense mutation as we described previously in other Japanese kindreds. For the deletional mutant allele, we developed a simple detection method and constructed the DNA haplotype.

Alleles↗
PubMed1992

Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived from arteriosclerotic lesion.

Vascular smooth muscle cells in atherosclerotic lesions are phenotypically different from those in the normal arterial wall, and no expression of macrophage colony stimulating factor (M-CSF) receptor encoded by the proto-oncogene c-fms has been demonstrated in normal smooth muscle cells. In the present study, we demonstrated expression of c-fms and high affinity binding of M-CSF in smooth muscle cells isolated from an experimental rabbit model of arteriosclerosis (intimal smooth muscle cells), while no expression of c-fms was shown in medial smooth muscle cells. In the immunocytochemical analysis, both types of smooth muscle cells similarly reacted with an antibody specific to muscle cells (HHF 35) but did not react with an antibody specific to rabbit macrophages (RAM 11). In intimal smooth muscle cells, when cells were incubated with acetylated low density lipoproteins (LDL), the binding of acetylated LDL and foam cell formation were observed. In response to M-CSF, tyrosine-phosphorylation, as analyzed by the detection of anti-phosphotyrosine-reactive proteins, and an increased rate of cell proliferation were observed in intimal smooth muscle cells. These results indicated that intimal smooth muscle cells have the characteristics of monocyte-macrophages such as the expression of c-fms, which may be related to their proliferation and phenotypic conversion into foam cells in atheromatous lesions.

Animals↗
PubMed1992

Overexpression of apolipoprotein E in transgenic mice: marked reduction in plasma lipoproteins except high density lipoprotein and resistance against diet-induced hypercholesterolemia.

Apolipoprotein E (apoE) has a high affinity to cell-surface low density lipoprotein (LDL) receptor. To determine the role of apoE in plasma lipoprotein metabolism, transgenic mouse lines with integrated rat apoE gene under the control of the metallothionein promoter were established. We found that a high expressor line produced rat apoE mainly in the liver, and the gene product was almost entirely associated with plasma lipoproteins. The plasma level of rat apoE in homozygotes for the transgene was 17.4 mg/dl after zinc induction (vs. 4.56 mg/dl of mouse apoE in controls). In this group, plasma cholesterol and triglyceride levels were 43% and 68% reduced as compared with controls, respectively. Heterozygotes showed decreases in both lipids to a lesser extent. Gel filtration chromatography showed that lipid reduction was mainly due to decreased very low density lipoproteins (VLDL) and LDL. Especially in zinc-treated homozygotes, VLDL had almost disappeared, and a remarkable decrease in LDL and a slight decrease in high density lipoprotein were also observed. Consistently, the plasma level of apoB, a structural protein of VLDL and LDL, was 78% lower than that of controls, indicating a marked reduction in lipoproteins containing apoB. Furthermore, the transgenic mice, in contrast to controls, did not develop hypercholesterolemia when fed a high cholesterol diet. These results demonstrated that overexpression of apoE reduces plasma cholesterol and triglyceride levels and prevents diet-induced hypercholesterolemia. From dramatic and dose-related decreases in plasma lipoproteins in transgenic mice, we conclude that apoE plays a key role in plasma lipoprotein metabolism.

Animals↗
PubMed1992

Ischemic injury in liver transplantation: difference in injury sites between warm and cold ischemia in rats.

Using liver allografts with warm or cold ischemia, we evaluated functional and morphological alterations in hepatocytes, sinusoidal endothelial cells and Kupffer cells in a rat transplantation model. All recipients of allografts with either 4 hr of cold or 30 min of warm ischemia lived more than 22 days and were judged viable. On the other hand, all recipients of grafts with 6 hr of cold or 60 min of warm ischemia died within 2 days and were therefore judged to be nonviable. With these viable and nonviable allograft models, hepatocyte function was evaluated by the bile output and serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase and serum lactate dehydrogenase levels; endothelial cell function was judged by the serum hyaluronic acid level, and Kupffer cell function was measured by an intravenous colloidal carbon clearance test. Hepatocyte injury was the prominent feature in warm ischemic grafts, especially in the nonviable ones. On the other hand, serum hyaluronic acid values were significantly higher in the nonviable cold ischemic group, compared with the viable counterpart, suggesting that the functional depression of endothelial cells was predominant in cold, nonviable livers. Histological examinations coincided with the above findings. The phagocytic activity of Kupffer cells was depressed by warm or cold ischemia, whereas the number of Kupffer cells was reduced in the warm ischemia group. We conclude that in liver allografts the main site of injury in warm ischemia is the hepatocytes and suggest that cold ischemia is associated with endothelial cell damage.

Animals↗
PubMed1992

Pretransplant assessment of human liver grafts by plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors.

In spite of the improved outcome of orthotopic liver transplantation (OLTx), primary graft nonfunction remains one of the life-threatening problems following OLTx. The purpose of this study was to evaluate plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors as a predictor of liver allograft viability prior to OLTx. Thirty-nine donors were studied during a 5-month period between April and August 1988. Allograft hepatectomy was performed using a rapid technique or its minor modification with hilar dissections, and the allografts were stored cold (4 degrees C) in University of Wisconsin (UW) solution. Early post-transplant allograft function was classified as good, fair, or poor, according to the highest SGOT, SGPT, and prothrombin time within 5 days following OLTx. Procurement records were reviewed to identify donor data, which included conventional liver function tests, duration of hospital stay, history of cardiac arrest, and graft ischemic time. Blood samples from the donors were drawn immediately prior to aortic crossclamp, and from these plasma LCAT activity was determined. Plasma LCAT activity of all donors was significantly lower than that of healthy controls (12.4 +/- 8.0 vs 39.2 +/- 13.3 micrograms/ml per hour, P less than 0.01). LCAT activity (16.4 +/- 8.3 micrograms/ml per hour) in donors of grafts with good function was significantly higher than that in those with fair (8.6 +/- 4.5 micrograms/ml per hour, P less than 0.01) or poor (7.3 +/- 2.4 micrograms/ml per hour, P less than 0.01) function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Immunohistochemical detection of desmosomes in oral squamous cell carcinomas: correlation with differentiation, mode of invasion, and metastatic potential.

An expression of desmosomal glycoprotein 1 (DG 1) was immunohistochemically examined in 77 biopsies and 21 metastatic cervical lymph nodes of oral squamous cell carcinomas (SCC). In the primary tumors the DG 1 expression was significantly reduced at the invasive site of poorly differentiated and highly invasive tumors. In cases of metastases in cervical lymph nodes, the DG 1 staining at the invasive site of the primary tumor was significantly less than that of nonmetastatic cases. The DG 1 expression in the metastatic lymph nodes was as weak as that in the primary tumor. Thus, we suggest that immunohistochemical investigation of DG 1 expression in oral SCC is valuable in predicting tumor behavior.

Carcinoma, Squamous Cell↗
PubMed1992

Cervical cord birth injury and subsequent development of syringomyelia: a case report.

A 2830 g full-term baby, born by breech delivery, exhibited weak crying and sucking and severe hypotonia of the extremities after birth. Magnetic resonance imaging (MRI) showed marked thinning of the cervical cord at the level of C4 and C5. This lesion evolved into focal syringomyelia by the fourth month after birth. In this patient, MRI was useful in detecting the initial spinal cord injury, which appeared as marked thinning, and the subsequent syringomyelia as well. The role of birth trauma in cervical spinal cord injuries is discussed.

Birth Injuries↗
PubMed1992

Antimony electrode for the determination of the intramyocardial pH during open-heart surgery.

The development of an antiomony electrode (Sb) and a pH meter as a substitute for a glass electrode(G) to measure the intramyocardial pH is reported, and the results of their clinical application. The determination of the pH of CPD (citrate-phosphate-dextrose) blood by Sb showed small differences when compared to G (less than 0.1). Sb was also temperature sensitive. The temperature coefficient of Sb was determined in buffers by varying their temperatures, and an antimony-thermocouple electrode and a temperature-compensated pH meter were subsequently constructed. In CPD blood of varying temperatures Sb showed similar tendencies to G. The results of the application of the new apparatus to 28 patients were statistically no different from those obtained previously by G on 22 patients, either in baseline pH or its fall following aortic cross-clamping. It is concluded that although Sb is not as accurate as G, it is a reasonable alternative for the determination of myocardial acidosis during open-heart surgery.

Antimony↗
PubMed1992

Superior and inferior vena caval flows during respiration: pathogenesis of Kussmaul's sign.

Respiratory induced changes in superior (QSVC) and inferior (QIVC) vena caval flows and abdominal pressures were evaluated in anesthetized closed-chest dogs. QSVC and QIVC were measured with ultrasound transit time flow probes (n = 5), and general (Pab) and regional subdiaphragmatic (Pd) abdominal pressures were measured by air-filled balloons (n = 5), during two respiratory maneuvers produced by phrenic nerve stimulation, i.e., simulated spontaneous inspiration (SSI), and Mueller maneuver (MM), with the airway occluded to minimize diaphragmatic descent. With hypervolemia: during SSI, QSVC decreased, QIVC increased, and right atrial pressure increased (P less than 0.05) despite a decrease in esophageal pressure (Pes), i.e., Kussmaul's sign; during MM, both QSVC and QIVC increased (P less than 0.05) without Kussmaul's sign. The ratios delta Pab/delta Pes and delta Pd/Pes were larger during SSI than MM (P less than 0.01). With hypovolemia: during SSI and MM, QSVC increased and QIVC decreased with a venous pressure gradient across the diaphragm (P less than 0.05), consistent with development of a vascular waterfall. These results suggest that 1) changes in abdominal pressure may affect the patterns of QSVC and QIVC during respiration, depending on blood volume status; 2) a prolonged inspiration with hypovolemia may decrease QIVC because of the development of a vascular waterfall; 3) QSVC and QIVC may be interdependent during respiration; and 4) the essential mechanism of Kussmaul's sign is a substantially larger inspiratory increase in abdominal pressures produced by diaphragmatic descent compared with the decrease in intrathoracic pressure under hypervolemic conditions, rather than the presence of pericardial pathology or right heart dysfunction.

Animals↗
PubMed1992

Influence of pericardial constraint on atrioventricular interactions.

The effects of the pericardial constraint in control, tamponade, and absent pericardium conditions was studied in 18 anesthetized open-chest dogs. Atrial pressures and systolic and diastolic inflow volumes per beat in the superior (SVC), inferior vena cavae (IVC), and pulmonary vein (PV) were measured. With increasing tamponade, 1) the systolic-diastolic distribution of venous flow became almost exclusively systolic in the SVC (P less than 0.001) and IVC (P less than 0.05), as the gamma-descent disappeared; 2) similar but lesser left-sided changes occurred in PV flows (P less than 0.001) and pressure; and 3) the systolic-diastolic distribution of venous flow was modulated by heart rate. The results imply that during tamponade 1) increased pericardial liquid pressure associated with an increased pericardial constraint couples reciprocal atrial and ventricular volume changes; 2) the atria fill during ventricular ejection (atrioventricular interaction); 3) total heart volume must have been relatively constant throughout a cardiac cycle; and 4) differences in right and left heart compliances may explain persistent diastolic PV flow. Pericardiotomy produced a small increase in the ratio of diastolic to systolic venous inflow volumes (P less than 0.025), suggesting that normally the pericardium has a minor influence on atrioventricular interaction, the volume changes in the atria and ventricles being relatively uncoupled. With severe tamponade, a homogeneous pericardial fluid column tightly couples atrial and ventricular volume changes and accounts for the characteristic changes in atrial pressure waveforms and patterns of venous flow.

Animals↗
PubMed1992

Apolipoprotein E prevents the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Apo E plays an important role in plasma lipoprotein metabolism through its high affinity binding to cell surface LDL receptor. In the present study, we studied the effects of apo E on the atherogenic process in Watanabe heritable hyperlipidemic rabbits which are deficient in LDL receptor and an animal model for familial hypercholesterolemia. We isolated apo E from plasma of 1% cholesterol-fed rabbits and administered 10 mg of purified apo E intravenously into five Watanabe heritable hyperlipidemic rabbits three times a week from their age of 2.5 months to 11 months for 8.5 months. After sustained administration to apo E, we found a significant reduction in the accumulation of cholesterol ester in aortae (1.55 +/- 0.07 mg/g tissue) as compared to control rabbits (4.32 +/- 0.61 mg/g tissue). Supporting this, the percentage of the surface area of the aorta with macroscopic plaque was remarkably decreased in apo E-treated animals (18.8 +/- 5.1% vs. 38.8 +/- 8.0% in control). Thus, apo E definitely prevented the progression of atherosclerosis in Watanabe heritable hyperlipidemic rabbits.

Animals↗
PubMed1992

Plasma lipoprotein metabolism in transgenic mice overexpressing apolipoprotein E. Accelerated clearance of lipoproteins containing apolipoprotein B.

We have reported that transgenic mice overexpressing rat apo E shows marked reduction of plasma cholesterol and triglyceride levels due to the disappearance of VLDL and LDL. In this study, we investigated the metabolism of plasma lipoproteins in transgenic mice. After intravenous injection, the rates of clearance of 125I-VLDL and 125I-LDL were 3.0- and 2.4-fold greater in transgenic mice than in controls, respectively. Furthermore, clearance of chylomicron remnants estimated by oral retinyl palmitate-loading test was markedly enhanced in transgenic mice. The hepatic expression of LDL receptors by immunoblot analysis was similar in both groups. These data suggest that elimination of lipoproteins containing apo B was due to enhanced clearance of these lipoproteins enriched with apo E through hepatic LDL receptors. When fed a high cholesterol diet, controls showed twofold elevation of plasma cholesterol levels with marked increases in VLDL and LDL cholesterol on gel filtration chromatography. In contrast, cholesterol-fed transgenic mice showed resistance against these increases. High cholesterol feeding decreased the activity of hepatic LDL receptors and had no effect on enhancement of chylomicron remnant clearance in transgenic mice. Thus, overexpression of apo E facilitates metabolism of lipoproteins containing apo B presumably primarily via the LDL receptor pathway and possibly through an interaction with the chylomicron remnant receptor.

Animals↗
PubMed1992

The distribution of tissue insulin receptors in the mouse by whole-body autoradiography.

The distribution of insulin binding sites in the mouse was investigated by in vivo whole-body autoradiography. Male mice were injected intravenously with 125I-insulin in the absence of and, in the presence of, excess unlabeled insulin. Three, 6, 15, 30 and 60 minutes after injection, the animals were perfused and subjected to autoradiographic procedures. Specific insulin binding was observed in the choroid plexus, liver, gastrointestinal tract, spleen, pancreas, deferent duct, and Harderian gland. In the liver and spleen, the distribution of binding sites was heterogeneous. In the liver, the density of the binding was higher around the branches of the portal vein than around the central vein. In the spleen, the marginal zone exhibited a higher density than the white and red pulp. The kidney cortex, and the thyroid gland showed a high degree of insulin binding, but the binding was nonspecific. The binding of insulin to other tissues and organs, including the skeletal muscle and fat, was weak, and most of the binding was nonspecific.

Animals↗
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↗
PubMed1992

Detection of three separate DNA polymorphisms in the human lipoprotein lipase gene by gene amplification and restriction endonuclease digestion.

A rapid detection method was developed for DNA polymorphisms in the human lipoprotein lipase (LPL) gene. The examined polymorphisms include an A-C transversion in the 5'-region of intron 3, a T-G transversion that occurs within a Hind III site of intron 8, and the previously described C-T transition that causes a Pvu II polymorphism in intron 6. Gene fragments encompassing each polymorphic site were amplified by the polymerase chain reaction (PCR) and digested with an appropriate restriction enzyme whose recognition site was either naturally affected by the polymorphism or artificially created with a mismatched PCR-primer. According to the digestion profiles, genotypes were unambiguously distinguished. With this method, respective allelic frequencies were determined for 50 or 70 normal subjects. The procedure will facilitate LPL genotyping in the large population.

Base Sequence↗