Search PubMed⌕ Search

Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 577 records · Page 32Linked to original sources

Localization of superoxide anion in the red tide alga Chattonella antiqua.

To investigate the localization of superoxide anion generated in the red tide alga Chattonella antiqua, we added to the incubation medium 3,7-dihydro-6-[4-(2-(N'-(5-fluoresceinyl)thioureido) ethoxy)phenyl]-2-methylimidazo(1,2-a)pyrazin-3-one (FCLA), which is a Cypridina luciferin analogue and a specific fluorescent probe for detecting O2- and 1O2. The live phytoplankter was observed with the laser scanning microscope. At high magnification (x 6400) it was found that the plankter has many large and small verruciform protrusions on the cell surface. When the cell was irradiated with an argon laser (488 nm), a very intense fluorescence was noted at each protrusion. This fluorescence was completely inhibited by the addition of superoxide dismutase to the incubation medium, thus suggesting O2- generation at each verruciform protrusion on the cell surface.

Animals↗

Development of the sleep and wakefulness rhythm in preterm infants discharged from a neonatal care unit.

The purpose of this study was to investigate the effect of constant light in a neonatal care unit on the development of the sleep-and-wakefulness rhythm in preterm infants. Two groups of infants (57 preterm infants without other complications and 58 healthy term infants) were prospectively studied over infancy by a day-by-day plot method, by which sleep-and-wakefulness states were recorded at home for more than 14 d to compare developmental courses of the sleep-and-wakefulness rhythm between the two groups at corrected and postnatal ages. In the two groups, there were no significant differences in distribution of emergence of periodicity of sleep states and wakeful states, total sleep time, nocturnal sleep time, diurnal sleep time, longest sustained sleep period, and longest sustained wakeful period at the same corrected ages. Moreover, the SD of the time of onset of the longest sustained sleep period of each subject diminished with increase in postconceptional weeks. The results suggest that the development of the sleep-and-wakefulness rhythm in preterm infants is not necessarily retarded if they are discharged from the neonatal care unit under constant light before an infant's innate biologic clock is mature enough to respond to an environmental cycle; rather it depends on their corrected ages.

Circadian Rhythm↗

Ultrastructure and cytochemical characteristics of leukocyte infected with Hepatozoon canis.

We have observed the ultrastructure of a canine leukocyte infected with Hepatozoon canis by transmission electron microscope. The infected leukocytes contained many small vesicles and a few typical granules in the cytoplasm. They also contained a few rough surfaced endoplasmic reticula, mitochondria and a segmented nucleus with condensed chromatin. Cytochemical analysis indicated that the infected leukocytes with H. canis contained little alkaline phosphatase, peroxidase, naphthol AS-D chloroacetate esterase or alpha naphthol acetate esterase. These results suggested that the infected leukocytes were neutrophils or monocytes which lost their typical characteristics.

Alkaline Phosphatase↗

[A basic study on usefulness of bleomycin incorporated in poly DL-lactic acid].

Poly DL-lactic acid (PLA) is one of the biodegradable polymers. Bleomycin (BLM) incorporated into small cylinders of PLA blends was prepared as a new dosage (BLM-PLA). When BLM-PLA was preserved in saline, the dissolution rate of BLM from BLM-PLA was 49.2% after 7 days, 85.2% after 14 days and 99.7% after 21 days, respectively. BLM-PLA was implanted subcutaneously into the back of 36 rats. On days 3, 7, 14, 21, 28 and 35, the connective tissues near the implants, lymph node, lung, liver and kidney were removed and BLM activity was measured. The BLM concentration was maintained at a high level in the connective tissues until 14 days, and in the lymph node between 21 and 28 days. On the other hand, the BLM level was low in the lung, liver and kidney. Consequently, it was suggested that PLA is useful as a carrier for drug delivery system and that administration of BLM-PLA is an effective anti-cancer modality, especially in local chemotherapy.

Animals↗

Uptake of bleomycin adsorbed on to activated carbon particles by regional lymph nodes of the esophagus in dogs.

Two bleomycin (BLM)-containing agents (BLM-CH, BLM-SOL) were prepared, and the possible usefulness of BLM-CH in the targeting of chemotherapy for esophageal cancer was studied. BLM-CH is an agent in which BLM is adsorbed on to activated carbon particles, and BLM-SOL is an aqueous solution of BLM. BLM-CH or BLM-SOL was injected into the submucosa of the middle thoracic esophagus of 14 mongrel dogs under endoscopic control. Three days after the administration, regional lymph nodes, connective tissues, liver, lung and spleen were removed, and BLM in the specimens was measured. When BLM-CH was administered, BLM was demonstrated not only in the lymph nodes near the injection site but also in the cervical and abdominal ones. In contrast, BLM was not detected in any lymph nodes when BLM-SOL was administered. Light and electron microscopic observation showed that activated carbon particles diffused and were distributed in the lymph nodes. The latter findings also revealed their existence in the interstices of lymphatic tissues and macrophages. When BLM-CH was injected, BLM in the blood was significantly lower when compared with the results of BLM-SOL administration. The results obtained indicate that BLM-CH may probably become a useful tool in targeting chemotherapy for esophageal cancer.

Adsorption↗

Autoradiographic distribution of [14C]tetrahydrobiopterin and its developmental change in mice.

Tetrahydrobiopterin (BH4) is a regulatory factor of phenylalanine degradation as well as of catecholamine, serotonin and nitric oxide synthesis. To understand the in vivo metabolism of BH4, whole-body autoradiography was performed on mice at various developmental stages after injection of a low dose (45 micrograms/kg) of radiolabeled BH4. In adult mice, high levels of radioactivity were accumulated in the liver and kidney, suggesting that BH4 in these organs is supplied not only by intracellular de novo biosynthesis but also by uptake from the blood. In contrast, little radioactivity was found in the brain, adrenal medulla and bone marrow, in which high levels of endogenous BH4 are found, suggesting that BH4 in these organs is supplied mainly by intracellular biosynthesis. Biopterin, a fully oxidized form of BH4, was not accumulated in any tissues and was excreted rapidly. In pregnant mice, maternal BH4 passed through the placenta and was distributed uniformly to the fetal tissues. Neonatal (5- and 7-day-old) mice had a similar distribution pattern of labeled BH4 to that of adult mice, except for the liver and kidney: in the liver, selective accumulation of BH4 in the adult was not observed in 5-day-old mice; in the kidney, the distribution of high radioactivity to the inner cortex observed in the adult was found in neither 5- nor 7-day-old mice. The developmental increase in hepatic BH4 accumulation was correlated with those of the activities of phenylalanine hydroxylase and GTP cyclohydrolase I, the rate-limiting enzyme of the BH4 biosynthetic pathway.

Aging↗

[Changes of peripheral airways through mechanical ventilation in acute respiratory failure].

To evaluate the morphologic changes in the peripheral airways associated with positive pressure ventilation, fine fiberoptic bronchoscopy (1.8 mm outer diameter) was performed in 12 patients who had no history of prior pulmonary failure. In 19 examinations, the main morphologic findings were paleness and bronchial dilatation in the peripheral airways where increased secretions, pigmentation and stenosis or collapse were also observed. Patients with bronchial dilatation had longer periods of mechanical ventilation (17 +/- 8 days) compared to those without dilation (10 +/- 5 days). The structural destruction in the peripheral airways observed in patients on prolonged positive pressure mechanical ventilation suggests that barotrauma may be more widespread than previously recognized.

Acute Disease↗

[Successful treatment of fungal endocarditis and mediastinitis after fenestrated Fontan operation--a case report].

Fenestrated Fontan operation was performed in a 19-year-old male with a diagnosis of right isomerism syndrome. Postoperatively, fungal endocarditis due to Candida Albicans and mediastinitis by Methicilin resistant Staphylococcus Aureus (MRSA) occurred. For Candida endocarditis, combined surgery and medical treatment with amphotericin B was effective. MRSA mediastinitis was successfully treated by continuous closed irrigation with 0.5% povidone-iodine solution. This is the 17th reported case of fungal endocarditis after open heart surgery in Japanese literature.

Adult↗

Liver resection and intractable postoperative ascites.

Among 211 patients who, between 1985 and 1990, underwent liver resection in Kyushu University Hospital, uncontrollable ascites occurred in 53 (25%). A univariate analysis revealed that postoperative death with liver failure occurred more frequently in patients with intractable ascites (p < 0.05). Alanine amino transferase levels were significantly higher in patients with intractable ascites (p < 0.05), but serum bilirubin, alkaline phosphatase and serum albumin levels did not differ significantly. Portal pressure (p < 0.05), the operation time (p < 0.01) and blood loss (p < 0.01) were significantly higher in patients with intractable postoperative ascites. A multiple analysis showed a correlation between the operation time, portal hypertension and postoperative intractable ascites. Postoperative histology revealed that a larger number of patients with cirrhosis had intractable ascites (p < 0.05). We conclude that cirrhosis, portal pressure and operating time are the most important factors related to intractable ascites in the case of hepatectomy. Areas of the liver to be resected should be limited in cirrhotic patients with portal hypertension.

Adult↗

Extracorporeal hepatic resection for previously unresectable neoplasms.

BACKGROUND: Some hepatic tumors are judged inoperable solely for anatomic reasons, such as the proximity of the tumor with the major vasculature. This is because of high mortality and morbidity rates, as well as a compromised surgical margin. METHODS: We successfully performed extracorporeal hepatic resections in two patients who were judged to have inoperable tumors by conventional means. RESULTS: Both patients had an uneventful postoperative course, and although one patient had intrahepatic recurrence 6 months after operation, the other patient shows no recurrence 10 months later. CONCLUSIONS: Advances in techniques for liver transplantation and organ preservation now allow resection of anatomically unresectable hepatic tumors that were deemed inoperable in the past.

Extracorporeal Circulation↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗