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Biomedical subjects

M Shimada

Publications and source records attributed to M Shimada.

At least 379 records · Page 21Linked to original sources
PubMed1996

Postnatal development of adrenergic terminals in rat locus coeruleus, with special reference to growth of noradrenergic neurons.

The postnatal development of noradrenergic (NA) neurons and adrenergic (AD) terminals in the rat locus coeruleus (LC) was studied immunohistochemically. Cell body size was measured after staining of NA neurons with anti-tyrosine hydroxylase (TH) serum, and AD terminals were visualized with anti-phenylethanolamine N-methyltransferase serum. NA neurons in the LC were strongly TH-immunoreactive throughout the postnatal period. At birth, their mean cell body volume was 660 +/- 30 microns 3. It reached a maximum of 2580 +/- 230 microns 3 at postnatal day (PD) 14, and decreased thereafter to 930 +/- 50 microns 3 at PD 60. This transient enlargement of NA neurons may be closely related to the development of the cerebral cortex. AD afferents to the LC had terminals forming predominantly asymmetric junctions at birth (about 96% of all junctions). They occasionally made axo-somatic contact, suggesting that AD input already modulated the activity of LC neurons at this stage. AD terminals making axo-spinous synapses increased in number until PD 31, but still represented a minor proportion of these LC terminals, since there were more than 80% in contact with dendritic shafts at all ages examined.

Animals↗
PubMed1996

Activation of ventral tegmental GABAB receptors inhibits morphine-induced place preference in rats.

The effect of microinjection of a GABAB receptor agonist, baclofen, into the ventral tegmental area on the rewarding effect of morphine was investigated using the conditioned place preference paradigm in rats. Morphine (1-8 mg/kg, s.c.) caused a dose-related place preference for the drug-associated place. In contrast, microinjection of baclofen (0.1-1 nmol/side) into the ventral tegmental area did not produce a significant preference for either compartment of the test box. Pretreatment with baclofen (0.1-1 nmol/side) into the ventral tegmental area dose dependently suppressed the morphine (8 mg/kg, s.c)-induced place preference. This suppression of the morphine (8 mg/kg, s.c.)-induced place preference by baclofen (1 nmol/side), but not with the GABAA receptor antagonist bicuculline (1 nmol/side). The present results suggest that a decrease in GABAB neurotransmission in the ventral tegmental area, which may be produced via inhibition of a tonic GABAergic input by morphine, may be involved in the expression of the rewarding effect of morphine.

Animals↗
PubMed1996

Role of the low density lipoprotein (LDL) receptor pathway in the metabolism of chylomicron remnants. A quantitative study in knockout mice lacking the LDL receptor, apolipoprotein E, or both.

Two receptor pathways are thought to mediate the hepatic clearance of chylomicron remnants, (i) the low density lipoprotein receptor (LDLR) pathway and (ii) non-LDLR pathway. The current study was undertaken to quantitatively assess the contribution of each receptor pathway to hepatic catabolism of chylomicron remnants, by using mice that are deficient in apolipoprotein E (apoE) (apoE(-/-)), the LDLR (LDLR(-/-)), and both (apoE(-/-);LDLR(-/-)). Vitamin A fat tolerance tests showed that the area under the curves of the plasma excursions of retinyl ester in the LDLR(-/-), apoE(-/-), and apoE(-/-);LDLR(-/-) mice were 4, 12, and 12 times larger than those in wild-type mice. The retinyl ester accumulated in the plasma of the LDLR(-/-) mice was distributed in larger subfractions of triglyceride-rich lipoproteins, chylomicrons through very low density lipoprotein-C. These results indicate that the LDLR constitutes the major pathway for the clearance of retinyl ester. In support of this, agarose gel electrophoresis revealed that an oral fat load resulted in retention of chylomicrons in the LDLR(-/-) mice, which was not seen in wild-type mice. The observation that the apoE(-/-) mice showed larger retinyl ester excursion than LDLR(-/-) mice indicates that an apoE-dependent non-LDLR pathway is involved in the rest of the clearance of the retinyl ester. Together, we conclude that the LDLR pathway plays a significant role in the chylomicron remnant metabolism in mice fed a normal chow.

Animals↗
PubMed1996

Epidemiology of childhood leukemia in Hokkaido, Japan.

The population-based epidemiological indices (crude incidence, survival rate, mortality, etc.) of childhood leukemia (0-14 years of age) from 1969 to 1993 in Hokkaido Prefecture, Japan, were calculated, using data obtained from the Registry of Childhood Malignancies in Hokkaido Prefecture. A total of 1,084 cases of leukemia were diagnosed in the 1969-93 period. The annual incidence of all types of leukemia from 1984 to 1993 was about 4 per 100,000 children aged 0-14 years, with the incidence of ANLL decreasing slightly and that of ALL increasing. The ratio of ALL/ANLL could similarly be seen to be increasing in all age groups. Out of a cohort of 100,000 live births, about 65 children developed leukemia by 14 years of age, and in this longitudinal observation the ratio of ALL/ANLL was increasing. The incidence of ALL and ANLL and the ratio of ALL/ANLL in Japanese children are approaching those of Caucasians. Approximately 80% of the ALL cases were of the LI type (FAB classification), and about 65% of these could be immunologically classified as "common" ALL. The 5-year survival rate of T- and B-cell ALL cases was 50% or less, while that of "common" ALL cases was about 80%.

Adolescent↗
PubMed1996

Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase.

Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Conflicting results have been reported concerning its role in atherogenesis. To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO). On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice. Larger lipoprotein particles of intermediate density lipoprotein (IDL)/LDL were selectively reduced in LPL/LDLRKO mice. On an atherogenic diet, both mice exhibited severe hypercholesterolemia. But, mean plasma cholesterol levels in LPL/ LDLRKO mice were still suppressed as compared with that in LDLRKO mice (1357 versus 2187 mg/dl). Marked reduction in a larger subfraction of IDL/LDL, which conceivably corresponds to remnant lipoproteins, was observed in the LPL/LDLRKO mice. LDLRKO mice developed severe fatty streak lesions in the aortic sinus after feeding with the atherogenic diet for 8 weeks. In contrast, mean lesion area in the LPL/LDLRKO mice was 18-fold smaller than that in LDLRKO mice. We suggest that the altered lipoprotein profile, in particular the reduced level of remnant lipoproteins, is mainly responsible for the protection by LPL against atherosclerosis.

Animals↗
PubMed1996

Lipoprotein(a) is an independent risk factor for multiple cerebral infarctions.

In an attempt to ascertain whether Lp(a) is a risk factor for multiple cerebral infarctions (MCI), we have studied 83 patients with proven MCI and 39 subjects without MCI by computed tomography (CT). Seventy-one patients with non-insulin-dependent diabetes mellitus (NIDDM) were included: 52 with and 19 without MCI. Serum Lp(a) levels were significantly higher in patients with MCI than in subjects without MCI. There were no differences in serum Lp(a) levels between NIDDM and non-diabetic patients with MCI. The logistic regression analysis revealed that Lp(a) and hypertension were independent risk factors for the cerebral event. The current study demonstrated that Lp(a) and hypertension are significant risk factors for multiple cerebral infarctions.

Aged↗
PubMed1996

Distinct effects of phenobarbital and its N-methylated derivative on liver cytochrome P450 induction.

The relationship between barbiturate structures and their effects on induction of rat cytochrome P450 forms was studied in primary cultured hepatocytes. Treatment of hepatocytes cultured on matrigel with 1 mM barbital, N-methylbarbital, cyclobarbital, hexobarbital, phenobarbital (PB), or mephobarbital (N-methyl-PB) resulted in increased amounts of CYP2B1/2 and CYP2C6 forms. Microsomal CYP3A content was also enhanced by treatment with these barbiturates, except for barbital. Although no relationship was observed between the levels of CYP2B1/2 and CYP3A, ratios of CYP3A/CYP2B1 plus CYP2B2 contents were invariably higher with hepatocytes treated with N-methylated barbiturates than with the nonmethylated analogs. Consistent results were also observed in vivo in rats treated with PB and N-methyl-PB. These results indicate the difference in the structure requirement for induction of CYP2B and CYP3A. In addition, N-methyl-PB was found to suppress PB-mediated induction of CYP2B1. Hepatic levels of CYP2B1 mRNA and protein were increased by treatment with PB or N-methyl-PB alone, but decreased by cotreatment with 1 mM PB and N-methyl-PB. The suppression has been shown to occur at the transcriptional level of the CYP2B1 gene by using a chloramphenicol acetyltransferase reporter-CYP2B1 fused gene system.

Animals↗
PubMed1996

Postoperative hepatitis status as a significant risk factor for recurrence in cirrhotic patients with small hepatocellular carcinoma.

BACKGROUND: Recurrence of small hepatocellular carcinoma (HCC) is common. Recent studies have suggested that the status of the underlying liver parenchyma is a significant risk factor for recurrence of HCC. METHODS: The postoperative values of transaminase were examined every 6 months after surgery in 57 patients with a surgically resected solitary small HCC measuring up to 3 cm in greatest dimension. Based on the patterns of the transaminase values, the patients were divided into two groups. Group 1 (n = 20) had a high transaminase level; the values of postoperative transaminase were always more than 100 IU/L. Group II (n = 37) had a low transaminase level; the values of postoperative transaminase were sometimes lower than 100 IU/L. RESULTS: The cumulative carcinoma-free survival rates in Groups I and II were 91% and 80%, respectively, at 1 year, 64.5% and 5.5%, respectively, at 3 years, and 48.2% and 0%, respectively, at 5 years after surgery. The disease free survival rates in Group I were significantly lower than those in Group II (P = 0.0007), although no significant differences in histologic risk factors for recurrence or in clinical backgrounds were observed. With regard to the recurrence pattern, solitary recurrence was more frequently observed in Group I (P = 0.02), compared with the patients in Group II. A histologic comparison between the primary and recurrent tumor in patients who underwent re-resection for solitary recurrence demonstrated the possible multicentric occurrence of HCC in 2 of 8 patients (25%) in Group I. CONCLUSIONS: This study suggests that the hepatitis status of the remnant liver plays an important role in the recurrence rates and patterns of small HCC after hepatectomy.

Carcinoma, Hepatocellular↗
PubMed1996

Difference in types of radiation-induced structural chromosome aberrations and their incidences between Chinese and Syrian hamster spermatozoa.

The effects of ionizing radiations on sperm chromosomes were studied in the Chinese hamster (Crisetulus griseus) and the Syrian (golden) hamster (Mesocrisetus auratus). Testes of mature male Chinese hamsters (CH) were irradiated with X-rays (0.91, 1.82 and 3.63 Gy) and gamma-rays (1.10, 2.15, 2.95 and 4.01 Gy) at a single acute dosage, whereas the irradiation was done with lower doses of X-rays (0.45, 0.91 and 1.82 Gy) and gamma-rays (0.49, 0.99 and 1.98 Gy) in mature male Syrian hamsters (SH), taking the higher radiosensitivity of this species into consideration. They were mated with normal females within 6 days of exposure. Sperm-derived chromosomes were analyzed in 1125 and 1966 fertilized ova of the CH and the SH, respectively. In both species, there was no great difference in the induction of structural chromosome aberrations between X-irradiated and gamma-irradiated spermatozoa. Chromosome-type aberrations were predominantly induced. The incidence of breakage-type aberrations increased linearly, and that of exchange-type aberrations linear-quadratically with increase of dosage. A species-specific difference in chromosomal radiosensitivity of spermatozoa was clear. In spite of the same radiation dosage, the incidence of chromosomally abnormal spermatozoa in the SH was about twice as high as that in the CH (e.g. 27.0% vs. 14.7% at 0.91 Gy of X-rays). The incidences of breakage-type aberrations (69-89%) were far higher than those of exchange-type aberrations (11-31%) in the SH, while the disparity of the two incidences was much smaller in the CH (46-65% vs. 35-54%). Exchange-type aberrations consisted of both chromosome-type and chromatid-type in the SH, while almost all of them were of the chromosome-type in the CH. These results suggest that the DNA-repairing capacity of oocytes is much higher in the CH than in the SH. Moreover, it seems likely that radiation-induced sperm DNA damage is repaired with both pre-replication repair (excision repair) and post-replication repair systems in SH oocytes, whereas the excision repair system operate most exclusively in CH oocytes.

Analysis of Variance↗
PubMed1996

Mechanisms of retinoid resistance in leukemic cells: possible role of cytochrome P450 and P-glycoprotein.

Retinoic acid (RA) regulates the differentiation and proliferation of a wide variety of different cell types and all-trans RA induces complete remission in a high proportion of patients with acute promyelocytic leukemia (APL). However, clinical resistance to retinoids may develop and poses a serious problem for differentiation-inducing therapy. We studied the effects of RA in combination with a cytochrome P450 inhibitor (clotrimazole) and a P-glycoprotein antagonist (verapamil) on cell growth and differentiation of RA-resistant HL-60 cells and fresh RA-resistant leukemic cells from two APL patients. RA-resistant HL-60 cells and APL cells differentiated to mature granulocytes when cultured with all-trans RA and either clotrimazole and verapamil but not with either of the agents alone. These findings were confirmed in these cells by their increased expression of CD11b antigen and migration-inhibitory factor-related protein-8/14 mRNAs and decreased levels of c-myc mRNA. These combinations also markedly decreased the number of viable cells and inhibited cellular proliferation. After isolation of microsomes, measurements showed that levels of cytochrome P450 activities in both wild-type and RA-resistant HL-60 cells were almost comparable. Moreover, expression of the CYP1A1-type cytochrome P450 gene could not be detected in either cell type. However, RA-resistant HL-60 cells and APL cells, but not RA-sensitive HL-60 cells and APL cells, expressed multidrug-resistance-1 gene transcripts. Taken together, acquired resistance to RA may be explained in part by drug metabolism in leukemic cells. Possible mechanisms for accelerated clearance of RA include the induction of non-CYP1A1 cytochrome P450 enzymes and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1996

Immunolocalization of vinculin in the heart of the early developing rat embryo.

BACKGROUND: The interaction of cells and extracellular matrix (ECM) components is important in the morphogenesis of the developing heart and is thought be mediated in part by adhesion plaques associated with vinculin, paxillin, talin, integrin, and other proteins. We investigated the patterns of expression of vinculin in the early embryonic rat heart to evaluate the role of vinculin in cardiac morphogenesis. METHODS: Vinculin expression was studied immunohistochemically in developing Sprague-Dawley embryonic rat hearts between days 11.5 and 15.5. RESULTS: Vinculin expression was transient and specific in the aorticopulmonary septum on day 13.5 and in the conal septum on day 14.5, when the respective septations were complete. Less vinculin immunoreactivity was detected in the atrioventricular cushion or ventricular septum, where obvious morphological alteration takes place. CONCLUSIONS: Sites that were immunoreactive for vinculin in the present study are reportedly associated with the distribution of neural cell adhesion molecules (N-CAM) or of soluble tropoelastin. Thus vinculin appears to play a key role in aorticopulmonary septation, where neural crest cells are transformed into ectomesenchyme. Vinculin appears to be involved in elastogenesis and is contributed by ectomesenchyme derived from the neural crest cells.

Animals↗
PubMed1996

Genetic mechanisms in esophageal carcinogenesis: frequent deletion of 3p and 17p in premalignant lesions.

Although dysplasia of the esophagus is thought to be the precursor lesion of esophageal squamous cell carcinoma (ESC), the sequence of genetic events during esophageal carcinogenesis is unclear. Using the polymerase chain reaction, we examined allelic losses at microsatellite loci in DNAs isolated from 106 lesions among 32 patients with ESC. Allelic losses on 3p or 17p occurred frequently even in dysplastic lesions (9 of 21 and 13 of 24 samples, respectively) including lesions with mild dysplasia (3p, 4 of 10 samples; 17p, 6 of 14 samples, respectively), and allelic losses on these chromosomal arms were also observed in cancerous tissues. We also detected allelic losses of the short and long arms of chromosome 9 at a low frequency in lesions with mild dysplasia and often in lesions with severe dysplasia and in intraepithelial cancers. Our results suggested that inactivation of tumor suppressor genes on 3p and 17p occurs at a very early stage of esophageal carcinogenesis and that genes on 9p and 9q are likely to play important roles in malignant changes. Comparison of the genetic alterations in precancerous dysplastic lesions with those in carcinomas supports the idea that ESC arises from the dysplastic lesion.

Alleles↗
PubMed1996

Cardiac complications after hepatic resection.

During a period of 94 months between 1985 and 1993, 474 hepatic resections were performed in 451 patients, of whom 23 (5 per cent) had cardiac problems: ischaemic heart disease in 16 (previous myocardial infarction in five and angina pectoris in 11), arrhythmic disorders in three, valvular disease in three (previous mitral valve replacement in two) and hypertrophic cardiomyopathy in one. The cardiac patients had a higher incidence of cardiac complications (24 versus 0 per cent, P < 0.0001) including two myocardial infarctions, and of non-cardiac complications consisting of postoperative liver failure (16 versus 4 per cent, P < 0.01) and bile leak (16 versus 5 per cent, P = 0.02), as well as hospital death (16 versus 3 per cent, P < 0.001). However, long-term survival was similar in the two groups. Patients with preoperative cardiac conditions appear to be at increased risk for early postoperative morbidity and mortality after hepatic resection.

Adolescent↗
PubMed1996

Thromboxane A2 in preservation-reperfusion injury: the effect of thromboxane A2 synthetase inhibitor.

It has been suggested that thromboxane A2 (TXA) plays important roles in preservation/reperfusion organ injury. In this report, we investigated the prostanoid release from the liver and the effect of a selective TXA synthetase inhibitor (E)-3-[p-(1H-imidazol-yl-methyl)-phenyl]-2-propenoic acid, OKY046) during cold preservation and after reperfusion. Rat livers were preserved in lactated Ringer's solution at 4 degrees C for 2, 4, and 6 hr and perfused with oxygenated Krebs-Henseleit buffer using recirculating perfusion system, and prostanoids were measured during cold preservation and after reperfusion. OKY046 and a novel TXA receptor antagonist [(9,11), (11,12)-Dideoxa-9a, 11a-dimethyl-methano-11,12-methano-13,14-dihydro-13-aza-14-oxo-15-cyclo pentyl-16,17,18,19,20-pentanor-15-epi-TXA, ONO3708] were added into the preservation solution and perfusate. Along with the preservation time, both the production and release of TXA was observed to increase; however, almost all the produced TXA was stored in the liver tissue. Afterwards, the stored TXA was released into perfusate in 15 min after reperfusion. OKY046 significantly decreased both the production and release of TXA. In addition, OKY046 improved the histological damage and trypan blue uptake of liver cells. Our results demonstrate that TXA, stored in the liver during preservation, might therefore be a potential trigger of reperfusion injury, and as a result, OKY046 reduces reperfusion injury by decreasing the production of TXA during preservation.

6-Ketoprostaglandin F1 alpha↗
PubMed1996

Distribution of immunoreactive 2',5'-oligoadenylate synthetase in mouse reproductive organs.

Although 2', 5'-oligoadenylate synthetase (2-5AS) is an enzyme induced by inferferon (IFN) or viral infections and mediates one of the principal antiviral pathways turned on by IFN, low constitutive levels of the enzyme can be detected in various "normal" animals that have not been treated with IFN or virus. The distribution of this enzyme in the female and male reproductive organs of normal healthy mice was studied by Western blotting and by an immunohistochemical method, using a specific monoclonal antibody. On Western blotting, an antibody to 42-kD 2-5AS reacted with extracts from the ovary, oviduct, uterus, vagina, and placenta among the female reproductive organs, and testis, epididymis, and ductus deferens in the male. Immunohistochemically, the 2-5AS was localized on the following cells in the female reproductive organs: oocytes in the ovary; epithelium in the oviduct, uterus, and vagina; and trophoblasts in the placenta. Furthermore, the 2-5AS was localized on the epithelium and muscular layer in the ductus deferens and epithelium in the penis of the male mice, whereas the epithelium of the testis, epididymis, and seminal vesicle were stained faintly. It is well known that IFN is produced continuously in normal mice, so the 2-5AS in the tissues of normal mice is considered to be induced by such IFN produced under physiological conditions. Expression of the 2-5AS on the epithelium and trophoblasts in the reproductive organs may be responsible for the prevention of viral infections. However, the enzyme in oocytes may have some functions other than as an antiviral agent, since the enzyme was not detectable in embryos during early development.

2',5'-Oligoadenylate Synthetase↗
PubMed1996

Lupus peritonitis mimicking acute surgical abdomen in a patient with systemic lupus erythematosus: report of a case.

A 25-year-old Japanese woman who had been suffering from systemic lupus erythematosus (SLE) for 12 years was admitted to our hospital with a suspected diagnosis of peritonitis after suddenly developing severe abdominal pain and distention which could not be relieved by treatment with anodyne. Noninvasive examinations did not provide enough evidence to rule out acute appendicitis, bowel perforation, or ischemia due to vasculitis. Therefore, in consideration of the severity of her uncontrollable abdominal pain, an exploratory laparotomy was performed. The operative findings revealed nonbacterial peritonitis with a large amount of ascites and an edematous small bowel. No perforation of the intestine was found. On post-operative day (POD) 3, the severe abdominal pain redeveloped, but responded well to steroid pulse therapy. Based on the operative findings and her clinical course, the most likely diagnosis was thought to be acute lupus peritonitis. It is often difficult to ascertain whether abdominal pain in an SLE patients is due to lupus peritonitis or to an underlying cause requiring surgery. Thus, it is essential that continuous and careful assessment of the surgical abdomen is performed when a patient with SLE develops acute abdominal pain, and if a surgical condition cannot be ruled out, a laparotomy should be performed without delay.

Abdomen, Acute↗