Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 127 records · Page 7Linked to original sources

PubMed1999

Expression of cyclooxygenase-2 in human hepatocellular carcinoma: relevance to tumor dedifferentiation.

Cyclooxygenase (COX) is a key enzyme in the synthesis of prostanoids. Two isoforms of this enzyme have been identified: COX-1 and COX-2. Recent studies have suggested that COX-2, but not COX-1, may play a role in colorectal tumorigenesis. In the present study, we investigated the expression of COX-2 as well as COX-1 in human hepatocellular carcinoma (HCC) tissues using immunohistochemistry and immunoblotting. Forty-four surgically resected HCC tissues with adjacent nontumorous livers (NTs), involving 17 cases of chronic viral hepatitis and 27 cases of cirrhosis, and 7 surgically resected, histologically normal liver tissues were used. The well-differentiated HCC expressed COX-2 more frequently and strongly than less-differentiated HCC or hepatocytes of NTs. Less-differentiated HCCs expressed less COX-2 than hepatocytes of NTs, which showed scattered, strong COX-2 expression. Histologically normal liver was weakly positive for COX-2. The expression of COX-1 was weaker than that of COX-2 in hepatic neoplastic and non-neoplastic parenchymal cells. An enhanced expression of COX-1 was not observed in well-differentiated HCCs. Immunoblotting also confirmed up-regulation of COX-2, but not COX-1, in well-differentiated HCCs. The present study is the first to demonstrate a high expression of COX-2 in well-differentiated HCC and a low expression in advanced HCC, in contrast to its continuous expression during colorectal carcinogenesis. These findings suggested that COX-2 may play a role in the early stages of hepatocarcinogenesis, but not in the advanced stages, and may consequently be related to HCC dedifferentiation.

Adult↗

PubMed1999

Interleukin-4 inhibits granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha expression by human monocytes in response to polymethylmethacrylate particle challenge in vitro.

The outcome of total joint arthroplasty is determined by biological events at the bone-implant interface. Macrophages phagocytose implant or wear debris at the interface and release proinflammatory mediators such as interleukins 1 and 6, tumor necrosis factor-alpha, and prostaglandin E2. These mediators are thought to contribute to the resorption of periprosthetic bone. Previous studies of tissues harvested from the bone-implant interface of failed orthopaedic implants demonstrated a possible role for two other cytokines, granulocyte-macrophage colony-stimulating factor and interleukin-4. The present study examined the effects of in vitro challenge with polymethylmethacrylate particles on the expression of granulocyte-macrophage colony-stimulating factor by primary human monocytes/macrophages and the role of interleukin-4 in regulating this expression. The polymethylmethacrylate particles caused a dose-dependent release of granulocyte-macrophage colony-stimulating factor at 48 hours. This release was accompanied by increased expression of interleukins 6 and 1beta and tumor necrosis factor-alpha. Release of the lysosomal enzyme hexosaminidase also increased in response to the particles. Interleukin-4 inhibited the expression of granulocyte-macrophage colony-stimulating factor, interleukin-6, and tumor necrosis factor-alpha at 48 hours in a dose-dependent manner. The data presented in this study confirm the hypothesis that interleukin-4 downregulates particle-induced activation of macrophages, as demonstrated by the decreased release of proinflammatory mediators.

Dose-Response Relationship, Drug↗

PubMed1999

An ascending aortic aneurysm caused by giant cell arteritis: report of a case.

A 69-year-old woman was referred to our hospital for investigation of an abnormality detected by a chest roentgenogram, and was subsequently found to have an ascending aortic aneurysm. She had not suffered any symptoms such as headache or polymyalgia rheumatica. Aneurysmectomy and reconstruction of the ascending aorta was performed using cardiopulmonary bypass, and pathological examination of the aneurysmal wall revealed giant cell arteritis (GCA). Preoperatively, she had not suffered any temporal pain, and no signs of inflammation were detected serologically. GCA is a rare cause of aortic aneurysm in the Japanese population, and a brief review of the literature on this unusual entity is presented following this case report.

Aged↗

PubMed1999

Fate of atrial flap used in repair of total anomalous pulmonary venous connection.

Histological changes in the right atrial flap used in repair of total anomalous pulmonary venous connection were observed when the patient underwent repair of peripheral pulmonary venous stenosis after two months. The flap, 35 mm in length and 15 mm in width, was thin and soft. Microscopically, endocardium and myocardium were preserved well, with only moderate thickening of the epicardium. We can anticipate the viability of the right atrial flap, but care should be taken to keep blood supply to the flap intact.

Cardiac Surgical Procedures↗

PubMed1999

Modification of low density lipoprotein potentiates its inhibitory effect on catecholamine secretion in cultured bovine adrenal medullary cells.

Low density lipoprotein (LDL) and lipoprotein(a) suppress catecholamine secretion in cultured adrenal medullary cells. Modification of LDL by oxidation or acetylation potentiates various atherogenic actions of LDL. In the present study, we investigated whether the modification of LDL influences catecholamine secretion in cultured bovine adrenal medullary cells. The exposure of LDL to CuSO4 caused a time-dependent oxidation of LDL. Maximal oxidation of LDL was observed after exposure to CuSO4 for 24 h. Native LDL inhibited catecholamine secretion induced by carbachol to 68.5% of control. Oxidized LDL caused further inhibition of carbachol-evoked secretion to 37.6% of control. Acetylated LDL inhibited it to 41.0% of control. There was a good correlation between the extent of LDL oxidation and the inhibition of catecholamine secretion. These results suggest that oxidation or acetylation of LDL augments its inhibitory effect on the secretion of catecholamines. Since catecholamines are a risk factor of atherosclerosis, the inhibitory effect by such modified LDL may be a mechanism inhibiting atherosclerotic progression.

Adrenal Medulla↗

PubMed1999

Bile ductular proliferation as a prognostic factor in biliary atresia: an immunohistochemical assessment.

PURPOSE: The correlation between the histological findings of the intrahepatic biliary epithelium and postoperative bile drainage in biliary atresia (BA) was investigated. METHODS: The patients with BA were classified into 2 groups, consisting of a good bile drainage group (GBD, n = 14, mean age at initial operation, 57.6+/-18.0 days) and a poor bile drainage group (PBD, n = 11, mean age at initial operation, 86.9+/-42.7 days). Liver specimens from an initial Kasai's operation were examined by immunostaining using anticytokeratin 7 (CK7) antibody and anti-MIB-1 antibody. The number of CK7-positive cells in the bile ductules was microscopically calculated within the 40-microm-thick interstitium along the limiting plate (LP), and the CK7-positive cell number per unit length of the LP was estimated. In addition, the MIB-1 index in bile ductules also was determined. RESULTS: The number of CK7-positive cells in PBD was significantly higher than that in GBD (167.6+/-45.6 v 117.8+/-32.4/ mm, P<.05). However, the MIB-1 index in biliary cells did not differ between the 2 groups. CONCLUSION: An increased number of intrahepatic bile duct epithelial cells in liver specimens at the initial operation may be a poor prognostic factor in BA and appears to depend on the duration of bile stasis rather than the degree of bile stasis.

Analysis of Variance↗

PubMed1999

Living related liver transplantation: histopathologic analysis of graft dysfunction in 304 patients.

Between June 1990 and August 1997, 304 mainly pediatric patients underwent a total of 311 orthotopic living related liver transplantations (LRLTs) under tacrolimus immunosuppression at Kyoto University Hospital. Congenital biliary atresia was the most common underlying disease. The donor was a parent, and the left lateral segments were used as grafts in most cases. The average number of loci of HLA-A, -B, and -DR mismatches between the donor and the recipient were 2.1. Forty-three transplants were ABO-incompatible. Liver histology at the time of abnormal liver function after transplantation was analyzed. Preservation injury was rare and mild. Acute cellular rejection (ACR) occurred in 36% of transplants during the first 6 months. Average rejection activity index (the Banff schema) was 4.2 and severe rejection was rarely seen. The number of mismatching HLA loci and immunosuppression regimens affected the incidence of ACR. Chronic rejection (CR) occurred in 2% of transplants. Concerning humoral rejection, no hyperacute rejection was seen. However, hepatic artery thrombosis (delayed hyperacute rejection) was seen in an ABO-incompatible transplant. Acute hepatitis, including those related to cytomegalovirus and Epstein-Barr virus, occurred in 17% of transplants. Chronic hepatitis, including hepatitis B and C, developed in 3%. Acute or chronic cholangitis occurred in 16%, and a significantly higher incidence of cholangitis was found in ABO-incompatible transplants. Posttransplantation lymphoproliferative disease developed in 2%. In LRLT, milder preservation injury and less frequent ACR and CR were suggested, probably because of the short cold-ischemia time and the advantages of HLA histocompatibility, respectively.

Adolescent↗

PubMed1999

Alteration of mRNA levels of delta-aminolevulinic acid synthase, ferrochelatase and heme oxygenase-1 in griseofulvin induced protoporphyria mice.

Human erythropoietic protoporphyria (EPP) is an inherited disorder of porphyrin metabolism and its experimental murine model can be produced by treatment with griseofulvin (GF). We investigated the alteration of mRNA expression in ferrochelatase (FeC), delta-aminolevulinic acid synthase (ALAS) and heme oxygenase-1 (HO-1) in liver, skin and peripheral blood cells of GF-treated mice. In liver, ALAS mRNA was enhanced dramatically by GF administration, in accord with thesis that the expression of ALAS is regulated by feedback mechanism. The expression of HO-1 mRNA increased most rapidly and drastically in liver, however its mechanism of regulation may be different from that of ALAS mRNA. The level of FeC mRNA in liver was less affected with GF treatment. Our results indicate that the inhibition of FeC by GF administration might occur primarily at post-transcriptional level. Similar effects were observed in the ALAS and HO-1 mRNA expression in peripheral blood cells, 2-fold increase in the ALAS mRNA and increase from undetectable level to detectable level in the HO-1 mRNA. In skin of GF-treated mice, average increases of 1.3-fold in the ALAS mRNA and 1.6-fold in the HO-1 mRNA were statistically insignificant. The FeC mRNA level was not altered in peripheral blood or in skin of GF-treated mice. The present study indicates that the molecular analysis is practicable in skin and peripheral blood. In further study, this model could contribute to investigate the pathogenesis of clinical manifestation including possibly cutaneous changes in EPP.

5-Aminolevulinate Synthetase↗

PubMed1999

Simultaneous typing of the STR loci, vWF and HumTPO, using discontinuous polyacrylamide gel electrophoresis.

Analyses of short tandem repeat (STR) loci are very useful for improving the accuracy of paternity determination. Combined use of several STRs makes this test even more accurate. We have devised a simple but effective method which consists of the co-amplification of two STR loci (vWF and HumTPO) in a single test tube, separation of the PCR products using discontinuous polyacrylamide gel electrophoresis, and detection using sensitive silver staining. An appropriate combination of PCR primer pairs gave a high resolution and good separation of the two STR bands in the same lane on the same gel. Many combinations of STR loci have potential usefulness in paternity and individualization testing or population genetic studies in forensic practice.

Journal Article↗

PubMed1999

Molecular, biochemical and immunological studies of hen pancreatic deoxyribonuclease I.

Deoxyribonuclease I (DNase I) was purified from the hen pancreas to electrophoretic homogeneity using six-step column chromatography. The purified enzyme showed a molecular mass of about 33 kDa and maximum activity at pH 7.0. It required divalent cations, Mg2+ and Ca2+, for its activity and was inhibited by EDTA, EGTA and an antibody specific to the purified enzyme but not by G-actin. A 1066-bp cDNA encoding hen DNase I was constructed from the total RNA of a hen pancreas using a combination of the reverse transcriptase-polymerase chain reaction and rapid amplification of cDNA ends methods, followed by sequencing. The cDNA was expressed in Escherichia coli, and the recombinant polypeptide exhibited significant enzyme activity. The mature hen DNase I protein was found to consist of 262 amino acids. In human and bovine DNase I four amino acid residues, Glu-13, Tyr-65, Val-67 and Ala-114 are involved in actin binding, whereas in the hen DNase I these positions were occupied by Asp, Phe, Ser and Phe, respectively. A survey of the DNase I distribution in 15 hen tissues showed that the pancreas had the highest levels of both DNase I enzyme activity and DNase I gene expression. The results of our phylogenetic and immunological analyses indicate that the hen DNase I is not closely related to the mammalian enzymes. This is the first report in which has been described the results of molecular, biochemical and immunological analyses on hen DNase I.

Amino Acid Sequence↗

PubMed1999

High-Fat diet enhances accumulation of hexachlorobenzene in rat dams and delays its transfer from rat dams to suckling pups through milk.

Effect of diets on the distribution and transfer of hexachlorobenzene (HCB) from dams to fetuses and suckling pups was investigated. In pregnant rats, the amount of HCB accumulated in fat tissues of the high-fat diet group was higher than that of the control diet group (P < 0.05). The amounts of HCB in fetuses of the high-fat and control diet groups were estimated to be about 0.28 and 0.12% of the dam's total intake during pregnancy, respectively. In both groups, a large proportion of HCB in dams disappeared during lactation period and was transferred to their pups through the milk. In the pups of the high-fat diet group, the amount of HCB in stomach contents was lower immediately after birth and decreased slowly compared with that in the control diet group during lactation. These results showed that a high-fat diet reduced the speed of the transfer of HCB from the dams to their suckling pups through milk.

Adipose Tissue↗

PubMed1999

Polymorphisms in the dopamine D2 receptor gene and their relationships to striatal dopamine receptor density of healthy volunteers.

The density of striatal dopamine D2 receptors has been shown to vary considerably among healthy subjects. This variability might be due to genetic or environmental factors. In the present analysis we searched for relationships between dopamine D2 receptor gene (DRD2) polymorphisms and striatal dopamine D2 receptor density in vivo, as measured by positron emission tomography and [11C]raclopride in 56 healthy subjects. There was a significant association between presence of a putative functional DRD2 promoter allele (-141C Del) and high striatal dopamine receptor density (t= 2.32, P= 0.02). In agreement with some previous studies the presence of the DRD2 TaqIA1 allele was associated with measures of low dopamine receptor density (t=2.58, P=0.01). Also the DRD2 TaqIB1 allele was associated with low dopamine receptor density (t= 2.58, P= 0.01) wheras there was no significant relationship between another common silent intronic DRD2 short tandem repeat polymorphism (STRP) and striatal dopamine D2 receptor density. The results suggest that DRD2 genotypes may participate differentially in the regulation of striatal dopamine D2 receptor density in healthy human subjects. The results should be interpreted with caution because of the limited sample size.

Adult↗

PubMed1999

A rare case of extramedullary spinal cord germinoma.

A rare case of spinal cord germinoma in a 20-year-old Japanese female is presented. The tumor was detected at the level of T11 and L3 by myelography. Histological findings of the resected tumor were identical to germinoma, which is characterized by polygonal tumor cells, lymphocytic infiltrate, and granuloma. Tumor cells and lymphocytes reacted with antibodies for placental alkaline phosphatase and CD45, respectively. A few multinucleated giant cells, negative immunohistochemically for human chorionic gonadotropin were also seen. The present case is the 10th case of spinal cord germinoma and is thought to be the first case of such a tumor located extramedullary. Diagnosis of such a rare tumor in an unusual location needs proper histological, ultrastructural and immunohistochemical evaluation.

Adult↗

PubMed1999

Reduction of vascular tone by introduction of troglitazone to the canine coronary artery.

The insulin-sensitizing agent troglitazone ((+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-ylmethoxy++ +)benzyl]-2,4- thiazolidinedione, CAS 97322-87-7), has been reported to reduce vascular tone in the rat tail artery. This study was designed to examine whether troglitazone could relax the precontracted canine coronary artery in vitro. Isometric tension of coronary arterial rings was measured, and analysis by Mann-Whitney U-test revealed that significant relaxation was induced even with 1 mumol/l troglitazone. This relaxation was not affected by blocking of NO synthase, cyclooxygenase, the large and intermediate conductance Ca(2+)-activated K+ channel, the ATP-sensitive K+ channel, or the Na(+)-K+ pump. The exact mechanism of the reduction of vascular tone by troglitazone remains unclear. However, the finding that troglitazone acts as a vasorelaxant in the coronary artery may be clinically useful, since troglitazone is mainly used for type II diabetic patients with insulin resistance, which is associated with increased risk for coronary artery disease.

Animals↗

PubMed1999

Clinicopathological features of early gastric cancer: results of 100 cases from a rural general hospital.

OBJECTIVE: To evaluate 100 patients with early gastric cancer from the point of view of early detection, clinicopathological variables, and long term results. DESIGN: Retrospective study. SETTING: Rural general hospital, Japan. SUBJECTS: 100 patients with early gastric cancer (confined to the epithelium, lamina propria, or submucosa) out of a total of 197 who had gastric cancers resected for cure between May 1986 and April 1996. INTERVENTIONS: Subtotal gastrectomy (n = 87), total gastrectomy (n = 8), proximal gastrectomy (n = 2), and local wedge resection (n = 3). MAIN OUTCOME MEASURES: Histopathological features and outcome. RESULTS: The mean annual incidence of early gastric cancer was 51% (range 35%-70%). 16/59 patients with mucosal cancer (37%) and 18/41 with submucosal cancer (44%) presented with symptoms of the disease. The diagnosis was made in 62 by endoscopy, and in only 2 by upper gastrointestinal radiographic examination. None of the 59 with mucosal cancer had lymphatic invasion, and only 1 had a lymph node metastasis. Among the 41 with submucosal cancer, however, 15 had lymphatic invasion (37%), 13 had venous invasion (32%), and 2 had lymph node metastases (5%). 83 patients were alive with no sign of recurrence at the time of writing (median follow up 62 months, range 12-136). One patient with a tumour that produced alpha-fetoprotein died of hepatic metastases 23 months after subtotal gastrectomy. 9 patients developed second cancers, and 6 died of these with no signs of recurrence of early gastric cancer. The overall 5 and 10 year survival rates were 82% and 66%, and the corresponding disease-specific survival rates for 85 patients were both 98%. CONCLUSIONS: Excellent long term results can be achieved in the treatment of early gastric cancer, even in a non-specialist centre. Patients with early gastric cancer should have their alpha-fetoprotein concentration measured, and be examined for the presence of other malignant disease both before and after treatment of the gastric cancer.

Adenocarcinoma↗

PubMed1999

Mechanisms of hypoxic coronary vasodilatation in isolated perfused rat hearts.

We pharmacologically investigated the potential involvement of nitric oxide (NO), prostacyclin, adenosine, adenosine triphosphate (ATP)-sensitive K (K(ATP)) channel opening and Ca2+-activated K (K(Ca)) channel opening in coronary vasodilatation during 15 min of hypoxia in isolated rat hearts perfused at a constant pressure of 70 mm Hg. The coronary flow suppressed by 10(-4) M Nomega-nitro-L-arginine methyl ester (L-NAME), which corresponds to the NO-dependent flow, decreased to almost zero during hypoxia. In contrast, the NO-dependent coronary flow amounted to approximately 40% of the total coronary flow during normoxia. The suppression of coronary flow by 10(-5) M 8-phenyltheophylline (8-PT), which corresponds to the adenosine-dependent flow, was remarkable in the middle and the late phases of a 15-min hypoxia. The coronary flow suppressed by 2 x 10(-6) M glibenclamide, which corresponds to the K(ATP) channel opening-dependent flow, depended on the agents added to the perfusate. However, there was a marked increase in coronary flow in the early phase of hypoxia in the heart perfused with the combination of 8-PT, 10(-2) M tetraethylammonium (TEA) and L-NAME. During hypoxia, the coronary flow suppressed by TEA, which corresponds mainly to the K(Ca) channel opening-dependent flow, also depended on the agents added to the perfusate. However, during reoxygenation, there was a transient significant increase in any combination of the agents. Our study suggests that hypoxia almost completely inhibits NO production, and that K(ATP) channel opening immediately after hypoxia and subsequent enhanced adenosine production cause a marked hypoxic coronary vasodilatation. It also suggests that K(Ca) channel opening causes vasodilatation during reoxygenation.

Animals↗

PubMed1999

Detection of human papilloma virus type 58 in a case of a perianal Bowen's disease coexistent with adult T-cell leukemia.

A case of Bowen's disease (BD) that appeared in the perianal region of a 65-year-old Japanese woman coexistent with chronic adult T cell leukemia (ATL) is described. Histopathological findings revealed that irregularly arranged tumor cells with atypical nuclei throughout the epidermis, which itself disclosed hyperkeratosis, dyskeratotic cells, and clumping cells. Positive staining for HPV antigens was immunohistochemically seen in several nuclei of the tumor cells. Electron microscopic study of the tumor tissue disclosed virus particles of about 50 nm in diameter form the squamous cells. A positive band at 256 bp was obtained by PCR using HPV-L1 primer. The amplified DNA by L1 primer completely corresponded to that of HPV-58.

Aged↗

PubMed1999

Vascularization of small hepatocellular carcinomas: correlation with differentiation.

BACKGROUND: Hepatocellular carcinoma (HCC) is generally considered a hypervascular tumor when visualized by angiography. However, small HCCs are not always found to be hypervascular. METHODS: To evaluate this, 50 HCCs < or =3 cm in diameter were studied. The 50 tumors consisted of 16 well-differentiated HCCs, 25 moderately differentiated HCCs, and 9 that were each a mixture of well- and moderately differentiated HCC. RESULTS: The mean number of portal tracts in the well-differentiated HCCs was 34% of the number in the surrounding nontumorous liver, and few intratumoral arterioles were seen. In contrast, the mean number of portal tracts in the moderately differentiated HCCs was 0.6% of the number in the surrounding nontumorous liver, and abundant intratumoral arterioles were seen. For HCCs that contained both well-differentiated and moderately differentiated tumor, the distribution of portal tracts and intratumoral arterioles in each portion was similar to that seen in well-differentiated or moderately differentiated HCC alone, respectively. HCCs that were larger than 1.5 cm in diameter had fewer portal tracts and more intratumoral arterioles than HCCs whose diameters were < or =1.5 cm. CONCLUSIONS: As small HCCs increase in size and become increasingly dedifferentiated, the number of portal tracts apparently decreases and intratumoral arterioles develop. These findings may reflect changes in the hemodynamics as the HCC develops.

Actins↗