Biomedical subjects

M Sakurai

Publications and source records attributed to M Sakurai.

At least 289 records · Page 16Linked to original sources

PubMed1996

Mixed germ-cell tumor of the brain. Pathologic study of six autopsy cases.

Intracranial mixed germ-cell tumors are rare. We describe the findings from six autopsies of patients with these tumors. The patients were all young at presentation (mean age, 16 years), and five of the six were male. Headache, vomiting, polyuria and diplopia were common symptoms. Radiographic evaluation demonstrated a mass on the midline of the brain. The patients were treated mainly with radiation, but survival (mean, 3.7 years) was not as long as predicted. At autopsy, the tumors occupied most of the ventricular spaces, and ranged from being well-circumscribed to invasive. All tumors contained both germinoma components and nongerminomatous germ-cell tumor components. Because the distribution of these components was not homogenous, at least two sections were necessary for the diagnosis. Immunoreactivity for placental alkaline phosphatase was found in all tumors. Immunostaining for human chorional gonadotropin, alpha-fetoprotein and carcinoembryonic antigen was usually associated with abnormally high serum levels of these tumors markers in life. A number of the cells in both kinds of tumor components expressed proliferating cell nuclear antigen, probably reflecting the intense malignant potential.

Adolescent↗

PubMed1996

An increased NM23H1 copy number may be a poor prognostic factor independent of LOH on 1p in neuroblastomas.

In a study of 154 neuroblastomas, loss of heterozygosity (LOH) was observed on 1p (13%, 19/143), 11q (19%, 11/59), 14q (15%, 15/97), 17p (5%, 5/105) and 17q (17%, 9/52). We also found an increase in NM23H1 copy number in 14% (13/95) of neuroblastomas. All except one tumour with an increased copy number stained positive with anti-NM23H1 monoclonal antibody. Event-free survival (EFS) was significantly shorter in 19 patients with LOH on 1p than in 128 without (41% vs 77% 4 year EFS, P=0.0093), and in 13 patients with increased NM23H1 copy numbers than in 82 with normal copy numbers of the gene (61% vs 84% 4 year EFS, P=0.0103). LOH on 11q, 14q or 17q did not affect EFS. Most tumours with LOH on 1p, increased NM23H1 copy numbers or MYCN amplification occurred in patients aged 12 months or more, those with advanced stage disease, and those who showed near diploidy or pseudodiploidy. However, LOH on 1p was found in only 1 of the 13 tumours with increased NM23H1 copy numbers, and MYCN amplification of four copies occurred in only one other such tumour. These findings suggest that the increased NM23H1 copy number may be a predictor for poor prognosis, independent of LOH on 1p, and probably also of MYCN amplification.

Alleles↗

PubMed1996

Isolation and characterisation of Kasumi-1 human myeloid leukaemia cell line resistant to tumour necrosis factor alpha-induced apoptosis.

Tumour necrosis factor (TNF)-alpha induces apoptosis in a human acute myeloid leukaemia cell line, Kasumi-1. To examine the role of protein phosphorylation in signal transduction of TNF-alpha-induced apoptosis, a variant cell line resistant to TNF-alpha was established by an intermittent challenge of Kasumi-1 cells with increasing concentrations of TNF-alpha for 6 months. The mechanism of resistance to TNF-alpha appears to be in the post-receptor pathway because expression of p55 TNF receptor in the variant cells is increased compared with that of the parental Kasumi-1 cells. In renaturation assays, TNF-alpha induced a rapid activation of different protein kinases of different molecular weights, including the 50 kDa protein kinase (PK50) followed by the 35 kDa protein kinase (PK35), in the parental Kasumi-1 cells. The dose-response of TNF-alpha required to activate PK50 and PK35 was closely related to concentrations of TNF-alpha that induced apoptosis. Treatment of Kasumi-1 cells with ceramide also activated PK35. In TNF-resistant variant cells, activation of PK35 in response to TNF-alpha or ceramide was practically nil. These findings suggest that activation of PK35 through the ceramide pathway may play an important role in signal transduction of TNF-alpha in the Kasumi-1 cell line, while the decreased activation of PK35 may explain the insensitivity of the variant cells towards TNF-alpha.

Apoptosis↗

PubMed1996

Inhibition of natural killer (NK) cell activity against varicella-zoster virus (VZV)-infected fibroblasts and lymphocyte activation in response to VZV antigen by nitric oxide-releasing agents.

The addition of nitric oxide (NO)-releasing agents, S-nitroso-N-acetyl-DL-penicillamine (SNAP), 1-hydroxy-2-oxo-2,3-bis(2-aminoethyl)-1-triazene (NOC18), 30{(+/-)-(E)-ethyl-2'-[(E)-hydroxyimino]-5-nitro-3-hexenecarbam oyl} -pyridine (NOR4) significantly inhibited NK cell activity against VZV-infected cells, while antibody-dependent cell-mediated cytotoxicity (ADCC) against VZV-infected cells was unaffected. Interferon-alpha (IFN-alpha) production by non-adherent peripheral blood mononuclear cells (NPBMC) cultured with VZV-infected cells was decreased by the addition of NO-releasing agents. Lymphocyte proliferation and the expression IL-2 receptor (CD25) in response to VZV antigen were also inhibited by the addition of NO-releasing agents. These results suggest that the production of NO by an inflammatory process may lead to inhibition of NK cell- and T cell-mediated immunity to VZV infection.

Adult↗

PubMed1996

Diagnosis of borderline adenomas of the stomach by endoscopic mucosal resection.

BACKGROUND AND STUDY AIMS: The correct histological diagnosis of gastric borderline adenomas is often difficult, especially in excluding malignancy, since the usual diagnostic methods, such as radiography and histological examination of forceps biopsy specimens, are of limited accuracy. The aim of this study was to retrospectively analyze the value of endoscopic mucosal resection in establishing the correct diagnosis of borderline adenomas. RESULTS: Fourteen borderline adenomas were finally diagnosed as containing early gastric cancer type IIa (well-differentiated tubular adenocarcinoma) after endoscopic mucosal resection, of the remaining 36 tubular adenomas, six represented mild dysplasia, 24 moderate dysplasia, and six severe dysplasia. Most parts of the 14 adenomas containing early gastric cancers had regions of structural atypia, and cellular atypia was moderate in all. Seven of 14 cancers were completely resected, all patients being tumor-free after a follow-up of 33-61 months. CONCLUSIONS: These results suggest that diagnosing borderline adenoma on the basis of radiographic and endoscopic-bioptic findings is generally unreliable, because biopsy specimens may not be representative of the entire lesion. Borderline adenomas of the stomach should be completely resected by endoscopic mucosal resection to obtain a final diagnosis and - depending on the size and type of the lesion - possibly also definitive treatment.

Adenoma↗

PubMed1996

Role of adhesion molecules in natural killer cell-induced DNA fragmentation of cytomegalovirus-infected fibroblasts.

We investigated the roles of CD11a, CD11b, CD18, and CD54 adhesion molecules in non-adherent peripheral blood mononuclear cells (NPBMC)-induced DNA fragmentation of cytomegalovirus (CMV)-infected cells. DNA fragmentation in the supernatant from CMV-infected cells and NPBMC was assayed, and cytotoxicity against CMV-infected cells was calculated. Treatment of NPBMC with monoclonal antibodies to CD11a, CD11b, CD18, and CD54 significantly reduced cytotoxicity against CMV-infected cells. A combination of anti-CD11a, anti-CD11b, and anti-CD18 antibodies further inhibited cytotoxicity against CMV-infected cells. Cytotoxicity against CMV-infected cells treated with anti-CD54 antibody was also significantly inhibited. Binding of effector cells to target cells was not affected by treatment of NPBMC or CMV-infected cells with antiadhesion molecule antibodies. These results indicate that LFA-1 (CD11a/CD18), Mac-1 (CD11b/CD18), and ICAM-1 (CD54) adhesion molecules are involved in natural killer (NK) cell-induced DNA fragmentation in CMV-infected cells.

Adult↗

PubMed1996

Adherence of peripheral blood leukocytes to cytomegalovirus-infected fibroblasts.

Peripheral blood monocytes and B cells adhered to cytomegalovirus (CMV)-infected fibroblasts, whereas T cells and polymorphonuclear leukocytes did not adhere to either CMV-infected or uninfected fibroblasts. When T cells were activated with anti-CD3 antibody, activated T cells demonstrated adherence and cytotoxicity to both CMV-infected and uninfected fibroblasts. Adherence of peripheral blood mononuclear cells (PBMC) and cytotoxicity mediated by adherent activated T cells were blocked by treatment of CMV-infected fibroblasts with anti-ICAM-1 antibody and by treatment of leukocytes with anti-LFA-1 antibody. These data suggest that an interaction of ICAM-1 and LFA-1 is responsible for the adherence of leukocytes and for adherent activated T cell-mediated cytotoxicity against CMV-infected fibroblasts.

B-Lymphocytes↗

PubMed1996

Sinusoidal capillarization and arterial blood supply continuously proceed with the advance of the stages of hepatocarcinogenesis in the rat.

Hepatocellular carcinoma (HCC) is supplied only with arterial blood and has capillaries instead of sinusoids, unlike the normal hepatic tissue. In order to reveal the sequential changes of sinusoidal structure and blood supply during hepatocarcinogenesis, we examined hyperplastic nodules (HPN), atypical hyperplastic nodules (AHPN) and HCC in F344 rats fed with 2-acetylaminofluorene for 25-35 weeks. The extent of arterial blood supply and the degree of sinusoidal capillarization were assessed by the staining of hepatic nodules with arterially infused ink and by immunohistochemical and ultrastructural analyses of the sinusoids, respectively. The proportion of arterialized nodules was 47% in HPN, 57% in AHPN and 85% in HCC, which indicates that arterialization begins at the stage of HPN and a few HCC still receive portal venous blood. The proportion of Factor-VIII-related antigen (F-VIII)-positive nodules was 25% in HPN, 40% in AHPN and 100% in HCC. Non-arterialized nodules did not express F-VIII, while some F-VIII-negative nodules were already arterialized. Electron microscopically, non-arterialized HPN exhibited normal features of sinusoids, while arterialized HPN showed disappearance of Kupffer cells and partial defenestration of sinusoidal endothelial cells. In non-arterialized and arterialized AHPN, basement membrane became continuous and lipid droplet-containing stellate cells were no longer seen. In HCC, endothelial fenestrae were diminished and basement membrane became thick. The present study has demonstrated that sinusoids are altered in the following order as hepatocarcinogenesis advances from HPN to HCC; onset of arterialization and decrease of endothelial fenestrae, expression of F-VIII by endothelial cells, disappearance of Kupffer cells, diminution of lipid droplets in stellate cells and thickening of basement membrane.

Animals↗

PubMed1996

Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas.

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm in diameter were investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocellular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), laminin and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences in tumor size, vascularity and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well-differentiated' HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.

Aged↗

PubMed1996

Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: a case report and review of the literature.

As patients with glycogen storage disease type I survive longer, cases with hepatic tumor have been increasingly documented. A 16 year old boy with glycogen storage disease type I was evaluated for multiple liver tumors. He was diagnosed on clinical features at 9 months of age and underwent a mesocaval shunt operation at 5 years of age. The biopsy of one of the masses showed focal nodular hyperplasia. This is uncommon in patients with glycogen storage disease type I, compared to those with adenoma or malignant hepatic tumor. The association of a portacaval shunt with focal nodular hyperplasia is significant compared to other tumors. An environment of high estrogen concentration or sex hormone binding globulin accompanied by shunt operation may cause focal nodular hyperplasia to develop in the liver of patients with glycogen storage disease type I.

Adolescent↗

PubMed1996

Clinical features of measles in immunocompromised children.

Measles is often fatal for immunocompromised hosts. Protective immunity against measles has been studied but is still not completely understood. Recently, five cases of measles were encountered in immunocompromised children. Two of these were allogeneic bone marrow transplanted cases (one common variable immunodeficiency and one severe aplastic anemia) in remission, one Wilms' tumor case in remission, one hepatoblastoma case after cytotoxic therapy at disease onset and one exaggerating hemophagocytic syndrome case with suppressed natural killer cell activity. Clinical symptoms, laboratory findings and the immunologic backgrounds of these five patients were investigated. One of the patients, an 8 year old boy with hemophagocytic syndrome, died of giant cell pneumonia which was confirmed in the section of necropsy lung specimen. Two other patients who received allogeneic bone marrow transplants were not immune to measles, despite their own and their donors' immunizations. Their clinical symptoms were rather severe but both patients recovered and have remained seropositive for as long as 13 months. This fatality from measles is the first reported in a patient with hemophagocytic syndrome. Suppressed natural killer cell activity may be a poor prognostic factor. Also, secondary immunization failure for measles can occur in bone marrow transplanted patients with rather severe clinical symptoms.

Adult↗

PubMed1996

A case of prolonged human parvovirus B19 DNA-emia associated with polyclonal B cell activation.

The current paper reports an 8 year old girl with arthralgia and polyclonal B cell activation induced by human parvovirus B19 infection (HPV B19). The infection was diagnosed by the presence of the virus genome in sera. The patient presented with transient arthritis in the wrist, ankle joint and neck and elevation of immunoglobulin IgM antibodies to HPV B19 and rubella, antibodies to Mycoplasma and antistreptolysin O but without the typical clinical features of erythema infectiosum. The polyclonal B cell activation was paralleled by the presence of the virus genome of HPV B19 in sera. In some children with arthralgia, it is important to examine the genomes of viruses that may cause arthritis as well as the antibody titers to the viruses.

Arthralgia↗

PubMed1996

Enteric pathogens in severe forms of acute gastroenteritis in Ghanaian children.

Diarrheal disease is the major cause of childhood morbidity in developing countries. Although malnutrition is known as a risk factor for severe gastroenteritis, the role of enteric pathogens in the clinical severity is unclear. The present study was conducted in well nourished Ghanaian preschool children during a 3 month period of the rainy season to assess the relationship between enteric pathogens and severe gastroenteritis. Two hundred and twenty-five children with acute gastroenteritis and 64 age-matched control children were prospectively examined for the severity of dehydration and enteric pathogens in their stools. Of the 225 children with gastroenteritis, 69.8% (157/225) had mild dehydration and 30.2% (68/225) had severe dehydration. Bacteria were similarly isolated in stool samples from children with mild and severe dehydration and controls. Rotavirus accounted for 20.6% of children with severe dehydration and was more often isolated in stools from patients with severe dehydration than those from controls. Furthermore, the mixed infections associated with rotavirus and bacteria were more often found in patients with severe dehydration than those with mild dehydration or controls. Parasites were similarly found at low incidences among the three groups. The present study implied that rotavirus was more responsible for severe gastroenteritis than bacteria or parasites. However, factors other than enteric pathogens must be sought in a considerable number of severe cases. A large scale study throughout a year is recommended to obtain more precise information that would reflect the seasonal variation of rotavirus infections.

Acute Disease↗

PubMed1996

Detection of measles virus-induced apoptosis of human monocytic cell line (THP-1) by DNA fragmentation ELISA.

Measles virus (wild strain, Toyoshima strain)-induced cell death is characterized by cell shrinkage, chromatin condensation, and nuclear fragmentation in a human monocytic cell line (THP-1). DNA fragmentation of measles virus-infected THP-1 cells was demonstrated by DNA agarose gel electrophoresis as well as by DNA fragmentation ELISA. When measles virus-infected THP-1 cells were cultured on monolayers of fibroblasts or human umbilical vein endothelial cells (HUVEC), the percentage of measles virus antigen-positive THP-1 cells and DNA fragmentation were significantly decreased. Addition of anti-intercellular adhesion molecule (ICAM)-1 (CD54) monoclonal antibody to culture of measles virus-infected THP-1 cells reduced significantly DNA fragmentation induced by measles virus. These findings suggest that inhibition of virus spread by fibroblasts and HUVEC reduces apoptosis, and ICAM-1 (CD54) may participate in the DNA fragmentation pathway.

Antibodies, Monoclonal↗

PubMed1996

Evaluation of in-vivo transdermal absorption of cyclosporin with absorption enhancer using intradermal microdialysis in rats.

The purpose of this study was to evaluate the effect of absorption enhancer on in-vivo transdermal absorption of cyclosporin using intradermal microdialysis in rats. Cyclosporin oily solutions (0.5, 2, 8% w/v) were prepared from Sandimmun (10% w/v oily oral preparation of cyclosporin) by diluting with olive oil. 1-[2-(Decylthio)ethyl] azacyclopentan-2-one (HPE-101) and glycerin were added to the cyclosporin formulation as an absorption enhancer at various concentrations between 1 and 20%. These formulations were applied to the shaved abdomen of rats treated with intradermal microdialysis at a flow rate of 2.5 microL min-1 for 6 h. Cyclosporin was immediately detected and attained a plateau in the dermal dialysate after topical application of cyclosporin oily solution alone. Cyclosporin levels in the dialysate increased with increasing cyclosporin concentrations in the formulation from 0.5 to 8% (w/v). HPE-101 did not influence cyclosporin absorption at concentrations less than 6% (w/v). Addition of 10% (w/v) HPE-101 significantly enhanced an apparent absorption rate of cyclosporin by 4.9 times. However, 20% (w/v) HPE-101 did not show the enhancing activity. On the other hand, addition of glycerin at concentrations of 6, 10, and 20% (v/v) significantly enhanced an apparent absorption rate of cyclosporin by 3.0, 6.4, and 6.9 times, respectively. The time lag for cyclosporin absorption was less than 0.21 h in all tested cases. This microdialysis study shows that glycerin is a suitable enhancer for improving the in-vivo cyclosporin absorption from the skin.

Administration, Cutaneous↗

PubMed1996

Cellular uptake and biological effects of antisense oligodeoxynucleotide analogs targeted to herpes simplex virus.

In this study, we synthesized antisense oligodeoxynucleotides (ODNs) with phosphodiester, phosphorothioate (S-ODNs), or methylphosphonate linkages complementary to the splicing acceptor site of immediate-early pre-mRNA 5 of herpes simplex virus type 1 (HSV-1). The antiviral activity of each analog on cytopathic effect in cells infected with HSV-1 or HSV-2 was assessed and compared with the cellular uptake of the analog. We found that antisense S-ODNs showed the most potent antiherpetic activity, with 50% inhibitory concentrations of 5 microM for HSV-1 and 0.25 microM for HSV-2. The antiviral effect of antisense S-ODNs was stronger and longer acting than that of acyclovir. Cell association of S-ODNs was the highest and paralleled antiviral activity. Furthermore, some fluorescein isothiocyanate (FITC)-labeled S-ODNs were recognized in the nuclei in HSV-1 infected cells by confocal laser scanning microscopy. S-ODNs located in the nucleus could access the targeted mRNA, which might be responsible for the antiviral activities. Although our study also showed non-sequence-specific activity, which implies that multiple mechanisms are involved, S-ODNs are a promising novel anti-herpetic agent.

Animals↗

PubMed1996

Long-term in vitro culture and characterisation of avian embryonic stem cells with multiple morphogenetic potentialities.

Petitte, J.N., Clarck, M.E., Verrinder Gibbins, A. M. and R. J. Etches (1990; Development 108, 185-189) demonstrated that chicken early blastoderm contains cells able to contribute to both somatic and germinal tissue when injected into a recipient embryo. However, these cells were neither identified nor maintained in vitro. Here, we show that chicken early blastoderm contains cells characterised as putative avian embryonic stem (ES) cells that can be maintained in vitro for long-term culture. These cells exhibit features similar to those of murine ES cells such as typical morphology, strong reactivity toward specific antibodies, cytokine-dependent extended proliferation and high telomerase activity. These cells also present high capacities to differentiate in vitro into various cell types including cells from ectodermic, mesodermic and endodermic lineages. Production of chimeras after injection of the cultivated cells reinforced the view that our culture system maintains in vitro some avian putative ES cells.

Alkaline Phosphatase↗

PubMed1996

Increased deoxycytidine kinase activity by etoposide in L1210 murine leukemic cells.

Deoxycytidine kinase (dCK) is a rate-limiting enzyme for the activation of ara-C. It is responsible for the phosphorylation of ara-C which is widely used in the treatment of leukemia. We examined the effect of etoposide on dCK in L1210 cells and found that incubation with 10 microM etoposide for 1 h increased dCK activity to 170% of the control. This effect of etoposide on dCK activity was concentration-dependent up to at least 100 microM of the substance.

Animals↗