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Biomedical subjects

A Asai

Publications and source records attributed to A Asai.

At least 91 records · Page 5Linked to original sources
PubMed1997

Synthesis and antitumor activity of duocarmycin derivatives: A-ring pyrrole compounds bearing cinnamoyl groups.

A series of N-cinnamates of the A-ring pyrrole compound of duocarmycin were synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells and in vivo antitumor activity against murine sarcoma 180 in mice. The 4'-methoxy- and 4'-BocNH-cinnamates exhibited strong in vitro anticellular activity among the synthesized compounds. The ortho substitution of the 4'-methoxycinnamate did not affect the anticellular activity and contributed to an enhancement of water solubility. Most of the 8-O-(N,N-dialkylcarbamoyl) derivatives of the 4'-methoxycinnamate displayed remarkably superior in vivo antitumor activity to duocarmycin A or B2. Moreover, it is noteworthy that these 8-O-(N,N-dialkylcarbamoyl) derivatives exhibited significant antitumor activity at wider range of doses as compared with the A-ring pyrrole derivatives having the trimethoxyindole skeleton in segment B.

Animals↗
PubMed1997

Ultrasonographic evaluation of gastric emptying in normal children and children after pyloromyotomy.

Gastric emptying in the fundus, body, and antrum of the stomach was evaluated by ultrasonography (US) in 41 control children aged 2 to 18 years and 30 patients aged 1 to 19 years who had undergone pyloromyotomy because of hypertrophic pyloric stenosis. The gastric emptying curve decreased in an exponential manner for both control children and patients, while there was no significant difference in gastric emptying time (GET) between control children and patients within any of the age groups. However, GET was faster for younger children in both groups. An X-ray contrast study of the stomach performed in 2 patients who showed markedly delayed GET showed delayed gastric emptying but no significant deformities of the prepylorus. Our results suggest that US is a reliable method of measuring GET in children.

Adolescent↗
PubMed1997

A rare case of hamartoma in the lateral ventricle: case report.

BACKGROUND: Intraventricular manifestation of a hamartoma is an unusual clinical entity. CASE DESCRIPTION: A 12-year-old girl was admitted with complaints of dizziness and head heaviness. Computed tomography and T1-weighted magnetic resonance imaging (MRI) demonstrated an isodensity or isointensity mass lesion with cystic component in the right lateral ventricle, which showed relatively high signal intensity on T2-weighted MRI and lacked contrast enhancement. Histopathologic examination on the surgically removed specimens using glial fibrillary acidic protein, Klüver-Barrera, Bodian stainings, bromouridine labeling index, and MIB-1 immunohistochemical staining confirmed that the tumor had glial and neuronal components and low proliferative potentiality. CONCLUSION: This case is the first report of intraventricular hamartoma, although some reports on intracranial hamartoma located in areas other than the hypothalamus have been published. The radiologic findings, including relatively high signal intensity on T2-weighted MRI and absence of contrast enhancement, may be suggestive of the diagnosis of intraventricular hamartoma; however, the specific stainings for glial and neuronal cells and proliferative evaluation are essential to the precise diagnosis of hamartoma. Clinical manifestation of hamartoma in the ventricular system, though rare, should be kept in mind.

Brain Diseases↗
PubMed1997

Circulating matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 as serum markers of fibrosis in patients with chronic hepatitis C. Relationship to interferon response.

BACKGROUND/AIMS/METHODS: The imbalance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is considered to be an important determinant of extracellular matrix deposition and breakdown. We measured serum MMP-1, MMP-2, TIMP-1 and TIMP-2 levels using the respective one-step sandwich enzyme immunoassays in 98 patients with chronic hepatitis C treated with interferon beta to examine their clinical significance for assessment of liver histology and to determine whether they can be useful as predictors of the interferon response. RESULTS: Serum TIMP-1 levels showed a positive correlation with the degree of fibrosis (r(s)=0.30, p= 0.004). Serum MMP-2 levels revealed positive relationships with the degree of periportal necrosis (r(s)= 0.32, p=0.002), the degree of fibrosis (r(s)=0.26, p= 0.01) and total score of histological activity index (r(s)=0.24, p=0.02). Serum MMP-2 levels were significantly higher in patients with no response than in those with sustained and transient response (p<0.01 and p<0.05, respectively), while serum MMP-1 levels did not differ among the three groups. Compared with the levels in sustained responders, the total amounts of serum TIMP-1 were significantly lower in transient responders and non-responders (p<0.01 and p<0.001, respectively). As for serum TIMP-2 levels, a significant decrease was found in transient responders and non-responders (p<0.01). The ratios of serum MMP-2 to TIMP-1 levels were significantly higher in transient responders and non-responders than in sustained responders (p<0.001, respectively) even when HCV RNA levels were low in patients with HCV genome subtype 1b or when the HCV genome subtype was 2a or 2b. Sustained response was never found in type 1b patients with ratios of serum MMP-2 to TIMP-1 levels of over 6.0. In logistic multivariate regression analysis, the ratios of serum MMP-2 to TIMP-1 level (p=0.0001), HCV genome subtype (p=0.005) and serum TIMP-2 level (p=0.03) were the independent predictors for sustained response, while serum MMP-2 level (p=0.0006) was the only predictor for no response. CONCLUSIONS: Serum MMP-2 and TIMP-1 levels might be useful for estimating the degree of liver fibrosis. The ratio of serum MMP-2 to TIMP-1 levels may serve as a new predictor of interferon response in patients with chronic hepatitis C.

Alanine Transaminase↗
PubMed1997

Studies on duocarmycin SA and its derivatives.

New duocarmycin SA derivatives have been synthesized and evaluated for in vitro anticellular activity against HeLa S3 cells, and in vivo antitumor activity against murine sarcoma 180 in mice. The results suggested that the N,N-dialkylcarbamoyl derivatives bearing the p-methoxy cinnamoyl group, which was prepared from duocarmycin SA, showed good in vivo antitumor activities superior to native duocarmycin SA.

Animals↗
PubMed1997

Thiol-independent DNA cleavage by a leinamycin degradation product.

To understand the mechanism of action of a novel antitumor antibiotic leinamycin (1) which induces single-strand scission of DNA in the presence of thiol, the reaction of 1 with thiol in aqueous conditions was investigated. Two major degradation products were obtained from 1 in the presence of thiol. 2 was an inactive product, while 3 caused DNA cleavage in the absence of thiol. The DNA-cleaving activity of their synthetic derivatives indicates that the DNA alkylation and subsequent strand scission by leinamycin require the conversion of leinamycin to an electrophilic episulfonium species.

Alkylation↗
PubMed1997

Proliferative activity of central neurocytoma: measurement of tumor volume doubling time, MIB-1 staining index and bromodeoxyuridine labeling index.

Central neurocytoma is considered to be a benign intracranial neoplasm, but little is known about the biological behavior of this type of tumor. Proliferative activity of central neurocytoma was measured in 10 cases using MIB-1 staining for Ki-67 antigen. The MIB-1 staining value varied from < 0.1% to 5.6%, to indicating that some of these tumors have proliferative potential similar to that of anaplastic astrocytoma or malignant meningioma. The bromodeoxyuridine labeling index (BUdR LI, BrdU LI) was measured in 2 cases and the results correlated well with those of the MIB-1 analysis. Tumor volume doubling time (Td) measured in one case was 358 days which is similar to that of malignant meningioma. In one case, the MIB-1 value taken before and after 58 Gy of radiation treatment decreased markedly from 5.6% to 0.2%. The other 9 cases were also treated by radiation therapy (50-60 Gy) and no tumor recurrence was observed during follow-up periods ranging from 23 to 160 months. Another two patients with partially removed and 3 with subtotally removed tumors showing relatively high MIB-1 values might also have benefited from radiation therapy.

Adult↗
PubMed1997

Application of antisense ribonucleic acid complementary to O6-methylguanine-deoxyribonucleic acid methyltransferase messenger ribonucleic acid for therapy of malignant gliomas.

OBJECTIVE: A derivative of chloroethylnitrosoureas, 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU), is a drug of choice for the chemotherapy of human malignant brain tumors. However, the cytocidal effect of ACNU is effectively repressed through repair of ACNU-mediated deoxyribonucleic acid lesions by O6-methylguanine-deoxyribonucleic acid methyltransferase (MGMT). Because a variety of human tumors, including brain tumors, contain high levels of MGMT activity, we investigated the effect of antisense ribonucleic acid (RNA) complementary to MGMT messenger RNA on ACNU resistance in tumor cells. METHODS: We established a stable ACNU-resistant clone, C6AR, from the rat glioma cell line C6 exposed to a stepwise increasing concentration of ACNU. We transfected a plasmid deoxyribonucleic acid-encoding antisense MGMT RNA under the control of the human metallothionein promoter into C6AR cells and determined the effect of the antisense RNA on ACNU resistance of tumor cells by a colony-forming efficiency assay. RESULTS: C6AR cells expressed abundant MGMT messenger RNA, although the transcription level of the MGMT gene in parental C6 cells was below the lower limits of detection under the same assay conditions. ACNU resistance of C6AR cells was significantly repressed by transfected gene-dependent antisense MGMT RNA expression that resulted in decreased survival of the tumor cells. CONCLUSION: ACNU resistance resulting from the expression of MGMT in rat glioma cells is significantly overcome by the expression of antisense MGMT RNA. This result suggests that the antisense MGMT RNA system might be a useful strategy for overcoming ACNU resistance in the treatment of intractable malignant gliomas.

Animals↗
PubMed1997

HIV and the primary care physician in Japan.

Primary care physicians in Japan must provide comprehensive medical care and counseling for persons both infected with and at risk for HIV/AIDS. Despite existing activities and education programs, HIV case numbers continue to rise in Japan, and only a limited number of hospitals and physicians offer care to those with HIV/AIDS. Some doctors in Japan refuse to accept patients with HIV/AIDS because of the complex treatment often involved, prejudice regarding AIDS, and fear of transmission. Other impediments to effective treatment of HIV/AIDS in Japan include insufficient risk evaluation through outpatient services, lack of privacy, and restrictions and policies at medical facilities. If Japan's primary care physicians cannot participate in caring for those with HIV/AIDS, it will be impossible for every patient with HIV/AIDS to receive correct and adequate medical care. To enable primary care physicians to provide high-quality service and prevention counseling to those with HIV/AIDS, prejudice, fear, and logistic impediments must be eradicated. Comprehensive practice guidelines that protect patients' rights and privacy should be established immediately. The guidelines should direct primary care physicians toward a logical and proper approach to HIV/AIDS care by addressing fundamental treatment and effective prevention counseling as well as the social problems surrounding HIV/AIDS. In addition, research on the general knowledge level and prevalent attitudes among Japan's primary care physicians regarding HIV/AIDS would clarify which specific issues the guidelines should emphasize.

Ambulatory Care↗
PubMed1997

A functional role for death proteases in s-Myc- and c-Myc-mediated apoptosis.

Upon activation, cell surface death receptors, Fas/APO-1/CD95 and tumor necrosis factor receptor-1 (TNFR-1), are attached to cytosolic adaptor proteins, which in turn recruit caspase-8 (MACH/FLICE/Mch5) to activate the interleukin-1 beta-converting enzyme (ICE)/CED-3 family protease (caspase) cascade. However, it remains unknown whether these apoptotic proteases are generally involved in apoptosis triggered by other stimuli such as Myc and p53. In this study, we provide lines of evidence that a death protease cascade consisting of caspases and serine proteases plays an essential role in Myc-mediated apoptosis. When Rat-1 fibroblasts stably expressing either s-Myc or c-Myc were induced to undergo apoptosis by serum deprivation, a caspase-3 (CPP32)-like protease activity that cleaves a specific peptide substrate, Ac-DEVD-MCA, appeared in the cell lysates. Induction of s-Myc- and c-Myc-mediated apoptotic cell death was effectively prevented by caspase inhibitors such as Z-Asp-CH2-DCB and Ac-DEVD-CHO. Furthermore, exposing the cells to a serine protease inhibitor, 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF), also significantly inhibited s-Myc- and c-Myc-mediated apoptosis and the appearance of the caspase-3-like protease activity in vivo. However, AEBSF did not directly inhibit caspase-3-like protease activity in the apoptotic cell lysates in vitro. Together, these results indicate that caspase-3-like proteases play a critical role in both s-Myc- and c-Myc-mediated apoptosis and that caspase-3-like proteases function downstream of the AEBSF-sensitive step in the signaling pathway of Myc-mediated apoptosis.

Animals↗
PubMed1997

Medical decisions concerning the end of life: a discussion with Japanese physicians.

OBJECTIVES: Life-sustaining treatment at the end of life gives rise to many ethical problems in Japan. Recent surveys of Japanese physicians suggested that they tend to treat terminally ill patients aggressively. We studied why Japanese physicians were reluctant to withhold or withdraw life-support from terminally ill patients and what affected their decisions. DESIGN AND PARTICIPANTS: A qualitative study design was employed, using a focus group interview with seven physicians, to gain an in-depth understanding of attitudes and rationales in Japan regarding medical care at the end of life. RESULTS: Analysis revealed that physicians and patients' family members usually make decisions about life-sustaining treatment, while the patients' wishes are unavailable or not taken into account. Both physicians and family members tend to consider withholding or withdrawing life-sustaining treatment as abandonment or even killing. The strongest reason to start cardiopulmonary resuscitation- and to continue it until patients' family members arrive-seems to be the family members' desire to be at the bedside at the time of death. All physicians participating in our study regarded advance directives that provide information as to patients' wishes about life-sustaining treatment desirable. All expressed concern, however, that it would be difficult to forego or discontinue life-support based on a patient's advance directive, particularly when the patient's family opposed the directive. CONCLUSION: Our group interview suggested several possible barriers to death with dignity and the appropriate use of advance directives in Japan. Further qualitative and quantitative research in this regard is needed.

Adult↗
PubMed1996

Regional distribution of heparin-binding epidermal growth factor-like growth factor mRNA and protein in adult rat forebrain.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a recently described member of the EGF family that binds to and stimulates phosphorylation of the EGF receptor (EGFR). In this study, we examined the cellular localization of HB-EGF gene transcripts and protein in adult rat forebrain. In situ hybridization studies showed that neurons in various regions, including cortex, hippocampus, and deep structures, express HB-EGF mRNA. Positively labeled cells were also present in white matter, which suggests that both neurons and glia express HB-EGF mRNA. Immunohistochemical studies with an antibody specific to proHB-EGF, a transmembrane form of HB-EGF, demonstrated ubiquitous immunoreactivity in neurons and glial cells in white matter. In view of the wide expression of its cognitive receptor, EGFR, in central nervous system neurons, our results suggest that HB-EGF is an endogenous ligand for EGFR in the central nervous system and may play an important role in physiological conditions.

Animals↗
PubMed1996

Increased expression of schwannoma-derived growth factor (SDGF) mRNA in rat tumor cells: involvement of SDGF in the growth promotion of rat gliomas.

Schwannoma-derived growth factor (SDGF) is a member of the epidermal growth factor (EGF) family, having mitogenic activity on rat astrocytes, fibroblasts and Schwann cells. The SDGF gene is significantly expressed in the newborn rat lung and in the adult rat sciatic nerve. However, except for one rat schwannoma cell line, from which SDGF and its cDNA were isolated, nothing is known about SDGF expression in established tumor cell lines. We examined the expression level of the SDGF gene in a variety of rat tumor cell lines by Northern blotting and found that it was increased in 11 of 25 established lines. The most abundant SDGF mRNA, which was about 50-fold higher than in the newborn rat lung, was expressed in rat liver adenoma dRLa74 cells. In rat glioma cell lines, such as C6, 9L and T9, and in the rat hepatoma dRLh84 and H411E cells, the SDGF expression level was about 10-fold higher than in the newborn rat lung. In 8 of 13 cell lines expressing SDGF mRNA, the EGF receptor (EGFR) gene, the product of which is regarded as a functional receptor of SDGF, was co-expressed. In addition, transfected gene-dependent anti-sense SDGF RNA expression under the control of the human metallothionein promoter significantly suppressed the in vitro growth as well as in vivo tumorigenicity of 9L glioma cells. Our results suggest that SDGF acts as an autocrine growth factor in the development and growth of rat tumors such as gliomas.

Amphiregulin↗
PubMed1996

Myc-mediated apoptosis.

Mammalian cells contain an intron-less myc gene, such as the rat s-myc gene and human myc L2 gene, which are expressed in rat embryo chondrocytes and human testis, respectively. Our recent findings demonstrated that s-Myc expression suppresses the growth activity and tumorigenicity of glioma cells, indicating that s-Myc acts as a negative regulator in tumor growth. In addition, we found that s-Myc overexpression can effectively induce apoptotic cell death in human and rat glioma cells without serum deprivation, which is distinct from c-Myc-mediated apoptosis.

Amino Acid Sequence↗
PubMed1996

Clinical and histopathological analysis of proliferative potentials of recurrent and non-recurrent meningiomas.

Proliferative potentials of meningiomas from 127 patients were examined immunohistochemically using the anti-Ki-67 monoclonal antibody, MIB-1, on paraffin sections, and the correlation among MIB-1 staining index (SI), histopathological finding, and clinical course of the disease was analyzed retrospectively. The mean MIB-1 SI of 50 male patients with meningioma was 5.5%, whereas that of 77 female patients was 2.7%. Higher MIB-1 SI were observed for younger patients. These age- and sex-related differences in MIB-1 SI were statistically significant. The patients were assigned to one of three groups: those with non-recurrent meningioma (n = 73); those with recurrent meningioma in whom the specimens obtained during the initial surgery were used to calculate the MIB-1 SI (n = 21); and those with recurrent meningioma for whom the specimens obtained during the surgery for recurrent tumors were used to calculate the MIB-1 SI (n = 33). The mean MIB-1 SI in these patients were 1.6%, 3.6%, and 8.8%, respectively, and there were statistically significant differences among these three groups. Statistical analyses reveal that meningiomas with a MIB-1 SI of 3% or more have a significantly high tendency for recurrence during the clinical courses, especially within the first 10-year follow-up periods. Moreover, there is statistically significant correlation between MIB-1 SI and recurrence in each Simpson's grade. The time interval to the next recurrence for recurrent meningiomas is associated with the proliferative potential represented by the MIB-1 SI, and a correlation equation has been proposed to predict the date of the next recurrence. Analyses on cellularity of meningiomas revealed no statistically significant difference in cellularity between non-recurrent and recurrent meningiomas. There was no statistically significant relationship between cellularity and MIB-1 SI of meningiomas. In conclusion, examination on proliferative potentials of meningiomas using MIB-1 SI is very important for biological and histopathological analyses and the prediction of future recurrence.

Adult↗