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Biomedical subjects

A Asai

Publications and source records attributed to A Asai.

At least 109 records · Page 6Linked to original sources
PubMed1996

Up-regulation of c-myc gene expression following focal ischemia in the rat brain.

Changes in gene expression including that of c-fos occur following cerebral ischemia. Proto-oncogenes c-myc and s-myc and oncosuppressor gene p53 are known to induce apoptosis in some types of cells, whereas proto-oncogene bcl-2 inhibits apoptosis. Possible induction of mRNAs for c-myc, N-myc, s-myc, c-fos, p53 and bcl-2 was examined following focal ischemia in the rat anterior cortex, hippocampus, thalamus and cerebellum by Northern blot analysis. Animals were decapitated 1, 2, 6, 12, and 24 hours following the left middle cerebral artery (MCA) occlusion. In sham-operated control rats, the mRNAs for c-myc, N-myc, c-fos and p53 were present in the anterior cortex, hippocampus, thalamus on both sides, and in the cerebellum, whereas those for s-myc and bcl-2 were not. The c-myc gene expression was rapidly and markedly induced by the MCA occlusion in the ipsilateral anterior cortex, hippocampus and thalamus in a time-dependent manner. In these regions, the c-fos gene expression was also induced as early as 1 hour after the MCA occlusion. The p-53 mRNA was induced in the ipsilateral hippocampus at 24 hours after MCA occlusion. In contrast, mRNAs for N-myc, s-myc and bcl-2 were not induced following MCA occlusion. These results indicate a possibility that high-level expression of the c-myc gene may be involved in the ischemic cellular events including apoptosis.

Animals↗
PubMed1996

Pharmacotherapeutic effects of toki-shakuyaku-san on leukorrhagia in young women.

Toki-shakuyaku-san is a traditional Chinese herbal prescriptions that is composed of 6 herbal plants, i.e., peony root, atractylodes lancea rhizome, alisma rhizome, hoelen, cnidium rhizome and Japanese angelica root. Administration with Toki-shakuyaku-san normalized irregular menstrual cycle, healed cervical pseudo-erosion and reduced leukorrhagia in young women who had insufficient luteal function.

Adult↗
PubMed1996

Synthesis and antitumor activity of duocarmycin derivatives: modification of segment A of duocarmycin B2.

Several A-ring pyrrole derivatives of duocarmycin B2 were synthesized effectively from the 3-hydroxy compounds by utilizing an interesting acid-catalyzed rearrangement, their anticellular activity was preliminarily evaluated by assays of growth inhibition of HeLa S3 cells (in vitro) and antitumor activity against murine sarcoma 180 (in vivo). The 8-O-N,N-dialkylcarbamoyl derivatives of the A-ring pyrrole compound showed remarkably potent in vivo antitumor activity, superior to that of duocarmycin B2. these derivatives were subjected to further biological evaluation. They exhibited potent antitumor activity toward murine solid tumors including M5076 sarcoma, B-16 melanoma and Colon 26 adenocarcinoma. Their most noteworthy feature was their efficacy against various human xenografts including LC-6 (lung), St-4 (stomach), and Co-3 (colon).

Animals↗
PubMed1996

Disinfection of removable dentures using ozone.

Over time, removable dentures tend to become unsanitary and emit unpleasant odors, and oral mucosa sometimes becomes inflamed or denture stomatitis is caused by denture plaque. Recently, various cleaning products designed to keep removable dentures sanitary have appeared on the market. It is known that denture plaque is mainly composed of Candida albicans (C. albicans), and that ozone seems to inhibit these micro-organisms. Accordingly, a denture cleaner using ozone bubbles (ozone concentration of about 10 ppm) was considered as clinically appropriate because of its strong disinfecting and deodorizing power, and high biological safeness. The effectiveness of this cleaner against C. albicans was investigated using. Results showed that C. albicans decreased to about 1/10 after 30 min and to 1/10(3) after 60 min.

Candida albicans↗
PubMed1995

Attitudes of Japanese and Japanese-American physicians towards life-sustaining treatment.

Doctors in different countries have different approaches to bioethical problems. We studied how attitudes to life-sustaining treatment for terminally ill patients differ in Japan and the USA by administering a questionnaire to Japanese (136) and Japanese-American (77) physicians. In a series of clinical scenarios the questionnaire asked what life-sustaining interventions the doctors would recommend to a patient with metastatic gastric cancer. Most Japanese physicians would recommend blood transfusions for gastrointestinal bleeding (74%), total parenteral nutrition for malnutrition (67%), and vasopressors for life-threatening hypotension (61%) when the patient did not know of his diagnosis and outlook. Significantly fewer Japanese physicians would want these interventions for themselves: 29% would want transfusion, 36% would want total parenteral nutrition, and 25% would want vasopressors. 36% of Japanese physicians would override the explicit request of a competent moribund cancer patient to withdraw all life-support. By contrast, among Japanese-American physicians only 42% would recommend blood transfusions, 33% total parenteral nutrition, and 34% vasopressors to a terminally ill cancer patient who did not know of his diagnosis or outlook. Cross-cultural studies in medical ethics can help physicians and the public in different countries to take a fresh look at accepted practices and the ethical reasons behind them.

Adult↗
PubMed1995

Elevated levels of eukaryotic translation initiation factor eIF-4E, mRNA in a broad spectrum of transformed cell lines.

Translation initiation factor eIF-4E, which binds to the 5' cap structure of eukaryotic mRNAs, is believed to play an important role in the control of cell growth. Over-expression of eIF-4E in fibroblasts results in their malignant transformation. However, no information on eIF-4E expression in established transformed cell lines has been available. We report here that a variety of tumor cell lines, chemically, virally and oncogenically transformed, exhibit elevated levels of eIF-4E mRNA expression as compared to their normal counterparts. Overexpression of eIF-4E, which is normally rate-limiting in protein synthesis, may stimulate the translation of regulatory and oncogenic proteins involved in transformation.

Animals↗
PubMed1995

Investigation of chemoresistance-related genes mRNA expression for selecting anticancer agents in successful adjuvant chemotherapy for a case of recurrent glioblastoma.

BACKGROUND: Glioblastoma multiforme represents one of the most malignant forms of primary intracranial tumors, often intractable to multimodality of treatment including chemotherapy. The unsatisfactory results of chemotherapy are chiefly attributed to chemoresistance. Since various molecules that could confer drug resistance have been elucidated, screening of the amount of such molecules in the tumor cells could provide possibilities for predicting their chemoresistance beforehand and help select more effective drugs. METHODS: We present a 45-year-old woman with recurrent glioblastoma multiforme in the cerebellum and invading the brain stem, treated successfully by postoperative chemotherapy. In this patient, anticancer drugs were determined by measurements of mRNA expression of chemoresistance-related genes, such as O6-methylguanine-DNA methyltransferase (MGMT), mdr1, glutathione S-transferase (GST)-pi, and metallothionein (MT) in the resected tumor. RESULTS: Northern blot analysis demonstrated the moderate mRNA level of MGMT, a major molecule causing ACNU (1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitroso ure a hydrochloride) resistance. On the other hand, expression levels of mdr1 which codes the P-glycoprotein responsible for multidrug resistance, and GST-pi, a detoxification enzyme, were low. Transcript of MT, another thiol containing molecule for cellular detoxification possibly associated with cisdiamminedichloroplatinum(II) (CDDP) resistance, was only faintly detectable. Postoperatively, the patient was treated initially with intravenous administration of ACNU and etoposide (VP16), resulting in a minor response of tumor regression. For maintenance therapy, we changed ACNU to CDDP according to the findings of the Northern blot analysis. Consequently, the residual tumor showed a marked response and almost disappeared after two courses of systemic chemotherapy with CDDP and VP16. CONCLUSIONS: The successful tumor regression in this case suggests that Northern blot analysis on expression of these chemoresistance-related genes in tumor tissues could provide beneficial information for determination of optimal anticancer agents to improve the efficacy of chemotherapy.

Antineoplastic Agents↗
PubMed1995

Cervical flexion myelopathy associated with cervical spina bifida occulta--case report.

A 16-year-old boy presented with segmental muscular atrophy of the bilateral distal upper extremities. Cervical spine x-ray films showed occult spina bifida from C-1 to T-1 associated with an abnormal long club-like bone located parallel to the epidural space between C-5 and C-7. In neck flexion, the cervical spinal cord was stretched and compressed to the posterior aspect of the vertebral body. Moreover, the dorsally placed abnormal bone migrated ventrally, indenting the dorsal portion of the spinal cord. This is quite an unusual case of so-called "flexion myelopathy," aggravated by the abnormal bone located dorsally.

Adolescent↗
PubMed1995

s-Myc acts as a transcriptional activator and its sequence-specific DNA binding is required for induction of programmed cell death in glioma cells.

We previously reported that s-Myc expression effectively induces programmed cell death (PCD) by apoptosis in glioma cells that express only mutated p53. To determine the molecular mechanism of s-Myc-induced PCD, we examined the correlation between transcriptional activation of s-Myc and its ability to induce PCD. Using a reporter plasmid having an upstream promoter region containing four repeats of the hexanucleotide CACGTG, we found that s-Myc can activate transcription of a reporter gene from this plasmid. Two mutated forms of s-Myc protein, s-MycCKII and s-MycmBR, were created. While s-MycCKII whose casein kinase (CK) II cognate sequence was restored in the internal acidic domain activated transcription as efficiently as wild-type s-Myc and induced PCD in glioma cells, s-MycmBR having a mutated basic region unable to bind the CACGTG motif did not. These findings suggest that transactivation activity of s-Myc through sequence-specific DNA binding may be indispensable for induction of PCD but that lack of a CK-II cognate sequence in the internal acidic domain may have little effect on these functions of s-Myc.

Journal Article↗
PubMed1995

Should physicians tell patients the truth?

The medical literature suggests that most patients want to be told the truth about a diagnosis of cancer. Despite this evidence of their patients' wishes, physicians in many countries still hesitate to disclose this and other diagnoses. Physicians frequently ignore their patients' wishes when they consider the appropriateness of truth telling. A complete shift from nondisclosure to mandatory disclosure without considering patients' preferences may lead to serious harm to patients who do not want to be told the truth. Because physicians cannot satisfactorily treat patients without knowing their preferences toward disclosure of a diagnosis, I propose a simple strategy to break this long-standing ethical dilemma--physicians must develop the habit of inquiring about their patients' preferences.

Humans↗
PubMed1995

[MRI of traumatic anosmia].

On MRI, the authors were able to demonstrate the contused lesions of bilateral rectal gyri near the crista galli in all of five cases of traumatic anosmia. Thin slice coronal and sagittal images of MRI were very useful for detecting the lesions. Conventional CT scans failed to demonstrate the lesions in 3 out of the 5 cases, but, even in these cases, MRI was able to clearly depict the contused lesions of bilateral rectal gyri. Therefore, the depicted lesions of bilateral rectal gyri on MRI can be evidence of traumatic anosmia and this may be very significant in medico-legal cases.

Adolescent↗
PubMed1995

Abundant expression of translation initiation factor EIF-4E in post-meiotic germ cells of the rat testis.

BACKGROUND: Eukaryotic translation initiation factor EIF-4E is a key component in the regulation of translational efficiency of MRNAs and its increased expression may accelerate cell growth and division. EIF-4E has the potential to transform rat embryo fibroblast cells by cooperation with v-Myc or adenovirus E1A. Our previous study showed that a variety of tumor cells examined exhibited elevated levels of eIF-4E gene expression. Thus it is thought that overexpression of EIF-4E can result in aberrant growth and cell transformation. EXPERIMENTAL DESIGN: To characterize rat EIF-4E, a clone containing rat eIF-4E cDNA was isolated from a rat testis cDNA library by screening with a synthetic probe prepared by the reverse transcription-polymerase chain reaction (RT-PCR) method. Based on the conserved nucleotide sequences between mouse and human eIF-4E cDNA, two oligonucleotide primers for RT-PCR were synthesized chemically. The cloned cDNA was sequenced and used as a probe for analysis of the expression level of eIF-4E mRNA in normal, differentiated rat tissues by Northern blot analysis. In situ hybridization analysis with digoxigenin-labeled antisense eIF-4E RNA as a probe was carried out to identify the eIF-4E-expressing sites in rat tissues. In addition, to analyse the phosphorylation level of EIF-4E, the proteins were fractionated from rat tissues by affinity column chromatography followed by isoelectric focusing (IEF)-gel electrophoresis. RESULTS: The nucleotide sequence of the eIF-4E cDNA is highly conserved in human, rat, and mouse. Extraordinarily elevated expression, more than 50-fold compared with that in the adult rat prostate, of eIF-4E was observed in testicular germ cells of rats of reproductive age, which was much greater than that in any tumor cell lines examined so far. The amount of EIF-4E fractionated from the adult rat testis was approximately 10 times higher than that from the adult rat liver. At least half of the purified testicular EIF-4E proteins were phosphorylated, a ratio similar to that in other rat tissues such as liver. In situ hybridization analysis demonstrated that elevated expression of eIF-4E mRNA was mainly observed in post-meiotic germ cells. CONCLUSIONS: Full activity of EIF-4E in translation requires the phosphorylation of the protein on a specific serine residue. Thus the elevated level of EIF-4E observed in the adult rat testis should be reflected in increase of the functional activity of EIF-4E. Based on the results of in situ hybridization analysis and characterization of EIF-4E, it was concluded that abundant EIF-4E in the testis may play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development.

Amino Acid Sequence↗
PubMed1994

Characteristics of antitumor activity of KW-2189, a novel water-soluble derivative of duocarmycin, against murine and human tumors.

Methyl(1S)-1-bromomethyl-7-methyl-5-[(4-methylpiperazinyl)-carb onyloxy]- 3-[(5,6,7-trimethoxy-2-indolyl)-carbonyl]-1,2-dihydro-3H-pyrolo[3, 2-e] indole-8-carboxylate hydrobromide (KW-2189), a novel derivative of duocarmycin B2, was selected for extensive evaluation based on its improved antitumor activity, water solubility, and stability in the culture medium, as compared with duocarmycin B2. Although the in vitro cell growth-inhibitory activity of KW-2189 was less potent than that of duocarmycin B2, it significantly inhibited the growth of five murine solid tumors including Colon 26 adenocarcinoma, Colon 38 adenocarcinoma, and B16 melanoma in vivo. KW-2189 was also effective against murine P388 leukemia and L1210 leukemia not only by local administration (i.p.-i.p. system), but also by systemic administration (i.p.-i.v. or i.v.-i.v. system). The most remarkable feature of KW-2189 was its efficacy against various human xenografts, which was observed in 14 tumors among 16 tested tumors including drug-insensitive tumors by single i.v. administration. Tumor regression was observed in mice bearing LC-6 lung, St-4 and St-40 stomach, Li-7 liver, PAN-2 pancreas, and MX-1 breast carcinomas. In many cases, the activities of KW-2189 were more than those of clinically active agents, mitomycin C, Adriamycin, cisplatin, and cyclophosphamide. Delayed lethal toxicity, which was reported in mice treated with CC-1065 whose structure was similar to KW-2189, was not observed in mice treated with KW-2189. KW-2189 inhibited DNA synthesis more significantly than RNA or protein synthesis, although DNA strand breaks were not observed. KW-2189 was activated by porcine liver esterase, mouse liver homogenate or Hep G2 homogenate, and DU-86-DNA adducts were detected in KW-2189-treated HeLa S3 cells, suggesting that KW-2189 was converted to DU-86 in the cells. These results indicate that KW-2189 is an interesting candidate for further development as a novel antitumor agent.

Animals↗
PubMed1994

The reversible DNA-alkylating activity of duocarmycin and its analogues.

Intact drugs with spirocyclopropylhexadienone moieties can be regenerated from the covalent DNA adducts induced by antitumor antibiotics duocarmycin (DUM) A, SA and some DUMA analogues in neutral aqueous solution. We detected the reversible nature of DUMs by determination of the antimicrobial activity and cytotoxicity of DUM-DNA adducts. All of the adducts selectively inhibited the growth of a sensitive strain of Bacillus but not that of the wild type strain, a property of parent DUM and its analogues. Most of the DNA adducts were also cytotoxic to HeLa S3. These results suggested that active drugs can be released from their covalent DNA adducts under these biological assay conditions. Regeneration of intact drugs was quantitatively analyzed by HPLC and the amount of free drug released from DNA adducts revealed that the rate and efficiency of this reversal were dependent on structural variables among the drugs. The differences in rates of reversibility were correlated with the biological activity of DUMs. The effect of pH, temperature and salt concentration on the regeneration of drugs from their DNA adducts suggest a catalytic role of double-helical DNA on the reversal pathway.

Alkylating Agents↗