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Biomedical subjects

M Sugihara

Publications and source records attributed to M Sugihara.

At least 37 records · Page 2Linked to original sources

Decreased expression of telomerase-associated RNAs in the proliferation of stem cells in comparison with continuous expression in malignant tumors.

Telomerase, an enzyme associated with cellular immortality, is expressed by malignant tumor and stem cells, especially germ cells. Normal somatic cells, however, usually do not express telomerase. In the malignant tumor, deregulation of telomerase is thought to facilitate tumorigenesis and cellular immortality by providing cancer cells unlimited proliferation capacity. We investigated the relationship between proliferation activity and in situ expression of the telomerase RNA component (human telomerase RNA component, hTERC). In addition, in situ hybridization of the telomerase-associated proteins (telomerase-associated protein 1, TEP1; human telomerase reverse transcriptase, TERT), and MIB-1 immunohistochemistry for proliferation activity were performed, using the malignant tumors of adenocarcinoma, squamous cell carcinoma, and malignant lymphoma, and somatic tissues of testis, endometrium, stomach, skin, and lymph nodes. In the somatic tissues, the stem cells expressed telomerase-associated RNA, but no proliferation activity. When the proliferation activity of the stem cells increased, however, the telomerase-associated expressions decreased. In the malignant tumors, both proliferation activity and expression of the telomerase-associated RNA significantly increased. Deregulation of telomerase, in addition to proliferation activity, is associated with tumorigenesis.

Antigens, Nuclear↗

Pitx2, a bicoid-type homeobox gene, is involved in a lefty-signaling pathway in determination of left-right asymmetry.

Signaling molecules such as Activin, Sonic hedgehog, Nodal, Lefty, and Vg1 have been found to be involved in determination of left-right (L-R) asymmetry in the chick, mouse, or frog. However, a common signaling pathway has not yet been identified in vertebrates. We report that Pitx2, a bicoid-type homeobox gene expressed asymmetrically in the left lateral plate mesoderm, may be involved in determination of L-R asymmetry in both mouse and chick. Since Pitx2 appears to be downstream of lefty-1 in the mouse pathway, we examined whether mouse Lefty proteins could affect the expression of Pitx2 in the chick. Our results indicate that a common pathway from lefty-1 to Pitx2 likely exists for determination of L-R asymmetry in vertebrates.

Animals↗

Nodal T-cell lymphoma in an HTLV-I-endemic area: proviral HTLV-I DNA, histological classification and clinical evaluation.

Adult T-cell leukaemia/lymphoma (ATLL) is a human malignancy associated with human T-cell leukaemia virus type I (HTLV-I). The histology usually indicates a pleomorphic type, but is not consistent. To clarify the relationship between the histological classification and prognosis in ATLL, and to confirm the significance of clonal HTLV-I integration, we reclassified 572 cases with nodal T-cell lymphoma in which the T-cell phenotype and/or genotype was confirmed. In all cases the clonal integration of HTLV-I proviral DNA in the lymph nodes was examined by Southern blot analysis. In addition, anti-ATL antigen (ATLA) determination in the serum or PCR analysis of HTLV-I pX amplification in lymph nodes was also performed. 66/313 (21%) cases with ATLA had no evidence of clonal HTLV-I integration. 572 cases were classified into three groups: (A) cases with clonal integration (247 cases), (B) cases with ATLA without clonal integration of HTLV-I proviral DNA (66 cases), (C) cases without ATLA (259 cases). Histologically, groups B and C frequently demonstrated large cell type and angioimmunoblastic lymphadenopathy with dysproteinaemia (AILD) type; however, group A tended to show a pleomorphic type. Clinically, group A showed a poorer prognosis than groups B and C. In conclusion, group A cases were defined as ATLL (HTLV-I-associated T-cell lymphoma), whereas group B was classified as T-cell lymphoma, which had coincidently occurred in HTLV-I infected carriers. The simplified classification of REAL indicated clinical outcome: the prognosis of ATLL was poor, the unspecified type was intermediate, whereas the other types of lymphoblastic, AILD and anaplastic large cell type were all relatively favourable.

Blotting, Southern↗

Clinicopathological study of severe chronic active Epstein-Barr virus infection that developed in association with lymphoproliferative disorder and/or hemophagocytic syndrome.

Chronic active Epstein-Barr virus (CAEBV) infection has been previously reported to be sometimes associated with an aggressive clinical course. However, the role of EBV in the CAEBV is not well clarified. A retrospective study was performed on nine adult and five child patients (eight males and six females). Histologically, at first admission, the presence of neoplastic lesions could not be confirmed. The lymph nodes in half of all cases revealed paracortical hyperplasia with transformed lymphocytes (hyperplastic type). Half of the cases showed non-suppurative necrosis and an increased number of histiocytes with phagocytosis (histiocytic type). Activated histiocytes with lymphokine positivity were frequently detected in the histiocytic type. In the phenotypical study, 10 of the examined 11 cases showed increased numbers of natural killer (NK) cells and/or CD8-positive T lymphocytes. In situ hybridization (ISH) showed EBV-infected lymphoid cells, but the number of EBV-infected cells varied. Double-labeling immunochemistry/ISH demonstrated EBV-infected T cells, including NK cells, but not B cells. In addition, three cases showed a monoclonal dissemination of EBV terminal repetitive sequence (TR), and two cases showed oligoclonal dissemination. From those findings, monoclonal, oligoclonal and polyclonal populations of EBV-infected T or NK cells were considered to be present in CAEBV states. During the clinical course, 12 of the 14 cases died within 5 years. Six cases died from EBV-associated hematopoietic tumors (histiocytic tumor, T cell lymphoma, B cell lymphoma, plasmacytoma, and NK cell leukemia); one from non-EBV-associated acute myelogenous leukemia, and five due to hemophagocytic syndrome. The examined EBV-associated hematopoietic tumors showed monoclonal EBV terminal repetitive sequences. There is a possibility that the monoclonal dissemination of EBV-infected cells develops from oligoclonal or polyclonal EBV-infected cells. And active histiocytes with lymphokine positivity were frequently detected in the cases with histologically histiocytic type. These findings seem to be related with the causes of death due to hemophagocytic syndrome.

Adolescent↗

[A guide for the timing of peripheral blood stem cell harvest in patients with lung cancer].

Harvest of peripheral blood stem cells (PBSC) was performed 57 times in 17 lung cancer patients after standard-dose chemotherapy (cisplatin, etoposide) supplemented with granulocyte-colony stimulating factor (G-CSF). In every case, more than 1.5 x 10(6)/kg CD 34+ cells were collected by 2-5 apheresis. Statistical significance was noted between peripheral leukocyte counts (WBC) and collected CD 34+ cell counts (p = 0.0298), between peripheral platelet counts and collected CD 34+ cell counts (p = 0.0009), and between the peripheral immature granulocyte ratio and collected CD 34+ cell counts (p < 0.0001). Because of the remarkable relationship between collected CD 34+ cell counts and peripheral WBC counts, peripheral platelet counts and the peripheral immature granulocyte ratio, these parameters were useful for determining the correct timing of PBSC harvest.

Adult↗

Polyostotic fibrous dysplasia. A long-term follow up of 8 patients.

Eight patients who had polyostotic fibrous dysplasia were followed up for more than 10 years. One had the Albright syndrome. Two of 3 proximal femoral lesions which were treated before puberty by either curettage and bone grafting or by osteotomy, developed progressive deformity during the growth period. One of 2 proximal femoral lesions treated by curettage and bone grafting after the age of 18 also developed a deformity. Two tibial lesions operated on at the age of one and 30 years remained stable. The histological findings showed more active lesions in young patients compared with adults.

Adolescent↗

Development of oral dosage form for elderly patients: use of agar as base of rapidly disintegrating oral tablets.

Rapidly disintegrating tablets as an oral dosage form for elderly patients with impaired swallowing were investigated using agar powders (AG) or treated agar powders (TAG). When the compression pressure was changed from 0.4 to 2.0 ton/cm2, the disintegration time of AG tablets increased from about 60 to about 160s, and the hardness significantly increased from 3 to 13 kgw. The disintegration time and hardness of the TAG tablets were scarcely affected by the compression pressure: the disintegration time was 5--6s, and the hardness was 2--3 kgw. The rapid disintegration of the TAG tablets seemed due to the rapid water penetration into the tablet resulting from the large pore size and large overall pore volume. It was found that rapidly disintegrating oral tablets with proper hardness can be prepared using TAG.

Absorption↗

New oral dosage form for elderly patients: preparation and characterization of silk fibroin gel.

The pharmaceutical utility of silk fibroin as a possible material for an oral dosage form for elderly patients was investigated. Silk fibroin gel (SFG) was prepared from its aqueous solution. The gel formation was studied as a function of adjusted pH and concentration of silk fibroin (SF). On the basis of Fourier transform infrared spectroscopy of SFG, the transition from the random coil to the beta-structure was observed. The rate of gelation was sufficiently accelerated by the addition of glycerol to the SF aqueous solution. The glycerol content also affected the rate of gelation of the SF solution. Rheological properties of SFG were evaluated using a creep meter. The SF content and/or glycerol content affected the breaking stress of SFG. Moisture desorption from SFG was retarded with an increase in glycerol content. It was found that SFG was able to be prepared at room temperature (20 +/- 5 degrees C), and the SF content and glycerol content affected the formation and physicochemical properties of SFG.

Administration, Oral↗

New oral dosage form for elderly patients. II. Release behavior of benfotiamine from silk fibroin gel.

Silk fibroin gel (SFG) containing benfotiamine (BTMP) was prepared. The release behavior of BTMP from SFG was studied as a function of silk fibroin (SF) content and glycerol content, and the influence of the existence of beta-cyclodextrin (beta-CD) on the physicochemical properties of SFG were investigated. The release rate of BTMP from SFG was retarded by an increase in SF concentration. The addition of beta-CD affected both the release properties and rheological properties of the SFG. It was found from the results of the "paddle-bead method" that the release profiles of BTMP from SFG were inversely proportional to the SFG firmness.

Adjuvants, Immunologic↗

Improvement of coronary vasomotion with eicosapentaenoic acid does not inhibit acetylcholine-induced coronary vasospasm in patients with variant angina.

Impaired function of the endothelium may be a mechanism of the coronary vasospasm induced by acetylcholine. We examined whether purified eicosapentaenoic acid (EPA), a major component of fish oil, improves the coronary vasomotion in response to acetylcholine, and the effect of purified EPA on acetylcholine (ACh)-induced coronary vasospasm in 22 patients with variant angina. ACh was infused into the coronary artery both before and after 4 months of EPA treatment (EPA 1.8 g/day, n = 12). In the control group (n = 10) that did not receive EPA, the response of the coronary diameter to ACh did not change over time. In the EPA-treated group, the cholinergic response in non-spastic sites changed from vasoconstriction to vasodilation, while ACh-induced coronary vasospasm persisted at the spastic sites. Therefore, EPA treatment improved the coronary vasomotor responsiveness to ACh, but did not inhibit ACh-induced coronary vasospasm.

Acetylcholine↗

[Advertisements in newspapers and magazines about patent medicines in the Meji era (The first dissertation) (Part 1)].

In February 1869, the government first permitted newspapers to be published. The Yokohama-mainichi, the Tokyo-nichi-nichi, the Nisshin-shinjishi and so on were published. The traders of medicine quickly turned their attention to the newspapers. Jihei Morita put an advertisement about "Houtan" in the newspaper issued in July in the 4th year of the Meiji era (1871) and Ginko Kishida put an advertisement about "Seikisui" in the Mainichi in Yokohama dated August 18th in the 4th year of the Meiji era. After that, the traders of medicine advertised in newspapers one after another, and the contents of advertisements were expressly the efficacy of medicine. As Yukichi Fukuzawa doubted if the trend was really desirable, he carried his comment against the trend in the Katei Sodan published by Keio-Gijuku, but the contents of advertisements were not changed. Advertisements emphasising the efficacy of medicine were prominent.

Advertising↗

[Advertisements in newspapers and magazines about patent medicines in the Meiji era (The first dissertation) (Part 2)].

On January 20th of the 10th year of the Meiji era (1877) the government enforced the laws regulating patent medicines. Since then patent medicines were frequently attacked in the newspapers. Abuses of patent medicines became the target of criticism. Yukichi Fukuzawa had carried his comments against abusing patent medicines in "Minkanzasshi" for 4 days from March 24th in the 11th year of the Meiji era. Abuses of patent medicines prevented medical science from progressing. He pointed out the responsibility of newspapers which printed advertisement of ineffective patent medicines. "The kanayomi" which was a small newspaper company refuted his comments. Jihei Morita published the magazine "Houtan" in person, and he ran many advertisements about patent medicines. In October in the 15th year of the Meiji era, the law, which imposed a tax on patent medicines was enacted. In addition to the censure against patent medicines were an account in the newspaper successively. However, at the same time, these accounts had serious consequences the traders of medicine and they went to law by the reason which they led to serious interference with their business.

Advertising↗

[Advertisements in newspapers and magazines about patent medicines in the Meiji era (the first dissertation) (Part 3)].

After the conclusion of the trial was carried out on december 25th in the 18th year of the Meiji era, write-ups decreased graduallly. Under these circumstances, the traders of medicine began their own publication at their convenience and they put advertisements in them. "Eisei-tebako" by "Kishida ginko" and "Houtan-keikenroku" by "Morita Jihei" were the typical of them. While patent medicines were extremely popular, pharmacists at that time never denied the necessity of patent medicines. Junichiro Shimoyama and Keizo Tanba, who were representatives of pharmacists in Japan, suggested that pharmacists had ought to manage patent medicines and pointed out that excessive write-ups exacerbated the situation.

Advertising↗

Induction of differentiation by radiation and hyperthermia in neuroblastoma-glioma hybrid cells.

The effects of either radiation or hyperthermia on the differentiation potential of NG108-15, a neuroblastoma-glioma hybrid cell line, were studied. After radiation and hyperthermia, the outgrowth of neurites from NG108-15 cells was potentiated, and polarizing current and voltage pulses induced a distinct action potential and a diphasic (inward following outward) current, respectively. An increase in the specific activity of acetylcholinesterase was also observed. In addition, both treatments induced an elevation of the concentration of intracellular calcium in some cells. The increase in intracellular calcium concentration caused by applying the calcium ionophore, A23187, induced differentiation. It is suggested that both the radiation- and the hyperthermia-induced increases of electrical excitability and acetylcholinesterase activity may have originated from an increase in intracellular Ca2+ concentration.

Acetylcholinesterase↗

Effects of continuous intravenous infusion of isosorbide dinitrate on development of tolerance to vasodilating action in human epicardial coronary arteries.

This study was performed to determine the effects of long-term intravenous infusion on the coronary vasodilating actions of continuous intravenous and bolus intracoronary administration of isosorbide dinitrate (ISDN). With quantitative coronary angiography, the coronary diameter and the vasodilating response to intracoronary ISDN (1 mg) at angiographically normal segments were studied before and after intravenous administration of ISDN, 10 to 60 micrograms/min for 1 hour, 2 days, or 5 days. The vasodilating effects of intravenous ISDN were 72% +/- 13%, 65% +/- 21%, and 6% +/- 11% of the response to intracoronary ISDN in the baseline study in each group. Irrespective of the duration of intravenous infusion, subsequent intracoronary ISDN dilated coronary arteries to extent similar to that observed in each baseline study. In conclusion, significant coronary vasodilating effects of intravenous ISDN were observed after a 2-day infusion, whereas tolerance to the vasodilating effects apparently developed within 5 days of infusion. The vasodilating response to bolus intracoronary ISDN was preserved even when the vasodilating effects of intravenous ISDN were no longer present.

Angina Pectoris↗

Release profiles of phenytoin from new oral dosage form for the elderly.

Utilization of the solid mass containing phenytoin, sodium caseinate and microcrystalline cellulose (MCC) as a new dosage form for the elderly was studied. The solid mass was prepared by treatment of the powder mixture with high pressure steam at 115 degrees C for 10 min. The stability of phenytoin in the solid mass was confirmed by infrared spectroscopy and high performance liquid chromatography. The extent of swelling of the solid mass containing phenytoin was investigated by water absorption test and gel strength test, and the swelling property was almost independent of the presence of phenytoin. The release profile of phenytoin from the solid mass was determined under various conditions, and was found to be influenced by the extent of swelling and the swollen state. It was observed that the protein adsorption to the phenytoin crystal surface and the addition of digestive enzyme also affected the release profile. In water, the solid mass prepared from a ground mixture of phenytoin and MCC showed remarkable improvement of release profile of phenytoin.

Absorption↗

[Japanese medicines studied by Hepburn, an American missionary, in 1860s].

In the last days of the Tokugawa shogunate when Japan was opened its door to trade, J.C. Hepburn came to Japan, and he contributed to the modernization of Japan as a missionary, a doctor and an instructor. His great academic achievement was publishing a Japanese-English and English-Japanese dictionary. The dictionary contained words which were generally used in those days. It is said that it was way of living and culture in Japan as seen by an American. Words about medicine show the conditions of the business of medicine in those days. Until 1889 a pharmacist was not professionalized yet, nor was the separation of dispensary from medical practice effective. As most of doctors were Chinese herb doctors, there was not the word "MD." As Chinese doctors were the leading ones, lots of words about herb were mentioned. We can find only a few words about chemicals. The common people used patent medicine such as Daranisuke, Mankintan. Less than 100 years, sorts of medicine in Japan have changed to those of medicine in Western countries.

Dictionaries as Topic↗