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Biomedical subjects

M Fukushima

Publications and source records attributed to M Fukushima.

At least 217 records · Page 12Linked to original sources
PubMed1997

Molecular epidemiology of rubella by nucleotide sequences of the rubella virus E1 gene in three East Asian countries.

Twenty-six strains of rubella virus were compared with each other for a molecular epidemiologic study of the virus in three East Asian countries, using the E1 gene of 1443 nucleotides and the following 41 nucleotides in a noncoding region. Nucleotide substitution rates among strains were 0.0-9.4/100 nucleotides. A phylogenetic tree drawn indicated that 2 of 3 Chinese strains were quite different from the other 24 strains; all isolates in the 1960s were classified into a single group independent of the place of isolation, which includes isolates from Japan, the United States, and the United Kingdom; 11 strains of Japanese isolates collected during 1976-1991 made one subbranch derived from the 1960s group; and 2 isolates from the northeast part of Japan in 1990 made a third but minor unique branch. Therefore, at least two groups of the virus cocirculated in Japan around 1990. Antigenic variation of the virus was very small among these strains.

Amino Acid Sequence↗
PubMed1997

In vivo sequence variability of human immunodeficiency virus type 1 envelope gp120: association of V2 extension with slow disease progression.

According to the rate of depletion of CD4 cell counts, we grouped 12 cases of human immunodeficiency virus type 1 (HIV-1) infection as 6 rapid (21.0 to 33.8 cells per microl per month) and 6 slow (0.9 to 7.9 cells per microl per month) progressors and determined the individual viral quasispecies patterns by sequencing the genome region encoding the V1, V2, and V3 loops of envelope protein. Although the quasispecies structures varied widely from one individual to another, a strong correlation was observed between a low rate of disease progression and a high degree of genetic diversity of HIV-1. Furthermore, the V2 loop extension was observed specifically in individuals with slow or no disease progression, whereas basic amino acid substitutions in V3 characteristic of a viral phenotype shift from non-syncytium inducing to syncytium inducing were observed in patients with advanced stages of disease regardless of their rate of disease progression. Studies with recombinant viruses suggested that elongation of V2 potentially restricts the capacity of HIV-1 to replicate in macrophages. Thus, our results suggest the association of distinct sequence features of both V3 and V2 with particular patterns of disease progression. Elongation of the V2 loop may be a good predictor of slow disease progression, while basic substitutions of V3 without elongation of V2 are characteristic of rapid progression.

Amino Acid Sequence↗
PubMed1997

Commitment of motoneuron progenitors of chick embryo along the anterior-posterior axis.

To identify molecules that might be involved in the early development of motoneurons, we performed RT-PCR for receptor tyrosine kinases (RTKs) and mRNA differential display with embryonic day 5 (E5) chick motoneurons enriched by panning. In situ hybridization revealed that Cek88 RTK among the cloned molecules was specifically expressed on motoneurons at the brachial and lumbar segments of the spinal cord which innervate limb muscles. We found that the expression of Cek8 in limb motoneurons was already intrinsically determined at E2. To analyze how motoneurons acquire regional specification along the anterior-posterior (A-P) axis and in the transverse plane, we observed the expression of Cek8, Islet-1, SC1 and low-affinity NGF receptor on ectopic motoneurons induced by implanting a supernumerary notochord or floor plate. The ectopic motoneurons induced by the graft obtained from either the thoracic or lumbar segments had the same expression profile as the in situ motoneurons at each A-P level. These findings suggest that regional specification of motoneurons is independent of the notochord and the floor plate and that the whole neural tube is committed to differentiate into the motoneuron subtypes along the A-P axis at the operative stages.

Animals↗
PubMed1997

History of vitamin D treatment of renal osteodystrophy.

Vitamin D treatment was tried when renal osteodystrophy was first recognized in the early 20th century, using vitamin D2, D3, or dihydrotachysterol. Large doses of vitamin D2 or D3 (150,000-500,000 IU) were prescribed by monitoring serum calcium, phosphate, and alkaline phosphatase. After the discovery of 1,25-dihydroxycholecalciferol, this compound or 1 alpha-hydroxycholecalciferol was applied to the treatment of renal osteodystrophy. In a preclinical study, especially of 1 alpha-hydroxycholecalciferol, nephritogenoside nephritis was the most responsive condition. These active vitamin D preparations are now widely used in patients with chronic renal failure under hemodialysis. Other active vitamin D compounds, such as hexafluoro-1,25-dihydroxycholecalciferol and 22-oxacalcitriol, are also under investigation.

Animals↗
PubMed1997

[Development of "assessment guideline of family power for healthy life"].

The purpose of this study is to develop "assessment guideline of family power for healthy life" aiming at expanding self-care power of family in community nursing practice. The subjects of this study covered those families in one hundred and fifty six instances that we had seized as subject for nursing care and study. The method of this study had constructed assessment guideline inductively out of each case, and modified it by applying to cases of families with health problems and others. As a result, we had formed nine items of "family power for healthy life" and three items of "conditions influencing family power for healthy life" for "assessment guideline of family power for healthy life".

Community Health Nursing↗
PubMed1997

[Antitumor effect and mechanism of a novel multifunctional nucleoside, 3'-ethynylnucleoside, on human cancers].

The antitumor activity of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl) uracil (EUrd), designed as a potential multifunctional antitumor nucleoside to inhibit RNA and DNA syntheses, was examined. ECyd and EUrd inhibited the growth of 47 kinds of cultured human cells in vitro and also showed strong antitumor effects on 15 human solid cancers xenografted into nude mice at a dose of 0.25 mg/kg (ECyd) or 2 mg/kg (EUrd) by intravenous administration for 10 consecutive days. The in vitro cytotoxic effect of ECyd and EUrd was prevented dose dependently by cytidine and uridine, suggesting that ECyd and EUrd may require phosphorylation by uridine/cytidine kinase for antitumor activity. ECyd and EUrd strongly inhibited RNA synthesis and slightly inhibited DNA synthesis. ECyd and EUrd have shown potent antitumor activity against human experimental solid type tumors with minimal toxic effects in vivo, suggesting that ECyd and EUrd is a promising agent with a unique mechanism of action for the treatment of cancer.

Animals↗
PubMed1997

[The correlation between thymidylate synthase expression and cytotoxicity of 5-fluorouracil in human cancer cell lines: study using polyclonal antibody against recombinant human thymidylate synthase].

To estimate the relationship between the expression of thymidylate synthase (TS) in tumors and clinical response and prognosis in cancer patients treated with 5-fluorouracil (5-FU), the anti-TS polyclonal antibody against recombinant human TS (rhTS) was prepared and purified. At the initial stage, we attempted to clarify the relationships between the expression of TS protein and the cytotoxicity of 5-FU in established human cancer cells in vitro. Our purified anti-TS antibody was demonstrated to react specifically with intracellular TS as revealed by western blot analysis and immunohistochemistry. Furthermore, it was revealed that the expression of TS proteins correlated with cytotoxicity (IC50 value) of 5-FU against human colorectal tumor cells, both sensitive and those with acquired resistance to 5-fluoropyrimidines, and other cancer cell lines as well. These results suggest that our anti-TS polyclonal antibody (IgG) is suitable for clinical prospective and retrospective studies on TS expression in various cancers as a prognostic factor and 5-FU response-predicting parameter.

Antibodies↗
PubMed1997

[A case of mediastinal goiter with hyperthyroidisms].

A 65-years-old woman admitted to the hospital in order to treat of the mediastinal tumor, but she suffered from palpitation, slight fever, sweating, uneasiness, sleeplessness and weightloss. On the physical examination, she was experiencing tachycardia, fevering (37.2 approximately 37.6 degrees C). Skin was moist but had no exophtalmos or neck tumor. Chest X-ray showed an abnormal shadow in the upper mediastinum. On chest CT, a tumor mass (9 x 5 x 4 cm) with cystic regions and scattered calcifications occupied from anterior to posterior mediastinum. The tumor compressed trachea to the left and right brachiocephalic vein and SVC to the right. Lower portion of the tumor intruded into behind of the trachea. Lymph node swelling of mediastinum was also detected. Results of general laboratory examination were within normal limits. Thyroid function test revealed hyperthyroidism; T3U 58%, free T3 24.4 pg/ml, free T4 6.0 ng/dl and thyroglobulin 967 mg/dl, but TSH was < 0.01 microIU/ml. After daily administration of methimazole (300 mg/day) for 4 weeks, thyroid function became to normal level and symptoms of hyperthyroidism was disappeared. The tumor was completely extirpated with right hemithyroidectomy and lymph node dissection under neck colla incision and median sternotomy. Pathological finding of the tumor showed follicular-fetal adenoma of thyroid with hyaloid degeneration and cystic change. There was no finding suspected of Graves' disease. She is well without any complications for 8 months after operation. Some discussion of the literature was mentioned.

Adenoma↗
PubMed1997

[Preoperative evaluation of the right ventricular function using the pulsed Doppler echocardiogram in the patients scheduled for the elective pulmonary resection].

Preoperative evaluation of the both right ventricular (RV) systolic and diastolic function using the pulsed Doppler echocardiogram were examined for 46 patients scheduled for the pulmonary resection of the pulmonary tumorous lesions. The parameters which included the RV inflow pattern at the tricuspid orifice and the RV ejection flow pattern at the RV outflow tract were obtained by the pulsed Doppler echocardiogram. Following results were obtained. 1) The RV afterload shown by the parameters of the acceleration time (AT, time beginning of RV ejection to peak velocity) were higher in the aged patients, the low FEV 1% populations, and the patients having the deteriorated left ventricular contraction. 2) The RV diastolic dysfunction were present preoperatively in aged patients over the 60 years old. This phenomenon was characterized by a high degree of atrial contraction and an increased ratio of the peak velocity in atrial contraction phase to that in early rapid filling phase (A/E). When we evaluate the RV inflow and ejection Doppler flow patterns after the major lung resection, these findings must be considerable thing.

Adolescent↗
PubMed1997

[Profiles of effects of traditional oriental herbal medicines on central nervous systems in humans--assessment of saiboku-to and saiko-ka-ryukotsu-borei-to using EEG and pharmacokinetics of herbal medicine-derived ingredients as indices].

To elucidate usefulness of traditional oriental herbal medicines in psychiatric fields, we investigated their influences on central nervous systems in humans by using EEG and pharmacokinetics of herbal medicine-derived ingredients as the indices. The subjects were 12 healthy male volunteers who received single oral administration and after that received repeated oral administrations at a daily dose of Saiko-ka-ryukotsu-borei-to or Saiboku-to; EEG was recorded before administration, 1, 3, 6 hours and 10 days after administration. On direct comparison of global field powers calculated from 19-lead EEG before and after administration, it was verified that Saiboku-to possessed effects on central nervous systems. For assessment of pharmacokinetics of ingredients derived from Saiboku-to, pre- and post-treatment serum samples were assayed by HPLC and two ingredients were detected, besides individual differences being observed in their pharmacokinetic profiles. Given that these pharmacokinetics could be interpreted as the phenomena associated with Sho (traditional physical status classifications of patients), the subjects were classified into groups according to individual differences whereby quantitative pharmaco-EEG were employed to elucidate neurotropic effects of Saiboku-to. As the result, following two groups were evidenced: (1) a group demonstrating the mood elevator type after a single administration despite of no changes after repeated administrations, and (2) a group with a shift from the mood elevator type to the nootropics type being observed over time, delineating overt differences in EEG profiles among groups. Consequently, individual differences were evidenced to be involved in onset of neurotropic effects of Saiboku-to, permitting prediction of possible responses following repeated administrations by using EEG profiles. It was also suggested that neurotropic effects of respective ingredients could be anticipated by monitoring the time-course changes of both EEG and plasma levels of these ingredients. In summary, once further studies on oriental herbal medicines might progress based on efficacy assessments of respective ingredients with a clue of the present study, it is conceivable that these findings would play an important role as the objective indices in clinical application of herbal medicines in psychiatric fields, resulting in broadening the usefulness of oriental herbal medicines.

Adult↗
PubMed1997

Cytotoxic mechanisms of new antitumor nucleoside analogues, 3'-ethynylcytidine (ECyd) and 3'-ethynyluridine (EUrd).

The cytotoxic mechanisms of 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) were studied with mouse mammary tumor FM3A cells and human fibrosarcoma HT1080 cells. ECyd and EUrd are converted to ECyd 5'-triphosphate (ECTP) in the cells. ECTP has also outstanding stability in the cells; the half life of ECTP in FM3A cells was more than 3 days. The metabolisms and mechanisms of these analogues may play a key role in a potent antitumor activities against slow-growing solid tumors.

Animals↗
PubMed1997

Escherichia coli tmRNA (10Sa RNA) in trans-translation.

Here we show that Escherichia coli tmRNA (10Sa RNA) has a dual function both as an mRNA and as a tRNA in vitro. The function as a tRNA is prerequisite for the function as an mRNA. These observations strongly support the trans-translation hypothesis.

Amino Acid Sequence↗
PubMed1996

Interaction of 10Sa RNA with ribosomes in Escherichia coli.

10Sa RNA is a bacterial small stable RNA, in which the 5'- and 3'-end sequences are folded into a tRNA-like structure. The RNA accepts alanine in vitro, and interacts with 70S ribosomes in the cells. In this study, we examined the ribosome-binding properties of Escherichia coli 10Sa RNA in vivo, and found that the aminoacylation ability of 10Sa RNA with alanine is necessary for the binding to 70S ribosomes. 10Sa RNA was also found to bind only to 70S monosomes and not to polysomes. Recently, E. coli 10Sa RNA was suggested to be used as mRNA for tag peptides, which were found to attach to the C-termini of truncated peptides synthesized in vivo. The present results are consistent with the 'trans-translation' model, which has been proposed for tag-peptide synthesis.

Escherichia coli↗
PubMed1996

Nucleosides and nucleotides. 158. 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)-cytosine, 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil, and their nucleobase analogues as new potential multifunctional antitumor nucleosides with a broad spectrum of activity.

We previously designed 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)uracil (EUrd) as a potential multifunctional antitumor nucleoside antimetabolite. It showed a potent and broad spectrum of antitumor activity against various human tumor cells in vitro and in vivo. To determine the structure-activity relationship, various nucleobase analogues of EUrd, such as 5-fluorouracil, thymine, cytosine, 5-fluorocytosine, adenine, and guanine derivatives, were synthesized by condensation of 1-O-acetyl-2,3,5-tri-O-benzoyl-3-C-ethynyl-alpha,beta-D-ribo-pentofur anose (6) and the corresponding pertrimethylsilylated nucleobases in the presence of SnCl4 or TMSOTf as a Lewis acid in CH3CN followed by debenzoylation. The in vitro tumor cell growth inhibitory activity of these 3'-C-ethynyl nucleosides against mouse leukemia L1210 and human nasopharyngeal KB cells showed that 1-(3-C-ethynyl-beta-D-ribo-pentofuranosyl)cytosine (ECyd) and EUrd were the most potent inhibitors in the series, with IC50 values for L1210 cells of 0.016 and 0.13 microM and for KB cells of 0.028 and 0.029 microM, respectively. 5-Fluorocytosine, 5-fluorouracil, and adenine nucleosides showed much lower activity, with IC50 values of 0.4-2.5 microM, while thymine and guanine nucleosides did not exhibit any activity up to 300 microM. We next evaluated the tumor cell growth inhibitory activity of ECyd and EUrd against 36 human tumor cell lines in vitro and found that they were highly effective against these cell lines with IC50 values in the nanomolar to micromolar range. These nucleosides have a similar inhibitory spectrum. The in vivo antitumor activities of ECyd and EUrd were compared to that of 5-fluorouracil against 11 human tumor xenografts including three stomach, three colon, two pancreas, one renal, one breast, and one bile duct cancers. ECyd and EUrd showed a potent tumor inhibition ratio (73-92% inhibition relative to the control) in 9 of 11 and 8 of 11 human tumors, respectively, when administered intravenously for 10 consecutive days at doses of 0.25 and 2.0 mg/kg, respectively, while 5-fluorouracil showed potent inhibitory activity against only one tumor. Such excellent antitumor activity suggests that ECyd and EUrd are worth evaluating further for use in the treatment of human cancers.

Animals↗
PubMed1996

C-type natriuretic peptide as an autocrine/paracrine regulator of osteoblast. Evidence for possible presence of bone natriuretic peptide system.

C-type natriuretic peptide (CNP) is a local regulator in the brain and vascular wall. We present data to demonstrate the production and action of CNP in the osteoblast. CNP increased cGMP production, far more potently than atrial natriuretic peptide (ANP) in an osteoblastic cell line, MC3T3-E1. Since ANP and CNP are the ligands for two particulate guanylate cyclases, guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B), respectively, these results reveal the expression of GC-B in MC3T3-E1. In addition, CNP mRNA and CNP-like immunoreactivity were detected in cell extracts from MC3T3-E1 and its culture medium, respectively. Both CNP and 8-bromo cGMP dose-dependently decreased [3H]thymidine uptake, without affecting alkaline phosphatase activity. These results indicate that CNP is a novel autocrine/paracrine regulator of osteoblast and suggest the presence of "bone natriuretic peptide system."

3T3 Cells↗
PubMed1996

Antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1) against human colon carcinoma orthotopically implanted into nude rats.

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Adenocarcinoma↗