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Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 253 records · Page 14Linked to original sources
PubMed1992

[Study on the therapy of multiple myelomas--initial induction therapy (MP, IFN alpha, steroid pulse) and maintenance therapy (VMP, MP continuous, VEP, MCNU)].

Untreated twenty patients of multiple myeloma were treated with the chemotherapy protocol as follows: Initial induction therapy;MP continuous or MP intermittent----IFN alpha----steroid pulse. Maintenance therapy;alkylating agents which have no cross resistance were used ((V) MP----(MP)----(V) EP----MCNU). Remission rate (CR+PR) after the initial MP therapy was 45%, and that after including IFN alpha and steroid pulse therapy was 50%, Fifty percent survival rate was almost as same as those reported previously (34M). Our protocol presented here was based on the idea that, initially, myeloma cells with proliferative activity could be affected by MP therapy, and subsequent IFN alpha therapy would have effect even on the residual myeloma cells. Serial checks of 3H-TdR uptake of myeloma cells during the therapy supported this idea. During the maintenance therapy, clinical responses to the initial induction therapy were not aggravated in the responded cases when evaluated by the variation of serum M-protein level. We propose that considering from a point of proliferative activity of myeloma cells is important for designing therapeutic protocols for multiple myeloma.

Adult↗
PubMed1991

Rolling-circle replication of the plasmid pKYM isolated from a gram-negative bacterium.

Plasmid pKYM isolated from a Gram-negative bacterium encodes a Rep protein that is essential for plasmid replication. A comparison of Rep protein from pKYM to Rep proteins encoded by other plasmids shows that it has homology to Rep proteins of the pUB110 plasmid family from Gram-positive bacteria. These plasmids replicate by a rolling-circle mechanism in which a tyrosine residue in the Rep protein acts as the acceptor for the 5' end of the single-strand break introduced by the Rep protein. A Tyr----Phe substitution in the pKYM Rep protein abolishes its activity. Strand-specific single-stranded circular plasmid DNA can be recovered from the cells carrying pKYM and thus we propose that the plasmid pKYM replicates by a rolling-circle mechanism.

Adenosine Triphosphatases↗
PubMed1991

Meningeal involvement in Bence Jones multiple myeloma.

A case of Bence Jones kappa multiple myeloma with meningeal involvement in a 64-year-old woman is presented. Three years after the diagnosis of multiple myeloma, gait disturbances developed followed by visual disorders and impaired consciousness. A lumbar puncture revealed numerous atypical plasma cells in the cerebrospinal fluid. Craniospinal irradiation and intrathecal injections of methotrexate, cytarabine, and prednisolone were effective for a short period. At autopsy, the leptomeninges were infiltrated diffusely with atypical plasma cells. A review of the literature showed that multiple myeloma with meningeal involvement is accompanied frequently by circulating atypical plasma cells or plasma cell leukemia. Meningeal involvement is a rare complication and shows poor prognosis in cases of multiple myeloma.

Female↗
PubMed1991

Effects of pulsing electromagnetic fields on cultured cartilage cells.

In order to evaluate the effects of pulsing electromagnetic fields (PEMFs) on cell proliferation and glycosaminoglycan (GAG) synthesis and to study the action site of PEMF stimulation in the cells, we performed a series of experiments on rabbit costal growth cartilage cells and human articular cartilage cells in culture. A PEMF stimulator was made using a Helmholz coil. Repetitive pulse burst electric currents with a burst width of 76 ms, a pulse width of 230 microseconds and 6.4 Hz were passed through this coil. The magnetic field strength reached 0.4 mT (tesla) on the average. The syntheses of DNA and GAG were measured by 3H-thymidine and 35S-sulfuric acid incorporations. The effects on the cells treated with lidocaine, adriamycin and irradiation were also measured using a colony forming assay. The PEMF stimulation for the duration of 5 days promoted both cell proliferation and GAG synthesis in growth cartilage cells and intermittent stimulation on and off alternatively every 12 h increased them most significantly, while, in articular cartilage cells, the stimulation promoted cell proliferation, but did not enhance GAG synthesis. PEMF stimulation promoted cells treated with lidocaine more significantly than with other agents. These results present evidence that intermittent PEMF stimulation is more effective on both cell proliferation and GAG synthesis of cartilage cells than continuous stimulation, and that the stimulation could exert effects not by nucleus directly, but by the cellular membrane-dependent mechanism. This study provides further basic data to encourage the clinical application of PEMF stimulation on bone and cartilage disorders.

Animals↗
PubMed1991

Effects of physical training on pulmonary arterial pressure during exercise under hypobaric hypoxia in rats.

In this investigation, we assessed the effects of physical training on exercise-induced systemic and pulmonary hemodynamic changes under hypobaric hypoxia in catheter-implanted rats. We made continuous measurements of pulmonary and systemic arterial pressures during progressive treadmill exercises under hypobaric hypoxia (equivalent to altitudes of 2500 and 5500 m) in 46 control and 41 trained rats. Trained rats were exercised on two running schedules: 4 weeks (4-trained) and 6 weeks (6-trained). Both these groups of trained rats were exercised for the same length of running time each day. The increase in resting mean pulmonary arterial pressure (Ppa) with increasing equivalent altitude was lower in the two trained groups than in the control group. The increase in Ppa with progressive intensity of exercise was lower in the 6-trained than in the 4-trained and control groups at 610 and 2500 m. The 6-trained rats showed higher pH, Pa CO2 and O2 saturation in their blood than did the control group, whereas the Pa O2 was less. Lung tissue cyclic AMP concentration at rest was higher in the 6-trained than in the control group. Finally, it may be noted that exercise-induced lung tissue vasodilator responses seem to be enhanced in well-trained rats under both normobaric normoxia and hypobaric hypoxia. This study indicates that exercise training may be useful in preventing pulmonary hypertension resulting from both hypoxia and exercise.

Altitude↗
PubMed1991

Multiple coronary stenoses of unknown etiology.

The case of a 13-year-old girl with multiple coronary stenoses and abundant collaterals, but no risk factors, is described. She was not suspected of having ischemic heart disease until an abnormal electrocardiographic pattern was detected during a routine examination in school. All children with electrocardiographic abnormality should be carefully examined, even though they have neither symptoms nor coronary risk factors.

Adolescent↗
PubMed1991

Effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy--echocardiographical follow-up.

To evaluate the effectiveness of long-term beta-blocker therapy for dilated cardiomyopathy (DCM), two groups (Group I: 18 patients, Group II: 17 patients) with DCM divided by the order at the entry were followed echocardiographically for 16.9 +/- 3.0 months in Group I and 21.4 +/- 3.9 months in Group II. Metoprolol (final dose: 60 mg/day) was administered in Group I, but not in Group II (the control), although the conventional treatment for heart failure was continued. The left ventricular end-systolic dimension and ejection fraction assessed by echocardiography improved significantly after 6 months in Group I, but not in Group II, even after 48 months, although there were no significant differences in baseline data between the two groups. The end-diastolic dimension decreased significantly after 12 months in Group I only. It was estimated, using the point count method on a left ventricular endomyocardial biopsy specimen taken at entry, that the improvement (delta EF) of the ejection fraction 12 months after metoprolol administration inversely correlated (r = -0.677, p less than 0.01) with percent fibrosis, indicating that the more myocardium remains, the more improvement is expected. These findings suggested a favorable effect of beta blockade in DCM, especially in cases with less fibrosis, showing that the endomyocardial biopsy could be of clinical use in selecting candidates for chronic beta-blocker therapy in DCM.

Adrenergic beta-Antagonists↗
PubMed1991

A subtype of human papillomavirus 5 (HPV-5b) and its subgenomic segment amplified in a carcinoma: nucleotide sequences and genomic organizations.

A subtype of human papillomavirus 5 (HPV-5b) is closely associated with carcinomas in the disease epidermodysplasia verruciformis (EV). The complete genome was cloned from virus particles in benign lesions of a patient with EV and sequenced: it was 7779 nucleotides long and consisted of six open reading frames (ORFs) (E6, E7, E1, E2, E4, and E5) in the early region, three ORFs (L2, L3, and L1) in the late region, and a noncoding region, all existing on one DNA strand. The 40% segment of the HPV-5b genome specifically amplified in carcinomas was cloned from a primary carcinoma of the same EV patient and sequenced: it was 3143 nucleotides long and corresponded to a segment of the original HPV-5b genome containing the entire sequences of E6, E7, and the noncoding region and portions of E1 and L1. Compared to the whole genomic DNA, no mutations were detected in this probable malignancy-associated viral subgenomic segment cloned from carcinoma. These results suggest that amplification of the viral segment containing E6, E7, and the noncoding region may play a role in the malignant conversion of HPV-5b-infected benign lesions and that mutations in these genes or regions are not necessarily required.

Base Sequence↗
PubMed1991

Lipophilic peptides: synthesis of lauroyl thyrotropin-releasing hormone and its biological activity.

Thyrotropin-releasing hormone (TRH) was derivatized by chemical attachment of lauric acid to the N-terminal pyroglutamyl group. The product was confirmed to be more lipophilic than TRH by high-performance liquid chromatography and measurement of partition coefficients. The central nervous system activity and endocrine activity of the lauroyl derivative were only slightly reduced, to 81 and 64% of the parent TRH, respectively. Lipophilic derivatization may be generally applicable to transmembrane delivery of peptides.

Amino Acid Sequence↗
PubMed1991

Enhanced secretion of human nerve growth factor from Saccharomyces cerevisiae using an advanced delta-integration system.

We have designed an advanced delta-integration system (integration of genes into the delta-sequence of yeast retrotransposon Ty) and used it for secretion of human nerve growth factor (hNGF) from Saccharomyces cerevisiae. The expression and secretion of hNGF was directed by the PGK promoter and MF alpha 1 prepro-signal. Using two selectable markers (URA3 and leu2-d), haploid yeast strains were constructed with approximately 20 copies of a delta-integrated hNGF expression cassette on four chromosomes. The strain secreted hNGF at levels 3-4 fold higher than a 2 micron-based plasmid. Northern and Western analyses revealed that the oversecretion was caused by an increased amount of mRNA. We also detected an unusual processing of the MF alpha 1 prepro-hNGF fusion protein that required the pep4 mutation. Application of this system for industrial purposes is discussed.

Biotechnology↗
PubMed1991

Psychoactive drug prescribing in Japan: epistemological and bioethical considerations.

Today in Japan psychoactive drugs are widely prescribed for various psychiatric disorders including so-called 'functional' disorders. They are undoubtedly effective in relieving various psychological and behavioral symptoms. However, Japan has yet to address some basic questions: (1) uncertainty concerning the cause of various psychiatric functional disorders; (2) unknown factors that affect the function of psychotropic drugs in patients; (3) the difficulty in obtaining objective data concerning the effects of these medications both on the brain and the psychological symptoms (behavior); and most importantly, (4) due to both the behavioral and organic (brain and CNS) effects of psychoactive drugs, the difficulty in evaluating the risk/benefit ratio between the behavioral (primary) effect and the organic (side) effect. In addition, there are bioethical problems, since these uncertainties tend to permit too broad a range of intention and too many modes of intervention in (a) prescribing and (b) taking psychoactive drugs on the part of therapists and patients, respectively. Though the increased risk of the inappropriate use of these drugs--the non-therapeutic uses, and their over-prescription--has been indicated in other industrialized countries, it has not yet been fully recognized and adequately discussed in Japan. Moreover, it is necessary to establish a sound basis for the 'somato-psychic' evaluation of these effects in the context of the physician-patient relationship, including the patient's family and even the broader society.

Attitude to Health↗
PubMed1991

Promotion of BALB/3T3 cell transformation by the okadaic acid class of tumor promoters, okadaic acid and dinophysistoxin-1.

Okadaic acid and dinophysistoxin-1 are non-12-O-tetradecanoylphorbol-13-acetate (non-TPA)-type tumor promoters, which enhance chemically induced tumorigenesis on mouse skin through a different mechanism from that of TPA. In the present study, we examined the promoting effects of these okadaic acid class tumor promoters on a two-stage transformation using BALB/3T3 cells which was designed to simulate in vivo two-stage carcinogenesis. Cells were treated first with a low dose of the initiator 3-methylcholanthrene (MCA) and then with a test chemical. Okadaic acid and dinophysistoxin-1 significantly enhanced the MCA-induced cell transformation. Okadaic acid tetramethyl ether, an inactive compound, did not affect the transformation of MCA-treated cells. The okadaic acid class of tumor promoters failed to induce transformation without pretreatment by MCA. Okadaic acid did not show initiating activity in the two-stage transformation assay in which cells were treated first with okadaic acid and then with TPA. These results indicate that this transformation assay with BALB/3T3 cells is useful to predict tumor-promoting activity of non-TPA-type as well as TPA-type tumor promoters, before long-term in vivo two-stage carcinogenesis experiments are carried out.

Animals↗
PubMed1991

Homotypic cell aggregations of human myeloma cells with ICAM-1 and LFA-1 molecules.

Some myeloma cells freshly isolated from bone marrow aspirates in human myelomas and some myeloma cell lines formed spontaneous cell aggregations in vitro (homotypic cell aggregations). In order to clarify the surface molecules involved in homotypic cell aggregations and physiological roles of these cell aggregations, we investigated the expressions of intercellular adhesion molecule 1 (ICAM-1) and lymphocyte function-associated antigen 1 (LFA-1) on 20 samples of freshly isolated myeloma cells and three myeloma cell lines and the effect of anti-ICAM-1 and anti-LFA-1 alpha antibodies on myeloma cell proliferation in vitro. All myeloma cells that we tested expressed ICAM-1 on their surface. Among them, myeloma cells that strongly coexpressed LFA-1 alpha, formed homotypic cell aggregates in vitro. These spontaneous cell aggregations were completely released by adding either anti-ICAM-1 or anti-LFA-1 alpha antibody. During short-term culture, spontaneous proliferation of myeloma cells in vitro and their proliferative responses to recombinant interleukin-6 (rIL-6) were not affected by pretreatment of myeloma cells with anti-ICAM-1 or anti-LFA-1 alpha antibody. Therefore these data suggest that homotypic cell aggregation of myeloma cells is mediated by ICAM-1 and LFA-1 molecules, but myeloma cell proliferation may not be modulated by these adhesion molecules during short-term cultures.

Antigens, CD↗
PubMed1991

Increased expression of the c-myc gene may be related to the aggressive transformation of human myeloma cells.

Alteration and abnormal expression of the c-myc oncogene were investigated in human multiple myeloma. Human myeloma cells were highly purified (more than 95%) from bone marrow aspirates in 14 cases of advanced multiple myelomas and one case of plasma cell leukaemia. Southern blotting revealed that a rearranged configuration of c-myc gene was found in only one case of them, but this was a novel truncation of the gene in its coding exon II; a rearranged 3.4 kb band was detected by digestion with Xba I using c-myc exon II probe, but no rearranged band was found using exon III probe. In this case, the truncated c-myc allele was not transcribed; normal sized (2.4 kb) c-myc mRNA was markedly expressed, but no aberrant mRNA was detected. On the other hand, by Northern blotting, the nine cases, including the case with the rearranged c-myc gene, showed increased expression of normal sized (2.4 kb) c-myc mRNA. Elevated c-myc mRNA expressions were well related to the in vitro proliferation (3H-TdR uptake), but not to IL-6 response. Interestingly, extremely high expressions of c-myc mRNA were detected in two cases of aggressive myelomas, including the case with the rearranged c-myc gene, and in one of plasma cell leukaemia. These two cases of aggressive myelomas were the ones who showed the markedly high 3H-TdR uptakes, and had the common clinical features with the formation of an extramedullary mass and very short survival. These results suggest that the activation of c-myc gene could induce high proliferative activities and the subsequent aggressive transformation of myeloma cells.

Blotting, Northern↗
PubMed1991

Current comprehensive therapy of habitual abortion.

Habitual abortion is sometimes an incurable pathogenetic state. Even more serious to both the patient and gynecologist is that the incidence of repeated reproductive wastage is higher in subsequent pregnancies. We registered more than 1,000 women with repeated spontaneous abortions in this clinic for 5 years and analyzed their pathogenesis for the wastages by several different approaches. One hundred twenty-four women were diagnosed as having a congenital uterine abnormality. Metroplasty was performed in 50 patients, resulting in 82% successful subsequent pregnancies, whereas more than 98% of the pregnancies had terminated in spontaneous abortion before the operation. By measuring anticardiolipin antibody (ACA) and lupus anticoagulant (LA), the present study diagnosed several cases as antiphospholipid syndrome, and successfully pregnant patients were observed and treated with appropriate medications. Fifty-five partners of 54 couples had either a chromosomal abnormality or normal variants, showing a high incidence of spontaneous abortion in each type of abnormality. In the other 311 cases, female partners were treated by the immunotherapy of the husbands' lymphocytes in pre- and postgestational periods. Among them, 200 women became pregnant, and 147 cases successfully maintained the pregnancy. These studies indicate that early diagnosis through comprehensive examinations is essential for effective treatment of curable fetal loss in human reproduction.

Abortion, Habitual↗