Search PubMed⌕ Search

Biomedical subjects

M Wada

Publications and source records attributed to M Wada.

At least 487 records · Page 27Linked to original sources

Anemia in new congenital adult type polycystic kidney mice.

Mechanisms for the development of anemia and the effects of recombinant human erythropoietin (r-HuEPO) on hematological parameters were studied in new congenital adult type polycystic kidney (DBA/2FG-pcy) mice. The majority of DBA/2FG-pcy mice showed progressive anemia and an elevation of blood urea nitrogen, while a minority showed progressive anemia following polycythemia. Kidneys with numerous cysts in the cortex and medulla occupied virtually the entire abdominal cavity, and the combined kidney weight taken as a percentage of body weight reached 13.5% in the DBA/2FG-pcy mouse. The osmotic fragility of DBA/2FG-pcy mice erythrocytes was significantly increased compared with that of normal control mice. In addition, two-fold increases in serum EPO levels, determined by radioimmunoassay, and a decreased number of colony forming unit-erythroid (CFU-E) were observed in the DBA/2FG-pcy mice. The administration of r-HuEPO during anemia significantly increased the red blood cell count, hemoglobin concentration, hematocrit and reticulocyte percentage in a dose-dependent manner. These findings indicate that anemia in the DBA/2FG-pcy mouse is due to increased fragility of erythrocytes, a deficiency in EPO for the degree of anemia and a decreased number or a decreased response of erythroid progenitor cells. We suggest that the DBA/2FG-pcy mouse is a useful spontaneous model of chronic progressive renal failure.

Anemia↗

Development of macromolecular Sn(II) complex for preparation of 99Tcm radiopharmaceuticals.

Macromolecular Sn(II) complex (R-Sn) was developed using a chelating resin containing aminophosphonic acid groups as a reducing agent of 99Tcm(VII) in the preparation of 99Tcm radiopharmaceuticals. Since Sn(II) was bonded strongly to the resin by chelation, release of Sn from R-Sn was rarely observed in saline solution. 99Tcm labelling with a yield greater than 90% was performed by mixing R-Sn, 99Tcm pertechnetate solution and a ligand, such as human serum albumin and diethylenetriamine pentaacetic acid, for a short time. The 99Tcm radiopharmaceuticals were almost free from Sn(II) and the reducing activity of R-Sn was quite stable despite long-term storage without any special care.

Adsorption↗

Preparation of recombinant protein A-lymphotoxin chimeric protein and its antitumor effects in mice.

We have investigated the in vivo function of a chimeric protein constructed by recombinant DNA techniques. The behavior and antitumor activity of a protein A-lymphotoxin chimera (ALT) was examined on a murine tumor in mice in comparison with amino-terminal 19 amino acid-deleted lymphotoxin (dLT). Seven-week-old male BALB/c mice were implanted intradermally with Meth-A fibrosarcoma on day 0. ALT and dLT caused tumor regression, hemorrhagic necrosis and complete regression in a dose-related way when each agent was given intratumorally 5 times (days 5-9). The ratio of the median effective doses for complete tumor regression was 1.6 between ALT and dLT on a molar basis. ALT caused tumor regression and body weight loss when given intravenously on the same schedule. Biodistribution studies with 125I-labeled ATL and dLT demonstrated that, after intratumoral administration, ALT was retained longer in the administered site and was cleared more slowly from the mouse body than dLT. These findings suggest that a protein A-lymphotoxin chimeric protein expresses both antitumor activity similar to that of lymphotoxin and characteristic in vivo behavior of the fused protein A portion.

Animals↗

Relation between nucleolar size and growth characteristics in small cell lung cancer cell lines.

Relationships among cytological features, doubling time, S-phase percentage, expression of myc-family oncogenes, DNA ploidy and biochemical properties were studied in thirteen small cell lung cancer cell lines. Six cell lines that grew slowly (average doubling time 99 h) and had lower S-phase percentages (average 32%) showed inconspicuous nucleoli (average area of 1.5 microns 2), and the remaining seven cell lines that grew quickly (average doubling time 45 h) and had higher S-phase percentages (average 44%) showed large and prominent nucleoli (average area of 6.1 microns 2). DNA index value obtained from flow cytometric DNA histograms showed that all cell lines except for H-69 cell line displayed aneuploidy. Ribbon-like cell arrangements were observed in the 7 cell lines that grew quickly, and in 1 cell line that grew slowly. Biochemically, six slow-growing cell lines and four fast-growing cell lines showed high levels of aromatic L-amino acid decarboxylase activity, while in the remaining three fast-growing cell lines its level was low. A high level of c-myc or N-myc oncogene expression was observed in all 7 cell lines that grew quickly, but not in any of the 6 cell lines that grew slowly. It appears that small cell lung cancer cell lines that grow quickly can be expected to have large nucleoli and ribbon-like cell arrangements and to express high levels of myc-family oncogenes, and that nucleolar size is a good indicator for growth characteristics.

Animals↗

The effect of chronic exercise on the pituitary-adrenocortical response in conscious rats.

1. This study was designed to investigate the effect of chronic exercise on exercise-induced changes in plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosterone in rats. Corticotrophin releasing factor (CRF) and ACTH were injected I.V. in order to assess the responsiveness of the pituitary and adrenal glands after chronic exercise. 2. The concentrations of ACTH and corticosterone in the plasma increased significantly after acute exercise in both the control and the exercised groups but both responses were significantly smaller in the exercised group. 3. The ACTH response to I.V. CRF was also significantly smaller in the exercised rats. However, both groups of animals showed similar increases in plasma corticosterone levels after the administration of exogenous ACTH. 4. The ACTH response to CRF attenuated by repeated administration of CRF. 5. These results suggest that attenuated ACTH and corticosterone responses to acute exercise after chronic exercise result from reduced responsiveness of the pituitary gland to CRF.

Adrenal Glands↗

Isolation of a human DNA sequence which spans the fragile X.

To identify the sequences involved in the expression of the fragile X and to characterize the molecular basis of the genetic lesion, we have constructed yeast artificial chromosomes (YACs) containing human DNA and have screened them with cloned DNA probes which map close to the fragile site at Xq27.3. We have isolated and partly characterized a YAC containing approximately 270 kb of human DNA from an X chromosome which expresses the fragile X. This sequence in a yeast artificial ring chromosome, XTY26, hybridizes to the two closest DNA markers, VK16 and Do33, which flank the fragile site. The human DNA sequence in XTY26 also spans the fragile site on chromosome in situ hybridization. When a restriction map of XTY26, derived by using infrequently cutting restriction enzymes, is compared with similar YAC maps derived from non-fragile-X patients, no large-scale differences are observed. This YAC, XTY26, may enable (a) the fragile site to be fully characterized at the molecular level and (b) the pathogenetic basis of the fragile-X syndrome to be determined.

Chromosome Mapping↗

[An effect of priming task repetition on memory processes in an epileptic with amnesia].

The purpose of this paper is to investigate memory processes in an epileptic with amnesia. Selective impairment of memory in organic amnesia has been reported in some clinical observations. They also demonstrated that organic amnesia can retain some aspects of learning experience, despite their inability to recollect them. We investigated an effect of priming task repetition on memory processes in a female with organic amnesia aged 28 (probable encephalitic patient) and eight control college students aged 20-26. In this paper, her memory processes were analyzed, using the same picture priming task, carried twelve times during the period of seven months. We used semantic priming paradigm. Three types of prime-target pair were used: identical, semantically related and unrelated. After a prime picture, a target picture appeared on the CRT display. She was asked to name each target as rapidly and accurately as possible. We analysed reaction time (RT) in naming the picture targets, error rate, and verbal reports of the priming task in the pre- and post-examination interview. In the first examination, priming effect was observed in her RT as in the controls'. This suggests that she retained some amount of semantic memory, and the structure of her semantic memory closely resembled that in the controls. Naming RT reduced and error rate decreased with repetition of the examination. This suggests that she acquired picture naming skill during early few examinations. However it was difficult for her to recognize and recollect the picture stimuli in this period. Further, she did not show any episodic memory of the examinations. There was dissociation between improved RT performance and poor verbal reports during early few examinations. When the same priming task was repeated in early few examinations, the priming effect became weaker in her RT. In the controls, on the contrary, the priming effect remained during the whole task repetition. Semantic strategy was apparently used in the controls, but not in the amnesic patient. She apparently used strategy of non-semantic association between the prime and target. In the last few examinations, her naming RT delayed and the priming effect was observed again as in the first examination. She seemed to use semantic strategy. In addition to this priming effect, she re-collected a few pictures and showed some episodic memory of the examination.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Promoters and autogenous control of the Escherichia coli hupA and hupB genes.

Three start sites and a single start site for transcription of the hupB and hupA genes, respectively, have been identified in Escherichia coli. Preceding the RNA start sites are DNA sequences that conform to canonical promoter consensus sequences. The two most upstream promoters of the hupB gene function in vivo at comparable efficiency, while the third is not expressed significantly. Both hupB and hupA genes possess a DNA sequence with a rho-independent transcriptional terminator in their respective regions downstream from the coding regions. The hup genes are both transcribed in vivo into monocistronic mRNA molecules. Upon introduction of an HU-overproducing plasmid carrying either the hupB or the hupA gene into the wild-type and hup single deletion mutants, the intracellular levels of mRNA from the chromosomal hup genes are reduced. The HU-1 and HU-2 proteins both repress both hup genes, repression of the hupB gene being less efficient. The HU protein selectively represses mRNA synthesis starting at the hup promoters in the hupB promoter-CmR and hupA promoter-KmR fusion genes, but does not have a negative regulatory effect on mRNA synthesis from the true CmR and KmR promoters. These findings suggest that the signals for the actions of HU proteins are located in the DNA regions upstream from the sites near the 5' extremities of the coding regions of the hupB and hupA genes.

Bacterial Proteins↗

Cytotoxic T lymphocyte triggering via CD16 is regulated by CD3 and CD8 antigens. Studies with T cell receptor (TCR)-alpha beta+/CD3+16+ and TCR-gamma delta+/CD3+16+ granular lymphocytes.

The role of CD3 and CD8 Ag in CD16-mediated CTL triggering was studied in TCR-alpha beta+ and TCR-gamma delta+ granular lymphocytes (GL). In TCR-alpha beta+/CD3+4-8+16+ GL obtained from patients with GL-proliferative disorders, antibody-dependent cellular cytotoxicity was inhibited by anti-CD3 and anti-CD8 mAb. Anti-CD3 mAb also inhibited antibody-dependent cellular cytotoxicity activity of TCR-gamma delta+/CD3+4-8-16+ GL from a patient and that of TCR-gamma delta+/CD3+4-8+/-16+ T cell clones established from patients with proliferating TCR-gamma delta+ GL. In TCR-gamma delta+ T cell clones, cytotoxicity against Fc gamma R+ targets was induced by stimulation of CD16 Ag with anti-CD16 mAb, and such cytotoxicity was also inhibited by anti-CD3 mAb. These results indicate that CD3 and CD8 molecules play a regulatory role in CD16-mediated CTL triggering.

Antibody-Dependent Cell Cytotoxicity↗

Favourable associations between the myosin heavy-chain and light-chain isoforms in human skeletal muscle.

Histochemical and biochemical analyses were performed in order to examine the relationship between myosin light-chain (LC) isoforms and fibre-type distributions in whole human skeletal muscle. Muscle biopsies were obtained from the vastus lateralis muscle in six healthy men, and analysed for the relative area occupied by each fibre type (percentage of fibre type area) and the molar ratio of each LC isoform. The percentage of type I fibre area was positively correlated with the molar ratio of slow LC (LC1s and LC2s) to total LC. The regression line was located below the line of unity. Also, the ratio of percentage of type IIa fibre area to that of type II fibre area was positively correlated with the molar ratio of the fast alkali LC LC1f to fast alkali LCs LC1f and LC3f. These results support previous study, having shown that in human skeletal muscle some type I fibres express various amounts of fast LC in addition to slow LC and suggest that fast myosin heavy-chain HCIIa is favourably associated with LC1f, whereas HCIIb is favourably associated with LC3f.

Adult↗

Temperature modulation of photoperiodically induced LH secretion and its termination in Japanese quail (Coturnix coturnix japonica).

Long days induced LH release in photosensitive Japanese quail and ambient temperature did not affect this process. Temperature also did not affect the levels of circulating LH concentrations at the steady state of LH release on long days. On the other hand, low ambient temperature was required to reduce circulating LH to a nonbreeding level together with the change of the photoperiod from long to short days; the changes of the photoperiod without low ambient temperature induced a decrease of circulating LH only to a certain level (1-2 ng/ml) which could maintain reproductive activity. The results also indicated that there were three levels of circulating LH in quail which were tentatively designated as a nonbreeding level (less than 0.5 ng/ml), a basal breeding level (1-2 ng/ml), and a steady breeding level (ca. 4 ng/ml). By photostimulation, levels of circulating LH increased to the steady breeding level directly and gradually, or leveled off after overshooting it. Photoperiodic changes from long to short days under moderate temperature resulted in a decrease in circulating LH to the basal breeding level which, however, could keep the gonad and the accessory sex organs active. Photoperiodic changes under cold ambient temperature reduce circulating LH to the nonbreeding level at which the gonad and the accessory sex organs regressed completely. These results suggest that ambient temperature is involved in the mechanism controlling an annual reproductive cycle, especially at the termination of the reproductive activity, in Japanese quail.

Animals↗

Magnetic resonance imaging of spinal cord injury without radiologic abnormality.

A 3-year-old girl with spinal cord injury without radiologic abnormality (SCIWORA) is reported. Magnetic resonance imaging (MRI) showed an abnormal intensity of the spinal cord at the level of C7 to Th1 in the acute stage and severe atrophic change in the chronic stage. This is the first report of SCIWORA with positive diagnostic imaging. The mechanism of SCIWORA is discussed based on the positive MRI findings.

Child, Preschool↗

Acute cytogenetic effects of tyramine and MTCAs on mouse bone marrow cells in vivo by the micronucleus test.

We studied the acute cytogenetic effects of tyramine and MTCAs--precursors of the mutagen present in soy sauce--on mouse bone marrow cells in vivo by the micronucleus test. The incidence of MNPCE in bone marrow cells gradually increased and reached a maximum level 24 h after intraperitoneal injection of tyramine or MTCAs and decreased within 36 h. A dose-dependent increase in MNPCE was clearly observed for both compounds. Compared to the values for the untreated control, significant positive results were obtained with 0.5 mmole tyramine/kg (68.5 mg/kg) and with 0.1 mmole MTCAs/kg (23 mg/kg) 24 h after intraperitoneal administrations. Micronuclei were significantly induced but no severe reduction in the ratio of PCEs/NCEs was observed.

Animals↗

Acute and subacute cytogenetic effects of the trihalomethanes on rat bone marrow cells in vivo.

The mutagenic effects of the trihalomethanes (THMs: chloroform, CHCl3; dichlorobromomethane, CHCl2Br; dibromochloromethane, CHClBr2; bromoform, CHBr3), found in chlorinated drinking water have been studied for their ability to induce chromosome aberrations (CA) in vivo in rat bone marrow cells. THMs were administered intraperitoneally (i.p. acute) and orally (subacute). Using a maximal dose of 1 mmole/kg body weight, positive results were noted for CHCl3, CHCl2Br, CHClBr2 and CHBr3 with i.p. treatment, and for CHCl3 and CHBr3 with oral treatment. The time-dependent increase in CA showed a maximum level at 12 h after i.p. injection and at 18 h after the fifth and last day of oral treatment.

Administration, Oral↗

Acute cytogenetic effects of tyramine, MTCAs, NaCl and soy sauce on rat bone marrow cells in vivo.

The acute cytogenetic effects of tyramine and MTCAs, precursors of the mutagen present in soy sauce, were studied with the in vivo chromosome aberration test in rat bone marrow cells. The chemicals were administered intraperitoneally. Statistically significant positive results were obtained with tyramine at a dose of 5 mmole/kg (686 mg/kg) body weight and with MTCAs at doses over 0.50 mmole/kg (115 mg/kg) body weight, respectively. Chromosome aberrations (CA) induced by L-proline co-administered with either tyramine or MTCAs were significantly lower than those induced by each chemical alone. These data suggest that L-proline, after endogenous nitrosation, became nitrosoproline and suppressed CA, and that, as a result of in vivo nitrosation of tyramine and MTCAs, they became mutagenic nitroso compounds showing positive results. Statistically significant positive results were obtained by administration of 40 mmole NaCl/kg body weight (2338 mg/kg). The cocarcinogenic role of NaCl with tyramine was suggested because soy sauce contains about 18% NaCl.

Animals↗

Production of a protein A--lymphotoxin hybrid protein for cancer-targeted therapy.

A hybrid protein between staphylococcal protein A and human lymphotoxin, ALT, was produced in Escherichia coli by expression of a recombinant plasmid containing the respective genes. IgG-binding activity of ALT was confirmed by Western blotting analysis and by affinity purification with IgG-Sepharose column chromatography. The purified ALT had cytotoxicity on mouse L-929 cells and its specific activity was approximately 3.5-5.0 X 10(6) U mg-1. ALT was partially degraded by a protease including in the E. coli lysate or trypsin and was converted to lymphotoxin which lacks the NH2-terminal 19 residues but possesses higher cytotoxic activity than ALT.

Amino Acid Sequence↗