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Biomedical subjects

K Murata

Publications and source records attributed to K Murata.

At least 217 records · Page 12Linked to original sources

Recombinant viruses expressing a human malaria antigen can elicit potentially protective immune CD8+ responses in mice.

Extensive studies on protective immunity to rodent malaria provided the basis for the current experiments in which mice were immunized with recombinant (re) influenza and vaccinia viruses expressing selected sequences of the circumsporozoite (CS) protein of the human malaria parasite Plasmodium falciparum. Mice of different H-2 haplotypes immunized with re influenza viruses expressing the immunodominant B cell epitope of this CS protein produced high titers of antibodies to the parasite. A cytotoxic T lymphocyte epitope of the CS protein of P. falciparum, PF3, recognized by CD8+ T cells of H-2(k) mice, was expressed in a re vaccinia virus (VacPf) and a re influenza virus (FluPf). Immunization of mice with either FluPf or VacPf elicited a modest CS-specific CD8+ T cell response detected by interferon gamma secretion of individual immune cells. Priming of mice with FluPf, followed by a booster with VacPf, resulted in a striking enhancement of this T cell response. The reverse protocol, i.e., priming with VacPf followed by a booster with FluPf, failed to enhance the primary response. VacPf also greatly enhanced the primary response of mice injected with P. falciparum sporozoites or with a lipopeptide containing PF3. A booster with FluPf also amplified the response of lipopeptide- or sporozoite-primed mice but less than a VacPf booster did. Although mice are not susceptible to infection by P. falciparum sporozoites, we demonstrated that administration of two distinct immunogens expressing PF3 elicited activated, extravasating CS-specific T cells that protected against an intracerebral VacPf challenge.

Amino Acid Sequence↗

Possible association between adult T-cell leukemia/lymphoma and acute myeloid leukemia.

BACKGROUND: To the authors' knowledge, an association between adult T-cell leukemia/lymphoma (ATL) and acute myeloid leukemia (AML) has been reported only in four patients. The authors identified five additional patients with both neoplasms. METHODS: A review of the clinical records of patients with AML, ATL, or lymphoid neoplasms other than ATL diagnosed between 1986 and 1995 was performed. Cytokine levels were assayed in selected patients. The authors searched for reports from other institutions using MEDLINE and the proceedings of two Japanese hematology societies. RESULTS: ATL was diagnosed in 134 patients, whereas 180 had AML. Five patients with both neoplasms were identified (3.7% of ATL patients and 2.8% of AML patients). In seven of the nine patients (including four patients in the literature) with ATL and AML, the ATL was diagnosed prior to the AML, whereas in the remaining two patients both neoplasms were diagnosed simultaneously. Six of the nine cases were therapy-related (t)-AML, which developed after chemotherapy for ATL. Monoclonal integration of proviral human T-lymphotropic virus type 1 was detected in ATL cells but not in AML cells in the six patients examined. The plasma levels of macrophage colony-stimulating factor (M-CSF), granulocyte-colony stimulating factor, and granulocyte-macrophage-colony stimulating factor (GM-CSF) were elevated in 3, 1, and 1, respectively, of the 4 patients examined at AML onset who had active ATL. In one case, the levels of several cytokines, including GM-CSF and M-CSF, in the supernatant fluid of short term cultured ATL cells were elevated. Three patients with de novo ATL and AML received remission induction therapy, and two achieved a complete remission (CR) of both diseases. Among the four patients who received chemotherapy for t-AML, two achieved CR. CONCLUSIONS: ATL patients also can develop AML, irrespective of treatment with chemotherapy for ATL. This association does not indicate exclusive chemoresistance of both neoplasms. Cytokines produced by ATL cells may support the growth of AML cells.

Acute Disease↗

Podophyllotoxin and nocodazole counter the effect of IKP104 on tubulin decay.

Tubulin, the subunit protein of microtubules, undergoes a time-dependent loss of functional properties known as decay. We have previously shown that the drug 2-(4-fluorophenyl)- -(2-chloro-3,5-dimethoxyphenyl)-3-methyl-6-phenyl-4(1H)-pyridinone (IKP104) accelerates decay, but that in the presence of colchicine, IKP104 becomes a stabilizer of tubulin. To see if this is due to conformational effects specific to colchicine or simply to occupancy at the colchicine site, we examined the effects of nocodazole and podophyllotoxin, two well-known competitive inhibitors of colchicine for binding to tubulin, on IKP104's acceleration of decay. We found that podophyllotoxin abolished IKP104's accelerating effect and, like colchicine, turned it into a stabilizer of tubulin. Nocodazole's effects were similar to those of podophyllotoxin and colchicine, in that it abolished IKP104-induced enhancement of decay; however, in the presence of nocodazole, IKP104 caused little or no stabilization of tubulin. Since colchicine, nocodazole, and podophyllotoxin have very different interactions with tubulin, but all inhibit the IKP104-induced enhancement of decay, our findings suggest that this inhibition arises from occupancy of the colchicine site rather than from a direct conformational effect of these two drugs.

Alkylation↗

Distinct and overlapping binding sites for IKP104 and vinblastine on tubulin.

IKP104 is one of a group of tubulin-binding drugs whose interaction with tubulin suggests that it may bind to the protein at or close to the region where vinblastine binds. By itself IKP104 is a potent enhancer of tubulin decay as evidenced by the fact that it induces the exposure of the sulfhydryl groups and hydrophobic areas on tubulin. In this respect, IKP104 differs from vinblastine and other drugs such as phomopsin A, dolastatin 10, rhizoxin, and maytansine which are competitive or noncompetitive inhibitors of vinblastine binding. In contrast, however, in the presence of colchicine, IKP104 behaves differently and strongly stabilizes tubulin, to an extent much greater than does colchicine alone. IKP104 appears to have two classes of binding site on tubulin, differing in affinity; the acceleration of decay appears to be mediated by the low-affinity site (Chaudhuri et al., 1998, J. Protein Chem., in press). We investigated the relationship of the binding of IKP104 and vinblastine. We found that the high-affinity site or sites of IKP104 overlap with or interact with the vinblastine-binding sites, but that the low-affinity site is distinctly different.

Alkylation↗

Calcium disodium ethylenediaminetetraacetate-chelated lead as a predictor for subclinical lead neurotoxicity: follow-up study on gun-metal foundry workers.

OBJECTIVES: To examine if chelated lead was a more predictive indicator of the subclinical effect of lead on conduction velocities of faster or slower nerve fibers as compared with blood lead (BPb). METHODS: Distribution of conduction velocities (DCV) in large myelinated fibers of the sensory median nerve was measured twice at a 1-year interval in 17 male gun-metal foundry workers with BPb concentrations of 22-59 (mean 40.2) microg/dl and a mobilization yield of lead into urine (MPb) by calcium disodium ethylenediaminetetraacetate of 0.15-2.09 (mean 1.19) mg/24 h for the 1st year and in 20 healthy males (controls). RESULTS: Yearly changes in the conduction velocities of faster fibers were significantly correlated with the corresponding change in MPb (P < 0.05) but not with that in BPb (P > 0.05). In ten workers showing an increase in MPb during the 1-year period (0.44 mg/24 h on average) the conduction velocities of faster fibers were decreased significantly, resulting in the values being significantly lower in all the workers combined than in the controls (P < 0.05). On the other hand, in the remaining workers, who showed a lesser extent of reduction in MPb (0.08 mg/24 h on average), the DCV did not change (P > 0.05). CONCLUSION: Chelated lead might be a more predictive indicator of the effect of lead on the conduction velocities of faster fibers than blood lead.

Adult↗

A temperate phage with cohesive ends induced by mitomycin C treatment of Lactobacillus casei.

A temperate phage, named PL-2, was induced from Lactobacillus casei ATCC 27092 by mitomycin C treatment of the cells at exponential growth phase. The phage had an isometric head of 45 nm in diameter and a flexible, non-contractile tail, 150 nm long and 10 nm wide, with a sharp tip. Along the tail axis, about 40 regularly spaced striae were seen. The phage DNA had complementary cohesive ends. The restriction enzyme map of the DNA was constructed by using 13 different restriction endonucleases. The size of the DNA was 35.2 kb, 83% in size of that of phage PL-1 lytic for the same Lb. casei strain.

Bacteriophages↗

Malignancies of human thyroid tumors and dynamic magnetic resonance imaging (MRI).

Time intensity curves for gadolinium-diethylene triaminepentacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), namely dynamic MRI, were determined for thyroid diseases and compared with findings of histopathologic examination. Time intensity curves for solid lesions were determined, excluding cases with secondary changes such as calcification, hemorrhage, necrosis and fibrosis. Three different patterns of time intensity curves were observed: rapid washout, delayed washout and no change. In our previous study, malignant grades of thyroid tumors were estimated immunohistochemically by epidermal growth factor receptor (EGFR) antibody. In most of malignant diseases and a few benign diseases that had marked cell proliferative activity with staining EGFR strongly, the time intensity curve displayed a delayed washout pattern, in which intensity was above 1/2-maximal value within 10 min after injection Gd-DTPA. Almost all benign diseases and a few well differentiated carcinomas displayed a rapid washout pastern, in which intensity was decreased to lower than 1/2 of peak grade within 10 min following injection and showed staining EGFR weakly. Benign diseases showing no change of time intensity curve, did not almost show aEGFR positive cell. These findings suggested that the time intensity curve obtained from dynamic MRI might indicate differentiated grades and cell proliferating activity of thyroid tumors.

Contrast Media↗

Radioimmunoassay for TA-0910, a new stable thyrotropin releasing hormone analogue and its metabolite, TA-0910 acid-type, in human plasma and urine.

Radioimmunoassay (RIA) was investigated for the determination of TA-0910 and its main metabolite, TA-0910 acid-type, in human plasma and urine. TA-0910 is a new metabolically stable analogue of thyrotropin releasing hormone (TRH). Antiserum was raised in the rabbit against the 1-fluoro-2,4-dinitrophenyl derivative of TA-0910 or TA-0910 acid-type conjugated to keyhole limpet hemocyanin (KLH). The radioligand was prepared by iodination with 125I of the histidine imidazole ring of TA-0910 or TA-0910 acid-type. Cross-reactivities of anti-TA-0910 or TA-0910 acid-type antiserum for TA-0910, its metabolite and related compounds were low. The calibration range was 0.02-5 ng ml-1 using 100 microliters human plasma or urine. Inter-day variations of TA-0910 and TA-0910 acid-type assay in plasma were 3.5-15.5 and 1.8-9.4%, respectively. The variations of the assay in urine were the same as those in plasma. The recovery of TA-0910 and TA-0910 acid-type spiked in plasma or urine samples was approximately 100%. Furthermore, this method was applied to the determination of TA-0910 and TA-0910 acid-type in human plasma and urine samples, for the evaluation of the pharmacokinetics of TA-0910 in humans. From the results it was demonstrated that he developed RIA was useful for the determination of TA-0910 and TA-0910 acid-type in human plasma and urine, and was applicable to pharmacokinetic studies in humans.

Administration, Oral↗

Mental arithmetic is a useful diagnostic evaluation in white coat hypertension.

It remains unclear whether patients with white coat hypertension are more susceptible to mental stress than are those with essential hypertension. To compare the pressor responses to mental arithmetic between the two types of hypertension, 21 untreated female outpatients, aged 42 to 64 (mean 55) years, with hypertension, were studied. After 2 weeks of self-monitoring blood pressure, 11 patients were diagnosed as having white coat hypertension and the remaining 10 patients were diagnosed as having essential hypertension. The systolic and diastolic blood pressure responses to mental arithmetic testing were significantly greater in the patients with white coat hypertension (+38 +/- 18/+24 +/- 13 mm Hg) than in those with essential hypertension (+21 +/- 8/+13 +/- 6 mm Hg). These differences also were statistically significant in controlling for the effects of age and baseline blood pressures. These data suggest that mental arithmetic testing may be a useful tool for the diagnosis of white coat hypertension.

Adult↗

Long-term observation after soft posterior meatal wall reconstruction in ears with cholesteatoma.

We performed tympanoplasty with reconstruction of the soft posterior meatal wall for the prevention of post-operative retraction pocket formation. Our method is characterized by the reconstruction of the soft posterior meatal wall, non-obliteration with permanent or temporary materials, including Gelfoam, no use of a Palva flap and the use of fibrin glue for attaching the fascia to the posterior meatal skin. None of the patients experienced post-operative narrow-neck retraction pocket formation, and whenever aeration of the middle ear was disturbed, a balloon-like retraction was observed. Not all the posterior meatal walls retracted. The final position of the posterior meatal wall varied among the subjects. No serious cavity or hearing problems have occurred since surgery. Due to the strong possibility of post-operative retraction pocket formation in cases with a large balloon-like retraction, we rejected adopting the canal wall up technique or hard posterior meatal wall reconstruction.

Cholesteatoma, Middle Ear↗

Tubulin stability and decay: mediation by two distinct classes of IKP104-binding sites.

IKP104, a novel antimitotic drug, has two classes of binding sites on bovine brain tubulin with different affinities. IKP104, by itself, enhances the decay of tubulin, but in the presence of colchicine or podophyllotoxin, it stabilizes tubulin instead of opening up the hydrophobic areas [Luduena et al. (1995), Biochemistry 34, 15751-15759]. Here, we have dissected these two apparently contradictory effects of IKP104 by cleaving the C-terminal ends of both alpha and beta subunits of tubulin with subtilisin. We have found that the selective removal of the C-terminal ends from both the alpha and beta subunits of alphabeta tubulin lowers the sulfhydryl titer by approximately 1.5 mol/mol of dimer. Interestingly, IKP104 does not increase either the sulfhydryl titer or the exposure of hydrophobic areas of this subtilisin-treated tubulin (alpha(s)beta(s)). Moreover, IKP104 lowers the sulfhydryl titer of alpha(s)beta(s) tubulin approximately by 1 mol/mol and appears to inhibit completely the time-dependent decay of alpha(s)beta(s) tubulin. The cleavage at the C-terminal ends of both alpha and beta modulates the effect of IKP104 on the beta subunit, but not on the alpha subunit. Fluorometric binding data analysis suggests that IKP104 binds to the alpha(s)beta(s) tubulin only at the high-affinity site; the low-affinity site(s) disappear almost completely. The sulfhydryl titer data for alpha and beta and the fluorometric data therefore suggest that the interaction of IKP104 at the high-affinity site on tubulin is not regulated by the C-terminal domains of alpha and beta and the effect of the high-affinity site is restricted largely to the alpha subunit, while the low-affinity-site binding is modulated by the C-terminal domain of beta. It also appears that the stabilization and the acceleration of the decay of tubulin are mediated by distinct interactions of IKP104 with its high- and low-affinity sites on tubulin, respectively.

Animals↗

The third egg envelope subunit in fish: cDNA cloning and analysis, and gene expression.

The inner layer of the egg envelope of a teleost fish, the medaka, Oryzias latipes, consists of two major subunit groups, ZI-1,2 and ZI-3. On SDS-PAGE, the ZI-1,2 group presents three glycoprotein bands that were considered to be composed of a common polypeptide moiety derived from their precursor, choriogenin H (Chg H). ZI-3 is a single glycoprotein derived from the precursor, choriogenin L (Chg L). In the present study, a fraction of a novel subunit protein was found in the V8 protease digest of ZI-1.2 that was partially purified from oocyte envelopes. This protein fraction was not present in the purified precursor, Chg H. By RT-PCR employing the primers based on the amino acid sequence of this fraction, a cDNA for the novel subunit was amplified, and a full-length clone of the cDNA was obtained by screening a cDNA library constructed from the spawning female liver. The clone consisted of 2025 b.p. and contained an open reading frame encoding the novel protein of 634 amino acids. This protein included Pro-X-Y repeat sequences in two-fifths of the whole length from its N-terminus. Northern blot analysis revealed that the gene expression for this protein occurred in the liver but not in the ovary of spawning female fish. This protein is considered as the third major subunit of the inner layer of the egg envelope of medaka.

Amino Acid Sequence↗

A method for prevention of arterialized venous flap necrosis.

The authors used a delayed arteriovenous (A-V) shunt method to prevent congestion and necrosis of arterialized venous flaps. Two weeks before elevating the flap, an A-V shunt between the central artery and vein was created at the more proximal flap end. Twelve rabbits (24 flaps) were used for this experiment. Flaps were followed for 4 weeks. Twelve of 24 flaps survived completely; another 10 flaps showed partial necrosis; and two flaps became completely necrotic. These results demonstrated that this method is superior to a simple A-V shunt in preventing congestion and necrosis in the arterialized venous flap.

Animals↗

Serotonin derivative, N-(p-coumaroyl) serotonin, inhibits the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 by endotoxin-stimulated human blood monocytes.

We have reported that N-(p-coumaroyl) serotonin (CS) and its derivatives with antioxidative activity are present in safflower seeds. As reactive oxygen species (ROS) are implicated in the signaling of lipopolysaccharide (LPS), we examined whether CS has a suppressive effect on inflammatory cytokine generation from human monocytes in vitro. CS at 50-200 microM reduced tumor necrosis factor (TNF), interleukin-1 (IL-1), and IL-6 activities in the culture supernatants from LPS-stimulated human blood monocytes without cytotoxicity. ELISA assay revealed that the production of TNF-alpha, IL-1alpha, IL-1beta, and IL-6 was inhibited by CS. Northern blot analysis showed that LPS-induced expression of these cytokine mRNA in monocytes was suppressed by CS. NF-kappaB activation was also inhibited by CS. These findings indicate that CS has a suppressive effect on proinflammatory cytokine production from monocytes, and this effect is based in part on the suppression of cytokine mRNA expression through inhibition of NF-kappaB activation.

Cells, Cultured↗

Prolongation of allograft survival by administration of mAb specific for the three subunits of IL-2 receptor.

The IL-2 receptor (IL-2R) gamma chain, the so-called common gamma (gamma(c)) chain, which is shared with multiple cytokine receptors, plays important roles in the immune system. Here we assessed the immunosuppressive ability of mAb specific for the gamma(c) chain in induction of cytotoxic T lymphocytes (CTL) and allograft rejection in combination with mAb specific for the alpha and beta chains of IL-2R. CBA/N (H-2k) mice were injected i.p. with allogeneic splenocytes from BALB/c (H-2d) mice, and then administered with combinations of anti-IL-2R alpha, anti-IL-2R beta and anti-gamma(c) mAb or a control mAb. Addition of anti-gamma(c) mAb together with anti-IL-2R alpha and anti-IL-2R beta mAb induced a complete inhibition of CTL response. The numbers and populations of CD4+ CD8- and CD4- CD8+ T cells were not significantly affected by administration of the three anti-IL-2R mAb, whereas NK cells were completely depleted in spleens of mice treated with the anti-IL-2R mAb. Furthermore, skin allograft survival was also significantly prolonged by administration of the three anti-IL-2R mAb. These results suggest that the anti-gamma(c) mAb in combination with anti-IL-2R alpha and anti-IL-2R beta mAb is capable of suppressing induction of CTL and NK cells, resulting in prolongation of skin allograft survival.

Animals↗

Comparison of different computed tomography scanning methods for quantifying emphysema.

Computed tomography (CT) is used to detect emphysematous changes in the lungs of living patients. It is therefore important to develop a standard method for the radiographic quantification of emphysematous lesions using CT. The authors determine the best CT scanning methods for assessing the degree of pulmonary emphysema. Computed tomography scanning was performed in 85 consecutive patients with stable chronic obstructive pulmonary disease. Scans were obtained using 2-mm or 5-mm collimation, at full inspiration or full expiration, and with standard or high spatial-resolution reconstruction images (eight images each). Emphysema was then assessed by visual scoring using a five-point scale for each lung. Emphysema was scored as significantly less severe using standard reconstruction images. There were no significant differences in CT-scored emphysema on scans obtained with 2-mm and 5-mm collimation. Emphysema was scored as significantly less severe on expiratory scans. The postbronchodilator forced expiratory volume in one second value correlated better with emphysema scored on expiratory scans. Computed tomography-scored emphysema obtained by all methods correlated well with the diffusion capacity and total lung capacity, regardless of the method used. Using a visual scoring system with a five-point scale, narrow collimation is probably not necessary for the quantification of emphysema, although a high spatial-resolution reconstruction appears to be of value. Scans obtained in exhalation appear to underemphasize the severity of emphysema.

Aged↗

A preliminary study on delayed vestibulo-cerebellar effects of Tokyo Subway Sarin Poisoning in relation to gender difference: frequency analysis of postural sway.

To evaluate delayed (long-term) effects of acute sarin poisoning on postural balance, nine male and nine female victims of the Tokyo Subway Sarin Poisoning in Japan (sarin cases) were examined by computerized posturography 6-8 months after the poisoning. Their plasma cholinesterase activities (ChE) on the day of the poisoning (March 20, 1995) were 13-95 (mean 68.2) IU/l for females and 19-131 (mean 75.9) IU/l for males, which were not significantly different between the two sexes. In females, the postural sway of low frequency (0-1 Hz) in the anterior-posterior direction and area of sway with eyes open was significantly larger in the cases than in the controls. Romberg quotients for the low-frequency sway in the anterior-posterior direction for females and low-frequency sway and length of sway in the medio-lateral direction for males were significantly related to log ChE. It is suggested that a delayed effect on the vestibulo-cerebellar system was induced by acute sarin poisoning; females might be more sensitive than males.

Adult↗