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Biomedical subjects

M Nakano

Publications and source records attributed to M Nakano.

At least 523 records · Page 29Linked to original sources
PubMed1995

Cytotoxic lymphocytes in the peripheral blood of patients with B cell lymphomas.

In order to analyze systemic immune surveillance in patients with B cell non-Hodgkin's lymphomas (B-NHL), we investigated circulating lymphocytes using two-color flow cytometry. The proportions of CD3-CD56+ natural killer (NK) cells and CD8++(bright) S6F1++ killer-effector T cells corresponding to activated cytotoxic T lymphocytes (aCTL) were studied in the peripheral blood of 26 patients with indolent lymphoma (IL) and 24 with aggressive lymphoma (AL). The AL patients with both limited disease and advanced disease had an increased proportion of NK cells. However, this feature was not evident in IL patients with either limited or advanced disease. In contrast, an increased proportion of aCTL was observed only in IL patients with advanced disease. These findings indicate that IL may differ from AL in terms of immune surveillance against neoplastic B cells.

Adult↗
PubMed1994

Intraoperative radiation therapy (IORT) for head and neck cancer.

PURPOSE: To determine the efficacy of intraoperative radiation therapy (IORT) for patients with advanced or recurrent head and neck cancer. METHODS AND MATERIALS: Intraoperative radiation therapy was given at 30 sites in 25 patients using a 6-18 MeV electron beam with or without conventional external beam irradiation. A single dose of 10-30 Gy was delivered after surgical resection. Sites treated with IORT were classified into three types after surgical resection: gross residual disease (GR, n = 7), microscopic residual disease (MR, n = 12), and close margin (CM, n = 11). Local control rate, patterns of recurrence, survival rate, and complications were analyzed. RESULTS: The 2-year cumulative local control rate within the IORT port was 54.1% for all cases, 0% for GR, 54.5% for MR, and 81.8% for CM. There were significant differences between GR and MR (p < 0.05), and GR and CM (p < 0.01). The majority of the failures inside the IORT port were associated with recurrence outside the port. Distant metastases occurred in five patients. Four of these had GR. The 2-year cumulative survival rate was 45.1% for all, 0% for GR, 33.0% for MR, and 70.0% for CM. Five patients (22%) experienced late complications. The 2-year cumulative complication rate was 32.8%. Four sites developed osteoradionecrosis and three developed carotid artery blowout. Incidence of complications increased when patients received over 20 Gy with a single dose of IORT. CONCLUSIONS: Considering both therapeutic ratio and patterns of failure, it is not suitable to treat patients with gross residual disease with IORT. We could not firmly determine the therapeutic value of IORT for patients with microscopic residual disease and close margin. For this subset, further study of moderate dose (less than 20 Gy) IORT combined with adequate postoperative irradiation is needed.

Adult↗
PubMed1994

Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohistochemistry.

Some Ki-1 lymphomas carry a specific chromosomal translocation, t(2;5)(p23;q35). We have recently found a novel hyperphosphorylated 80-kD protein tyrosine kinase, p80, in a human Ki-1 lymphoma with this translocation. Subsequent cDNA cloning showed that p80 is a fusion protein of two different genes on chromosome 2p23 and 5q35, the novel tyrosine kinase gene and nucleophosmin gene, respectively. In this study, we intended to detect p80 on lymphoma tissues with immunologic methods. Thus, we developed rabbit polyclonal antibody using a synthetic peptide corresponding to a part of its kinase domain. The antibody (anti-p80) immunoprecipitated and immunoblotted p80 specifically from AMS3. Then, to examine whether t(2;5)(p23;q35) was present on biopsied lymphomas, reverse transcriptase-polymerase chain reaction (RT-PCR) covering the fusion junction of p80 mRNA was performed. Among 10 Ki-1 lymphomas and 10 additional lymphomas other than the Ki-1 lymphomas, expression of p80 mRNA was detected in three cases exclusively. When these 20 cases and additional 30 lymphomas were immunostained with anti-p80, positive staining was noted exclusively in the three cases found by PCR to have harbored the p80 mRNA. Thus, the present immunostaining, as well as PCR, was shown to be efficient for detecting lymphomas producing this chimeric protein/mRNA.

Amino Acid Sequence↗
PubMed1994

Age-related accumulation of lipofuscin in three different regions of rat brain.

The rate of accumulation of auto-fluorescent granules (lipofuscin) in three different regions of rat brain was investigated at various ages from very young to old animals (1, 2, 3, 6, 12 and 30-34 months of age. The accumulation of lipofuscin increased with age in the three brain regions. The first appearance of lipofuscin granules was at 8 weeks of age in the hippocampus and in the thalamus. In the case of cerebral cortex (laminae III), lipofuscin granules were first found in 3-month-old rats. The rate of lipofuscin accumulation was the highest in the hippocampus (y = 0.286x - 0.099, r = 0.963) among the three regions examined. In the case of cerebral cortex and thalamus, a slower rate of lipofuscin accumulation was observed (y = 0.072x - 0.14, r = 0.797 for cerebral cortex; y = 0.067x - 0.14, r = 0.953 for thalamus). It was noted that the most abundant accumulation and the highest rate of lipofuscin accumulation was in the hippocampus. But the rate and magnitude of lipofuscin accumulation in the hippocampus were low compared with cardiac muscles. From these results, it is suggested that brains have better protective system against oxidative stress than other organs.

Aging↗
PubMed1994

Characterization of the zona pellucida glycoproteins from bovine ovarian and fertilized eggs.

Bovine zona pellucida (ZP) glycoproteins from ovarian egg emerged as three bands with molecular mass of 78 kDa, 64 kDa and 21 kDa in SDS-PAGE under reducing conditions. Endo-beta-galactosidase (E beta G) digestion of the glycoproteins yielded five products with molecular mass of 76 kDa (E beta G-76), 68 kDa (E beta G-68), 63 kDa (E beta G-63), 47 kDa (E beta G-47) and 21 kDa (E beta G-21) under the same conditions. The N-terminal amino acid sequences of E beta G-76 and E beta G-21 were identical. This fact together with the results of diagonal SDS-PAGE indicated that E beta G-21 (N-terminal region) is linked to E beta G-63 (C-terminal region) through disulfide bond to form E beta G-76. Immunoblot analysis using anti-pig ZP protein antibodies revealed that bovine E beta G-76, E beta G-68 and E beta G-47 correspond to pig PZP2, PZP3 alpha and PZP3 beta glycoproteins, respectively. The E beta G-76 and E beta G-68 components were shown to be specifically cleaved during fertilization.

Amidohydrolases↗
PubMed1994

Identification of the 65-kDa phosphoprotein in murine macrophages as a novel protein: homology with human L-plastin.

We demonstrated that a 65-kDa cytosolic protein (pp65) was most heavily phosphorylated in murine macrophages in response to bacterial lipopolysaccharide (J. Immunol. 146:3617, 1991). The pp65 phosphorylation closely correlated with cellular responses in the macrophages. We have thus performed amino acid sequence analysis of the two pp65-derived peptide fragments in order to elucidate its structure and function. The results indicated that pp65 is a novel protein existing almost exclusively in hemopoitetic cells and has the strong homology with human L-plastin, a substrate which has recently been identified as a novel protein transformation-dependently expressed in neoplastic human cells. Our pp65 is apparently the first purified protein whose phosphorylation has been augmented by stimulation with bacterial lipopolysaccharide and whose primary structure has been clarified. Because L-plastin possesses the unique functional domains, detailed investigation of the pp65 phosphorylation should lead to progress in our understanding of the mechanisms of macrophage activation.

Amino Acid Sequence↗
PubMed1994

A simple luminescence method for detecting lipid peroxidation and antioxidant activity in vitro.

The excited carbonyl species formed during lipid peroxidation may transfer their energy to dye molecules containing heavy atoms such as rose bengal to produce excited singlet state dye molecules. The excited dye then emits photons to return to its ground state. The aim of the present study was to investigate the relationship between methemoglobin (metHb)-induced lipid peroxidation, rose bengal luminescence, and O2 consumption in a system containing 0-850 mu M phospholipid and 1 mu M metHb and 1 mu M rose bengal in Tris-HCl buffer, pH 7.4. The rapid rise in rose bengal luminescence was accompanied by a rapid rise in O2 consumption. Further, the luminescence of rose bengal could be quenched by alpha -tocopherol or probucol present in the phospholipid liposomes, with the latter being strikingly more effective than the former. This simple luminescence method is a useful practical approach to detect lipid peroxidation and determined antioxidant effects of water insoluble compounds in vitro.

Antioxidants↗
PubMed1994

[Experimental study of differentiation between tumor and inflammation using MR imaging: correlation between VX2 tumors and croton oil induced inflammation in the rabbit's femoral muscle].

We evaluated the various Magnetic Resonance (MR) sequences for differentiation between tumors and inflammation. Experimental models of rabbit's tumors (VX2) and inflammation induced by croton oil in the femoral muscle were used for this evaluation. Both types of lesions presented a high intensity area on T2-weighted and heavy T2-weighted images. An inflammatory lesion was revealed with iso-/low intensity area and tumors were defined as high signal lesions on Sinc saturation fat suppression T1-weighted, standard T1-weighted and fat suppression T1-weighted images by the 3 Point dixon method. T1, T2 values of tumor and inflammatory lesions were also measured. The T1 value of the tumors was 1186 +/- 58 msec (n = 5) and that of the inflammatory lesion was 1097 +/- 40 msec (n = 3). The T2 value of the tumors was 71 +/- 13 msec (n = 5) and that of the inflammatory lesions was 70 +/- 5.5 msec (n = 3). There were no significant differences between both the T1 and T2 values. Calculated relative proton density was 0.69 +/- 0.14 (n = 4) in the tumors, and 0.42 +/- 0.12 (n = 3) in the inflammatory lesions. A statistical difference (p < 0.05) was found in both value. These results suggest that a T2-weighted image is not useful for differentiation between tumors and inflammation, and a T1-weighted image might be useful for such differentiation. This phenomenon is related to the difference of the proton density.

Animals↗
PubMed1994

Multistep regulation mechanisms for tolerance induction to lipopolysaccharide lethality in the tumor-necrosis-factor-alpha-mediated pathway. Application of non-toxic monosaccharide lipid A analogues for elucidation of mechanisms.

Lipid A is the active principle of lipopolysaccharide (LPS). Synthetic lipid A analogues with monosaccharide backbones, GLA-60, GLA-69 and GLA-58, which exhibit potent, weak and scarce agonistic activities of LPS, respectively, induced tolerance against LPS lethality in galactosamine-(GalN)-sensitized mice while none of them were pyrogenic in rabbits. The tolerance-inducing mechanisms were investigated focusing on the regulation of tumor-necrosis-factor-alpha(TNF-alpha)-mediated lethal pathway of LPS. Induction of serum TNF-alpha in LPS-challenged mice was suppressed by prior administration of these analogues as well as LPS. Prior treatment of murine macrophages with the substances suppressed LPS-stimulated TNF-alpha production in the culture supernatant and TNF-alpha mRNA expression in the cells as well. Lethal toxicity of TNF-alpha in GalN-sensitized mice was effectively suppressed by prior treatment with LPS, GLA-60 and GLA-69 but not by GLA-58. This protective effect was suggested to be mediated by endogenous TNF-alpha, which was induced by prior treatment with the effective substances, because either neutralization of endogenously induced TNF-alpha activity with an antibody or deletion of its induction by using LPS-resistant C3H/HeJ mice reduced the protective effect, and a detectable amount of TNF-alpha was produced by stimulating macrophages with the effective substances but not with GLA-58. These results indicated that multiple regulation steps (one is prior to and the others are following TNF-alpha production) are participating in the tolerance induction by LPS and some lipid A analogues and that GLA-58 is a characteristic compound which induces the tolerance by only blocking the step prior to TNF-alpha production.

Animals↗
PubMed1994

[Role of postoperative irradiation for carcinoma of the uterine cervix: multivariate analysis of prognostic factors and patterns of failure].

We retrospectively analyzed the patterns of recurrence in 48 patients who underwent postoperative irradiation following surgery for carcinoma of the uterine cervix. The end points of pelvic control, distant metastases and disease-free survival were analyzed for parameters including FIGO stage, nodal status, degree of stromal invasion, histology and tumor size. Univariate and multivariate analyses showed that some prognostic parameters had little influence on pelvic control rate, but had a marked impact on the incidence of distant metastases and disease-free survival rate. These results suggest that postoperative irradiation improves pelvic control rate, but has little therapeutic benefit in preventing distant metastases or improving survival rate. In conclusion, we should give more consideration to adjuvant systemic therapy in addition to postoperative irradiation for high-risk patients.

Adult↗
PubMed1994

Pharmacokinetic properties of a novel gastric proton pump inhibitor, (+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H-benzimidazole sodium salt, in healthy subjects.

The pharmacokinetics and safety of TY-11345 [(+/-)-2-[(4-methoxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9- yl)sulfinyl]-1H-benzimidazole sodium salt], a novel gastric proton pump inhibitor, were studied in healthy male volunteers after single (20, 40, and 80 mg) and repeated oral doses (60 mg, once daily for 7 days) as enteric-coated tablet. At the single doses of 20 and 40 mg, intragastric pH was continuously monitored in each of two subjects. No abnormal findings definitely attributable to the test drug were observed throughout the study. In the single-dose study, the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve of TY-11345 increased in a dose-proportional manner. The time to reach Cmax was about 3 h after dosing and plasma concentrations declined thereafter with a half-life of about 1 h irrespective of dose. The effect of food intake on the pharmacokinetic parameters of TY-11345, which was evaluated at the dose of 40 mg in a cross-over design, was not significant. TY-11345 was not detected in urine unchanged, while a main metabolite and its conjugate were identified in urine as 32-38% of the dose. An intragastric pH value over 4 was obtained about 3 h after the administration of 40 mg and maintained for more than 5 h, despite the fall of plasma concentration. This effect was less obvious at a dose of 20 mg. In the multiple-dose study, the pharmacokinetics exhibited no substantial difference between the first and last doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Dirofilaria immitis: a large-scale purification method and partial characteristics of a superoxide dismutase from adult worms.

A superoxide dismutase (SOD) from adult worms of Dirofilaria immitis was purified using ethanol-chloroform and acetone treatment, DE 52 cellulose, and Sephadex G-75 gel chromatography to obtain a 677-fold purification and a specific activity of 5483 units/mg of protein. The purified SOD was essentially homogeneous as judged by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and composed of two identical 18.5 kDa subunits. The purified SOD was inactivated completely by 3 mM potassium cyanide, and reduced to about 18% of the initial activity by incubation at 100 degrees C for 10 min and to 28% by treatment with 2% SDS. This means that D. immitis SOD differs markedly from the mammalian Cu/Zn SOD, although it is indeed a Cu/Zn SOD. Atomic absorption spectrometry revealed the presence of 0.80 mole of Cu and 0.78 mole of Zn per mole of subunit. The enzyme consisted of 22.6% acidic and 11.9% basic amino acids. No free amino acid was detected in the SOD by N-terminal amino acid sequencing.

Amino Acids↗
PubMed1994

Using ofloxacin as a time marker in hair analysis for monitoring the dosage history of haloperidol.

Hair samples were obtained 1-5 months after ingestion of the antimicrobial ofloxacin, which had been given for 1 or 3 days at the commencement of haloperidol administration, or when its dosage was reduced. The axial distribution of ofloxacin, haloperidol and its active metabolite, reduced haloperidol, was analysed in segments from single strands of hair. Ofloxacin was detected where the content of haloperidol and reduced haloperidol along the hair shaft showed a sharp change, corresponding to the change in dose. When we matched the time scale of the dosage history to the growth rate, which was estimated using ofloxacin as the time marker, the distribution of the haloperidol and reduced haloperidol precisely coincided with the rise and fall in the dose of haloperidol. These findings demonstrate that ofloxacin can serve as a time marker when drug distribution along the hair shaft is used to obtain the drug exposure history of an individual.

Adult↗
PubMed1994

Heparin and antithrombin III levels during cardiopulmonary bypass: correlation with subclinical plasma coagulation.

The anticoagulant effect of heparin in the milieu of altered antithrombin III levels was investigated in adult (n = 7) and pediatric (n = 14) patients undergoing open heart operations. The pediatric patients were subdivided into a control group (n = 8) and an antithrombin III group (n = 6), which received 1,000 units of antithrombin III. The reduction in antithrombin III levels during cardiopulmonary bypass was obvious in patients of all ages, showing a greater reduction (although not statistically significant) in the pediatric patients. However, the antithrombin III group patients maintained their preoperative levels of antithrombin III. The elevated fibrinopeptide A levels in pediatric and adult control group patients suggested that considerable subclinical plasma coagulation occurred during open heart operations, especially during the normothermic period of cardiopulmonary bypass and after the administration of protamine. Antithrombin III levels in the children were the most predictive (r = -0.58; p < 0.001) for production of fibrinopeptide A during moderate hypothermic cardiopulmonary bypass, but the heparin levels were most predictive (r = -0.57, p < 0.03) in the adults. This result may be related to the different actions of heparin when antithrombin III levels are reduced. Supplementation with antithrombin III succeeded in suppressing the activation of the coagulation cascade and resulted in no statistical change in fibrinopeptide A levels at any time. We conclude that heparin and (in some patients) antithrombin III levels are important variables for the inhibition of fibrin formation and the possible preservation of coagulation proteins.

Adult↗
PubMed1994

Sacroperineal anorectoplasty using intraoperative ultrasonography: evaluation by computed tomography.

A new operative technique that uses ultrasonography during sacroperineal or sacroabdominoperineal anorectoplasty was performed on seven patients with an intermediate or high anorectal malformation. Ultrasonography was used for the purpose of making a pull-through tunnel under visual guidance. The results of this technique were evaluated by computed tomography scanning to find the anatomic position of the pulled-through rectum in relation to the anal sphincter muscle. Postoperative computed tomography scans showed that the rectum was correctly placed in the center of the sphincter muscle in all patients.

Fistula↗
PubMed1994

Altered production of nerve growth factor in aganglionic intestines.

Nerve growth factor (NGF), a target-derived neurotrophic molecule, is required specifically by sympathetic and dorsal root ganglion cells for their survival and maturation during embryonic and early postnatal development. In the present study, the NGF expression was studied both at the protein and mRNA level in normal and aganglionic intestines of Piebald-strain mice and also in 10 human specimens using immunohistochemical and reverse transcriptase polymerase chain reaction (RT-PCR) techniques. In the aganglionic intestines of the mice, immunoreactive NGF was found on the giant nerve fibers in the submucosal layer, but not found in the mucosal layer. In the mRNA study, the signal for NGFmRNA was less intense in the aganglionic rectum of the congenitally megacolonic mice than in the rectum of the normal mice. In contrast, the distal dilated colon of the congenitally megacolonic mice had a more intense signal for NGFmRNA than did the colon of normal mice. The results obtained from human specimens were compatible with the findings in the Piebald mice; the distal colons harvested from the patients with Hirschsprung's disease (or its allied disease) had a uniformly more intense signal for NGFmRNA than did the normal colons. The results of this study may indicate that NGF production is altered in the aganglionic intestines and also in the "transitional zone" in Hirschsprung's disease. The altered production of NGF may be useful in increasing the accuracy of diagnosis of Hirschsprung's disease.

Animals↗