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Biomedical subjects

K Sakai

Publications and source records attributed to K Sakai.

At least 415 records · Page 23Linked to original sources

[Long-term results of operation for acute type A aortic dissection].

We report results of surgical treatment in 30 patients with acute type A aortic dissection. The average age of the 25 patients without the Marfan syndrome was 59.2 (range 51-76), and male/female ratio was 11/14. The average age of the five patients with the Marfan syndrome was 36.8 (range 27-48), and male/female ratio was 2/3. As an adjunct, we used deep hypothermic circulatory arrest during ascending aortic replacement, while selective cerebral perfusion was employed during aortic arch replacement. Operative procedures for the non-Marfan patients included 14 ascending aortic replacement and 11 ascending and aortic arch replacement, while the Marfan patients underwent extensive aortic replacement that included three aortic arch replacement combined with the Bentall operation, one extensive replacement from the ascending aorta to the descending thoracic aorta and one ascending and aortic arch replacement. One patient died early after the operation and the early mortality rate was 3.3%. No patient developed new brain complication related to the operation. During the follow-up period, three patients died and two patients required a total of three subsequent distal operations. Cumulative survival rate was 89% at one year, 85% at three years, 85% at five years. Cumulative cardiovascular event-free rate was 89% at one year, 85% at three years, 77% at five years. Early and long-term results of surgical treatment for acute type A aortic dissection was satisfactory. This seems to result from the use of deep hypothermic circulatory arrest and selective cerebral perfusion as an adjunct and application of aortic arch replacement when the aortic arch is dilated or intimal tear is located in the aortic arch or more distally.

Aged↗

Presumed venous infarction in spinal decompression sickness.

We describe the serial MR imaging findings in a patient with spinal decompression sickness. In the acute phase, the spinal cord was swollen, with increased T2 signal in the posterior part of the column; 1 month later, marked contrast enhancement was noted in the same location; and 2 months later, the swelling and T2 signal had decreased. MR imaging may facilitate the early diagnosis of spinal decompression sickness.

Decompression Sickness↗

Focal orbital amyloidosis presenting as rectus muscle enlargement: CT and MR findings.

We report a case of focal orbital amyloidosis involving rectus muscles, which is an extremely rare clinical condition. CT scans showed rectus muscle enlargement with punctate calcifications. Heterogeneous hypointensity was present on T2-weighted MR images, and homogeneous enhancement was seen on fat-saturated contrast-enhanced images of the muscles. These imaging findings seem to be suggestive of amyloidosis. Focal amyloidosis should be included in the differential diagnosis of extraocular muscle enlargement.

Amyloidosis↗

[Types and dimensions of mineral fibers in the atmosphere and from lungs of residents in the urban area].

OBJECTIVE: The objective of this study was to estimate the types and origin of the mineral fibers in the lungs of residents in the urban area. METHODS: Mineral fibers in the atmosphere from 21 urban areas were analyzed by direct transfer-analytical transmission electron microscopy (ATEM). Lung tissues of 36 urban residents without occupational asbestos exposure were also analyzed by ATEM after low temperature ashing. Measurement of dimensions of all types of mineral fibers, identification of asbestos, and classification of nonasbestos fibers according to the combination of main elements were carried out. RESULTS: 1. Chrysotile, amosite, actinolite, tremolite and 11 types of nonasbestos fibers were found in both the lung tissues and the atmospheric samples. The fibers, mainly composed of Al and Si, contributed 16.3% and 62.3% of the atmospheric samples and lung tissues respectively. On the other hand, the proportion of the fibers mainly composed of S and Ca were 43.7% and 0.0% in the atmosphere and lung tissues respectively. Those fibers mainly composed of P and Fe were 0.4% and 18.4% in the atmosphere and lung tissues respectively. 2. Fifteen types of nonasbestos fibers were found exclusively in the atmosphere. The average proportions for ten of these were less than 0.5% each. 3. Crocidolite was found exclusively in the lung tissues. 4. No significant difference in the geometric mean of length and diameter of asbestos was found between the atmospheric samples and lung tissues. Some types of nonasbestos fibers had significantly larger length and diameter in the atmospheres than in the lung tissues (p < 0.01). CONCLUSION: The results suggest that mineral fibers found in lung tissues could be classified into three groups on the basis of their behavior. 1) Some fibers, such as amphibole asbestos and fibers composed of Al and Si, are inhaled from the atmosphere and remain in the lung tissues for a long time. 2) Some fibers, such as those composed of S and Ca, are inhaled from the atmosphere and eliminated from the lung tissues within a relatively short time. 3) Some fibers found more in the lung tissues than in the atmospheres, such as those composed of P and Fe, are suspected to be generated in the lungs.

Air Pollutants↗

The role of vitamin E in T-cell differentiation and the decrease of cellular immunity with aging.

Spontaneously hypertensive rats (SHR) as a model for aging were used in this experiment and fed a regular (50 IU/Kg diet) or high vitamin E (500 IU/Kg diet) diet for 6 weeks. At 12 weeks old, they were killed and assayed. Although proliferation of thymic lymphocytes was significantly decreased in SHR fed the regular diet compared to Wistar Kyoto rats (WKY) fed the same diet, high vitamin E diet enhanced proliferation of thymic lymphocytes in SHR to almost the levels in WKY fed the regular diet. In addition, the expressions of both CD4 and CD8 antigens on CD+CD8+ T cells, immature T cells existing in thymic cortex, were also decreased in SHR, and significantly improved by high vitamin E diet. These results suggest that high vitamin E diet enhances thymic lymphocyte proliferation through increased T-cell differentiation in thymus. Then, the effect of vitamin E on T-cell differentiation in thymus was investigated by using male Fisher rats. Rats were divided into three groups; vitamin E-free, regular and high vitamin E groups and fed a diet containing various levels of vitamin E (0, 50 and 500 IU/Kg diet) for 7 weeks. Although the percentages of CD4+CD8- and CD4-CD8+ T cells in thymocytes were significantly greater in the high vitamin E group, the percentage of CD4+CD8- T cells inversely decreased in the vitamin E-free group compared to the regular group. We have tried to investigate the mechanism of the increased T-cell differentiation in thymus of rats fed the high vitamin E diet through cytokine production, and thymic epithelial cell (TEC) and macrophage functions. We have found that vitamin E enhances T-cell differentiation through the increase of not macrophage but TEC function in thymus, which is associated with the increased binding capacity of TEC to immature T cells via increased expression of adhesion molecule, ICAM-1. These results suggest that vitamin E is a potent nutrient for promoting health in the aged via the improvement of cellular immunity decreased with aging.

Aging↗

[Appearance of ovomucoid in coagulated egg yolk passing through from soluble fraction of coagulated egg white in boiled egg].

Ovomucoid is a egg white protein which has a strong allergenicity with a unique characteristic in heat-noncoagulable one contrast to heat-coagulable other major egg white proteins. By ELISA and immunoblots analysis, ovomucoid was detected in heat-coagulated egg yolk after immediate boiling of hen's egg for 15 min (boiled egg) at the concentration of 4.8 +/- 0.8 micrograms/g egg yolk, but not detected in raw egg yolk collected by insertion of a needle into the egg yolk cavity. Ovomucoid in heat-coagulated egg yolk was increased by standing the boiled eggs at room temperature for 10, 30, 60 and 120 min at the concentration of 7.5 +/- 3.4, 17.2 +/- 15.1, 28.1 +/- 5.9 and 78.8 +/- 31.3 micrograms/g egg yolk, respectively. The soluble fraction prepared from heat-coagulated egg white of boiled egg contained 37.7 +/- 3.2 mg/ml of proteins including 14.2 +/- 11.9 mg/ml of ovomucoid as a major and miners of detectable ovalbumin and ovotransfferin. These results suggested that the appearance of ovomucoid in coagulated egg yolk of boiled egg was due to passing the soluble fraction rich in ovomucoid in heat-coagulated egg white through into the coagulated egg yolk, which may have notable consequences for the present of ovomucoid as a major egg white allergen in yolk egg of boiled egg.

Allergens↗

Effects of azelastine on the level of serum interleukin-4 and soluble CD23 antigen in the treatment of nasal allergy.

Research findings and various published studies point to interleukin 4 (IL-4) and CD23 antigen as instrumental in allergic reactions of allergy patients because these two substances are part of the main triggering mechanisms in cells producing IgE antibodies. In this study it was investigated whether the control of IL-4 and CD23 levels result in a decrease of the severity of allergic reactions. It is well known that azelastine hydrochloride (AZ, CAS 79307-93-0) suppresses symptoms of nasal allergy. The antiallergic activity of this drug includes the suppression of IgE antibody production, antigen-antibody reactions, liberation of mediators and mediator antagonism. One report states that the cytokines IL-2, IL-3, and IL-4 were suppressed by AZ in cultured cells. There have been no reports regarding cytokines in clinical treatment using AZ. Therefore, the effects of AZ treatment on IL-4, soluble CD23, and RAST (radioallergosorbent test) levels in the sera of allergic rhinitis patients were studied. The results show that the levels of IL-4 and soluble CD23 were significantly reduced by the administration of AZ over a 4-week period, especially in patients with "excellent" or "good" efficacy of therapy.

Adult↗

Radioimmunoassay for a novel lignan-related hypocholesterolemic agent, S-8921, in human plasma after high-performance liquid chromatography purification and in human urine after immunoaffinity extraction.

The novel compound methyl-1-(3,4-dimethoxyphenyl)-3-(3-ethylvaleryl)-4-hydroxy-6,7,8- trimethoxy-2-naphthoate (S-8921) has hypocholesterolemic activity in animals and is expected to exhibit a similar activity in human. Reversed-phase high-performance liquid chromatography (HPLC) separation followed by radioimmunoassay (RIA) for human plasma samples (HPLC-RIA) and immunoaffinity extraction (IAE) followed by RIA for human urine samples (IAE-RIA) were developed for investigation of S-8921 behavior in clinical studies. For the RIA, antisera from rabbit and a radioiodine-labelled S-8921 were prepared by immunizing a conjugate of S-8921 with bovine serum albumin and by the Bolton and Hunter method, respectively. HPLC-RIA using a semi-micro column was very sensitive, that is a 0.05 ng/ml limit of quantitation in human plasma, and specific for unchanged form of S-8921. IAE-RIA using a centrifugal filtration tube completely eliminated the matrix effect of human urine, and was very feasible. The limit of quantitation was 0.10 ng/ml. RIA detection following HPLC or IAE proved to be very useful for the pharmaceutical analysis of extremely low drug concentrations in body fluids.

Anticholesteremic Agents↗

Protein modification by lipid peroxidation products: formation of malondialdehyde-derived N(epsilon)-(2-propenol)lysine in proteins.

Malondialdehyde (MDA), a naturally occurring dialdehyde produced in the membrane lipid peroxidation, is known to react with lysine residues of proteins, but the MDA-lysine adducts generated in the proteins have not been characterized adequately. In the present study, we provide evidence that the enaminal-type MDA-lysine adduct, N(epsilon)-(2-propenal)lysine, is formed in human low-density lipoprotein (LDL) upon reaction with MDA or Cu2+. We found that the incubation of N(alpha)-acetyllysine with MDA generated N(alpha)-acetyl-N(epsilon)-(2-propenal)lysine as the predominant product. In addition, a polyclonal antiserum raised against the MDA-modified protein was found to contain antibody populations that could be purified by affinity gel prepared by covalent attachment of N(alpha)-acetyl-N(epsilon)-(2-propenal)lysine. It was concluded that the affinity-purified anti-N(epsilon)-(2-propenal) lysine antibody was highly specific to the enaminal derivative of both lysine residues and phosphatidylethanolamine, based on the observations that (i) MDA was the only aldehyde which generated immunoreactive materials in proteins; (ii) among structurally defined MDA-lysine adducts tested, the antibody recognized the enaminal adduct only; and (iii) immunoreactivity to N-(2-propenal)serine was still significant but much weaker than its reactivity to N-(2-propenal)ethanolamine. Furthermore, analysis of antibody recognition sites with a variety of N-(2-propenal)alkylamines revealed that the mono-specific antibody recognized the N-2-propenal-N-ethyl moiety [-(CH2)2-NH-CH=CH-CHO] of enaminal adducts. Determination by a competitive enzyme-linked immunosorbent assay demonstrated that N(epsilon)-(2-propenal)lysine accounted for 33.7 and 3.1% of the lysine residues that disappeared during in vitro incubation of LDL with MDA and Cu2+, respectively. These results suggest that N(epsilon)-(2-propenal)lysine represents a major form of MDA covalently attached to proteins.

Antibodies, Monoclonal↗

A transgenic mouse line that retains Cre recombinase activity in mature oocytes irrespective of the cre transgene transmission.

The Cre/loxP site-specific recombination system derived from bacteriophage P1 provides a convenient tool for directed modifications of genomes in various organisms. To exploit Cre-mediated manipulation of mouse genomic sequences at the zygote stage, we have developed a transgenic mouse line carrying the CAG-cre transgene in which the cre gene is under control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid (CAG) promoter. The activity of the Cre recombinase at early stages of development was examined by crossing the CAG-cre transgenic mice to another transgenic mouse line carrying a reporter gene construct, CAG-CAT-Z, which directs expression of the E. coli lacZ gene upon Cre-mediated excision of the loxP-flanked chloramphenicol acetyltransferase (CAT) gene located between the CAG promoter and the lacZ gene. PCR-based analysis of F1 progeny from CAG-cre males x CAG-CAT-Z females showed that transmission of the CAG-cre transgene was accompanied by the complete deletion of the CAT gene of the CAG-CAT-Z transgene in all tissues, and that this deletion was never observed in the progeny without transmission of the CAG-cre gene. On the other hand, analysis of F1 mice from CAG-CAT-Z males x CAG-cre females showed that the CAG-CAT-Z transgene had undergone complete deletion of the CAT gene in all tissues irrespective of the cotransmission of the CAG-cre gene. This Cre-mediated recombination in F1 mice occurred before the two-cell stage of embryonic development, as shown by X-gal staining. The results suggest that the CAG-cre transgene is expressed in developing oocytes of CAG-cre transgenic mice, and Cre mRNA and/or protein are retained in mature oocytes irrespective of the transmission of the CAG-cre transgene, resulting in efficient Cre-mediated recombination of paternally derived target genes upon fertilization. The CAG-cre transgenic mouse should serve as a useful tool to introduce prescribed genetic modifications into the mouse embryo at the zygote stage.

Animals↗

Angiogenesis in endometrial carcinoma.

BACKGROUND: Tumor angiogenesis is essential for tumor growth and metastases. Recently, microvessel density (MVD), a measure of tumor angiogenesis, has been found to have prognostic significance for predicting metastasis and survival in many tumor types. This study was conducted to determine how MVD was related to several clinicopathologic parameters and correlated with metastasis and survival in patients with endometrial carcinoma. METHODS: From 1979 through 1989, 85 cases of clinical Stage I and II endometrial carcinomas treated initially by hysterectomy with pelvic lymph node dissection were reviewed histologically. All hysterectomy specimens were stained immunohistologically for factor VIII-related antigen. MVD was counted in a x200 field (x20 objective lens and x10 ocular lens, 0.785 mm2 per field) in the most active area of neovascularization. Results were expressed as the highest number of microvessels identified within any single x200 field. Statistical analysis included the Mann-Whitney U test, Kruskal-Wallis test of variance, and the Spearman rank correlation test. Survival was calculated using the Kaplan-Meier method and differences in survival were analyzed using the log rank test. MVD and several other prognostic parameters were examined for their correlation with progression free survival (PFS) and overall survival (OS) by a multivariate analysis according to the Cox proportional hazards model. RESULTS: MVD was significantly correlated with tumor grade (P = 0.0281), myometrial invasion (P = 0.0282), and lymph-vascular space invasion (P = 0.0073). There was no correlation between microvessel count and lymph node status and stage. Patients with a high MVD (> or =60) had significantly worse PFS and OS than those with a low MVD (<60) (log rank test, P = 0.0116 and P = 0.0096, respectively). Multivariate analysis showed that MVD correlated significantly and independently with PFS and OS. CONCLUSIONS: In this study, MVD was found to be an independent prognostic factor for PFS and OS in patients with endometrial carcinoma.

Adult↗

Efficacy of Post-operative Adjuvant Therapy for Stage IIIa Berast Cancer: Futraful vs Futraful+Tamoxifen for ER-positive Patients and Futraful vs Futraful+Adriamycin for ER-negative Breast Cancer.

A multi-center, randomized controlled collaborative study was conducted in 310 institutions located thruoughout Japan for 3 years and 9 months from February 1985 until October 1988 to evaluate the efficacy of post-operative adjuvant therapy for patients who had previously undergone curative surgery for treatment of Stage III a breast cancer. Patients with estrogen receptor-positive [ ER(+)] breast cancer were treated with two types of regimens, ie, cyclophosphamide+adriamycin+fluorouracil (CAF; 2 cycles) +Futraful(FT) or CAF (2 cycles+FT+tamoxifen (TAM), and the clinical benefit of additional use of TAM was evaluated. Of the 509 ER(+) patients registered for the trial, 473 patients (92.9%) were eligible for evaluation.The 5-year survival rate was 77.2% for the CAF+FT group and 74.6% for the CAF+FT+TAM group, and the 5-year disease-free survival rate was 56.7% for the CAF+FT group and 59.2% for the CAF+FT+TAM group. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. Analyses by factor revealed that the 5-year disease-free rate for lymph node-negative patients in the CAF+FT+TAM group was significantly higher than that for the corresponding patients in the CAF+FT group. No differences were noted in the incidence of adverse reactions between the two treatment groups, other than an increase in LDH (the frequency of which was higher in the CAF+FT+TAM group than in the CAF+FT group). Patients with estrogen receptor-negative [ ER(-)]breast cancer were treated with two types of regimens, ie, CAF+FT or CAF+FT+adriamycin(ADR), and the clinical benefit of the combined use of intermittent doses of ADR was evaluated. Of the 514 ER(-) patients registered in the trial, 478(93.0%) were eligible for evaluation. The 5-year survival rate was 64.9% for the CAF+FT group and 63.0% for the CAF+FT+ADR group, and the 5-year disease-free survival rate was 59.2% for both CAF+FT and CAF+FT+ADR groups. Neither the survival rate nor the disease-free survival rate differed significantly between the groups. There were no significant differences between these groups in analyses by nodal or menopausal status. The incidences of adverse reactions including anorexia, nausea/vomiting and alopecia were higher in the CAF+FT+ADR group than in the CAF+FT group.

Journal Article↗

D-aspartic acid localization during postnatal development of rat adrenal gland.

Developmental changes in cellular localization of D-aspartic acid (D-Asp) were investigated in rat adrenal gland with polyclonal anti-D-Asp antibody. At 1 and 3 weeks of age, immunoreactivity (IR) toward this amino acid was intense in the cytoplasm of cells in the zona fasciculata (ZF) and zona reticularis (ZR) of the adrenal cortex but was less so in the zona glomerulosa (ZG). Conversely at 8 weeks of age, intense IR was observed in the ZG and less in the ZF and ZR. In the adrenal medulla, IR was evident in large clusters of cells which were identified as adrenaline-storing cells. The emergence of D-Asp in specific types of cells at distinct periods of development of rat adrenal gland suggests that this amino acid may have a physiological role in the maturation of the organ.

Adrenal Cortex↗

A possible mechanism for hyperthermic radiosensitization mediated through hyperthermic lability of Ku subunits in DNA-dependent protein kinase.

DNA-dependent protein kinase (DNA-PK), composed of p470 catalytic subunit and p85/p70 heterodimer of Ku autoantigen, is considered a critical enzyme in DNA double-strand break repair. We purified DNA-PK from human leukaemic MOLT-4 cells by successive column chromatography and separated into p470 and Ku subunits by ultracentrifugation in glycerol gradient. We studied hyperthermic stability of DNA-PK holoenzyme and its separated subunits to test a possible role of DNA-PK in hyperthermic radiosensitization. DNA-PK was found to lose its activity rapidly at hyperthermic 44 degrees C, and further, Ku subunits instead of p470 catalytic subunits were found to be sensitive to hyperthermia. These results indicate a possibility that hyperthermic radiosensitization is mediated through the heat lability of Ku subunits of DNA-PK, impairing repair of radiation-induced double-strand break of DNA.

DNA Damage↗

Animal fatty acid synthase: functional mapping and cloning and expression of the domain I constituent activities.

Animal fatty acid synthase (FAS; EC 2.3.1.85) is a homodimer of a multifunctional subunit protein and catalyzes the synthesis of palmitate from acetyl-CoA, malonyl-CoA, and NADPH. The subunit (Mr approximately 270,000) carries seven distinct component activities and a site for the prosthetic group 4'-phosphopantetheine (acyl carrier protein). Based on proteolytic mapping, the organization of the activity domains along the subunit polypeptide from the N terminus is as follows: beta-ketoacyl synthase, acetyl and malonyl transacylases, beta-hydroxyacyl dehydratase, enoyl reductase, beta-ketoacyl reductase, acyl carrier protein, and thioesterase. By comparing the amino acid sequences of the chicken, rat, and human synthases, we found that kallikrein cleavage sites occur in the least conserved regions of the FAS polypeptide subunit. Determining the amino acid sequences of the N-terminal end of the major kallikrein cleavage peptides helped delineate the most likely boundaries of the component activities in the cDNA-derived amino acid sequence. To confirm this organization, we cloned the chicken FAS cDNA coding for domain I and expressed it in Escherichia coli as a maltose-binding fusion protein. The isolated recombinant protein contained the activities of the acetyl and malonyl transacylases and the beta-hydroxyacyl dehydratase. Based on the boundaries of the acetyl and malonyl transacylases and the beta-hydroxyacyl dehydratase, we also cloned the appropriate cDNA fragments encoding the domains that contain the transacylases and the dehydratase in pET vectors and expressed them in E. coli as thioredoxin-6xHis fusion proteins. The purified recombinant proteins contained, respectively, the activities of the acetyl and malonyl transacylases and the dehydratase. These results not only confirmed the order of the component activities in domain I, but also paved the way for successful expression and characterization of the remaining activities.

Amino Acid Sequence↗

Usefulness of directional coronary atherectomy in patients with acute anterior myocardial infarction.

To assess the usefulness of directional coronary atherectomy (DCA) in acute myocardial infarction (AMI), 139 consecutive patients with anterior wall AMI undergoing successful catheter intervention were studied. The reocclusion rate was significantly lower in the last 70 patients who underwent DCA as aggressively as possible compared with the first 69 patients treated with coronary balloon angioplasty (12.1% vs 3.0%, p <0.05).

Aged↗

Role of acute cochlear neuritis in sudden hearing loss in multiple sclerosis.

We report a patient with definite multiple sclerosis (MS) who developed unilateral sudden hearing loss coincident with exacerbation of central nervous system symptoms. Involvement of the peripheral cochlear nerve, suggested by auditory findings including auditory brainstem response, was confirmed by magnetic resonance imaging. The clinical, electrophysiological and neuroradiological abnormalities disappeared in response to steroid pulse therapy. These findings suggest that acute inflammatory demyelinative lesion of the peripheral cochlear nerve can occur in MS, manifesting sudden hearing loss.

Acute Disease↗