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Biomedical subjects

T Nagano

Publications and source records attributed to T Nagano.

At least 271 records · Page 15Linked to original sources

Child neglect followed by marked thymic involution and fatal systemic pseudomonas infection.

The case of a 9-month-old baby girl who failed to develop normally due to nutritional neglect and secondary immunodeficiency characterized by marked thymic involution is reported. The child died of systemic Pseudomonas aeruginosa (P. aeruginosa) infection manifested in pneumonia, lung abscesses, bacterial endocarditis and ecthyma gangrenosum. At autopsy the child was 64 cm in height (normal for a 4- to 5-month-old child) and 5.1 kg in weight (normal for a 2- to 3-month-old child). Multiple gangrenous ecthymas, consisting of deep ulcers, induration and inflammation, were observed in the skin over the entire body. The lungs showed hemorrhagic pneumonia, multiple lung abscesses, and necrotizing arteritis in the abscesses and surrounding areas. The thymus weighed 2.3 g and showed marked involution. Histological examination showed so-called nutritional thymectomy characterized by severe cortical atrophy and clustering, cystic dilation and amorphous changes of the Hassall's corpuscles. In the heart, dark brown verrucae were present at the attachment sites of the tendinous cords of the papillary muscle in the anterior and posterior cusps of the mitral valve, suggesting infectious endocarditis. Bacteriological examination demonstrated P. aeruginosa in the ecthymas, lung abscesses and blood. As primary immunodeficiency was considered unlikely, immunodeficiency secondary to thymic involution following malnutrition seemed to have led to a fatal systemic infection with P. aeruginosa, whose virulence is generally weak. This suggests a close association of the development of such infection and immunodeficiency with child neglect.

Child Abuse↗

Formation of superoxide by benzofurazans in Escherichia coli under aerobic incubation.

The superoxide (O2-.) production in Escherichia coli through the action of benzofurazans (BZs) was examined using the cytochrome c (cyt. c) reduction method. Adding BZs to E. coli cell suspensions caused the cyt. c reduction, which was completely inhibited by superoxide dismutase (SOD). The effects of BZs on cyt. c reduction was in the order of benzofurazan (1) approximately 4,7-dimethylbenzofurazan (2) approximately 4,7-dibromobenzofurazan (3) less than 4-bromo-6-cyanobenzofurazan (4) less than 4,7-dicyanobenzofurazan (5). This was correlated with the toxicity of BZs against E. coli growth (1 approximately 2 approximately 3 less than 4 less than 5) and with the redox potentials of BZs (1 approximately 2 less than 3 less than 4 less than 5). The formation of compound 5 anion radical in the cell suspensions in the absence of dioxygen (O2), was determined using ESR spectrum. The ESR signal of the anion radical disappeared with the addition of O2. The BZs effected the O2-. production in E. coli cells.

Aerobiosis↗

[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species].

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.

Free Radical Scavengers↗

Novel iron complexes behave like superoxide dismutase in vivo.

Novel iron and copper complexes having tris[N-(5-methyl-2-pyridylmethyl)-2-aminoethyl]amine (5MeT-PAA), tris[N-(3-methyl-2-pyridylmethyl)-2-aminoethyl]amine (3MeTPAA), tris[N-(5-methoxycarbonyl-2-pyridylmethyl)-2-aminoethyl]amine (TNAA), tris[(2-thienylmethyl)-2-aminoethyl]amine (TTAA), tris[(2-furylmethyl)-2-aminoethyl]amine (TFAA) or tris[(2-imidazoyl)-2-aminoethyl]amine (TIAA) as ligand, were synthesized to examine the superoxide dismutase (SOD) activity. The concentrations of Fe-3MeTPAA and Fe-TIAA equivalent to 1 unit of SOD (IC50) were 0.5 microM and 1.0 microM, respectively. Fe-3MeTPAA and Fe-TIAA had higher SOD activity than other Fe and Cu complexes and protected Escherichia coli cells from paraquat toxicity. In case of using tris[N-(6-methyl-2-pyridylmethyl)-2-aminoethyl]amine (6MeTPAA) as ligand, the Fe complex could not be obtained, which may be due to the steric hindrance of 6-methyl substituent. Generally, Cu complexes had low SOD activity, compared with Fe complexes, and could not suppress paraquat toxicity.

Copper↗

Identification of pyruvate carboxylase in 3T3-L1 cells by transblot and its correlation with differentiation into adipocytes.

The 3T3-L1 preadipocytes treated with insulin, dexamethasone and 3-methyl-1-isobutylxanthine (IBMX) two days before reaching monolayer undergo differentiation into adipocytes. Cell lysates were prepared from these cells under various conditions and analyzed by SDS-PAGE and transblot. Peroxidase-conjugated avidin used to detect endogenous proteins interacted strongly with a protein with an estimated molecular weight of 120 kDa, corresponding to pyruvate carboxylase, in the differentiated 3T3-L1 cells. On the other hand, this protein was not detected in undifferentiated 3T3-L1 cells.

1-Methyl-3-isobutylxanthine↗

[Primary myelofibrosis transforming into multiple subcutaneous monoblastoma--a case report].

A 83-year-old man was diagnosed with primary myelofibrosis based on the presence of leukoerythroblastosis, splenomegaly, chromosome 46 XY, a dry tap bone marrow aspiration and fibrosis on bone marrow biopsy, when he was admitted for herpes zoster in June 1987. He was admitted for a second time with multiple subcutaneous tumors over his entire body in July, 1989. He had mild splenomegaly, but no hepatomegaly nor lymphadenopathy. Laboratory tests were as follows: RBC 214 x 10(4)/microliters, Hb 5.1 g/dl, Ht 17.7%, WBC 3,200/microliters with leukoerythroblastosis, platelets 11.6 x 10(4)/microliters, s-lysozyme 251 micrograms/ml, u-lysozyme 770 micrograms/ml, NAP ratio 98%, score 278. Bone marrow aspiration resulted in a dry tap. Bone marrow biopsy showed marked fibrosis. Histologic examination of subcutaneous tumor biopsy specimens revealed a diffuse infiltration of monocytes with flexuous nuclei. These cells were positive for alpha-naphtyl butyrate esterase stain, and negative for peroxidase, alpha-naphtol ASD chloroacetate esterase stain and platelet glycoprotein IIb/IIIa stain (APAAP). Ultrastructurally, these cells were mostly monocytes and promonocytes, while phenotypically, CD11b, CD13, CD14, CD33 and HLA-DR were positive. These date indicated that the subcutaneous tumors originated from monocytes.

Aged↗

Improved on-line thoracic duct drainage for lymphocytapheresis.

Lymphocytapheresis using thoracic duct drainage (TDD) is a recognized technique of extracorporeal immunomodulation for various autoimmune diseases such as rheumatoid arthritis (RA), and its clinical benefit has been reported and generally accepted. Lymphocytapheresis using TDD is very selective for removing lymphocytes (especially helper T-cells) but raises some problems such as hypoproteinemia due to the massive removal of lymph, and difficulties in repeated treatment. Along with the development of a new polyester fiber filter, we have developed a simple and effective method of lymphocytapheresis for wide adoption for these techniques. We performed lymphocytapheresis using TDD in patients with RA and previously reported its clinical efficacy indicated by the significantly lower number of peripheral lymphocytes and T4/T8 ratio. We present here our newly-developed on-line system designed to prevent hypoproteinemia. Furthermore we report on the advantages with a new subcutaneous vascular access device set up to manage the problems of repeated treatments. A small reservoir for keeping the thoracic duct open and returning lymph to the patient permitted sufficient lymph drainage and removal of lymphocytes and the clinical application of TDD is discussed.

Arthritis, Rheumatoid↗

[Treatment and prognosis of pT2 endometrial carcinoma].

Between January, 1966 and December, 1988, 66 patients with surgical-pathological stage II adenocarcinoma of the endometrium who were treated with abdominal simple or radical hysterectomy at the Osaka National Hospital were studied retrospectively. The 5-year survival rate for all patients was 75.7%. In 33 patients adenocarcinoma had invaded the cervical stroma. These patients demonstrated a significantly lower survival (60.0%) than those patients whose involvement was limited to the endocervical gland (91.7%) (p less than 0.05). For all patients, both with endocervical glandular involvement and cervical stromal invasion, radical hysterectomy improved survival rates more than did simple hysterectomy, but the difference was not statistically significant. The factor found to have a significant influence on survival was the maximal depth of invasion of the myometrium (p less than 0.05). The histologic grade, on the other hand, did not appear to influence survival. It is suggested that patients with minimal involvement of the cervix can be satisfactorily treated with simple hysterectomy, while patients with gross cervical spread should be treated with radical hysterectomy.

Adenocarcinoma↗

Relationships in the structure-tissue distribution of basic drugs in the rabbit.

The relationship between the tissue-to-plasma partition coefficients (Kp) and drug lipophilicity was investigated using highly lipophilic drugs with apparent partition coefficients of 150 or above in an octanol-water system at pH 7.4. Ten clinically popular basic drugs with different dissociation coefficients (pKa) and lipophilicity were used. The Kp values were determined in nondisposing organs after the i.v. administration of individual drugs in rabbits. The free fraction in plasma and the blood-to-plasma concentration ratio were determined in vitro. Then the tissue-to-plasma ratios of nonionized and unbound drug concentrations (Kpfu) were calculated from Kpf (ratio of unbound drug). The true octanol-water partition coefficient of the nonionized drugs (P) was used to analyze the Kpf and Kpfu. In all tissues, log Kpfu was more highly correlated with log P than log Kpf.

Animals↗

Toxicities of dicyanobenzofurazans with formation of superoxide in Escherichia coli.

The toxicities of some benzofurazans (BZs), benzofurazan (1), 4,7-dimethylbenzofurazan (2), 4,7-dibromobenzofurazan (3), 4-bromo-6-cyanobenzofurazan (4), 4,7-dicyanobenzofurazan (5) and 4,5-dicyanobenzofurazan (6), were examined on Escherichia coli. Compound 5 at 4 microM and compound 6 at 7 microM completely inhibited the growth of E. coli in a simple nutritionally restricted medium (GM medium). These compounds were more toxic in GM medium than in a nutritionally rich medium (YE medium), which contained yeast extract as an additive in GM medium. Compound 4 also inhibited the growth of E. coli at 300 microM in GM medium. The toxicities of BZs were in the order of 1 approximately 2 approximately 3 less than 4 approximately 5 approximately 6. Compounds 4, 5 and 6 induced manganese-superoxide dismutase (Mn-SOD) and catalase activities of E. coli in YE medium. The induced SOD and catalase provide a defense against the potential cytotoxicities of O2- and H2O2. The rate of dioxygen uptake in cyanide-resistant respiration of E. coli was dependent on the concentration of 5, and was correlated with the induction of SOD and catalase. The reduction potentials of BZs followed the order of 1 approximately 2 less than 3 less than 4 less than 5 approximately 6. Compounds 5 and 6, which had redox potentials higher than those of the other BZs, are thought to be more readily reduced in the living system.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoxazoles↗

[A case of intrapulmonary lymph node simulating small carcinoma of the lung].

A 48-year-old male was admitted for further examination of a coin lesion with a diameter of 8 mm seen on chest X-ray. The patient was a heavy smoker and his serum level of CEA was elevated to 29.8 ng/ml. Since the broncho-fiberscopic examination was not able to yield a definitive diagnosis, an operation was performed as lung cancer was suspected. According to the histological examination, the small nodule was diagnosed as an intrapulmonary lymph node with anthracosis and silicotic nodules. A review of the limited number of case reports shows that men are more prone to intrapulmonary lymph nodes, and that the patients were all smokers but not necessarily with occupational experience of exposure to silica.

Carcinoma, Small Cell↗

[An autopsy case of sudden death due to hyperthyroidism].

A rare autopsy case of death due to thyroid crisis is reported. A 45-year-old lean woman with pigmentation of the skin was found dead at the seaside. The autopsy findings were as follows: The enlarged thyroid gland (35.5 g) had a histological finding of diffuse hyperplastic goiter (hyperthyroidism). The thymus (28.5 g) was enlarged and parenchymatous. The lymphocytes in the thymus and spleen were conspicuously proliferated, probably due to secondary adrenal cortex insufficiency. The adrenal cortex was slightly atrophic. Hemosiderin-laden macrophages in the lung, and centrilobular necrosis, microscopic bleeding, fibrosis, and nodular regenerative hyperplasia of the liver indicated the persisted heart failure. A small pericardial scar was found at the right ventricle of the heart (280 g), and the histological finding of the heart was only congestion. Acetone was detected in a relatively high concentration in the blood (72 micrograms/ml), urine (139 micrograms/ml), bile (32 micrograms/ml) and gastric contents (38 micrograms/g), probably due to metabolic disorder from thyroid crisis. In conclusion, the cause of death was diagnosed as sudden death due to thyroid crisis from hyperthyroidism.

Death, Sudden↗

Functional characterization of lymphocyte response to fractionated house dust mite antigens (Dermatophagoides pteronyssinus) in atopic and non-atopic individuals.

This study investigated the cellular response of human lymphocytes to Dermatophagoides pteronyssinus crude antigen and 14 molecular weight (MW) fractions. The cells were derived from atopic patients and healthy individuals who were skin test-positive or skin test-negative to mite antigen. When stimulated with crude antigen, the group of patients showed elevated proliferation and production of lymphokine in comparison with the healthy skin test-negative individuals (P less than 0.01). By stimulation with fractions, there was a remarkable variety in the responding patterns to each fraction. However, when expressed as a mean value, the patient group exhibited a sharp and high peak at 95,000 MW, which is different from IgE responses. In the other two groups, no apparent peak response was observed. Lymphokine production by fraction stimulation was studied in six distinct individuals. The most important fractions for inducing lymphokine production differed in each individual tested. Moreover, fractions which induced active lymphokine production were not necessarily the main targets of proliferative response in atopic patients.

Allergens↗

Superoxide dismutase mimics based on iron in vivo.

Novel metal complexes, Fe(II)-tetrakis-N,N,N',N' (2-pyridylmethyl)ethylenediamine(Fe-TPEN) and Fe(III)-tris[N-(2-pyridylmethyl)-2-aminoethyl]amine (Fe-TPAA), catalyzed the dismutation of superoxide, and 0.8 microM Fe-TPEN and 7.5 microM Fe-TPAA were equivalent to 1 unit of superoxide dismutase (SOD) activity in the xanthine oxidase-cytochrome c assay. Addition of serum albumin had no effect on the activities of Fe-TPEN and Fe-TPAA but depressed those of the Cu(salicylate)2 and Cu(diisopropylsalicylate)2 complexes. Both iron complexes blocked the toxic effect of paraquat on Escherichia coli growth and survival without causing induction of SOD. In contrast, this behavior was not seen with other SOD mimics containing copper or manganese. These results support the view that the SOD activities of these iron complexes remain intact in living cells.

Chelating Agents↗

Stage-specific localization of cytoskeletal actin mRNA in murine seminiferous tubules and intestinal epithelia as demonstrated by in-situ hybridization.

In-situ hybridization experiments have been performed using isoactin (beta and gamma)-specific riboprobes in various tissues of the rat and mouse. Distribution of the grains of actin mRNAs for both beta and gamma types was similar throughout sections of the rat testis. Although both mRNAs were evenly distributed in the seminiferous tubule, extremely heavy labeling was observed in about 10% of the seminiferous tubules that could be identified as stage XII of spermatogenesis. At high magnification, grains of the mRNA were found in the cytoplasm of elongating spermatids and in the Sertoli cell cytoplasm at the adluminal side. Much higher density of the grains of mRNA was observed in the neck region of the spermatids at stage XII. Thus, the dense distribution of cytoskeletal actin mRNAs is stage-specific in the tubule during spermatogenesis in the rat. The high expression of both beta and gamma actin mRNAs was also observed in the epithelial cells of the intestinal crypts.

Actins↗