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Biomedical subjects

H Nakao

Publications and source records attributed to H Nakao.

At least 19 recordsLinked to original sources

Elevated serum manganese superoxide dismutase in acute leukemias.

We measured the serum levels of manganese-superoxide dismutase (Mn-SOD) in acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). Serum Mn-SOD level for normal subjects was 94.1 +/- 23.5 ng/ml (mean +/- S.D.), the levels for AML and ALL patients were 159.6 +/- 77.1 ng/ml and 154.4 +/- 77.0 ng/ml, respectively. The serum Mn-SOD levels were unrelated to individual intracellular Mn-SOD levels, but correlated well with serum lactate dehydrogenase values. Regression of the leukemia was accompanied by decrease in the serum level of Mn-SOD. Serum Mn-SOD may thus serve as a measure of the activity of the disease.

Enzyme-Linked Immunosorbent Assay

Glycosidase inhibitors (castanospermine and swainsonine) and neuraminidase inhibit pokeweed mitogen-induced B cell maturation.

Castanospermine (CSP), an inhibitor of alpha-glucosidase, enhanced immunoglobulin (Ig) release in a Staphylococcus aureus Cowan I (SAC)-induced lymphocyte culture (Scand. J. Immunol. 1990. 32: 529). In a pokeweed mitogen (PWM)-human lymphocyte culture, unlike the SAC-stimulated system, CSP strongly decreased the number of IgG-, IgA- and IgM-secreting cells as well as that of Ig-bearing cells. Peripheral blood lymphocytes treated with swainsonine, a mannosidase II inhibitor, or with neuraminidase also showed a reduced response to PWM. In cross-culture experiments, only a mixture of B cells pretreated with either agent and untreated T cells showed such a suppressive effect. Adhesion was decreased between B cells treated with either agent and untreated T cells, but not between treated T cells and untreated B cells. These results demonstrate that a certain alteration in B cell membrane oligosaccharides inhibited the T cell-B cell adhesion in the PWM culture, leading to an arrest of B cell maturation. Considering that these inhibitors eventually prevent terminal sialic acid addition, the present study provides evidence that sialic acids on B cell surface oligosaccharides play a biological role in the T cell-B cell interaction.

B-Lymphocytes

Effects of retinoic acid on estrogen- and thyroid hormone-induced growth in a newly established rat pituitary tumor cell line.

In order to elucidate the complex mechanism(s) of action of steroid hormones, thyroid hormone and retinoic acid in pituitary mammotrophs, a clonal cell line (G3) was isolated from the rat pituitary tumor MtT/F84. G3 cells were found to secrete prolactin constitutively and to contain receptors for estrogen, glucocorticoid, progesterone and thyroid hormone. Stimulation of G3 cells with thyroid hormone resulted in a modest but significant increase in estrogen and progesterone receptor levels, however, retinoic acid treatment had no effect. Simultaneous addition of thyroid hormone and estrogen showed an additive effect on progesterone receptor levels in G3 cells. Thyroid hormone as well as estrogen enhanced the growth of G3 cells. Interestingly, retinoic acid was also found to enhance their growth but its enhancement was less potent than thyroid hormone and estrogen. Low concentrations of estradiol and thyroid hormone showed additive effects, but G3 cells stimulated with high concentrations of thyroid hormone failed to elicit an additive effect with estrogen, suggesting the presence of a common pathway in the growth-stimulatory actions of these hormones. In addition, exposure of G3 cells to retinoic acid completely abolished the effects of estrogen or thyroid hormone in terms of cell growth. These results suggest that there are complex interactions in the signalling pathways for estrogen, thyroid hormone and retinoic acid action in G3 cells.

Animals

Impact of the advances in age on the gastrointestinal microflora of beagle dogs.

The gastrointestinal microflora of male beagle dogs in two different age groups; I) less than month 12 of age, and II) more than year 11 of age, was compared. No detectable difference occurred on the microflora of stomach, duodenum, jejunum, and ileum in both dogs. Large bowel (cecum, colon and rectum) microflora in both dogs yielded the different microbial populations. In all regions of large bowel, the levels of bacteroides, eubacteria, peptostreptococci, bifidobacteria, lactobacilli, and staphylococci in the elderly dogs were lower than those in the younger animals, whereas the numbers of Clostridium perfringens and streptococci in the elderly animals were higher than those in the youngers. The high incidence of lecithinase-negative clostridia was observed with advances in age, but not that of spiral shaped rods. The result of this study shows that the advances in age of beagle dogs yield some changes in the microbial population of large bowel in the animals.

Aging

Remarkable increase in CD26-positive T cells in patients with human T lymphotropic virus type I (HTLV-I) associated myelopathy.

We used two-color flow cytometric analysis to investigate CD26+ (Ta1+) cells in peripheral blood T lymphocytes from patients with human T-lymphotropic virus type-I (HTLV-I)-associated myelopathy (HAM). The percentage of CD26+ cells among CD3+ cells was markedly increased in patients with HAM, compared with anti-HTLV-I seropositive carriers (p < 0.001) and seronegative controls (p < 0.01). Within the subpopulation of T cells, a significantly high percentage of CD26+ cells was detected in both CD4+ and CD8+ cell populations. Furthermore, analysis of HLA-DR+ T cells revealed similar results. In contrast CD4+CD45RA+ cells were significantly decreased in comparison with controls. These results suggest that immunologically activated or memory T cells found in peripheral blood may be etiologically relevant to HAM.

Adult

Pulmonary intralobar sequestration accompanied by aneurysm of an anomalous arterial supply.

A 47-year-old woman presented with hemoptysis and her chest X-ray films showed an opacity suggesting a mass in the left lower lung field. Based on radiographic investigations, the mass was diagnosed as an aneurysm develop in an anomalous vessel and was considered to be a Pryce type I pulmonary intralobar sequestration. Resection of the left lower lobes was performed and the aneurysm was found to be filled with thrombus. It is rare for an aneurysm to form in an aberrant vessel. This complication may have been the result of regional sclerosis affecting the anomalous artery as well as systemic atherosclerosis.

Aneurysm

Marinesco-Sjögren syndrome with reduced cytochrome c oxidase in muscle.

The present study deals with the sisters of Marinesco-sjögren syndrome without parental consanguinity. Cranial MRI of sisters in a 0.5T superconducting magnet revealed the cerebellar hypoplasia or atrophy, especially in vermis and tonsils with dilatation of IVth ventricle. Microscopic findings of muscle biopsy indicated moderate variation of fibers with phagocytosis, rimmed vacuoles and no ragged red fibers with markedly decreased cytochrome C oxidase activity. 1H-NMR study of urine indicates the secondary decreased turnover rate in urea cycle due to high concentration of 3-hydroxy-n-butyrate.

Biopsy

Thyroid function in premature infants.

The present study was performed using the simultaneous assays of free T4 and TSH levels in dried blood spots of filter paper for mass-screening of inborn errors of metabolism in order to clarify the thyroid function of premature infants. The subjects were divided in three groups: A group infants less than 1500 g at birth (n = 34, 27.4 +/- 2.6 weeks of gestational age), B group infants from 1500 to 2500 g at birth (n = 104, 35.6 +/- 2.4 weeks) and C group infants over 2500 g at birth (n = 490, 39.0 +/- 1.2 weeks). TSH levels were 4.51 +/- 3.03, 2.62 +/- 2.24 and 2.84 +/- 2.06 microU/ml in A, B and C group respectively and significant difference was recognized in group A and C. Free T4 levels were 0.71 +/- 0.42, 1.81 +/- 0.96 and 2.15 +/- 0.67 ng/dl, in group A, B and C respectively, and significant differences were recognized in all three groups. There was positive correlation between free T4 levels and gestational ages (Y = -2.413 +/- 0.11725X, r = 0.206, p less than 0.05).

Humans

[Cricoarytenoid joint involvement in rheumatoid arthritis].

The cricoarytenoid (CA) joint, which controls the vocal cords, is diarthrodial; it is composed of two cartilages with a ligamentous capsule lined by synovial membrane. It has been known that inflammation of CA joint occurs sometimes in patients with rheumatoid arthritis (RA). Yet, so far, no detailed full-report on this subject has ever been made in this country. Here we report four RA cases with CA joint ankylosis or abduction disturbance due to progression of CA arthritis. Episodes of inspiratory dyspnea were observed in all cases and tracheostomy was performed in case 1 and case 2. Further surgical intervention i.e., tracheoplasty was necessary in case 2. Case 3 and case 4 have been followed conservatively thus far. Clinical surgical interventions were necessitated mainly with joint replacement, 3) there exists severe destruction of cervical spines as well as temporomandibular joints. Rheumatologist must be fully aware of how urgent this clinical entity is and not miss-diagnose+ these patients.

Arthritis, Rheumatoid

Hypogalactosylation of immunoglobulin G sugar chains and elevated serum interleukin 6 in Castleman's disease.

Immunoglobulin G (IgG) molecule has two N-linked complex type oligosaccharides, consisting of a mixture of at least 12 different structures. The pattern of these oligosaccharides is fairly constant in healthy individuals. In three patients with Castleman's disease, in whom serum interleukin 6 (IL-6) levels were elevated, agalactosyl species of serum IgG oligosaccharides were markedly increased as compared to those of normal healthy controls. A close relationship between increased IL-6 and altered IgG oligosaccharide structure is suggested.

Adult

Effects of lobenzarit disodium on human endothelial cells. Lobenzarit disodium inhibits proliferative response, HLA-DR antigen expression, and T cell adherence toward endothelial cells.

The therapeutic action of lobenzarit disodium (CCA) on the function of endothelial cells (EC) isolated from human umbilical cord veins was investigated. CCA suppressed 3H-thymidine incorporation into EC in a dose-dependent manner. Significant inhibition was detected at a concentration of 50 micrograms/ml. The expression of HLA-DR antigen on the surface of EC was increased when EC were cultured with recombinant interferon-gamma (rIFN gamma). Treatment of EC with either IFN gamma or interleukin-1 enhanced the adhesion of T cells to EC. The kinetics of HLA-DR antigen expression by EC cultured with IFN gamma was different from the kinetics of T cell-EC adhesion, however. Neither anti-HLA-DR nor anti-HLA-ABC monoclonal antibody inhibited T cell binding to EC monolayers. CCA suppressed the expression of HLA-DR antigen by EC cultured with rIFN gamma. In an EC monolayer adhesion assay, CCA also inhibited T cell adhesion to EC in the presence of either IFN gamma or interleukin-1. Significant inhibition was observed at a CCA concentration of 10 micrograms/ml, a level that is easily attainable in serum. These results suggest that CCA may suppress rheumatoid synovitis by reducing the angiogenesis and emigration of chronic inflammatory cells from the blood into the synovium.

Cell Adhesion

Effects of ubenimex, a biological response modifier, on myelodysplastic syndrome and chronic leukemia.

Twenty cases of myelodysplastic syndrome (MDS) were treated with ubenimex. Seventeen cases were treated with the drug over 90 d. Among these, 10 showed improvement of anemia, 12 an increase in platelet count which had decreased before treatment and 10 an increase in neutrophil count; however, 14 showed an increase in blast percentage in bone marrow aspirate. CD4/CD8 ratio was increased in 4 cases and shifted to a normal from an abnormal range in 6 cases. When the MDS cases were observed in refractory anemia (RA) and refractory anemia with excess blasts (RAEB), great improvement was seen, but in RAEB increase in blast percentage was also observed. CD4 increased mostly in RA and CD8 increased in RAEB. Ten cases of chronic myelocytic leukemia (CML) were first treated with ubenimex and cytostatics, then with ubenimex only. Six cases attained partial remission within 3 months, but one case showed a marked increase in white cell count and blast count and in another case a progression of splenomegaly associated with increase in white cell count. From these findings we conclude that ubenimex could be utilized in MDS or CML if the patient was at risk for strong chemotherapy.

Adult

Purification and some properties of carboxynorspermidine synthase participating in a novel biosynthetic pathway for norspermidine in Vibrio alginolyticus.

Carboxynorspermidine synthase, mediates the nicotinamide-nucleotide-linked reduction of the Schiff base H2N(CH2)3N = CHCH2CH(NH2)COOH. This is formed from L-aspartic beta-semialdehyde (ASA) and 1,3-diaminopropane (DAP) and is reduced to carboxynorspermidine [H2N(CH2)3NH(CH2)2CH(NH2)COOH], an intermediate in the novel pathway for norspermidine (NSPD) biosynthesis. The enzyme was purified to apparent homogeneity from Vibrio alginolyticus and characterized. The overall purification was about 1800-fold over the crude extract, with a yield of 33%. The enzyme displayed an apparent Mr of 93500 +/- 1000 by gel filtration and 45100 +/- 500 by SDS-PAGE, indicating that the native form is probably composed of two subunits of similar size. The specific activity of the purified enzyme was 31.0 mumol carboxynorspermidine produced min-1 (mg protein)-1. The enzyme was activated by dithiothreitol, and inhibited by SH-reactive compounds. The pH and temperature optima were 7.25-7.5 and 37 degrees C, respectively. The Km value for the Schiff base was 4.68 mM, measured by varying the ASA concentration while keeping the DAP concentration constant. Putrescine was slightly active as a substrate, forming carboxyspermidine (at about 7% of the rate of DAP), but ethylenediamine, cadaverine and D-ASA were inert. The Km value for NADPH was 1.51 mM. NADH was a much poorer cofactor than NADPH. When V. alginolyticus was grown in the presence of 5 mM-NSPD, the specific activity of this enzyme was reduced by approximately 70%. NSPD also repressed two other enzymes responsible for its biosynthesis, 2,4-diaminobutyrate decarboxylase and carboxynorspermidine decarboxylase.

Chromatography, Gel

1H-NMR studies of urine in propionic acidemia and methylmalonic acidemia.

The present study deals with the usefulness of 1H-NMR spectroscopy in the chemical diagnosis of propionic acidemia and methylmalonic acidemia. A Varian VXR-500 spectrometer was used. 1H-NMR spectra of urine from a patient with propionic acidemia show peaks of 3-hydroxy-n-valerate, methylcitrate, propionyl glycine, 3-hydroxy-n-butyrate, lactate, 3-hydroxypropionate, tiglylglycine and hippurate. The assignment was made possible by the use of 2D COSY. The spectra from a patient with methylmalonic acidemia show methylmalonate and glycine. 1H-NMR spectroscopy has the advantages of requiring a short time for analysis, relatively small amounts of urine and no preliminary extraction.

Amino Acid Metabolism, Inborn Errors

Occurrence of L-2,4-diaminobutyrate decarboxylase activity in Acinetobacter.

Three strains of the genus Acinetobacter grown in a polyamine-free synthetic medium contained very high amounts of 1,3-diaminopropane, and there were also high concentrations in the extracellular growth medium. Little, if any, of the usual polyamines, putrescine, spermidine and spermine were found. There was no detectable activity of aminopropyltransferase (greater than 0.2 nmol spermidine formed/mg protein/h), which would be responsible for the formation of spermidine or spermine, expected precursors of 1,3-diaminopropane. These observations suggested the possibility of another mode of 1,3-diaminopropane biogenesis. Decarboxylation activity towards L-2,4-diaminobutyrate leading to the formation of 1,3-diaminopropane was detected in extracts of all three strains examined. The decarboxylase was partially purified from A. calcoaceticus ATCC 23055. The enzyme was active against only L-2,4-diaminobutyrate among the diamino acids tested and required pyridoxal phosphate as a cofactor. Mg2+ activated the enzyme.

Acinetobacter

[Recognition of stress in workers (report 1)--relationship between recognitions of causes of stress and stress reaction].

Three aspects of the recognition of stress in 665 workers were investigated; namely, causes of stress, stress reactions and modifying factors. We examined the relationship among these aspects, in order to determine some different types of recognition. Several characteristics of the different recognition groups were also examined. 1) The workers who recognized that the causes of their stress were mainly "daily hassles" or "minor events which happened occasionally" accounted for 82.5% of all subjects, and the workers who recognized that their stress was caused mainly by "major life events" accounted for the remaining 17.5%. 2) The subjective stress of the workers in the "major life events" group was significantly larger than that of the workers in "daily hassles". 3) The group with stress due to "daily hassles or minor events" recognized the stress reaction mainly as "irritability", and their actual stressor was "busyness in work". In contrast, the recognition of a stress reaction due to a "major life event" group was represented by "depression/anxiety", and their actual stressors were not only major events such as "promotion or transfer" but also psychological factors such as "low emotional support of family members". 4) The mean age and rank of the "major life event" group were significantly higher than those of the other group.

Adult