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Biomedical subjects

K Aoki

Publications and source records attributed to K Aoki.

At least 415 records · Page 23Linked to original sources

A novel gene, Translin, encodes a recombination hotspot binding protein associated with chromosomal translocations.

We have identified a novel gene, Translin, encoding a protein which specifically binds to consensus sequences at breakpoint junctions of chromosomal translocations in many cases of lymphoid malignancies. The encoded protein, Translin, is a previously undescribed type with no significant similarity to known proteins. In the native form, Translin polypeptides form a multimeric structure which is responsible for its DNA binding activity. Nuclear localization of Translin is limited to lymphoid cell lines, raising the intriguing possibility that nuclear transport of Translin is regulated in a physiologically significant way such that active nuclear transport is associated with the lymphoid specific process known as Ig/TCR gene rearrangement.

Amino Acid Sequence↗

Activation of protein kinase C by mycobacterial cord factor, trehalose 6-monomycolate, resulting in tumor necrosis factor-alpha release in mouse lung tissues.

Cord factors are mycoloyl glycolipids in cell walls of bacteria belonging to Actinomycetales, such as Mycobacterium, Nocardia and Rhodococcus. They induce granuloma formation in the lung and interstitial pneumonitis, associated with production of macrophage-derived cytokines. We studied how cord factors induce biological activities in the cells. Cord factors isolated from M. tuberculosis, trehalose 6-monomycolate (mTMM) and trehalose 6,6'-dimycolate (mTDM), enhanced protein kinase C (PKC) activation in the presence of phosphatidylserine (PtdSer), diacylglycerol and Ca2+, and mTMM activated PKC alpha more strongly than PKC beta or gamma under the same assay conditions. Kinetic studies of mTMM in response to PKC activation revealed that mTMM increased the apparent affinity of PKC to Ca2+ in the presence of both PtdSer and diolein. Although this is similar to observations with unsaturated fatty acids, such as arachidonic acid, mTMM was synergistic with PtdSer for PKC activation, but arachidonic acid was not. mTMM was also different as regards PKC activation, as phorbol ester was. A single i.p. administration of mTMM to mouse induced tumor necrosis factor-alpha (TNF-alpha) in serum and in the lung, which is a unique target tissue of cord factors. Based on our recent finding that TNF-alpha is an endogenous tumor promoter, the correlation between lung cancer and pulmonary tuberculosis is discussed.

Animals↗

Suppression of natural killer cell activity by monocytes following immunotherapy for recurrent spontaneous aborters.

PROBLEM: Natural killer (NK) cell activity has previously been shown to decrease in normal pregnancy as compared with the nonpregnancy state. The purpose of this study was to determine NK cell activity in recurrent aborters and to investigate the kinetics of NK cell activity following immunotherapy. METHODS: Recurrent aborters (N = 17) were immunized with husbands' mononuclear cells (1 x 10(8)) twice during the early stage of current pregnancy. NK cell activity of recurrent aborters as well as that of normal pregnant (N = 12) and nonpregnant (N = 6) women (controls) was determined by 51Cr release assay. Monocytes were depleted from the mononuclear cell fraction and its effect on the NK cell activity was determined as well. RESULTS: At around 5 wk of gestation, NK cell activity in recurrent aborters before treatment was significantly higher (28.0 +/- 5.1%) than that in normal pregnancy (18.9 +/- 4.3%) (P < 0.01). Following immunotherapy, NK cell activity of recurrent aborters (N = 13) who maintained their pregnancy decreased significantly (21.7 +/- 8.9%) (P < 0.05). In contrast, NK cell activity of recurrent aborters (N = 4) who aborted their current pregnancy did not decrease. Depletion of monocytes resulted in a significant increase in NK cell activity (P < 0.05). CONCLUSIONS: This study suggests that the immunotherapy induces suppression of NK cell activity which may contribute for the maintenance of pregnancy. Moreover, monocytes may be involved in this suppression.

Abortion, Habitual↗

Clinical significance of anti-GM3 antibodies in recurrent pregnancy loss with elevated level of antiphospholipid antibodies.

PROBLEM: The ganglioside-GM3 neutralizes the reactivity of antiphospholipid antibodies (APLs) to phospholipids in vitro. The question of whether anti-GM3 antibodies might exert influence in APLs-positive recurrent pregnancy loss patients who are undergoing prednisolone and aspirin (PSL/ASA) treatment was investigated. METHOD: The anti-GM3 antibody assay of sera was accomplished by ELISA. Sera of 56 patients with recurrent pregnancy loss, including 30 APLs-positive cases given PSL/ASA treatment, were examined. RESULTS: Patients positive for IgG or IgM type anti-GM3 antibodies constituted 13/30 (43%) of the APLs-positive group as compared with only 2/26 (8%) of those who were negative (P < 0.01). In pregnant women with APLs-positive treated with PSL/ASA, live births occurred in only 6/13 (46%) patients with detectable anti-GM3 antibodies, while in 16/17 (94%) who tested negative for anti-GM3 antibodies (P < 0.01). CONCLUSIONS: This observation suggests the possibility that presence of anti-GM3 antibodies may be an indicator for determining the prognosis in recurrent pregnancy loss with elevated level of APLs.

Abortion, Habitual↗

Anticardiolipin antibodies in patients with pregnancy loss induce factor Xa production in the presence of beta 2-glycoprotein I.

PROBLEM: Anticardiolipin antibodies (aCL) are commonly associated with recurrent pregnancy loss, though the mechanism is uncertain. Some investigators have indicated that aCL may be directed at a complex made up of cardiolipin and a blood anticoagulant, beta 2-glycoprotein I (beta 2GPI). We therefore investigated the effects of beta 2GPI-dependent aCL IgG enriched fractions, isolated from sera of patients with pregnancy losses, on blood coagulation. METHOD: beta 2GPI-dependent aCL were prepared from sera of three women with second trimester pregnancy losses, by cardiolipin affinity column chromography, following by anti-beta 2GPI affinity column chromatography. The effects of beta 2GPI and beta 2GPI-dependent aCL on the activation of factor X in vitro were examined. RESULTS: beta 2GPI inhibited the activation of factor X and beta 2GPI-dependent aCL blocked this inhibitory effect in a dose dependent manner. CONCLUSION: These results imply the possibility of beta 2GPI-dependent aCL induce hypercoagulation or thrombus by blocking the inhibitory effect of beta 2GPI on activation of factor X, which may result in pregnancy loss.

Abortion, Habitual↗

Overexpression of the PRAD1 oncogene in a patient with multiple myeloma and t(11;14)(q13;q32).

The t(11;14)(q13;q32) chromosomal translocation is associated with several B-cell lymphoproliferative disorders and is thought to result in upregulation of expression of PRAD1/cyclin D1 proto-oncogene. A patient with multiple myeloma of IgG kappa-type with t(11;14)(q13;q32) is now shown to overexpress PRAD1. The clinical stage of the disease was advanced (IIIA), with a myeloma cell count of 94.6% in the bone marrow. Chromosomal analysis of bone marrow cells showed t(11;14)(q13;q32) in five of 20 metaphases as well as other karyotypic features. Northern blot analysis of RNA prepared from myeloma cells revealed overexpression of PRAD1. Multiple myeloma with t(11;14)(q13;q32) has been associated with an aggressive clinical course. Although neither myeloma cells in the peripheral blood nor extramedullary lesions were apparent in the present patient, the myeloma was refractory to several chemotherapeutic regimens from the beginning. Detection of PRAD1 expression may offer an easier alternative to cytogenetic analysis in myeloma and is a potentially useful indicator of a poor prognosis.

Blotting, Northern↗

Successful pregnancy in a Churg-Strauss syndrome patient with a history of intrauterine fetal death.

Allergic granulomatosis and angiitis was first reported as a disease entity separate from polyarteritis nodosa in 1951 by Churg and Strauss. It is characterized by bronchial asthma, eosinophilia, and vasculitis and is especially rare in women of reproductive age, though, when present, may be associated with fetal mortality in pregnancy. We report a successful pregnancy in a patient who previously experienced intrauterine fetal death at 30 weeks of gestation.

Adult↗

Specific antiphospholipid antibodies (aPL) eluted from placentae of pregnant women with aPL-positive sera.

The mechanism by which antiphospholipid antibodies (aPL) cause recurrent pregnancy loss remains unclear. It has however been reported that aPL may affect cytotrophoblasts in vitro and thus direct placental damage might occur. Therefore, we investigated whether aPL are bound directly to placental tissues in patients with immunoglobulin G (IgG)-aPL positive sera. The material investigated comprised the placentae of six patients with a history of recurrent pregnancy loss and subclinical autoimmune disorder and one with systemic lupus erythematosus, who were treated with a combination of prednisolone and aspirin. Normal controls consisted of placentae derived from six women, negative for serum aPL, with no medical or obstetrical complication during their pregnancy. Five kinds of IgG- and IgM-antiphospholipid (anti-PS, PI, PA, PG and CL) antibodies were eluted from the placentae of both patients and controls, which were measured by enzyme-linked immunosorbent assay. IgG-aPL were detected in the placental eluates of four of seven (57%) patients, whereas IgM-aPL were not found in any. With respect to the pregnancy outcome of the four patients with IgG-aPL-positive placental eluates, one experienced intrauterine fetal death (IUFD) at 23 weeks of gestation and three demonstrated intrauterine growth retardation (IUGR). In contrast, the remaining three patients, evaluated negative for IgG-aPL in placental eluates, gave birth to one baby with IUGR and two appropriate-for-date babies. The placentae of the four mothers with IgG-aPL-positive placental eluates pathologically showed severe thrombotic findings. These results suggest that IgG-aPL can directly bind to placental tissue and might cause pathologic damage resulting in IUFD or IUGR.

Abortion, Habitual↗

Cloning, sequence analysis, and expression of the gene encoding formaldehyde dismutase from Pseudomonas putida F61.

The gene (fdm) coding for formaldehyde dismutase (EC 1.2.99.4) from a genomic library of formaldehyde-tolerant Pseudomonas putida F61 was cloned and expressed in Escherichia coli. The nucleotides of the cloned DNA were sequenced; they included a single open reading frame of 1200 base pairs, coding for a putative protein with a molecular weight of 42,848. Sequencing of the first 20 N-terminal amino acid residues and of an internal part of the enzyme purified from P. putida F61 established the identity and the start codon of fdm. Comparison of the amino acid sequence predicted from fdm with that of alcohol dehydrogenase from horse liver suggested a putative pyridine-dinucleotide-binding domain in fdm, and also potential ligands for the catalytic domain and the second zinc atom-folding domain. fdm seemed to be expressed in E. coli under control of the promoter of fdm; there was an E. coli promoter-like sequence upstream from the gene. The enzyme expressed in E. coli was purified to homogeneity. The molecular weight and the sequence of the first 20 N-terminal amino acid residues were identical with those of P. putida formaldehyde dismutase. Each subunit contained 1 mol of NAD(H) and 2 mol of zinc per mol of protein. The enzyme produced in E. coli catalyzed the dismutation of formaldehyde to form methanol and formic acid at the ratio of 1:1 in the absence of the exogenous electron acceptor, NAD(H).

Alcohol Dehydrogenase↗

Insulin sensitivity and negative insulin feedback after pancreas transplantation in insulin-dependent diabetic patients.

The aims of this study were to determine the change in the rate of insulin-stimulated glucose disposal (insulin sensitivity) and the ability of insulin to inhibit its own secretion in four pancreas-kidney transplant recipients with insulin-dependent diabetes mellitus. Insulin sensitivity (glucose infusion rate, GIR) was measured by a euglycemic hyperinsulinemic clamp technique before and 2, 6 and 12 months after transplantation. The GIR values in the four recipients were normalized within 2 months and remained normal for 12 months after transplantation, despite long-term steroid therapy for immunosuppression. Physiological hyperinsulinemia (50-70 microU/ml) suppressed plasma C-peptide, but its nadirs were still higher than the basal levels in normal controls. Taking into account evidence of a minimal increase in the concentration of circulating insulin that inhibits insulin secretion in healthy subjects and evidence of increased insulin secretion in pancreas recipients, the authors speculate that defective feedback inhibition of insulin secretion could contribute, at least in part, to the disproportionate basal hyperinsulinemia in patients with a denervated, transplanted pancreas in the absence of insulin resistance.

Adult↗

Influence of different doses of methyl ethyl ketone on 2,5-hexanedione concentrations in the sciatic nerve, serum, and urine of rats.

Rats were injected subcutaneously with 2,5-hexanedione (2,5-HD 2.6 m mol/kg) alone (HD group) or with 2,5-HD and methyl ethyl ketone (MEK) (2.6 m mol/kg of each agent, HD&MEK group) or with 2,5-HD 2.6 m mol/kg and 5 times that dose (13.0 m mol/kg) of MEK (HD&5MEK group). The concentration of 2,5-HD in serum and in the sciatic nerve was determined 0.5, 1, 2, 4, 8, and 16 h after administration. Urinary 2,5-HD concentration was determined from the beginning of administration up to 16 h afterward. 1) The concentration of 2,5-HD in the serum, the sciatic nerve, and the urine was increased significantly (p < 0.05) in the co-administered groups; the higher the MEK doses were, the greater was the increase. 2) The clearance of 2,5-HD from both the serum and the sciatic nerve was delayed in the co-administered groups. The highest concentration in serum and the sciatic nerve appeared at 1 and 2 h respectively. After administration, the biological halflife (t1/2) of 2,5-HD from 1 to 8 h in serum was 6.5, 5.8 and 12.0 h for the HD, HD&MEK, and HD&5 MEK groups respectively. From 8 to 16 h, the t1/2 in serum was 1.2, 3.2 and 16.6 h for the HD, HD&MEK, and HD&5MEK groups, respectively. In nerve tissue, the prolongation of clearance in the co-administered groups was greater than that in serum, the t1/2 from 2 to 8 h being 5.2, 9.6 and 19.9 h for the HD, HD&MEK, and HD&5MEK groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

A study on indices of body fat distribution for screening for obesity.

In order to screen high risk obesity groups for coronary heart disease, the relationships between certain body fat distribution indices and coronary risk factors (CRFs) were analyzed. Body circumference at various measuring points and skinfold thickness were measured in 938 male clerical workers, and some indices of body fat distribution were calculated. The results are as follows: (1) The body mass index (BMI) showed the highest correlation with systolic blood pressure, and skinfold thickness showed a high correlation with serum total cholesterol (TC) and LDL-cholesterol. (2) In body fat distribution indices, the waist/stature ratio (WSR) showed the highest correlation with CRF measurements, especially with serum triglyceride (TG) and diastolic blood pressure (DBP). (3) WSR showed the highest sensitivity and specificity for screening for abnormal hypertension groups TG and TC. (4) There were significant differences in the mean value for all CRF measurements between the high WSR group (> = 0.49) and the low WSR group (< 0.49), and the rates for high CRF persons in the high WSR group were almost twice those of the low WSR group. These results show that WSR is useful for the screening for obesity to prevent coronary heart disease.

Adipose Tissue↗

Vasorelaxant effect of isocarbacyclin methyl ester incorporated into lipid microspheres on isolated canine arteries.

TTC-909 is a preparation of isocarbacyclin methyl ester (CAS 88931-51-5, TEI-9090) incorporated into lipid microspheres. The characteristics of vasorelaxation induced by TTC-909 were investigated in isolated canine arteries. TTC-909 produced concentration-dependent relaxation of prostaglandin F2a(PGF2a)-induced and U-46619 (TXA2 receptor agonist)-induced contraction in basilar, coronary, renal, mesenteric, and femoral arteries. The vasorelaxant potency of TTC-909 was compared with the potencies of TEI-9090, TEI-7165 (CAS 88911-35-7, free acid of TEI-9090), prostaglandin I2 (PGI2), and prostaglandin E1 (PGE1) on PGF2a-induced contraction in basilar and femoral arteries. The relaxing potency of TTC-909 was similar to the values for TEI-9090, TEI-7165, and PGI2, and more potent than that of PGE1 in both of these arteries. An esterase inhibitor, diisopropyl fluorophosphate (DFP), reduced the vasorelaxant effect of TEI-9090, but not that of TEI-7165, on PGF2a-induced contraction in femoral arteries. These results suggest that TTC-909 has vasorelaxant potency similar to that of PGI2 and greater than that of PGE1. Further, it appears that TEI-9090 was converted to TEI-7165 by esterase and then produced its vasorelaxing effect.

Animals↗

[Epidemic of tuberculosis in Meiji and Taisho eras in Japan and excess deaths from tuberculosis in females].

Acute increase in tuberculosis mortality between 1885 and 1910 could be explained by rapidly increased birth rate, consequently large expansion of noninfected population, and gradual increase in opportunity of contact with infectious patients by changing working environments and living conditions. Prevalence of tuberculosis patients was not so few in the beginning of Meiji era. Vicious spiral of increased young susceptibles, many infectious sources and increased opportunity of infection had been continued for long. Lower nutrition from infant to adult, hard work and poor living conditions had worsen prognosis of the patients. Nation-wide tuberculosis control campaign, mainly avoiding contact with patients and contaminated materials had started around 1910 and then issued Factory act which had been improved working conditions in the factories, although the speed was very slow. Tuberculosis mortality began to decrease in 1910s, but sharp temporary rise of tuberculosis mortality was marked in 1918-19 by epidemic of influenza, then the mortality had been declined again. Excess mortality by influenza caused temporary reduction of infectious sources, which had affected mortality rate of tuberculosis in the younger ages after 1920. Large raise-up of wages for factory workers around 1920 and increase trend in income for other workers by economic growth since 1900 had been improved not only working and living conditions, but also dietary life with increased higher intake of animal foods. Female excess deaths from tuberculosis comparing those of males had continued until 1930, then male mortality exceeded females. Mobilization of young women to spinning and textile industries in Meiji and Taisho eras forced to increase in tuberculosis mortality among them.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Transient cerebellar mutism after removal of a posterior fossa tumor in two cases].

We have reported the cases of two young patients who presented transient mutism in the course of recovery from removal of a cerebellar medulloblastoma. Although cerebellar symptoms were observed immediately after surgery, neither consciousness disturbance nor sensory aphasia was observed when the patients were mutic. From the analysis of serial magnetic resonance imaging (MRI). Gd-enhanced regions were noticed in the dentate nucleus and the cerebellar peduncle when mutism appeared, and they disappeared when mutism was gone. Although the mechanism of this interesting symptom is not clear, these MRI findings may indicate that focal ischemia or edema associated with surgical procedure may play a role in the appearance of this symptom.

Adolescent↗