Biomedical subjects
Publications and source records attributed to Y Takeuchi.
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Thirty-nine children with Kawasaki disease have undergone coronary revascularization since 1976. The attrition rate of saphenous vein grafts (SVG) was so high that we have used the internal thoracic artery (ITA) as the graft since 1984. ITA showed excellent early and mid-term patency. We, however, still had to use SVG for the distal portion of right coronary artery (RCA) and left circumflex artery (LCx) where ITA was difficult to reach. In 1988, we first successfully applied the right gastroepiploic artery (GEA) for revascularization to the posterior descending artery of a six-year-old boy. Nine children were then bypassed with the combination of ITA and GEA. GEA was anastomosed to the distal portion of RCA (7 cases) and the branch of LCx (2 cases). In 4 cases GEA showed string sign 1 month after surgery, but the angiographic finding revealed improvement after 1 year interval in 2 cases. The patency of GEA grafts was excellent after 1 month (100%:9/9) and 1 year (100%:9/9), respectively. The use of GEA in addition to ITA as the arterial graft may contribute to the improvement of long-term graft patency in revascularization of children with Kawasaki disease.
We investigated the effect of gamma-interferon (gamma-IFN) on three cellular parameters: cell membrane fluidity and expression of two antigens that have been associated with cell proliferation, namely transferrin receptor (Tf-R: a cell surface protein) and Ki-67 antigen (Ki-67: a nuclear protein). We observed small, yet significant changes in the first two parameters, but not the third parameter. These were investigated in K562 cells, a human chronic myelocytic leukemia cell line. These results suggest that the microviscosity changes and the surface Tf-R density were closely associated, and that gamma-IFN was involved in increasing proliferative activity of the cells by decreasing membrane fluidity and upregulating Tf-R expression.
Cardiovascular changes associated with Graves' disease are generally considered to be secondary to the increased levels of thyroid hormone. We describe a case of Graves' disease in a 25-year-old man, who developed cardiomyopathy with severe heart failure. Pathological examination of the myocardial biopsies showed fibroblast infiltration and degenerative changes. After the cardiomyopathy subsided the patient developed a goitre and signs of hyperthyroidism, followed by Graves' ophthalmopathy, which was treated successfully with a combination of high-dose corticosteroids and orbital radiotherapy. These findings suggested a common pathogenesis for the cardiomyopathy and ophthalmopathy, and prompted us to investigate the expression of TSH receptor (TSH-R) in human heart. TSH-R mRNA was identified in human heart using the reverse transcriptasepolymerase chain reaction (RT-PCR) and DNA sequencing. Taken together, these data suggest that autoimmunity against the TSH-R might contribute to both the cardiomyopathy and ophthalmopathy in similar cases of Graves' disease.
The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.
We present a female patient who received an allogeneic bone marrow transplantation for primary refractory Philadelphia-positive acute biphenotypic leukemia. Since leukemic blasts were persistently present in peripheral blood and bone marrow, in spite of the evidence for engraftment of male donor hematopoiesis, we performed donor leukocyte transfusions and discontinued immunosuppression. An initial complete remission was obtained 15 weeks after allogeneic bone marrow transplantation, and lasted for 24 weeks. We concluded that the prominent mechanism for the eradication of the refractory leukemic clone in the patient was the graft-versus-leukemia effect.
An 8 year old boy with adrenoleukodystrophy and his asymptomatic brother, both with abnormal electro-encephalography as the initial sign of adrenoleukodystrophy, are reported. After suffering from aseptic meningitis caused by Echo virus 30, the first case was suspected of having a complication of meningitis because of persistent abnormal electro-encephalography (i.e. slow wave bursts in the occipital region). This patient was finally diagnosed as having adrenoleukodystrophy because of the increased level of very long chain saturated fatty acids, and typical occipital lesions demonstrated by magnetic resonance imaging and computed tomography. Dietary therapy was tried, but the course was progressive. The brother's electro-encephalography was also abnormal and so was diagnosed as having asymptomatic adrenoleukodystrophy because of an increased level of very long chain saturated fatty acids, although brain magnetic resonance imaging was normal. Abnormal electro-encephalography can therefore be an initial sign of adrenoleukodystrophy even if magnetic resonance imaging shows no abnormality in the brain.
Concentrations and fiber size distribution of asbestos in the lung tissue of 16 ( 8 males and 8 females) rural residents living close to the serpentinite area (neighboring group) were analyzed by low temperature ashing-analytical transmission electron microscopy, and were compared with those of 5 (5 males) rural and 53 (34 males and 19 females) urban residents living away from the serpentinite area (reference group). The results are as follows; 1. Pulmonary asbestos fibers were found in all rural residents. The types of asbestos fibers were chrysotile, amosite, crocidolite, actinolite, and tremolite. These findings were very similar to results for urban residents. 2. In males, the geometric mean concentration of actinolite-tremolite in the neighboring group (1.78 x 10(6) fibers/g dry lung) was significantly higher than those in the reference groups (rural: 0.32 x 10(6), urban: 0.31 x 10(6), p < 0.01). In females also, the geometric mean concentration of actinolite-tremolite in the neighboring group (0.59 x 10(6)) was significantly higher than that in the reference group (urban: 0.16 x 10(6), p < 0.05). There were no significant differences in the actinolite-tremolite concentrations between males and females in the neighboring group. 3. The serpentinite in this area have contained not only chrysotile but also both actinolite and tremolite. There was no significant relationship between actinolite-tremolite concentration and occupational history in the neighboring group. It is possible that actinolite and tremolite are liberated from the serpentinite to the atmosphere and inhaled by the residents near the serpentinite area which increases pulmonary actinolite-tremolite concentration. 4. The difference in the geometric mean concentration of chrysotile between the neighboring and the reference group was not statistically significant for both sexes, possibly due to the poor durability of chrysotile in the lung tissue. 5. There were no significant differences in the geometric mean of fiber length and diameter of actinolite-tremolite between the neighboring and the reference group.
The correlation between S- and G2/M-phase fractions and MIB-1 index in meningiomas was investigated. Flow cytometric analyses were performed on cell suspensions from 81 samples of paraffin-embedded tissue from 29 patients with a total of 28 meningiomas and 1 hemangiopericytoma using the modified Hedley's method. Sections from the paraffin-embedded tissues were stained with anti-MIB-1 monoclonal antibody after microwave oven processing. Five hundreds cells were scored. Correlations between data were estimated using linear regression. DNA aneuploidy was present in 4/29 tumors. Mean S- and G2/M-phase fractions in the 25 nonrecurrent tumors were 1.77 and 4.76%, and in the recurrent tumors were 2.41 and 5.81%, respectively. The proliferative index (PI = S + G2/M fraction) was 6.52% in the nonrecurrent tumors and 8.29% in the recurrent tumors. The mean MIB-1 score in the nonrecurrent tumors was 1.25% and in the recurrent tumors was 2.69%. There was a linear correlation between percentage of S-phase fraction or PI and the MIB-1 score. Both methods are useful to assess the proliferative activity in meningioma.
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Azithromycin (AZM), a new macrolide antibiotic, in fine granules and in capsules was studied for pharmacokinetic and clinical evaluation in the pediatric patients. Antibacterial activity of AZM against 43 clinical isolates: AZM exhibited slightly lower activity against Gram-positive bacteria and 2-8-fold higher activity against Gram-negative bacteria than erythromycin or clarithromycin. Plasma or urine samples were collected from eight patients receiving the drug in fine granular form, and two patients receiving it in capsules for the determination of drug levels. The elimination half-lives of AZM after administration at dose of 10 mg/kg/day for 3 days were 50.0 and 51.2 hours for fine granules, and 41.5 hours for capsules. AUC0-infinity was 11.7 and 24.3 micrograms.hr/ml for fine granules, and 8.3 micrograms.hr/ml for capsules. The cumulative excretion rates up to 120 hours after the start of treatment were 8.24 and 13.84% for fine granules, and 3.83% for capsules. AZM was administered to 123 patients once daily at 3.7-20.0 mg/kg body weight over 3 to 5 days with reference to the standard dose of 10 mg/kg. The drug was used to treat patients with pharyngitis, tonsillitis, scarlet fever, pneumonia, mycoplasmal pneumonia, chlamydial pneumonia, otitis media, pertussis, intestinal infection, and SSTI. The effectiveness of AZM was evaluated in 109 cases. The drug was rated "excellent" in 65.1% of the patients and "good" in 29.4%, resulting in an efficacy rate of 94.5%. Furthermore, AZM eradicated 43 of 46 (93.5%) bacteria that had been identified before the treatment. Three patients complained of side effects of urticaria (1 case) and diarrhea (2 cases). Abnormal laboratory changes were reported as follows: decreased leukocyte (3 cases), increased eosinophil (5), increased platelet (2), increased eosinophil and platelet, elevated GPT (1), and elevated GOT and GPT (1). The abnormalities, however, were mild enough to raise no clinically significant problems. In conclusion, AZM in once daily regimen was effective and safe in treatment of pediatric infections.
We recently reported that gastrin and glycine-extended progastrin processing intermediates (G-Gly) exert growth-promoting effects on AR4-2J cells (derived from rat pancreas) via interaction with distinct receptors. In this study we sought to investigate the mechanisms by which gastrin and G-Gly stimulate cell proliferation. While gastrin increased [Ca2+]i in AR4-2J cells, G-Gly had no effect. Similarly, G-Gly had no effect either on basal and 10(-7) M vasoactive intestinal polypeptide-stimulated cAMP generation, although gastrin is known to inhibit cAMP generation. Gastrin dose dependently stimulated AR4-2J cell mRNA content of both c-fos and c-jun, two genes known to function in regulating cell proliferation, but G-Gly had no effect. Gastrin also induced the expression of luciferase in AR4-2J cells transfected with a construct consisting of a luciferase reporter gene coupled to the serum response element of the c-fos gene promoter. In similar fashion, gastrin stimulated the activity of mitogen-activated protein kinase, an enzyme known to mediate the induction of the c-fos serum response element in response to growth factor stimulation. Although G-Gly had none of these effects of gastrin in AR4-2J cells, it stimulated activity of c-Jun amino-terminal kinase, an enzyme known to phosphorylate and transcriptionally activate c-Jun. These data support the notion that gastrin stimulates cell proliferation by inducing c-fos and c-jun gene expression, while G-Gly acts by post-translationally regulating early gene transcriptional activation. Our studies represent a novel model in which both the precursor and the product of a key processing reaction, peptide alpha-amidation, act cooperatively to stimulate cell proliferation via distinct receptors linked to different signal transduction pathways.
Many plant viruses have single-stranded RNAs as their genomes. During the course of replication, genomic RNAs and their complementary template RNAs are likely to form double-stranded (ds) RNA at least transiently. To attack replication intermediates of many plant RNA viruses specifically, we introduced a yeast-derived ds-RNA specific RNase gene called pac 1 into plants. The transformed plants showed a decrease in lesion numbers when they were challenged with tomato mosaic virus, and a delay in the appearance of symptoms when inoculated with cucumber mosaic virus or potato virus Y.
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MPD1, a yeast gene the overexpression of which suppresses the inviability caused by the loss of protein disulfide isomerase (PDI) was isolated and characterized. The MPD1 gene product retained a single disulfide isomerase active site sequence (APWCGHCK), an N-terminal putative signal sequence, and a C-terminal endoplasmic reticulum (ER) retention signal, and was a novel member of the PDI family. The gene product, identified in yeast extract, contained core size carbohydrates. MPD1 was not essential for growth, but overexpression of the gene suppressed the maturation defect of carboxypeptidase Y caused by PDI1 deletion, indicative of the related function to PDI in the yeast ER.
The age-related changes of serotonergic fibres and S-100 beta-positive astrocytes in the rat dentate gyrus were examined using immunohistochemistry. A significant reduction in the number of the serotonergic fibres and S-100 beta-positive astrocytes was observed throughout the dentate gyrus of the aged rat. A positive correlation was noted between the decrease of serotonergic fibres and S-100 beta-positive astrocytes in the aged rat dentate gyrus. These findings support the hypothesis that the age-related degeneration of serotonergic fibres in the dentate gyrus is caused by the decrease in serotonergic neurotrophic factor S-100 beta in the astrocytes.
T-cell lines chronically infected with laboratory adapted, T-cell tropic HIV-1 strains (RF, LAI, CBL-4, and NY5) induced syncytia after cocultivation with primary macrophages. Such fusion-competent strains, however, replicated inefficiently after cell-free infection of macrophage cultures. Evidence based on proviral DNA synthesis, pseudotype penetration, and a V3 loop mutation revealed that cell-free infection was restricted at a prepenetration stage in entry and controlled by envelope sequences. Our results suggest that primary macrophages are sensitive to cell-to-cell but not to virion-to-cell fusion induced by the envelope glycoproteins of several T-cell tropic HIV-1 strains.
We show that gamma-immunoglobulin (IgG) binds calmodulin (CaM) in a Ca(2+)-independent manner, with Kd value of (1.7 +/- 0.5) x 10(-7) M. A single IgG molecule maximally bound 10 CaM molecules. The binding is to the heavy chain or Fab portion, but not the Fc portion, of the IgG molecules. Ca2+ greatly diminished the interaction between IgG and CaM, with IC50 = 8-9 microM. These data give a novel insight into protein-protein interactions.