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Biomedical subjects

S Uehara

Publications and source records attributed to S Uehara.

At least 19 recordsLinked to original sources

The outcome of pregnancy and prenatal chromosomal diagnosis of fetuses in couples including a translocation carrier.

In order to evaluate the relation between chromosomal translocation and the outcome of pregnancy, 50 couples were examined. Subjects consisted of 35 couples that included a reciprocal translocation carrier; 13 included a Robertsonian translocation carrier and 2 included a carrier of a mosaic reciprocal translocation. The reasons for performing chromosomal examinations were mainly infertility and abnormality of neonates. The rates of miscarriages and neonatal abnormalities in prior pregnancies were significantly higher than the birth rate of morphologically normal newborns. The presence of a translocation is closely related to reproductive failure because of the chromosomal imbalance. However, prenatal chromosomal examination after the 15th gestational week in subsequent pregnancies revealed that almost half of the fetuses showed normal karyotypes and only 12.8 per cent of the fetuses showed a chromosomal imbalance. Many chromosomally imbalanced fetuses are spontaneously aborted before amniocentesis. The risk of chromosomal imbalance is relatively low in prenatal diagnosis, but partial trisomies of small rearrangements tend to be preserved.

Adult

Iron(II) sulphate (Fricke solution) oxidation yields for 8.9 and 13.6 keV X-rays from synchrotron radiation.

The oxidation yields (G) for 8.86 and 13.55 keV X-rays produced by synchrotron radiation were measured using an iron(II) sulphate (Fricke) solution. Monoenergetic X-rays were produced using a silicon crystal monochromator. The X-rays were absorbed in 0.4 M sulphuric acid-iron(II) sulphate solution and FeIII ion yields were measured and corrected for escape fractions resulting from scattering using Monte Carlo calculations. Doses in the solution were determined using a thin window, parallel plate chamber calibrated against a primary standard free-air chamber at the Electrotechnical Laboratory (Osaka, Japan). Yields (G) of 1.50 +/- 0.06 and 1.43 +/- 0.06 mumol J-1 were obtained for 8.86 and 13.55 keV X-rays respectively.

Oxidation-Reduction

[Terpenoids and curcuminoids of the rhizoma of Curcuma xanthorrhiza Roxb].

The fresh rhizomes of Curcuma xanthorrhiza Roxb. were investigated for terpenoids and curcuminoids. Nine sesquiterpenoids, alpha-curcumene (1), arturmerone (2), xanthorrhizol (3), germacrone (4), beta-curcumene (6), beta-sesquiphellandrene (9), curzerenone (10), alpha-turmerone (11) and beta-turmerone (12), and three curcuminoids, curcumin (7), mono-demethoxycurcumin (8) and bis-demethoxycurcumin (13), were isolated and one monoterpenoid, camphor (5), was identified by capillary GC-MS. Four species of C. xanthorrhiza could be classified into two chemotypes by their bisabolane-type sesquiterpenoid compositions. The first type contained large amounts of 2, 11 and 12 (CX I type). The second type contained large amounts of 1, 3 and 6, and none of 2, 9, 11 and 12 (CX II type). These two chemotypes, CX I type and CX II type, were compared with the two chemotypes of C. longa L., CL I type and CL II type, on their contents by capillary GC and HPLC analysis. It was found that all of them contained curcuminoids, 7, 8 and 13 and large amounts of various bisabolane-type sesquiterpenoids.

Chromatography, Gas

Pericentric inversion of chromosome 9 in prenatal diagnosis and infertility.

In order to evaluate the relation between pericentric inversion of chromosome 9 (inv(9)) and clinical problems, the characteristics of inv(9) were investigated on the basis of chromosomal analyses of fetuses and infertile couples. The incidence of such inversion in fetuses with parents having an offspring who suffered from various clinical problems was significantly higher than the basic incidence obtained in fetuses karyotyped by reason of advanced maternal age. In the chromosomal examination of the parents whose fetuses were diagnosed as inv(9), it was revealed that either parent might be the carrier. Furthermore, in the inv(9) carrying fetuses, the number of females was significantly greater than that of males. Analysis of infertile couples revealed that the incidence of such inversion in males was significantly higher than the basic incidence mentioned above. Moreover, infertile couples with an inv(9) carrier showed a significantly higher incidence of intrauterine fetal death, compared with infertile couples with a translocation carrier or those in which the etiology was unknown. These results indicate that inv(9) may often cause clinical problems in offspring of the carrier and infertility with unknown mechanisms related to sex.

Chromosome Aberrations

Relation between fetal blood gas levels and the outcome of babies in severe preeclampsia.

The purpose of this study is to ascertain that fetal blood gas values obtained by cordocentesis could be a clinical standard to decide whether or not we should terminate pregnancy and switch to exutero salvage for avoiding hypoxic damage. Fetal blood sampling was performed 38 times in 36 cases of severe preeclampsia. The relation between fetal blood gas values and the prognosis of the baby was statistically examined. Six of 36 fetuses of severe preeclampsia died prenatally or postnatally. There were significant differences in delta-values (difference from the normal mean value in each gestational week) of pO2, pCO2, and pH between survivors and non-survivors. delta pO2 value is most reliable to predict fetal prognosis. Since conventional fetal evaluation methods such as fetal heart rate monitoring are unreliable in the early gestational period, fetal gas evaluation is preferable to decide further intervention.

Blood Gas Analysis

The role of T cells in pathogenesis and protective immunity to murine malaria.

T-cell-mediated immunity to a virulent strain of Plasmodium berghei NK65 (Pb NK65) and to an attenuated derivative (Pb XAT) of the strain were examined in CBA mice by the administration of monoclonal antibodies against T-cell subsets or interferon-gamma (IFN-gamma). The injection of anti-CD8+ or anti-IFN-gamma delayed the mortality of mice infected with Pb NK65, although it did not affect the parasitaemia. In the late stage of PB NK65 infection, T cells, especially CD8+ T cells, were increased in number in the liver at the expense of splenic CD8+ T cells. These CD8+ T cells released IFN-gamma in culture without antigen stimulation and were thought to induce tumour necrosis factor-alpha (TNF-alpha) production by the cells in the liver. In mice infected with Pb XAT, or mice primed with Pb XAT and then challenged with Pb NK65, CD4+ T cells had a crucial role in preventing parasite growth and in protective immunity. IFN-gamma was again the key molecule in protective immunity. These results suggest that T cells stimulated with malaria antigen play important roles both in protective immunity and pathogenesis depending upon their subsets; CD8+ T cells in pathogenesis, and CD4+ T cells in protective immunity. These apparently contradictory responses may be mediated by the same cytokine, IFN-gamma.

Animals

Changes in polymorphonuclear neutrophil-elastase in pancreatitis.

In cases of acute and chronic pancreatitis, we measured the amount of polymorphonuclear neutrophil (PMN)-elastase. There was a significantly larger increase in PMN-elastase in patients with pancreatitis than normal adults. Especially, there was a particularly notable increase in amount of PMN-elastase in patients with severe pancreatitis. Furthermore, the peak of PMN-elastase increase throughout the course of the pancreatitis was seen to be 1-2 days after peak increase in pancreatic enzymes. In the experiment in which pancreatic juice and pig pancreatic kallikrein were added to granulocytes in vitro, we recognized a gradual release of PMN-elastase. From these data, we suggested that timely measurements of PMN-elastase are useful to marker of monitoring clinical changes in severe pancreatitis.

Acute Disease

[Immunological mechanism of pregnancy and miscarriage--a study with a murine spontaneous miscarriage model].

In order to investigate the immunological mechanisms of pregnancy, fluorocytometric and immunohistochemical analysis of the cells was performed in the placenta and spleen of a murine spontaneous miscarriage model (CBA/J x DBA/2) and control (CBA/J x BALB/c). There was a significant difference between the miscarriage rate for the miscarriage model and that for the control, even though H-2 in these two group is matched. The analysis also was performed in a miscarriage model immunized with male splenocytes. Moreover, the effect of gamma-interferon, a potentiator of NK cell activity, on pregnancy was examined. Interferon treatment increased the miscarriage rate. In pregnancy, the number of splenocyte positive Asialo-GM1 or LFA-1 decreased and the intensity of these antigens decreased, as well. Interleukin-2R positive cell increased in number as well as intensity. In the miscarriage model group successfully treated by immunization, the number of Asialo-GM1 positive cells and L3T4 positive cells decreased, whereas they increased in the unsuccessfully treated group. Asialo-GM1 positive cells in the placenta of successful pregnancy decreased in number, and those in miscarried pregnancy increased. In conclusion, the success of the immunization treatment for habitual abortion depends on how to suppress NK cell activity in a linkage with the helper T-cell.

Abortion, Habitual

[Prenatal diagnosis of carbamyl phosphate synthetase deficiency by fetal liver biopsy].

Carbamyl phosphate synthetase deficiency (CPSD) is one of the enzyme defects of the urea cycle and inherited as an autosomal recessive. A definitive enzymatic diagnosis of CPSD can be made by biochemical assay of liver biopsy material, but not of cultured fibroblasts. In pregnancy at risk for CPSD, prenatal diagnosis was attempted by fetal liver biopsy, performed at 22 weeks of gestation. CPS activity was present and a healthy baby was delivered at term. The technique employed for fetal liver biopsy is described together with an evaluation of its possible role in prenatal diagnosis.

Amino Acid Metabolism, Inborn Errors

Regulation of human renin and angiotensinogen genes.

We have constructed pUCSV0cat with low background of chloramphenicol acetyltransferase (CAT) activity and pUCSV3cat (positive control), both containing a SV40 polyadenylation signal 5' to the CAT-coding gene and to the SV40 promoter, respectively. Using this modified pUCSV0cat, we found that human embryonic 293 cells have the ability to activate the promoter of the human renin gene. In addition, we identified the cis-acting sequences responsible for cell-specific expression of the human angiotensinogen gene in its 5'-flanking region.

Angiotensinogen

Biophysical profile and its relation to fetal blood gas level obtained by cordocentesis.

Biophysical profile (BPP) score was assessed immediately before fetal blood sampling by cordocentesis in 150 fetuses referred to our hospital, 95 after and 55 before 30 weeks of gestation. In 95 fetuses after 30 weeks of gestation, 39 fetuses were evaluated with BPP scores of 12, 35 were from 8 to 11 and 21 were less than 7. In 55 fetuses before 30 weeks of gestation, 8 fetuses were evaluated with BPP scores of 12, 27 were from 8 to 11 and 20 were less than 7. pO2, pH and pCO2 in fetuses with a score less than 7, either before or after 30 weeks of gestation, (with a score less than 7) did not significantly differ, in comparison to the other two groups. No variables in the biophysical profile precisely reflect fetal hypoxemia, acidemia or hypercarbia. Since even the fetus with a BPP score of greater than 8 may not always be assured of well-being and not all fetuses with a score of less than 7 are necessarily in a deteriorated condition, it is necessary to evaluate fetal condition on the basis of fetal blood gas data obtained by cordocentesis, especially when the fetus is additionally handicapped by prematurity or morbidities such as growth-retardation.

Blood Specimen Collection

[Incidence of fetal chromosomal aberration in prenatal cytogenetic examination].

One thousand forty-seven fetal samples were obtained from women who received the prenatal cytogenetic examination for different reasons. In this study, the incidence of fetal chromosomal aberration related to each reason was analyzed. The incidence of de novo chromosomal aberration in the fetuses of the higher maternal age group was 1.5% (8/525: 4 cases of 21-trisomy, 2 cases of 18-trisomy and 2 cases of 47,XXY). The incidence in the group of women who had borne (a) chromosomally abnormal child(ren) was 0.5% (1/202). There was no repeat of 21-trisomy, 18-trisomy or 13-trisomy in this study. The incidence in the group of women who had ultrasonographic abnormalities was 16.9% (26/154). In this study, abnormal amniotic fluid volume, intrauterine growth retardation, malformation, hydrops fetalis, intestinal obstruction, omphalocele, single cord artery and cerebellar hypoplasia were related to chromosomal aberrations. The incidence in the group of women whose husband or herself was cytogenetically abnormal was 40.0% (26/65). This high value indicated that parental translocation and inversion are easily transmitted to their offspring.

Adult

Structure and expression of the human angiotensinogen gene. Identification of a unique and highly active promoter.

We have isolated the human angiotensinogen gene from a genomic library and determined the exon-intron junction sequences. The gene is 12 kilobases long and consists of five exons interrupted by four introns, as a single copy in the human genome. Of particular interest are the positions of the introns in the human angiotensinogen gene which are identical to those in the highly homologous human alpha 1-antitrypsin and alpha 1-antichymotrypsin genes, as well as rat and mouse angiotensinogen genes. Northern blot analysis showed that human hepatoma cells (HepG2) produce a large amount of angiotensinogen mRNA but not human glioma cells (T98G). To assay the promoter activity, the 1.3-kilobase genomic fragment containing the 5'-flanking region, first exon, and a part of first intron at positions -1222 to +44 was fused upstream to the chloramphenicol acetyltransferase gene, then transfected into HepG2 and T98G cells. The gene sequence was active only in HepG2 cells, suggesting the presence of a functional promoter. Analysis of deletion mutants demonstrated that the 76-base pairs region from -32 to +44 containing the TATA box and first exon is the minimal promoter, whose activity is as high as that of the SV40 enhancer-promoter. Since the basal expression of the human angiotensinogen gene is much higher in HepG2 than T98G cells, these results may reflect cell-specific differences in the gene transcription.

Amino Acid Sequence

[A case of penicillin-resistant pneumococcal meningitis and antibiotic susceptibility of Streptococcus pneumoniae isolated from children].

Recently, isolation of penicillin-resistant S. pneumoniae has been increasing. The first Japanese case of penicillin-resistant pneumococcal meningitis was reported in 1988. We experienced a case of a one-year-old boy with penicillin-resistant pneumococcal meningitis who dead on arrival on his third day of illness. Minimal inhibitory concentration (MIC) of penicillin G or S. pneumoniae isolated from cerebrospinal fluid and blood was 0.6 micrograms/ml. We evaluated the antibiotic susceptibility of 163 strains of S. pneumoniae isolated from children from 1985 to 1988. Penicillin G (PCG), ampicillin (ABPC), cefotaxime (CTX), imipenem (IPM), and vancomycin (VCM) had good susceptibilities to S. pneumoniae. Twelve of the 163 isolates (7.3%) were penicillin-resistant strains whose MIC of PCG were more than 0.1 microgram/ml, and all of them were intermediately resistant. The annual penicillin-resistant rates were 12.5% in 1985, 1.3% in 1986, 0% in 1986, and 19.0% in 1988. We also evaluated the MIC distribution and MIC90 of antibiotics available for meningitis against penicillin-sensitive and -resistant S. pneumoniae. MIC90 of PCG and ABPC against penicillin-resistant strains was 1.56 micrograms/ml, and it might be dangerous to use PCG or ABPC for central nervous system pneumococcal infections. MIC90 of IPM against penicillin-resistant strains was 0.1 microgram/ml, and that of VCM was 0.4 micrograms/ml. There was little fall of susceptibilities of resistant strains in IPM and VCM. We evaluated the MIC distribution and MIC70 of antibiotics for oral usage against penicillin-sensitive and -resistant S. pneumoniae. Although there were falls of susceptibilities of resistant strains in PCG and ABPC, these two antibiotics had the best susceptibilities among the oral antibiotics.

Anti-Bacterial Agents

[Radiotherapy of aged cancer patients].

Although it is not a categorized modality, cancers of aged patients, generally characterized by a slow growth, histologically high differentiation and low radiosensitivity due to co-existing chronic anemia, should have more individualized treatment because there is a wide spectrum of differences in functional reservoir and tolerance dose of each organs and individuals. In aged cervical cancer of the uterus, we decrease the fractionated and total irradiation dose of a whole pelvic cavity by 10%. For patients more than 80 years old, we principally abandon external beam and singularly chose an intracavitary treatment. In our protocol, there could find no significant difference in 5 year survival between 51-70 y.o. 51.9% (120/231) and 71-80 y.o. 57% (61/107), but in the over 80 y.o. group, it was decreased to 13.6% (3/22) by increased death of other diseases 61.9% (13/21) compared with 18.4% (36/195) in 51-80 y.o. In radiotherapy of advanced lung cancer in aged, we decreased fractionated and total dose by 10 to 20% with minimum irradiation field. In non-small cell carcinoma, a median survival time was 11.5 months in both over and under 70 y.o., although the response rate (CR + PR) was resulted relatively low in aged, 33.3% (N = 45), compared with under 70 y.o., 38.4 (N = 146). The degrees of impairment in respiratory and bone marrow function were similar in both groups. Accordingly, we convinced the efficacy and the necessity of individualized radiotherapy for aged cancer patients.

Aged

[Risk factors relating to coronary artery disease in the elderly].

A total of 224 patients with coronary artery disease (CAD) and 167 healthy control beings (C) were evaluated for coronary risk factors. Analysis of low age subset (age less than 55) disclosed hypertension and hypercholesterolemia were more common findings in CAD compared with C. Significantly elevated plasma triglyceride (TG) and low density lipoprotein cholesterol (LDL-C), and reduced high density lipoprotein cholesterol (HDL-C) concentrations were found in CAD, accompanied by significant increase of atherogenic index (AI). In CAD, a decreased number of males and smokers was noted in high age subset (age over 65). Significantly reduced plasma TG and elevated HDL-C were observed in the elderly compared with the young. AI was also significantly higher in this group. Therefore, in CAD, the level of coronary risk factors seemed to be attenuated in the hig age subset compared with the low age group, which was different from the findings in C in whom significantly increased AI was noted in the elderly. In 61 CAD cases, lipid profiles were monitored for 5 years in average. Significant changes recognized during this period were the reduction of TG, LDL-C and AI along with the elevation of HDL-C, suggesting their risk to be improved. To examine the metabolic effects of diuretics, 52 patients with essential hypertension on trichlormethiazide for long periods were subjected to the substitution of this drug by the inhibitor of angiotensin converting enzyme, enalapril, for more than 3 months. At the end of each treatment, measurements of blood sugar (BS) and insulin (IRI) were made together with lipid analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors

Role of the kallikrein-kinin system in human pancreatitis.

Various factors in the kallikrein-kinin system were evaluated in acute and chronic pancreatitis. It was noted in particular that plasma trypsin and glandular kallikrein increased markedly in acute phase of pancreatitis and its correlation with amylase was observed. Plasma prekallikrein (PPK) decreased in acute pancreatitis, but increased in chronic pancreatitis. A negative correlation was noted between PPK and kallikrein like activity. Both HMW and LMW kininogen decreased in acute pancreatitis. It was presumed from these findings that the increase in kinin and its activation at the acute phase of pancreatitis might be due to kallikrein or trypsin originating from the pancreas.

Acute Disease