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Biomedical subjects

S Kozuma

Publications and source records attributed to S Kozuma.

At least 55 records · Page 3Linked to original sources

Analysis of human leukocyte antigen-G polymorphism including intron 4 in Japanese couples with habitual abortion.

PROBLEM: The purpose of this study was to clarify whether there is a difference between the allele frequency of human leukocyte antigen (HLA)-G in healthy Japanese people and that of Japanese couples with habitual abortion. METHOD OF STUDY: Exons 2, 3, 4, and intron 4 of the HLA-G gene were analyzed in 20 couples with habitual abortion, using polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Intron 4 of the HLA-G gene was also analyzed in 54 healthy individuals. The nucleotide sequence of the PCR product of intron 4 was further determined by direct sequencing. RESULTS: Two kinds of nucleotide sequence were identified in intron 4 of the HLA-G gene, one of which was identical to that of HLA-G*01011, and the other was identical to that of HLA-G*01012, G*01013, and G*0104. The frequency of each allele in affected women and their husbands did not significantly differ from that of healthy individuals, and no mutation was found in any affected couple. CONCLUSION: HLA-G allelic abnormality seemed to have little, if any, implication in the pathogenesis of habitual abortion.

Abortion, Habitual↗

Quantitative assessment of human leukocyte antigen-G protein in amniotic fluid by a double-determinant enzyme-linked immunosorbent assay using anti-human leukocyte antigen-G-specific antibody '87G'.

PROBLEM: The objective of this study was to establish an enzyme-linked immunosorbent assay (ELISA) system, in an attempt to quantify the amount of human leukocyte antigen (HLA)-G protein in amniotic fluid. METHOD OF STUDY: We established a double-determinant ELISA system using the anti-HLA-G specific mouse monoclonal antibody '87G' as a capture antibody and the horseradish-peroxidase labeled rabbit anti-human beta2-microglobulin antibody as a detection antibody. We then measured the concentration of HLA-G protein in amniotic fluid samples from nine normal second-trimester pregnant women and in serum samples from eight normal males. RESULTS AND CONCLUSION: HLA-G protein was detected in amniotic fluid at a concentration of 275 ng/ml (197-343 ng/ml) (median value and 95% confident range), whereas the concentration of HLA-G protein in male serum was below the minimum detection level.

Adult↗

Fetal abnormalities: evaluation with real-time-processible three-dimensional US--preliminary report.

PURPOSE: To assess the usefulness of real-time-processible three-dimensional (3D) ultrasonography (US) in the evaluation of fetal abnormalities. MATERIALS AND METHODS: The apparatus comprised a conventional US scanner with a specially designed unit for real-time-processible 3D US and a transabdominal 3D probe. A 3D US examination was performed in 19 women with abnormalities of the fetus (13-35 weeks gestation) that had been detected at two-dimensional (2D) US. RESULTS: Thirty-six abnormalities were detected with conventional 2D US, real-time-processible 3D US, or both in 19 fetuses with abnormalities. Seventeen (47%) of the 36 abnormalities were demonstrated and confirmed clearly with real-time-processible 3D US, and nine of these had been seen with 2D US. Eighteen intrafetal abnormalities had been demonstrated clearly with 2D US, but 14 of these could not be demonstrated with real-time-processible 3D US. CONCLUSION: Real-time-processible 3D US is useful for evaluating fetal abnormalities as a supplement to 2D US, particularly for abnormalities of the face, ears, fingers, and anatomic axis, but real-time-processible 3D US is unlikely to be helpful for detecting intrafetal abnormalities except for skeletal abnormalities and some pathologic changes with fluid accumulation.

Computer Systems↗

Fetal size as a determinant of obstetrical outcome of post-term pregnancy.

HYPOTHESIS: We hypothesized that there might be differences in the outcomes of post-term pregnancy according to fetal size. METHODS: A retrospective analysis of 143 women with uncomplicated pregnancy that persisted beyond 42 weeks was conducted. Ultrasound dating was performed between 8 and 14 weeks in all cases. The obstetrical outcomes were compared between the cases in which neonatal birth weight was <3,600 g (non-large group) and >/= 3,600 g (large group). RESULTS: In primiparous women, there was no significant difference between the non-large and large groups in terms of the rate of cesarean section, but the rate of cesarean section for fetal distress in the non-large group was significantly higher than that found in the large group. In addition, the non-large group showed a significantly higher incidence of low pH (<7.20) compared with the large group (14/58 vs. 0/22, p < 0.01). In contrast, the rate of prolonged labor (>24 h) and induction failure in the non-large group were significantly lower than that in the large group. In multiparous women, there was no significant difference in obstetrical outcomes between the non-large and large groups. CONCLUSIONS: Primiparous women who were delivered of fetuses weighing not less than 3,600 g at post-term periods were at lower risk of fetal distress on the one hand and at higher risk of induction failure associated with infavorable cervix on the other. This study suggests that post-term pregnancy should be dealt with differently based on fetal weight.

Birth Weight↗

Goat fetuses disconnected from the placenta, but reconnected to an artificial placenta, display intermittent breathing movements.

To investigate whether placental factors are involved in the intermittent breathing movements in goat fetuses, we assessed electrocortical activity (ECoA) and tracheal pressure in 5 fetuses (124-135 days) separated from the placenta and connected for 48 h to an extrauterine fetal incubation system that provided umbilical arteriovenous extracorporeal membrane oxygenation. The fetal physiological condition on this system was almost the same as that in utero for at least 48 h after the preparation. All fetuses showed intermittent low-voltage ECoA and breathing movements. The breathing movements occurred almost exclusively during periods of low- voltage ECoA. The proportions of time spent in low-voltage ECoA and breathing movements were 48-57% and 46-56%, respectively. In conclusion, breathing movements of fetuses on the extrauterine incubation system were episodic, suggesting that intermittent breathing movements are intrinsic to fetuses, independent of placenta-derived factors.

Animals↗

Effects of sairei-to and tokishakuyaku-san on cytokine release from peripheral blood mononuclear cells upon recognition of HLA-G protein in the treatment of recurrent abortion.

Human leukocyte antigen (HLA)-G has been shown to play a role in establishing pregnancy through the mechanism of modulating cytokine secretion from maternal lymphocytes. To elucidate the mechanisms of actions of the herbal medicines, Sairei-to and Tokishakuyaku-san, in the treatment of recurrent abortion, we investigated whether these medicines modulate cytokine secretion from peripheral blood mononuclear cells (PBMCs) upon recognition of HLA-G protein on trophoblasts. Sairei-to and Tokishakuyaku-san increased the interleukin (IL)-1 beta and tumor necrosis factor (TNF)-alpha secretion and decreased the IL-3 secretion from PBMCs regardless of whether these cells recognized HLA-G protein or not. Accordingly, Sairei-to nullified the effects of HLA-G to reduce the secretion of IL-1 beta and TNF-alpha and to enhance the secretion of IL-3. Tokishakuyaku-san also abolished the effect of HLA-G to reduce IL-1 beta and TNF-alpha secretion but did not affect the increase in IL-3 secretion. Thus, it is conceivable that Sairei-to may normalize Th1/Th2 balance by enhancing Th1 polarization in autoimmunity-related recurrent abortion in which Th1/Th2 balance might be shifted towards Th2 polarization. However, the mechanisms of action of Tokishakuyaku-san when used in treating unexplained recurrent abortion, cannot be explained only by the Th1/Th2.

Abortion, Habitual↗

[Recurrent transient increases in liver enzymes specifically after isoflurane anesthesia].

A 69 y-old female underwent orthopedic surgery 12 times in our hospital. A variety of agents were used for anesthesia. She developed episodes of transient increase in liver enzymes only after each of three isoflurane anesthesia (GOT : 311, 292, 328 IU.l-1, GPT: 341, 264, 274 IU.l-1). We suspected drug-induced liver dysfunction, but results of a lymphocyte stimulation test were negative. We conclude that her liver dysfunction was not severe enough to cause clinical symptoms. In such susceptible patients we should be careful of our choice of anesthetic drugs.

Aged↗

Structure, chromosomal location, and expression profile of EXTR1 and EXTR2, new members of the multiple exostoses gene family.

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder that is characterized by the appearance of multiple outgrowths of the long bones (exostoses) at their epiphyses. Genetical heterogeneities have segregated at least on chromosome 8, 11, and 19 and been designated EXT1, EXT2, and EXT3, respectively. Recently, the responsible genes for EXT1 and EXT2 have been isolated and appeared to define a structurally related gene family. In the present study, we have identified novel genes which share significant sequence homologies with the EXT genes. The predicted protein products of the novel EXT-related genes, EXTR and EXTR2 (for EXT-related genes 1 and 2), consist of 919 and 330 amino acid residues, respectively. These genes were transcribed ubiquitously in various tissues. Based on PCR-assisted analyses of both a human/rodent mono-chromosomal hybrid cell panel and a radiation hybrid mapping panel, EXTR1 was localized to the chromosome 8p21 region, where loss of heterozygosity has been frequently observed in various tumors, and EXTR2 was assigned to the chromosome 1p21 region, where osteopetrosis, a dominant hereditary disease of bone, has been mapped by genetic linkage analysis, implying that the protein products of these two EXT-related genes, as well as of the EXT genes, have potential tumor suppressor activity.

Amino Acid Sequence↗

Local dynamic changes of the cervix associated with incompetent cervix before and after Shirodkar's operation.

A 31-year-old woman, gravida 2 para 1, visited our clinic for routine follow-up at 20 weeks' gestation. Although she had no abdominal pain or pressure, digital vaginal examination revealed dilatation of the internal cervical os of 1.5 cm, and transvaginal sonography demonstrated dynamic changes in the shape of the cervical canal. The patient underwent Shirodkar's operation. Routine postoperative assessment of the cervix with transvaginal sonography showed dynamic dilatation of the upper cervix (above the cerclage), which was accompanied by a sensation of pelvic pressure but no apparent uterine contractions. A healthy male infant weighing 2,980 g was delivered at 38 weeks' gestation.

Adult↗

Assignment of the ZIP kinase gene to human chromosome 19p13.3 by somatic hybrid analysis and fluorescence in-situ hybridization.

A cDNA for a putative member of the serine/threonine kinase family was cloned from an adult human testis cDNA library. The predicted translation product was identical to ZIP kinase, which has been suggested to play an important role in the induction of apoptosis. The messenger RNA was ubiquitously expressed in various tissues. The chromosomal location of the gene was determined by fluorescence in-situ hybridization and polymerase chain reaction-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel. This gene was mapped on the q13.3 region of chromosome 19.

Adult↗

Chromosomal assignment of the gene for human DNA-PKcs interacting protein (KIP) on chromosome 15q25.3-q26.1 by somatic hybrid analysis and fluorescence in situ hybridization.

We report the chromosomal location of the gene for DNA-PKcs interacting protein KIP. Based on fluorescence in situ hybridization and polymerase chain reaction (PCR)-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel, this gene was mapped to q25.3-q26.1 region on chromosome 15.

Calcium-Binding Proteins↗

Differential developmental process of respective behavioral states in human fetuses.

The presence of behavioral states has been recognized in human fetuses. However, developmental process of fetal behavioral states remains to be clarified. In thirty-one normal pregnant women between 20 and 41 weeks' gestation, fetal movements were examined by using multiple ultrasonic machines. The entire period was divided into eye movement (EM), no eye movement (NEM), and unclassified periods according to the mode of appearance of rapid eye movements. We investigated changes in the ratio of EM and NEM periods and the incidence of various fetal movements in these periods. The ratio of EM periods increased stepwise between 20 and 32 weeks. The difference in the incidence of "startle" and jaw movements between EM and NEM periods was found at 24-27 and 32-35 weeks, respectively. We found a significant decrease in the incidence of total body movements exclusively in NEM periods at 36-39 weeks and a significant increase in the incidence of "rolling" in EM periods at 40-41 weeks. Eye opening was ultrasonographically recognized, providing evidence for awake state in the human fetus. This study revealed the characteristic appearance of fetal movements as related to the presence or absence of EM during the second half of pregnancy, and thereby pointed to differential development process of behavioral states of human fetuses.

Adult↗

Immunotherapy before and during pregnancy improves pregnancy outcome in women who suffer from recurrent abortion and did not benefit from immunotherapy before pregnancy.

PROBLEM: The appropriate modality of immunotherapy with the husband's mononuclear cells in women with a history of recurrent abortion who aborted despite the immunotherapy performed before pregnancy was explored. METHOD OF STUDY: Nineteen patients who had suffered from recurrent abortion who had received the immunotherapy only before pregnancy and had aborted were treated with further immunotherapy performed either only before pregnancy or twice: before and during pregnancy. RESULTS: In 9 out of the 19 women who received further immunotherapy before pregnancy, 2 had healthy babies and 7 aborted again. In the remaining 10 patients who received further immunotherapy twice, before and during pregnancy, 8 had healthy babies and 2 aborted again. CONCLUSION: Our results indicate that immunotherapy performed before and during pregnancy produces a better outcome compared with that performed only before pregnancy, especially in patients who showed no benefit from the immunotherapy performed only before pregnancy.

Abortion, Habitual↗

Secretion of interleukin-2 from unstimulated peripheral blood mononuclear cells is a possible pathogenic mechanism in recurrent abortion.

PROBLEM: The objective of this study was to evaluate the activated status of helper T cells in women with recurrent abortion. METHOD OF STUDY: The spontaneous secretion of interleukin (IL)-2 from peripheral blood mononuclear cells (PBMCs) obtained from 12 women with primary partner-specific recurrent abortion and 7 normal females and 10 normal males was measured. RESULTS: IL-2 concentrations in medium conditioned with PBMCs from the recurrent abortion group were 1.44 +/- 0.32 (mean +/- standard deviation) U/ml, whereas those from the normal female and male groups were below the minimum detectable concentration. CONCLUSION: The fact that PBMCs from recurrent aborters spontaneously secrete IL-2 suggests that helper T cells are activated in recurrent aborters.

Abortion, Habitual↗

Peripheral blood mononuclear cells from women with recurrent abortion exhibit an aberrant reaction to release cytokines upon the direct contact of human leukocyte antigen-G-expressing cells.

PROBLEM: In search for pathogenesis of recurrent abortion, we examined whether lymphocytes/macrophages from women with recurrent abortion exhibited an aberrant ability to release cytokines upon the direct contact of human leukocyte antigen (HLA)-G. METHOD OF STUDY: The amounts of cytokines released from peripheral blood mononuclear cells (PBMCs) from women with recurrent abortion were compared with those from normal multiparous women or normal nulligravidous women when cocultured with or without HLA-G-expressing target cells. RESULTS: When cocultured with HLA-G-expressing target cells, the amount of interleukin-1 beta released from PBMCs was increased in recurrent aborters whereas it decreased in both normal multiparous and nulligravidous women. The amount of interleukin-3 released from PBMCs did not differ with or without HLA-G-expressing cells in recurrent aborters, whereas it increased in the presence of HLA-G-expressing cells in normal controls. The amount of tumor necrosis factor-alpha released from PBMCs was decreased in the presence of HLA-G-expressing cells in both recurrent aborters and normal controls. CONCLUSION: The aberrant reaction of maternal lymphocytes/macrophages in releasing cytokines upon the contact of HLA-G expressed on trophoblasts may impact negatively on trophoblastic growth, which may be pathogenic in recurrent abortion.

Abortion, Habitual↗

Metabolic and endocrine responses to cold exposure in chronically incubated extrauterine goat fetuses.

To investigate developmental aspects of metabolic and endocrine responses to cold exposure in fetuses, we conducted experiments on six goat fetuses, three aged 95-116 d of gestation (dGA; group I), and three aged 122-134 dGA (group II), using an extrauterine fetal incubation system that provided arterio-venous extracorporeal membrane oxygenation (A-V ECMO). The fetuses were cannulated via the umbilical vessels, and their blood gas exchange was totally supported by A-V ECMO, while they were maintained in an isothermal incubator containing artificial amniotic fluid. After confirming that fetuses were in metabolically stable condition in the extrauterine incubation system, fetal core temperature was lowered by 2 degrees C over 2 h by decreasing the temperature of incubating fluid from 39.5 degrees C. During and after cold exposure, fetal heart rate and arterial blood pressure remained unchanged. We observed significant increases in oxygen consumption and plasma concentrations of norepinephrine, epinephrine, adrenocorticotropic hormone, and cortisol in group II but not in group I fetuses. In addition, based on regression analysis, maximal changes of these parameters during cold exposure were linearly correlated with gestational age significantly, and the regression lines were found to intersect the x (gestational age) axis at around 98-106 dGA. These results suggest that metabolic and endocrine responses to cold exposure develop with gestational age in the goat fetus, the responses being manifested around 100 dGA.

Animals↗