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Biomedical subjects

T Makino

Publications and source records attributed to T Makino.

At least 19 recordsLinked to original sources

Survey of 1120 Japanese women with a history of recurrent spontaneous abortions.

Our recent 7-year clinical survey showed that among the 1120 women with repeated spontaneous abortions registered in this clinic, 2898 out of a total of 3216 pregnancies (90.1%) had terminated in spontaneous abortion. Among these wastages, 84.2% occurred before 12 weeks of gestation, and 11.1 percent occurred between 12 and 15 weeks. Through routine examination of reproductive wastage, 82 (9.9%) of the 825 Japanese couples examined were shown to have either a chromosomal abnormality or normal variants in the wife and/or husband, thus demonstrating no racial difference in the incidence of chromosomal abnormalities in infertile patients in comparison with studies performed in other countries. One hundred and forty-seven congenital uterine anomalies (14.7%) were found in 1000 hysterosalpingographies, and 12 of 148 examined females were positive for anti-cardiolipin antibody. 393 other females with no major abnormalities likely to induce spontaneous abortions were indicated for immunotherapy. Ample time spent on genetic counseling prevented further reproductive wastage, and ideal metroplasty resulted in a successful post-operative pregnancy course in more than 85% of cases. Immunosuppressant and anticoagulant therapy decreased the serum titer of anti-cardiolipin antibody, enabling pregnancies to be maintained to term. Immunotherapy utilizing the husband's lymphocytes also brought more than 80% of pregnancies to successful completion, with 200 deliveries achieved with this therapy. In contrast, 64.1% of pregnancies again terminated spontaneously in patients who were indicated for immunotherapy but did not receive treatment. The findings of the present study suggest that the causes of reproductive wastage, especially the etiology of early recurrent spontaneous abortion, are complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Abortion, Habitual

Quick measurement of serum unconjugated estrogens, and its clinical application to abnormal pregnancies and ovarian follicle maturation.

Using an automated HPLC system reported recently by us (J Clin Lab Anal 4:410-413, 1990), serum unconjugated estriol and estradiol (u-E3 and u-E2) can be measured within 22 min. The clinical value of this method was evaluated in this study with abnormal pregnancies, twin pregnancies, and pregnancies associated with fetal anencephaly or complicated by gestational toxicosis or diabetes mellitus. A significant correlation was demonstrated between an abrupt decrease in serum u-E3 level and an abnormal pattern on fetal heart rate monitor. Since urinary E3 was not sensitive enough to detect any depressed fetal condition, serum u-E3 is better biochemical parameter for assessment of fetal well-being. In addition, u-E2 was measured in the sera of nonpregnant women with separation chromatography as a pretreatment in order to obtain higher sensitivity of the system. This modified HPLC system enabled us to determine the serum u-E2 in about 60 min with the minimal detectable value of 80 pg/ml; the coefficient of correlation with RIA was 0.822. As a result, this quick measurement of u-E3 and u-E2 by our HPLC system revealed to be useful not only for evaluating fetoplacental function but also for monitoring ovarian follicle maturation.

Anencephaly

Flow-cytometric analysis of immune cell populations in human decidua from various types of first-trimester pregnancy.

We undertook an investigation in which flow cytometry was used to characterize immune cell populations in the decidua of first-trimester normal pregnancies, spontaneous abortions, and ectopic pregnancies in comparison to the nonpregnant endometrium to demonstrate how the proportions of immunocompetent cell populations at the fetomaternal interface are influenced by the presence and state of a fetoplacental allograft. No significant differences were found in the decidua of the different types of first-trimester pregnancy in the proportions of the CD45+, CD14+, CD3+, CD4+, CD8+, CD19+, CD3-/CD16+ and/or CD56+, CD3+/CD16+ and/or CD56+, CD4+/Leu-8+, CD4+/Leu-8-, CD8+/CD11b+, CD8+/CD11b-, and CD3+/HLA-DR- decidual leukocyte subsets. However, the percentage of decidual CD3+/HLA-DR+ cells, which are characteristic of activated T cells, was significantly higher in spontaneous abortions than in normal pregnancies (p less than 0.05). This suggests that the accumulation of decidual leukocytes may be regulated mainly by hormones and/or cytokines rather than by the presence and state of an intrauterine conceptus and that on/off-switching of activation of decidual T cells may be associated with successful maintenance of the implanted embryo.

Abortion, Spontaneous

A single optical fiber fluorometric device for measurement of intracellular Ca2+ concentration: its application to hippocampal neurons in vitro and in vivo.

We developed a new system to measure the intracellular Ca2+ concentration in the deep region of the central nervous system with a single optical fiber (300 microns in diameter), used for both excitation and detection of the fluorescence of previously loaded fura-2. With this system, a brain region loaded with fura-2 was illuminated by a rotating disc bearing three different interference filters of 340, 360 and 380 nm at a rate of 600 rpm. The emitted fluorescence was collected by the same fiber connected to a photomultiplier whose output was fed into a computer which regulates the timing of illumination and detection. The time course of the change in the fluorescence due to 340, 360 or 380 nm excitation was measured simultaneously at the maximum sampling rate of 10 points/s. Ratios of fluorescence intensities were obtained after the experiment. After confirming that this system was sensitive enough to detect the change of intracellular Ca2+ concentration in cultured hippocampal neurons and hippocampal slices during depolarization by high potassium medium (50 mM), we applied this system to anesthetized rats. In the hippocampus preloaded with fura-2, characteristic changes in fluorescence intensities ascribed to an increase in intracellular Ca2+ concentration were detected after asphyxia. The system is potentially useful for investigating the physiological and pathological roles of Ca2+ in the brain.

Anesthesia

Promoting effects of both dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated by N-nitrosobis(2-oxopropyl)amine in Syrian golden hamsters.

The effects of dietary cholesterol and cholestyramine on pancreatic carcinogenesis initiated with N-nitrosobis(2-oxopropyl)amine (BOP) were investigated in 120 female Syrian golden hamsters. BOP (70 mg/kg body weight) was injected s.c. once at the beginning of the experiment. Starting 2 weeks later, the animals were then maintained on basal diet or diets containing either 0.5% cholesterol or 1% cholestyramine for a further 16 weeks. All surviving hamsters were killed at week 18, and the pancreas tissues examined histologically. The incidences of pancreatic carcinomas in hamsters fed cholesterol and the cholestyramine supplement were 40.0 and 30.0% respectively; in both cases significantly higher than the 6.9% incidence in the basal diet group. Cholesterol contents of the serum, pancreas and liver were significantly increased by cholesterol feeding and significantly decreased by the cholestyramine diet. The cholesterol diet also significantly increased pancreatic protein and DNA contents, and the concentration of total bile acids and the level of lithocholic acid in gallbladder bile. The cholestyramine diet significantly increased total pancreatic DNA and protein contents, and pancreatic weight. The results thus indicated that both dietary cholesterol and cholestyramine can enhance BOP-initiated pancreatic carcinogenesis in hamsters.

Adenocarcinoma

Electrotransfection of protoplasts from tomato, wild tomato, barley and chrysanthemum with tobacco mosaic virus RNA.

Protoplasts isolated from tomato, wild tomato, barley and chrysanthemum were electrotransfected with tobacco mosaic virus (TMV) RNA under almost the same optimum electric conditions: five square DC pulses of 50 microseconds duration at 500 to 800 V/cm, with the protoplasts suspended at 2 x 10(5)/ml in 0.5 M-mannitol containing 100 microM-MgCl2 and 10 to 20 micrograms/ml TMV RNA. ELISAs of these transfected protoplasts showed that the yields and the growth curves of the virus were quite similar, indicating a lack of host specificity in the initially infected cells of these plants.

Chrysanthemum cinerariifolium

Oligonucleotide sequences required for natural killer cell activation.

Based on the previous finding that certain 30-mer single-stranded oligodeoxyribonucleotides (oligonucleotides) having particular 6-mer palindromic sequences could induce interferon-alpha and -gamma, and enhance natural killer activity, the present study was carried out to clarify the entire relationship between the activity and the sequence of 30-mer oligonucleotides. The results indicated that the activity depended critically on the presence of particular palindromic sequences including the 5'-CG-3' motif(s). The size and the number of palindromes as well as the extra-palindromic sequences also influenced the activity. An oligonucleotide with a 10-mer palindrome and extra-palindromic oligoguanylate sequences showed the strongest activity among the oligonucleotides tested.

Animals

Pulmonary artery disease in Takayasu's arteritis: angiographic findings.

One hundred sixteen arteriographic examinations in 98 patients with Takayasu's arteritis were studied retrospectively to evaluate the extent of aortic and pulmonary disease. Stenosis was the most frequent finding in the aorta and its branches, but occlusion, dilatation, and aneurysms were also seen. Adventitial vascular structures, consistent with dilated vasa vasorum, were observed in five patients (5%) and systemic artery-pulmonary artery communication was seen in six (6%). Twenty-one (70%) of 30 patients who had pulmonary arteriography were shown to have pulmonary artery involvement. Upper lobe pulmonary arterial branches showed abnormalities most frequently; segmental branches, followed by subsegmental branches, were most often involved. The frequency of abnormal findings on pulmonary arteriograms correlated with the number of involved brachiocephalic vessels. Stenotic lesions in the aorta and its branches progressed in five (45%) of 11 patients, and those in the pulmonary artery progressed in one (33%) of three cases. Takayasu's arteritis characteristically involves the systemic and pulmonary arteries, and the extent of arteritis in the major branches of the aortic arch appears to correlate with pulmonary arterial involvement. Both thoracic and abdominal aortographic studies and pulmonary arteriography are necessary to properly diagnose the extent of the disease, and angiography should be repeated for appropriate patient follow-up.

Adolescent

[Prostatic specific antigen (PA) in mass screening for prostate cancer].

The usefulness of prostatic specific antigen (PA) was compared with that of prostatic acid phosphatase (PAP). PA was determined in the serum of 2,183 patient examined by the mass screening for prostate cancer from 1987 to 1990. The serum samples of these patients were obtained from our serum bank. PA was measured by the E test "TOSOH" II (PA). The relationship of PA and PAP to prostate size estimated by digital rectal examination (DRE) and ultrasound tomography (US), and age was investigated. PA and PAP correlated with aging and prostate size estimated by DRE. However PA was more apparently related with these things. The correlation between PA and prostatic size estimated by US was relatively high (r = 0.53), but the correlation between PAP and prostate size estimated by US was low (r = 0.20). When the upper limit of normal range was set at 6.0 ng/ml, the sensitivity, specificity and efficiency was 64%, 97% and 62%, respectively. PA was more sensitive than PAP and could be more useful since none of the patients with prostate cancer was PAP positive and PA negative. We conclude that PA should be a reliable tumor marker in our mass screening system.

Acid Phosphatase

[Endoscopic analysis of gastric mucosal lesions in patients with adult T-cell leukemia during chemotherapy].

Gastric mucosal lesions in 13 patients with adult T-cell leukemia (ATL) were endoscopically studied at least at 2 occasions during chemotherapy for these patients. X-ray examinations by using barium meal showed deformities in 10 patients and abnormal mucosal pattern in 11 out of 13 patients with ATL. The endoscopic examinations revealed gastric ulcers in 5 patients, erosion in 8, diffuse bleeding in 2, tumorous mucosal folds in one, and submucosal tumor in one patient. In 9 out of 12 ATL patients, pathological study revealed that ATL cells had invaded the mucosal area of the stomach. The ulcers and erosions were improved by chemotherapy in 3 out of 5 and 5 out of 8 patients, respectively, whereas the erosion was not reduced in 2 and even aggravated in one patient. Interestingly, the gastric lesions formed by ATL cell invasion were improved by the administration of anticancer agents in 5 out of 9 patients. However, these lesions reappeared together with systemic lesions of ATL.

Adult

[Cyclic thrombocytopenia with chronic thyroiditis and ankylosing spondylitis].

A 58-year-old man with cyclic thrombocytopenia who was initially diagnosed as idiopathic thrombocytopenic purpura (ITP), concomitant with chronic thyroiditis and ankylosing spondylitis, was reported. Serum level of T 3 (0.48 ng/ml) and T 4 (2.1 micrograms/ml) were both subnormal and that of TSH (257.1 microU/ml) was markedly elevated. Thyroid test (6400X) and microsome test (6400X) was both positive, but anti-nuclear antibodies were negative. Radiographic findings of lumbar spine showed the typical "bamboo spine" and HLA B 27 was positive. Therapies for ITP, such as adrenocorticosteroids including steroid pulse therapy, high-dose intravenous gamma-globulin, danazol, slow infusion of vinca alkaloids and splenectomy, were only effective transiently. After these therapies platelet counts began to fluctuate from 0.4 X 10(10)/L to 34.4 X 10(10/L, therefore the diagnosis of cyclic thrombocytopenia was done. Interestingly low-dose methotrexate (MTX) was effective, and the cyclic fluctuation of platelet counts disappeared. These observations in this case were very suggestive of the pathogenesis of cyclic thrombocytopenia and mechanisms of cyclic change of platelet counts.

Humans

A possible mechanism of immunotherapy for patients with recurrent spontaneous abortions.

The mechanism of the beneficial effect of immunotherapy for human reproductive wastage remains to be elucidated. Induction of blocking antibodies such as anti-HLA class II antibodies and anti-idiotypic antibodies was investigated as the mechanism of specific immunosuppression in pregnancy. We reported the changes in the mixed lymphocyte reaction (MLR), T-cell subsets, and generation of anti-idiotypic antibodies after immunotherapy compared to before immunotherapy. MLR was significantly (P less than 0.001) inhibited after the immunization. The mean inhibition rate was 50.2%, suggesting that MLR blocking antibodies were induced by immunotherapy. Binding of autoantibodies to alloactivated maternal lymphoblasts against the paternal lymphocytes was detected in postimmunization cases in two-color flow-cytometric experiments. This suggests that anti-idiotypic antibodies were induced by the immunotherapy. The percentage of cytotoxic T-cells was significantly decreased (P less than 0.05) and the percentage of suppressor T-cells was significantly increased (P less than 0.01) after the immunotherapy, suggesting that a cell-mediated immune response was induced by the immunotherapy.

Abortion, Habitual

Phorbol ester-induced LH release in pituitary gonadotrophs: effects of antagonists of calmodulin and GnRH.

The phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of Ca(2+)- and phospholipid-dependent protein kinase (C kinase), stimulates luteinizing hormone (LH) release from rat pituitary cells. The actions of TPA upon LH release were compared with those of the GnRH superagonist [D-Ala6] des-Gly10-GnRH N-ethylamide (GnRHa) in cultured pituitary cells. LH release was stimulated by 0.1 nM TPA and the maximum response at 10 nM TPA was 50% of the LH response to GnRHa. The ED50 values for TPA and GnRHa were 1.2 and 0.037 nM, respectively, and the maximum stimulatory effects of TPA and GnRHa on LH release were not additive. GnRHa-stimulated LH release was decreased by calmodulin (CaM) antagonists including pimozide, trifluoperazine, W5 and W7, being most effectively reduced (by 70%) by 10 microM pimozide. In contrast to their inhibition of GnRH action, these antagonists enhanced TPA-stimulated LH release, so that 10 microM pimozide and W7 doubled the maximum LH response. The potent GnRH antagonist [Ac-D-p-Cl-Phe1.2, D-Trp3, D-Lys6, D-Ala10]GnRH, which completely inhibited GnRHa-stimulated LH release with ID50 of 6.8 nM, also reduced maximum TPA-stimulated LH release by about 50%. These results suggest that both Ca2+/CaM and C kinase pathways are involved in the LH release mechanism, and indicate that C kinase plays a major role in the action of GnRH upon gonadotropin secretion. The synergism between CaM antagonists and TPA suggests that blockade of CaM-mediated processes leads to enhanced activation of the C kinase pathway, possibly by removal of an inhibitory influence. Furthermore, the partial inhibition of TPA-stimulated LH release by a GnRH antagonist suggests that the pathway(s), specifically connected with LH release in the diverse effects of C kinase, might be locked by the continuous receptor inactivation by antagonist and indicates the complicated pathways which diverge from the receptor and converge into specific cellular response.

Animals

Lack of effect of histidyl-proline diketopiperazine on basal level and TRH-induced response of cytosolic calcium concentration in rat lactotrophs.

Histidyl-proline diketopiperazine [cyclo(His-Pro)] has recently been shown to inhibit prolactin (PRL) secretion in vitro and in vivo. This peptide is well known as a metabolite of thyrotropin-releasing hormone (TRH), which is one of the endogenous secretagogues of PRL. In this study, we investigated the effect of cyclo (His-Pro) on the cytosolic Ca2+ concentration [[Ca2+]i) in cultured lactotrophs by using a lactotroph-enriched fraction separated from female rat pituicytes by centrifugal elutriation. TRH (10 nM) induced a rapid rise in [Ca2+]i in the lactotrophs, followed by a plateau phase of prolonged increase in [Ca2+]i. In contrast, the addition of 100 microM of cyclo (His-Pro) caused no changes in the basal level or the TRH-induced plateau response of [Ca2+]i. Although pretreatment with cyclo (His-Pro) tended to decrease the biphasic increase in [Ca2+]i induced by TRH, the inhibitory effect was not statistically significant. These results demonstrated that cyclo (His-Pro) has no effect on [Ca2+]i in lactotrophs, and does not affect the TRH-induced increase in [Ca2+]i, indicating that the inhibition of PRL secretion by cyclo (His-Pro) may be primarily mediated by other intracellular messengers such as cyclic nucleotides and secondarily involved in other inhibitory systems including that of dopamine.

Animals