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Biomedical subjects

M Ichijo

Publications and source records attributed to M Ichijo.

At least 73 records · Page 4Linked to original sources

The mechanism of human placental urea transport: a study using placental brush border (microvillous) membrane vesicles.

To elucidate the mechanism of placental amino acid transport, the transport of amino acids into brush border membrane vesicles was investigated using brush border membrane vesicles (BBMV) separated from the human full-term placenta. 1. The transport of l-alanine and l-glutamine into the brush border membrane vesicles prepared from either early gestational placenta or full-termed placenta disclosed a typical overshooting phenomenon in the presence of H+ concentration gradient (extravesicular pH greater than intravesicular pH). 2. The H(+)-dependent overshooting transport of urea into the brush border membrane vesicles disappeared in the presence of H+ ionophore. 3. The initial velocity of H+ concentration gradient dependent uptake of urea into the brush border membrane vesicles was regulated by the saturation kinetics determined by the concentration of urea. The values of Km and Vmax, calculated as the kinetic parameters of urea transport by reciprocal plotting of the initial velocity of uptake and the concentration of urea, were 10.8 mM and 410 mumol/mg protein/10 sec, respectively. The above results indicate that a transport system which transports urea in exchange for H+ exists in human full-term placental microvillous membrane.

Biological Transport↗

Pharmacokinetics of vitamin K in mothers and children in the perinatal period: transplacental transport of vitamin K2 (MK-4).

In order to examine the pharmacokinetics of vitamin K2, vitamin K2 (MK-4) was intravenously injected into mothers, and its transfer to placental tissue and the fetuses was examined. While incorporation of vitamin K2 into placental tissue was relatively active, transfer of vitamin K2 to fetal blood (cord blood) was small. So it was indicated that vitamin K2 incorporated into placental tissue from maternal blood is initially stored in the placenta and then gradually released into the fetal blood. Since vitamin K deficiency has been pointed out, release of vitamin K2 into milk was also examined. When vitamin K2 (MK-4) was injected into mothers, the release of vitamin K2 into milk increased with time even after the plasma vitamin K2 concentration in maternal blood decreased. So the presence of a vitamin K2 concentrating mechanism in the mammary tissue was indicated.

Animals↗

Changes in plasma levels of lipid peroxide and vitamin E during pregnancy.

The present study was undertaken in order to determine the changes in blood levels of lipid peroxide and vitamin E during pregnancy. 1. The man plasma level of lipid peroxide was 0.89 +/- 0.13 nmole/ml for non-pregnant women, while in pregnant women it was increased as the progressed pregnancy reaching 2.71 +/- 0.29 nmole/ml at full term. 2. The mean plasma, red cell and platelet levels of vitamin E were 6.6 +/- 0.9 micrograms/ml, 3.55 +/- 0.38 micrograms/ml packed cell and 99 +/- 25 micrograms/g protein for non-pregnant women, while in pregnant women the levels changed as the progressed pregnancy becoming 15.5 +/- 0.9 micrograms/ml, 2.43 +/- 0.24 micrograms/ml packed cell, and 244 +/- 19 micrograms/g protein at full term. It was shown in this study that during pregnancy the plasma level of lipid peroxide increased while the levels of vitamin E which inhibited the formation of lipid peroxide, increased in plasma and platelets, but decreased in red cells.

Adult↗

[The study on the degradation of prostacyclin activity in tissue culture supernatant of human placental villi].

To clarify the role of placental villi in maintaining microcirculation in the placenta, we investigated the action to protect the activity of prostacyclin in the tissue culture supernatant of human placental villi. 1. The platelet aggregation inhibiting activity of prostacyclin was decreased very rapidly in Ringer buffer. 2. The tissue culture supernatant of human placental villi has an action which protects the activity of prostacyclin. On the other hand, in the tissue culture supernatant of human placental decidua no such action is prominent. 3. Human chorionic gonadotropin (hCG) also has an action which protects the activity of prostacyclin. These results indicated that human placental villi play an important role in maintaining placental microcirculation by producing substances which have a protective on the activity of prostacyclin.

Chorionic Gonadotropin↗

[A study of underlying immunoglobulin production by neonates].

During the prenatal period the ability of the fetus mononuclear cells (MNC) to produce antibodies is impaired. 1. In term infants, IgG production with only Staphylococcus aureus Cowan I strain (SAC) stimulation was significantly decreased (p less than 0.00005) as compared with adults. However, when adult MNC supernatant stimulated with Pokeweed mitogen (PWM-sup) was given to full term infants, antibody production significantly increased. 2. The activity inducing antibody production in the full term infant MNC is present primarily in the adult T cell culture supernatant. 3. B cell differentiation factor gamma (BCDF gamma) and BCDF mu, which induce IgG and IgM production, respectively, were significantly reduced in premature and full term infants (p less than 0.00005) as compared with adult. 4. By giving adult PWM-sup to the under 33-week-old infants MNC with SAC stimulation, the induction of both IgG and IgM was reduced, and IgG production was especially inadequate. From the above, it is thought that in full term infants, the production of BCDF gamma and BCDF mu which are produced by T cells is reduced compared to that of adults, and that this is mainly responsible for the reduced antibody production. In addition, in the under 33-week-old infants, the immaturity of B cells and inadequate BCDF production induce underlying poor or inadequate immunoglobulin production.

Adult↗

[The role of vitamin E during pregnancy--anti-platelet aggregation activity of alpha-tocopherol].

To clarify the role of vitamin E (alpha-tocopherol) during pregnancy, we mainly investigated the relation between platelet function and vitamin E and obtained the following results. 1. The concentration of vitamin E (alpha-tocopherol) in plasma and platelet increased gradually during pregnancy. The concentration of vitamin E in plasma was 6.65 micrograms/ml in non pregnant women and 15.5 micrograms/ml in full term pregnant women. And the concentration of vitamin E in platelet was 99 micrograms/g protein in non pregnant women and 244 micrograms/g protein in full term pregnant women. 2. Vitamin E (alpha-tocopherol) inhibited platelet aggregation induced by ADP (adenosine diphosphate) and PAF(platelet activating factor). At a concentration of 500 micrograms/ml vitamin E almost completely inhibited platelet aggregation induced by ADP and PAF. 3. There exists a strong platelet aggregation inhibiting activity in human placental brush border membrane vesicles. At a protein concentration of 20 micrograms/ml the brush border membrane vesicles almost completely inhibited platelet aggregation induced by ADP and PAF. 4. With the co-existence of the brush border membrane vesicles, the platelet aggregation inhibiting activity of vitamin E (alpha-tocopherol) increased prominently. These results indicate that vitamin E plays an important role in the regulation of platelet function and might contribute to the maintenance of placental microcirculation by inhibiting platelet aggregation.

Adenosine Diphosphate↗

Leuko-araiosis, cerebral atrophy, and cerebral perfusion in normal aging.

To elucidate the role of leuko-araiosis observed on computed tomographic imaging among normal populations, 37 neurologically and cognitively normal volunteers ages 18 to 88 years were studied. Local cerebral blood flow was measured using stable xenon-enhanced computed tomography. Severity of leuko-araiosis and cerebral atrophy were graded on computed tomographic images. Leuko-araiosis was observed in 21.6% of normal volunteers, in 52.2% of patients with multi-infarct dementia (n = 23), and in 61.5% of patients with dementia of the Alzheimer type (n = 13). When multiple regression analysis was applied among normal volunteers, the degree of cerebral atrophy, advancing age, and local cerebral blood flow reductions of subcortical white matter correlated and contributed in that order of precedence to the presence and severity of leuko-araiosis. Combination of the unusual vascular anatomy of periventricular white matter together with cerebral hypoperfusion appears to be related to the occurrence of leuko-araiosis observed among neurologically and cognitively normal subjects. Further investigations should determine whether leuko-araiosis among this population is a risk factor for later cognitive impairments.

Adolescent↗

Cortical and subcortical hyperperfusion during migraine and cluster headache measured by Xe CT-CBF.

High-resolution, color-coded images of local cerebral blood flow (LCBF) were made utilizing stable xenon-enhanced computed tomography among patients with common migraine (n = 18), classic migraine (n = 12) and cluster headache (n = 5). During spontaneously occurring headache in common and classic migraine patients, LCBF values for cerebral cortex and subcortical gray and white matter were diffusely increased by 20-40% with the exception of the occipital lobes. LCBF increases involved both hemispheres whether the head pain was unilateral or bilateral. No significant differences were noted in the degree or pattern of LCBF increases during headaches of common and classic migraineurs. Similar cerebral hyperperfusion of greater magnitude was observed during cluster headaches but was more prominent on the side of the head pain. Present observations do not support the hypothesis of spreading cortical depression as a cause of classic migraine. From a hemodynamic viewpoint, LCBF increases during headaches of common or classic migraine or cluster appear similar. Evidence is adduced that sympathetic hypofunction with denervation hypersensitivity of cerebral vessels plays a role in the cerebral hyperperfusion of migraine headaches. More pronounced unilateral autonomic derangements appear to account for the symptoms and cerebral hyperperfusion associated with cluster headaches.

Adult↗

Pregnancy zone protein inhibits production of interleukin-2 but does not affect interleukin-2 receptor expression on T cell activation.

The effect of pregnancy zone protein (PZP), which exhibits increased levels in the blood during pregnancy, on T cells was examined. PZP was found to suppress DNA synthesis following stimulation with phytohemagglutinin (PHA), concanavalin A (ConA) or CD3 antigen or in the mixed lymphocyte reaction (MLR). This effect of PZP was mediated by a reduction in interleukin-2 (IL-2) production, and was abolished by exogenous recombinant IL-2 administration. PZP did not affect the proliferation of T cells following stimulation with the calcium ionophore A23187 and phorbol 12-myristate 13-acetate (TPA). These results suggest that PZP acts on the T cell surface and reduces IL-2 production, but not IL-2R expression, and does not directly affect Ca2+ influx or protein kinase C.

Calcimycin↗

Production of IL-6 (BSF-2/IFN beta 2) by mononuclear cells in premature and term infants.

The production of interleukin 6 (IL-6) was examined in premature neonates (48 cases, including 3 miscarried fetuses) and fullterm neonates (20 cases). The IL-6 production by mononuclear cells was measured after stimulation with Staphylococcus aureus Cowan Strain I (SAC), phytohemagglutinin (PHA) or lipopolysaccharide (LPS). The production in full-term neonates was similar to that in healthy adults, whereas it was significantly lower in premature neonates without premature rupture of the membrane (PROM). However, in premature infants with PROM a normal level of IL-6 production was observed in mononuclear cells stimulated with SAC, PHA and LPS. Furthermore, there was a positive correlation between the IgM concentration in the cord serum and IL-6 production by LPS-stimulated mononuclear cells.

Humans↗

Differential expression of the interleukin 2 receptor beta (p75) chain on human peripheral blood natural killer subsets.

The interleukin-2 receptor (IL-2R) is composed of at least two subunits, the IL-2R alpha (P55, CD25/Tac) and IL-2R beta (p70-75) chains. In the present study we have identified the quantitative expression of IL-2R beta on subsets of NK cells in peripheral blood using flow cytometry and a recently established mAb against IL-2R beta (TU27). We demonstrate that NK cells are not a homogeneous population but that phenotypic subsets exist, and that the levels of IL-2R beta expression correlate with these subsets. The levels of IL-2R beta expression on NK subsets are CD3- CD16- CD56bright NK cells (immature NK) greater than CD16+CD4- NK cells (mature NK) greater than CD16+CD57+ NK cells (more mature NK) in adult peripheral blood lymphocytes. The level of IL-2R beta expression on CD16+ NK cells in cord blood is significantly higher than that in adult PBL. These findings suggest that there may be a inverse relationship between IL-2R beta expression and the differentiation of NK cells. IL-2R beta, preferentially expressed on the NK cells, may play an important role in differentiation and maturation of NK cells.

Adult↗

Identification of HTLV-I sequence in cord blood mononuclear cells of neonates born to HTLV-I antigen/antibody-positive mothers by polymerase chain reaction.

We developed a polymerase chain reaction (PCR) method which has high sensitivity and simple technique in order to investigate the presence or absence of human T lymphotropic virus type I (HTLV-I) provirus in cord blood mononuclear cells of neonates born to HTLV-I carrier mothers. Out of 40, three subjects were found to contain the HTLV-I provirus genome. These three subjects remained HTLV-I sequence-positive in follow-up study. On the other hand, when examined by a conventional technique for detection of HTLV-I-associated antigen on peripheral mononuclear cells, all 40 neonates were HTLV-I-associated antigen-negative. These results suggest that PCR is more sensitive than the conventional antigen detection method and is useful in early detection of HTLV-I infection in neonates born to HTLV-I carriers.

Base Sequence↗

Focal and segmental glomerulosclerosis in preeclamptic patients with nephrotic syndrome.

Etiology and pathogenesis of focal and segmental glomerulosclerosis (FSGS) in patients with toxemia of pregnancy remain controversial. We examined 15 preeclamptic patients presenting with nephrotic syndrome. None of the patients had urinary abnormalities and hypertension before pregnancy. Clinically, proteinuria first developed during pregnancy and disappeared completely in all but one patient lost to follow-up after 1-30 months from delivery. Renal dysfunction, hypertension and edema rapidly resolved in the postpartum period. None of the patients had a progressive clinical course. Renal biopsy specimens obtained postpartum revealed typical features of preeclamptic nephropathy. In addition, findings compatible with FSGS were observed in 13 patients including 4 in which such lesions were unearthed by additional serial sectioning. These results indicate that FSGS may not only be induced by preeclampsia but also be one of the representative glomerular changes in preeclamptic patients with nephrotic syndrome. A favorable clinical course ensues in a manner similar to that of patients with the garden - variety of preeclampsia.

Adolescent↗

p24 protein of a human T-lymphotropic virus type-I (HTLV-I) producing cell line (TCL-Kan) reacts with some normal pregnant women's sera.

Some HTLV-1 antibody carrying pregnant women, who are rated by the gelatin particle agglutination (PA) method, show no expression of HTLV-I antigen in their peripheral blood lymphocytes. Paying attention to this fact, the authors recently studied the reaction of the antibody contained in the PA-positive sera with the antigen protein used for the PA method. This study demonstrated that the protein responsible for non-specific reaction has a molecular weight of 24,000 and that the isoelectric point of this protein differs from that of HTLV-I specific protein.

Agglutination Tests↗

[The maintenance of placental circulation--the study on the platelet inhibition activity of placental chorioepithelial brush border membrane].

We studied the platelet aggregation inhibiting activity of human placental syncytiotrophoblast brush border membrane vesicles (BBMV) and obtained the following results. 1. There existed a very strong platelet aggregation inhibiting activity in placental BBMV. The BBMV almost completely inhibited the platelet aggregation induced by ADP, arachidonic acid and ristocetin. 2. There existed a very strong ADP degrading activity (ADPase activity) in the placental BBMV. ADP was quickly decomposed to AMP by BBMV. 3. Placental BBMV inhibited platelet TXA2 (TXB2) production. In the 0.04 mg/ml protein concentration of BBMV, platelet TXA2 production was almost completely inhibited. 4. There existed a very strong platelet aggregation inhibiting activity in solved BBMV. Soluble BBMV almost completely inhibited the platelet aggregation induced by ADP and arachidonic acid but did not inhibit the platelet aggregation induced by ristocetin. 5. ADP decomposing activity and platelet TXA2 production inhibiting activity were separated by anion exchange column chromatography of soluble BBMV. 6. When BBMV was treated with ultrasonic waves to destroy the membrane structure, only the activity inhibiting ristocetin-induced platelet aggregation was markedly decreased.

Adenosine Diphosphate↗

[Detection of HTLV-I genome in infants born to HTLV-I seropositive mothers by polymerase chain reaction].

We developed a new method to detect human T cell leukemia virus type I (HTLV-I) provirus by amplifying the pX region of the HTLV-I genome by means of the polymerase chain reaction (PCR) method. This new method was used to examine babies delivered by HTLV-I carrier women for HTLV-I vertical transmission. It was found that intra-uterine infection with HTLV-I can occur, though rarely, and some babies carry HTLV-I provirus despite their negative response to HTLV-I antibody, and, noticeably, some of the babies found negative by the conventional antigen detection method may be positive when tested by the PCR method. It was also confirmed with the PCR method that the incidence of vertical transmission of HTLV-I can be reduced to about 1/5 by replacing breast feeding with bottle feeding and frozen mother's milk feeding. It was also found that vertical transmission of HTLV-I can occur at high incidence rates even when the duration of breast feeding is 3 months or less.

Breast Feeding↗

[Intraperitoneal (i.p.) chemotherapy in the management of ovarian cancer--pharmacokinetics and methods of sequential i.p. chemotherapy].

We studied the systemic efficacy of intraperitoneal (i.p.) chemotherapy which has been used as a locoregional chemotherapy for ovarian cancer. The following results were obtained. 1) The CDDP-based i.v. and i.p. regimen obtained a 90% response rate for ascites and a 35% response rate for measurable lesions. 2) According to the pharmacokinetic analysis of i.p.-chemotherapy, BH-AC showed a regional advantage because of a high AUC-ratio. Meanwhile CDDP and etoposide demonstrated a low AUC-ratio, that has direct effects in the abdominal cavity and anti-tumor effects from the vascular side of the tumor. 3) We performed sequential i.p.-chemotherapy using three types of drainage tubes according to the stage and the size of the residual tumor at operation. The abdomino-centesis using a peel-away introducer for the poor risk patients was very easy and this method could carry out sequential CDDP-i.p.. No patients had signs or symptoms of chemical peritonitis. 4) On the base of these date, we have designed a protocol of i.p. chemotherapy for patients with ovarian cancer.

Adult↗