[Transmission of HTLV-I infection from mothers to children].
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Biomedical subjects
Publications and source records attributed to M Ichijo.
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The patients with cartinomatous peritonitis were treated with the intraperitoneal administration (ip) of N4-behenoyl-1-beta-D-arabinofuranosylcytosineine (BH-AC: analogue of Ara-C), and the pharmacokinetics of BH-AC ip was studied. The following results were obtained (1) Immediately after ip administration, the concentration of BH-AC in ascites became as high as 10(6) ng/ml. At 24 hours following BH-AC ip, 10(4) ng/ml of BH-AC was detected in ascites. (2) Immediately after ip administration the concentration of Ara-C derived from BH-AC in ascites became as high as 10(3) ng/ml. At 24 hours, more than 10 ng/ml of Ara-C was detected in the ascites. (3) Ara-U in ascites was detected also soon after BH-AC ip was performed. Accordingly, it is expected that deaminase may be present in ascites. (4) As compared with in ascites, Ara-C in plasma showed very low level (less than 1 ng/ml). These findings indicate that BH-AC is suitable drug for intraperitoneal administration, because BH-AC revealed low peritoneal and high plasma clearances.
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The concentration of taurine in fetal blood and in mother's milk is very high. In the present study, in order to elucidate the nutritional role of taurine during fetal and neonatal age we investigated the urinary taurine excretion and the blood taurine concentration change in premature babies. 1. The blood taurine concentration of infants on the first postnatal day decreased along with gestation between 7-10 gestational months. On the other hand, there was no difference in the concentrations of blood total amino acids in infants on the first postnatal day in 7-10 gestational months. 2. The blood taurine concentration of infants decreased remarkably during one week after birth. This tendency to decrease was more prominent in premature infants--those at 8 to 10 gestational months. 3. The urinary excretion of taurine and total amino acids of infants remarkably decreased along with gestation between 7-10 gestational months. This tendency to decrease was the most prominent in infants between 7 and 8 gestational months.
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HTLV-I is commonly believed to be transmitted from HTLV-I seropositive mothers to infants via breast milk. In 11 of 24 breast-fed infants born to HTLV-I seropositive mothers, HTLV-I antigen-positive cells were detected in peripheral blood samples obtained 12 months after birth. In sharp contrast, they were detected in only one of 11 bottle-fed infants of HTLV-I seropositive mothers. Thus bottle-feeding appears to be an effective method to avoid HTLV-I transmission from HTLV-I seropositive mothers to infants.
To investigate the placental DHA-S (dehydroepiandrosterone sulfate) transport mechanism, the uptake of DHA-S into microvillous membrane vesicles prepared from human term placenta was studied using the rapid filtration technique. 1. The uptake of DHA-S into microvillous membrane vesicles was not dependent on both Na+ electrochemical gradient and membrane potential difference. 2. The uptake of DHA-S into microvillous membrane vesicles was dependent on temperature. The initial uptake rate of DHA-S at 37 degrees C was three times as great as at 4 degrees C. 3. The initial rate of DHA-S transport exhibited saturation kinetics with respect to the DHA-S concentration; an apparent Km of 0.067 mM and Vmax of 1.01 nmol/mg protein/20 sec were calculated. 4. The uptake of DHA-S into microvillous membrane vesicles was inhibited by DHA, but not by estriol. These results indicated that placental DHA-S transport was carrier mediated and a passive one.
To study the toxic effect of inorganic mercury on the placenta we elucidate the effect of inorganic mercury on placental amino acid transport using microvillous membrane vesicles isolated from human normal full term placenta. The transport of amino acids into microvillous membrane vesicles was studied by a rapid filtration technique using a millipore filter. The transport of L-alanine across placental microvillous membrane was Na+ electrochemical gradient dependent and 0.1 mM inorganic mercury inhibited 77% of this Na+ dependent L-alanine transport and 1 mM inorganic mercury inhibits 90% of this Na+ dependent L-alanine transport. The transport of L-lysine across microvillous membrane vesicles was sodium independent and 0.1 mM inorganic mercury inhibited 34% of this transport and 1 mM inorganic mercury inhibited 50% of this transport. These results indicated that one of the toxic effects of inorganic mercury on placenta-fetus unit was the inhibition of placental nutrient transport.
Using microvillous membrane vesicles prepared from human full term placenta, we studied the placental beta-amino acid transport mechanism. The transport of amino acids into microvillous membrane vesicles was studied by a filtration technique using a millipore filter. The uptake of beta-alanine into microvillous membrane vesicles was dependent on Na+ electrochemical gradient (extravesicular greater than intravesicular). The initial rate of this Na+ gradient dependent beta-alanine transport exhibited saturation kinetics with respect to the beta-alanine concentration: an apparent Km of 0.24 mM and Vmax of 46 pmol/mg protein/20 sec were calculated. Taurine inhibited beta-alanine uptake into microvillous membrane vesicles, but on the other hand L-alanine didn't inhibit this beta-alanine uptake. The L-alanine uptake into microvillous membrane vesicles was Na+ electrochemical gradient dependent and the initial rate of this Na+ dependent L-alanine uptake into vesicles was faster than the uptake of Na+ itself into vesicles. On the other hand, the initial rate of Na+ dependent beta-alanine and taurine uptake into vesicles was slower than the uptake of Na+ itself into vesicles. These results indicated that there existed a beta-amino acid specific transport system in human placental microvillous membrane, and placental taurine transport was carried out by this system. And it was also indicated that this placental beta-amino acid transport mechanism is quite different from that of L-alanine.
To elucidate the role of glutathione (GSH) on placental amino acid transport, we investigated L-lysine transport using microvillous membrane vesicles prepared from full term human placenta. 1. The transport of L-lysine into microvillous membrane vesicles was not affected by glutathione. 2. The transport of L-lysine into microvillous membrane vesicles was inhibited by inorganic mercury (Hg2+), and 0.1mM Hg2+ inhibited 34% of this transport and 1mM Hg2+ inhibited 50%. 3. The transport of L-lysine inhibited by Hg2+ was almost completely restored when glutathione was added simultaneously. These results indicated that glutathione defended the inhibitory action of inorganic mercury on L-lysine transport across microvillous membrane.
On the mechanism underlying the repression of antibody production encountered in the new-born, in this study we used the induction of antibody-producing cells on mitogen stimulation of PWM and SAC, identification of T-cell subsets through two-color FACS and the evaluation of cytokine production of IL-1, IL-2 and BCGF with the following results; 1. The cord blood IgG level rose with gestational weeks due to active transport from the mother. The IgM level was low in full term infants. A natural antibody first appeared in the 16th week. 2. Antibody production on mitogen stimulation in infants was remarkably less than in adults. The inability to produce antibodies appears to be closely related to T-cell factors. 3. In examination of the cell surface maker, new-born infants show less suppressor T-cell but significantly more suppressor inducer T-cell than in adults and that its much smaller number of helper T-cells are insufficient for antibody production. 4. Production of IL-1 in full term infants was significantly lower and that in premature subjects was much lower than that in adults. In full term infants, IL-2 was about the same as in adults, and BCGF production was greater than in adults not depressed in full term infants, and were significantly higher in premature infants than that in adults.
To elucidate the change in EPH gestosis placental amino acid transport activity, we investigated the uptake of L-alanine into microvillous membrane vesicles prepared from EPH gestosis placenta and from normal placenta by using a rapid filtration technique. 1. Alkaline phosphatase (ALP) was the marker enzyme of microvillous membrane vesicles (MMV). The ALP activity of mild EPH gestosis placental MMV didn't differ from that of normal placental MMV. On the other hand, the ALP activity of severe EPH gestosis placental MMV decreased compared to that of normal placental MMV. 2. The uptake of L-alanine into human placental MMV was dependent on the Na+ electrochemical gradient, so the transport across human placental MMV was a secondarily active one. The L-alanine transport activity of mild EPH gestosis placental MMV didn't differ from that of normal placental MMV. On the other hand, the L-alanine transport activity of severe EPH gestosis placental MMV decreased prominently compared to that of normal placental MMV.
In order to elucidate the effect of antibiotics (gentamicin) on placental amino acids transport, we investigated L-alanine transport using microvillous membrane vesicles prepared from full-term human placental by a rapid filtration technique. 1. The active transport of L-alanine into microvillous membrane vesicles was dependent on Na+ electrochemical gradient (extravesicular greater than intravesicular). And the double reciprocal plot of this Na+ dependent initial uptake rate versus L-alanine concentration exhibited an apparent Km of 0.79 + 0.23mM and a Vmax of 3.56 + 0.70n mol/mg protein/20 sec. 2. Gentamicin did not affect the Km value of this Na+ dependent L-alanine transport kinetics (0.77 + 0.19 mM [lmM gentamicin], 0.79 + 0.21mM [10mM gentamicin]). On the other hand, gentamicin apparently decreased, the Vmax value of this transport kinetics (1.99 + 0.48n mol/mg protein/20 sec [1mM gentamicin], 1.12 + 0.32n mol/mg protein/20 sec [10mM gentamicin]).
Ontogenic development of human NK cells and LAK cells was evaluated in fetuses in spontaneous abortion, premature infants and full term infants. Additionally, we examined the effect of the production of interleukin-2(IL-2) of cord blood lymphocytes on PHA stimulation. The results were as follows. The NK activity of full term infants was significantly lower than that of adults. But augmented NK activity by recombinant IL-2 (20 U/ml) of term infants was the same as adult levels. However, before 32 weeks gestation, both NK activity and augmented NK activity by recombinant IL-2 were lower than that in full term infants. Using two color flow cytometry, after 16 weeks gestation, the percentage of Leu7- Leu11+ cells was almost equal to the adult level, but only a small number of Leu7+ Leu11+ and Leu7+ Leu11- lymphocytes was noted in premature infants and full term infants. LAK activity was evaluated in fetuses. Fetus that had advanced to 19 weeks of gestation had sufficient LAK activity. After 16 weeks gestation, fetal lymphocytes had good IL-2 production. Therefore in infants, LAK cell can play an important role in immunological surveillance against neoplastic tumor.
using brush border membrane vesicles prepared from human mid gestational fetal intestine (jejunum), the intestinal D-glucose transport mechanism was studied using a rapid filtration technique. The uptake of D-glucose into the vesicles was osmotically sensitive. This finding indicated that the uptake of D-glucose into the vesicles represented transport into the vesicles. A Na+ electrochemical gradient (extravesicular greater than intravesicular) stimulated the initial rate of D-glucose uptake, and Na+ dependent uptake of D-glucose into vesicles showed a typical overshoot phenomenon. This overshoot and the initial rate of uptake were markedly increased when the intravesicular space was rendered electrically more negative by membrane diffusion potentials induced by the use of highly permeant anions. A similar stimulation of D-glucose uptake was observed, when membrane potential (inside negative) was imposed by K+ diffusion potentials via valinomycin. These results indicated that a sodium dependent uptake of D-glucose into the brush border membrane vesicles was dependent on the electrical potential difference of the membrane. The initial rate of D-glucose transport exhibited saturation kinetics with respect to the D-glucose concentration; an apparent Km of 3.2mM and Vmax of 8.1n mol/mg protein/20 sec were calculated. In conclusion the mid gestational fetal intestine (jejunum) already has a D-glucose absorption system which is comparable to the adult one.
Nonenzymatic glucosylation is a reaction in which glucose binds nonenzymatically to hemoglobin, serum protein and glomerular basement membrane collagen etc. It has been thought that nonenzymatic glucosylation results in functional and chemical changes in those substances (hemoglobin etc) and contributes to the pathological changes in diabetes mellitus. This time we investigated whether nonenzymatic glucosylation occurred in human placental trophoblast basement (TrBM) collagen or not. The ability of glucose to interact with TrBM collagen (nonenzymatic glucosylation of TrBM collagen) was examined by incubating TrBM collagen with 3H-D-glucose in vitro. As a result it was shown that nonenzymatic glucosylation occurred in TrBM collagen and nonenzymatic glucosylation of TrBM collagen depended on the glucose concentration, reaction time and reaction temperature. These results indicate that possibly hyperglycemia, via nonenzymatic glucosylation modifies the function and chemistry of TrBM collagen and is related to the placental pathological changes in diabetic pregnancy.
Immediately after CDDP-ip, the level of free Pt in ascites reached nearly 100 micrograms/ml, and the AUC (area under the curve) for ascites was 20-140 times greater than that for serum. The free Pt in serum following CDDP-ip administration was detected for several hours, and interestingly, the AUC for serum after ip therapy was 0.4-2.2 times greater than that after iv therapy. As a result, free Pt was found to act on cancer cells in the abdominal cavity directly at a high concentration. At the same time, the possibility of an antitumor effect from the vascular side of the tumor was also suggested. On the other hand, cases of ovarian cancer had various levels of peritoneal clearance (CLp), which depended on the severity of their carcinomatous peritonitis. The CLp had a great influence on the peak plasma concentration and on the AUC of free Pt in serum. In particular, the peak plasma concentration produced by CDDP-ip was 40-80% of the plasma concentration produced by CDDP-iv. These findings indicate that high-dose CDDP-ip is possibly effective and useful for advanced ovarian cancer, producing only very mild side effects.
A tracer technique for injections into rat fetal abdomen in utero was employed to obtain a better knowledge of amino acid metabolism in fetal hind limb and fetal liver. Calculation of tissue fluid distribution via 3H-inulin space made possible an estimation of the fetal hind limb and fetal liver intracellular amino acid concentration based upon the fetal plasma and fetal tissue amino acid concentration. A significant concentration gradient between fetal plasma and fetal hind limb was found for glutamate (37.3) but not for alanine (9.7) or leucine (3.0). The radioactivity of fetal hind limb and fetal liver after the injection of 1 microCi of radioactive 14C-glutamate 14C-alanine or 14C-leucine into fetal abdomen was measured. In fetal hind limb, significant radioactivity was recognized after 14C-alanine administration, but not after 14C-glutamate administration as against the significant concentration gradient. However, in fetal liver, significant radioactivity was recognized after 14C-glutamate administration, but not after 14C-alanine administration. We concluded that in fetus, glutamate was released from the hind limbs and a large amount taken up by fetal liver.