Biomedical subjects
Publications and source records attributed to I Moriyama.
The nasal cavity is a rare site for an acinic cell carcinoma. We have treated one such tumor in a 68-year-old man. He underwent a Denker's operation under general anesthesia and then received postoperative irradiation at 50 Gy. He has been kept asymptomatic for the past 2 years. To the best of our knowledge, this case is the third report on the acinic cell tumor in the nasal cavity. A brief literature review is also presented.
IL-2 production by PHA-stimulated human lymphocytes in umbilical blood was studied ontogenetically. Lymphocytes from the 16-week-old fetus produced appreciable amounts of interleukin-2 (IL-2). In 16- to 36-week-old fetuses the IL-2 production rate was found to be significantly higher than that in adults. When signal transduction, which is mediated by high affinity IL-2 receptors (IL-2R), was studied after adding exogenous IL-2 to PHA-blast lymphocytes, the response of the 24-week-old fetus was similar to that of adults. These results indicate that the attainment of IL-2 production and the function of IL-2 receptors are completed at a relatively early stage of fetal development.
In recent years, remarkable progress has been made in thermotherapy. However, there is little information on localized laser hyperthermia (laserthermia) or on conventional hyperthermia technique applied to head and neck cancers. We have developed a ceramic probe to insert into tumor tissue and irradiate the Nd:YAG laser omnidirectionally. This probe can heat a spherical range of 1.5 cm to 43 degrees C. This paper concerns experimental and clinical studies on the effectiveness of laserthermia using our technique in the tumor of head and neck regions. The results obtained were as follows: histological findings and biochemical studies of arachidonic acid metabolites on normal rabbit tongue after laserthermia showed very slight effect and relatively short duration of the concomitant inflammation. The combination of laserthermia and CDDP chemotherapy was found to give a much better cytocidal effect on the tumor tissue in nude mice implanted with human thyroid cancer cells. In a clinical study on 21 cases with head and neck cancers, four cases showed complete and 13 cases showed partial remission after combined treatments of laserthermia and radiochemotherapy. Both basic experimental and clinical results have indicated a role for laserthermia in the treatment of head and neck cancer. Possible uses include the treatment of early cancer as well as advanced or recurrent cancer, where its therapeutic effect may be increased by combination with radiotherapy or chemotherapy.
A phase II study of FT-207 suppository (Futraful Suppository) for head and neck cancer was conducted at the Kagoshima University Hospital Dept. of Otorhinolaryngology and its 6 affiliated hospitals. Forty cases with head and neck cancer were entered in the trial, of which 37 were perfectly evaluable. Partial response (PR) (16.7%) was achieved in one of 6 patients with maxillary cancer, in 2 of 9 cases with oral cancer (22.2%), in one of 7 with laryngeal cancer (14.3%), in 3 of 13 with pharyngeal cancer, while 2 of the same 13 achieved a complete response (CR) (38.5%), for a total response rate of 24.3%. FT-207 suppository was continuously administered as standard, at a dose of 750 mg each twice daily, or 1,500 mg/day. The response rate was dose-dependent; 2 CR cases with a total dose of 105 g for administration over a total period of more than 150 days. Adverse effects appearing in 35.0% of the overall were mainly anorexia, nausea and vomiting; none of them, however, were serious.
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.
A synthetic ceramic probe allows a wider angle of irradiation and diffusion of low power energy, below 3W, using an interstitial technique for producing local hyperthermia of Nd: YAG laser (Laserthermia). We studied the influences of this laserthermia procedure in experimental animals and patients with head and neck cancer. The histological findings after laserthermia in the rabbit tongues showed no marked tissue damage in the heated area. Biochemical analysis of arachidonic acid cascade metabolites in these tissues revealed an immediate increase of 12-, 15- HETEs and PGE2 and 3 at days after hyperthermia, but at 8 days these metabolites returned to control levels. The effectiveness of laserthermia on human thyroid cancer implanted in nude mice was compared with that in cisplatin treatment and in combined therapy with both. The most predominant effectiveness was found in the animals receiving therapy combining cisplatin and laserthermia. Laserthermia in combination with radio-chemotherapy was applied in 21 cases with head and neck cancer. Good efficacy was obtained in 17 patients, especially in those with oropharyngeal cancer, showing CR in 4 cases and PR in 13 cases.
A glycopeptide comparable to human renal nephritogenic glycopeptide (nephritogenoside) of glomerular basement membrane (GBM) origin was isolated and purified from human placenta. Trophoblast basement membranes (TrBM) were isolated from placental terminal villi by ultrasonic disruption, and digested with trypsin and then with pronase. TrBM were then fractionated by zone electrophoresis, concanavalin A (Con A) affinity column chromatography and Bio-Gel P200 column chromatography. From 250 g (wet weight) of human placental terminal villi, we obtained a purified sample of 0.7 mg (dry weight) of glycopeptide. Ouchterlony gel diffusion demonstrated the existence of a common precipitin line between purified human placental glycopeptide and antiserum against human renal nephritogenic glycopeptide prepared from GBM. The sugar composition of this glycopeptide was rich in glucose (glucose, galactose and mannose were in the ratio of 1.00:0.30:0.33) and the amino acid composition of this glycopeptide contained no collagenous components. These results indicate that at least one of the nephritogenic substances common to the placenta and kidney is a glycoprotein rich in glucose and different from the collagenous component of the basement membrane.
The placental transport mechanism of glutathione (GSH) was investigated using microvillous membrane vesicles prepared from human term placenta. Using (3H-glycine)-labeled-GSH, it was clarified that GSH in the extravesicular compartment of placental microvillous membranes was rapidly degraded by gamma-GTP (gamma-glutamyltranspeptidase) and resulting amino acid, and 3H-labeled-glycine was actively transported via a sodium cotransport system. AT-125 treated microvillous membrane vesicles almost entirely lost its gamma-GTP activity, and showed intact GSH transport. Using AT-125 treated microvillous membrane vesicles, it was revealed that GSH was transported across the microvillous membrane as an anion via a membrane potential-dependent mechanism. These results indicated that gamma-GTP which existed in microvillous membrane played a role in GSH metabolism and that intracellular GSH was translocated out of the syncythiotrophoblast cell into the maternal blood space via a specific carrier in microvillous membrane because the GSH concentration was higher in intracellular than extracellular and extracellular membrane potential was positively charged.
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.
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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.
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.