Biomedical subjects
Publications and source records attributed to M Tsutsui.
By the use of the peroxidase-labeled antibody method, significant localization of IgG, IgA, albumin and transferrin was demonstrated in the deep lesion of 20 carious teeth, where the secretory component was absent. These serum proteins formed a distinct zone, surrounding the overlying, shallow lesion infected with bacteria.
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Pharmacological properties of procaterol (PRO) in the peripheral organs were examined in comparison with those of sulbutamol (SAL) and isoproterenol (ISO). PRO slightly enhanced twitch tension of the tibialis anterior muscle but affected little the mono- and poly-synaptic spinal reflexes and ganglionic transmission. PRO depressed spontaneous contractions of the isolated ileum, non-pregnant and pregnant uterus and also the gastrointestinal and uterine movements in vivo. PRO prolonged the time of peroral charcoal transport in the intestine. Potencies of PRO in producing these effects were between those of ISO and SAL except those on the uterus in which PRO was more potent than ISO and SAL. Pro depressed gastric and bile secretion but had no effect on pancreatic secretion. ISO, PRO and SAL reduced resistance of the common carotid, femoral and renal arteries and the relative potencies of PRO and SAL to ISO were significantly less in the renal artery than in the other arteries. In accelerating heart rate in conscious rats and dogs, PRO (p.o. or s.c.) was almost equipotent to SAL. Urine flow, GFR, RPF, free water and osmolar clearance and also excretion of electrolytes were reduced by PRO with the concomitant fall of systemic blood pressure. PRO has no effect on blood coagulation and hemolysis but inhibited carrageenin edema and an increase in permeability of blood vessels induced by acetic acid. PRO had no alpha-adrenolytic, cholinolytic and anti-histaminic effects.
The mechanism of transport of the tumor localizing agent, meso-tetra(p-sulfophenyl)porphine (TPPS4), was investigated in Vero and HEp-2 cells in vitro. Vero cells proved to be basically impermeable to the porphyrin, but a slow transport was observed. The uptake was linear with time and appeared to be carrier mediated, as it was strongly inhibited by cyanide or low temperature and demonstrated saturation kinetics. Transport in HEp-2 cells was more rapid and non-linear, reaching a plateau after about 2 h. Analysis of this uptake over a 20-fold range of porphyrin concentration revealed it to be biphasic. A low affinity, high capacity component appeared to be unsaturable and was unaffected by low temperature or metabolic inhibitors. This system is probably one of a passive diffusion. The high affinity, low capacity phase is probably carrier mediated. The tumor cells appear to be "leaky" to the porphyrin, with respect to the Vero cells. This may explain part of the localizing ability of TPPS4.
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meso-Tetra(p-sulfophenyl)porphine (TPPS4) has been found to accumulate in the tumors of mice bearing a murine sarcoma virus-induced rhabdomyosarcoma to a greater degree than in all other tissues except for the kidney. Tumor to tissue ratios of from 3:1 (tumor to liver) to 9:1 (tumor to muscle) were observed. The uptake of TPPS4 was found to be dose dependent, and the highest tumor to tissue ratios were found 96 hours after injection. The water-soluble TPPS4 appears to be cleared through the kidneys and absolute concentrations there are reduced with increasing time after injection. These data are compared with previous studies on TPPS4 localization in Walker 256 carcinosarcoma-bearing mice. In view of this localizing ability and its relative lack of toxicity, TPPS4 seems to represent an ideal candidate for a tumor-localizing agent if high levels of the porphyrin in the kidneys can be reversed.
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