[Development and clinical application of the monoclonal antibodies KM01-antibody and KM02-antibody for pancreatic cancer screening].
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Biomedical subjects
Publications and source records attributed to M Nishida.
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In order to investigate the effect of UFT, a new antitumor agent, 5-fluorouracil (5-FU) levels in serum and various tissues were measured by the gas chromatographic-mass fragmentographic method. The subjects used for the study were nude mice which had received implants of human endometrial carcinoma. The results were as follows: As compared with tegafur, the concentration of 5-FU in serum rose quickly when UFT was administered, and the values were clearly high. The concentration of 5-FU obtained in tumor tissues with the use of UFT were 2.5 times higher than those obtained by the use of tegafur. Even with one third of the dose of UFT, values were still 1.5 times higher. In normal tissues, the administration of UFT against that of tegafur resulted in higher concentrations of 5-FU. On the other hand, when one third of the dose of UFT was used, 5-FU concentrations in major organs, such as the liver or kidney, showed clearly low values. Based on these findings, it became clear that the 5-FU concentration in tumor tissue is specifically raised by tegafur coadministered with Uracil (UFT), while such an effect is prevented from proceeding in normal tissue.
A new human endometrial adenocarcinoma cell line, Ishikawa cells, was established from an endometrial adenocarcinoma from a 39-year-old woman and has been maintained in vitro for more than 3 years. The cells were found to form a monolayer in a mosaic fashion and to tend to pile up. Population doubling time was calculated to be about 36, 29 and 27 hours at the 9th, 40th and 50th generations, respectively. The modal chromosomal number of the cells fell in a diploid range. Histology of the tumor induced in athymic nude mice showed it to be a well differentiated adenocarcinoma which closely resembled the original human tumor. Estrogen receptor and progesterone receptor were demonstrated to occur not only in the induced tumor in athymic nude mice but also in in vitro culture cells. From the fact that the cell growth was maintained in an estrogen-free medium, it appeared that the cells had no estrogen dependency.
Cefotaxime (CTX) was administered to 130 children with various bacterial infections of 41 to 400 mg/kg/day for 2 to 21 days. The clinical effect of CTX was very satisfactory in respiratory tract infection, urinary tract infection and meningitis. The overall clinical effect was excellent in 59, good in 39, fair in 17 and failure in 8 with effective rate of 79.7%. During this therapy, side effects were seen in 3 cases, diarrhea in 1 and rash in 2. Abnormal laboratory findings were seen in 5 cases, elevation of GOT in 1, GOT, GPT and A1-P in 1, GOT, GPT and T. Bil. in 1, elevation of BUN, increase of number of basophils and albuminuria in 1 and observation of albuminuria in 1. The above results demonstrate that CTX is a clinically useful antibiotic for the therapy of pediatric infections.
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The severity of isolated pulmonary valvular stenosis (PS) was evaluated noninvasively and quantitatively using two-dimensional pulsed Doppler echocardiography (2D-PDE). The subjects consisted of 17 patients with PS diagnosed by cardiac catheterization (3 to 15-year-old with a mean age of 7.9 years) and 28 healthy children (3 to 12-year-old with a mean age of 7.2 years). Flow signals by 2D-PDE were recorded in the right ventricular outflow tract just below the pulmonary valve and in the main pulmonary artery. The following three parameters were measured from the flow signals in the right ventricular outflow tract: the right ventricular pre-ejection period (RPEP) from the onset of the QRS in the electrocardiogram to the beginning of RV ejection in 2D-PDE, the acceleration time from the onset of RV ejection to peak velocity (AcT), and the right ventricular ejection time (RET) from the onset to the end of right ventricular (RV) ejection. Acceleration time index (AcT/RET), and systolic time intervals including RPEP/RET, RPEP/square root RR and RET/square root RR in PS were compared with those of the controls. The correlations between the above-mentioned parameters and pressure gradients and RV systolic pressures in PS were examined. Data were expressed as mean value +/- SD. AcT/RET ranged from 0.37 to 0.53 (0.45 +/- 0.04) in the controls and from 0.54 to 0.76 (0.62 +/- 0.07) in PS. The mean AcT/RET was significantly greater in PS than in the controls (p less than 0.001). There was a highly positive correlation of AcT/RET with pressure gradients (r = 0.94) and RV systolic pressures (r = 0.93). RPEP/RET ranged from 0.32 to 0.47 (0.37 +/- 0.04) in the controls and from 0.24 to 0.35 (0.29 +/- 0.03) in PS, and the mean was significantly lower in PS than in the controls (p less than 0.001), and this was caused by the short RPEP and prolonged RET. RPEP/square root RR ranged from 102 to 160 msec (122 +/- 16 msec) in the controls and from 86 to 136 msec (107 +/- 16 msec) in PS, and the mean was significantly shorter in PS (p less than 0.05). RET/square root RR ranged from 300 to 345 msec (323 +/- 13 msec) in the controls and from 308 to 417 msec (363 +/- 27 msec) in PS, and the mean was significantly longer in PS (p less than 0.001). The pressure gradient and RV systolic pressure in PS did not correlate with RPEP/RET, RPEP/square root RR and RET/ square root RR.4+ 102 to 160 msec (122 +/- 16 msec) in the controls and from 86 to 136 msec (107 +/- 16 msec) in PS, and the mean was significantly shorter in PS (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)
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An investigation and comparison of the competitive effect of ceftizoxime, a new cephalosporin, and other beta-lactam antibiotics on in vitro binding of bilirubin to human serum albumin showed that at a normal range of serum albumin (3.48 g/dl) and bilirubin (0.94 mg/dl) in healthy infants, free bilirubin did not increase in the presence of any of the test antibiotics at concentrations up to 640 micrograms/ml. When the albumin concentration was decreased to one-fifth of the normal human range, only ceftizoxime caused no bilirubin displacement.
The isolated cells were obtained from hog thyroid glands treated with dispase. More than 95% of the cells obtained were intact and viable immediately after preparation, and the cell viability did not change during incubation in the experimental conditions. ATP added to the external medium of whole cell suspensions was hydrolyzed in the presence of various divalent cations, especially Mg, and the rate of hydrolysis of ATP was not significantly different between the Mg-ion system and the completed ion system (Mg+Na+K). When whole cell suspensions were disrupted with homogenizer, the hydrolysis of ATP was markedly increased by adding Na plus K. But there was no difference in the Mg-ion system between cell homogenates and whole cell suspensions. ADP, AMP and adenosine as reaction products were found in the reaction mixture which resulted from the hydrolysis of ATP by whole cell suspensions. Our data suggest that Mg-ATPase in the thyroidal isolated cells is an ectoenzyme whose active site(s) are exposed to the external surface of plasma membrane, and that ATP is finally hydrolyzed to adenosine via ADP and AMP by the enzyme(s).
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The protective effect of an immunoactive peptide, D-lactoyl-L-alanyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(L)-glycine (FK-156) and a related compound, heptanoyl-gamma-D-glutamyl-(L)-meso-diaminopimelyl-(D)-alanine (FK-565) was determined in mice with various kinds of microbial infections. FK-156 and FK-565 were given to mice either subcutaneously or orally before challenge. The drugs enhanced significantly the defense of mice against acute systemic infections induced by various extracellular and facultative intracellular organisms, and subcutaneous abscess by Staphylococcus aureus. The protective effect of these drugs against Escherichia coli infection differed considerably depending on the route of administration; FK-156 was only effective by the parenteral route; however, FK-565 was effective by both parenteral and oral routes. After subcutaneous dosing with FK-156, the enhancement of host defense of mice against E. coli infection was more rapid than against Listeria infection. The enhancing effects of FK-156 and FK-565 on host defense of mice against pseudomonal infection was more potent than other immunoactive drugs.
The immunoactive peptides, FK-156 and its analogue, FK-565 were evaluated in various models of mice immunosuppressed with cyclophosphamide, hydrocortisone, mitomycin C, carrageenan and tumor cells. Treatment with FK-156 (subcutaneous) and FK-565 (oral) markedly restored host defense ability against microbial infection. The therapeutic effect of ticarcillin or gentamicin alone against pseudomonal infection in cyclophosphamide- and hydrocortisone-treated mice and tumor-bearing mice was much lower than in normal mice. The therapeutic effect of these antibiotics against pseudomonal infection in immunosuppressed mice was enhanced markedly by combined use with FK-156. The killing ability of macrophages and polymorphonuclear leukocytes of the immunosuppressed mice was also markedly enhanced by dosing with FK-156.
We investigated the effect of immunoactive peptides, FK-156 and FK-565 on host defense mechanisms against microbial invasion. It was shown that these drugs given to normal mice increased the counts of phagocytes in both peripheral blood and peritoneal cavity, and enhanced the chemotactic, phagocytic and killing activities of peritoneal macrophages and polymorphonuclear leukocytes, and stimulated the phagocytic function of the reticuloendothelial system. Enhanced host resistance to microbial infection by these immunoactive peptides might be induced by both increase in counts and enhancement of functions of phagocytes. FK-156 restored decreased counts and functions of phagocytes in mice immunosuppressed by cyclophosphamide, hydrocortisone or tumor. These findings suggest that these immunoactive peptides could be applied to prevent intractable infection in immunocompromised hosts.
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