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Biomedical subjects

M Ishida

Publications and source records attributed to M Ishida.

At least 379 records · Page 21Linked to original sources

Double antibody radioimmunoassay for monitoring metastatic breast cancer.

We previously reported the production of a panel of murine monoclonal antibodies which recognize glycoproteins abnormally expressed in human breast tumours. Using two of these antibodies, a double antibody radioimmunoassay was designed to quantify levels of these breast tumour marker glycoproteins in serum. Marker levels greater than 28 units were considered abnormal. Using this criterion, 63% and 75% of patients with breast cancer stages I and II, respectively, and 88% of those with metastatic disease were found to have elevated marker levels. Thirteen percent of patients with non-malignant breast disease also had elevated marker levels. Elevated marker levels were also detected in patients with non breast neoplasms. One hundred and eleven women with metastatic disease were followed. Eighty-two percent of those with progressive disease and 73% of those where disease regressed had 20% changes in marker levels. These changes in marker levels preceded by up to 6 months changes in disease state. From these results we conclude that this assay may be useful for monitoring the course of disease in breast cancer patients.

Antibodies, Monoclonal↗

Renal 25-hydroxyvitamin D3-1-hydroxylase in patients with renal disease.

Renal 25-hydroxyvitamin D3-1-hydroxylase (1-hydroxylase) activity has been measured in 20 patients with renal disease using the remaining portion of needle renal biopsy specimens taken for diagnostic purposes and in five patients using kidney tissue removed during transplantation. The 1-hydroxylase activity of 12 patients with asymptomatic proteinuria and/or hematuria (group A) measured 83.2 +/- 37.7 pg/mg tissue/20 min. Since these 12 patients did not show impaired mineral metabolism or pathological changes in the renal tubules, we have presumed that these results indicate normal activity in man. We also measured the 1-hydroxylase activity in four patients treated with prednisolone (group B). The 1-hydroxylase activity (81.1 +/- 27.1 pg/mg tissue/20 min) of group B did not differ from that of group A. However, the urinary excretion of calcium (ratio of calcium/creatinine) was increased (0.18 +/- 0.07 vs. 0.07 +/- 0.03, P less than 0.01) by prednisolone therapy. These data suggest that glucocorticoid-induced changes in urinary calcium excretion are not the result of a direct effect of glucocorticoid on renal 1-hydroxylase. In the three patients with mild renal insufficiency (group C), the 1-hydroxylase activity (75.4 +/- 22.4 pg/mg tissue/20 min) did not differ from that of group A. However, in five patients with severe renal insufficiency (group D), the 1-hydroxylase activity (8.5 +/- 3.7 pg/mg tissue/20 min) was significantly decreased (P less than 0.01).

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

Effects of the administration of phosphate on nuclear 1,25-dihydroxyvitamin D3 uptake by duodenal mucosal cells of Hyp mice.

Effects of the administration of phosphate on nuclear 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] uptake by duodenal mucosal cells of Hyp mice were investigated. In Hyp mice fed a high phosphate diet (1.1% Ca and 2.0% phosphate) for 2 weeks, maximal nuclear 1,25-(OH)2D3 binding by duodenal mucosal cells is significantly increased from 5.01 +/- 0.49 x 10(3) to 8.23 +/- 1.10 x 10(3) sites/cell (P less than 0.05). No significant change was observed in normal mice fed the same diet. The serum phosphate concentration of Hyp mice increased significantly (P less than 0.01), whereas no significant change was found in normal mice. On this regimen, serum calcium, urinary cAMP to creatinine ratio, and cytosolic 1,25-(OH)2D3 receptor number in Hyp mice were not changed significantly. On the basis of these data, we speculate that the recovery of serum phosphate in Hyp mice fed a high phosphate diet affects the recovery of nuclear 1,25-(OH)2D3 uptake by duodenal mucosal cells. The mechanism for this recovery is not related to either the secondary hyperparathyroidism or the change in cytosolic 1,25-(OH)2D3 receptor content but, rather, to increased binding of 1,25-(OH)2D3-receptor complex to nuclei. Hypophosphatemia, therefore, appears to play a role in the vitamin D resistance in Hyp mice.

Animals↗

Distribution and progression of coronary arterial and aortic lesions in the conventional Watanabe heritable hyperlipidemic rabbit--quantitative analysis.

The distribution and progression of coronary arterial and aortic lesions were examined in 40 conventional Watanabe heritable hyperlipidemic (WHHL) rabbits. They were classified according to age into stage I (3-5 months old, 14 rabbits), stage II (6-12 months old; 12 rabbits) and stage III (14-28 months old; 14 rabbits). Fifteen normal Japanese rabbits served as controls. The findings obtained from serial and transverse sections of each of the extramural coronary arteries (ECA) and transverse sections of 4 to 5 equal pieces of whole ventricle for intramural coronary arteries (ICA) were quantified by an image analyzer. Atherosclerosis with positive Sudan III stain was seen in aorta, ECA and ICA over 200 mu in diameter. Atherosclerotic lesions were noted in the aortic arch in stage I rabbits and in the whole aorta in stages II and III rabbits. In ECA, stenosis due to atherosclerosis was noted in 14, 33 and 93% of stages I, II and III rabbits, respectively. Stenosis of over 75% in the orifices of the left and right coronary arteries was noted frequently (71%), while mural thrombi, hemorrhage, intimal rupture and recanalization were seen rarely. Striking features were non-atherosclerotic stenosis with negative Sudan III, seen in the ICA less than 200 mu in diameter of almost all the hearts of stages II and III rabbits. Acute and old myocardial infarction appeared in 5 of the 14 hearts of the stage III rabbits and the infarct-related ECA showed severe stenosis of over 90%. In conclusion, to detect coronary atherosclerosis, serial and transverse sections of ECA are needed. In conventional WHHL rabbits, the incidence of stenosis in ECA is very high, compared with that of the previous reports, and myocardial infarction is due to severe stenosis in ECA. Non-atherosclerotic lesions in ICA occur before the appearance of the atherosclerotic lesions in ECA.

Animals↗

[Antitumor effect of UFT on human ovarian cancer grafted to nude mice and 5-FU concentration in tumor and normal tissues].

Antitumor effects of UFT, tegafur (FT-207), cisplatin (CDDP) and the combination of UFT with CDDP on a human ovarian cancer xenograft in nude mice and the concentration of 5-FU in the tumor tissue and major organs were studied. UFT (48.6mg/kg/day X 20) or tegafur (15.0mg/kg/day X 20) was daily administrated orally, and CDDP (5mg/kg/day X 3) was administrated intraperitoneally at an 7-day interval. The inhibition rates of the tumor growths were 49.6% with UFT, -2.3% with tegafur and 17.7% with CDDP, respectively. In the combination of UFT with CDDP, severe side effect were observed. The concentration of 5-FU in UFT-treated group was higher than tegafur group: about 2 times in the tumor, 5 times in the liver, 9 times in the kidney and 4 times in the spleen, respectively. In the combination of UFT with CDDP, the concentration of 5-FU in major organs, especially in the kidney, in nude mice that died at 10 day after drug administration were higher than in those of UFT. These findings indicate that UFT increases the intratumoral concentration of 5-FU to elicit better antitumor effect and also the concentration of 5-FU in various normal organs after long time administration.

Animals↗

[Preoperative intra-arterial infusion of adriamycin in advanced breast cancer with reference to estrogen receptor status].

Preoperative intra-arterial infusion of adriamycin [I I A] for advanced breast cancer was performed in 22 cases, and correlation of the estrogen receptor (ER) status with the effect of I I A therapy was histologically examined. Fifty-five percent of all cases responded to I I A; 80% of ER-negative cases responded, whereas only 33% of ER-positive cases did. I I A was significantly effective in ER-negative cases (p less than 0.05). The histological effect of I I A was also remarkable in ER-negative cases and was related to the clinical effect. The ER status was thought to be a parameter not only for hormonal therapy, but also for chemotherapy. Additionally, drill biopsy was performed in order to examine the correlation between the therapeutic effect and histological type in 16 cases before I I A therapy. Scirrhous carcinoma was more responsive to the I I A therapy than other histological types.

Adult↗

[Nuclear morphometry of cancer cells in stage III breast cancer with special reference to prognosis].

The nuclear area (NA) and nuclear form factor (NFF) (NFF = 4.pi.NA/P2. Na, nuclear area; P, perimeter) have been measured in fifteen stage III patients with an invasive ductal breast cancer, using an image analyzer (IBAS-2000, Zeiss). The NA has been revealed as being 41.8 +/- 8.82 micrograms2 (mean +/- S.D.) in five-year survivors (n = 8), and 59.4 +/- 12.9 micrograms2 in non-survivors (n = 7). The NFF was found to be 0.74 +/- 0.038 in those who survived, and 0.69 +/- 0.028 in non-survivors. The NA was significantly lager (p less than 0.01) and the NFF significantly lower (p less than 0.05) in the non-survivors than in the survivors. NA and NFF are considered to be helpful in determining the prognosis of breast cancer patients in stage III.

Breast Neoplasms↗

Inhibitory effects of long-chain alkyltrimethylammonium ions on aggregation of bovine platelets and the relation of their effects to Ca2+ mobilization.

The inhibitory effects of alkyltrimethylammonium ions on ADP- and thrombin-induced aggregation of bovine platelets were investigated. The ammonium cations inhibited the two aggregation reactions to similar extents. The relationship between their inhibitory effects on ADP-induced aggregation and their alkyl chain lengths from C8 to C18 was investigated. Results showed that the inhibitory effects of ammonium cations increased with increase of their alkyl chain lengths up to C16, and that the increase was linear with chain lengths of up to C14. This linear relation and slope of the linear regression line suggested that the inhibitory effects of the ammonium cations depended on their partitioning into the membrane. However, unlike long-chain unsaturated fatty acids, they did not affect the membrane fluidity of the platelets. Fluorescence analysis of fura-2 loaded platelets revealed that, in the concentration range where the alkyltrimethylammonium ions inhibited aggregation, they inhibited agonist-induced increase in cytosolic Ca2+ both in the presence and absence of extracellular Ca2+. These results suggest that inhibition of platelet aggregation by alkyltrimethylammonium ions is mainly due to their inhibition of increase in cytoplasmic Ca2+ by inhibition of both intracellular Ca2+ mobilization and Ca2+ uptake.

Adenosine Diphosphate↗

Calcium homeostasis in premature infants and treatment of early hypocalcaemia by 1,25-dihydroxycholecalciferol.

We studied calcium homeostasis and the serum calcium response to oral 1,25-dihydroxycholecalciferol [1,25 (OH)2D3] at a low pharmacological dosage of 0.1 microgram/kg daily in 14 early hypocalcaemic asymptomatic neonates. Seven hypocalcaemic neonates were not treated. In hypocalcaemic neonates serum PTH levels were normal, the urinary C-AMP response after PTH stimulation was poor and plasma 1,25 (OH)2D3 was low. Treatment with 1,25(OH)2D3 resulted in a rapid increase of serum calcium. The increase was more rapid in neonates treated with 1,25(OH)2D3 than in untreated subjects. A similar result was obtained in one of a pair of identical twins. These results suggest that a low dose of 1,25(OH)2D3 is effective in treating neonatal hypocalcaemia. However, the response was delayed for 48 h. The reason for this delay is not clear.

Calcitriol↗

Intranasal absorption of salmon calcitonin.

Eight normal subjects and 4 children with osteogenesis imperfecta were administered salmon calcitonin (S-CT) intranasally, and the pharmacokinetics of S-CT were studied. In the normal subjects, the plasma S-CT concentration showed a dose-dependent increase over a dosage range of 200-400 IU. Maximal plasma concentrations were reached 20-60 min after intranasal administration of S-CT. The plasma calcium concentration was significantly decreased 60 min after the administration. In the children, S-CT was also absorbed through the nasal mucosa. This suggests that nasal spraying may be an efficient method for administration of S-CT.

Administration, Intranasal↗

Modification of drug-induced tremor by systemic administration of kainic acid and quisqualic acid in mice.

The effects of excitatory amino acids, kainic acid and quisqualic acid, on the tremorine- and harmaline-induced tremor were quantitatively examined in mice using the power spectral analyzing method. The severity of the tremor was determined quantitatively in terms of the cumulative sum of the mean square value of the data. Kainic acid enhanced the tremor induced by tremorine but depressed the tremor induced by harmaline. Quisqualic acid depressed the tremor induced by both tremorine and harmaline in a dose-dependent manner. Kainic acid shifted the frequency of each component of the tremor induced by tremorine to the high frequency side, but quisqualic acid did not affect the frequency of tremor of the tremor induced by tremorine. The frequency of tremor of the tremor induced by harmaline was shifted by both excitatory amino acids to the low frequency side, and another component of tremor in the power spectral densities developed, of which the mean square values were very small. The present results suggest that, at least in part, the glutamatergic system can take a role on the modification of drug-induced tremor.

Animals↗