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Biomedical subjects

K Kagawa

Publications and source records attributed to K Kagawa.

At least 163 records · Page 9Linked to original sources

[Feulgen-DNA cytofluorometry of the liver cell carcinomas].

Twenty-four autopsy cases of liver cell carcinomas were investigated by Feulgen-DNA cytofluorometry (NIKON SPM-RF 1-D) on paraffin-embedded tissue materials. The methods employed for tissue preparation and cytofluorometry were previously reported by us. The ploidy pattern based on cytofluorometry of the liver cell carcinomas exhibited wide DNA content distributions, in which many S phase cells having intermediate DNA content values ranging from diploid level to various, higher ploidy levels were included. From the comparative studies on both the histopathological findings and the ploidy pattern of the liver cell carcinomas, it was indicated that the peak value of the DNA content distribution was shifted from the diploid to the tetraploid level with the increasing appearance of the polyploid cells, and also that the degree of polyploidization appeared to correspond to the extent of the histological malignancy.

Adult↗

[Cell kinetics and nuclear ploidy pattern in relation to the growth of gastric cancers as analyzed by DNA-RNA cytofluorometry].

We investigated the cell kinetics and nuclear ploidy pattern of human gastric cancers (12 early and 30 advanced cancers) using DNA-RNA cytofluorometry (NIKON SPM-RF1-D) with AO stain. The results showed that the gastric cancers studied could be divided into two main groups on the basis of ploidy pattern determined both by DNA and RNA contents: group I without, and group II with polyploidization. Cells having nuclear DNA contents between 2 n and 4 n were regarded as representing those in the S phase, and it was found that both groups had similar proliferative activity. In group I, cell proliferation without polyploidization seemed to be maintained during tumor growth regardless of the extent of invasion, and the fraction of 2 n cells was 72-94%, compared to 93-99% in control cells from the non-neoplastic gastric epithelium. In group II, however, the extent of polyploidization appeared to be increased in association with both the tumor growth and its invasion into deeper tissues; thus the fraction of 2 n cells was low, ranging from 12 to 79%. Especially, the fraction of 2 n cells in cancers with aneuploid-polyploidization was further decreased to 6-25%. Based on these results, it is hypothesized that, in the early stages of gastric cancers, the cell population may be composed mostly of diploid cells, but with both further tumor development and its invasion, the neoplastic cells may gradually differentiate into two distinct cell populations.

Adult↗

Inhibition of pulmonary metastasis by Nocardia rubra cell wall skeleton, with special reference to macrophage activation.

The antimetastatic activity of Nocardia rubra cell wall skeleton (N-CWS) with or without cyclophosphamide was examined in an experimental model of pulmonary metastasis induced by Lewis lung carcinoma in C57BL/6 mice. Lewis lung carcinoma cells were implanted into the footpads of mice, and the implanted tumors were removed 9 to 10 days later. Pulmonary metastatic nodules began to develop a few days after the implanted tumor was removed. The inhibitory effect of N-CWS was evaluated from the number of pulmonary surface nodules about 3 weeks after tumor implantation. The antimetastatic activity of N-CWS depended upon the dose, time, and route of its injection. Injection of N-CWS i.v. after removal of the implanted tumor caused the greatest inhibition of development of pulmonary metastases. Therapy with N-CWS plus cyclophosphamide prolonged significantly the survival of mice with metastases. The cytotoxic activities of peritoneal macrophages and macrophages in the lung against Lewis lung carcinoma cells were enhanced in mice treated with N-CWS. Injection i.v. of peritoneal macrophages activated with N-CWS inhibited pulmonary metastases. The role of macrophages in inhibition of micrometastasis in the lung is discussed.

Animals↗

[DNA-RNA cytofluorometry for a primary cancer of the stomach and choledochus].

We standardized DNA-RNA cytofluorometry with AO stain using a NIKON SPM-RFI-D instrument for cell smears. We applied this technique in a 72-year-old woman with primary double cancer of the stomach and choledochus. We first suspected malignancy of the choledochus and examined the desquamated cells in the bile cytofluorometrically to obtain by X-Y plotting the irregularly increased polyploid cells with a high percentage of cells in S phase. These polyploid cells and S phase cells were found to have an increased RNA content. Before operation, the presence of another malignancy of the stomach was also ascertained. The surgical specimens were diagnosed histopathologically as well differentiated, tubular adenocarcinoma of the stomach and moderately differentiated, tubular adenocarcinoma of the choledochus. By cytofluorometric analysis similar results were obtained, i.e., polyploidization with increase of S phase cells. Based on these results, we concluded that our method is useful for the diagnosis of alimentary tract malignancy, and that the criteria of malignancy appear to be unusual polyploidization with increased fractions of S phase cells.

Adenocarcinoma↗

Isolation and characterization of nucleic-acid-like polymers containing glucose from Ehrlich ascites tumor cells.

1. Novel nucleic-acid-like polymers containing glucose, glucose 'nucleic acid', were isolated from cytoplasmic particles of Ehrlich ascites tumor cells. It is assumed that the basic structure of the polymers is similar to those of known nucleic acids except that their sugar constituents are glucose derivatives instead of ribose or deoxyribose. 2. When the glucose 'nucleic acid' was incubated with venom phosphodiesterase, four kinds of glucose 'nucleotides' containing bases of cytosine, adenine, guanine and thymine were obtained. 3. When the polymers were incubated with both venom phosphodiesterase and alkaline phosphatase, inorganic phosphates of glucose 'nucleotides' were removed and each nucleotide was converted to a glucose 'nucleoside'.

Animals↗

beta-Adrenoceptor alterations coupled with secretory response in rat parotid tissue.

Simultaneous studies on the secretory response of amylase and the neurotransmitter receptors of rat parotid gland, after brief treatment with agonists, showed selective alteration in beta-adrenoceptors with specific change in amylase secretion, suggesting a regulatory role of the receptors in the secretory response. The beta-adrenergic agonist (+/-)-isoprenaline (IPR) stimulated amylase secretion from rat parotid tissues much more than did the same concentration of an alpha-adrenergic or cholinergic agonist. The stimulatory effects of IPR were studied by pre-treating rat parotid tissues with IPR for 10 min and then incubating the tissue in fresh medium for 10 min. Pre-treatment with 10 microM-IPR for 10 min resulted in increased amylase secretion during further incubation with IPR and also in a lower EC50 value of amylase secretion for IPR. This treatment also resulted in selective changes in the number and affinity of beta-adrenoceptors, assessed by measuring binding of [3H]dihydroalprenolol (DHA): the maximal binding sites increased from 286/357 f-mole to mg protein and the IC50 value (the concentration for 50% inhibition of specific [3H]DHA binding) of beta-agonists, not antagonists, decreased significantly. An increase in the period of pre-treatment with IPR to 30 min resulted in a decrease in the maximal binding sites of beta-adrenoceptors and a decrease in amylase secretion during further incubation with IPR. Experiments with other agonists showed that supersensitivity of the secretory response was induced specifically by beta-agonists. Binding studies with [3H]WB-4101 and [3H]quinuclidinyl benzilate showed that alpha-adrenoceptors and muscarinic ACh receptors in rat parotid did not change under the conditions tested. The alteration in beta-adrenoceptors was parallel with a change in amylase secretion after IPR pre-treatment, but not with a change in cyclic AMP content.

Acetylcholine↗

Time course of biochemical and histological alterations following a single feeding of carbon tetrachloride to mice.

Carbon tetrachloride (0.02, 0.5 or 1.5 ml/kg) was given through a stomach tube to female C57BL/6J mice. Liver weights, the quantities of nine liver (protein, free glucose, glycogen, triglyceride, phospholipid, free and esterified cholesterol, DNA and RNA) and three blood components (glucose and free and esterified cholesterol), and SGOT activities were measured at 15, 24, 39, 48, 63, 87, 159 or 327 hr after carbon tetrachloride feeding. Livers were examined histologically. Chemical components of the liver and blood changed generally in a dose-related manner, but more slowly in the larger-dose groups. The biochemical alterations were reflected well in the histological findings. Degenerative and regenerative findings occurred later in the larger-dose animals. Histological changes appeared first in the midzones in the 0.5 and 1.5 ml/kg groups.

Animals↗

Characteristics of [3H]E-643-binding to alpha adrenoceptors.

Radiolabeled E-643, a newly developed antihypertensive compound, bound specifically to a preparation obtained from rat brain with a maximum of 85 f moles of binding sites per mg protein and a dissociation constant of 0.59 nM. Prazosin markedly inhibited the binding. While yohimbine and clonidine were only weak inhibitors. Other characteristics of the binding of [3H]E-643 to the brain and its specific binding to preparations of peripheral rat organs were also studied. The present findings suggest that [3H]E-643 is useful for labeling alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

Inhibitory action of the combination of aminopyrine and secobarbital on EEG activation, neocortical recruiting and augmenting responses in rabbits.

The effect of the combination of aminopyrine and secobarbital at a molar ratio of 2:1, the mixture and molecular compound, on rabbit EEG activation was examined. Secobarbital 40 mg/kg p.o. elevated threshold voltages in the neocortical and hippocampal EEG activation by high frequency electrical stimulation of the midbrain reticular formation (MRF), nucleus centralis medialis (CM) of the thalamus, and posterior hypothalamus (PHA) by 40, 40 and 80% respectively. Aminopyrine 80 mg/kg p.o. alone did not affect the arousal responses. The molecular compound 120 mg/kg p.o. has more potent and long-lasting actions in inhibiting the arousal responses induced by the stimulation of MRF (80%) and CM (50%) than with secobarbital alone. The inhibitory action of the mixture 120 mg/kg p.o. on the PHA-arousal response (40%) was significantly weaker than that of the molecular compound (80%). Secobarbital and the molecular compound slightly inhibited the neocortical augmenting and recruiting responses. Our findings suggest that although aminopyrine exerts a synergistic effect with secobarbital in inhibiting the EEG activation produced by MRF stimulation, in inhibiting the PHA-arousal response, there is no synergistic effect of the two drugs when they were given as the mixture. Moreover, the molecular compound rather than the mixture has a more potent inhibitory action on the EEG activation, particularly with PHA stimulation.

Aminopyrine↗