[Undifferentiated sarcoma of the liver--its histopathological peculiarities].
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Biomedical subjects
Publications and source records attributed to Y Hata.
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Chemosensitivity of liver cell carcinoma was studied by subrenal capsule assay. The method of assay was based on Bogden's one, but the antitumor activity was evaluated by tumor growth inhibition rate (TG-IR). The anticancer agent with more than 50% TG-IR was judged as positive in the chemosensitivity test. Of 3 human hepatoma cell lines transplanted in the subcutaneous space of nude mice, all of 3 were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 66.7%, 100%, 66.7%, 100% and 0%, respectively. Of 24 patients who provided fresh tumor specimens for the assay, 12 (50%) were evaluable. The positive rates of ADR, MMC, CDDP, 5-FU and CPA were 25%, 16.7%, 16.7%, 33.3% and 8.3%, respectively. Our study suggested that 5-FU, MMC and ADR were comparatively active against the hepatoma cell, CDDP was less active than these 3 agents, CPA was inactive. These results seem to justify the use of current anticancer agents against hepatic cell carcinoma and indicate the usefulness of SRC assay for selecting chemotherapeutic agents against liver cell carcinoma.
Cefbuperazone (CBPZ) at a dose of 2 g was administered postoperatively by intravenous drip infusion to 9 patients subjected to radical mastectomy and 10 others subjected to thyroidectomy then levels of CBPZ in postoperative exudates were measured and its prophylactic effect on postoperative infections was determined. 1. Serum CBPZ levels in the patients after cancer mastectomy and thyroidectomy on postoperative day 1 were similar to those in healthy adults. 2. Levels of CBPZ in the postoperative exudates in patients subjected to cancer mastectomy reached a mean peak value of 66.3 micrograms/ml (range: 26.0-99.6 micrograms/ml) in 0-3 hours after administration, and the mean CBPZ level at 6 hours after administration was 33.3 micrograms/ml (range: 19.1-54.1 micrograms/ml). 3. As compared to the cases of cancer mastectomy, levels of CBPZ in postoperative exudates in patients subjected to thyroidectomy varied considerably from a patient to another: a mean peak level of 76.4 micrograms/ml (range: 31.3-128 micrograms/ml) appeared in 0 to 6 hours after administration. 4. There was no correlation between CBPZ levels in the exudate and hemoglobin levels or hematocrit values. 5. Likely because of the CBPZ administration at 4 g/day for 2 to 6 days postoperatively to 19 patients, postoperative infection was absent and no side effect attributable to this drug occurred in any of the patients. Because levels of CBPZ in postoperative exudates in patients subjected to cancer mastectomy or thyroidectomy were greater than MICs for principal Gram-positive and Gram-negative bacteria, it is likely that this drug is a useful agent for prophylaxis against postoperative infections in patients undergoing cancer mastectomy or thyroidectomy.
The action of insulin-like growth factor II (IGF-II) on calcium influx was studied in BALB/c 3T3 cells. IGF-II did not affect calcium influx rate in either quiescent or platelet-derived growth factor-treated "competent" cells. In contrast, IGF-II induced an approximately 2-fold sustained increase in calcium influx rate in competent cells briefly primed with epidermal growth factor ("primed competent" cells). The IGF-II-stimulated calcium influx was dependent on extracellular calcium and was inhibited by lanthanum, cobalt, and tetramethlin but not by nitrendipine. The IGF-II-stimulated [3H]thymidine incorporation was also dependent on extracellular calcium and was inhibited by cobalt and tetramethlin. A pharmacological stimulation of calcium influx by BAYK8644 resulted in an increase in [3H]thymidine incorporation in primed competent cells but not in either quiescent or competent cells. Pretreatment of primed competent cells with pertussis toxin completely abolished subsequent action of IGF-II on both calcium influx and [3H]thymidine incorporation. Inhibitory actions of pertussis toxin correlated well with toxin-induced ADP-ribosylation of a 41-kDa protein. The binding of 125I-IGF-II to membrane fraction was inhibited by guanosine 5'-O-(thiotriphosphate), and this inhibition was reversed by pretreatment of the cell with pertussis toxin. These results suggest that IGF-II stimulates calcium influx in primed competent BALB/c 3T3 cells by a mechanism involving G protein and that calcium influx may be a message of IGF-II action on cell proliferation.
CS-514 is a metabolic product of compactin and has a potent cholesterol-lowering effect in vitro and in animal studies by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase. The efficacy and adverse effects of the agent were studied in 41 hypercholesterolemic subjects by administering daily doses of 5, 20, or 40 mg for four weeks under double-blind conditions. Mean total serum cholesterol level was reduced by 11.1% in the 5-mg group, 18.8% in the 20-mg group, and 25.3% in the 40-mg group. Marked reduction of total serum cholesterol level was also observed in heterozygous familial hypercholesterolemics. Mean low-density lipoprotein cholesterol level and apolipoprotein B concentration decreased by 38.5% and 28.8%, respectively, in the 40-mg group, while high-density lipoprotein cholesterol level increased by 11.8%. No serious clinical and laboratory abnormalities were observed. Plasma cortisol and testosterone levels were not significantly affected. These results suggest that CS-514 will be a useful agent in the treatment of nonfamilial and heterozygous familial hypercholesterolemia.
Endogenous alpha-amylase inhibitor from wheat has been crystallized by a microdialysis method. There are two forms of monoclinic crystal in a microdialysis cell with a space group of P2(1). The unit cell dimensions are a = 43.5 A, b = 64.8 A, c = 32.2 A, beta = 113 degrees for the rod-like crystal, and a = 42.5 A, b = 65.2 A, c = 32.2 A, beta = 112 degrees for the plate-like crystal. The former is suitable for structure analysis because it gives the sharp diffraction beyond 2.0 A resolution, and the latter tends to form a twin crystal. A heavy-atom derivative has been successfully prepared with the heavy-atom reagent K2PtCl4, and structure analysis is in progress.
The xylan-degrading enzyme xylanase, from Bacillus pumilus IPO, has been crystallized. The crystals are monoclinic, space group P21 with a = 40.8 A, b = 66.8 A, c = 34.7 A and beta = 103.0 degrees. The asymmetric unit contains one molecule of Mr 22,500. The crystals diffract to at least 2.5 A resolution, and they are suitable for X-ray crystal structure analysis at high resolution.
To clarify the relationship of aziridine biotransformation to their cytotoxic activities, the metabolism of optical isomers of typical cytotoxic and non-cytotoxic aziridines was studied in isolated hepatocytes, rat liver microsomes, mitochondria and L-1210 mouse leukemia cells. Cytotoxic 1-methyl-2-beta-naphthylaziridine (NAZ) gave nitrosomethane as one of the bioactivation products in isolated hepatocytes and simultaneously induced a marked decrease in cellular ATP followed by cell lethality. NAZ itself did not directly affect the respiratory function of mitochondria in isolated hepatocytes or in buffer solution, however, it inhibited the mitochondrial activity in the presence of microsomes in the buffer solution. Nitroso-t-butane or nitrosomethane dimer, used as a substitute for extremely labile nitrosomethane, strongly inhibited the respiration of mitochondria. On the other hand, optical isomers of 2-aziridinecarboxylic acid (AZC) which did not give nitrosomethane in isolated hepatocytes or microsomes also did not show cytotoxicity. Thus, the cytotoxicity of NAZ seems to be induced by bioactivation via cellular oxidases with the nitrosomethane generated being a major toxic component. This may occur with most of the cytotoxic aziridine derivatives.
The authors investigated histologically the process of neocartilage formation in vascularized transplantation of rabbit ear perichondrium. The chondrocytes made their first appearance 4 days after transplantation, and the appositional growth of neocartilage lasted for about 3 weeks, although maximum growth occurred in the first 9 days after transplantation. The neoperichondrium of neocartilage was not observed until its gradual appearance at the end of this period of remarkable appositional growth. The time required for the neocartilage to become mature varied, and some cartilage was still not mature at 6 months after transplantation.
A case of unilateral athelia with a subcutaneous dermoid cyst in the area in question is reported. The histologic features of the cyst wall suggest that it is derived from a base in the nipple-areola complex. Dozens of cases of congenital absence of the breast have been reported, some of them associated with congenital anhidrotic ectodermal dysplasia, others with additional musculoskeletal abnormalities, and still others normal in other respects. But to our knowledge, the combination of athelia and corresponding subcutaneous dermoid cyst has not been reported.
1. Effects of microionophoretic application of acetylcholine (ACh) and its antagonists on neuronal responses to visual stimuli and to electrical stimulation of the lateral geniculate nucleus were studied in the cat striate cortex. 2. Responses elicited visually and electrically were facilitated by ACh in 74% of the cells tested, whereas the responses were suppressed in 16%. These ACh effects were blocked by a muscarinic antagonist, atropine, but not by a nicotinic antagonist, hexamethonium, indicating that the ACh effects are mediated through muscarinic receptors. A single application of atropine suppressed visual responses of cells facilitated by ACh, whereas it enhanced those of cells inhibited by ACh, suggesting that endogenous ACh may tonically modulate visual responsivity of cortical neurons. 3. In most cells with the facilitatory ACh effect, responses with single spikes to the electrical stimulation became more consistent, often with double spikes, during the ACh application. The suppressive effects of ACh were noted most often in cells with a longer response latency to electrical stimulation of lateral geniculate nucleus. 4. In most of the facilitated cells the spontaneous activity remained null or very low during ACh application, in spite of marked enhancement of visual responses, suggesting that ACh may improve the signal-to-noise ratio (S/N) of cortical neuron activity. To confirm this suggestion, we calculated a S/S + N index by counting the total number of spikes in the responses (S) and that in peristimulus time histogram (S + N) and found that it was improved during the ACh application in about a half of the cells, whereas it became worse in about one-fifth. 5. In most of the facilitated cells, ACh enhanced visual responses not only to optimal but also to nonoptimal stimuli, resulting in no improvement or even worsening of the orientation selectivity. This was also the case in the selectivity of direction of stimulus movement. 6. The laminar location of the facilitated cells was biased toward layers V and VI of the cortex, although they also made up the majority in layers II + III and about half the tested cells in layers IVab and IVc. 7. In the light of recent understanding of cortical circuitry, these results suggest that the cholinergic innervation to cortical neurons may play a role in improvement of the S/N ratio of information processing in the striate cortex and in facilitation of sending processed informations to other visual centers.
1. Unilateral lesions of the nucleus basalis magnocellularis (nBM), a source of cholinergic projection to the cerebral cortex, were produced by injection of kainic acid in the cat. The lesions caused a significant reduction in density of choline acetyltransferase-immunoreactive terminals in the visual cortex ipsilateral to the lesions. 2. In the primary visual cortex ipsilateral to the lesions [acetylcholine (ACh)-depleted cortex], about half of the cells had weak or undetectable visual responses, whereas in the contralateral visual cortex almost all the cells had normal responsivity. The response selectivity, such as orientation and direction selectivities, of cortical cells was not affected by the depletion of ACh. 3. The microionophoretic application of ACh to cells under observation facilitated visual responses in 83% of the cells recorded from the ACh-depleted cortex, whereas it suppressed the responses in only 9%. The application of a muscarinic antagonist, atropine, to cells in the ACh-depleted cortex was ineffective, suggesting no residual ACh activity. 4. The mean current required to induce facilitation in the cortex ipsilateral to the lesion was significantly smaller than that required in the contralateral cortex and the visual cortex of the normal cat, suggesting a supersensitivity of receptors mediating the effect or a reduction in catabolism of exogenous ACh in the ACh-depleted cortex. 5. More than half of the cells that had been unresponsive to visual stimuli became clearly responsive during the ACh application. The response magnitude of cortical cells, as a whole, increased to the same degree as that observed during the ACh application in the normal cat. 6. In addition to the decrease in the average response magnitude, there was a remarkable variability in responses of cells to motion of the slit from sweep to sweep in the ACh-depleted cortex. The application of ACh to cortical cells decreased the variability of responses and consequently made the responses much more consistent. 7. These results suggest that without ACh supplied from the nBM, most of the cortical neurons could not respond briskly and consistently to excitatory inputs and that exogenously applied ACh could reverse such an impairment of cortical neurons through intact or even supersensitive postsynaptic receptors.
A surgical approach to tumors of the septum is discussed. Two patients who had tumors in the posterior two thirds of the septum are shown in this paper. One had a benign mixed tumor and the other had an extramedullary plasmacytoma in the posterior two thirds of the septum. They underwent resection of the tumors with the septum by lateral rhinotomy. The first case additionally underwent an oval-shape resection of the palate. The postoperative profiles of the nose are good.
A case of a 19-year-old man with a right parasellar chondroma examined with computed tomography (CT) and nuclear magnetic resonance (NMR) scan is reported. The literature about CT and NMR scan findings of intracranial chondroma is reviewed. Typical CT findings are a round, high density mass with calcification, that is only slightly enhanced by contrast medium.
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