[Treatment of cerebral infarction in the acute stage with synthetic antithrombin MD-805: a multicenter clinical study].
Explore the source record for details and available documents.
Antithrombins↗
Biomedical subjects
H Tsuda
Publications and source records attributed to H Tsuda.
Correlative histochemical studies on preneoplastic and neoplastic lesions in the kidney of rats treated with nitrosamines.
Renal tubular lesions induced in male rats by two different carcinogens, N-nitrosomorpholine (NNM) and N-ethyl-N-hydroxyethylnitrosamine (EHEN), using a limited exposure "stop" protocol were investigated histochemically to demonstrate phenotypic cellular changes. The parameters measured included basophilia, glycogen content and the activity of the enzymes glucose-6-phosphatase (G6PASE), glycogen synthetase (SYN), glycogen phosphorylase (PHO), glucose-6-phosphate dehydrogenase (G6PDH), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), succinate dehydrogenase (SDH), alkaline phosphatase (ALP), acid phosphatase (ACP) and gamma-glutamyl transpeptidase (gamma-GT). The lesions observed were predominantly of either basophilic or oncocytic types. In each case, tubular lesions (altered tubules) appeared to give rise to epithelial tumors (epitheliomas) with the same cellular phenotype. Basophilic tubules and epitheliomas proved to be strongly positive for GAPDH and G6PDH while demonstrating a reduction or loss of G6PASE, ALP, ACP, gamma-GT, and SDH compared with controls and the surrounding proximal or distal tubules. In addition, large basophilic epitheliomas demonstrated an increase in both SYN and PHO activities. In contrast, most oncocytic tubules and oncocytomas characterized by abundant densely granular cytoplasm showed a reduction in the activity of G6PDH, but were intensely positive for SDH. However, a few oncocytic lesions demonstrated a decrease in both SDH and G6PDH activity. Rarely, decreased SDH and elevated G6PDH activities were observed in altered tubules resembling oncocytic tubules. It remains to be clarified whether these tubules represent a variation of the oncocytic lesions or, perhaps, another type of tubular lesion. The results indicate that basophilic and oncocytic epithelial tumors differ in their cytochemical pattern and histogenesis. In line with earlier suggestions, the basophilic tumors apparently originate from the proximal renal tubules, while the oncocytomas develop from the distal parts of the nephron. The basophilic tumors are characterized by an increased pentose phosphate pathway and glycolysis, with a corresponding reduction in mitochondrial respiration. However, the majority of the oncocytomas show an increased activity of the mitochondrial enzyme SDH, and a marked decrease in the activity of the key enzyme of the pentose phosphate pathway.
Animals↗
Histopathological classification of nephroblastomas in slaughtered swine.
A histological classification of 74 nephroblastomas found in slaughtered swine is reported. The tumours were classified into 4 main types; nephroblastic (29 cases); epithelial (38 cases); mesenchymal (one case), and miscellaneous (6 cases), on the basis of their histological characteristics and especially on their relative contents of epithelial and mesenchymal elements. The nephroblastic type was further divided into 3 subtypes: nephroblastic only (one case), nephroblastic predominance 13 cases) and nephroblastic equal to epithelial (15 cases). Similarly, the epithelial type was classified into two subtypes: epithelial only (one case) and epithelial predominance (37 cases). The histological features of these tumours were compared with those of human nephroblastoma. The classification of swine nephroblastomas made in this study closely resembles that of human tumours. Two examples of the nephroblastic type were metastasized but none of the other types.
Animals↗
Enhancement of cyclic adenosine monophosphate content in bone cells by the factor extracted from a pancreatic cancer associated with hypercalcemia.
A woman with exocrine pancreatic cancer presented a syndrome of humoral hypercalcemia of malignancy (HHM). Either urea extract or acid/ethanol extract of the tumor showed a dose-dependent activity to elevate cyclic adenosine monophosphate (AMP) level in rat bone cells in primary culture. When each population obtained by the sequential digestion of rat fetal calvaria was cultured individually and cyclic AMP responses to parathyroid hormone (PTH), calcitonin, and tumor extract were examined, tumor extract-sensitive cells showed a similar distribution to PTH-sensitive cells. Tumor extract and PTH, but not calcitonin, increased cyclic AMP in osteogenic cell line MC 3T3-E1. PTH receptor-mediated increase of cyclic AMP was indicated by an antagonistic action of PTH analogue, (3-34) hPTH, on increase of cyclic AMP in MC 3T3-E1 elicited by tumor extract. Human breast cancer derived cell line MCF-7 had calcitonin-sensitive adenylate cyclase, but neither PTH nor tumor extract increased cyclic AMP in the cells. On Bio-Gel P-60 column, the activity to stimulate bone cell cyclic AMP was eluted as a single peak at the molecular size between 6.5 K and 12.4 K. It was concluded that pancreatic cancer, although rather exceptional as a cause of HHM, produced a factor very similar to that reported in representative HHM tumors of human and animal models.
Animals↗
Aberrant regulation of carbohydrate metabolism and metamorphosis during renal carcinogenesis.
Systematic studies of the sequence of cellular changes during renal carcinogenesis induced in rats by stop experiments with N-nitrosomorpholine or streptozotocin and of human renal cell carcinomas led to the following main results and conclusions: All types of epithelial kidney tumors known from human pathology, namely clear-cell, acidophilic (granular), basophilic, chromophobic and oncocytic tumors, can be induced by the chemicals. Phenotypically altered epithelia resembling those in the tumors appear in single or multiple tubules long before unequivocal tumors develop. The progression from the preneoplastic tubular lesions to the tumors is an autogenous process which is independent of the further action of the carcinogen. At least three different types of tubular lesions can be distinguished: (a) Clear cell tubules storing glycogen in excess, (b) chromophobic or basophilic tubules frequently accumulating acid mucopolysaccharides (glycosaminoglycans, proteoglycans), and (c) oncocytic tubules accumulating atypical mitochondria. Whereas the precise site of origin of the clear cell tubules within the nephron remains unclear, the fine structural and cytochemical findings suggest that the chromophobic and basophilic tubules originate from the proximal and the oncocytic tubules from the distal nephron. Each type of tubular lesion is apparently the precursor of a cytologically specific tumor type. The well-known aberration in carbohydrate metabolism in renal tumors might occur in response to a carcinogen-induced metabolic derangement which is frequently associated with excessive storage of polysaccharides or lipids persisting for weeks and months until fast-growing tumors appear. Whereas the primary biochemical lesion leading to the persisting storage phenomena is most probably fixed at the genetic level, epigenetic changes, namely an adaptation of cellular enzymes gradually activating alternative metabolic pathways, might be responsible for the ultimate neoplastic transformation of the cell.
Adenoma↗
Spontaneous production of eosinophil chemotactic factors by T lymphocytes from patients with subcutaneous angioblastic lymphoid hyperplasia with eosinophilia.
Subcutaneous angioblastic lymphoid hyperplasia with eosinophilia (SALH) was reviewed with respect to eosinophil chemotaxis. Lymphoid cells separated from the granuloma spontaneously released at least two different eosinophil chemotactic factors (ECF): low-molecular-weight and high-molecular-weight ECF according to the profile on gel filtration (LMW-ECF, about 500; HMW-ECF, 45,000 to 70,000). The cells, however, failed to produce chemotactic activity for macrophages and neutrophils. By analysis with monoclonal antibodies against lymphocyte subpopulations, the granuloma T cells, probably OKT4-positive cells, were shown to be responsible for spontaneous production of these two ECF. Furthermore, the blood mononuclear leukocytes were separated from the patients with SALH. An ECF closely resembling HMW-ECF was also spontaneously produced by the blood OKT4-positive T lymphocytes, whereas no LMW-ECF was released. Mononuclear leukocytes from healthy donors, however, could produce an ECF resembling HMW-ECF and chemotactic activities for macrophages and neutrophils by stimulation with concanavalin A (Con A). Protein synthesis appeared to be essential for spontaneous ECF and for Con A-induced ECF production. These results suggest that the granuloma OKT4-positive T lymphocytes of the patients with SALH are in activated condition to release LMW- and HMW-ECF, whereas the blood OKT4-positive T lymphocytes are in activated condition to release only HMW-ECF. Such spontaneous and prolonged production of HMW-ECF by the cells can be one of the diagnostic means of SALH.
Angiolymphoid Hyperplasia with Eosinophilia↗
Effect of timing of partial hepatectomy on the induction of preneoplastic liver foci in rats given hepatocarcinogens.
Beginning 2 weeks after an intraperitoneal injection of diethylnitrosamine (DEN), rats were fed diet containing either 2-acetylaminofluorene (2-AAF), 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB), alpha-isomer of 1,2,3,4,5,6-hexachlorocyclohexane (alpha-HCH), or phenobarbital (PB) for 6 weeks and subjected to partial hepatectomy (PH) after various periods of chemical administration. The effect of timing of PH was most apparent in rats fed 2-AAF. The size of gamma-glutamyl transpeptidase positive foci was largest when PH was performed 1-3 weeks after the start of chemical feeding. Similar tendency was slightly observed with 3'-Me-DAB or alpha-HCH administration, but not with PB or basal diet feeding. Thus, the enhancing effect of PH on the induction of the preneoplastic liver foci was affected by the type of chemical and the timing of the operation.
2-Acetylaminofluorene↗
The influence of subsequent dehydroepiandrosterone, diaminopropane, phenobarbital, butylated hydroxyanisole and butylated hydroxytoluene treatment on the development of preneoplastic and neoplastic lesions in the rat initiated with di-hydroxy-di-n-propyl nitrosamine.
The comparative modifying potential of dehydroepiandrosterone (DHEA), diaminopropane (DAP), phenobarbital (PB), butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) on the development of lesions initiated by dihydroxy-di-n-propyl nitrosamine (DHPN) in F344 rats were investigated. DHEA, BHA and BHT were all associated with significant reduction in numbers of glutathione-S-transferase P form (GST-P) positive foci in the liver whereas PB brought about their enhanced development. BHT and PB exerted promoting activity on the incidence of thyroid adenomas while DAP similarly increased lung adenoma formation. The results illustrate the advantages to be gained from two stage experiments using broad spectrum carcinogen initiation for comparative analysis of 'modifiers' of the neoplastic process and suggest that studies of enzyme alteration within putative preneoplastic lesions may be directly relevant to elucidation of mechanisms underlying such modification.
Animals↗
Modification potentials of ethyl alcohol and acetaldehyde on development of preneoplastic glutathione S-transferase P-form-positive liver cell foci initiated by diethylnitrosamine in the rat.
The modification potentials of ethyl alcohol (EA) and acetaldehyde (AA) on development of immunohistochemical glutathione S-transferase (placental type)-positive (GST-P+) liver cell foci were examined in an in vivo short-term assay system. Rats were given a single intraperitoneal injection of diethylnitrosamine (DEN) and then various concentrations of EA (20, 10, 5%) or AA (5, 2.5%) in their drinking water from week 2 till termination in week 6. All rats were subjected to two-thirds partial hepatectomy in week 3. Animals given EA (20% and 10%) or AA showed significant decrease in liver and body weight. However, only EA caused significant dose-related inhibition of development of areas of foci (mm2/cm2), but AA had no effect on their development.
Acetaldehyde↗
Colony stimulating factor-induced differentiation of murine M1 myeloid leukemia cells is permissive in early G1 phase.
Granulocyte-colony stimulating factor (G-CSF) induces differentiation of M1 murine myeloid leukemia cells into mature granulocytes/macrophages and also causes accumulation of the cells in the G1 phase of the cell cycle. We examined, therefore, whether synchronization of M1 cells in the G1 phase could affect G-CSF-induced differentiation as quantitated by expression of Fc fragment receptors (FcR) and lysozyme activity. Cells were arrested in early G1 by density inhibition in the absence of serum and in late G1 by addition of aphidicolin. Cells synchronized in early G1, when stimulated with G-CSF, showed enhanced expression of FcR and lysozyme activity. Eighty percent of the cells expressed FcR 18 hr after addition of G-CSF while, in exponentially growing cells, this percentage was reached 72 hr after addition of G-CSF. Cells synchronized in late G1 did not show enhanced expression of differentiation markers. These results imply that with respect to G-CSF-induced differentiation, the G1 phase can be separated into an early permissive and a later nonpermissive stage.
Animals↗
Elimination of metabolic cooperation by glycyrrhetinic acid, an anti-tumor promoter, in cultured Chinese hamster cells.
The effect of glycyrrhetinic acid (GA) on the metabolic cooperation between 6-thioguanine-resistant (6TGR) and sensitive (6TGS) Chinese hamster V79 H3 cells, was investigated. Because GA has been reported to inhibit strongly tumor formation in mouse skin induced by 7,12-dimethylbenz[a]anthracene (DMBA) plus teleocidin or DMBA plus 12-O-tetradecanoylphorbol-13-acetate (TPA), we expected that GA might restore the metabolic cooperation inhibited by TPA. The results were contrary to our expectations. GA (20-50 microM) acted cumulatively with TPA to inhibit metabolic cooperation even more, and GA (20-75 microM), by itself, was found to be a strong inhibitor of metabolic cooperation. GA was not mutagenic at the concentrations examined (0-100 microM).
Animals↗
Modifying influence of dehydroepiandrosterone on the development of dihydroxy-di-n-propylnitrosamine-initiated lesions in the thyroid, lung and liver of F344 rats.
Following initial treatment of F344 rats with dihydroxy-di-n-propylnitrosamine, exposure to dehydroepiandrosterone (DHEA) administered in the diet at a concentration of 0.6% brought about significant decrease in weight gain, independent of food consumption, and inhibited the development of thyroid tumors and hepatocyte-altered enzyme foci. In addition to inducing a diffuse increase in glucose-6-phosphatase dehydrogenase (G6PD) and gammaglutamyl transpeptidase in the liver. DHEA treatment was associated with development of small numbers of basophilic hepatocellular foci which differed markedly in enzyme phenotype from the clear cell (glycogen storing) lesions predominating in the carcinogen-treated animals maintained on basal diet. The results are consistent with the concept that DHEA-modification of neoplastic development, as reported earlier in a number of different organs and here in the liver and thyroid, may be in some way partly mediated by changed expression of the key enzyme of the pentose phosphate pathway, G6PD, and related metabolic systems. Heterogeneity in the quality of initiated hepatocytes with regard to capacity for inhibition or promotion indicated by the present data point to the existence of more than one pathway to tumour development in the rat liver.
Animals↗
Dehydrogenase histochemistry of N-ethyl-N-hydroxyethylnitrosamine-induced focal liver lesions in the rat--increase in NADPH-generating capacity.
Histochemical investigation of altered dehydrogenase enzyme activity in putative pre-neoplastic lesions induced by N-ethyl-N-hydroxyethylnitrosamine in the rat liver revealed a clear increase in NADPH-generating potential, most markedly within nodules. Glucose-6-phosphate dehydrogenase, malic enzyme and isocitrate dehydrogenase all showed elevated activity while the activities of succinate dehydrogenase and beta-hydroxybutyrate dehydrogenase were reduced. Alteration in enzyme activity suggested an adaptive shift in metabolism, the increase in levels of enzymes responsible for generation of reduced NADP possibly conferring enhanced drug detoxifying or cholesterogenic potential.
Animals↗
Adenoid squamous cell carcinoma of the skin overlying the right breast. An autopsy case clinically manifested with rapid growth and widely spreading metastases.
An autopsy case of a 62-year-old woman with a poorly differentiated, aggressive form of adenoid squamous cell carcinoma arising in the skin overlying the right breast was studied. The tumor, 9 X 8 cm in diameter, had rapidly enlarged since one year before admission from a verrucous lesion of 20 years duration. The histologic features of the tumor showed a well-differentiated squamous cell carcinoma mainly in the superficial areas, which transformed into, with a zone of transition in between, an alveolar or adenoid structure in the deep invading portion. The adenoid tumor cells exhibited an undifferentiated appearance with prominent nucleoli and frequent mitotic figures. These cells partly showed dyskeratotic or acantholytic features. Mucin was negative. The patient died at 8 months after the operation. Autopsy revealed widely spreading metastases in which an adenoid structure was outstanding. These unusual pathological features and an aggressive behavior of this tumor, which were hitherto rarely described for adenoid squamous cell carcinoma, seemed to be a poorly differentiated variant of the tumor. This malignant transformation might be derived from loss of cohesion of the pre-existing usual well-differentiated squamous cell carcinoma in the basal and parabasal layers, inparting marked invasiveness of these cells into the supporting connective tissue.
Aged↗
Modifying effects of antioxidants on chemical carcinogenesis.
Studies were made on the carcinogenic activity of butylated hydroxyanisole (BHA) in rats, mice, and hamsters and the effect of the antioxidants BHA, butylated hydroxytoluene (BHT), ethoxyquin (EQ), sodium L-ascorbate (SA), ascorbic acid (AA), sodium erythorbate (SE), propyl gallate (PG), and alpha-tocopherol, on two-stage chemical carcinogenesis in rats initiated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 1,2-dimethylhydrazine (DMH), diethylnitrosamine (DEN), 7,12-dimethylbenz(a)anthracene (DMBA), N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), N-ethyl-N-hydroxyethylnitrosamine (EHEN), or N-methylnitrosourea (MNU). BHA clearly induced squamous cell carcinomas in both the rat and hamster forestomach. The tumorigenic action of crude BHA on the forestomach is largely due to 3-tert-BHA. In two-stage chemical carcinogenesis, BHA promoted MNNG or MNU-initiated forestomach and BBN- or MNU-initiated urinary bladder carcinogenesis and inhibited DEN- or EHEN-initiated liver and DMBA-initiated mammary carcinogenesis. BHT demonstrated promotion potential for urinary bladder and MNU-initiated thyroid carcinogenesis and inhibited DMBA-initiated ear duct carcinogenesis. EQ promoted EHEN-initiated kidney carcinogenesis and inhibited DMBA-initiated mammary and EHEN-initiated liver carcinogenesis. SA promoted forestomach and urinary bladder carcinogenesis and SE likewise enhanced urinary bladder carcinogenesis. alpha-Tocopherol inhibited ear duct carcinogenesis. No effects of any of the antioxidants on glandular stomach carcinogenesis were found. The results clearly demonstrated that antioxidants have different effects (promoting or inhibitory influences) depending on the organ studied and suggest the importance of a whole body approach to their investigation.
Animals↗
T3 surface molecules on adult T cell leukemia cells are modulated in vivo.
Cells from eight patients with adult T cell leukemia (ATL) and from four patients with non-ATL were examined to see if the T3 antigen of these cells could be modulated in vitro. We found a low density of T3 antigen and the presence of Tac antigen on cells from all patients with ATL. The density of T3 antigen on non-ATL cells was normal, and Tac antigen was not detected. Modulation of T3 antigen and an increase in Tac antigen-positive cells occurred when cells from patients with T4 non-ATL were cultured with OKT3 monoclonal antibody (mAb). Those changes in T3 antigen density and the appearance of Tac antigen-bearing cells by OKT3 mAb were not so marked when ATL cells were used. But the modulation of T3 antigen and the increase in Tac antigen-bearing cells by OKT3 mAb were closely related in cells from six ATL patients. These findings suggest that T3 T cell antigen receptor complexes on ATL cells are not functionally "frozen" by leukemic changes and might be modulated in vivo. In addition, modulation of T3 surface antigen on ATL cells was not induced by cultivation with human T cell leukemia virus type I particles and envelope proteins obtained by gene technology.
Acute Disease↗
Inhibitory effects of ethoxyquin, 4,4'-diaminodiphenylmethane and acetaminophen on rat hepatocarcinogenesis.
Four antioxidant species, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), ethoxyquin and alpha-tocopherol, and three other compounds, 4,4'-diaminodiphenylmethane (DDPM), acetaminophen and glutathione, were tested for inhibitory effect on hepatocarcinogenesis in male F344 rats. Rats were initially given a single ip injection of diethylnitrosamine (200 mg/kg body weight) and fed basal diet containing 0.02% 2-acetylaminofluorene from week 2 to week 8. Animals were subjected to partial hepatectomy at the end of week 3. From week 12 to week 36, they were given basal diet containing 2% BHA, 1% BHT, 0.8% ethoxyquin, 1% alpha-tocopherol, 0.1% DDPM, 1% acetaminophen, or 1% glutathione, then killed at week 40, 4 weeks after cessation of treatment with the test chemicals. The incidence of hepatocellular carcinoma (HCC) was significantly decreased in the groups given ethoxyquin or DDPM. Quantitative analysis of the number and area of HCC per unit liver area revealed a significant decrease in the area of HCC in the groups given ethoxyquin, DDPM or acetaminophen. The results suggest that ethoxyquin, DDPM and acetaminophen exerted an inhibitory effect on the development of HCC, while BHA, BHT, alpha-tocopherol and glutathione had no significant effect.
2-Acetylaminofluorene↗
[Cardiac angiosarcoma with gastrointestinal bleeding, hypoxemia, thrombocytopenia and microangiopathic hemolytic anemia].
This report describes cardiac angiosarcoma in a 62-year-old man. The patient presented with metastatic pulmonary and extradural spinal cord tumors of unknown origin. During the course, he developed hypoxemia, gastrointestinal bleeding, thrombocytopenia, and microangiopathic hemolytic anemia. Anticancer therapy could not be initiated because of his poor general condition, and he died. Autopsy revealed angiosarcoma in the right atrium. Metastases were found in the lungs, liver, adrenals, gingiva and vertebrae. The various hematologic abnormalities were probably the result of aberrant hemodynamics caused by the presence of a large amount of neoplastic vascular tissue.
Anemia, Hemolytic↗