Transplantation of porcine fetal organs to discordant canine recipients.
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Biomedical subjects
Publications and source records attributed to T Satoh.
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Ninety-five specimens from patients with endometrial carcinoma (82 of endometrial type, 6 of adenoacanthoma, 4 of adenosquamous carcinoma, 3 of atypical endometrial hyperplasia) and 13 with ovarian endometrioid carcinoma were stained immunohistochemically with a rabbit polyclonal antibody prepared against the placental form of the enzyme glutathione S-transferase pi (GST-pi). Histological studies showed that the degree of staining decreased as the tumor lost its differentiation in endometrial carcinoma, but the degree of staining was independent of the differentiation in the case of ovarian endometrioid carcinoma. A comparison between the grade of staining of GST-pi in 82 cases of the endometrial type of endometrial carcinoma and 13 cases of ovarian endometrioid carcinoma revealed a stronger stain for the endometrial carcinoma than for ovarian endometrioid carcinoma (p < 0.01, Mann-Whitney's U test). Therefore, the GST-pi value for endometrial carcinoma was different from that for endometrioid carcinoma. In general, as compared with ovarian endometrioid carcinoma, endometrial carcinoma is considered to be resistant to chemotherapeutic agents. In conclusion, these results suggest that there is an apparent correlation between the GST-pi value and chemoresistance of the tumor.
The glutathione S-transferase (GST) pi has been studied in association with the mechanisms of multidrug resistance and as a marker for malignant tumors. In this study, specimens from 92 cases of cervical neoplasms and 10 cases of normal squamous epithelium adhering to myoma were stained immunohistochemically with a rabbit polyclonal antibody to GST-pi. In 6 cases of normal squamous epithelium, the intermediate layer was positively stained with the GST-pi antibody. In all 20 cases of dysplasia, the cells with koilocytotic atypia were stained positively. In all 10 cases of carcinoma in situ and all 16 cases of stage Ia squamous cell carcinoma, various intensities of GST-pi staining were demonstrated. Forty-six specimens of stage Ib or more squamous cell carcinoma were positive for GST-pi binding except only one case. In general, squamous cell carcinoma of the uterine cervix is resistant to chemotherapeutic agents. GST-pi is most frequently stained in cervical squamous cell carcinoma as compared with ovarian or endometrial carcinoma. In conclusion, these results suggest that GST-pi may be a marker for cervical squamous cell carcinoma.
We evaluated the incidence of synchronous or metachronous multiple primary cancer, hereditary or familial cancer, and the familial aggregation of cancer in 142 patients who were treated for endometrial cancer at Tsukuba University Hospital in the period 1977 to 1995. Synchronous multiple primary cancers were identified in 6 of the 142 patients (4.2%). Eleven patients (7.7%) had a history of extraendometrial cancer. Patients with endometrial cancer had a significantly high incidence of a history of breast cancer. Endometrial cancer was diagnosed in two patients who were screened before menopause. Four patients with endometrial cancer (2.8%) subsequently developed extraendometrial forms of cancer. One patient (0.7%) was considered to have a hereditary form of cancer, and 5 patients (3.5%) had familial forms of cancer. A total of 86 cases of cancer were found among 53 kindred (37.3%). More detailed studies are needed to elucidate the aggregation of cancers in the families of patients with endometrial cancer in Japan. Patients with a history of breast cancer should be screened for the presence of endometrial cancer.
A case of a 73-year-old woman with acute renal failure due to toxic shock syndrome (TSS) is reported. The patient was admitted to our hospital with the complaints of high fever, disturbance of consciousness and shock. Laboratory findings on admission were; CRP 25.11 mg/dl, WBC 35000/ microl, Plt 1.6 x 10(4)/ microl, GOT 155 U/l, GPT 65 U/l, CPK 4202 U/l (CPK-MM 96%), BUN 123 mg/dl and SCr 7.0 mg/dl. Because of anuria, hemodialysis was performed. This patient was treated with dopamine, methyl prednisolone (MP), frozen fresh plasma, AT III, antibiotics, and platelet transfusion. The bacterial cultures of blood and cerebrospinal fluid were negative, but MRSA was isolated subsequently from the pharynx and vagina. We investigated the production of toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxins (SE). The isolated MRSA produced TSST-1, SEB and SEC. Accordingly, we made the diagnosis of TSS. After improvement of acute renal failure and the patient's general condition, MRSA persisted and TSST-1 was still found in the patient's blood. Finally we eradicated the MRSA and TSST-1 after administration of ciprofloxacin hydrochloride (CPFX) and Rifampicin (RFP).
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We previously showed that a polymorphism for E6123 [(S)-(+)-6- (2-chlorophenyl)-3-cyclopropanecarbonyl-8,11-dimethyl-2,3,4,5- tetrahydro-8H-pyrido[4',3':4,5]thieno[3,2-f][1,2,4]triazolo[4,3-a] [1,4]diazepine] metabolism exists only in rhesus monkeys. In the present study, we purified, from rhesus monkey hepatic microsomes, three amido hydrolases that are involved in the metabolic polymorphism. Two forms of amido hydrolase from an extensive metabolizer and one from a poor metabolizer were purified by Q-Sepharose Fast Flow, Red A-agarose, octylamino-Sepharose 4B, and hydroxyapatite-Ultrogel chromatography, after solubilization with Lubrol. The three purified enzymes had the same molecular mass (47 kDa), and their amino-terminal amino acid sequences were identical. The enzymes were different from various known carboxylesterases in terms of substrate specificity, molecular mass, and amino-terminal amino acid sequence. They resembled arylacetamide deacetylase from human hepatic microsomes with respect to molecular mass and amino-terminal amino acid sequence. The KM values of the high and low affinity enzymes in the extensive metabolizer and the sole enzyme in the poor metabolizer were 37.6, 73.0, and 76.5 microM, respectively. The Vmax values were 3312.4, 504.8, and 427.9 pmol/min/mg of protein, respectively. The high affinity enzyme in extensive metabolizer appears to be quite distinct, whereas the low affinity enzyme in extensive metabolizer in similar or identical to the sole enzyme in poor metabolizer. Thus, the metabolic polymorphism in rhesus monkey may depend upon the existence of the high affinity enzyme in extensive metabolizer.
A case of congenital penile curvature is reported. A 21-year-old man was admitted because of penile pain curvature to the left at the erection and the difficulty of intercourse. He had no signs of Peyronie's disease and no history of penile fracture so that he was considered to have congenital penile curvature. By Nesbit's method the curvature of the penis was appropriately corrected. There were no signs of recurrence at either 1 or 5 months after the operation.
A 43-year-old female with HELLP syndrome underwent an emergency caesarean section under general anesthesia. Anesthesia was induced by fentanyl and thiopental with oxygen inhalation. Bolus injection of nicardipine was used to treat hypertensive crisis during operation. Continuous intravenous infusion of prostaglandin E1 was started after delivery to normalize arterial blood pressure. After surgery, both the patient and her baby were discharged uneventfully. It is suggested that a suitable dosage of fentanyl is effective without causing serious side effects for neonate. Prostaglandin E1 may have cytoprotective action in vital organs, such as the liver and the kidney, and may stabilize the arterial blood pressure.
An 81-year-old man was scheduled for cervical lymph node biopsy. His laboratory data were within normal ranges. After induction of anesthesia with thiopental 175 mg and succinylcholine chloride (SCC) 40 mg, moderate masseter spasm was observed. Anesthesia was maintained with nitrous oxide, oxygen and sevoflurane. After the operation he had severe muscle pain and CK was elevated up to 81,400IU.l-1. The body temperature was not elevated above 37.2 degrees C during and after the operation. The skinned fiber examination, performed one month later, showed his calcium-induced-calcium-release (CICR) to be within normal ranges. We diagnosed him as rhabdomyolysis induced by coadministration of SCC and sevoflurane, especially SCC. We concluded that even in an elderly man, SCC should be administered cautiously.
The ultrastructure of the Harderian gland of the rabbit has been studied. The gland can be divided into two lobes (pink and white) by the naked eye. At the microscopic level, their epithelial cells differ morphologically, the vacuoles in the cells of the pink lobe being large, while those of the white lobe, small. In addition to the pink and white lobes, an intermediate area can be distinguished around the boundary between the two lobes on the basis of epithelial cell compositions. The acini on this area consist of two epithelial cell types, one is similar to that found in the white lobe, the second consists of the same cells as the pink lobe Myoepithelial cells are located between the secretory epithelium and its basal lamina. Mast cells, macrophages and plasma cells are found in the interstitial connective tissue of the Harderian gland.
Ishikawa cells, which derive from a well differentiated human endometrial adenocarcinoma, were cloned using the limiting dilution method in an attempt to preserve well differentiated cells. Eighteen clones were obtained. According to their morphologic characteristics, there were six well differentiated, seven moderately differentiated, three poorly differentiated and two adenosquamous carcinoma clones. All of them were transplantable into node mice. Fifteen of the 17 clones were positive for estrogen receptors and all of the clones examined were positive for progesterone receptors. There were no significant differences in terms of population doubling time, plating efficiency or saturation density among these clones. On the basis of these results, we concluded that Ishikawa cells are not as homogeneous morphologically as we thought, since cells with varying degrees of differentiation have already mingled with the parent cell line. It is verified that the adenosquamous cell carcinoma of the endometrium can arise from one stem cell. It would be impossible to revive the cultured cells after having undergone their changes to the original conditions. Therefore, to preserve the characteristics of an established cell line, the cells should be frozen at a very early stage. It is also important to avoid frequent passages when special characters of the cells are necessary for a given investigation.
Epidemiological features, risk factors and preventive methods of sudden death (SD) derived from studies the authors have performed since 1987 together with colleagues in Niigata University School of Medicine were reviewed. When SD was defined as death occurring within 24 hours of the onset of symptoms, the annual incidence was 145/100,000 for people aged 15 years and older in Niigata Prefecture. The incidence increased sharply along with the advance of age, while the proportion of SD to natural death due to circulatory diseases was higher in younger people. Though diseases of the circulatory system made up approximately 90 percent of all causes of death, SD due to ischemic heart disease was less frequent in Japan than in western countries. SD showed various patterns in seasonal and "within-a-day" occurrences according to sex, age and cause of death. The months of the highest SD occurrence differed by occupation and matched the busiest work periods. A decrease in sleeping hours and mental stress experienced during the preceding week were related to the occurrence of both sudden death and non-fatal acute myocardial infarction. People having structural circulatory diseases were shown to be predisposed to SD when stress occurred, because fatal arrhythmia is easily induced by the above factors in such people. Health examinations were shown to have preventive effects, though limited, against SD. Differences in the resuscitated rates in cases where a witness was present and where one was not indicates that educating people about correct resuscitation methods is important to minimizing SD.
To investigate the mechanism of serum deprivation-induced apoptosis in PC12 cells, we performed flow cytometry with the viable cell-specific fluorogen, fluorescein diacetate (FDA). Intact PC12 cells were positive when stained with FDA, and those cells were identical with the major population which possess larger forward and side scattered light. Apoptotic PC12 cells decreased the forward and side scatter light associated with the loss of FDA-positive cells. Nerve growth factor (NGF) and the bcl-2 protein protected the cells from serum deprivation-induced apoptosis. These data suggested that the process of apoptosis in PC12 cells can be analyzed with flow cytometry.
The neurofibromatosis type 1 (NF1) gene encodes a protein, neurofibromin, containing GTPase-activating protein-related domain (GRD) that stimulates intrinsic GTPase activity of Ras protein. By screening a randomly mutagenized NF1-GRD library in Saccharomyces cerevisiae, we isolated two NF1-GRD mutants (NF201 and NF204) with single amino acid substitutions, which suppress the heat shock-sensitive phenotype of the RAS2(G19V) mutant. The NF1-GRD mutants also suppress the oncogenic Ras-induced transformation of NIH 3T3 mouse fibroblasts (Nakafuku, M., Nagamine, M., Ohtoshi, A., Tanaka, K., Toh-e, A., and Kaziro, Y. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 6706-6710). In this paper, we investigated the molecular mechanism of inhibition of the transforming Ras-specific function by the NF1-GRD mutants in mammalian cells. In human embryonic kidney (HEK) 293 cells, the mutant NF1-GRDs attenuated the stimulation of mitogen-activated protein kinase by Ras(G12V), but not by platelet-derived growth factor. In cell-free systems, purified recombinant NF1-GRD mutants showed an inhibitory effect on the association of Ras.guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) with Raf at several times lower concentrations than the wild type. Furthermore, it was revealed that the binding affinity of the mutant NF1-GRDs toward Ras.GTP gamma S is approximately 5-10 times higher than the wild type. These results suggest that the mutant NF1-GRDs tightly bind to an oncogenic Ras in its GTP-bound active conformation and block the interaction between Ras and its effector, Raf.
It has been demonstrated that Ras is involved in interleukin 3 (IL-3)-stimulated signal transduction in various hematopoietic cultured cells (Satoh, T., Nakafuku, M., Miyajima, A., and Kaziro, Y. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 3314-3318; Duronio, V., Welham, M. J., Abraham, S., Dryden, P., and Schrader, J. W. (1992) Proc. Natl. Acad. Sci. U.S.A. 89, 1587-1591). However, it has not been fully understood which of IL-3-promoted cellular responses, i.e. proliferation, survival, and differentiation, requires Ras function. We employed a system of inducible expression of the dominant-negative (S17N) or dominant-active (G12V) mutant of Ras in BaF3 mouse pro-B cell line to analyze the role of Ras in IL-3-stimulated signal transduction. Induction of the dominant-negative Ras(S17N) effectively inhibited the IL-3-induced activation of c-Raf-1 and mitogen-activated protein kinase (MAPK). Furthermore, the activation of fos gene promoter following IL-3 stimulation was almost completely abolished when Ras(S17N) was induced. Under these conditions, Ras(S17N) exhibited no inhibitory effect on IL-3-dependent proliferation assessed by the increase of cell numbers and a mitochondrial enzyme activity. The results indicate that Ras-dependent pathways, including the Raf/MAPK/Fos pathway, are dispensable for IL-3-induced growth stimulation. When BaF3 cells were treated with a tyrosine kinase inhibitor, herbimycin A, IL-3-dependent proliferation of the cells was impaired, suggesting that tyrosine kinase-mediated pathways are critical for growth promotion. On the other hand, apoptotic cell death caused by deprivation of IL-3 was prevented by the induction of the activated mutant Ras(G12V), although the rate of cell number increase was markedly reduced. Thus, it is likely that Ras-independent pathways play important roles to facilitate the proliferation although they may not be essential for IL-3-stimulated antiapoptotic signal transduction.
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Serum is an essential requirement for the growth and long-term survival of human endothelial cells, even in the presence of such defined elements such as polypeptide growth factors and hormones. A polypeptide from fetal bovine serum was isolated and characterized on the basis of long-term survival of human endothelial cells in serum-free culture. The endothelial cell viability maintaining factor has been purified to homogeneity by a combination of polyethylene glycol precipitation, hydroxylapatite, gel permeation and reverse-phase high performance liquid chromatography. The final purified endothelial cell viability maintaining factor has a molecular weight of 65,000 (reduced) and has been identified as bovine apolipoprotein H by amino-terminal amino acid sequence analysis and Western blot analysis. Endothelial cell viability maintaining factor improved a long-term viability of human endothelial cells at maximal concentrations of 2.5-5 micrograms protein/ml in serum-free medium.