Biomedical subjects
Publications and source records attributed to M Ueki.
The structure of UK-1 isolated from the mycelium of Streptomyces sp. 517-02 was elucidated to be a novel benzoxazole dimmer derivative (1) on the basis of spectroscopic methods.
Intercellular adhesion molecule-1(ICAM-1), one of the adhesion molecules, plays an important role in target-cell lysis by immune cells. In this study we examined the expression of ICAM-1 in 15 cases of cervical cancer. We also examined ICAM-1 expression on cervical cancer cell lines in response to cytokines. Immunohistochemistry revealed expression (4 positive among 15 cases) of ICAM-1 in cervical cancer. Furthermore, the expression of ICAM-1 on cervical cancer was correlated with the degree of mononuclear cell infiltration, bearing CD3. On the other hand, the expression of ICAM-1 was not correlated with Class I or Class II antigens in cervical cancer. The expression of ICAM-1 on cervical cancer cell lines was augmented by in vitro treatment with interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha. These results suggest that the expression of ICAM-1 on cervical cancer might be modified by cytokines, and ICAM-1 expression on cervical cancer might augment the host immune reaction. So it will be possible to use cytokines in immunotherapy.
The effects of ulinastatin (UTI) on rat renal energy metabolism during ischemia and reperfusion were studied by 31P nuclear magnetic resonance spectroscopy (31P MRS) in vivo. Rat kidney was exposed to ischemia for 30 min by clamping the abdominal aorta above the renal arteries. Pre-ischemic administration of UTI inhibited the decline of intracellular pH (pHi) during ischemia and improved the recovery of renal energy metabolism and pHi after reperfusion. This result suggests that UTI might inhibit anaerobic metabolism during renal ischemia and an improve energy metabolism during reperfusion. 31P MRS provided a unique tool to study intact cellular function continuously in noninvasive fashion, allowing assessment of metabolic function during ischemia and after reperfusion.
Spinorphin, a potent inhibitor of enkephalin degrading enzyme isolated from the bovine spinal cord, produces a dose-related inhibition of electrically evoked contractions of both MVD (mouse vas deferens) and GPI (guinea-pig ileum). Analgesic activity of Spinorphin was evaluated by the tail pinch method. The intraventricularly injected Spinorphin produced antinociceptive effect in a dose-dependent manner, in dose of 50-200 micrograms.mouse-1. Most Spinorphin was degraded when incubated in the spinal cord for 24 hs. However, approximately 86% of the Spinorphin was intact on HPLC when incubated with probestin, which is an inhibitor of aminopeptidase-M. Spinorphin has a high inhibitory activity against enkephalin degrading enzymes when compared to the various hydrolysis products. In conclusion, the most important structure for enkephalin inhibitory activity in Spinorphin. It is suggested that Spinorphin acts as a neuromodulator of enkephalin metabolism in the spinal cord.
In this paper, we investigated how epidermal growth factor (EGF) acts on growth and regulation of extracellular matrix components and their degenerative enzymes in uterine cervical adenocarcinoma cells in vitro. Effects of EGF on cell growth, DNA synthesis, and laminin, collagen IV, and tissue plasminogen activator (t-PA) production of human uterine cervical adenocarcinoma cell line OMC-4 were examined, together with the characteristics of its EGF receptors. Scatchard plot of EGF binding to OMC-4 indicated two classes of binding sites with a dissociation constant of 170 pM and 510 pM. The total binding sites were 1.6 x 10(5)sites/cell. The number of OMC-4 cells did not increase in the presence of EGF, whereas 3H-thymidine incorporation was inhibited by EGF at concentrations of 1 and 10 nM. The production of laminin and collagen IV by OMC-4 cells was inhibited by EGF, whereas that of t-PA was significantly promoted at the physiological concentration of 0.1 nM. These results suggest that EGF is closely associated with regulation of proliferation and extracellular matrix degradation of uterine cervical adenocarcinoma cells.
Fibronectin (FN)-induced chemotactic migration of NIH-L13 fibroblasts was suppressed by the inhibitors of cysteine proteases, leupeptin (IC50 = 3 microM), and the epoxysuccinyl derivatives [E-64c (10 microM), SUT-8801 (45 microM), and SUT-8818 (28 microM)], but hardly by phenylmethanesulfonyl fluoride (> 1 mM) and 1-tosyl-amido-2-phenylmethyl chloromethyl ketone (> 1 mM). E-64d, a membrane-permeant derivative of E-64c, was much more effective (IC50 = 4 microM) than E-64c in preventing the cell migration. Furthermore, the FN-induced cell migration was blocked partially with EGTA and was reversed by addition of Ca2+ ion. These results suggest that intracellular Ca(2+)-dependent cysteine proteases may be involved in the FN-induced chemotactic migration of NIH-L13 fibroblasts.
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The levels of peripheral-blood, naturally occurring aliphatic polyamines, such as putrescine, spermidine, and spermine, from 21 bronchial asthmatic patients (11 atopics and 10 nonatopics) were measured by postcolumn derivatization high-performance liquid chromatography analysis. None of the patients, except the 44-year-old woman in the case report below, were given prednisolone, and they were instructed to take only regular medication during the tests. Blood was drawn from the patients in a fasting state, and the polyamine levels were compared between the times when they were free of asthmatic symptoms and when they had mild spontaneous attacks. Nine (5 atopics and 4 nonatopics), 6 (3 atopics and 3 nonatopics), and 4 (3 atopics and 1 nonatopic) out of 20 patients, when they had relatively mild asthmatic attacks, showed higher putrescine, spermidine, and spermine levels, respectively, than those of normal healthy control subjects. The levels of peripheral blood polyamines from a 44-year-old atopic bronchial asthmatic woman, who was admitted to the hospital with severe asthmatic attacks, were measured serially, and the putrescine and spermidine levels were found to be elevated during the asthmatic attacks, returning to normal levels in parallel with the clinical course. These data may suggest a role for naturally occurring aliphatic polyamines in bronchial asthma.
The effect of various anesthetics on the functional-metabolic coupling of cerebral cortex was studied in rats submitted to unilateral somatosensory stimulation. The regional cerebral metabolic rate of glucose (CMRglc) was measured autoradiographically using the 2-deoxyglucose method, and somatosensory activation was carried out by electrical stimulation of the left forepaw. In animals treated with 70% nitrous oxide, 0.5% halothane/70% nitrous oxide or 40 mg/kg pentobarbital, CMRglc of somatosensory cortex did not change despite generation of primary evoked cortical potentials. Anesthesia with 80 mg/kg alpha-chloralose, in contrast, led to a focal increase of CMRglc in the primary somatosensory cortex from 52.1 +/- 18.3 to 73.1 +/- 18.9 mumol/100 g/min (means +/- s.d.). Metabolic activation was strictly confined to the forelimb (FL) area of somatosensory cortex, and it exhibited a laminar pattern with maximal activation in layers I, II and IV. The preservation of functional-metabolic coupling under a surgical dose of chloralose renders this anesthetic particularly suited for the investigation of coupling processes under conditions where the experimental requirements preclude the use of unanaesthetized animals.
The mraR gene, which has a coding frame of 363 bp and lies close to and upstream of the ftsI gene of Escherichia coli, is involved in both cell division and cell lysis. It is thought to function in regulating the two distinct steps of the cell cycle, as two different one-base mutations in this unique gene caused different phenotypical changes in the cell. Comparison of nucleotide sequences of the mutant type mraR DNAs with the wild type suggested that filamentation of the cell was caused by a mutation in the putative start codon, whereas lysis of the cell was caused by a mutation which led to a change of one internal glutamate residue to lysine.
Contact Nd.YAG laser conization (laser cone) was performed in 500 patients with preoperatively diagnosed cervical intraepithelial neoplasia (CIN) since September 1983. The patients treated were followed for 12 to 96 months (39.2 months on average). Average operation time was 11.4 minutes. A cure with laser cone (single treatment) was achieved in 98.6%, including cases with microinvasive and invasive carcinoma, post-operatively. There were only 7 (1.4%) true residual cases of 47 cases (9.4% of total cases) with incomplete excision. High spontaneous cure rates (85.1%) in cases with incomplete excision are considered to be a characteristic of laser cone treatment. The contact laser cone method also got good specimens for histologic examinations. They gave a large amount of information for our follow-up. The results indicate that contact Nd.YAG laser conization for CIN is an excellent conservative therapy from the point of cure rate, safety, indication, operation time and cone specimen, even compared with CO2 laser conization.
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In this study, we investigated problems on the management of dysplasia on the basis of our clinical data obtained in the past ten years. In addition, we also examined the biological significance of protooncogene expression and human papilloma virus (HPV) infection in the initiation and promotion of dysplasia. Among 540 cases of dysplasia we have managed, 48.8% of the cases of mild, moderate and severe dysplasia which we followed up for more than 6 months regressed, and 24.1% of the cases progressed. The cure rate for laser therapy based on the follow up for 6 to 96 months was significantly high (97.9%) in 342 cases treated by the cone method, and low (89.5%) in 38 cases treated by the vaporization method. Preoperative histological findings confirmed 60.5% of postoperative findings, and several early cervical carcinomas were found in preoperative cases of dysplasia by laser conization. Among 28 cases (8.2%) of incomplete excision, 24 cases (85.7%) regressed spontaneously. On the other hand, the positive rate of immunostaining of epidermal growth factor receptor (EGF-R) and c-myc oncogene product (c-myc protein) increased from mild or moderate to severe dysplasia, and the positive rate for EGF-R was significantly high (80.0%) in the progressive group. The positive rate for HPV genome was quite low (16.0%) in dysplasia. Among them, EGF-R was most associated with the prognosis of dysplasia. These results suggest that laser conization should be performed for many cases of dysplasia because of the preoperative possibility of the existence of early cancer, and EGF-R is also useful in determining the necessity for therapy for dysplasia.
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The mechanism of the invasion and proliferation of endometrial cancer is closely related to interactions between the endometrial glands and stroma. In this study, we examined the biological role of sex steroids (estradiol; E2, progesterone; P) and growth factors (epidermal growth factor; EGF, transforming growth factor-beta; TGF-beta) on cell growth and laminin, collagen IV and tissue plasminogen activator (t-PA) production of normal endometrial cells and endometrial cancer cells in culture. Normal endometrial gland cells and stromal cells, and endometrial cancer cell lines (Ishikawa, OMC-2) were used. E2, P, EGF and TGF-beta were added to the culture in physiological concentrations. The growth of normal endometrial gland cells was promoted by E2 and EGF, whereas that of Ishikawa cells and OMC-2 cells was promoted by EGF. E2 enhanced the effects of EGF in normal endometrial gland cells. The growth of normal endometrial stromal cells was not affected by them. OMC-2 was inhibited by anti-EGF receptor antibody. On the other hand, the production of laminin and collagen IV of these cultured cells was inhibited by EGF and promoted by TGF-beta, whereas that of t-PA was promoted by EGF and inhibited by TGF-beta. These results suggest that the growth of normal endometrial gland cells with estrogen receptor (ER) is controlled by both E2 and EGF, whereas that of endometrial cancer cells is affected only by EGF, and those cells without ER depend particularly on the autocrine growth mechanism of EGF.(ABSTRACT TRUNCATED AT 250 WORDS)
We administered cisplatin and etoposide into the peritoneal cavity of 13 postoperative patients with gynecological malignancies, and studied the pharmacokinetics and toxicity in the combination of both drugs. Cisplatin 100 mg/body and etoposide 200 mg-400 mg/body were mixed together in 500 ml or 1,500 ml of normal saline and administered intraperitoneally on the day of operation and two or three weeks later. The peritoneal peak level of free cisplatin, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. However, there was no difference in the peritoneal and plasma AUC. The peritoneal level and AUC of etoposide, diluted with 500 ml, was about two times higher than that, diluted with 1,500 ml. Among the groups of 1,500 ml, peritoneal and plasma levels and AUC were almost proportional to the doses. Nausea and vomiting were experienced in all patients. With the increase of etoposide, more marrow suppression was observed. However, we encountered no other significant side effects. In conclusion, intraperitoneal administration of cisplatin and etoposide in this setting can be used safely with minimum side effects, and the dilution of 1,500 ml seems to be better.
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Quantification of disease severity was studied in 72 patients with ulcerative colitis, who had undergone total 85 clinical courses. We performed a multiple stepwise regression analysis, according to Truelove and Witts' classification, with disease severity as a dependent variable, and with 18 clinical, laboratory, and endoscopic parameters as independent variables. Results showed that disease severity in patients with ulcerative colitis is significantly influenced by five factors, namely, bloody stool, bowel movements, erythrocyte sedimentation rate (ESR), hemoglobin (Hb), and serum albumin. The activity index (AI) developed for ulcerative colitis is expressed as follows: AI = 60 x blood stool + 13 x bowel movements + 0.5 x ESR - 4 x HB - 15 x albumin + 200. Index values below 150, values between 150 and 220, and values above 220 nearly corresponded to mild, moderate, and severe disease, respectively, in Truelove and Witts' classification. We believe that the activity index is useful in evaluation of the effect of medical treatment in patients with ulcerative colitis. Its most important value will be in therapeutic trials.