Biomedical subjects
Publications and source records attributed to M Miyahara.
Highly stereoselective synthesis of (2'R)-[2'-2H]-2'-deoxyribonucleosides (2'R:2'S = > 99:1) were accomplished by treating 2'-bromo-3',5'-O-TPDS-2'-deoxyribonucleosides with tributyltin deuteride at lower temperatures such as -60 degrees C in the presence of triethylborane. Moreover, synthesis of some oligodeoxyribonucleosides involving them will be described.
Although it is well known that diabetics have high mortality rates due to ischemic heart disease (IHD), controversies still exist about the severity of coronary artery disease in diabetics compared to nondiabetics. We compared coronary arteriographies of 50 diabetics with IHD to those of 50 nondiabetics with IHD. In regard to coronary risk factors, incidence of obesity was significantly higher in diabetics. Incidence of hypertension, hypercholesteremia, hyperuricemia was higher, although not significant, in diabetics. Incidence of smoking was significantly higher in nondiabetics. The diabetic group showed a significantly higher incidence of patients with more than two or three diseased vessels, and a significantly higher number of diseased coronaries with more than 50% stenosis per patient compared to nondiabetics (5.6 +/- 3.7 vs 3.7 +/- 3.2). The distribution of diseased coronaries with more than 75% stenosis showed no difference between diabetics and nondiabetics. The incidence of coronary spasm was significantly lower in diabetics (12% vs 28%). The high incidence of multiple vessel disease in diabetics was thought to be due to other complicated coronary risk factors, especially hypertension and hypercholesteremia.
Severe septic complications account for the high mortality of patients with esophageal cancer. We examined the levels of immunoglobulins and complements together with infection-related complications in a large number of patients. Enhancements of IgG, IgA, C3, C4, and CH50 were evident in patients with esophageal cancer and were more predominant compared to findings in cases of gastric cancer. Average levels of IgG and IgA immediately before surgery were significantly higher in esophageal cancer patients with postoperative septic complications than in those without such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of immunoglobulins and complements. It would thus appear that the enhancement of IgG and IgA is associated with the occurrence of infectious complications following surgery for patients with esophageal cancer.
Correlations between defective cell-mediated immunity (CMI) and infections following surgery for esophageal cancer were evaluated. Peripheral lymphocytes, T cells, B cells, PHA transformation, and PPD skin test were measured in 81 patients with esophageal cancer, 58 with gastric cancer, and 50 healthy controls. The depression of CMI was predominant to a similar extent in patients with esophageal cancer and in those with gastric cancer. The average level of PHA transformation immediately before surgery was significantly lower in the esophageal cancer patients with fatal septic complications than in those without such problems. Although preoperative radiation therapy markedly depressed the levels of the four parameters, this association was also noted in 28 patients not given radiation. It thus appears that PHA transformation may be valuable in the prediction of fatal septic complications after major surgery in patients with esophageal cancer.
The expression of ras oncogene product p21 was examined in 45 paraffin-embedded sections of primary advanced colorectal cancers, using the anti-v-H-ras p21 monoclonal antibody Y13-259. Fourteen of these specimens (31 percent) were stained positively. The incidence of lymphatic vessel invasion of cancer cells and lymph node metastasis correlated statistically with the overexpression of ras p21. The depth of invasion and incidence of liver metastasis in the p21-positive group were more prominent than in the p21-negative group. Statistically significant differences were evident in operative curability and clinical stage at initial surgery and in the long-term survival rate between these groups (P less than 0.05). We propose that ras p21 overexpression may serve as a marker to predict the prognosis of colorectal cancer.
Lymphoscintigraphy (LS) and computed tomography (CT) were used preoperatively to assess nodal involvement in 23 patients with esophageal cancer. LS predicted nodal involvement with a high sensitivity and low specificity since false positives were frequent while in contrast, CT predicted it with high specificity and low sensitivity. The combination of LS and CT improved sensitivity by up to 87 per cent but not specificity. The positive image of nodes in LS was associated with malignant cell involvement and/or reactive changes in the nodes, especially sinus histiocytosis and germinal center hyperplasia. When cervical nodes were involved, bilateral images of lymph flows were often lost and by using the images of lymph flow as well as those of the nodes, the combination predicted cervical nodal involvement with a sensitivity of 83 per cent and a specificity of 86 per cent. Thus, the combination of LS and CT is beneficial for preoperatively estimating cervical nodal involvement in esophageal cancer.
Based on the findings that the enhancement of serum alpha 2-macroglobulin (A2M) is associated with the occurrence of infectious complications following surgery in patients with esophageal cancer, we examined possible factors which could contribute to the alterations of serum acute phase protein levels in patients with this disease. A multiple linear regression analysis was made for 71 patients with esophageal cancer and 58 with gastric cancer. In patients with esophageal cancer, protein calorie malnutrition (PCM) and age factors more strongly contributed to the alteration of 6 acute phase protein levels than did the malignant tumor when compared to those with gastric acner. PCM was negatively associated with A2M levels while it was positively associated with alpha 1-acidglycoprotein (A1AG) and haptoglobin (Hp) levels. Age did not contribute to the A2M levels but did have a negative effect on the Hp, ceruloplasmin (Cp) and fibronectin (Fn) levels. On the other hand, the malignant tumor was positively related only to the A1AG levels. Since none of these factors contributed to the elevation of A2M levels, it is suggested that the presence of chronic infection might be a factor contributing to the A2M increase which was associated with the occurrence of postoperative infectious complications in patients with this disease.
Severe septic complications are the major cause of operative mortality in patients with esophageal cancer. We examined the levels of acute phase proteins together with infection-related complications after surgery in a large number of patients with esophageal cancer and compared them with a group of patients with gastric cancer and healthy controls. Elevations in alpha 1-antitrypsin, alpha 1-acidglycoprotein, haptoglobin and ceruloplasmin were evident in patients with esophageal cancer, being more predominant when compared to the findings in patients with gastric cancer. Although the mean levels of alpha 2-macroglobulin were not significantly elevated in either patients with esophageal cancer or those with gastric cancer, the average level immediately prior to surgery was higher in esophageal cancer patients with postoperative septic complications than in those without any such problems. Preoperative radiation therapy and total parenteral nutrition did not significantly alter the levels of acute phase proteins. It would thus appear that the elevation in alpha 2-macroglobulin is associated with the occurrence of infectious complications following surgery in patients with esophageal cancer.
Prolonged storage of red blood cells in a liquid state was achieved by replacing the preservative using a sextuple-bag system. The bag system consists of one primary bag containing citrate-phosphate-dextrose (CPD) solution, three satellite bags containing saline-adenine-glucose-phosphate-maltose (SAGP-maltose) solution, and two empty satellite bags to remove plasma and buffy coat. Preservative can be exchanged three times in this closed system. The system is able to supply nutrients, such as glucose, and to remove harmful metabolites, such as lactic acid, by exchanging the preservative during storage. As a result, red cells stored by this method showed much higher levels of total adenylate and morphological score after the second preservative exchange, when compared with red cells stored by the conventional method (P < 0.01). Judging from these two in-vitro parameters, red cells may tolerate storage for at least 10 weeks in a liquid state. This method might be useful for 'predeposit autologous transfusion', as it is more convenient and more cost effective than the freeze-preservation method.
In an effort to determine the lowest acceptable temperature for liquid preservation of red blood cells, the latter were stored at 5, 0, -2 and -5 degrees C. When polyvinylchloride (PVC) bags plasticized with di(2-ethylhexyl)phthalate (DEHP) were used as containers, hemolysis of red cells stored for 42 days at 0 degree C was lower than at the other three temperatures. Adenosine triphosphate (ATP) levels, morphology scores, and deformability indices were also best maintained at 0 degree C, and erythrocyte osmotic fragility did not increase at that temperature. On the other hand, when blood was stored in glass bottles at 0 degree C, hemolysis and erythrocyte osmotic fragility increased. The addition of DEHP to red cells stored in glass bottles at 0 degree C decreased hemolysis and erythrocyte osmotic fragility to levels equal to those in PVC bags. Thus, storage of red cells can be done at temperatures as low as 0 degree C, if PVC bags are used as the container. Previous negative assessments of storage temperatures below 4 degrees C, may be due to the use of glass bottles as containers for blood preservation.
We experienced a long-term survived case with unresectable Stage 4 esophageal carcinoma well responded to chemoradiotherapy of combination of cisplatin (C), vindesine (V) and peplomycin (P) with radiotherapy (R). The patient was a male, aged 53, and diagnosed to have carcinoma, 8 cm in length, located at the IuCe region of the esophagus and right subclavicular lymph node metastasis on admission. He received radiotherapy at total dose of 60 Gy for the primary and metastatic lesions, and also 2 cycle CVP chemotherapy concomitantly. The mass of the primary lesion endoscopically changed to a flat area with small erosion while the right subclavicular metastatic node disappeared and was not found on CT after the end of the treatment. Objective response of this case was determined to the partial response since carcinoma cells were still found at the flat lesion. After discharge, 9 cycles of CVP therapy were further given in 3-year periods. At present, the patient is alive well although a part of the primary esophageal lesion is proved to have malignancy on biopsy.
A new restriction endonuclease (ENase), PshAI, has been isolated from Plesiomonas shigelloides 319-73, an organism that causes food poisoning in humans. The enzyme was stable and produced a yield of 410 units/g of cells. In the presence of 10 mM MgCl2, PshAI recognizes and cleaves the nucleotide sequence 5'-GACNN/NNGTC, producing blunt ends. PshAI will be useful for structural analysis and molecular cloning of DNA, because no ENases recognizing sequence GACNNNNGTC have been previously described.
A new type II restriction endonuclease, SshAI, was purified from Salmonella shikmonah TK139 of kangaroo origin. The recognition and cleavage specificity of Ssh AI was determined to be 5'-CC/TNAGG-3', identical to that of SauI from Streptomyces aureofaciens and Bsu36I from Bacillus subtilis. Based on closely related and in part overlapping recognition specificities of Ssh AI and other restriction endonucleases, a close evolutionary relationship is proposed for all known Salmonella restriction endonucleases.
Specific restriction endonucleases were detected in three serotypes of Salmonella spp. isolated from humans in Japan from 1970 to 1987: an isoschizomer of AvaII endonuclease at a frequency of 0.91 in Salmonella infantis, an isoschizomer of KpnI at a frequency of 0.34 in Salmonella thompson, and an isoschizomer of StyI at a frequency of 0.30 in Salmonella blockley. Of interest is that restriction endonuclease-producing S. thompson was detected at high frequencies in the 1970s but at low frequencies in the 1980s.
In order to elucidate anti-inflammatory action of Sho-saiko-to, its components were analyzed and purified by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC), and their effects on lipid peroxidation were compared with those of Sho-saiko-to in guinea pig neutrophils, rat liver mitochondria and microsomes. The results obtained were as follows: 1) Sho-saiko-to gave no effect on arachidonate- and PMA (phorbol 13-myristate 12-acetate)-induced NADPH-O2- generation in neutrophils though it gave a weak LPS-like effect on the cells. No inhibition of reduced nicotinamido adenine dinucleotide phosphate (NADPH) oxidation was shown in liver microsomes. However, it markedly inhibited iron-induced lipid peroxidation in microsomes and mitochondria. 2) The active components to suppress lipid peroxidation could be concentrated in a lipid-soluble fraction from the Sho-saiko-to solution. The ED50 values to give 50% inhibition of the mitochondrial lipid peroxidation were 160 ng/mg prot, and 50 micrograms/mg prot, for the lipid-soluble fraction and Sho-saiko-to, respectively. 3) The components in the lipid-soluble fraction were further separated by TLC and HPLC, and their inhibitory effects on the lipid peroxidation were examined. The active components were baicalein, ginsenoside Rf and baicalin, of which ED50 values were 0.2, 0.2 and 1 nmol/mg prot, respectively. Glycyrrhizin and its derivatives, ginsenoside (except ginsenoside Rf), and saikosaponins gave no effect in the concentration examined. 4) From these results anti-inflammatory action of Sho-saiko-to was discussed.
The case was a 82-year-old man with advanced gastric Borrmann 3 cancer on the posterior wall of the cardia. Laparotomy revealed peritoneal dissemination (P3) and liver metastasis (H1). Because of his advanced age and on the basis of local findings, gastrectomy was not performed. In order to treat peritoneal dissemination with two-route chemotherapy, two tubes were placed beneath the cul-de-sac of Douglas and the left subphrenic cavity and at the same time, for the purpose of intra-arterial chemotherapy, one more tube was inserted into the proper hepatic artery. At day 12 and day 25 after the operation, 5-FU (500 mg)-Lipiodol (10 ml) emulsion was infused through the tube inserted into the proper hepatic artery. Within 24 hours following the infusion, hyperthermotherapy was carried out at 42 degrees C for 40 minutes. In addition, two-route chemotherapy with CDDP (100 mg)-STS was given at day 14 and day 28 after the operation. Furthermore, one course of FAM [5-FU (1,500 mg), ADM (30 mg) and MMC (10 mg)] therapy was initiated five weeks after the operation. Although no further chemotherapy was performed thereafter, both gastric endoscopy and CT scanning disclosed complete disappearance of the tumor one year after the operation. This result suggests that combined chemotherapy according to the part of progression is effective for advanced gastric cancer.
In order to indicate the three fields lymph node dissection method to wider ranges of patients with esophageal cancer, the two stages technique was applied to those with moderate disturbance of general physical conditions. Fifty eight patients with esophageal cancer admitted to our clinic from January 1986 to December 1988 and 38, in whom those with cervical esophageal cancer were excluded, employed esophagectomy. Of them, 26 patients (68%) received the three fields dissection method, 13 being due to the one stage technique and the remaining 12 being due to the one stage technique and the remaining 13 being due to the two stages technique. The three fields dissection method was indicated to patients who were younger than 75 years of age, were expected to receive curative resections or had no, mild and moderate disturbances of the physical conditions. The one stage technique was applied to patients with no and mild disturbances of the physical conditions while the two stages technique was to those with moderate disturbance. The general physical conditions were evaluated with the past history, underlying diseases, functions of the main organs and the ability of host defense. In the first operation of the two stage technique, subtotal esophagectomy and dissection of the regional lymph nodes including the paratracheal ones were performed. After approximately one month, esophageal reconstruction with the gastric tube and dissection of the regional nodes of the abdomen and neck were done in the second operation.(ABSTRACT TRUNCATED AT 250 WORDS)
An "organ function index" (OFI) predicting the risk of operative mortality was presented. OFI was estimated on the basis of dysfunction of the systemic organs in patients with esophageal cancer. The pulmonary, cardiac, hepatic and renal functions were assessed by 23 parameters in 108 patients when they were admitted. Operative death was defined as death due to operative complications occurring within 120 days after esophagectomy or by-pass operation. For a discriminant analysis, patients were limited to those in the early period (from October 1981 until December 1985) when the incidence of operative mortality was relatively higher and the parameters were also limited to statistically evaluable ones. Then, a discriminant analysis was performed using data on 18 parameters of four organs in 35 patients each of whom had no deficit in these data. Operative death occurred in 8 out of these 35 patients. Based on the data, an equation to calculate OFI was generated. It consisted of 7 parameters regarding pulmonary, hepatic and renal functions. The values of OFI less than zero predicted no operative death while those more than zero did predict operative death. The prediction rate on presence or absence of operative mortality by this equation was 91.4% in 35 patients. For clinical application, the predictable risk of operative mortality based on OFI was classified as high (OFI less than 1.4), intermediate (0 less than OFI less than 1.4), or low (OFI less than 0).(ABSTRACT TRUNCATED AT 250 WORDS)