Studies on the biosynthesis of fosfomycin. 2. Conversion of 2-hydroxypropyl-phosphonic acid to fosfomycin by blocked mutants of Streptomyces wedmorensis.
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Fosfomycin↗
Biomedical subjects
S Imai
Publications and source records attributed to S Imai.
[Clinical evaluation of intra-arterial infusion of hyperthermo-chemotherapy in gastric cancer].
We performed intra-arterial infusion hyperthermochemotherapy by retaining an intra-arterial reservoir in 17 lesions of 12 patients with non-resectable, metastatic or recurrent gastric cancers. The 12 patients consisted of one with a primary gastric cancer lesion, 6 with a solitary gastric cancer lesion metastasizing to the liver, 4 with gastric cancer accompanied by hepatic metastasis, lymph node metastasis or local recurrence, and one with a gastric cancer lesion metastasizing to Douglas' pouch. A catheter was retained in the hepatic artery of all 6 patients with a solitary gastric cancer lesion metastasizing to the liver, and a catheter was retained in the aorta of the patient with a primary lesion, 3 of the 4 patients with two or more metastatic lesions, and the patient with a lesion metastasizing to Douglas' pouch. The duration of each hyperthermia session was 50 minutes, and one or two sessions were performed within a week. One course consisting of 5 or 6 sessions was repeated. Antineoplastic drugs such as MMC, 5-FU, ADR, epi-ADR, CDDP and VP-16 were injected in bolus form or administered serially through the reservoir. Nine of the 12 patients had polypharmacy. One to 3 courses or 4 to 20 sessions at maximum (average 9.8 sessions) were given. The rate of efficacy of intra-arterial infusion hyperthermochemotherapy was 44% for hepatic metastasis and 25% for lymph node metastasis. The local recurrent lesions, the lesion metastasizing to Douglas' pouch and the primary lesion did not respond to therapy.
Adenocarcinoma, Mucinous↗
The clinical status and histopathological factors affecting natural killer cells of peripheral blood lymphocytes in patients with gastric cancer.
The in vivo function of NK cells is still uncertain, and there are various contradictory reports on NK cells in gastrointestinal cancer. In the present study the activity and proportion of NK cells (Leu 11 + cells) in peripheral blood were assessed in 71 patients with gastric cancer, and analysed with respect to the clinical and histopathological factors, such as the clinical stage, tumor size, degree of invasion, metastasis, histology, etc. There were no differences in the proportions and activities of NK cells between normal volunteers and gastric cancer patients. A low NK cell activity was associated with early gastric cancers (carcinoma in the mucosa or submucosa) less than 2 cm in diameter, large advanced tumors (invasion beyond the muscularis propria) greater than 8 cm in diameter, and metastasis of adjacent regional (perigastric) nodes. Liver metastasis did not affect the NK cell activity, however a high NK activity was found in patients with peritoneal dissemination. The NK activity did not correlate with the proportion of Leu 11 + cells in normal volunteers or in patients with early gastric cancer, however the activity and proportion of NK cells correlated with each other in patients with advanced gastric cancer. These results suggest that the preoperative evaluation of circulating NK cells in gastric cancer patients may be beneficial to assess the extent of nodal metastasis, the degree of tumor invasion, and peritoneal dissemination.
Adult↗
[A non-invasive quantitative measurement of cerebral blood flow using N-isopropyl-[123I]p-iodoamphetamine and single photon emission CT].
A non-invasive quantitative method using N-isopropyl-[123I]p-iodoamphetamine (IMP) was described for assessing regional cerebral blood flow (rCBF). Twenty four cases, composed of 11 patients with brain tumors, 9 patients having cerebrovascular disease and 4 other patients aged 15-73 years, all underwent the SPECT 133Xe inhalation method (Xe-SPECT) and IMP-SPECT using a Tomomatic 564. In the IMP-SPECT cases, 111-222 MBq (3-6 mCi) of IMP was injected intravenously and then sequential imaging was performed 9.5 +/- 1.2 (mean +/- SD) min (E1 image), 20.6 +/- 1.2 min (E2 image), 227.5 +/- 22.1 min (D1 image), and 236.6 +/- 22.4 min (D2 image) after the injection. The IMP-uptake value (counts/pixel/sampling time) in the region of interest (ROI), which was chosen in the non-affected cortex in the middle cerebral artery territory (MCAC), was counted on each image (E1 value, E2 value, D1 value and D2 value) and the E1/D1 ratios and E2/D2 ratios were consequently calculated. On the other hand, the absolute value of the ROIrCBF (Xe-rCBF) was obtained by Xe-SPECT. There were significant correlations noted between both the E1/D1 ratios and the E2/D2 ratios, and the Xe-rCBFs. Those correlation coefficients were found to be: r = 0.741 and 0.810 respectively. Based on this significant relationship, equations were deduced to involve the rCBF values by use of IMP-SPECT: y = Ax + B (y: rCBF, x: E1/D1 ratio (E2/D2 ratio), A = 52.8 (68.2), B = 6.3 (-14.9), where A and B indicate the slope and deviation of the regression line).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
[Effects and complications of continuous hepatic arterial infusion chemotherapy using implantable reservoir for liver metastases from colorectal cancer].
Continuous arterial infusion chemotherapy using implantable reservoir was performed for unresectable liver metastases from colorectal cancer and the therapeutic effects, side effects and complications were evaluated. Eleven patients were treated with four kinds of arterial infusion courses that mainly consisted of 5-FU. The arterial infusion courses were discontinued in 2 patients because of nausea and vomiting, and in one patient because of diarrhea. The catheters were dislocated in 2 patients and another 2 developed fistulous between the hepatic artery and bile duct. Three patients developed duodenal ulcer. Serum CEA was reduced in 4 patients (36%). After all, response rate was 9% (1/11). The one-year survival rates of all cases and cases treated with more than 4 courses were 36.3% and 80.0%, respectively.
Antineoplastic Combined Chemotherapy Protocols↗
Occurrence and subcellular location of NADH- and NADPH-linked aquacobalamin reductases in human liver.
1. Both activities of NADH- and NADPH-linked aquacobalamin reductases were found in some human tissues, liver, kidney pancreas, heart, spleen, lung, cerebrum, cerebellum, adrenal glands, stomach, duodenum, jejunum, ileum, colon and bone marrow. 2. Human liver contained both enzymes with higher specific activities than any other tissues. 3. The liver NADH-linked enzyme was distributed in both mitochondrial (approx. 60%) and microsomal (40%) fractions; similar to the distribution of the NADPH-linked enzyme, but of which 40% activity was found in the mitochondria and the remaining activity was recovered in the microsomes. 4. The results suggest that the synthetic systems of the cobalamin coenzymes occur in both mitochondria and microsomes of human liver.
Cell Fractionation↗
The 70-kDa epileptic cortical protein elicits bursting activity accompanied by a reduction of outward current in Euhadra neurons which is inhibited by an antibody against this protein.
The effect on membrane properties of 70-kDa protein (namely P70), a specific protein found in cobalt-induced epileptic cortex of rats, was examined electrophysiologically in identified neurons of the snail, Euhadra peliomphala. Injection of P70 into the neurons elicited a bursting activity resembling the paroxysmal depolarization shift seen in mammalian epileptic neurons and a reduction of the outward current, which were suppressed by Ca2(+)-free saline or tetraethylammonium. The injection of P70-antibody into neurons, preceding the P70 injection, markedly inhibited the bursting activity and the reduced outward current elicited by P70. These findings suggest that P70 causes a reduction of Ca2(+)-dependent potassium conductance which may be one of the mechanisms generating epileptic bursting activity.
Animals↗
Possible involvement of different GTP-binding proteins in noradrenaline- and thrombin-stimulated release of arachidonic acid in rabbit platelets.
Noradrenaline (NA) stimulated the release of arachidonic acid (AA) from the [3H]AA-labelled rabbit platelets via alpha 2-adrenergic receptors, since the effect of NA was inhibited by yohimbine. The stimulatory effect of NA in digitonin-permeabilized platelets was completely dependent on the simultaneous presence of GTP and Ca2+. The NA- and thrombin-stimulated releases of AA were markedly decreased by the prior ADP-ribosylation of the permeabilized platelets with pertussis toxin. Antiserum directed against the pig brain Go (a GTP-binding protein of unknown function), recognizing both alpha 39 and beta 35,36 subunits, but not alpha 41, of pig brain, reacted with 41 kDa and 40 kDa bands, with not one of 39 kDa, in rabbit platelet membranes. Anti-Go antiserum inhibited guanosine 5'-[gamma-thio]triphosphate-, A1F4(-)-, NA- and thrombin-stimulated AA releases in the membranes. Although the effect of thrombin was inhibited by low concentrations of anti-Go antiserum, high concentrations of the antiserum was needed for inhibition of the NA effect. Antiserum directed against the pig brain G1 (inhibitory G-protein), recognizing both alpha 41 and beta 35,36 subunits, but not alpha 39, of pig brain, reacted with the 41 kDa band in platelets. Anti-G1 antiserum inhibited only the effect of NA. Reconstitution of the platelet membranes ADP-ribosylated by pertussis toxin with Go, not Gi, purified from pig brain restored the thrombin-stimulated release of AA. In contrast, reconstitution of those membranes with Gi, not Go, restored the NA-stimulated release of AA. These results indicate that different GTP-binding proteins, Gi- and Go-like proteins, may be involved in the mechanism of signal transduction from alpha 2-adrenergic receptors and thrombin receptors to phospholipase A2 in rabbit platelets.
Aluminum↗
A specific 70 kDa protein induced in the epileptogenic cortex of rats elicits bursting activity and inactivation of potassium current in snail neurons.
The capability of a specific 70 kDa (P70) protein produced in cobalt-induced epileptogenic cortex of rat cerebrum in promoting epileptic bursting activity was examined in snail neurons, using the voltage clamp method in combination with the pressure injection technique. Injection of P70 into the neurons elicited bursting activity with paroxysmal depolarization shift together with a reduction in the delayed outward current which was suppressed by tetraethylammonium. These changes of membrane properties induced by P70 were dose-dependently inhibited by prior treatment with the anticonvulsant phenytoin. These findings indicate that P70 causes an inactivation of potassium conductance which may generate epileptic bursting activity.
Animals↗
Acute lymphocytic leukaemia after Epstein-Barr-virus-positive malignant lymphoma.
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Child↗
Genetic analysis of resistance to radiation lymphomagenesis with recombinant inbred strains of mice.
Induction of lymphomas by radiation in mice is controlled by genetic factors. We analyzed the genetic control of radiation lymphomagenesis using the CXS series of recombinant inbred strains derived from two progenitor strains: one highly susceptible to radiation induction of lymphoma [BALB/cHeA (C)] and one extremely resistant [STS/A (S)]. The best concordances between strain distribution patterns of genetic markers and resistance (or susceptibility) to radiation lymphomagenesis were observed in a region with the b and Ifa genes on chromosome 4. This indicates that one major locus controls the incidence of radiogenic lymphomas in mice. We designated this locus as the Lyr (lymphoma resistance) locus. Backcrosses of (CXS)F1 to the two progenitor strains showed an intermediate incidence of lymphomas between their parental mice and did not significantly differ from (CXS)F1 mice. This and previous observations that (CXS)F1 mice also showed an intermediate incidence, differing from both progenitor strains, indicate that more genes are involved in the resistance (or susceptibility) to lymphoma induced by irradiation.
Animals↗
[A double blind study to evaluate the optimal dose and its frequency for oral administration of OK-432 (picibanil) by immunological parameters (the 2nd report)].
The present study was designed to determine the optimal dose and frequency of oral administration of a biological response modifier, OK-432 (Picibanil), which has been used for cancer immunotherapy by injection. Ninety one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40KE, once or 3 times a week before operation (5KE X 1/W, 20KE X 1/W, 40KE X 1/W, or X 3/W). Misregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. In the 1st report, we already showed that 5KE X 3/W might be the optimal regimen to augment the natural killer (NK) activity of regional lymph node lymphocyte (RNL). In the 2nd report, we searched for the optimal regimen to augment the antitumor immunity of T lymphocytes. The proliferative response of RNL to SuPR (protein derived from OK-432) was augmented in all the groups administered OK-432. The responsiveness of PBL to autologous tumor extract enhanced by IL-2 was augmented by 5KE X 1/W, and that of RNL was augmented by 5KE X 3/W. The killer/suppressor (Leu2+15-/Leu2+15+) ratio in RNL increased in all the groups administered OK-432 especially in 20KE X 3/W group. Oral administration of OK-432 augmented both non-specific and the specific antitumor immunity of PBL as well as RNL, and 5KE X 3/W may be the optimal regimen to augment the antitumor immunity, especially of RNL.
Administration, Oral↗
[Intraoral ultrasound of the tongue tumor].
Transcutaneous ultrasonography scanned through the submandibular triangle has been effectively utilized for the evaluation of tongue tumors. However, because of lacking an appropriate sonic window, tumors located in the anterior portion of the tongue can not be demonstrated on the transcutaneous ultrasonogram. Intraoral ultrasonography using an echoendoscopy was effective for evaluating neoplasms of the tongue, and could clearly demonstrate tongue tumors, which failed to be shown on the transcutaneous ultrasonograms. In addition, intraoral ultrasonograms could provide more accurate anatomical informations concerning the tumor extent than the transcutaneous ultrasonograms.
Endoscopy↗
[A double blind study of the evaluation of the optimal dose and its frequency in oral administration of OK-432 (Picibanil) by immunological parameters (the 1st report)].
A biological response modifier, OK-432 (Picibanil) administered by injection has been used for cancer immunotherapy. The present study was designed to determine the optimal dose and frequency of oral administration of OK-432. Ninety-one stomach cancer patients were randomly assigned into 7 groups and were administered a placebo or OK-432 at a dose of 5, 20 or 40 KE, once or 3 times a week before their operation (5 KE X 1/W, 20 KE X 1/W, 40 KE X 1/W, or X3/W). ++Missregistration excluded 3 patients and the data of 88 patients were analysed. There was no significant difference in the background status of the patients in each group. The NK activity of PBL was augmented by the administration of 40 KE X 1/W or 20 KE X 3/W and that of RNL was augmented by the administration of 5 KE X 3/W or 40 KE X 1/W, in conjunction with an increase in the number of % positive cells of leu 11a+ or leu 19+ analysed by flow cytometry. The killing activity of PBL, RNL, or MNL against allogeneic lined gastric cancer cells (KATO III) was not augmented by the oral administration of OK-432 for one week. The skin reactivity to Su-PS or PPD, serum levels of tumor markers, or serum levels of immunoglobulins did not help in determining the optimal dose or its frequency. These results suggest that 5 KE X 3/W may be the optimal regimen to augment the antitumor immunity of RNL.
Administration, Oral↗
[Chemotherapy with fluoropyrimidines for MOPC-104E plasmacytoma transplanted in mice with CCl4 induced chronic liver dysfunction].
The masked compounds of 5-fluorouracil (5-FU) have been widely used for chemotherapy in digestive organ cancer. Among them it has been considered that FT (Tegafur) is metabolized into the active form by the drug-metabolizing enzyme P-450 in the microsomes of hepatocytes, and that their activation and anti-tumor activity may decrease under the condition of chronic liver dysfunction. However, this hypothesis has never been experimentally proved. In the present study the therapeutic effect and metabolism of 5-FU and its masked compounds: FT, UFT (uracil + FT), HCFU (Carmofur), 5'-DFUR (Doxifluridine) were assessed by using MOPC-104E plasmacytoma transplanted subcutaneously in BALB/c mice with CCl4-induced chronic liver dysfunction. Agents were administered daily directly into the stomach with stainless steel canule over days 7 to 13 after tumor transplantation, and the tumor weights, drug concentrations in the liver or the tumor, and serum levels of GOT, GPT and LDH were measured on day 14. In mice with chronic liver dysfunction the tumor-inhibitory effect of 5-FU, FT, UFT and HCFU did not necessarily decrease and serum levels of GOT, GPT and LDH of mice administered with 5-FU, FT, HCFU and 5'-DFUR were higher than in normal animals treated with them. By contrast UFT had no influence on them. The most remarkable difference was observed in uracil concentrations, which were significantly lower in the tumor and the liver of mice with chronic liver dysfunction than in those of normal mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Chemosensitivity correlation between the primary tumors and simultaneous metastatic lymph nodes of patients evaluated by DNA synthesis inhibition assay.
The chemosensitivities of primary tumors (PT) and simultaneous metastatic lymph nodes (MN) to mitomycin C (MMC), 5-fluorouracil (5-FU), Adriamycin (ADR) (doxorubicin; Adria Laboratories, Columbus, OH), carboquone (CQ), or cisplatin (CDDP) were assessed in a group of 29 patients (11 gastric, 8 colorectal, 4 breast, and 6 other cancers) by a DNA synthesis (3H-thymidine incorporation) inhibition assay. PT and MN from the same patient showed heterogeneity in chemosensitivity. MN were more sensitive to the agents than PT. PT were sensitive to 5-FU, whereas MN were sensitive to CDDP. An analysis of the sensitivity correlations showed that the sensitivities of PT to MMC, 5-FU, CQ, and CDDP correlated with each other, but ADR sensitivity correlated with only CQ sensitivity. The sensitivities of MN correlated with each other, except for those to ADR and CDDP. In contrast, MMC, ADR, or CQ sensitivity showed a correlation between PT and MN. These results suggest that patients should be treated according to the sensitivity of the target lesion. However, if the sensitivity assay is not available, the sensitivity correlation may be useful when choosing the agent. It also may be important that ADR sensitivity does not correlate with the sensitivities of other agents.
Breast Neoplasms↗
Epstein-Barr virus in nasal T-cell lymphomas in patients with lethal midline granuloma.
Five cases of lethal midline granuloma were identified histologically and phenotypically as peripheral T-cell lymphomas. Epstein-Barr virus (EBV) DNA was detected in the nasal tumour biopsy specimens by Southern blotting and in-vitro hybridisation with simultaneous detection of EBV-determined nuclear antigen (EBNA) and T-cell surface markers by two-colour immunofluorescence. Further immunofluorescence and northern blotting revealed that EBNA2 gene and also latent membrane protein gene were expressed in the nasal tumour cells. The patients had high titres of antibodies to EBV. These findings suggest that lethal midline granuloma is causally associated with EBV.
Adult↗
Induction of epileptic seizure activity by a specific protein from cobalt-induced epileptogenic cortex of rats.
To evaluate the protein-related mechanism for epileptogenesis, we examined protein behavior during cobalt-induced epileptic seizure activity and the effect of injection of cobalt-induced proteins into cerebral cortex on electrocorticographic discharge in rats. Cobalt-induced epileptic seizure activity caused an increase in two proteins that migrated at about 84 kDa (P84) and 70-71 kDa (P70) and a decrease in a protein of about 57 kDa (P57) as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Among these proteins, P70 evoked epileptic discharges on the electroencorticograph and behavioral seizure, when it was intracortically injected into the motor region of the normal rat cerebrum. The data suggest that P70 may be a factor for epileptogenesis.
Animals↗