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K Matsui

Publications and source records attributed to K Matsui.

At least 415 records · Page 23Linked to original sources
PubMed1991

[High-dose Tegafur (FT) for primary lung cancer: a phase I trial].

A phase I clinical study of intravenous Tegafur was conducted in nineteen previously treated patients with primary lung cancer. The dose of Tegafur was elevated from 1.0 to 3.0 g/m2/day for five consecutive days to determine the maximum tolerated dose. The dose-limiting factors were gastrointestinal and neurological toxicity and fatigability observed with the dose level of 2.5 g/m2/day for 5 days. Hematologic, hepatic and renal toxicities were not observed. Gastrointestinal toxicity including nausea, vomiting, anorexia and diarrhea of over grade 2 were seen to result from the dose of 2.5 g/m2/day. Neurological toxicity consisted of headache, dizziness, anxiety and depression. At the dose level of 2.0 g/m2/day, one patient, who had epileptic seizures in the past, experienced a psychomotor seizure. Depression (Grade 2 CNS toxicity) was observed at the dose level of 3.0 g/m2/day. Dose limiting factors were neurological toxicities. The pharmacokinetics of tegafur and 5-FU (the active form of Tegafur) has been studied in all patients. Serum level of tegafur was measured by HPLC method, and serum level of 5-FU was analyzed by GC-MS method. At the dose level greater than 2.0 g/m2/day for 5 days, the mean serum 5-FU values appear over the therapeutic range (0.1 micrograms/ml). In conclusion, 2.5 g/m2/day for 5 days was considered to be MTD, and 2.0 g/m2/day for 5 days intravenous administration was recommended for the phase II trial of single agent chemotherapy.

Drug Administration Schedule↗
PubMed1991

Hyperthermic purging in vitro of murine leukemia cells (MK-8057): surviving fractions of normal and leukemic stem cells and the long-term survival of mice injected with the post-hyperthermic leukemia cells.

Hyperthermic purging of leukemic cells has been applied in clinical trials, although an accurate evaluation system to compare the effect on leukemia cells with that on normal hemopoietic cells has not been established. We evaluated the heat-sensitivity of murine leukemia cells, MK-8057, and compared differences in heat-sensitivity between surviving fractions of leukemic stem cells (leukemic spleen colony-forming units, L-CFU-S) and normal hemopoietic stem cells (spleen colony-forming units, CFU-S). Using the spleen colony assay, the survival fraction of L-CFU-S was compared with that of CFU-S after various hyperthermic treatments. One of the most efficient conditions, that is, hyperthermia at 42 degrees C for 3 h, allowed only 0.17% of L-CFU-S to survive, whereas 26.5% of normal CFU-S survived. Hyperthermia at 44 degrees C for 45 min further reduced the L-CFU-S (0.13%); however, the relative ratio of L-CFU-S to CFU-S was less than that at 42 degrees C for 3 h, because there was a larger reduction at 44 degrees C in normal CFU-S (5.1%). Recipient mice injected with MK-8057 cells treated with hyperthermia survived longer in proportion to the decreasing number of surviving L-CFU-S injected. This extension of the survival of recipient mice given MK-8057 cells after hyperthermia was also proportional to the estimated survival fraction of L-CFU-S. The survival fraction of MK-8057 cells after hyperthermia that was independently calculated through the extended survival of the recipients showed a good correlation with the surviving fraction of L-CFU-S, seen as the leukemic spleen colonies, at a correlation coefficient of r = 0.985. The number of surviving mice receiving the post-hyperthermic MK-8057 cells and the number of L-CFU-S calculated to have been injected had a relationship based on a Poisson distribution. Thus, the calculated results imply that the hyperthermia proportionally targets L-CFU-S, which are the only cells responsible for killing the recipient mice.

Animals↗
PubMed1990

Reduction of nerve growth factor level in the brain of genetically ataxic mice (weaver, reeler).

By a highly sensitive enzyme immunoassay we measured the level of nerve growth factor (NGF) in the cerebellum and cerebrum of the neurologically mutant mice, weaver, reeler and Purkinje cell degeneration (PCD). A significant decrease in NGF level was observed in both cerebellum and cerebrum of weaver and reeler mutants of either sex. However, there was no such difference between normals and mutants in the case of the PCD mice. These results show that weaver and reeler mice have abnormalities of NGF synthesis and/or degradation not only in the cerebellum but also in the cerebrum.

Animals↗
PubMed1990

[Nontraumatic hemorrhage in abdomen and retroperitoneum--CT, sonographic and clinical findings].

Sixteen patients with nontraumatic abdominal or retroperitoneal hemorrhage were examined with ultrasound (n = 16), and CT (n = 14). The lesions of the 10 patients with signs on the onset of hemorrhage were four rectus sheath hematomas, three renal subcapsular and perirenal hematomas, and subcapsular hematoma, pararenal hematoma, perirenal and parenal hematoma, on each. Fall in periphery blood hematocrit values within 24 hours after the onset was observed in only three patients. As the hematocrit value was increased, fluid area of hematoma was replaced by high density on CT and by hypoechoic area on ultrasound. The lesions of the remaining 6 patients were four renal subcapsular hematomas, one hepatic parenchymal and subcapsular hematoma, and one iliopsoas hematoma. CT is superior to ultrasound in evaluation of the nontraumatic hematomas. However, clinicians require to pay more attention to this disorder which occasionally mimick other disorders.

Abdomen↗
PubMed1990

Lymphokine-regulated differential expression of mRNA for p75kDa-IL-2R and p55kDa-IL-2R in a cloned B lymphoma line (BLC1-CL-3 cells).

IL-5 renders BCL1-CL-3 (CL-3) cells responsive to IL-2 by increasing the number of high affinity IL-2R, whereas IL-4 prohibits such action of IL-5 to prepare CL-3 cells responsive to IL-2. Here we have found that genes for p75kDa-IL-2R and p55kDa-IL-2R are differentially regulated by IL-4 and IL-5. Nonstimulated CL-3 cells constitutively express mRNA for p75kDa-IL-2R and p55kDa-IL-2R. IL-5 stimulation principally augments the expression of p75kDa-IL-2R mRNA (4- to 8-fold), although modestly increasing the expression of p55kDa-IL-2R mRNA. Kinetic studies have revealed a maximal increase in p75kDa-IL-2R mRNA expression at 12 h and a decline thereafter, substantiating our previous kinetic study of the expression of high affinity IL-2R after the IL-5 stimulation. By contrast, IL-4 stimulation modestly increases the expression of p75kDa-IL-2R mRNA, whereas markedly reducing the expression of p55kDa-IL-2R mRNA, irrespective of whether CL-3 cells were stimulated with IL-4 alone or together with IL-5 and IL-2. Moreover, addition of IL-4 into the culture containing IL-5 and IL-2 causes striking reduction in the level of J-chain mRNA, which otherwise is markedly induced by stimulation with IL-5 and IL-2. These results clearly illustrate the differential regulation of p75kDa- and p55kDa-IL-2R-gene expression by IL-5 and IL-4, and reinforce our notion that increased expression of high affinity IL-2R induced by IL-5 is responsible for the IL-2 competent state, and decreased expression of p55kDa-IL-2R by IL-4 is responsible for IL-2 unresponsive state.

Animals↗
PubMed1990

Evaluation of high-dose etoposide combined with cisplatin for treating relapsed small cell lung cancer.

The synergism of combined high-dose etoposide with standard dose cisplatin (HD-EP) was evaluated in 20 patients who had relapsed after treatment of small cell lung cancer. Each patient was given etoposide at 500 mg/m2/day on days 1 to 3 and cisplatin at 80 mg/m2 (two patients given 120 mg/m2) on day 1; autologous bone marrow was not transplanted. Five patients were given recombinant human granulocyte colony-stimulating factor (rhG-CSF, 50 micrograms/m2) in an attempt to reduce HD-EP induced neutropenia. The overall response was 50% (9 of 18); one complete response (6%), eight partial responses (44%), seven no change (39%), and two progressions of disease (11%). Of the 18 evaluable patients, 12 had been treated with regimens of conventional doses of etoposide with conventional doses of cisplatin or carboplatin, and of these, five (42%) achieved a partial response. The median duration of response was 8.4 weeks (range, 5.3 to 17.7) and the median survival time was 20.3 weeks (range, 1.6 to 91). All of the patients developed severe myelosuppression; rhG-CSF did not shorten the period of the leukopenia. Mucositis and liver dysfunction were the major nonhematologic manifestations of toxicity. Two treatment-related deaths resulted from sepsis. These results suggest that the activities of high doses etoposide with standard doses of cisplatin are synergistic against small cell lung cancer.

Aged↗
PubMed1990

Combination chemotherapy with or without radiation therapy in small cell lung cancer. An analysis of a 5-year follow-up.

From January 1978 to March 1984, a series of 159 patients with newly diagnosed small cell lung cancer (SCLC) was treated with combination chemotherapy with or without chest radiation at the Osaka Prefectural Habikino Hospital. By March 31, 1989, ten patients (6.3%) had survived for 5 years or more after the initial chemotherapy, including nine of 95 patients (9.5%) with limited disease and one of 64 patients (1.6%) with extensive disease. All these 5-year disease-free survivors, except for one patient whose response could not be assessed by chest radiograph because of radiation fibrosis, had a complete response. Nine of the 71 patients (12.7%) treated with combination regimens containing doxorubicin survived 5 years or more, and only one of the 88 (1.1%) treated with regimens without doxorubicin had long-term survival (P less than 0.01). The sex, performance status (PS), and chest radiation after systemic chemotherapy did not correlate statistically with long-term survival (P greater than 0.05). Three of the ten patients died free of SCLC. Two of the ten patients (20%) developed second malignancies and died. The remaining patient died of pneumonia. The Cox regression analysis identified the PS and doxorubicin-containing regimens as important factors indicating improved survival. Combination regimens containing doxorubicin have, therefore, been found to be very effective in improving survival and achieving long-term survival.

Adult↗
PubMed1990

Osmoregulatory expression of porin genes in Escherichia coli: a comparative study on strains B and K-12.

Escherichia coli K-12 produces both the OmpF and OmpC porins, the relative amounts of which in the outer membrane are affected in a reciprocal manner by the osmolarity of the growth medium. In contrast, E. coli B produces only the OmpF porin, regardless of the medium osmolarity. In this study, it was revealed that there is an extensive deletion within the ompC locus of the E. coli B chromosome. Cloning and nucleotide sequencing of the regulatory gene, ompR, of E. coli B revealed that there are two amino acid alterations (Lys-6 to Asn and Ala-130 to Thr) in the amino acid sequence of the OmpR protein, as compared with that of E. coli K-12. It is suggested that these particular amino acid alterations are responsible for the constitutive expression of the ompF gene observed in E. coli B.

Bacterial Outer Membrane Proteins↗
PubMed1990

IL-5 up-regulates but IL-4 down-regulates IL-2R expression on a cloned B lymphoma line.

Both IL-4 and IL-5 demonstrate B cell growth activity. IL-5 can render a cloned neoplastic B cell line, BCL1-CL-3 cells, responsive to IL-2, whereas IL-4 has no such activity. The response to IL-5 and IL-2 proceeds in two phases: the first phase which clearly depends upon IL-5 is the obvious increase in number of high affinity IL-2R (3.1-fold) with modest increase of low affinity IL-2R (1.2-fold) and gain of the ability of facilitated IL-2-binding and internalization of IL-2, and the second phase which is induced by IL-2 in the IL-5-stimulated CL-3 cells comprises the striking increase of low affinity IL-2R (8.5-fold). Kinetic study has revealed that high affinity IL-2R expressed on CL-3 cells begins to increase at 6 h and reaches to maximum at 12 h after stimulation with IL-5 or IL-5 plus IL-2, whereas low affinity IL-2R expression increases at 18 h and becomes maximal at 24 h after stimulation of CL-3 cells with IL-5 and IL-2. However, in the presence of IL-4, IL-5 cannot induce an increase in number of high affinity IL-2R on CL-3 cells. Thus, CL-3 cells stimulated with the mixture of IL-5 and IL-4 cannot respond to IL-2, and fail to show up-regulated expression of low affinity IL-2R. IL-4 also has a capacity to modestly interfere with the action of IL-2 to up-regulate low affinity IL-2R expression on IL-5-pretreated CL-3 cells. Thus, this monoclonal B cell system provides an excellent model system to define the roles of IL-5 and IL-4 involved in the B cell differentiation and to characterize the properties of B cells competent to IL-2 stimulation and the signal transduction mechanism which operates through IL-2/IL-2R system.

Animals↗
PubMed1990

Possible association between gastrectomy and subsequent development of esophageal cancer.

To clarify the possible association between gastrectomy and the subsequent development of esophageal cancer, we studied the incidence of subjective gastroesophageal reflux in 287 patients and analyzed the nutritional status and results of endoscopic examination of the esophagus in 62 patients who had survived for a long period after gastrectomy for nonmalignant diseases. The incidence of postoperative reflux was 22.6%. None of the patients had severe deterioration of blood parameters or nutritional status. Endoscopic observation revealed esophagitis in 24.2% of patients, mainly in the lower esophagus. Histologically, there was a high incidence of infiltration of neutrophils and lymphocytes, enlarged papillae, and basal cell hyperplasia. Epithelial dysplasia was detected in 41.9% of patients, and of these there were more patients in whom the degree of dysplasia was more severe in the lower esophagus than in other areas. These data suggest that postgastrectomy gastroesophageal reflux is more likely than postgastrectomy changes in nutritional status to be a possible contributory factor to the development of subsequent esophageal cancer.

Adult↗
PubMed1990

Tetralogy of Fallot with absent pulmonary valve detected by fetal echocardiography.

The tetralogy of Fallot (TOF) with an absent pulmonary valve is a rare congenital cardiac malformation. We recorded the fetal echocardiographic findings for a fetus with the TOF with absent pulmonary valve and review the literature on this condition. The infant died 5 days after birth and the autopsy showed no infundibular stenosis. The degree of infundibular stenosis may be correlated with the prognosis of infants with this disease.

Adult↗
PubMed1990

Purification, properties, and function of flavokinase from rat intestinal mucosa.

Flavokinase (ATP:riboflavin 5'-phosphotransferase) [EC 2.7.1.26] was purified to apparent homogeneity from rat intestinal mucosa by fractionation with ammonium sulfate, gel filtration, and flavin affinity chromatography. The addition of ATP to the enzyme solution was necessary for its binding to the affinity gel. The apparent molecular weight of the enzyme was estimated to be 13,500 by gel filtration on Sephadex G-100 and by SDS-PAGE. The properties of the enzyme, including its flavin specificity, were studied. Three types of riboflavin analogues were used for the flavin specificity study; namely, ones modified at the ribityl group, and at positions 3 and 8 of the isoalloxazine ring. Of the analogues modified at the ribityl group or position 3 of the isoalloxazine ring, only 2'-deoxyriboflavin was phosphorylated and then only weakly. On the other hand, most analogues modified at position 8 of the isoalloxazine ring were good substrates for the kinase, an appropriate increase in the substituent volume at position 8 of the isoalloxazine ring resulting in an increase in the Vmax value. In a previous paper on the mechanism of intestinal absorption of riboflavin, we proposed that one of the specific processes for the absorption of riboflavin is phosphorylation by flavokinase [Kasai, S. et al. (1988) J. Nutr. Sci. Vitaminol. 34, 265-280]. The present results support this conclusion because analogues that were absorbed at low concentrations through a process specific for riboflavin in our previous study were phosphorylated effectively by the enzyme, whereas those that were absorbed solely through simple diffusion at all concentrations were not phosphorylated or only phosphorylated weakly. The properties of the flavokinases from intestinal mucosa and liver were compared.

Animals↗
PubMed1990

Inhibitory effect of pseudo-aminosugars on oligosaccharide glucosidases I and II and on lysosomal alpha-glucosidase from rat liver.

We examined the inhibitory effect of three pseudo-aminosugars (validamine, valienamine, and valiolamine), which were isolated from the broth of Streptomyces hygroscopicus, on the oligosaccharide-processing glucosidases I and II involved in glycoprotein biosynthesis in rat liver. Both glucosidases I and II were inhibited to the same extent by the pseudoaminosugars, and valiolamine had a more potent inhibitory activity than validamine or valienamine. A 50% inhibition of valiolamine was observed at 12 microM for glucosidase I and glucosidase II activities acting respectively on the substrates Glc3Man9GlcNAc2 and p-nitrophenyl alpha-D-glucopyranoside. Further, in order to investigate further the ability of valiolamine to inhibit glucosidase I, reaction products were analyzed by gel filtration on a Bio-Gel P-4 column. We also compared the inhibitory action of these pseudo-aminosugars on the acid alpha-glucosidase of rat liver lysosomes. They competitively inhibited the hydrolysis of both substrates, maltose and glycogen. Valiolamine again had a more potent lysosomal alpha-glucosidase inhibitory activity than the other two. The Ki values of valiolamine for the hydrolysis of maltose and glycogen were 8.1 and 11 microM, respectively. Valiolamine is a particularly effective inhibitor of oligosaccharide glucosidases I and II and of lysosomal alpha-glucosidase. Hence valiolamine might be useful as a research tool in investigations of carbohydrate metabolism.

Amino Sugars↗
PubMed1990

Protective immunities induced by porins from mutant strains of Salmonella typhimurium.

The protective immunity against Salmonella typhimurium-infection in mice immunized with porins from mutant strains of S. typhimurium was studied. A high level of protection against S. typhimurium infection was achieved in mice immunized with native porins from S. typhimurium LT2 (wild-type strain) but not from S. typhimurium SH6017, SH6260, or SH5551 (mutant strains), which produce 34K, 35K, or 36K porin, respectively. Moreover, when mice were immunized with mixtures of 34K, 35K, and 36K porins (34K + 35K, 35K + 36K, 34K + 36K, or 34K + 35K + 36K porin) or LT2 porin heated at 100 C for 2 min in 2% SDS (heat-denatured LT2 porin), the degree of protective immunities in the mice was very much lower than that in the mice immunized with the native LT2 porin. However, antisera raised against these porins showed no significant differences of the antibody titer against LT2 porin or LT2 whole cells. On the other hand, mice immunized with the native LT2 porin--but not 34K, 35K, 36K, 34K + 35K + 36K, and the heat-denatured LT2 porins--exhibited significant levels of delayed-type hypersensitivity reaction and interleukin-2 production when they were elicited with whole cells of S. typhimurium LT2. These observations suggested that the high level of protection induced by the native LT2 porin immunization was dependent on the induction of cell-mediated immunity.

Animals↗
PubMed1990

Blue light photoreception in Neurospora circadian rhythm: evidence for involvement of the flavin triplet state.

The mechanism of the photoreceptor acting on the circadian conidiation rhythm of Neurospora crassa was studied, with the following results: (1) the efficiency of 8-haloflavins as sensitizers increased with their triplet yields. (2) Phase shifts were not abolished by removal of oxygen prior to illumination. (3) Oxygen inhibited phase shifts when introduced into the cultures after light treatment. It is proposed that the blue light photoreceptor for the circadian clock of Neurospora crassa acts (1) from its triplet state, but (2) not via singlet oxygen; (3) signal transduction involves (an) oxygen-sensitive intermediate(s).

Circadian Rhythm↗
PubMed1990

Cytoplasmic accumulations in rat primary brain cell cultures following treatment with E-64, a thiol protease inhibitor.

The present communication deals with morphological effects of E-64, a thiol protease inhibitor, on primary cultures dissociated from 15-day-old fetal rat brain. Brain cells were treated with different concentrations of E-64 varying from 0.1 to 50 micrograms/ml medium. Numerous cytoplasmic accumulations appeared in neuronal cells, astrocytes and oligodendrocytes exposed to a concentration of 1.0 micrograms/ml of E-64 or higher, and after withdrawal of E-64, the accumulations disappeared. These accumulations were immunocytochemically stained with the antibody against cathepsin B, a marker of lysosomal activity, and the staining patterns found with acid phosphatase were similar to those found with cathepsin B. It is hypothesized that the cytoplasmic accumulations were lysosomes and that the action of E-64 was reversible. Use of thiol protease inhibitors on primary brain cell culture may be an appropriate model system for studying protein storage diseases in neuronal cells.

Animals↗