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Biomedical subjects

K Satoh

Publications and source records attributed to K Satoh.

At least 325 records · Page 18Linked to original sources

[Expression of hepatocyte growth factor by activated eosinophiles in inflammatory lung tissue].

Hepatocyte growth factor (HGF) plays a multifunctional role in the regeneration of alveolar type-II and other epithelial cells. HGF is produced by various kinds of mesenchymal cells, including polymorphonuclear granulocytes. However, it was not evident that eosinophiles produce HGF. In this investigation, we utilized immunohistochemical techniques to show that Eol-1 cells, an eosinophilic leukemia cell line, as well as activated eosinophiles in inflammatory lung tissue, produce HGF. It was also shown that IL-5 induced the production of HGF by peripheral eosinophiles in vitro. These findings suggest that, in inflammatory lung diseases, eosinophiles activated in the presence of IL-5 produce not only tissue-injurious substances (e.g., eosinophilic cationic protein, major basic protein, and peroxidase) but also HGF; and that eosinophiles may play a role in the regeneration of injured lung tissue through the production of HGF.

Cells, Cultured↗

Autologous high-killing cytotoxic T lymphocytes against human lung cancer are induced using interleukin (IL)-1beta, IL-2, IL-4, and IL-6: possible involvement of dendritic cells.

Although CTLs bear main immune responses in human tumors, stable CTL clones against human lung cancer have rarely been generated. Our previous study demonstrated efficient autologous CTL induction in human gastric cancer and glioblastoma by cytokine combination of interleukin (IL)-1beta (167 IU/ml), IL-2 (67 IU/ml), IL-4 (67 IU/ml), and IL-6 (134 IU/ml). In this study, we demonstrated successful induction of autologous stable CTLs in five of six patients with lung adenocarcinoma from mixed-lymphocyte tumor culture using this cytokine combination. All CTLs revealed potent and specific killing activity against autologous target cells (over 75% in CD8+ CTLs and over 50% in CD4+ CTLs at an E:T ratio of 10 for 24 h). Using a series of antibodies, CD8+ CTLs showed to recognize tumor-specific antigens of lung cancer cells through HLA class I. In the separate experiments, failure of CTL induction from monocyte-depleted peripheral blood mononuclear cells and appearance of cells with characteristics of dendritic cells from adherent peripheral blood mononuclear cells in the culture of the same concentration of IL-1beta, IL-4, and IL-6 indicated that CTLs can be efficiently generated by this cytokine combination via possible dendritic cell induction. This is the first study of an efficient and reproducible in vitro CTL induction against human lung cancer.

Adenocarcinoma↗

[Quantitative study of 99mTc-Technegas SPECT for ventilatory impairment in pulmonary emphysema].

99mTc-Technegas scintigraphy is used to evaluate ventilation abnormalities in patients with pulmonary emphysema. Although abnormalities of ventilation distribution are easy to find, no objective index exits. Evaluation is subjective and differs with each radiologist. Thus, it is difficult to compare cases and the clinical course in the same case. The present study for quantitative evaluation demonstrated an excellent correlations between mean voxel values of the lung and stage classification. Furthermore, a correlation was observed between the mean and FEV1.0%. These findings indicate that the quantitative analysis of SPECT data is useful for classifying clinical stage and comparing cases.

Humans↗

[Analysis of the long-term prognosis for conjunctival malignant melanomas in Japan].

PURPOSE: To investigate the long-term prognosis for primary conjunctival malignant melanomas in Japan. MATERIALS & METHODS: We conducted a survey of 61 cases which had been reported in a 38-year period (1959 to 1996). We gathered information regarding the survival of patients, the post-operative follow-up period, the causes of death, and recurrences. Answers were obtained segarding 51 cases (84%). Detailed progress was identified in 23 of these cases. The survival rates were calculated using the Kaplan-Meier method. RESULTS: The survival rates were 95.1% after 1 year, 72.9% after 3 years, and 53.4% after 5 years. These values are relatively low compared with those reported in Europe and the United States.

Adolescent↗

[A trial of rapid assay of identification and susceptibility test of bacteria detected from blood culture by using VITEK AMS].

For rapid identification and susceptibility test of bacteria detected from bottles of blood culture, we tried a direct method that adjusted bacterial fluid by one time centrifugalization. Identification and susceptibility test were done using VITEK AMS. A result of having compared direct method with a standard method inspected from a colony of medium, an agreement rate was 82.1% of gram negative bacilli, 64.0% of gram positive cocci, 100% of yeast in identification test. In the same way, an agreement rate was 98.0% of gram negative bacilli, 97.2% of gram positive cocci in susceptibility test. The appearance rate of very major error was 0. 7% in gram negative bacilli, and 2.8% in gram positive cocci. As for this method, operation is simple, but it is necessary for confirmed examination in a kind of bacteria. But agreement rate with a standard method is high, direct method is useful to select an appropriate antibiotic until reporting of the last test result of bacteria.

Bacteria↗

[Genetic risk factors for chronic obstructive pulmonary disease (COPD)].

Cigarette smoking has been shown to be a major environmental risk factor predisposing to the development of chronic obstructive pulmonary disease (COPD). However, only 10-20% of cigarette smokers develop COPD, implying undue susceptibility compared with the remainder of the population at large. Studies of families and twins suggest that genetic factors also contribute to development of COPD. We review the genes which have been investigated as potential risk factors for COPD. The fully established genetic risk factor is only alpha 1-antitrypsin deficiency. Polymorphisms for the genes including alpha 1-antichymotrypsin, vitamin D-binding protein, microsomal epoxide hydrolase, cytochrome P450 1A1, Glutathione S-transferase and immunoglobulin A, have also been associated with the development of COPD. Other genetic factors are likely involved but have not yet been identified. Elucidation of additional genetic risk factors may provide useful insights into the pathogenesis of COPD. Potential interactions between the various environmental and genetic risk factors may be important determinants in development of COPD.

Gene Deletion↗

[Analysis of the long-term survived patients with P-N2 non-small cell lung cancer].

We had 308 patients with P-N2 non-small cell lung cancer who were treated with pulmonary resection therapy from June 1975 to March 1994. We analysed 9 patients who could survive for 5 years and more after the operation. All of them were male and the mean age was 61.1 years. Histologically, 2 patients had adenocarcinoma and 7 patients had squamous cell carcinoma. The clinical staging was T2N1M0 in 2 patients, T1N2M0 in one, T2N2M0 in 2, T3N2M0 in 2, and T4N2M0 in 2 patients. The histopathological staging was T1 in one patient, T2 in 4, T3 in 3, and T4 in one patient. Three patients who had absolute non-curative operation (residual carcinoma on bronchial stump in 2 patients and residual mediastinal lymph nodes in one patient) were treated with radiation therapy after having operation. The one level mediastinal lymph node metastasis was found in 7 patients and multi-level one in 2 patients. Four patients out of nine are still alive and free from the cancer and 2 patients died of other unrelated disease. The patient who even have P-N2 non-small cell lung cancer with mediastinal lymph node involvement will live long after curative operation.

Adenocarcinoma↗

[Dynamic generation of diagnostic knowledge from a database of well defined case clinical records].

To promote an evidence-based practice of laboratory medicine, we created a database of 1584 typical case records consisting of 30 common diseases. Cases without therapy or major complication were carefully selected. Characteristic clinical symptoms and signs indicating the severity were recorded together with general laboratory test results. A user-friendly computer system for interpretive laboratory diagnosis was also created. It features (1) automatic graphics for visualizing distributions of laboratory values and/or prevalence of clinical symptoms and signs, (2) simultaneous display of distributions of common test values for any combination of diseases, (3) quick subclassification of cases within a disease group by any clinical characteristic, (4) diagnostic guidance by dynamic calculation of a novel similarity index that represents matching of a given set of signs/values with those of typical cases in the database.

Clinical Laboratory Techniques↗

Alteration by maternal pinealectomy of fetal and neonatal melatonin and dopamine D1 receptor binding in the suprachiasmatic nuclei.

The effects of maternal melatonin on fetal and neonatal melatonin and dopamine D1 receptor systems in the central nervous system, mainly in the suprachiasmatic nuclei (SCN), were investigated after pinealectomy of rats at day 7 of pregnancy. 125I-labelled iodomelatonin injected intravenously into the pregnant rats (at day 21) was transferred in considerable amount into the fetal circulation. In vitro autoradiography data demonstrated an increase in the melatonin binding activity in the fetal (embryonic day 21) and early postnatal SCN (postnatal day 3) caused by maternal pinealectomy. This upregulation of the melatonin receptor in the SCN was then normalized after the melatonin system of the neonate started to work. The pregnant rats themselves did not show such a change in their melatonin receptors in the SCN following pinealectomy. Dopamine D1 receptor binding was affected by pinealectomy exclusively in the SCN of fetal and neonatal rats as well as in that of mothers. These results clearly indicate that the fetal circadian clock in the SCN is controlled and prepared before birth to some extent by maternal melatonin rhythm.

Animals↗

In vitro effects of gonadotropin-releasing hormone (GnRH) analogue on cancer cell sensitivity to cis-platinum.

Six endometrial cancer cell lines (Ishikawa, EIIL, HEC1A, 6, 50 and 59), one breast cancer cell line (MCF-7) and two ovarian cancer cell lines (OVHS-1, HRA) were treated for 24 or 168 h with a gonadotropin-releasing hormone (GnRH) analogue, Buserelin acetate, and the cellular growth profile was studied. All these cell lines except for the HRA line had positive GnRH receptor mRNA expression detected by reverse transcriptase polymerase chain reaction. GnRHa suppressed cell growth after 168 h of exposure, but not after 24 h. Suppression of cell growth by the exposure to cis-platinum (CDDP, 10 nM for 24 h) was significantly increased in the presence of GnRHa for 168 h. The mechanism of this growth inhibition was tested by examining both RNA components of human telomerase (hTR) expression and telomerase activity. The results showed that GnRHa inhibits telomerase activity without altering the RNA component of telomerase expression. The present data suggest that GnRH analogue may modulate endometrial, breast and ovarian cancer cell growth through modifying the telomerase activity. Since GnRHa increased the cytotoxic effects of CDDP and GnRHa is a compound of high patient compliance, the value of GnRHa as a tumor sensitizer to CDDP should be further tested in clinical trials.

Antineoplastic Agents↗

A novel inhibitory effect on prostacyclin synthesis of coupling factor 6 extracted from the heart of spontaneously hypertensive rats.

The possible presence of an unknown prostacyclin synthesis inhibitory substance has been reported in some strains of rats. We purified the inhibitory substance from the heart of spontaneously hypertensive rats by collecting active fractions after gel-filtration column chromatography and two steps of reverse-phase high performance liquid chromatography. The amino acid composition and automated gas-phase sequencing of the full-length substance and fragments cleaved by AspN indicated that the prostacyclin-inhibitory peptide was identical to coupling factor 6. Recombinant rat coupling factor 6, which was synthesized using a cleavable fusion protein strategy, attenuated base-line and bradykinin (10(-6) M)-induced prostacyclin synthesis and [3H]arachidonic acid (AA) release in human umbilical vein endothelial cells in a dose-dependent manner (10(-9)-10(-7) M). Exogenous AA- and prostaglandin H2-induced prostacyclin synthesis were unchanged even after treatment with 10(-7) M recombinant coupling factor 6. Base-line and bradykinin-induced [3H]AA release were suppressed by arachidonyltrifluoromethyl ketone, a relatively specific inhibitor of cytosolic phospholipase A2 at 40 microM, and simultaneous administration of coupling factor 6 showed no further effect. Neither oleyloxyethyl phosphorylcholine at 1 microM nor bromoenol lactone at 1 microM affected AA release. Preincubation (1 min) with 10(-7) M recombinant coupling factor 6 had no influence on adenosine diphosphate- and collagen-induced platelet aggregations. We conclude that coupling factor 6 possesses a novel function of prostacyclin synthesis inhibition in endothelial cells via suppression of Ca2+-dependent cytosolic phospholipase A2, although it is unclear whether coupling factor 6 functions in normal conditions or only in pathophysiological states.

Adenosine Triphosphatases↗

Altered glutathione transferase levels in rat skin inflamed due to contact hypersensitivity: induction of the alpha-class subunit 1.

Since glutathione transferases (GSTs) are suggested to be involved in the prevention of tissue damage by oxidative stress, quantitative and qualitative alterations of GST forms were examined in rat skin after induction of inflammation by 0.6 and 1% 1-chloro-2, 4-dinitrobenzene (CDNB) treatment. With 0.6% CDNB, the GST activity in supernatant preparations was 1.8-fold higher than that for control skin, with most GSTs in both cases being bound to S-hexyl-GSH-Sepharose. Major GST subunits of control skin were identified as subunits 7, 4 and 2 by HPLC and chromatofocusing at pH11-7. These subunits were increased in inflamed skin by 0.6% CDNB and, in addition, the subunit 1 of the Alpha class and subunit 6, both hardly detectable in control skin, were expressed. The specific activity value for GST 7-7 from the inflamed skin by 0.6% CDNB was 2. 4-fold lower than that from control skin. However, in the case of inflamed skin after application of 1% CDNB, GST activity was decreased to 69% of the control value and most activity was recovered in fractions binding to a GSH-Sepharose but not a S-hexyl-GSH-Sepharose column. GSTs eluted from the former column demonstrated a restored capacity to bind to the latter, suggesting the GSTs in inflamed skin to be partly inactivated and that they regained activity on exposure to GSH. The Km and Vmax values for GSH of GST 4-4 from inflamed skin after 1% CDNB treatment were 6-fold and 2-fold higher, respectively, than those for the enzyme from control skin, suggesting partial enzyme modification. These results suggest that not only quantitative but also qualitative alterations of GST subunits occur with CDNB-induced inflammation in vivo.

Animals↗

Loss of chromosome 18q is an early event in pancreatic ductal tumorigenesis.

Cytogenetic and molecular studies demonstrated that pancreatic cancer frequently shows specific chromosomal abnormalities, such as losses of 9p, 17p, and 18q, and gains of 8q and 20q. We have analyzed alterations in the copy number of specific chromosomal regions in cells from the pancreatic juices of 32 patients with various pancreatic disorders by fluorescence in situ hybridization (FISH) technique to pursue the possible clinical use of early diagnosis of pancreatic cancer. None of the chromosomal abnormalities were found in 13 specimens from individuals who had no neoplastic lesions. On the other hand, 12 specimens (63%) derived from the remaining 19 patients who had neoplastic lesions showed at least one chromosomal abnormality. Ten of these specimens were from pancreatic cancer patients; 7 cases (70%) showed chromosomal abnormalities. All but one of the 12 tumors with chromosomal abnormalities had loss of 18q. Furthermore, we detected a tumor in one patient in whom the routine cytological method and endoscopic retrograde chorangiopancreatography found nothing. Based on the results by FISH, we performed endoscopic ultrasonography and found a small serous cystadenoma in this patient. These results indicate that: (a) FISH analysis of cells from pancreatic juices obtained during endoscopic retrograde chorangiopancreatography is quite useful for detecting pancreatic ductal tumors; and (b) loss of chromosome 18q is one of the early genetic changes that provide very useful information in diagnosing pancreatic neoplasias.

Adolescent↗

Frabin, a novel FGD1-related actin filament-binding protein capable of changing cell shape and activating c-Jun N-terminal kinase.

We purified from rat brain a novel F-actin-binding protein with a Mr of about 105,000 (p105), which was estimated by SDS-polyacrylamide gel electrophoresis. We cloned its cDNA from a rat brain cDNA library and characterized it. p105 was a protein of 766 amino acids and showed a calculated Mr of 86,449. p105 consisted of one F-actin-binding domain at the N-terminal region, one Dbl homology domain and one pleckstrin homology domain at the middle region, and one cysteine-rich domain at the C-terminal region. This domain organization of p105 was similar to that of FGD1, which has been determined to be the genetic locus responsible for faciogenital dysplasia or Aarskog-Scott syndrome. We therefore named p105 frabin (FGD1-related F-actin-binding protein). Frabin bound along the sides of F-actin and showed F-actin-cross-linking activity. Overexpression of frabin in Swiss 3T3 cells and COS7 cells induced cell shape change and c-Jun N-terminal kinase activation, respectively, as described for FGD1. Because FGD1 has been shown to serve as a GDP/GTP exchange protein for Cdc42 small G protein, it is likely that frabin is a direct linker between Cdc42 and the actin cytoskeleton.

Actins↗

Competitive inhibition analysis of the enzyme-substrate interaction in the carboxy-terminal processing of the precursor D1 protein of photosystem II reaction center using substituted oligopeptides.

A clear parallelism was demonstrated between the efficiency as substrate of the substituted oligopeptides corresponding to the carboxy-terminal (C-terminal) sequence of the precursor D1 protein (pD1) in the in vitro enzymatic assay and their competitive inhibitory capacity toward the proteolytic C-terminal processing of the full-length pD1 integrated in the intact photosystem II complex embedded in the thylakoid membrane of Scenedesmus obliquus LF-1 mutant, as shown e.g. by the influence of L343A, A345G and A345V substitutions and the effect of C-terminal fragments. This suggests that the basic mechanism for substrate recognition by the processing protease elucidated in the enzymatic analysis using synthetic oligopeptides is also effective in vivo, although it can sometimes be difficult to detect the consequence of amino acid substitution in the integrated systems.

Algal Proteins↗

The role of the left inferior temporal cortex for visual pattern discrimination--a PET study.

We measured regional cerebral blood flow using positron emission tomography in seven normal volunteers during discrimination tasks for visual patterns. For the 'attention to right or left' tasks, the subjects were instructed to press a key when sample and test stimuli presented in the right or left visual fields, respectively, were identical. In the control task, subjects were instructed to press a key on every second presentation of the test stimulus. Both discrimination tasks activated the same area in the inferior temporal sulcus of the left hemisphere. The results indicate that the left inferior temporal cortex plays a dominant role in the discrimination of visual pattern in right handed subjects.

Adult↗

Intramolecular cross-linking of the extrinsic 33-kDa protein leads to loss of oxygen evolution but not its ability of binding to photosystem II and stabilization of the manganese cluster.

The extrinsic 33-kDa protein of photosystem II (PSII) was intramolecularly cross-linked by a zero-length cross-linker, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide. The resulting cross-linked 33-kDa protein rebound to urea/NaCl-washed PSII membranes, which stabilized the binding of manganese as effectively as the untreated 33-kDa protein. In contrast, the oxygen evolution was not restored by binding of the cross-linked protein, indicating that the binding and manganese-stabilizing capabilities of the 33-kDa protein are retained but its reactivating ability is lost by intramolecular cross-linking of the protein. From measurements of CD spectra at high temperatures, the secondary structure of the intramolecularly cross-linked 33-kDa protein was found to be stabilized against heat treatment at temperatures 20 degrees C higher than that of the untreated 33-kDa protein, suggesting that structural flexibility of the 33-kDa protein was much decreased by the intramolecular cross-linking. The rigid structure is possibly responsible for the loss of the reactivating ability of the 33-kDa protein, which implies that binding of the 33-kDa protein to PSII is accompanied by a conformational change essential for the reactivation of oxygen evolution. Peptide mapping, N-terminal sequencing, and mass spectroscopic analysis of protease-digested products of the intramolecularly cross-linked 33-kDa protein revealed that cross-linkings occurred between the amino group of Lys48 and the carboxyl group of Glu246, and between the carboxyl group of Glu10 and the amino group of Lys14. These cross-linked amino acid residues are thus closely associated with each other through electrostatic interactions.

Amino Acid Sequence↗