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Biomedical subjects

K Dobashi

Publications and source records attributed to K Dobashi.

At least 19 recordsLinked to original sources
PubMed1992

Carboxyl-terminal deletion and point mutations decrease the transforming potential of the activated rat neu oncogene product.

The rat neu oncogene encodes a constitutively activated growth factor receptor/transmembrane tyrosine kinase, p185Tneu, that is structurally similar to yet distinct from the epidermal growth factor receptor. To explore the role of the carboxyl-terminal region and of putative autophosphorylation sites in regulating the activity of the rat p185Tneu (T, transforming) protein, we used site-directed mutagenesis to generate a p185Tneu mutant in which a putative tyrosine autophosphorylation site (residue 1253) at the extreme carboxyl terminus was replaced by a phenylalanine residue and a mutant in which the carboxyl-terminal 122 amino acids were deleted. These proteins were expressed in NIH 3T3 cells at comparable levels and exhibited similar autophosphorylation activity, exogenous substrate phosphorylation ability, oligomerization levels, and responsiveness to a partially purified neu-activating factor. However, the mutant p185Tneu proteins displayed a decreased transforming capacity both in vitro and in vivo. This analysis demonstrated that the carboxyl-terminal domain and at least one putative tyrosine autophosphorylation site of p185Tneu play a role in positively regulating the cell growth-regulating properties of the neu protein.

3T3 Cells↗
PubMed1992

Complete excision and panpleuropneumonectomy resulting in long-term survival for a teenager with invasive thymoma: report of a case.

An 18-year-old girl with invasive thymoma and pleural dissemination underwent a complete removal of the tumor with combined resection of the pericardium and a panpleuropneumonectomy of the left lung. At the time of writing, 70 months later, she was doing well under the classification of grade I performance status with no signs of recurrence. Thus, complete surgical removal of this tumor can prolong the survival time of patients with invasive thymoma and pleural dissemination.

Adolescent↗
PubMed1992

Reconstruction of surgical defects using the gluteus maximus myocutaneous flap following radical vulvectomy.

Radical vulvectomy is often complicated by problems associated with insufficient closure of large skin defects involving postoperative necrosis of the suture line over the mons pubis and the inguinal areas. To resolve these problems, the present study compared radical vulvectomy (RV, 7 cases) with radical vulvectomy followed by reconstructive operation using the gluteus maximus myocutaneous flap (RVR, 5 cases). There was no significant difference in operation time and blood loss between the two groups. Three of the 7 RV patients had wound separations requiring reoperation, while only 1 patient in the RVR group did. The average hospital stay was 86 days in the RV group and 38 days in the RVR. Risks of postoperative infection and wound breakdown were reduced with the flap technique, and ambulation and rehabilitation could begin earlier in this group. Surgical wounds were stable and the quality of life after operation was improved dramatically using the flap technique.

Aged↗
PubMed1992

Effect of dexamethasone on antioxidant enzymes in fetal rat lungs and kidneys.

To determine if an enhancement in the fetal antioxidant enzyme (AOE) system by maternal dexamethasone (DEX) is specific to organ and dose, the lung and kidney of pups, whose mother received DEX (0.2 or 2 mg/kg) twice, were obtained on days 19 and 20 of gestation. Low-dose DEX increased the four AOE in the day-19 lung, but not in day-20 lung. High-dose DEX decreased the copper-zinc superoxide dismutase (SOD) and glutathione peroxidase in the lungs. Thus, the DEX-induced maturation of lung AOE is dependent on dose and timing. DEX enhanced the four AOE in the day-19 kidney at both doses. In the day-20 kidney, DEX enhanced the manganese SOD at the low dose and also catalase at the high dose, suggesting that DEX accelerates the maturation of kidney AOE as well.

Animals↗
PubMed1992

Immunohistochemical localization of superoxide dismutases in fetal and neonatal rat tissues.

We investigated the developmental profile of copper-zinc and manganese superoxide dismutase (CuZnSOD and MnSOD) in tissue sections obtained from fetal (Day 12 to 21 of gestation) and neonatal (Day 0 and 6) rats. Tissues were stained immunohistochemically with specific antisera against the respective rat SODs. There was a general trend towards richness of SODs in the epithelial linings and metabolically active sites, although differential distribution between the two SODs also existed. At Day 12 of gestation, immunoreactivity for both SODs was detected in the cardiomyocytes but not in other tissues. Hepatocytes expressed CuZnSOD at Day 14 and MnSOD at Day 17. By Day 18 CuZnSOD was detected in the epithelial cells of the gastrointestinal tract, respiratory tract, pancreatic islets, kidneys, and adrenals. These tissues exhibited MnSOD staining at Day 19. CuZnSOD occurred in the epithelia of the thyroid, thymus, and salivary glands at Day 19, while MnSOD was seen at Day 21. The increase in intensity of the staining for SODs occurred no later than postnatal Day 0, indicating that most tissues accumulated SODs during late gestation. Breathing atmospheric oxygen during early extrauterine life did not appreciably intensify the SOD staining. These results suggest that perinatal increase in SODs occurs as a general mechanism of preparation for birth.

Animals↗
PubMed1992

Evaluation of airway smooth muscle contractions in vitro by high-frequency ultrasonic imaging.

To visualize ASM contraction in vitro, we measured changes in cross-sectional area and inner circumference of isolated porcine and human bronchi in response to acetylcholine or carbamylcholine chloride (Carbachol) using high-frequency ultrasound. A mechanical ultrasonic catheter (20 MHz; diameter, 1.7 mm; echo element, 1 mm2) demonstrated three histologic layers (mucosa, cartilage and adventitia) and allowed measurement of dose-dependent contraction of porcine bronchi over time. Acetylcholine (10(-4)M) significantly decreased the cross-sectional area by 17 +/- 2.85 percent but did not change the circumference. The mean initial value for area was 0.6 +/- 0.08 cm2 and for circumference was 3.0 +/- 0.24 cm (n = 5). The EC50 of acetylcholine was 1.5 x 10(-8) M. Carbachol (10(-4)M)-induced contractions of human bronchi were also observed under the same conditions. In conclusion, high-frequency ultrasonic imaging can be used to study the morphology of ASM contractions in vitro, providing valuable information on the natural dynamics of ASM.

Acetylcholine↗
PubMed1992

[Panpleuropneumonectomy for primary lung cancer patients with pleural dissemination].

Twelve patients of non-small cell lung cancer with carcinomatous pleuritis were subjected to panpleuropneumonectomy between June 1981 and December 1988. The median survival time was 13 months. One-year and 3-year survival rates were 52% and 26%, respectively. There was no significant difference in prognosis compared with the results of other modality therapies such as pleurodesis with talc and tube drainage for pleural effusion. After panpleuropneumonectomy the patients were divided into the group with only pleural dissemination and the one with pleural effusion. The median survival time in the group of pleural dissemination was 14 months. The three-year survival rate was 50%. The one patient survived for 51 months and the other for 45 months. The median survival time of patients with pleural effusion was 4 months without over 1-year survivor. The statistically significant difference was found between the two groups (p less than 0.05). We concluded that panpleuropneumonectomy is indicated only for the patients of non-small cell lung cancer with diffuse pleural dissemination and no pleural effusion.

Adult↗
PubMed1992

[Evaluation of surgical treatment of spontaneous pneumothorax--assessment of postoperative recurrence and quality of life].

To assess the effect of surgical treatment for spontaneous pneumothorax, including the evaluation of the quality of postoperative life by a questionnaire method, we examined 139 patients with spontaneous pneumothorax who underwent the surgical treatment. The operation was performed 149 times and 154 sides for these patients. Of these, 95 cases (65.2%) were the first episode of the disease, since we often chose surgical treatment even for the first attack of the disease. Postoperative recurrence was seen in only one case (0.6%). Operative complications included 4 cases of empyema (in two of them requiring reoperation) and 18 cases of wound infection. The most common postoperative complaints were post-thoracotomy pain in 12 cases (12.6%), disturbance of sensation in the scar in 9 (9.5%), and limitation of exercise in 9 (9.5%). Four patients (4.2%) suffered from these symptoms and had difficulty in daily life. Forty-seven patients (49.5%) had a fear of recurrence. Quality of postoperative life was almost satisfactory. From the viewpoints of both prevention of the recurrence and postoperative quality of life, the surgical treatment is effective and safe method. We advocate the surgical treatment as the first choice of the treatment even in case of the first episode of the disease, especially in patients with high activities in social life.

Adolescent↗
PubMed1991

Characterization of a neu/c-erbB-2 protein-specific activating factor.

The neu oncogene encodes a tyrosine kinase with growth factor receptor-like properties. A neu protein-specific activating factor (NAF) was partially purified from medium conditioned by the transformed human T-cell line ATL-2. NAF was able to stimulate the tyrosine-specific kinase activity of the neu protein (p185neu), induce dimerization and internalization, and increase the growth of cells bearing the neu protein. The effects of NAF were mediated by an interaction with the p185neu extracellular domain. NAF had no effect on the epidermal growth factor receptor kinase activity and no effect on cells that express that receptor. Further analysis of NAF and of other recently described neu protein-activating activities should help clarify the role of the neu protein in cell growth and transformation.

Cell Division↗
PubMed1991

Isolation and characterization of a neu protein-specific activating factor from human ATL-2 cell conditioned medium.

The rat neu gene product is a 185 kD membrane bound tyrosine kinase that is closely related to, yet distinct from the epidermal growth factor receptor. The biochemical and cellular effects of a neu protein-specific activating factor (NAF) detected in human ATL-2 cell conditioned medium were recently described (1). To further characterize NAF, some of its physicochemical properties were examined and a method for purifying this factor from ATL-2 cell conditioned medium was developed. In these studies NAF was found to be heat stable and sensitive to the protease chymotrypsin. In addition, a method for purifying this activity was developed using a quantifiable, in vitro autophosphorylation assay system to measure NAF activity in fractions following ion-exchange and then reverse-phase HPLC.

Cell Line↗
PubMed1991

Interleukin 2 induces tyrosine phosphorylation and activation of p72-74 Raf-1 kinase in a T-cell line.

Interleukin 2 (IL-2) is a lymphokine, produced by T cells upon antigenic or mitogenic stimulation, that is a critical regulator of T-cell proliferation. Although the binding of IL-2 to its receptor has been well characterized, the molecular mechanisms by which IL-2 transmits its signal from the membrane to the interior of the cell are poorly understood. Like most other growth factors, IL-2 causes rapid phosphorylation of proteins within its target cells. Unlike many other growth factors, however, the known subunits of the IL-2 receptor lack tyrosine-specific kinase activity, and little is known about the kinases whose activities are regulated by IL-2. Here we show that IL-2 (but not IL-4) induces rapid phosphorylation of the p72-74 serine/threonine-specific kinase encoded by the c-Raf-1 protooncogene in an IL-2-dependent murine T-cell line, CTLL-2, and that this phosphorylation is associated with increased kinase activity in p72-74 Raf-1-containing immune complexes. The concentration dependence of IL-2-mediated elevations in Raf-1 kinase activity correlated well with IL-2-stimulated proliferation of CTLL-2 cells. Furthermore, much of the IL-2-stimulated phosphorylation of p72-74 Raf-1 occurred on tyrosines. To our knowledge, the Raf-1 kinase represents the first endogenous substrate of an IL-2-regulated tyrosine kinase to be identified.

Amino Acid Sequence↗
PubMed1991

Effect of diabetes mellitus induced by streptozotocin on renal superoxide dismutases in the rat. A radioimmunoassay and immunohistochemical study.

Two forms of superoxide dismutase, CuZn-SOD and MnSOD, have been investigated in the kidneys of streptozotocin-induced diabetic rats using both radio-immunoassay and immunoenzyme staining. The rats were killed 2, 8 and 12 weeks after the induction of diabetes mellitus and the kidneys excised. Two weeks after the induction of diabetes, the kidneys were hypertrophied because of the proliferation of renal tubular epithelium. However, the total CuZnSOD content of the kidneys did not increase and, because of the epithelial proliferation, the CuZnSOD concentration in each proximal tubular cell was decreased. Armanni-Ebstein lesions were found in the distal tubules 8 and 12 weeks after the induction of diabetes. The cells in these lesions were intensely stained for CuZnSOD, suggesting an adaptive response to the enhanced oxidative stress. The MnSOD staining in the thick ascending limbs of Henle's loops was enhanced in the diabetic kidneys, while that in the cortical tubules was unaltered. MnSOD was assumed to increase in response to hypermetabolism associated with the proliferation of renal tubules. This was most marked in the cells which were rich in mitochondria, again suggesting an adaptive response to enhanced oxidative stress induced by diabetes mellitus. The glomeruli of both the diabetic and control groups were not stained for SODs, and no significant microscopic change was found even 12 weeks after the induction of diabetes mellitus.

Animals↗
PubMed1991

Concentration of lipid peroxide in serum lipoproteins of insulin-dependent diabetic children.

Lipids, apolipoproteins and lipid peroxide were measured in the sera of 29 children with insulin-dependent diabetes mellitus. Ten non-diabetic children served as controls. High-density lipoprotein (HDL) was separated by heparin-MnCl2 precipitation. Lipid peroxides in HDL and non-HDL fractions were estimated by fluorimetric measurement of thiobarbituric acid-reactive substances. The patients were normolipidemic, and their HDL-cholesterol was increased. Apo A1 level in the patients was similar to that in the controls, while levels of apo A2 and apo B were decreased in the patients. Concentrations of lipid peroxides in the whole serum and non-HDL were unaltered, while that in the HDL was higher in the patients than in the controls. Hemoglobin AIc in the patients correlated with the triglyceride and urinary excretion rate of N-acetylglucosaminidase (NAG). The NAG correlated with the triglycerides. The triglycerides correlated with the atherogenic index, apo B and total cholesterol. The lipid peroxides in the non HDL correlated with the triglyceride, atherogenic index, and NAG. That in the HDL correlated with the HDL-cholesterol, apo A1 and endogenous creatinine clearance, and inversely with the atherogenic index and apo B. Lipid peroxides in HDL and non-HDL appeared to play different physiological roles from each other, and they have provided evidence suggesting that diabetic microvascular injury is mediated by reactive oxygen species.

Acetylglucosaminidase↗
PubMed1991

Immunohistochemical study on perinatal development of rat superoxide dismutases in lungs and kidneys.

It has been reported that levels of antioxidant enzymes are low in fetal rat lungs and kidneys, and that they increase rapidly during late gestation. Among the antioxidant enzymes, both copper-zinc and manganese superoxide dismutases (CuZnSOD and MnSOD) are assumed to play a key role in protection against oxidative tissue injury. To determine the nature of the rapid perinatal increase in CuZnSOD and MnSOD, immunoenzyme staining was performed in the lungs and kidneys of fetal (d 18 and 20 of gestation) and neonatal (d 22) rats. The CuZnSOD and MnSOD in the homogenates were assayed by RIA, and they were found to be higher in the neonatal organs than in the respective fetal organs. The neonatal bronchiolar epithelium was stained for both CuZnSOD and MnSOD more intensely than the fetal one. The CuZnSOD staining in the neonatal alveolar wall was more intense than that in the fetal one. There was a significant reactivity for MnSOD in the neonatal, but not in the fetal, alveolar walls. In the kidneys, the reactivities for CuZnSOD and MnSOD were confined to the undifferentiated tubules. Although the tubules were increased in numbers in the neonatal kidneys, the intensity of the staining for both CuZnSOD and MnSOD was unchanged. The histochemical study disclosed that CuZnSOD and MnSOD increased in the kidneys in a manner different from that in the lungs. The low concentration of both CuZnSOD and MnSOD in the fetal lung tissues may contribute to the vulnerability to oxygen toxicity. Such changes in the concentrations in specific tissues were not delineated in the kidneys.

Age Factors↗
PubMed1991

[A late phase II study of CPT-11 on uterine cervical cancer and ovarian cancer. Research Groups of CPT-11 in Gynecologic Cancers].

A late phase II study of CPT-11, a new derivative of camptothecin, in uterine cervical cancer and ovarian cancer was carried out by a cooperative study group at 26 institutions. Out of 144 patients enrolled, total cases were 110, involving 55 uterine cervical cancers and 55 ovarian cancers. In uterine cervical cancer, 5 cases of complete response (CR) and 8 cases of partial response (PR) were observed, with a response rate of 23.6% and a CR rate of 9.1%. In ovarian cancer, 13 cases of PR were observed, response rate was 23.6%. Both in uterine cervical cancer and ovarian cancer, the 95% confidence interval of response rate was 12.4-34.8%. In cases having undergone previous chemotherapy including platinum, derivatives, the response rate in ovarian cancer was 23.1% (12/52). In cases of uterine cervical cancer having previous radiotherapy, the response rate was 26.8% (11/41). In ovarian cancer of various histological types, a response was observed for not only serous cystadenocarcinoma but also mucinous cystadenocarcinoma, etc. A response was observed in distant metastatic lesions such as lung metastasis as well as primary lesion in uterine cervical cancer and ovarian cancer. Major adverse reactions were leukopenia, nausea and vomiting, diarrhea and anorexia, and these incidences (grade 2 or more) were 87.3, 60.3, 44.0 and 67.2%, respectively. Since some patients experienced severe adverse reactions, caution should be taken in treatment with CPT-11. Besides these reactions, alopecia was observed (33.1%), but severe adverse reactions such as nephropathy were not found. No significant difference in the efficacy and adverse reactions were observed between administration methods; A, 100 mg/m2 once weekly and B, 150 mg/m2 once every 2 weeks. Both were thought to be clinically useful. These results suggest that CPT-11 is clinically effective against uterine cervical cancer and ovarian cancer.

Adult↗
PubMed1990

Antioxidant enzymes and lipoperoxide in blood in uremic children and adolescents.

To determine whether oxidant-antioxidant balance is altered in chronic renal failure, antioxidant enzymes and lipid peroxide in peripheral blood cells and lipid peroxide in plasma were measured. Nine children and adolescents maintained on hemodialysis (HD), 9 on continuous ambulatory peritoneal dialysis (CAPD), and 14 controls were studied. Lipid peroxide was assayed fluorimetrically as thiobarbituric acid-reactive substances, superoxide dismutases by radioimmunoassays. Both manganese and copper-zinc superoxide dismutases in lymphocytes and monocytes in the HD and CAPD patients, and manganese superoxide dismutase in polymorphs in the HD patients were higher than in the controls. Copper-zinc superoxide dismutase, glutathione peroxidase, and catalase in erythrocytes were unaltered. The lipid peroxide level in plasma in the dialyzed patients was increased, whereas those in polymorphs and lymphocytes were unaltered. Triglyceride and total cholesterol in plasma in the dialyzed patients were also increased. The plasma lipid peroxide in the patients correlated with the triglyceride and total cholesterol level. This is the first study in which manganese superoxide dismutase is measured in nucleated cells of the patients with chronic renal failure. The present results suggest that increased superoxide dismutases protect against oxidative stress induced by chronic renal failure in nucleated cells but in neither erythrocytes nor plasma.

Adolescent↗
PubMed1990

Antioxidant enzymes and lipoperoxide in blood in patients with Kawasaki disease. Comparison with the changes in acute infections.

Increased production of active oxygen species from activated neutrophils is postulated to contribute to endothelial damage in Kawasaki disease, leading to the formation of coronary aneurysms. To determine whether an altered oxidant-antioxidant balance exists in acute phase of Kawasaki disease, antioxidant enzymes in peripheral blood cells and plasma lipid peroxide were measured in patients. The two isoenzymes of intracellular superoxide dismutase were assayed by specific radioimmunoassays. Lipid peroxide in plasma and manganese superoxide dismutase in both polymorphs and lymphocytes were increased in the acute phase of Kawasaki disease. The erythrocyte glutathione peroxidase and catalase were also increased. On the other hand, copper zinc superoxide dismutase in polymorphs, lymphocytes and erythrocytes was unaltered. Acute infections did not appear to modify the levels of either antioxidant enzymes or lipid peroxide in blood. These results suggest that increased oxidative stress in Kawasaki disease evokes a reactive increase in antioxidant enzymes, and that this response in the defense system is related to the reversible nature of the tissue damage in most patients with Kawasaki disease.

Acute Disease↗