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K Okada

Publications and source records attributed to K Okada.

At least 91 records · Page 5Linked to original sources
PubMed2001

Strain is more important than electrostatic interaction in controlling the pKa of the catalytic group in aspartate aminotransferase.

Systematic single and multiple replacement studies have been applied to Escherichia coli aspartate aminotransferase to probe the electrostatic effect of the two substrate-binding arginine residues, Arg292 and Arg386, and the structural effect of the pyridoxal 5'-phosphate-Asn194-Arg386 hydrogen-bond linkage system (PLP-N-R) on the pK(a) value of the Schiff base formed between pyridoxal 5'-phosphate (PLP) and Lys258. The electrostatic effects of the two arginine residues cannot be assessed by simple mutational studies of the residues. PLP-N-R lowers the pK(a) value of the PLP-Lys258 Schiff base by keeping it in the distorted conformation, which is unfavorable for protonation. Mutation of Arg386 eliminates its hydrogen bond with Asn194 and partially disrupts PLP-N-R, thereby relaxing the strain of the Schiff base. On the other hand, mutation of Arg292, the large domain residue that interacts with the small domain residue Asp15, makes the domain opening easier. Because PLP-N-R lies between the two domains, the domain opening increases the strain of the Schiff base. Therefore, the true electrostatic effects of Arg292 and Arg386 could be derived from mutational analysis of the enzyme in which PLP-N-R had been completely disrupted by the Asn194Ala mutation. Through the analyses, we could dissect the electrostatic and structural effects of the arginine mutations on the Schiff base pK(a). The positive charges of the two arginine residues and the PLP-N-R-mediated strain of the Schiff base lower the Schiff base pK(a) by 0.7 and 1.7, respectively. Thus, the electrostatic effect of the arginine residues is not as strong as has historically been thought, and this finding substantiates our recent finding that the imine-pyridine torsion of the Schiff base is the primary determinant (2.8 unit decrease) of the extremely low pK(a) value of the Schiff base [Hayashi, H., Mizuguchi, H., and Kagamiyama, H. (1998) Biochemistry 37, 15076-15085].

Arginine↗
PubMed2001

Kinetics of pro-inflammatory cytokines release in cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: Cytokine induction can occur routinely in cardiac surgery with cardiopulmonary bypass. We have studied the relationships between the kinetics of pro-inflammatory cytokine release and the postoperative organ function. METHODS: Ten adult patients (6 men and 4 women) undergoing elective cardiac surgery with cardiopulmonary bypass, at Hiroshima University Hospital were studied. Patients with acute infection, insulin-dependent diabetes, acute or chronic respiratory failure, renal or hepatic failure, acute cardiogenic shock, and emergency patients were not included. The age of the patient ranged from 44 to 78 years (mean 69 +/- 2.0 years). The type of surgical intervention performed was coronary artery bypass grafting in four patients, mitral valve plasty or replacement with modified maze procedure in another five patients, and both procedures in the other one patient. Plasma cytokine levels until 48 hours after aortic declamping were measured in blood samples. The Respiratory Index and the serum levels of choline esterase and creatinine were also measured. The plasma levels of the pro-inflammatory cytokines (interleukin-6 and interleukin-8) were measured. RESULTS: The highest interleukin-6 levels were significantly correlated with hepatic dysfunction (r = -0.80, p = 0.006) and with renal dysfunction (r = 0.78, p = 0.009). The highest interleukin-8 levels were significantly correlated with respiratory dysfunction (r = 0.86, p = 0.001). CONCLUSION: The highest proinflammatory cytokines levels at 1 hour after aortic declamping were related to damage to postoperative organ functions, involving the lung, kidney and liver.

Adult↗
PubMed2001

A clinicopathologic study of mucinous adenocarcinoma of the stomach.

BACKGROUND: Mucinous adenocarcinoma of the stomach is a rare histologic type of gastric adenocarcinoma and its features are still controversial. We attempted to clarify the clinicopathologic characteristics of this histologic type. METHODS: We reviewed the records of 112 patients with mucinous adenocarcinoma of the stomach (MUC) and 4160 patients with nonmucinous gastric adenocarcinoma (NMUC) for factors including age; sex; tumor location, size, and depth; lymph node metastasis; lymphatic or venous permeation; peritoneal dissemination; liver metastasis; and survival rate. We also investigated the relationship between cancer depth and lymph node metastasis. Statistical analysis included chi 2 and Student's t-tests. Survival rates were calculated by the Kaplan-Meier method and analyzed by the log rank test. RESULTS: MUC was found mostly in younger patients, in the lower part of the stomach and was of larger size, invading to or beyond the muscularis propria, positive for lymph node involvement, and associated with peritoneal dissemination. The overall 5-year survival rate in patients with MUC was lower than that in NMUC patients, because the MUC patients more frequently had advanced stage disease; however, the survival rates in the two groups did not differ significantly. As for the relationship between cancer depth and lymph node involvement, the frequency of lymph node metastasis increased when invasion reached the submucosa in patients with MUC compared with those with NMUC while the frequency of lymph node metastasis increased in the muscularis propria in patients with NMUC compared with those with NMUC. CONCLUSION: MUC was characteristically found in younger patients, at lower sites, at an advanced stage, and with peritoneal dissemination; MUC had a poor prognosis. Lymph node metastasis should be suspected when MUC invades to the submucosa or deeper.

Adenocarcinoma, Mucinous↗
PubMed2001

The effects of organ resection on rat urinary bladder carcinogenesis.

The effect of unilateral nephrectomy, orchiectomy or partial hepatectomy on the growth of chemically induced rat bladder tumors was investigated. Male F344 rats were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) for 5 weeks, and surgical resection of one of these organs was performed 2 weeks after the completion of BBN administration. Histological evaluation of the bladder 24 weeks after the start of the experiment revealed that unilateral nephrectomy and orchiectomy significantly increased the numbers of preneoplastic and neoplastic lesions as compared with the corresponding sham-operated groups. Partial hepatectomy also enhanced tumor growth, although not significantly. Immunohistochemical studies examining the effect of organ resection on normal bladder urothelium showed that BrdU immunostaining of urothelial cells significantly increased 7 days after unilateral nephrectomy or orchiectomy, while BrdU incorporation was minimum after partial hepatectomy or sham operation. C-met expression in the bladder urothelium was evident following unilateral nephrectomy or partial hepatectomy, while increased immunoreactivity of androgen receptor was noted following unilateral orchiectomy. Further study is needed to determine the exact mechanism of the bladder tumor growth-enhancing effect associated with organ restriction.

Animals↗
PubMed2001

Periosteal Ewing's sarcoma: radiological imaging and histological features.

Periosteal Ewing's sarcoma is very rare. In this report, we describe three cases of periosteal Ewing's sarcoma, illustrating the principal clinical, radiographic, and histologic features. The patients were aged 15, 16, and 20 years old, with an average of 17 years. The tumor occurred in the humerus in two and in the femur in one. Plain radiography showed a laminated periosteal reaction with a Codman's triangle over a subperiosteal soft-tissue mass or saucerization. The unusual site of Ewing's sarcoma was clearly visualized by computed tomography (CT) and magnetic resonance imaging (MRI) and confirmed by histological examination. Chemotherapy and/or irradiation was employed before and after wide excision. The patients have survived an average of 6 years after the primary surgery.

Adolescent↗
PubMed2001

Time-dependent expression of intestinal phenotype in signet ring cell carcinomas of the human stomach.

Signet ring cell carcinomas of the stomach are thought to arise from the proper gastric mucosa without intestinal metaplasia. It was recently reported that intestinal phenotypes appear along with tumor progression. In this study, we performed several experiments to reconsider the significance of this intestinalization in the growth of signet ring cell carcinoma. We applied mucin histochemistry with monoclonal antibodies MUC2 (Ccp58) and M1 (45M1), and paradoxical concanavalin A staining for class III mucin [PCS(III)] reaction to 29 intramucosal and 25 deeply invasive carcinomas of this type and correlated the phenotypic expression with the size of the mucosal spread and the depth of tumor invasion. It was found that the larger the size of the mucosal lesion, the more frequently the intestinal phenotypes were demonstrated. There was no significant increase in the expression of the intestinal phenotype as the tumor invaded the deeper part of the mucosa or as the intestinal metaplasia increased in the background mucosa. The intestinal expression appeared to be suppressed in the earlier phase of deep invasion. In the mucosal part of the tumor, the intestinal phenotype was often expressed regionally and incompletely, coexisting with gastric phenotypes at the cellular and the tissue levels. These findings indicate that the expression of the intestinal phenotype is a time-dependent and unstable phenomenon probably based on the accumulation of genetic changes and plays a neutral role in progression of signet ring cell carcinomas.

Adult↗
PubMed2001

Hepatocellular carcinoma with a sarcomatous appearance: report of a case.

A 59-year-old man was admitted with general fatigue, an epigastric mass, and remittent fever. Radiological examinations disclosed a huge solid-to-cystic mass in the right lobe of the liver, and the mass severely compressed the right diaphragm, the inferior vena cava, and the right atrium. In addition, the patient suffered from chronic hepatitis; however, the serum alpha-fetoprotein, carcinoembryonic antigen, and PIVKA II levels were all within the normal ranges. The serum C-reactive protein level was 7.71mg/dl. With a clinical diagnosis of a malignant hepatic tumor invading the right diaphragm, surgery was performed. The tumor originated from segments IV and VII of the liver, was well defined, and grew extrahepatically. The tumor was resected using an ultrasonic cavitational aspirator together with the infiltrated right diaphragm. The resected tumor measured 23 x 13 x 23cm in size and weighed 3,700 g. Histologically, the tumor was found to consist of hepatocellular carcinomatous component and sarcomatous component. In the sarcomatous component, spindle-shaped cells which were positive for the immunohistochemical localization of vimentin, alpha-smooth muscle actin, and keratin were identified. The postoperative course was uneventful. The value of the serum C-reactive protein returned to within the normal range, and the patient became afebrile. The patient received a postoperative combination chemotherapy (etoposide, epirubicin, and cisplatin), and remains well with no signs of recurrence 12 months after the operation.

Carcinoma, Hepatocellular↗
PubMed2001

Morphometric analysis, at electron microscope level, combined with hormone assay of nonfunctioning adrenocortical adenomas: comparison with aldosterone-producing adenomas.

We performed electron microscopic studies of eight nonfunctioning adrenocortical adenomas (NFA) and nine aldosterone-producing adenomas (APA) obtained from surgical specimens. A comparison of these two types of adenomas was conducted by morphometric analysis of random electron micrographs. The organelles measured included mitochondria (M), smooth-surfaced endoplasmic reticulum (SER), rough-surfaced endoplasmic reticulum (RER), lipid vacuoles (LV), and lysosomes (Ly). The content of steroid hormones, including 17-alpha hydroxyprogesterone (17-OHP), aldosterone (Ald), and other steroid hormones, was measured in adenoma tissue from six NFA and eight APA. The percentages of the areas of the organelles M, SER, and RER per total cell area in the NFA were significantly lower than those in the APA. The average content of Ald in adenoma tissues in APA was markedly higher than that in the NFA, while the mean content of 17-OHP in the NFA was significantly higher than that in APA. In conclusion, NFA are morphometrically characterized by a reduction in organelles such as M, SER, and RER, compared with findings in APA. From the quantitative analysis of steroid hormones, it was suggested that NFA produce more precursor substances with less hormone activity than APA and that steroidgenesis in NFA is shifted to a glucocorticoid pathway, as indicated by the elevated 17-OHP concentration.

Adenoma↗
PubMed2001

Clinical implication of orbital ultrasound monitoring during selective cerebral perfusion.

BACKGROUND: We evaluated clinical relevance of orbital ultrasound (OUS) monitoring to neurological events in aortic surgery associated with selective cerebral perfusion (SCP). METHODS: In 24 consecutive cases, blood flow was monitored at central retinal artery (CRA) and retrobulbar vessels. The threshold perfusion pressure for detecting CRA flow in the color Doppler mode (BPt) was determined in individual eyes. RESULTS: The BPt ranged from 25 to 71 mm Hg. Events (infarction, anisocoria, delirium) occurred in 8 cases. Infarction occurred in all 3 cases when retrobulbar flow was severely impaired for 40 minutes or longer, while none of the remaining 21 cases had infarction (p = 0.0005). Among the latter cases, perfusion pressure was below BPt for longer than 100 minutes in all 5 cases with events, and in 5 of 16 cases without events (p = 0.0124). No significant difference was found in age, duration of cardiopulmonary bypass, SCP, and circulatory arrest, and duration of blood pressure below 50 mm Hg. CONCLUSIONS: Sustained hypoperfusion detected with OUS monitoring is related to an occurrence of neurological events.

Aged↗
PubMed2001

Cardiac papillary fibroelastoma on the pulmonary valve: a rare cardiac tumor. okaken@mcai.med.hiroshima-u.ac.jp.

We report the case of a patient with a rare papillary fibroelastoma on the pulmonary valve visualized before surgical intervention. The tumor was an encapsulated, rounded mass. The gelatinous membrane on the surface tore easily, and multiple fronds appeared. This case emphasizes that when there is an encapsulated mass attached to a valve, the initial excision of valve tissue should be as minimal as possible. To avoid unnecessary injury to the valve, it is simple and practical to confirm that the tumor has the appearance of a sea anemone, thus identifying it as a papillary fibroblastoma, a benign tumor.

Aged↗
PubMed2001

Efficacy of pulmonary vein isolation for the elimination of chronic atrial fibrillation in cardiac valvular surgery.

BACKGROUND: Haissaguerre and colleagues emphasize the importance of the pulmonary veins as a source of ectopic foci for initiating paroxysmal atrial fibrillation (AF). We hypothesized that ectopic foci from the pulmonary veins could also act as drivers for maintaining chronic AF, and that surgical ablation of the pulmonary vein orifices could terminate chronic AF. METHODS: Using a computerized 48-channel mapping system, we performed intraoperative atrial mapping in 12 patients with chronic AF associated with mitral valve disease. Patient age ranged from 24 to 82 years (mean, 60.4 years). AF duration ranged from 3 to 240 months (mean, 92+/-84 months). Simple surgical isolation of the pulmonary vein orifices was performed during the mitral valve operation. RESULTS: Regular and repetitive activation was found in the left atria of 9 out of 12 patients, and irregular and chaotic activation was found in both atria of 3 out of 12 patients. Chronic AF in the 9 patients (75%) with regular and repetitive activation of their left atria was successfully treated by a simple surgical isolation of the pulmonary vein orifices. The other 3 patients did not recover sinus rhythm after this procedure. In 1 case of recurrent AF, the patient recovered sinus rhythm during the follow-up period (AF-free rate, 83%). CONCLUSIONS: Surgical ablation of the pulmonary vein orifices was effective in the treatment of chronic AF associated with mitral valve disease. Intraoperative mapping may be useful in predicting the efficacy of a single pulmonary vein orifice isolation procedure.

Adult↗
PubMed2001

Immunohistochemical localization of platelet-derived endothelial cell growth factor expression and its relation to angiogenesis in prostate.

OBJECTIVES: Tumor angiogenesis has been reported as a predictor for prognosis in patients with prostate cancer. The aim of this study was to determine the localization of one angiogenic factor, platelet-derived endothelial cell growth factor (PD-ECGF), in benign and malignant prostatic tissues and the correlation between PD-ECGF expression and microvessel density (MVD) in prostate cancer. METHODS: Forty cases of prostate cancer, 3 cases of benign prostatic hyperplasia, and 5 young autopsy cases without prostatic disease were processed with immunohistochemistry, using an anti-PD-ECGF antibody and anti-factor VIII-related antigen antibody. The PD-ECGF expression intensity and MVD were evaluated in each case. RESULTS: In the 40 cases with prostate cancer, the expression of PD-ECGF was noted in the stromal cells within cancer tissues in 80% of cases. Additionally, noncancerous glands next to cancer lesions were positive for PD-ECGF in 85% of cases. However, cancer cells were negative for PD-ECGF in all cases. In the 8 cases without cancer, both the prostatic glands and their surrounding stroma were positive for PD-ECGF only when they were accompanied by inflammation. There was a significant positive correlation (r = 0.636, P <0.001) between the intensity of PD-ECGF expression and MVD. MVD was significantly different when comparing the intensity of PD-ECGF expression of grade 0 versus grade 1 (P <0.05), grade 1 versus grade 2 (P <0.05), and grade 0 versus grade 2 (P <0.01). CONCLUSIONS: This study suggested that PD-ECGF expression in the stromal cells within cancer tissues might play an important role in tumor angiogenesis in prostate cancer.

Aged↗
PubMed2001

Prognostic value of nuclear area index in combination with the World Health Organization grading system for patients with renal cell carcinoma.

OBJECTIVES: To assess the diagnostic accuracy of the World Health Organization (WHO) grading system for renal cell carcinoma (RCC) in terms of nuclear size evaluation. Furthermore, the prognostic usefulness of the nuclear area index (NAI), a new nuclear morphometric parameter expressed as the mean nuclear area (MNA) ratio of cancer to normal tubular cells, is investigated. METHODS: Measurement of the nuclear areas of cancer and normal tubular cells was performed on the histologic slides from the 76 patients with RCC, and the distribution of MNA and NAI was compared among the WHO grades. The clinical usefulness of MNA, NAI, grade, and TNM categories for the prediction of the progression-free and cause-specific survival of the patients was examined. RESULTS: MNA for cancer cells and NAI significantly increased according to the grade. NAI was 1.0 or less in 9 of the 10 patients with G1 tumors and more than 1.0 in 12 of the 13 patients with G3 tumors, whereas the NAI ranged widely from 0.53 to 2.0 in 53 patients with G2 tumors. By multivariate analysis, including grade and TNM categories, NAI and MNA were independent variables for survival in all the patients as well as for cancer progression in localized disease. CONCLUSIONS: WHO G2 RCCs are actually composed of tumors with varying nuclear size, and the prognosis of the patients with G2 tumors varied as well. NAI could provide improved prognostic information for the patients with RCC, especially in G2 cases.

Adult↗
PubMed2001

Pelvic venoablation with ethanol for the treatment of erectile dysfunction due to veno-occlusive dysfunction.

OBJECTIVES: To perform pelvic venoablation with ethanol injection into the deep dorsal vein for the treatment of 10 patients with venogenic erectile dysfunction. This procedure was easily performed without any selective embolization technique. The efficacy and safety of this technique are discussed. METHODS: A total of 10 patients with veno-occlusive dysfunction, severe enough to make vaginal insertion impossible, underwent pelvic venoablation with ethanol. The mean patient age was 67.1 years. Under spinal anesthesia, after the venous leaks were identified by cavernosography, a 20-gauge flexible needle was inserted into the deep dorsal vein. The pelvic venogram obtained with deep dorsal venography was included in what was revealed by the venogram obtained with cavernosography. A mixture of absolute ethanol and contrast medium (4:1) was used as a sclerosing agent. Under fluoroscopic control, the sclerosing agents were injected into the deep dorsal vein through a flexible needle. Success was defined as the ability to achieve vaginal insertion without the aid of any drugs, vasoactive injections, penile prosthesis, or vacuum device. RESULTS: The follow-up ranged from 25 to 37 months (mean 32.3). At the short-term follow-up visit (less than 6 months), 7 patients (70%) reported erections sufficient for vaginal insertion; at the long-term follow-up visit, 5 men (50%) reported sustained, sufficient potency and 5 (50%) reported persistent erectile dysfunction. No serious complications occurred. CONCLUSIONS: Our pelvic venoablation technique using ethanol was effective, minimally invasive, and cost-effective.

Aged↗
PubMed2001

Surface hardness change of restorative filling materials stored in saliva.

OBJECTIVES: This study was to investigate the effect of saliva used as storage liquid and the length of storage effect on surface hardnesses of Fuji IX (GP) (FIX), Dyract (DR), Z-100 and Estio LC (ELC). METHODS: The materials were mixed according to the manufacturers' instructions and immersed in distilled water or human parotid saliva. Vickers hardness number (HVN) was measured 1, 7, 20 and 40 days after the materials were mixed. HVN was calculated from the indentation diameter after 100 or 300g loading on their surface for 15s. The two methods of characterization used in this work were X-ray photoelectron spectroscopy (XPS) for surface chemical composition and electron probe microanalysis (EPMA) for depth profile analysis. RESULTS: Only in FIX, did HVN increase with time at both storage conditions, distilled water and saliva. The increase rate of the value was higher when stored in saliva than distilled water. After 40 days storage in saliva, the HVN value of FIX increased by 39%. The increase for storage in saliva for DR was 22%, ELC 16%, and Z100 3%, compared to 1 day storage in distilled water. Ca and P peaks caused by saliva were detected by XPS and EPMA analysis, but these peaks did not exist in either composite resin or polyacid-modified composite resin by EPMA analysis. SIGNIFICANCE: Saliva has the remarkable effect of increasing surface hardness of Fuji IX (GP).

Compomers↗
PubMed2001

Phase I trial of weekly docetaxel combined with cisplatin in patients with non-small cell lung cancer.

The phase I study was conducted to evaluate the maximum tolerated dose (MTD) and toxicity of weekly administered docetaxel combined with cisplatin in patients with non-small-cell lung cancer (NSCLC). In a dose escalation study, 22 patients, under 75 years old, with unresectable and metastatic untreated NSCLC with performance status (0-1) were enrolled. Patients were treated with cisplatin (day 1) and weekly docetaxel (days 1, 8, 15). Dose escalation levels in mg/m(2) were for cisplatin and docetaxel; 70 and 15 (level 1), 80 and 15 (level 2), 80 and 20 (level 3), 80 and 25 (level 4), 80 and 30 (level 5), respectively. Chemotherapy was repeated for at least two cycles every 28 days. All patients were assessable for toxicities. Although grade 3 neutropenia occurred in one case in level 4, there were no significant modifications of chemotherapy schedule until level 4. Grade 3 neutropenia occurred in all cases receiving level 5. One patient developed an infection, and two had incomplete recovery of neutropenia by the 28th day after the first cycle of chemotherapy. Nonhematological toxicities, including nephrotoxicity, nausea/vomiting, alopecia and hypersensitivity reaction, were tolerable. However, one case developed severe hyponatremia. Among 21 patients evaluable for response, eight cases achieved partial response, thus the overall response was 39%. Weekly administration of docetaxel at 25 mg/m(2) (days 1, 8, 15) combined with cisplatin 80 mg/m(2) (day 1) is recommended for phase II studies. The responses observed in the present study suggest an identical high degree of activity against NSCLC with less hematotoxicity compared with a standard schedule of cisplatin and docetaxel.

Adult↗
PubMed2001

Endovascular stent-grafting via the aortic arch for distal aortic arch aneurysm: an alternative to endovascular stent-grafting.

OBJECTIVE: We have experienced transaortic stent-grafting for treating distal arch aneurysm or type B dissection. This paper is to mainly report the surgical aspect of these procedures. METHODS: Fifteen patients underwent this surgery, including 12 men and three women ranging from 47 to 83 years. Twelve had aneurysms and three aortic dissection. Concomitant surgery was necessary in seven patients (coronary artery bypass grafting in five, tricuspid annuloplasty in one, and replacement of ascending aorta and/or total arch replacement in three cases). A stent graft (Gianturco Z-stent and Intervascular prosthesis) was loaded in a 30-F sheath catheter. Under circulatory arrest, selective cerebral perfusion was established, and the sheath catheter was inserted through aortotomy into descending aorta and the stent graft was deployed at an appropriate level. The proximal end of graft was sutured to the aorta just distal to the left subclavian artery with inclusion method at the posterior wall. Concomitant surgery was done during cooling or rewarming period. TEE was utilized to visualize every endovascular manipulation to avoid unintended intimal injury or misplacement of graft and to assess the surgical results in the operative theater. RESULTS: Aneurysm was successfully excluded except in one patient who had a proximal endoleak and distal endoleak due to underestimation of aortic diameter. There was one operative mortality caused by cerebral infarction, possibly due to debris from femoral arterial cannulation. In the remaining patients, there was no enlargement of residual aneurysm. The excluded aneurysmal sac gradually regressed and disappeared within 2 years in five patients and the thrombosed false lumen completely shrunk within 1 year in two patients. One patient had paraplegia, possibly because the graft was intentionally advanced deeply to cover the thick and fragile atheromatous layer in order to avoid destruction of the atheroma by an expanded graft. CONCLUSIONS: Endovascular stent graft via the aortic arch is an acceptable treatment for distal arch aneurysms close to or involving left subclavian artery or type B dissections, especially for those cases requiring other cardiac procedures. It can lead to regression and disappearance of aneurysm or dissection in the mid-term follow-up.

Aged↗