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Biomedical subjects

K Tsuruta

Publications and source records attributed to K Tsuruta.

At least 37 records · Page 2Linked to original sources

The present mercury contents of scalp hair and clinical symptoms in inhabitants of the Minamata area.

A total of 191 fishermen and their family (32-82 years) living in some mercury-polluted areas along the Shiranui Sea volunteered for the present study. They made a living by fishery and had formerly eaten the methyl mercury-contaminated fish and shellfish caught there. The questionnaire on subjective symptoms, fish eating habits, and past living history was conducted on the subjects. In addition, they were clinically examined in detail by several neurologists and scalp hair was collected. With six exceptions, all the 185 subjects showed a normal total mercury level in hair (<10 ppm). The ratio of methyl mercury to total mercury was 79-94% on the average for each group examined, suggesting indirect contamination (perhaps through the food chain). Despite their low mercury level in scalp hair, however, the subjects showed various neurological symptoms, particularly, sensory disturbance (such as the glove and stocking type), at a very high rate. Thus, it seems fair to state that, in addition to officially recognized Minamata disease patients, there still exist many people with atypical, slight Minamata disease on the coast of the Shiranui Sea. The current hair mercury level is not necessarily useful as a criterion for diagnosing chronic Minamata disease because of the long lapse of time.

Adult↗

Characteristics of pancreatic carcinoma in the elderly.

CONCLUSION: Lymphogenous as well as hematogenous metastases were significantly less frequent in the elderly group of patients, although local invasion was comparable. Survival was comparable between both groups although palliative therapy alone was significantly more frequent in the elderly. BACKGROUND: The relative and absolute numbers of elderly patients continue to increase, as does the incidence of pancreatic carcinoma. To determine the optimal therapy for elderly patients with pancreatic carcinoma, we examined their clinicopathological features. METHODS: The clinical and histopathological features of pancreatic carcinoma in patients 70 yr of age or older (n = 89) were compared with those in patients aged 69 yr or less (n = 184). RESULTS: A total of 273 patients showed histologically tubular adenocarcinomas and their major variants. The male:female ratio peaked at 1:0.3 in patients under 49 yr old but gradually decreased to 1:1.2 in those aged over 80 yr. There were no significant differences between the two groups in the resectability, prognosis, location, or histology of the tumor. Hematogenous and lymphogenous metastases were detected at autopsy in 68 and 61% of patients old than 70, and in 82 and 80% of the younger group.

Adenocarcinoma↗

Fungal P450nor: expression in Escherichia coli and site-directed mutageneses at the putative distal region.

P450nor, nitric oxide reductase from Fusarium oxysporum, was expressed in the soluble fraction of Escherichia coli cells by modifying the N-terminal codons and utilizing the pCW vector. The modified P450nor purified to electrophoretic homogeneity had spectral and enzymatic properties identical to those of native P450nor obtained from the fungi. Residues 239 to 247 of the modified P450nor were replaced with Lys by site-directed mutagenesis. Thr-243 to His- and Arg-mutants were also created. Among 11 mutants, only the Thr-243 to Lys-mutant exhibited an absorption spectrum characteristic of a nitrogenous ligand-bound form of P450 at pH 8.0 in the ferric state, but the spectrum was altered to that of the wild-type P450nor as the pH was lowered. Other mutants had spectra typical of the low- and high-spin mixed form of P450 in the ferric state. In the ferrous state, all mutants showed the same spectrum as the wild-type P450nor. Nitric oxide reductase activity was considerably decreased by the replacement of Thr-243 with Lys, His, or Arg or Ala-239 with Lys. These findings indicate that Thr-243 is located more closely to the heme iron than other residues in the putative distal helix of P450nor and plays an important role in the catalytic activity, but a specific difference in the structure of the heme pocket from other P450s is suggested.

Amino Acid Sequence↗

Serum levels of soluble Fas/APO-1 receptor in human retroviral infection and associated diseases.

Fas/APO-1 mediates apoptosis via Fas and Fas ligand transduction. Recently, a soluble form of Fas (sFas) was described which seems to be functionally implicated in the Fas signal system, suggesting a relationship between some disorders and sFas function. We measured sFas-levels in sera from normal controls and patients with disorders linked to human retroviral infection of human immunodeficiency virus (HIV) and human T-cell leukemia virus type-1 (HTLV-1). The sFas level of normal controls. HTLV-1 carriers seronegative for HIV, and patients with HTLV-1 associated myelopathy/tropical paraparesis (HAM/TSP), adult T-cell leukemia (ATL), and AIDS was 1.62 +/- 0.49, 1.90 +/- 0.49, 2.00 +/- 0.59, 3.32 +/- 2.05, and 3.06 +/- 0.92 ng/ml, respectively. Although the level of sFas in patient groups with HAM/TSP, ATL, and AIDS was significantly high in comparison to that of normal controls (p < 0.01), the individual values were highly variable within the groups. The sFas level was statistically correlated to the soluble interleukin-2 receptor (sIL-2R) level, as well as to cells expressing membrane Fas (mFas), indicating the same cellular origin. In some ATL cases, however, serum sFas levels and mFas expression density on leukemic T-cells were discrepant, with especially high levels of the soluble form and a lack of expression of the membrane form observed in 2 cases, sFas detection could serve as a putative marker for active diseases in patients with ATL and AIDS.

Acquired Immunodeficiency Syndrome↗

Neuroendocrine differentiation in pancreatic duct carcinoma special emphasis on duct-endocrine cell carcinoma of the pancreas.

To evaluate the significance of neuroendocrine differentiation in duct carcinoma of the pancreas, we investigated 79 pancreatic carcinomas, applying histochemistry and immunohistochemistry (chromogranin A, Leu-7, synaptophysin and neuron-specific enolase (NSE), and correlated the morphologic differentiation pattern with clinicopathological characteristics. There were two types of neuroendocrine differentiation: scattered (n = 23) and diffuse (n = 3). The scattered type of pancreatic duct carcinoma contained scattered endocrine cells amounting to less than 10% of the neoplastic cells and was seen more frequently in well-differentiated carcinomas. There was no characteristic clinical feature found in the scattered type when compared with the tumors devoid of endocrine cells (n = 53). In contrast, the diffuse type showed diffuse immunostaining with NSE and synaptophysin in tumor cells and dense core granules ultrastructurally. These tumors showed a greater hypervascularity in angiography (p < 0.01) and the patients had relatively longer survival (33.3 months, p < 0.05) than unresectable cases of other histological types of pancreatic cancer. Two types of neuroendocrine differentiation (scattered and diffuse) existed in pancreatic ductal carcinoma. The diffuse type (Duct-Endocrine Cell Carcinoma of the Pancreas) showed synchronous duct and endocrine differentiation and particular clinical features.

Adenocarcinoma↗

Effect of purified eicosapentaenoate ethyl ester on fibrinolytic capacity in patients with stable coronary artery disease and lower extremity ischaemia.

BACKGROUND: Lower extremity ischaemia is often complicated by coronary artery disease (CAD). Patients with CAD often have impaired fibrinolytic capacity. Plasma plasminogen activator inhibitors (PAI) levels are known to be associated with levels of atherogenic lipids. Purified eicosapentaenoic acid reduces atherogenic lipid levels. OBJECTIVE: To examine the effect of purified eicosapentaenoic acid ethyl ester (EPA) on the fibrinolytic capacity in patients with stable CAD and arteriosclerosis obliterans (ASO). METHODS: Plasma levels of PAl activity and tissue-type plasminogen activator (t-PA) antigen were measured. We administered 1800 mg/day EPA for 8 weeks to 25 patients. RESULTS: Mean baseline plasma PAI activity (P < 0.01) and t-PA antigen (P < 0.01) levels were higher in the patient group than they were in the control group. At the conclusion of EPA administration, significant reductions in PAI activity (P < 0.01), t-PA antigen (P < 0.01) and serum levels of triglyceride (P < 0.01), total (P < 0.05) and low-density lipoprotein (P < 0.05) cholesterols were observed. Changes in PAI activity levels caused by EPA administration showed positive linear correlations with those in low-density lipoprotein cholesterol (r = 0.411, P < 0.05) and triglyceride (r = 0.652, P < 0.01). CONCLUSION: These findings indicate that the fibrinolytic capacity in patients with CAD and ASO is decreased by increased PAI activity, but that EPA may correct this fibrinolytic impairment by decreasing PAI activity via its inhibitory effect on atherogenic lipids.

Administration, Oral↗

Concentrations of vascular endothelial growth factor in the sera of normal controls and cancer patients.

Vascular endothelial growth factor (VEGF) is known to play crucial roles in tumor angiogenesis. We have investigated the circulating level of VEGF in sera from cancer patients as well as from healthy normal controls using a sensitive enzymatic immunoassay. Immunoreactive VEGF proteins were detectable in normal sera, and the cutoff level was determined to be 180 pg/ml. In examined patients with all types of cancer, including breast, gastrointestinal, hepatobiliary, and lung cancer, an aberrant increase in the circulating level of VEGF was detected. For example, in 137 primary breast cancer patients, 12 (8.8%) showed an aberrant increase in VEGF levels. This aberrant expression of VEGF in sera was significantly associated with the progression of the disease, and with VEGF protein expression in tumor tissues. In addition, a Western blot analysis confirmed the presence of the VEGF165 form in sera from a patient with recurrent breast cancer. It was concluded that VEGF was detectable in normal sera, and its level was increased in some populations of cancer patients. A positive angiogenesis regulator, VEGF might function as an endocrine growth factor, particularly for solid tumors.

Adult↗

Expansion of methylmercury poisoning outside of Minamata: an epidemiological study on chronic methylmercury poisoning outside of Minamata.

The first methylmercury poisoning by consumption of fish arose in Minamata, Japan, in 1953. Methylmercury dispersed from Minamata to the Shiranui Sea until 1968. Mercury concentration in the hair of residents on the coast of the Shiranui Sea was 10 to 20 times higher than that in nonpolluted people in Kumamoto Prefecture in 1960. People on the coast of the Shiranui Sea have consumed fish containing low-dose methylmercury without a ban over decades until 1968. We studied the effect of long-term consumption of methylmercury on those people 10 years later after the end of methylmercury dispersion. Our epidemiological study clarified that people in a fishing village (Ooura) on the coast of the Shiranui Sea showed a significantly higher frequency of neurological signs characteristic of methylmercury poisoning (hypoesthesia, ataxia, impairment of hearing, visual change, and dysarthria) in comparison with people in a nonpolluted fishing village (Ichiburi). The neurological disorders were still detected 10 years later in Ooura after the end of methylmercury dispersion from Minamata; hypoesthesia showed the highest frequency in Ooura. These results suggest that people on the coast of the Shiranui Sea were afected by long-term dietary exposure to methylmercury.

Adult↗

A case of pleomorphic carcinoma of the pancreas showing sequential histological change by immunohistochemical study.

Pleomorphic carcinoma of the pancreas is a rare, histologically characterized pancreatic tumor with a rapid and fatal course. We report a case of a resected pleomorphic carcinoma located in the body of the pancreas in a 61-yr-old male. Histological analysis of the resected specimen revealed the coexistence of pleomorphic carcinoma with adenocarcinoma, but the recurrent tumors at autopsy 20 mo later were only of the adenocarcinomatous type. Cells in the adenocarcinomatous component showed a diffuse reactivity for CA19-9, CEA, and cytokeratin, and a focal reactivity for vimentin. In contrast, vimentin was diffusely expressed in pleomorphic lesion. Adenocarcinoma at autopsy expressed CA19-9, CEA, and cytokeratin, but not vimentin. These findings suggest that the recurrent adenocarcinoma may have developed as a consequence of sequential change in the nature of the tumor.

CA-19-9 Antigen↗

The roles played by the D2 and D3 domains of recombinant human thrombomodulin in its function.

Thrombomodulin (TM) is composed of five domains. We investigated the roles of the sixth epidermal growth factor (EGF)-like structure (E6) in the second domain (D2) and of an O-glycosylation site rich domain (D3) in the function of TM in more detail using deletion analysis. Two soluble mutants of TM, TMD123 and TMD12, and three deletion mutants lacking respectively 6, 16, and 38 C-terminal residues of the E6 portion, TMD12 delta 6, TMD12 delta 16, and TMD12 delta 38, were expressed in COS cells and purified. The results of protein C-activating cofactor assay showed that TMD12 delta 6, TMD12 delta 16, and TMD12 delta 38, which lack the C-terminal region, had remarkably weak cofactor activities in comparison with TMD123 (9.1, 1.4, and 1.1% of TMD123 activity, respectively). Similar findings were obtained for anticoagulant activity. These findings indicate that the last loop structure in E6 is required for full activity of recombinant human TM. We also determined in vivo stabilities of TMD12, TMD123, and TMD12 delta 6 in a pharmacokinetic study in rats. TMD12 and TMD12 delta 6, which lack the D3 domain, exhibited increased clearance (about twice that of D123). This finding suggested that the D3 domain of TM plays an important role in stabilizing TM in vivo.

Anticoagulants↗

Hematogenous metastases of pancreatic ductal carcinoma.

To investigate the heterogeneity of hematogenous metastases of pancreatic ductal carcinoma, we investigated carcinomatous spread in 130 autopsy cases. Hepatic metastases occurred most frequently, in 81 cases (62%), which may be explained by the fact that all veins draining the pancreas flow into the portal system. We closely examined the 49 cases without hepatic metastases. Sixteen patients had pulmonary metastases without hepatic metastases, whereas seven had peculiar hematogenous metastases without hepatic or pulmonary metastases. Fifteen of these 23 patients had pancreatic body carcinomas. The unusual patterns of spread might be due to (a) hepatofugal portosystemic shunting induced by splenic vein obstruction, (b) retrograde lymphatic infiltration from metastatic tracheobronchial lymph nodes, or (c) aggressive characteristics of the tumors indicated by peculiar histologic features such as pleomorphic or mucoepidermoid carcinoma, etc. Sixteen patients showed only lymph node metastases and 10 had no distant metastases. Seventeen of these 26 cases had pancreatic head carcinoma. Histologically, two patients had mucinous cystadenocarcinomas, and six had adenocarcinomas producing rich mucin. The average age of the group with no distant metastases was higher.

Aged↗

[Phenotypical diagnosis of Japanese chronic lymphocytic leukemia--an international cooperative study based on the French-American-British classification of mature B-cell leukemias].

To better understand the accuracy in the diagnosis of chronic lymphocytic leukemia (CLL) and characterize the clinical features of CLL in Japan, where the disease is extremely rare, an international cooperative study was conducted by hematologists between Japan and UK. Blood and bone marrow films from 36 patients with a possible-diagnosis of CLL were referred to two laboratories of Nagasaki University Hospital (Nagasaki) and Royal Marsden Hospital (London). According to the FAB criteria, typical CLL 16 and CLL/PL 2, a subtype of atypical CLL, were completely accordant in diagnosis. However, phenotypical diagnosis of CLL mixed, the other of atypical CLL, and intermediate lymphocytic leukemia (ILL) in leukemic phase often gave inconsistent results. Especially, 8 cases of atypical CLL designated as likely CLL were equivocal between CLL and ILL, suggesting clinical feature more close to typical CLL than ILL. This indicates the presence of a relatively high incidence of atypical CLL in Japan which dose not exactly fit with the FAB Criteria. Finally, we would like to emphasize that an international cooperative study allows improvement of accuracy in diagnosis and better understanding of the disease entity of lymphoid malignancies, having on ethnically different morbidity.

Aged↗

Meningioma associated with intratumoral abscess formation--case report.

A rare case of meningioma associated with intratumoral abscess formation occurred in a 64-year-old female presenting with septic meningitis and a right frontal mass lesion after a gynecological operation under spinal anesthesia. The mass lesion was totally removed and revealed as an incidental meningioma with an intratumoral abscess. Hematogenous infection of Bacteroides oralis was thought to be the cause of the intratumoral abscess formation.

Brain↗

[A case of polycystic kidney associated with new growth of cerebral aneurysm after aneurysmal operation].

We have encountered a 66-year-old woman with a polycystic kidney (PCK). This was combined with the fact that the new growth of an aneurysm at the left anterior cerebral artery (A2-A3 junction) had ruptured 3 years after an operation for a right IC-PC aneurysm in 1985. The cause of the neogenesis and enlargement of an intracranial aneurysm is important because of the changes in the arterial wall due to congenital factors, hypertension, arteriosclerosis, etc, or hemodynamic stress caused by hypertension. We suspected that intracranial aneurysm formation was caused by hypertension due to PCK and the intracranial aneurysm is explained as being due to maldevelopment. In patients with PCK, it should be kept in mind that intracranial aneurysms may be present, and it is advisable to use cerebral angiography and MRA to see whether this is so or not. It should be also stressed that the control of hypertension is very important for the prognosis of patients with PCK. Not only new growth of cerebral aneurysms but also intracerebral hemorrhage is to be prevented.

Aged↗