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Biomedical subjects

T Watanuki

Publications and source records attributed to T Watanuki.

At least 19 recordsLinked to original sources

Stability of microcystins from cyanobacteria--IV. Effect of chlorination on decomposition.

Microcystins, the cyclic heptapeptide toxins produced by cyanobacteria such as Microcystis, show tumor-promoting activity through inhibition of protein phosphatases 1 and 2A. They potentially threaten human health, and are increasing the world-wide interest in the health risk associated with cyanobacterial toxins. In this study, the effect of chlorination on the decomposition of microcystins-LR and -RR was examined. The toxins were easily decomposed by chlorination with sodium hypochlorite, and the decomposition depended on the free chlorine dose. In this operation, many reaction products were formed, one of which was determined to be dihydroxymicrocystin formed through the chloronium ion at the conjugated diene of Adda [3-amino-9-methoxy-10-phenyl-2,6,8-trimethyl-deca-4(E), 6(E)-dienoic acid], followed by hydrolysis. Other products may be its stereoisomers and/or regioismers. No noxious products were detected from the chlorination process of microcystin-LR. Although these results suggested that chlorination at an adequate chlorine dose is very effective for the removal of microcystin in raw water, preoxidation of the cell itself with chlorine must be avoided, because it frequently causes toxin release from algae and produce trihalomethanes during water treatment.

Animals

Microcystin levels during 1992-95 for Lakes Sagami and Tsukui-Japan.

Toxic cyanobacterial blooms have been frequently observed in Lakes Sagami and Tsukui, Kanagawa Prefecture, Japan, which are used as drinking and recreational water sources. As the first step toward the control and removal of cyanobacterial toxins, the present study evaluated the microcystin level in these lakes. Our established method using HPLC and LC/MS to pursue trace amounts of microcystins was applied to the determination of microcystins within cyanobacteria cells and in water. We could determine precisely the intracellular and extracellular microcystin level in the water environment during 1992-95. Microcystins RR, LR, and YR were detected at 0.02-2.64 micrograms/L in cell-free water and at 0.02-378 micrograms/L in the cells. Although there were many cases in which microcystin concentrations in the cells exceeded the proposed guideline level (1 microgram/L), there was only one example of this happening in cell-free water samples. Because the present monitoring indicated that the amount of microcystins detected in water was much less than that estimated in cells, the release of microcystins from the cells and their stability in lake water were examined in the dark. The resulting toxins persisted at the same concentration level for 14 days and the microcystin concentrations steadily declined, showing that biodegradation using aquatic natural bacterial flora is an effective detoxification process under natural conditions.

Biodegradation, Environmental

Stability of microcystins from cyanobacteria--II. Effect of UV light on decomposition and isomerization.

Microcystins are very potent hepatotoxins and strong liver tumor promoters produced by cyanobacteria, and their occurrence has been reported all over the world. They could threaten human health when toxic Microcystis occurs in water supply reservoirs. In this study, we examined the stability of microcystins during photolysis with UV light. The toxins were easily decomposed by UV light at wavelengths around the absorption maxima of the toxins and the decomposition depended on the intensity of the light. The half-life of microcystin LR by 147 microW/cm2 UV irradiation was 10 min, and the toxin was completely decomposed by 2550 microW/cm2 UV after 10 min. When the toxins were irradiated with weaker UV light, isomerization was also observed by a different mechanism from that during photolysis by sunlight and pigment, and several products including three geometrical isomers of the conjugated diene of Adda were detected. Microcystin RR showed almost the same behavior as that of microcystin LR under the same conditions. Since no noxious products were formed in the present study, a water treatment including UV irradiation is very possible for removing microcystins from raw water.

Chromatography, High Pressure Liquid

[Hemophagocytic syndrome in a patient with immunoblastic lymphadenopathy-like T-cell lymphoma].

We report a 70-year-old male case of immunoblastic lymphadenopathy-like T-cell lymphoma (IBL-T) complicated by hemophagocytic syndrome (HPS) as a terminal event. The patient experienced fever and systemic lymphadenopathy after 22 months' remission of IBL-T. He developed acute hepatic failure and consumption coagulopathy rapidly, and died on the 7th hospital day. Serum levels of cytokines, including interferon-gamma and tumor necrosis factor-alpha, were elevated. Postmortem bone marrow aspirate showed a marked proliferation of benign-looking macrophages, some of which phagocytized erythrocytes and platelets. Because there were no preceding viral or bacterial infections, the HPS of this case was assumed to be associated with IBL-T at relapse.

Aged

Immunohistochemical comparison between anaplastic seminoma and typical seminoma.

In order to study the possible biological differences between anaplastic and typical seminoma, the following factors were studied in 11 cases of anaplastic seminoma and 15 cases of typical seminoma: mitotic activity, proliferating cell nuclear antigen (PCNA) expression, immunohistochemical analyses for cytokeratin, vimentin, placental alkaline phosphatase (PLAP), beta-human chorionic gonadotropin (beta-hCG), alpha-fetoprotein (AFP) and c-myc oncoprotein. Anaplastic seminoma was classified according to Mostofi's criteria, which is primarily based on the mitotic activity of the tumor. Mitotic activity was evaluated by both mitotic count and rate. Statistically significant correlations were observed between mitotic count and mitotic rate (R = 0.891), and between the mitotic count and PCNA labeling index (R = 0.792), in both typical and anaplastic seminomas. Immunostaining patterns for cytokeratin, vimentin, PLAP, beta-hCG, AFP and c-myc oncoprotein were not significantly different between typical and anaplastic seminoma. The present data indicated that no apparent clinicopathologic and immunohistochemical parameters discerning anaplastic seminoma from typical seminoma were present, when identifying anaplastic seminoma on the basis of high mitotic count. Anaplastic seminoma may therefore simply represent seminoma with high proliferative activity.

Adolescent

High incidence of leukemic phase in follicular lymphoma in Akita, Japan: clinicopathologic, immunological and cytogenetic studies.

A leukemic phase occurred in 7 of 11 (64%) Japanese patients with follicular lymphoma. The clinical and hematologic features at the onset of this phase were splenomegaly, anemia, and thrombocytopenia. The lymphoma cells expressed monoclonal surface immunoglobulins with moderate to strong intensity in all 7 of the patients diagnosed as leukemic. Various B-cell associated antigens were expressed as follows: CD19 (5/6), CD20 (7/7), and CD10 (6/7). The reactivity to these markers was comparable in the lymph node and blood samples. The expression of CD38 antigen was much lower in the lymphoma cells of the blood than in those of the lymph nodes. Cytogenetic studies of the lymph nodes of follicular lymphoma in leukemic phase revealed a common chromosomal aberration, of t(14;18)(q32;q21) and +18, in 2 patients successfully analyzed. Although the follicular lymphomas in the leukemic phase in these patients in Akita, Japan, were consistent with those in the West with respect to morphology, immunology and cytogenetics, the high incidence of leukemic manifestations may be a salient feature of Japanese cases.

Adult

Acute interstitial nephritis with symmetric enlargement of the lacrymal and salivary glands and systemic lymphadenopathy.

We describe a 40-year-old man who developed symmetric enlargement of the lacrymal and salivary glands and systemic lymphadenopathy. Laboratory findings included eosinophilia, polyclonal hypergammaglobulinemia, elevated circulating immune complexes, hypocomplementemia, and renal insufficiency. The lymph node pathology was atypical of angioimmunoblastic lymphadenopathy with disproteinemia (AILD), in that it lacked a prominence of arborizing small vessel proliferation. Despite extensive examinations, the cause of the atypical AILD process has not been identified. However, a flow-cytometric analysis of immunophenotypes of lymphoid cells from the lymph node revealed a predominance of activated helper/inducer T cells, indicating a hyperimmune state. Acute interstitial nephritis was secondary to the renal propagation of the atypical AILD process. Thus, atypical AILD can be a new cause of acute interstitial nephritis. A course of combined steroids and immunosuppressive treatment resolved those pathologic disorders for 5 years.

Acute Disease

An immunohistologic evaluation of C-erbB-2 gene product in patients with urinary bladder carcinoma.

BACKGROUND: Amplification or overexpression of the c-erbB-2 gene have been reported to correlate with poor patient prognosis in human breast, gastric, and ovarian cancer. Recently, the c-erbB-2 gene product was found to be expressed frequently in the urinary bladder carcinoma. In the current study, the presence of the c-erbB-2 gene product in urinary bladder carcinomas was compared with patient outcome to evaluate whether c-erbB-2 gene product could identify a subset of patients who are destined to have a poor prognosis. METHODS: Immunohistologic study of the c-erbB-2 gene product was done in formaldehyde-fixed paraffin-embedded tissue specimens obtained from 88 transitional cell carcinomas of the human urinary bladder. Eighty-three patients who underwent complete tumor resection by total cystoprostatectomy (30 patients) or by bladder-preserving operations such as transurethral surgery (50 patients) or partial cystectomy (3 patients) entered a follow-up study. The other five patients did not enter the follow-up study because of lost follow-up (2 patients) or distant metastasis at the time of surgery. RESULTS: The c-erbB-2 gene product was expressed in 23 of 88 patients (26%), showing an increase in the expression rate corresponding to the advancement of tumor grade (P < 0.05) and tumor stage (P < 0.2). The 5-year disease-free survival rate was 48.5% for patients with c-erbB-2 negative tumors versus 9.7% for those with c-erbB-2 positive tumors (P < 0.01). The 5-year actuarial survival rate was 65.5% for patients with c-erbB-2 negative tumors versus 41.8% for those with c-erbB-2 positive tumors (P < 0.05). Multivariate analysis using Cox regression model showed that the c-erbB-2 gene product tissue status was a significant prognostic factor independent of grade and stage of the tumor. CONCLUSIONS: The results suggest that the c-erbB-2 gene product could be a tumor marker to identify a malignant subgroup in bladder carcinomas.

Adult

[A retrospective comparison study of patients old and young with non-Hodgkin's lymphoma].

One hundred patients with diffuse non-Hodgkin's lymphoma were treated with combination chemotherapy including adriamycin. Seventy-one patients were under age 70 and 29 were 70 years or older. The clinical characteristics of the two groups were similar, except that the patients showed elevated serum BUN were in the elderly group. The complete remission rate in the elderly patients (66%) was slightly lower than that in the younger patients (75%) (p = NS). The average length of survival in the elderly patients was significantly shorter than in the younger patients (p less than 0.05) (projected 5-year survival: 28 +/- 11% vs 52 +/- 7%). The duration of remission for all patients in the elderly patients did not differ from that in the younger patients (projected 2-year survival: 40 +/- 10% vs 45 +/- 6%). Death during the induction chemotherapy from causes other than lymphoma occurred in 14% of patients over 70-year-old and in one percent of younger patients. At relapse, the response rate was significantly lower in the elderly patients than in the younger patients (CR+PR: 28% vs 78%, p = 0.03). To prevent toxic death in remission induction therapy, drug dose elderly patients should be attenuated according to their general conditions and performance status.

Age Factors

Diffuse large cell lymphoma occurring in a patient with Waldenström's macroglobulinemia. Evidence for the two different clones in Richter's syndrome.

The authors report a 60-year-old man with Richter's syndrome, or diffuse large cell lymphoma (DLCL) occurring in a patient with either chronic lymphocytic leukemia (CLL) or Waldenström's macroglobulinemia (WM). Surface marker analysis revealed that the WM showed mu kappa surface immunoglobulin (Ig) chains, and that the DLCL showed mu lambda Ig chains. Flow cytometric DNA analysis demonstrated DNA content differences between WM and DLCL, the former diploid and the latter aneuploid. The current study suggests that Richter's syndrome derives from two independent B-cell malignancies.

DNA

Expression of c-erbB-2 gene product in urinary bladder cancer.

Expression of the c-erbB-2 gene product and the epidermal growth factor receptor (EGF-R) was investigated in 54 cases of human bladder cancer immunohistologically and by Western blot analysis. For detection of the c-erbB-2 product, two specific antibodies, a rabbit polyclonal antibody directed to the intracellular domain and a murine monoclonal antibody recognizing an epitope in the extracellular domain, were used. Seventeen cases of bladder cancer were stained by the anti-c-erbB-2 polyclonal antibody, while 20 cases were stained by the monoclonal antibody, with good correlation on both stainings (p less than 0.01). There were four c-erbB-2 positive cases in 26 G1 tumors, four in 15 G2 tumors, and nine in 13 G3 tumors. There were also eight erbB-2 positive cases in nine muscle-invasive tumors, nine of 45 superficial tumors, four of five with lymph node metastasis, and seven of 14 without metastasis, as revealed by staining with the polyclonal antibody. Thus, the c-erbB-2 gene product was more frequently expressed in high grade tumors (p less than 0.01), in high stage tumors (p less than 0.01), and nodal metastatic tumors (N.S. by Chi-square test). Twenty-two of the 54 tumors were stained by an anti-EGF-R monoclonal antibody, 528 IgG. The expression of EGF-R was independent of histological grading, tumor stage, and nodal status, and no correlation was observed between expression of the c-erbB-2 product and EGF-R. The c-erbB-2 product may be applicable as a tumor marker for evaluation of malignant potential, invasiveness, and probably metastatic potential of human bladder cancer.

Antibodies, Monoclonal

Elevated expression of P-glycoprotein in kidney and urinary bladder cancers.

A monoclonal antibody, MRK16, recognizing specifically an epitope of P-glycoprotein (P-GP), a highly active efflux transporter of chemotherapeutic agents, was used to determine the degree of expression of P-GP in the normal human kidney and urinary bladder, and in kidney and urinary bladder cancers. P-glycoprotein was localized in the microvilli of the epithelial cells of the proximal renal tubules by immunoelectron microscopy, and detected immunohistochemically in 6 of 20 untreated kidney cancers and 11 of 31 untreated urinary bladder cancers. Some of the cancerous tissues were further examined with regard to P-GP expression by immunoprecipitation. In urinary bladder cancers, the degree of P-GP expression seemed to be somewhat correlated with tumor grading. These results indicate that our method to detect the degree of expression of P-GP by MRK16 may be applicable for the diagnosis of clinical multidrug resistant urinary cancers.

ATP Binding Cassette Transporter, Subfamily B, Mem

[Electrolyte abnormality and renal insufficiency in malignant lymphoma; clinical and pathological analysis in 123 cases].

The clinical studies about the electrolyte abnormality (EA) in patients with malignant lymphoma (ML) are rarely reported. We analyzed the EA and renal insufficiency in 123 patients with ML between June. 1976 and Jan. 1989; 8 patients with Hodgkin's disease, and 115 patients with non-Hodgkin's lymphoma (NHL). Before treatment, the incidence of the EA was 24.2% and hypercalcemia, hypocalcemia, and hyperkalemia were predominant. After treatment it became to 74.7% and the number of hyponatremia and hypokalemia increased. The incidence of proteinuria and renal insufficiency (serum creatinine above 1.5 mg/dl), were 7.3% and 2.4% before treatment, and became to 26.8% and 26.8% after treatment, respectively. There was a significant difference between two groups with and without the EA before treatment as for serum lactate dehydrogenase (LDH) levels (p less than 0.01), clinical stages (p less than 0.05) and the incidence of bone marrow involvement (p less than 0.01). In 34 autopsied cases, 3 cases showed massive renal involvement and about a half of cases showed various renal changes. The EA before treatment was caused by extrarenal factors, because the incidence of proteinuria and renal insufficiency were almost same to healthy controls. And renal factors play an important role on the E.A after treatment. Above results suggest that the EA before treatment indicates the progress of malignant lymphoma and the EA after treatment means not only the progress of the disease but also therapy-related renal damages.

Adult

[Non-Hodgkin's lymphoma of the nasal cavity and paranasal sinuses: clinicopathologic study of ten cases].

Ten patients with non-Hodgkin's lymphoma originated in the nasal cavity (four patients) and in the paranasal sinuses (six patients) were treated mainly with irradiation and combination chemotherapy including adriamycin. According to the TNM AJC staging system, four patients were in stage T1-T2, and six patients were in stage T3-T4. Nine patients, other than one with stage IV (Ann Arbor) disease, achieved complete remission. Death due to lymphoma occurred in four patients, 4 to 39 months following diagnosis. Three of these patients developed systemic extranodal dissemination, and died in a short time after relapse. Death due to second malignancies occurred in two patients. One died of acute myelogenous leukemia, and the other died of colon cancer, 26 and 53 months after diagnosis, respectively. Four patients were alive and disease-free, from 23 to 68 months following diagnosis (median 40 months). Out of four patients who died of disease, three were in stage T3-T4, and one was in stage T1. Two patients with stage T1 originated in the nasal cavity were both alive and disease-free. Except for lymphomas with stage T1 originated in the nasal cavity, more intensive chemotherapy should be instituted in an attempt to achieve better disease-free survival.

Adult

[Clinical significance of immunophenotype in diffuse non-Hodgkin's lymphoma: with special emphasis on the clinical characteristics of T-cell lymphoma].

The clinical significance of immunophenotyping of the non-Hodgkin's lymphomas (NHL) is still controversial. Therefore, we evaluated the prognostic significance of T- and B-cell phenotype in 102 patients having diffuse non-Hodgkin's lymphoma who had been treated in a majority with Adriamycin-containing regimens. The significant differences in pretreatment clinical variables between the two patient groups were the higher frequency of markedly elevated LDH (greater than or equal to X 2 normal) and the lower frequency of decreased cholesterol level in B-NHL (p less than 0.05). Patients with B-NHL had a higher complete remission (CR) rate (77% vs 59%: p = NS), a significantly better overall survival (62% vs 34% at 3-years: p less than 0.05) and longer duration of remission for all patients (50% vs 27% at 3-years: p less than 0.05). Among forty-five patients with stages III and IV disease of nodal origin (excluding those with diffuse small cleaved histology), the B-cell group was associated with a better prognosis; a higher CR rate (68% vs 41%: p = NS) and a longer duration of remission for all patients (44% vs 12% at 2-years: p less than 0.05). Furthermore, for patients with T-cell phenotype, the primary site was the only prognostic factor; the patients whose disease originated from Waldeyer's ring, nasal cavity, and paranasal sinuses, achieved a better CR rate (92% vs 40%: p less than 0.05) and a longer duration of remission for all patients (48% vs 15% at 2-years: p less than 0.05). We conclude that advanced T-cell lymphoma of nodal origin is a subgroup of patients with very poor prognosis if treated with less intensive chemotherapeutic regimens.

Adolescent