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Biomedical subjects

Y Mizukami

Publications and source records attributed to Y Mizukami.

At least 127 records · Page 7Linked to original sources

Omega-hydroxylation of lipoxin B4 by human neutrophil microsomes: identification of omega-hydroxy metabolite of lipoxin B4 and catalysis by leukotriene B4 omega-hydroxylase (cytochrome P-450LTB omega).

Lipoxin B4 (LXB4) is metabolized either by human neutrophils or by the neutrophil microsomes to a polar compound on a reverse-phase high-performance liquid chromatography. The metabolite is identified as 20-hydroxy-lipoxin B4 (20-OH-LXB4), a novel member in the arachidonic acid cascade, on the basis of ultraviolet spectrometry and gas chromatography-mass spectrometry. The neutrophil microsomes convert LXB4 to its 20-hydroxy derivative under aerobic condition in the presence of NADPH. The reaction is inhibited by carbon monoxide, an inhibitor of cytochrome P-450 (P-450), and by antibodies raised against NADPH-P-450 reductase. A P-450 is thus involved in the omega-hydroxylation of LXB4. The P-450 appears to be the one responsible for leukotriene B4 (LTB4) omega-hydroxylation, P-450LTB omega, based on the following observations. The formation of 20-OH-LXB4 is inhibited solely by substrates of P-450LTB omega such as LTB4 and leukotriene B5 among various fatty acids including prostaglandins. The order of the inhibitory potencies of these substances on the LXB4 omega-hydroxylation is the same as that of their affinities for LTB4 omega-hydroxylase. LTB4 inhibits the reaction in a competitive manner with the Ki value of 0.2 microM, which agrees with the Km value for the LTB4 omega-hydroxylation (0.3 microM).

Catalysis↗

Formation of a novel 20-hydroxylated metabolite of lipoxin A4 by human neutrophil microsomes.

Lipoxin A4 (LXA4) is a biologically active compound produced from arachidonic acid via interactions of lipoxygenases. Incubation of LXA4 either with human neutrophils or with the neutrophil microsomes leads to formation of a polar compound on a reverse-phase high-performance liquid chromatography. We have identified the metabolite as 20-hydroxy-LXA4, a novel metabolite of arachidonic acid, on the basis of ultraviolet spectrometry and gas chromatography-mass spectrometry. The LXA4 omega-hydroxylation requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide, by antibodies raised against NADPH-cytochrome P-450 reductase, or competitively by leukotriene B4 (LTB4) and LTB5, substrates of LTB4 omega-hydroxylase. These findings indicate that the formation of 20-hydroxy-LXA4 is catalyzed by a neutrophil cytochrome P-450, the LTB4 omega-hydroxylase.

Cells, Cultured↗

Internal mammary nodal status is a more reliable prognostic factor than DNA ploidy and c-erb B-2 expression in patients with breast cancer.

We evaluated the relationship among DNA ploidy, c-erb B-2 oncoprotein expression, and clinicopathologic prognostic factors, especially axillary and internal mammary node metastases, and their value in estimating the prognosis in 128 patients with operable breast cancer. There were significant correlations between DNA ploidy and clinical stage, tumor size, or axillary or internal mammary lymph node metastases, and between c-erb B-2 expression and clinical stage or axillary lymph node metastases. In a univariate study, overall or disease-free survival was significantly correlated to clinical stage, tumor size, DNA ploidy, c-erb B-2 expression, and axillary and internal mammary node metastases. In a multivariate study, however, only axillary and internal mammary node metastases were recognized as independent factors on overall survival, whereas on disease-free survival, only axillary lymph node metastases were identified as an independent indicator. Since the DNA ploidy status and c-erb B-2 expression were closely correlated with the axillary and/or internal mammary lymph node metastases, they did not appear as independent prognostic factors in this small series.

Adult↗

Risk of bilateral cervical lymph node metastases in papillary thyroid cancer.

We evaluated the risk of bilateral or contralateral cervical lymph node metastases in 135 patients with papillary thyroid cancer who underwent bilateral neck dissection. We confirmed that bilateral jugular lymph node metastases were frequent in patients with obvious carcinoma in both lobes of the gland, in those with cancers arising in the isthmus, in those with clinically detectable bilateral lymphadenopathy, and in those with recurrent thyroid cancer. However, only 24% of the patients who had cancer clinically confined to one lobe with no bilateral or contralateral lymphadenopathy had histologically detected bilateral or contralateral jugular lymph node metastases. But the occurrence of contralateral jugular lymph node metastases was significantly correlated with both clinical lymphadenopathy in the ipsilateral neck and contralateral paratracheal lymph node metastases. Bilateral lymph dissection might be beneficial for these patients.

Adolescent↗

Psychologic and cosmetic self-assessments of breast conserving therapy compared with mastectomy and immediate breast reconstruction.

Cosmetic and psychologic morbidity was evaluated by patients' self-assessment in 42 patients who underwent breast conserving therapy (BCT) and 48 patients who underwent mastectomy with immediate breast reconstruction (MIBR). Although sexual adjustment and fear of cancer recurrence were not significantly different between the two groups, body image was rated as significantly better in the BCT group. Additionally, in the MIBR group, nine patients expressed concern about abdominal or back scars and 15 related abdominal or back pain. Eighty-three percent of the BCT group indicated BCT as a future choice of treatment, whereas only 38% of the MIBR group indicated MIBR as a future choice of treatment. Therefore, body image and patients' satisfaction were thought to have been improved by BCT, but psychologic morbidity was the same in both groups.

Adult↗

A retrospective study on the clinical and biological prediction of axillary lymph node metastasis in breast cancer.

If axillary lymph node metastases were able to be accurately predicted, dissection could be avoided in some patients with breast cancer whose axillary nodes are clinically negative. In this study, we assessed the relationships between histological axillary lymph node metastases and clinical axillary nodal status, tumor size, DNA-ploidy, c-erbB-2 expression, and the score of the argyrophilic nucleolar organizer region. We then attempted to evaluate their predictive values for axillary lymph node metastasis in 173 patients with invasive breast cancer, retrospectively. The clinical and biological variables were significantly correlated with the presence and degree of axillary lymph node metastases. A metastatic index, calculated from the clinical and biological variables, proved especially useful for predicting axillary lymph node metastases in patients whose axillary nodes were clinically negative. However, the predictive abilities were still limited and thus it was concluded that as yet, only axillary dissection can provide accurate information on axillary lymph node metastases.

Adult↗

The psychological and cosmetic aspects of breast conserving therapy compared with radical mastectomy.

An evaluation of the psychological and cosmetic morbidity of 31 patients who had undergone breast conserving treatment (BCT group) and 71 patients who had undergone radical mastectomy (RM group) revealed that 85% and 73%, respectively, were satisfied with their operative results. BCT appeared superior to RM in relation to body image, with 93% of the BCT group indicating BCT as a future choice of treatment, whereas only 35% of the RM group indicated RM as a future choice of treatment. For 59% of the BCT patients, the results were considered excellent or good by a physician, but fear of recurrence was frequently expressed by both groups even though an early stage of breast cancer had been significantly more common in the BCT group than the RM group. Sexual adjustment was the same in both groups. Body image was thus concluded to have been improved by BCT rather than RM, but psychological morbidity was essentially the same in both groups.

Adaptation, Psychological↗

DNA ploidy and helix pomatia lectin binding as predictors of regional lymph node metastases and prognostic factors in breast cancer.

This study was designed to evaluate whether DNA ploidy and/or Helix pomatia lectin (HPA) staining would be useful for predicting regional lymph node metastases and patients' prognosis in 106 patients with invasive breast cancer. The combination of DNA ploidy and HPA staining correlated better with regional lymph node metastases than DNA aneuploidy or HPA staining alone. DNA ploidy and HPA staining in combination correlated strongly with overall and disease-free survival by univariate analysis. However, the prognostic significance of DNA ploidy and HPA staining in combination was lost in multivariate analysis when regional lymph node metastases were introduced into the models. This emphasized the relationship in survival between regional lymph node metastases and the combination of DNA ploidy and HPA staining. We therefore concluded that the combination of DNA ploidy and HPA staining might provide prognostic information for breast cancer patients in whom regional lymph node dissection has not been performed.

Adult↗

Demonstration of nucleolar organizer regions in lung carcinoma by silver staining.

Nucleolar organizer regions (NORs) were investigated in lung carcinomas by silver staining. This method was applied to 111 lung carcinoma specimens, including 40 with squamous cell carcinoma (SCC), 42 with adenocarcinoma (ADENO), 8 with adenosquamous carcinoma (ADESQ), 8 with small cell carcinoma (SMCC), 6 with large cell carcinoma (LGCC), and 7 with typical carcinoid tumors (CAOID). The mean AgNOR counts of ADENO, SCC, ADESQ, SMCC, and LGCC were significantly higher than those of the normal bronchial surface and those of the glandular or alveolar epithelium. The mean AgNOR count of CAOID was significantly higher than those of the normal glandular and alveolar epithelium but not that of the surface epithelium. The mean AgNOR count of SCC was significantly higher than that of bronchial squamous metaplasia, and the count of SMCC was significantly higher than that of CAOID. Within the same cancer category, the mean number of AgNORs increased in parallel with the histological tumor grades. These results indicate that the AgNOR method is useful for differentiating lung carcinoma from its normal counterparts and for evaluating histological tumor grades in the same lineage of lung carcinoma.

Adenocarcinoma↗

Visualization of the thymus with therapeutic doses of radioiodine in patients with thyroid cancer.

Two cases of papillary carcinoma of the thyroid are presented in which whole-body scans following therapeutic doses of iodine-131 revealed intense anterior mediastinal uptake. In both cases, the mediastinal uptake was absent from scans obtained after removal of the entire thymus. Histologically, the resected thymus glands showed hyperplasia and contained neither thyroid tissue nor metastatic foci of thyroid carcinoma. We therefore concluded that anterior mediastinal uptake of radioiodine may be caused by hyperplasia of the thymus.

Adult↗

Retroperitoneal fibrosis associated with scirrhous gastric cancer.

A case of retroperitoneal fibrosis associated with scirrhous gastric cancer is reported. A sixty two-year-old Japanese female was admitted because of acute renal failure. The patient's serum creatinine level showed 3.2 mg/dl while the blood urea nitrogen level was 23 mg/dl. An ultrasound study of the upper abdomen revealed bilateral hydronephrosis. Drip infusion pyelography revealed a dilated right renal pelvis without ureteral obstruction. The left kidney was not opacified, suggesting a functional disorder. Gastrography and gastrofiberscopy revealed scirrhous gastric cancer. Signet ring cell carcinoma was later demonstrated histologically by biopsy specimens. CT demonstrated a prominent thickening of the gastric wall and hydronephrosis, although no prevertebral soft tissue masses were observed. A total gastrectomy was performed with failure to surgically decompress the ureters because fibrous plaque had firmly enveloped the retroperitoneal structures. Biopsy specimens of the retroperitoneum revealed an invasion of the tumor cells and prominent fibrosis. As an etiology of renal failure, ureteral stenosis resulting from secondary retroperitoneal fibrosis was also considered.

Acute Kidney Injury↗

Influence of hormones on tumor growth, cell kinetics, estrogen receptor and insulin-like growth factor-I-related protein of human breast cancer (MCF-7) cells transplanted in nude mice.

The influence of estrogens and tamoxifen on estrogen receptor (ER)-positive human breast cancer (MCF-7) cells transplanted into athymic nude mice was investigated. The mice were divided into the following three groups: (1) an E2 group with mice receiving 17 beta-estradiol dipropionate; (2) a TAM group with mice receiving tamoxifen; (3) a control group with mice given no hormone. (1) Tumor growth was significantly increased in the E2 group, but significantly decreased in the TAM group compared to control; (2) the tumor contents of insulin-like growth factor-I (IGF-I) and the rate of IGF-I-positive cells were significantly lower in the E2 group, but significantly higher in the TAM groups compared to control; (3) the IGF-I-positive cell rates were in significant inverse correlation with the [3H]thymidine-labeled cell rates in the E2, TAM and control groups. Thus, the tumor contents of IGF-I and the rate of IGF-I-positive cells were inversely correlated to the tumor growth and the [3H]thymidine-labeled cell rate in this in vivo study, although IGF-I is known to be a mitogen for breast cancer cells in vitro. Further studies are necessary to answer the questions as to the in vivo roles of immunoreactive IGF-I in ER-positive breast cancer.

Animals↗

Clinical and biological prediction of axillary and internal mammary lymph node metastases in breast cancer.

We assessed the relationships among histological axillary (AX) or internal mammary (IM) metastases and clinical and biological variables, and then attempted to evaluate their predictive values for AX and IM metastases in 128 patients with invasive breast cancer. As the results, these clinical and biological variables were significantly correlated with AX and IM metastases. However, a metastatic index calculated from clinical and biological variables was not much better in prediction of the AX metastases than axillary nodal status, whereas it was useful to predict the IM metastases. Thus, the predictive ability was still limited. Since accurate prediction of AX and IM metastases is critical to therapeutic choice, however, further study would be required.

Adult↗

Mucin-producing poorly differentiated adenocarcinoma of the thyroid. A case report.

A rare case of mucin-producing poorly differentiated adenocarcinoma of the thyroid is reported in a 58-year-old man. Light microscopically, the tumor composed of columnar cells, cuboidal cells and spindle cells and these tumor cells showed a various growth pattern; glandular growth with columnar cells, microfollicular growth with cuboidal cells and solid growth with spindle cells. Mucin histochemistry showed scattered foci of mucin production. Immunohistochemistry showed a focal positive staining for thyroglobulin and carcinoembryonic antigen, but a negative staining for calcitonin throughout the tumor. The patient had cervical and axillary lymph node recurrences after the radical operation. The histologic finding of this tumor is peculiar; we report this case briefly.

Adenocarcinoma, Mucinous↗

Postpartum thyroiditis. A clinical, histologic, and immunopathologic study of 15 cases.

Fifteen specimens from 15 patients with clinically and laboratory-proven postpartum thyroiditis were examined histologically; 8 specimens were obtained during the hypothyroid phase and the other 7 during the recovery euthyroid phase. All specimens showed focal or diffuse chronic thyroiditis. In the eight specimens taken during the hypothyroid phase and four specimens during the early recovery phase, follicular disruption and hyperplastic change of the follicle were common and characteristic histologic features. In the three specimens taken during the late recovery phase, only focal infiltration of lymphocytes was observed. This histologic change resembled that in spontaneous silent thyroiditis, as shown in the authors' previous study. The authors believe that postpartum thyroiditis and spontaneous silent thyroiditis may fit the same category clinically and histologically. In addition to performing the histologic examination, the authors examined the intrathyroidal lymphocyte subsets and HLA-DR antigen expression in the follicular cells immunohistochemically and compared them with those in chronic thyroiditis (usual type). In postpartum thyroiditis, a significant increase of helper-T-cell numbers and increased expression of HLA-DR antigen in the follicular cells were observed, suggesting an enhancement of autoimmune reactivity.

Adult↗

Paget's disease of the esophagus.

Esophageal carcinoma simulated Paget's disease in a 60-year-old Japanese man with 3 months of difficulty swallowing and pain. Results of an esophageal biopsy indicated undifferentiated carcinoma, but after esophagectomy and partial gastrectomy, the resected esophagus showed that the mucosa was diffusely indurated with irregular, reticulated erosions. There was no tumor mass or ulcer. Histologic examination showed an extensive intraepithelial growth of cancer cells without any glandular or squamous cell differentiation. Tumor cells were large and round and contained large nucleoli and ample, clear, or pale-staining cytoplasm, similar to the cells of Paget's disease. Tumor cells multifocally invaded into the mucosal and submucosal ducts where they formed papillary and tubular nests, indicating adenocarcinomatous differentiation, but there was no invasive growth beyond the basement membrane. Tumor cells in the epithelial layer were negative for periodic acid Schiff (PAS) and alcian blue, but partly positive for epithelial membrane antigen (EMA) and CEA, whereas those in the submucosal ducts and glands were strongly positive for PAS, alcian blue, carcinoembryonic antigen, and EMA, especially at their luminal surfaces. Tumor cells were negative for S-100, neuron-specific enolase, and melanin. These findings indicate that the tumor in the present case was a primary esophageal carcinoma with partial adenocarcinomatous differentiation, showing an extensive intraepithelial Pagetoid growth of its undifferentiated component. This is the first case of esophageal Paget's disease presenting as intraepithelial growth alone.

Biopsy↗

Influence of esculetin on incidence, proliferation, and cell kinetics of mammary carcinomas induced by 7,12-dimethylbenz[a]anthracene in rats on high- and low-fat diets.

The effects of a high-fat diet and esculetin were investigated on 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. Rats were given a 5-mg dose of DMBA. Seven days later, they were fed either a high-fat (20% soybean oil) or low-fat (0.5% soybean oil) diet. A half of the rats received diets containing 0.03% esculetin. Esculetin significantly inhibited tumor incidence, growth and cell kinetics of the tumor in the rats fed the high-fat and the low-fat diets. Our findings indicate that DMBA-induced mammary tumorigenesis is affected by lipoxygenase products.

9,10-Dimethyl-1,2-benzanthracene↗