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Biomedical subjects

Y Mizukami

Publications and source records attributed to Y Mizukami.

At least 19 recordsLinked to original sources

Identification of the binding site of 55kDa tumor necrosis factor receptor by synthetic peptides.

We have synthesized a series of peptides, which cover almost the whole range of the N-terminal extracellular domain of human 55kDa TNF receptor (55kDa TNF-R). The peptides were examined for the binding activity to TNF by solid phase binding assay and for the inhibition of TNF cytotoxicity to mouse L-M cells. The peptide 159-178 exhibited remarkably higher binding activity to TNF than other peptides did. The specificity of the TNF binding to the peptides was confirmed by their inability to bind other cytokines. The peptide 159-178 also inhibited TNF cytotoxicity. These results indicate that the specific binding site of 55kDa TNF-R to TNF might reside within the peptide segment of amino acid numbers 159 to 178 in the N-terminal extracellular domain.

Amino Acid Sequence

Ectopic expression of the floral homeotic gene AGAMOUS in transgenic Arabidopsis plants alters floral organ identity.

The Arabidopsis floral homeotic gene AGAMOUS (AG) is required for development of the reproductive organs (stamens and carpels). In ag mutants, the loss of AG function leads to the conversion of these organs to the perianth organs (petals and sepals). In contrast, mutations in another floral homeotic gene, APETALA2 (AP2), result in the replacement of the perianth organs by the reproductive organs. On the basis of these observations, it has been proposed that AG and AP2 act in an antagonistic fashion. To test this hypothesis, we have studied the effects of ectopically expressed AG in transgenic Arabidopsis plants. The flowers of the transgenic plants exhibit a range of phenotypes mirroring those of ap2 mutants. These experiments provide direct evidence of the proposed antagonism between AG and AP2 functions, and the results strongly suggest that AG does indeed inhibit AP2 function.

Arabidopsis

[Evaluation of the internal mammary nodes by lymphoscintigraphy and ultrasonography in patients with breast cancer].

The efficacy of lymphoscintigraphy and ultrasonography was evaluated in the detection of internal mammary lymph node (IMN) metastases in patients with breast cancer. On histological examination of IMN, 10 patients had metastases (positive group) and 47 did not (negative group). On lymphoscintigraphy, lack of uptake in the parasternal region of the affected side was classified as abnormal. The frequency of this abnormal finding was not significantly different between both groups. On sonography, the thickness of the sonolucent internal mammary area was measured. The thickness of the affected side was 6 mm or more in two patients of the positive group and only one of the negative group. A thickness of over 6 mm on the affected side was statistically significant (p less than 0.05). The difference in thickness between the affected side and the healthy side was 3 mm or more in four patients of the positive group, and was less than 3 mm in all patients of the negative group. A difference in thickness of more than 3 mm between the two sides was extremely significant (p less than 0.001). In conclusion, sonography is valuable in detecting IMN metastases, while lymphoscintigraphy is not useful. Sonography is recommended as an efficient diagnostic modality for IMN metastases.

Adult

C-erbB-2 oncoprotein expression versus internal mammary lymph node metastases as additional prognostic factors in patients with axillary lymph node-positive breast cancer.

The relationship was assessed between c-erbB-2 oncoprotein expression and other prognostic factors in breast cancer, such as axillary and internal mammary node metastases. The value of these indicators was analyzed in estimating prognosis, especially in patients with axillary node-positive breast cancer. These results showed that c-erbB-2 is significantly related to clinical stage and axillary node metastases. A univariate study revealed that disease-free and overall survival were correlated significantly with clinical stage, tumor size, axillary and internal mammary node metastases, and 21N status. Among the patients with axillary node involvement, however, 21N status did not appear to be a significant additional prognostic factor. Internal mammary node metastases were significant. In a multivariate study, only axillary and internal mammary node metastases were significant prognostic factors for either the entire group of patients or those with positive axillary nodes. Therefore, axillary node dissection and biopsy of the internal mammary nodes may provide important prognostic information for patients with breast cancer.

Adult

Papillary thyroid cancer and its surgical management.

The surgical management in papillary thyroid cancer has been highly controversial. In the Department of Surgery (II), Kanazawa University Hospital, the surgical management especially for cervical lymph node metastases has changed since 1973 from a conservative approach to an aggressive one. In order to determine whether an aggressive approach is warranted, a retrospective multivariate analysis was carried out on 106 cases of papillary thyroid cancer. The patients have been followed for 10-28 years. Multivariate analysis was conducted following Cox's model. By this analysis, aggressive management appeared to have no impact on survival or relapse-free survival. However, age, sex, tumor size, and cervical lymphadenopathy were confirmed to be important prognostic factors in survival and/or relapse-free survival.

Adult

Alpha-fetoprotein production by hepatocellular carcinoma is prognostic of poor patient survival.

Immunohistochemistry using the avidin-biotin-peroxidase complex method was performed to study the production of alpha-fetoprotein (AFP) in hepatocellular carcinoma (HCC) tissue specimens which were obtained surgically. The relationship between staining for AFP and serum AFP levels or pathological findings was examined. The prognosis of the patients with HCC who underwent curative hepatic resections was studied with respect to the staining for AFP in their tumors. The mean serum AFP level in patients with positive AFP staining was significantly higher than in those with negative AFP staining. No significant relationship was found between AFP positivity and tumor size, tumor encapsulation, degree of vascular invasion, or the histological differentiation grade of the tumor. The patients with AFP-positive carcinomas had a poorer prognosis than did those with AFP-negative carcinomas (5-year survival rate of AFP-positive and negative groups were 26.7% and 56.5%, respectively.

Carcinoma, Hepatocellular

The relationship between lymph node metastases and DNA-ploidy status as prognostic factors in invasive breast cancer.

We evaluated the relationship between the regional lymph node metastases and the DNA ploidy status in 207 patients with invasive breast cancer, as well as their prognostic values in estimating the prognosis of breast cancer. A significantly higher incidence of aneuploidy was found in patients with a large T3 or T4 tumor, a positive axillary lymph node status, more than 4 positive axillary lymph nodes or positive internal mammary lymph nodes. In a univariate study, the overall survival was significantly correlated with tumor size, axillary lymph node status, axillary and internal mammary lymph node metastases, and DNA ploidy status. In the multivariate analysis, however, only axillary and internal mammary lymph node metastases were recognized as important independent prognostic factors on survival. In this series, the DNA ploidy status did not appear to be an independent prognostic factor either in the entire series or in negative axillary node patients, since it was closely correlated with the axillary or internal mammary lymph node metastases, and the axillary node negative patients had an extremely favorable prognosis.

Adult

Clinicopathologic study of alcohol-like liver disease in non-alcoholics; non-alcoholic steatohepatitis and fibrosis.

Alcohol-like liver injury (ALLI) in non-alcoholics has not been elucidated in Japan. The present study attempted to characterize the clinicopathologic features of ALLI in routine liver biopsies. ALLI was found in 1% of 561 biopsy cases obtained from 1988 to May, 1991 at Kanazawa University Hospital. Laboratory data characteristically showed only a mild to moderate degree of dysfunction, and none of the cases exhibited jaundice. Hepatic histology showed a mild to moderate degree of perivenular, pericellular and/or portal stellate fibrosis with a varying degree of fatty change and inflammatory cell infiltration. Portal stellate fibrosis with a varying degree of cell infiltration was more severe than the centrilobular or pericellular fibrosis in all cases. Intralobular inflammatory cell infiltration was associated with spotty or single hepatocyte necrosis, but extensive hepatocyte necrosis was not observed. Neutrophil infiltration was absent or minimal, and lymphocytes predominated in all cases. Mallory bodies were rare and were found in a few hepatocytes of only one of the 7 cases. The above histologic findings in ALLI were very similar to those seen in liver disease in Japanese alcoholics, and were somewhat different from ALLI reported in Western countries. In cases in which hepatic fibrosis, characterized by pericellular, perivenular or portal stellate fibrosis dominated without apparent hepatic necrosis and inflammation, the term "non-alcoholic steatofibrosis" is more suitable to depict its liver histology, being very similar to the alcoholic fibrosis frequently seen in Japanese alcoholics.

Adult

Chronic thyroiditis: thyroid function and histologic correlations in 601 cases.

Six hundred one patients with histologically proven "chronic thyroiditis" were assessed for the correlation of thyroid function to histologic findings. The histology of chronic thyroiditis was classified into four groups (oxyphilic, mixed, focal, and hyperplastic), and the thyroid function of patients was divided into hyperthyroid, euthyroid, latent hypothyroid, and overt hypothyroid, based on the laboratory data of serum triiodothyronine (T3), thyroxine (T4), and thyrotropin (TSH) levels, as well as thyrotropin-releasing hormone (TRH) tests. In the oxyphilic group (137 cases), 116 (85%) of the patients were classified as hypothyroid: 52 (38%) as latent hypothyroid and 64 (47%) as overt hypothyroid. In the mixed group (161 cases), the thyroid function of the patients varied. Thirty-seven (23%) of the patients were classified as hyperthyroid, 61 (39%) as euthyroid, 54 (33%) as latent hypothyroid, and nine (5%) as overt hypothyroid. In this group thyroid function was intimately related to the ratio of replacement by hyperplastic-changed follicles and oxyphilic-changed follicles. In the focal group (149 cases), 123 (83%) of the patients were classified as euthyroid, while 22 (14%) were classified as latent hypothyroid. The frequency of latent hypothyroid patients increased in parallel with the severity of cell infiltration. In the hyperplastic group (154 cases), 130 (85%) of the patients were classified as hyperthyroid. In this series 19 patients under 10 years of age were included, and no difference in the distribution of histologic varieties was observed between juvenile and adult patients. Thyroid needle biopsy is a useful and safe tool, not only for the histologic diagnosis of chronic thyroiditis, but also for the evaluation of thyroid function and the identification of causes for hyperthyroidism or hypothyroidism.

Adult

Wide resection with latissimus dorsi muscle transposition in breast conserving surgery.

In this study we evaluated whether the immediate transposition of the latissimus dorsi muscle (LDM) improves breast appearance and patient satisfaction after quadrantectomy. Twenty-three patients (transposed group) had the transposition of LDM immediately after quadrantectomy, but eight patients (non-transposed group) had quadrantectomy alone. For evaluation, breast size was classified as small (A or B cup) and large (C or D cup). Consequently, the cosmetic result was evaluated as excellent in 73% of the patients with transposed small breasts, but in only 25% of the patients with non-transposed small breasts and by none of the patients with transposed large breasts. On the other hand, all patients with transposed small breasts reported that they are satisfied with their operation, as opposed to 88% of the patients with transposed large breasts and 63% of the patients with transposed large breasts and 63% of the patients with non-transposed small breasts. It was concluded therefore, that the transposition of LDM is useful in correcting post-quadrantectomy breast deformity, especially in patients with small breasts.

Adult

Carcinoma of the thyroid at a young age--a review of 23 patients.

Twenty-three children and adolescents with thyroid carcinoma who were 20 years old or younger at the time of initial treatment were followed for a mean time of 9.5 years. Of the tumours, 21 were papillary and two follicular carcinomas. The majority (91%) of the 23 cases showed extra-thyroidal extension of the tumour. An association with chronic thyroiditis was observed in 30% of the cases. There was no history of irradiation of the head and neck in any patients. Relapse occurred in eight patients, lung metastases in two and local recurrences in six; one patient died from lung metastases 3 months after initial treatment. Male patients, advanced stage of tumour, less differentiated histological features and DNA aneuploidy were associated with a higher frequency of relapse. The prognosis of thyroid carcinomas in children and adolescents is not so good as is generally believed.

Adenocarcinoma

Papillary thyroid carcinoma in Kanazawa, Japan: prognostic significance of histological subtypes.

A retrospective analysis of 183 papillary thyroid carcinomas was made in order to assess the prognostic factors related to survival. The following factors were found to adversely affect the prognosis: trabecular subtype of papillary carcinoma, the extent of the primary tumour, regional lymph node involvement, the presence of distant metastases, old age, male sex and the extent of the neck dissection. The presence of the follicular variant of papillary carcinoma and the extent of the thyroidectomy did not influence the prognosis. The trabecular subtype of papillary carcinoma is characterized by a trabecular or solid arrangement of follicular cells with nuclei of ground-glass appearance. Univariate and multivariate analysis indicated that patients with this type of thyroid tumour had a poorer prognosis than those with the well-differentiated or follicular variants of papillary carcinoma. In our opinion the trabecular subtype of papillary carcinoma should be included as a separate entity in the WHO classification of thyroid tumours.

Adolescent

Histologic changes in Graves' thyroid gland after 131I therapy for hyperthyroidism.

The effect of 131I therapy was examined in 13 thyroid glands affected by Graves' disease 3 to 29 years after irradiation for hyperthyroidism. All of the patients had clinically palpable thyroid nodules. Two patients were in a latent hypothyroid, 6 in a euthyroid and 5 in a hyperthyroid state. The microscopic changes in the thyroids showed a pattern of multiple adenomatous nodules with cystic changes, marked oxyphilic cell changes with nuclear atypism and various degrees of chronic thyroiditis. Immunohistochemical staining for TG and T4 was negative to mildly positive in these oxyphilic cells and entirely negative for EGF and CEA. The DNA ploidy pattern was diploid pattern in 6 cases. One papillary-type microcarcinoma occurred, but there was no evidence of a relationship between the tumor and the irradiation. The pathologic findings in Graves' thyroid gland after 131I therapy are not specific, but pathologists should differentiate this lesion from adenomatous goiter, which occurs with no apparent cause, or from thyroid carcinoma because of the marked nuclear atypism of this lesion.

Adult

Effects of switching from a high-fat diet to a low-fat diet on tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats.

We investigated the stimulatory effect of a high-fat diet on tumorigenesis, tumor proliferation and cell kinetics of 7,12-dimethylbenz(a)anthracene-induced mammary carcinomas in Sprague-Dawley rats, and sought to determine whether switching the animals from a high-fat diet to a low-fat diet would suppress tumor proliferation and cell kinetics. The high-fat diet significantly stimulated tumorigenesis, tumor proliferation and cell kinetics. After the animals were switched from the high-fat diet to the low-fat diet, however, tumor growth decreased, the BrdUrd labeling indices of tumors significantly decreased, and the potential doubling times of tumors significantly increased. Therefore, switching from a high-fat diet to a low-fat diet may improve the prognosis of breast cancer.

9,10-Dimethyl-1,2-benzanthracene

Metabolic fate of [14C]triglyceride-entrapped lactosylceramide-bearing liposomes after intravenous injection into mouse.

We investigated the distribution and fate of liposomes after their intravenous injection into a mouse. Liposomes were composed of dimyristoylphosphatidylcholine, cholesterol and dicetylphosphate (7:2:1, molar ratio) with or without lactosylceramide. They were characterized as small unilamellar vesicles, approximately 100 nm in diameter, using gel-exclusion chromatography on a Sephacryl S-1000, freeze-fracture electron microscope and dynamic light scattering method. Liposomes were very stable in serum as seen by the results of leakage of the entrapped marker and electrophoresis experiments. We demonstrated that liposomes were internalized by way of an endocytotic process via coated vesicles detected in the electron microscope. The increase in liver uptake of lactosylceramide-bearing liposomes was mostly accounted for by enhanced uptake in the parenchymal cells, while uptake by non-parenchymal cells was only slightly increased. This observation supported the notion that a galactose-specific receptor was involved in liver uptake of lactosylceramide liposomes. The lactosylceramide-bearing liposomes were preferentially recovered in the liver and were found to first be predominantly localized in the mitochondria-lysosomal fraction. They were then decomposed by lysosomal enzymes, and the hydrolyzed components were reincorporated into membrane phospholipids in the microsomal fraction. At the same time, a rapid and reversible exchange of phosphatidylcholine between microsomes and mitochondria was demonstrated.

Absorption

Fluorescent probe-labeled lipid microsphere uptake by human endothelial cells: a flow cytometric study.

Lipid microspheres have been used as carriers of drugs such as prostaglandin E1 (lipo-PGE1) and corticosteroid (liposteroid). Lipo-PGE1 is used for the treatment of chronic arterial occlusive diseases because its activity is far greater than that of free PGE1 in vivo. To verify the fact that the drug carriers, lipid microspheres, are preferentially taken up by endothelial cells, we labeled lipid microspheres with a fluorescent probe, DiI (DiI-LM), and observed them in some in vitro models. Stoichiometric fluorescence was obtainable, and the fluorescence was stable between pH 3.3 and pH 8.9. Human umbilical vein endothelial cells and cells of a human endothelial cell line, ECV304, showed increased uptake of DiI-LM, 81% and 61%, respectively. In contrast, uptakes were less than 7% in human skin fibroblasts, 3T3 cells, and human neutrophils. Prominent perinuclear fluorescence was also observed in endothelial cells by fluorescence microscopy. DiI-LM and flow cytometric analysis will be useful for studies to elucidate the precise mechanism of the selective accumulation of lipid microspheres by cells in blood vessel walls.

Carbocyanines