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Biomedical subjects

M Yoshimoto

Publications and source records attributed to M Yoshimoto.

At least 163 records · Page 9Linked to original sources
PubMed1995

Non-A beta component of Alzheimer's disease amyloid (NAC) is amyloidogenic.

The non-A beta component of Alzheimer's disease (AD) amyloid (NAC) was identified biochemically as the second major component in the amyloid purified from brain tissue of AD patients. NAC, derived from its 140 amino acid long precursor, NACP, is at least 35 amino acids long (NAC35) although its amino terminus is not definitely determined. An antiserum, anti-NAC-X1, was raised against the amino-terminal 9 amino acid sequence of NAC35 and purified on a peptide affinity column. This affinity-purified anti-NAC-X1 antibody immunostained amyloid in AD brain sections and recognized NAC35 but not NACP on Western or dot blot. In aqueous solutions, synthetic NAC35 self-aggregated in a time-, concentration-, and temperature-dependent manner. NAC35 was detected initially as a monomer with a molecular mass of 3500 Da but became aggregated as a function of time into a higher molecular mass component that could not migrate into the gel. The aggregate of NAC35 showed green-gold birefringence after Congo red staining when analyzed under polarized light and fiber-like structure when analyzed ultrastructurally. These results suggest that NAC can form amyloid after it has been cleaved out of its precursor and may be a crucial factor in amyloidosis in the AD brain.

Alzheimer Disease↗
PubMed1995

Expression of matrix metalloproteinase matrilysin (MMP-7) was induced by activated Ki-ras via AP-1 activation in SW1417 colon cancer cells.

The matrix metalloproteinase matrilysin (MMP-7) is a member of the matrix metalloproteinase gene family, which is believed to play an important role in tumor invasion and metastasis. We have previously found that matrilysin mRNA is specifically expressed in colorectal cancers and adenomas and that its message is localized in the tumor cells themselves. We examined the effects of activated Ki-ras oncogene on the expression of matrilysin in colon cancer cells. We showed that both mRNA and the enzymatic activity of matrilysin were induced by the introduction of activated Ki-ras into SW1417 colon cancer cells. To understand the mechanisms regulating this induction, we analyzed alterations of AP-1 activity induced by activated Ki-ras, using the chloramphenicol acetyltransferase assay. AP-1 activity in SW1417 cells expressing activated Ki-ras was higher than that in control cells. The gel-shift assay also showed higher levels of AP-1 binding protein in SW1417 cells expressing activated Ki-ras than those in control cells. Our results suggest that activated Ki-ras may play a role in inducing expression of matrilysin through an AP-1-dependent pathway in colon cancer cells.

Choline O-Acetyltransferase↗
PubMed1995

Experience of quadrantectomy with axillary dissection without radiotherapy sustained by serial pathological examination for stage I breast cancer.

Breast conserving treatment usually consists of lumpectomy and axillary dissection followed by a limited dose of irradiation so that no significant side-effects occur. However, the precision of lumpectomy depends on the surgical maneuver and pathological evaluation performed at each institution. For this reason, post-operative irradiation to the preserved breast and for the occult carcinoma in the same breast is absolutely mandatory, and effectively becomes a routine step. In 1986, we started to adopt the new breast-conservation method of quadranectomy with axillary dissection for restricted stage I breast cancer without using radiotherapy, at the Cancer Institute Hospital, Tokyo, Japan. As an alternative to irradiation to ensure safety, we chose to administer an elaborate pathological examination on serial sections. The pathological proof has saved troublesome post-operative irradiation, and the results have shown this method to be safe and clear-cut compared to the traditional breast-conserving treatment cited in the literature. From July 1986 to December 1994, we performed 321 cases of quadranectomy and axillary dissection (Q+Ax). If the detailed pathological examination of 5-mm serial sections revealed the stump to be negative, we did not treat the preserved breast with radiotherapy. Out of 321 cases, 247 were analyzed as being stump-negative and of these 235 did not receive radiotherapy at all. During a 5 year 4 month observation period, we have not yet encountered any local recurrence. However, we have experienced 4 cases (1.70%) in which a second cancer developed in the conserved breast. The annual incidence rate was 0.32%. These results are the best so far compared to other published world reports.

Aged↗
PubMed1995

Incidence of latent breast cancer in Japanese women.

Detection of small or early neoplastic lesions is essential for the secondary prevention of cancer, and for this purpose information concerning their incidence and characteristics is required. Although data for latent or early cancers are available for various organs, details are limited in the case of the breast. The present investigation was carried out to cast light on the incidence of latent cancers, considered as lesions, in women with no symptoms and no palpable mass of the breast. Out of 2126 women visiting our hospital for initial breast examination during July to December in 1987, 542 (25.5%) had no complaint and neither a detectable mass on careful palpation nor a tumor shadow on mammography. However, 21 (3.9%) demonstrated microcalcification, 7 giving the impression of a possible malignancy. Subsequent biopsy of the 7 cases revealed 3 carcinomas. The detection rate of breast cancer in this population was thus 0.6% (3/542). Adopting the frequency (36%) of microcalcification detectable on mammography in 185 breast cancers diagnosed in this period as a base, the incidence of latent breast cancer among women visiting our hospital was calculated to be 1.5%.

Adult↗
PubMed1995

Immunogenetic heterogeneity in type 1 (insulin-dependent) diabetes among Japanese--class II antigen and autoimmune thyroid disease.

HLA-DQA1 and DPB1 alleles were examined in relation to autoimmune thyroid disease (AITD) in the Japanese type 1 diabetic patients. The subjects consisted of 14 type 1 diabetic patients with Graves' disease, 12 patients with Hashimoto's thyroiditis and 32 type 1 diabetic patients without AITD. Comparisons were made with 35 normal controls. Among the type 1 diabetic patients with Graves' disease, the age at onset of diabetes was 31.8 +/- 14.6 years old, which was later than that of those without AITD (P < 0.01). DR9 was increased (57.1% vs. 25.9%, P < 0.05, RR: 3.85, chi 2:4.36) in the patients with Graves' disease. DQA1*0301 was increased and DQA1*0103 was decreased in the patients with Graves' disease and those without AITD. HLA-DPB1*0501 was increased (92.9% vs. 54.3%, P < 0.05, RR: 11.0, chi 2:6.57) in the patients with Graves' disease. These findings suggest the existence of a Graves' complicated subgroup characterized by the increasing association of DPB1*0501 and late onset of diabetes in Japanese type 1 diabetic patients. There exists a heterogeneity in Japanese type 1 diabetes.

Adult↗
PubMed1995

The precursor protein of non-A beta component of Alzheimer's disease amyloid is a presynaptic protein of the central nervous system.

Non-A beta component of Alzheimer's disease amyloid (NAC) is the second component in the amyloid from brain tissue of patients affected with Alzheimer's disease. Its precursor protein (NACP) was shown to be a brain-specific protein. In rat brain, NACP was more abundant in the neocortex, hippocampus, olfactory bulb, striatum, thalamus, and cerebellum and less abundant in the brain stem. Confocal laser microscopy analysis revealed that anti-NACP immunostaining was colocalized with synaptophysin-immunoreactive presynaptic terminals. Ultrastructural analysis showed that NACP immunoreactivity was associated with synaptic vesicles. NACP sequence showed 95% identity with that of rat synuclein 1, a synaptic/nuclear protein previously identified in rat brain, and good homology with Torpedo synuclein from the electric organ synapse and bovine phosphoneuroprotein 14 (PNP-14), a brain-specific protein present in synapses. Therefore, NACP is a synaptic protein, suggesting that synaptic aberration observed in senile plaques might be involved in amyloidogenesis in Alzheimer's disease.

Alzheimer Disease↗
PubMed1995

Association of genetic alterations on chromosome 17 and loss of hormone receptors in breast cancer.

To investigate possible relationships between genetic alterations and hormonal deregulation during breast cancer development and/or progression, we examined 616 primary breast cancers for loss of heterozygosity (LOH) at chromosomal regions 16q24, 17p13.3 and 17q21, and for amplifications of the ERBB2 and c-MYC loci. A comparison of oestrogen receptor (ER) and progesterone receptor (PgR) status in tumour cells with data concerning these genetic alterations revealed that LOH at 17q21 was significantly correlated with absence of oestrogen receptors (ER) (P < 0.0003) or progesterone receptors (PgR) (P < 0.0001), and with the absence of both (P < 0.0001). Similarly, a significant association was observed between amplification of ERBB2 and the absence of either ER or PgR. LOH at 17p13.3 was associated with the absence of PgR (P < 0.01). These data suggest a possible relationship between specific genetic changes on chromosome 17 and hormonal deregulation in the progression of breast cancer.

Breast Neoplasms↗
PubMed1995

Frequent development of murine T-cell lymphomas with TcR alpha/beta+, CD4-/8- phenotype after implantation of human inflammatory breast cancer cells in BALB/c nude mice.

Tumors developed quite frequently in some of the visceral organs, including spleen and liver, in BALB/c nude mice upon subcutaneously xenografting surgical specimens from five different inflammatory breast cancer patients. All of these tumors developed within two and a half months to one year after the subcutaneous inoculation of surgical specimens. From these tumors, five independent transplantable tumors, including tMK-2, tHK-1, tYK-1, tYK-2 and tTY-1 have been established. Chromosome analysis, morphologic studies by light and electron microscopy and phenotype analysis indicated that these tumors are of mouse origin. The tMK-2 tumor was highly metastatic to the spleen and liver when it was subcutaneously transplanted into the right scapular region. In addition, the region where the tMK-2 tumor cells were subcutaneously inoculated showed an apparently inflammatory process represented by erythema. After subcutaneous inoculation into the right scapular region, tHK-1, tYK-1, 2, and tTY-1 tumors also metastasized to some of the visceral organs, including spleen and liver. From these tumors, in vitro cell lines were established. The cells grew in a stromal-cell dependent manner under in vitro culture conditions. The cells were again tumorigenic at the inoculated region and metastasized to various organs, including liver and spleen, of BABL/c nude mice. Histological examination revealed that the tumors showed features of malignant lymphoma. Phenotypically, these five tumors expressed early T lymphocyte markers as revealed by anti-mouse anti-TcR alpha/beta, anti-CD3, CD4 and CD8 monoclonal antibodies. To our knowledge, these cell lines are the first T-cell lines showing the phenotype of extrathymically differentiated T-cells in the liver.

Animals↗
PubMed1995

Serum hepatocyte growth factor levels in patients with chronic renal failure.

The serum levels of hepatocyte growth factor (HGF) were determined in chronic renal failure (CRF) patients. Nondialysis patients with renal insufficiency had significantly higher serum HGF than normal subjects (0.34 +/- 0.10 ng/ml, n = 21 vs. 0.19 +/- 0.05 ng/ml, n = 15; p < 0.001), and the elevated serum HGF correlated with their serum creatinine levels. Hemodialysis (HD) patients treated for 5-10 years showed higher serum HGF than those receiving HD for 1 year or less (0.45 +/- 0.14 ng/ml, n = 8 vs. 0.33 +/- 0.11 ng/ml, n = 9; p < 0.05). Continuous ambulatory peritoneal dialysis patients also showed elevated serum HGF levels comparable to those of HD patients. There was no difference in serum HGF levels in HD patients with or without acquired cystic disease of kidney. Consequently, serum HGF is elevated in CRF, which may be attributed to the increased production of HGF in response to the chronic renal injury, the effect of heparin, or reduced removal of serum HGF in CRF patients.

Adult↗
PubMed1995

Molecular cloning and expression of hardening-induced genes in Chlorella vulgaris C-27: the most abundant clone encodes a late embryogenesis abundant protein.

To investigate the effects of hardening on gene expression in Chlorella vulgaris Beijerink IAM C-27 (formerly Chlorella ellipsoidea Gerneck IAM C-27), a frost-hardy strain, 17 cDNA clones corresponding to hardening-induced Chlorella (hiC) genes were isolated by differential screening of a cDNA library from 6-h hardened cells. Northern blot analysis of transcripts of hiC genes showed that these genes are specifically induced by hardening and that their patterns of induction vary. Southern blots of genomic DNAs from two strains (Chlorella ellipsoidea Gerneck IAM C-102, chilling-sensitive; and C. vulgaris C-27, frost-hardy) of Chlorella indicated that ten hiC clones out of 17 hybridized only with DNA of strain C-27 and the other seven clones hybridized with DNA of both strains. However, of these seven clones, transcripts corresponding to six clones did not accumulate in strain C-102 at low temperatures. The sequence of a deduced protein encoded by the most abundant clone, hiC6, exhibited homology to sequences of Group III LEA (late embryogenesis abundant) proteins and had an amino-terminal amino acid sequence that was similar to the sequences of chloroplast transit peptides.

Acclimatization↗
PubMed1995

[Therapeutic efficacy of hepatectomy in the treatment of hepatic metastases from breast cancer].

This study was performed to evaluate whether or not surgical excision of hepatic metastases from breast cancer has any effect on the prognosis. Between September 1985 and April 1993, eight patients with hepatic metastases (solitary in four cases, multiple in four cases) underwent hepatectomy. Two patients among them had other remote recurrence besides that arising in the liver. Right hepatectomy in two cases, left hepatectomy in one, extended left hepatectomy in one and partial hepatectomy in four were done. No postoperative complications developed. Four patients incurred liver recurrence within an average period of 11.5 months after hepatectomy, with three of average period of 11.5 months after hepatectomy, with three of them dying from the disease within 16 to 36 months after hepatectomy. The other four were free of liver recurrence and remained alive for 3 to 65 months post-operatively. The 50% survival time was 36 months after hepatectomy and 40 months after the discovery of hepatic metastases. Although hepatectomy could only be applied to a restricted number of patients and these results are obviously insufficient, we believe that surgical procedure for liver metastases from breast cancer, if possible, is undoubtedly beneficial in prolonging the survival in such patients.

Breast Neoplasms↗
PubMed1995

Isolation and characterization of hardening-induced proteins in Chlorella vulgaris C-27: identification of late embryogenesis abundant proteins.

Hardening-induced soluble proteins of Chlorella vulgaris Beijerink IAM C-27 (formerly Chlorella ellipsoidea Gerneck IAM C-27) were isolated and purified by two-dimensional high-performance liquid chromatography (2D-HPLC) on an anion-exchange column, with subsequent reversed-phase chromatography. Some of the proteins were resolved by SDS-PAGE, characterized by amino-terminal sequencing and identified by searching for homologies in databases. Separation of the soluble proteins during the hardening of Chlorella by a combination of 2D-HPLC and SDS-PAGE revealed that at least 31 proteins were induced or increased in abundance. Of particular interest was the induction after 12 h of a 10-kDa protein with the amino-terminal amino acid sequence AGNKPITEQISDAVGAAGQKVG and the induction after 6 h of a 14-kDa protein with the amino-terminal sequence ALGEESLGDKAKNAFEDAKDAVKDAAGNVKEAV. The amino-terminal sequences of these proteins indicated that they were homologous to late embryogenesis abundant (LEA) proteins. Furthermore, the level of a 22-kDa protein also increased after 12 h. The amino-terminal sequence of this protein, AAPLVGGPAPDFTAAAVFD, indicated that it was homologous to thioredoxin peroxidase.

Amino Acid Sequence↗
PubMed1994

[A five-year follow-up of two different 131I treatment methods for Graves' disease and the factors affecting the outcome].

We employed two different methods of 131I treatment for Graves' disease in 285 patients and compared the results between the two. (We also analyzed the factors affecting the treatment outcome.) A single dose of 131I adjusted to the patients' thyroid weight was administered to 180 patients in group 1, while a relatively lower dose of 131I (approximately 30Gy) was given repeatedly to 105 patients in group 2. A 5-year follow-up showed that in group 1, 34% of the patients were euthyroid, 11% hypothyroid, 11% subclinical hypothyroid and 44% still remained hyperthyroid. In group 2, 43% of the patients were euthyroid, 5% hypothyroid, 35% subclinical hypothyroid and 17% hyperthyroid. The factors affecting the outcome of the treatment in group 1 patients were their thyroid weight, the duration of the disease and TRAb levels. No significant correlation was observed between the efficacy of 131I treatment and the patients' sex, age, 24hr 131I-uptake, effective half life of administered 131I or titers of antithyroid antibodies. We conclude that the repeated low dose administration of 131I provides the best outcome in a 5-year follow-up. However, we suggest that an adjusted dose of 131I in relation to the patients' thyroid weight should be employed to obtain a faster therapeutic response.

Adult↗
PubMed1994

Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin.

Matrilysin is believed to have a role in tumor progression. Its expression correlates with the occurrence of colorectal cancer. We have examined the expression of matrilysin mRNA in various colorectal disorders and its localization using RT-PCR and in situ hybridization. We have also examined whether Matrilysin is induced by cell to matrix interaction. Matrilysin mRNA was detected in all adenoma tissues examined, whereas none was detectable in hyperplastic polyps, mildly inflamed regions of ulcerative colitis or normal colon tissues, and its message was localized in adenoma cells themselves. In addition, levels of enzyme activities of matrilysin were lower in adenomas compared with cancers in casein zymography. Matrilysin mRNA was induced by immobilized truncated fibronectin or RGD peptide. Thus, matrilysin may play an important role in colorectal carcinogenesis.

Adenoma↗