Biomedical subjects

Y Miki

Publications and source records attributed to Y Miki.

At least 19 recordsLinked to original sources

PubMed1992

Expression of scavenger receptors on renal cell carcinoma cells in vitro.

Messenger RNAs and proteins of scavenger receptor thought to be macrophage specific protein were expressed in renal cell carcinoma (RCC) cells in vitro. Acetyl LDL was taken up into RCC cells and promoted the production of interleukin-6 (IL-6), an in vitro autocrine growth factor to proliferate the cells. These results suggested that RCC cells might have a scavenger pathway which has not yet been demonstrated except for macrophages.

Blotting, Northern↗

PubMed1992

Nuclear magnetic resonance abnormalities of the cerebral white matter in children with acute lymphoblastic leukemia and malignant lymphoma during and after central nervous system prophylactic treatment with intrathecal methotrexate.

BACKGROUND: A prospective study was conducted to test the feasibility of nuclear magnetic resonance (NMR) imaging in the early diagnosis of treatment-induced leukoencephalopathy. METHODS: The study group included 16 patients with acute lymphoblastic leukemia and 4 patients with malignant lymphoma. All were given intravenous and intrathecal (IT) methotrexate (MTX) for central nervous system prophylaxis. Serial NMR studies were performed before and/or during induction-consolidation cycles. RESULTS: NMR imaging disclosed leukoencephalopathy in 8 of the 20 patients (40%) in the early stages of treatment. In six of the eight, the leukoencephalopathy was resolved after temporary or permanent interruption of IT MTX, and chemotherapy was completed successfully. The other two patients are being treated. Transient neurologic abnormalities developed in two of the eight patients. CONCLUSIONS: The possible causal relationship between leukoencephalopathy and the antimetabolic effects of MTX is discussed. This study clearly shows that NMR imaging is valuable in the early diagnosis and management of treatment-induced leukoencephalopathy.

Adolescent↗

PubMed1992

Germ-line mutations of the APC gene in 53 familial adenomatous polyposis patients.

We searched for germ-line mutations of the APC gene in 79 unrelated patients with familial adenomatous polyposis using a ribonuclease protection analysis coupled with polymerase chain reaction amplifications of genomic DNA. Mutations were found in 53 patients (67%); 28 of the mutations were small deletions and 2 were 1- to 2-base-pair insertions; 19 were point mutations resulting in stop codons and only 4 were missense point mutations. Thus, 92% of the mutations were predicted to result in truncations of the APC protein. More than two-thirds (68%) of the mutations were clustered in the 5' half of the last exon, and nearly two-fifths of the total mutations occurred at one of five positions. This information has significant implications for understanding the role of APC mutation in inherited forms of colorectal neoplasia and for designing effective methods for genetic counseling and presymptomatic diagnosis.

Adenoma↗

PubMed1992

The human prohibitin gene located on chromosome 17q21 is mutated in sporadic breast cancer.

A gene called "prohibitin" was isolated as a candidate antiproliferating gene in rat liver cells. We have isolated the human homologue of the rat prohibitin gene and mapped it to chromosome 17q12-21 where a gene responsible for hereditary breast cancer was localized. DNA sequence analysis of 2 exons in this gene in 23 sporadic breast cancers, which showed loss of heterozygosity on the long arm of chromosome 17 or developed in patients 35 years old or younger, identified 4 cases of somatic mutation; 2 of these were missense mutations; 1 showed a 2-base deletion resulting in truncation of the gene product due to a frame shift; the other had a C to T transition in an intron adjacent to an intron-exon boundary. These results suggest that this gene may be a tumor suppressor gene and is associated with tumor development and/or progression of at least some breast cancers.

Amino Acid Sequence↗

PubMed1992

Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer.

The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.

Adenomatous Polyposis Coli↗

PubMed1992

Interstitial loss of the same region of 5q in multiple adenomas and a carcinoma derived from an adenomatous polyposis coli (APC) patient.

Accumulation of genetic alterations in oncogenes and tumor suppressor genes causes the transformation of a normal cell into a malignant cell. Recently, Fearon and Vogelstein (Cell 61:759-767, 1990) reported on a model for the genetic pathway in development of colorectal neoplasia. To investigate genetic alterations in colorectal carcinomas, we examined allelic losses on some chromosomes in adenomas and carcinomas derived from patients with adenomatous polyposis coli (APC). We found evidence for an interstitial deletion of 5q. Loss of heterozygosity (LOH) of 5q around the APC locus was observed in both adenoma and carcinoma in one case. The fact that the same region of chromosome 5 was lost in five adenomas and one carcinoma derived from the same patient suggests that a somatic interstitial deletion may be caused not by random mechanisms but by a specific mechanism.

Adenocarcinoma↗

PubMed1992

Isolation and partial characterization of a growth factor from human cementum.

Cementum is the mineralized interface through which collagen fibers of periodontal connective tissues are anchored onto the tooth surface. We have isolated and partially characterized a mitogenic factor from human cementum which has properties different from other growth factors. Cementum was harvested from healthy human teeth, extracted in 1.0 M CH3COOH and mitogenic activities were fractionated by heparin-affinity chromatography. Proteins eluted by 0.4-0.6 M NaCl, which contained most of the cementum mitogenic activity, were precipitated by trichloroacetic acid and resolved by HPLC through ion-exchange and reverse-phase columns. NaDodSO4-polyacrylamide gel electrophoresis revealed that the purified preparation contained a M(r) 23,000 protein and this protein was associated with mitogenic activity. The purified cementum-derived growth factor (CGF) was active alone, but at suboptimal concentrations its activity was potentiated by small quantities of plasma-derived serum and epidermal growth factor (EGF). The activity was resistant to heat, but it was destroyed by trypsin digestion. Reduction and alkylation destroyed the mitogenic activity, however electrophoretic mobility was not affected. Binding of EGF to fibroblast membranes was not affected by the CGF and assays to detect platelet-derived growth factor were negative. These characteristics indicated that CGF is a distinct molecular species. Our data show that cementum contains several mitogenic factors and that CGF is the major cementum mitogen.

Cell Division↗

PubMed1992

Somatic mutations of the APC gene in colorectal tumors: mutation cluster region in the APC gene.

We examined somatic mutations of the adenomatous polyposis coli (APC) gene in 63 colorectal tumors (16 adenomas and 47 carcinomas) developed in familial adenomatous polyposis (FAP) and non-FAP patients. In addition to loss of heterozygosity (LOH) at the APC locus in 30 tumors, 43 other somatic mutations were detected. Twenty-one of them were point mutations; 16 nonsense and two missense mutations, and three occurred in introns at the splicing site. Twenty-two tumors had frameshift mutations due to deletion or insertion; nineteen of them were deletions of one to 31 bp and three were a 1-bp insertion. One tumor had a 1-bp deletion in an intron near the splicing site. Hence, 41 (95%) of 43 mutations resulted in truncation of the APC protein. Over 60% of the somatic mutations in the APC gene were clustered within a small region of exon 15, designated as MCR (mutation cluster region), which accounted for less than 10% of the coding region. Combining these data and the results of LOH, more than 80% of tumors (14 adenomas and 39 carcinomas) had at least one mutation in the APC gene, of which more than 60% (9 adenomas and 23 carcinomas) had two mutations. These results strongly suggest that somatic mutations of the APC gene are associated with development of a great majority of colorectal tumors.

Adenoma↗

PubMed1992

Insertion/deletion polymorphism and other restriction fragment length polymorphisms in the MCC gene.

The MCC gene is a candidate as a tumor suppressor gene for colorectal neoplasms. Further, MCC is tightly linked to the familial adenomatous polyposis (FAP) locus by linkage and physical analysis. Hence, restriction fragment length polymorphisms (RFLPs) of this gene might be very useful for presymptomatic diagnosis of individuals in families segregating mutant alleles of the APC gene. Here we report the identification of five polymorphic systems in MCC gene (both cDNA and genomic), one of which is an insertion/deletion polymorphism that is detectable by a polymerase chain reaction method. These five RFLP systems should be useful for linkage studies in FAP and for examining loss of heterozygosity at this locus in colonic polyps and tumors.

Adenomatous Polyposis Coli↗

PubMed1992

Distribution of complement regulators (CD46, CD55 and CD59) in skin appendages, and in benign and malignant skin neoplasms.

Immunohistochemical studies were performed to establish the distribution of membrane cofactor protein (MCP; CD46), decay-accelerating (DAF; CD55) and homologous restriction factor (HRF20; CD59), in normal skin appendages, and in benign and malignant skin neoplasms. At least two of these regulators were detected on normal eccrine glands, apocrine glands and sebaceous glands. They were also found in cellular naevi (CN), seborrhoeic keratoses (SK), basal cell carcinoma (BCC), Bowen's disease (BD), squamous cell carcinoma (SCC) and Paget's disease (PD). Although there were slight differences in their distribution, these regulators were found in all the cells examined, indicating that they are essential factors in human skin as well as other organs, and in neoplasms, in preventing autologous complement attack.

Antigens, CD↗

PubMed1992

Mutations of the APC (adenomatous polyposis coli) gene in FAP (familial polyposis coli) patients and in sporadic colorectal tumors.

We have isolated several genes on chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One (APC) of them was also found mutations in the germ line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer.

Adenomatous Polyposis Coli↗

PubMed1992

[Transcatheter arterial infusion of adriamycin-lipiodol suspension to patients with metastatic liver tumor].

Adriamycin-Lipiodol suspension was administered to 44 patients with metastatic liver tumor using the transcatheter arterial infusion method. The result revealed 23% in the over all effect (partial response or more) of the therapy which was evaluated by comparing the CT images of the tumor, 47% in the 25% or more of the decrease of the tumor, and 65%, very effective in the decrease of the smaller tumor (less than 50 cm2). Except for a case of hepatic subcapsular hematoma after the infusion of Adriamycin-Lipiodol suspension, minor complications were experienced such as abdominal pain, slight fever, and so on. No serious exacerbation in liver function test and white blood cell count was noted.

Adult↗

PubMed1991

Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients.

Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.

Adenomatous Polyposis Coli↗

PubMed1991

Suicide process of renal cell carcinoma cells encountering mumps virus.

Renal cell carcinoma cells produced the substance(s) which killed them (suicide factor(s)) after co-culture with mumps virus. The suicide factor(s) were heat-sensitive and were degraded with trypsin. Furthermore, actinomycin D inhibited the production of the substance(s) by cancer cells. Considering these facts, the substance(s) were thought to be protein(s) derived from de novo synthesis in cancer cells. It was demonstrated that renal cell carcinoma cells proliferated with the autocrine loop of interleukin-6 (IL-6). Mumps virus almost completely inhibited the IL-6 production in several hours. Because of these two facts, the suicide process might be initiated in renal cell carcinoma cells after encountering mumps virus, i.e. inhibition of the autocrine growth loop of IL-6 followed by the induction of an autocrine killing loop of unknown substance(s).

Carcinoma, Renal Cell↗

PubMed1991

[Fast MR imaging of liver metastasis using FLASH and FISP--optimal sequences for T1- and T2*-weighted images].

This paper deals with a study to obtain the optimal sequence of gradient echo (GE) for T1- and T2*-weighted images similar to T1- and T2-weighted images of spin echo (SE). Two GE sequences, fast low angle shot (FLASH) and fast imaging with steady-state precession (FISP), were performed in 15 cases of liver metastasis in various combination of flip angle (FA), repetition time (TR), and echo time (TE). The optimal combinations were summarized as follows: 1) T1-weighted FLASH image with FA of 40 degrees, TR of 22 msec and TE of 10 msec, 2) T1-weighted FISP image with FA of 70 degrees, TR of 100 msec, TE of 10 msec, 3) both T2*-weighted FLASH and FISP images with FA of 10 degrees, TR of 100 msec and TE of 30 msec. Not only to provide the adequate T1- and T2*-weighted images but also to enable breath-holding MR imaging, GE sequences can optionally take place SE in cases of deteriorated images caused by moving artifacts. Other applications support the re-examination and further detailing when required, conveniently rather in short time.

Adult↗

PubMed1991

Hajdu-Cheney syndrome: MR imaging.

Hajdu-Cheney syndrome is a rare congenital disease with acro-osteolysis, osteoporotic changes of the spine and long bones of extremities and marked basilar invagination with an unusually deformed skull. Magnetic resonance imaging of a 32-year-old male revealed the deformed skull and almost horizontal basal angle and the elongated and upwardly shifted brain stem caused by the tip of the odontoid process of the second cervical vertebra invaginating the base of the skull. In addition there were atrophic pituitary gland, widely open sella turcica and symmetrical fluid collections along the optic nerve sheath.

Adult↗

PubMed1991

Lectin staining of neoplastic and normal background colorectal mucosa in nonpolyposis and polyposis patients.

A lectin histochemistry approach was adopted for comparative assessment of a colon cancer risk. Binding of Ulex europaeus agglutinin-I (UEA-I), peanut agglutinin (PNA), Griffonia simplicifolia agglutinin-II (GSA-II), and Dolichos biflorus agglutinin (DBA) was investigated in tumor and background tissue from a total of 34 adenoma and 44 cancer patients and compared with reaction patterns in control and familial adenomatous polyposis (FAP) patients. Adenoma patients with UEA-I positive rectal mucosa were found to have a 33.3 percent familial history of large bowel cancer, which was significantly higher (P less than 0.05) than the respective 4.0 percent figure for patients with negative rectal mucosa. In the cancer patients, an even stronger correlation was noted, with a 63.2 percent UEA-I positive family history association being recorded, as opposed to 4.0 percent in the negative rectal mucosa patients (P less than 0.01). Thus, the results suggest that, apparently, normal rectal background mucosa of individuals genetically at high risk for colon and rectal cancer demonstrates a specific lectin binding ability similar to that of FAP patients and that the simple method using UEA-I staining of rectal biopsy specimens can be of practical use in identification of high-risk colorectal cancer.

Adenoma↗

PubMed1991

Selective release of glutathione transferase subunits from primary cultured rat hepatocytes by carbon tetrachloride and deoxycholic acid.

The change in the activity of glutathione (GSH) transferases by carbon tetrachloride or deoxycholic acid, which induced hepatotoxicity, was studied using primary cultured rat hepatocytes. The activity of GSH transferases in the hepatocytes was decreased after the treatment with carbon tetrachloride or deoxycholic acid in their concentration- and incubation time-dependent manners. On the other hand, these compounds elicited the release of the activity of GSH transferases into the medium. Glycyrrhizin, an antihepatotoxic agent, inhibited the release of both aspartate transaminase (AST) and GSH transferases induced by carbon tetrachloride or deoxycholic acid. All subunits comprised of GSH transferases could not be released by these compounds. The main subunits of GSH transferases released by hepatotoxicity were identified as 3 and 4. These results indicate that hepatotoxicity is accompanied by the selective release of GSH transferase isozymes (class mu) following the loss of the enzymes activity in the cells.

Animals↗