Search PubMed⌕ Search

Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 361 records · Page 20Linked to original sources

Multiple genetic alterations in human carcinogenesis.

Cancer development in man appeared to be a multistage process as suggested by epidemiological studies on commonly occurring gastric, colon, and breast cancers and also on human retrovirus-related leukemia, and by the finding by physicians and surgeons of precancerous lesions for many types of neoplasias. In the last 10 years it has become evident that human cancers have multiple genetic alterations caused by point mutations, recombinations, amplifications, and/or deletions. The genes affected include both oncogenes and tumor-suppressor genes and genes that accelerate cell proliferation and metastasis. Cancers with more malignant properties and poorer prognosis are generally associated with larger numbers of genetic alterations. These multiple genetic alterations are considered to be a direct reflection of the multiple steps involved in carcinogenesis. The multiple genetic alterations are caused by multiple environmental carcinogenic substances or factors, each of which usually exists only at minute concentrations and does not exert any major impact alone except under particular occupational, iatrogenic, and locally geographic conditions. The fact that carcinogenesis is a multistep process involving multiple genetic alterations clearly needs to be taken into consideration in assessing the risks of environmental carcinogenic substances or factors. The increasing incidence of multiple primary cancers is also most easily understood from the viewpoint of multiple steps in carcinogenesis. Possible multiple approaches to cancer prevention should therefore be considered in relation to multistep carcinogenesis and multiple carcinogenic factors.

Animals↗

Calcitonin gene-related peptide (CGRP)-immunoreactive nerves in the tracheal epithelium of rats: an immunohistochemical study by means of whole mount preparations.

The airway mucosa is known to be densely supplied with several types of peptidergic nerve fibers. The distribution of the nerve fibers in a large extent of the mucosa, however, has been difficult to visualize by observation of conventional thin sections. In the present study, whole mount preparations of the rat tracheal mucosa were designed to demonstrate calcitonin gene-related peptide (CGRP)-containing nerves which are most predominant among peptidergic nerves in the trachea. The mucosal sheet of the trachea was separated from the cartilaginous base by means of dispase, a protease, to be processed to immunohistochemistry for CGRP. In the cartilaginous portion, thick nerve bundles immunoreactive for CGRP ran transversely between the cartilage rings, sending terminal branches toward the epithelium. In the membranous portion, immunoreactive nerve bundles were thinner than those in the cartilaginous portion and ran longitudinally. A very dense nerve plexus of CGRP-immunoreactive fibers was demonstrated to extend in the basal part of the epithelium; every epithelial cell appeared to contact more than one nerve fiber. Immunohistochemistry of the whole mount preparations also clearly demonstrated the distribution and entire shape of broncho-pulmonary paraneurons scattered in the epithelium. Ultrastructurally, the CGRP-immunoreactive intraepithelial nerves were found to lack myelin and Schwann sheaths, and to run through the bases of the epithelial cells; they were most frequently surrounded by the cytoplasmic processes of the epithelial cells. The present study demonstrates that immunohistochemistry of whole mount preparations is a useful tool to morphologically analyze neuronal and paraneuronal distribution throughout the tracheal epithelium.

Animals↗

A case of adenoid cystic carcinoma of the bronchus producing cancer-associated antigen, CA19-9.

A 73-year-old male was admitted to Hyogo College of Medicine Hospital for further evaluation of chest x-ray abnormalities. Chest roentgenogram taken at admission showed right lower lobe atelectasis and bronchoscopic examination revealed an endobronchial tumor obstructing the left lower lobe bronchus. The biopsy specimen showed cribriform adenoid cystic carcinoma. The serum CA19-9 level was markedly elevated at admission, leading to immunohistochemical analysis of the biopsy specimen. As a result, in the tumor, CA19-9 was positively stained. This is probably the first reported case of adenoid cystic carcinoma of the bronchus which produces CA19-9.

Aged↗

Motility studies of the cervical esophagus with intrathoracic gastric conduit after esophagectomy.

Gastric emptying, upper esophageal sphincter pressure and intrathoracic gastric motility were studied in esophagectomized patients, ten with a gastric conduit in the posterior mediastinum and ten with a conduit in the retrosternal space. In addition, the clinical state was reassessed more than 6 months after esophageal reconstruction. Gastric emptying, assessed with Tc-99m Sn colloid in a semisolid test meal, did not differ between the two groups. In manometric studies a high-pressure zone distal to the upper esophageal sphincter was associated with dysphagia. A high-pressure zone at the anastomosis was found in 60% of the retrosternal group and 20% of the posterior mediastinal group. As regards food intake, the posterior mediastinal route seems to be preferable in esophageal replacement, since it permits more physiologic motility of the conduit.

Adult↗

Alterations of the p53 gene are common and critical events for the maintenance of malignant phenotypes in small-cell lung carcinoma.

To clarify the incidence, timing and pathogenetic significance of p53 gene alterations in the progression of small-cell lung carcinoma (SCLC), 17 primary tumors, 13 metastases and nine cell lines from 27 patients were analysed by a polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Allelic losses and mutations of the p53 gene were detected in 24 out of 25 informative cases (96%) and 23 out of 27 cases (85%) respectively. Simultaneous losses and mutations were detected in all 16 stage III-IV tumors, while these alterations were detected only in 3 of 6 stage I-II tumors. When allelic losses and/or mutations were detected in the primary tumors, the same alterations were always maintained in the process of metastasis. In three cases, identical p53 alterations were detected among different organ metastases. The mutations detected in five cell lines were also detected in the corresponding original tumors. These results suggest that the alterations of the p53 gene are common and early events, but probably not the first events, in the development of SCLC, and that these alterations are essential for the maintenance of malignant phenotypes in the progression of SCLC.

Base Sequence↗

[Immunohistochemical analysis of CA19-9, SLX, and CA125 in adenoid cystic carcinoma of trachea and bronchus].

We examined the usefulness of 3 carbohydrate antigens, CA19-9, CA125, and SLX, as tumor markers in adenoid cystic carcinoma of the trachea and bronchus, immunohistochemically and clinically. CA19-9 and SLX were detected immunohistochemically in normal tracheal and bronchial glands, but CA125 was not detected. Bronchial secretions obtained from 7 patients without cancer contained high levels of these 3 carbohydrate antigens. There was positive immunohistochemical staining for CA19-9, CA125, and SLX in 5 of 9, 1 of 9, and 3 of 8 patients with tracheal or bronchial adenoid cystic carcinoma, respectively. In a case of bronchial adenoid cystic carcinoma in whom pretreatment serum CA19-9 showed a very high level, this marker changed in parallel with the clinical course. These results suggest the possibility that CA19-9 and SLX could be used as useful markers in patients with tracheal and bronchial adenoid cystic carcinoma.

Antigens, Tumor-Associated, Carbohydrate↗

[Two-stage Jatene procedure after Mustard or Senning operation].

We have successfully performed a two-stage Jatene procedure in four patients who showed severe anatomical right ventricular dysfunction after atrial switch (Mustard or Senning) operation for transposition of the great arteries. All four patients developed an adequate left ventricular pressure for the arterial switch operation by one or two-stage pulmonary artery banding. Left ventricular posterior wall thickness increased sufficiently enough after the banding although left ventricular ejection fraction showed significant decrease. After Jatene procedure left ventricular ejection fraction recovered, and RV end-diastolic volume which had been prominently enlarged preoperatively was dramatically normalized. Cardiac index increased from 3.6 +/- 1.6 l/min/m2 preoperatively to 5.3 +/- 6.1 l/min/m2 postoperatively with the decrease in left atrial pressure. Postoperative electrophysiological study revealed the recovery of sinus node function and atrial conduction by means of the take-down of atrial switch operation previously performed. We conclude that the Jatene procedure should be an ideal alternative in patients with right ventricular dysfunction after atrial switch operation. The left ventricle could be prepared by an effective pulmonary artery banding in most instances.

Cardiac Surgical Procedures↗

[Surgical treatment of total anomalous pulmonary venous connection Darling type Ib using pedicled right atrial flap].

A one-month-old baby with total anomalous pulmonary venous connection (TAPVC) type Ib underwent a total correction with a pedicled right atrial (RA) flap, which was made by incising the RA wall in a quadrangular configuration. The common pulmonary vein (PV) was cut back into the left atrium (LA). Then the RA flap was sutured along the limbus of PV recess and atrial septal defect (ASD) to create a new pulmonary venous channel. The defect in the RA wall was directly closed without any prosthetic patch. Absorbable sutures (# 6-0 PDS) were used throughout. Postoperative course was uneventful and echocardiogram showed widely opened PV channel draining into the LA. We think that this procedure could be applied in various types of total and partial anomalous pulmonary venous connection, avoiding pulmonary venous obstruction on the assumption that the RA flap should grow.

Heart Atria↗

Human hst-2 (FGF-6) oncogene: cDNA cloning and characterization.

The hst-2 gene was previously identified by its close homology to the hst-1 gene. Cosmid clones containing the hst-2 gene were cloned from a normal human genomic library. Focus-forming activity was observed for the hst-2 cosmids when NIH3T3 transfection assay was performed in a serum-free medium, whereas induction of morphological transformation was difficult to detect in an ordinary serum-supplemented medium. The hst-2 cDNA was cloned from the NIH3T3 transformant. Nucleotide sequence analysis of the cDNA indicates that the hst-2 gene encodes a 198 amino acid transforming protein containing a signal peptide with the characteristics of a heparin-binding growth factor. The coding sequence was almost identical to the published portion of the exon sequence of the FGF-6 gene, indicating that hst-2 is identical to FGF-6. The hst-2 cDNA fragment, when inserted into an expression vector, was able to transform NIH3T3 cells effectively, and the resulting transformant formed a well-vascularized tumor in nude mice, thus suggesting an angiogenic property similar to some other members of the family. RNA blot analysis revealed the expression of the hst-2 gene in human leukemia cell lines with platelet/megakaryocytic differentiation potential.

Animals↗

Deletion mapping of chromosomes 14q and 1p in human neuroblastoma.

It has been suggested that loss of heterozygosity (LOH) on the short arm of chromosome 1 is a critical event for the development of neuroblastoma, and we have previously shown frequent LOH on chromosome 14 in neuroblastoma. To pursue these observations, especially to define further the regions which are commonly deleted in the tumor, we examined for allelic losses in 27 cases of neuroblastomas by using a number of polymorphic DNA markers for chromosomes 14q and 1p. LOH was observed in 10 out of the 25 informative cases (40%) on chromosome 14q and in eight out of the 21 informative cases (38%) on 1p. The commonly deleted regions were distal to the D14S13 locus (14q32-qter) on chromosome 14 and distal to the D1S112 locus (1p36.1-pter) on chromosome 1. These results strongly suggest that tumor-suppressor genes important in the pathogenesis of human neuroblastoma are located on the distal part of both chromosomes 14q and 1p.

Alleles↗

A broadly neutralizing monoclonal antibody that recognizes the V3 region of human immunodeficiency virus type 1 glycoprotein gp120.

Previous studies have demonstrated that the principal neutralizing determinant of human immunodeficiency virus type 1 (HIV-1) is located in the V3 loop of glycoprotein gp120. Antibodies prepared against this region using gp120 or peptides as immunogens have been predominantly HIV-1-isolate-specific. In the present studies, murine monoclonal antibodies (mAbs) were prepared against the HIV-1MN strain. One mAb, designated NM-01, was selected for its ability to neutralize both the MN and IIIB strains. Neutralization of H9-cell infectivity as determined by reverse transcriptase assay demonstrated an ID50 of less than 1 microgram/ml for both MN and IIIB. mAb NM-01 also blocked MN and IIIB infectivity in the MT-2 assay and inhibited their reactivity in syncytium formation. The results further demonstrate that mAb NM-01 binds to the V3 loop of gp120 at amino acids 312-326. This mAb reacted equally well with loop peptides from the MN, IIIB, RF, and CDC4 isolates. In contrast, there was less affinity with a similar peptide from the NY5 strain and little if any reactivity with loop peptides from the Z2, Z6, and ELI strains. We also demonstrate that peptides corresponding to the V3 loops of MN and IIIB, but not Z6, block neutralization of IIIB virus by mAb NM-01. These findings indicate that mAb NM-01 reacts with diverse HIV-1 isolates through the Gly-Pro-Gly-Arg sequence of the V3 loop.

Amino Acid Sequence↗

p53 gene mutations in gastric cancer metastases and in gastric cancer cell lines derived from metastases.

Structural alterations of the p53 gene were investigated in tissue specimens of gastric and cervical cancers and in cell lines of gastric, esophageal, and cervical cancers, by polymerase chain reaction-single-strand conformation polymorphism analysis. Two of the four gastric cancer metastases and four of the eight cell lines originally established from gastric cancer metastases were found to have p53 gene alterations in the exon 5 to 11 region; point mutations and amino acid replacements were detected in a liver and an ovary metastasis at exon 7, in the TMK1 and MKN1 cell lines at exon 5, and in the OKAJIMA cell line at exon 10. The normal allele was not found in these cell lines. In the KATO-III cell line, gross deletion and rearrangement of the p53 gene were noted. However, no p53 mutations were identified in 19 primary lesions of gastric cancer, suggesting that the p53 gene abnormality preferentially occurs in the advanced stages of gastric cancer. In contrast to the gastric cancer, none of the 13 esophageal cancer cell lines, including two cell lines established from metastases, and none of the four cervical cancer cell lines showed any aberration in exons 5 to 11 of the p53 gene. During the course of the study, a novel polymorphism in intron 7 of the p53 gene was found, which can be recognized by restriction enzyme digestions of the polymerase chain reaction product.

Amino Acid Sequence↗

Increased serum levels of basic fibroblast growth factor in patients with renal cell carcinoma.

The serum level and urinary output of basic and acidic fibroblast growth factors (FGFs) were measured by sandwich enzyme immunoassay (EIA) in patients with renal cell carcinoma. In over fifty percent (16/31) of renal cell carcinoma patients, basic FGF was elevated (greater than 30 pg/ml) in their sera. There is relatively good correlation between serum levels of basic FGF and tumor stage or grade, while urinary daily output of basic FGF did not correlate with increased malignancy. The present results indicate that serum basic FGF level of patients with renal cell carcinoma is a useful diagnostic and prognostic marker for renal cell carcinoma. On the other hand, acidic FGF was not detectable in all sera and urine.

Antibodies, Monoclonal↗

Allelic loss on chromosome 17p and p53 mutations in human endometrial carcinoma of the uterus.

To understand the involvement of allelic losses and inactivation of tumor suppressor genes for the development of endometrial carcinoma of the uterus (EC), 24 cases of EC were examined for loss of heterozygosity (LOH) using a total of 57 polymorphic DNA markers covering all 23 pairs of chromosomes. LOH was observed at 27 loci on 10 different chromosomes, i.e., chromosomes 1, 3, 6, 11, 13, 15, 17, 18, 20, and 21, but was not detected at loci on chromosomes 4, 5, 7, 9, 10, 12, 14, 16, and X. It was observed only in seven of 24 cases, and the other 19 cases did not show LOH at any loci examined, including five cases of tumors with a high proportion of adenomatous hyperplasia. Among seven tumors with LOH at one or more loci, five tumors showed LOH at loci on the short arm of chromosome 17. Furthermore, mutations of the p53 gene, which is located on the short arm of chromosome 17, were detected in three of these 24 tumors by a polymerase chain reaction-single strand conformation polymorphism analysis and subsequent DNA sequencing. In two of these three tumors, p53 mutations were accompanied by the loss of wild-type p53 alleles. These results suggest that inactivation of the p53 gene is involved in the development of EC as in the case of several other types of human cancers.

Alleles↗

Frequent allelic losses and mutations of the p53 gene in human ovarian cancer.

The p53 gene on chromosome 17p is considered to be a tumor suppressor gene, and frequent mutations of the p53 gene have been found in a wide variety of human cancers. We examined 31 ovarian cancers for allelic losses and mutations of the p53 gene by polymerase chain reaction-single strand conformation polymorphism analysis as well as restriction fragment length polymorphism analysis. Allelic loss of the p53 gene was detected in 16 of 20 cases (80%). Mutations were detected in 9 of 31 cases (29%): 2 cases in exon 4; 5 cases in exons 5-6; and 2 cases in exons 7-8. In 8 of 9 cases, p53 mutations were accompanied by losses of the normal allele. These alterations of the p53 gene were commonly detected from stage I to stage IV. These results suggest that alterations of the p53 gene play an important role in the development of human ovarian cancers.

Base Sequence↗

[A study of new retrievable expandable metallic stent].

The authors improved retrievable expandable metallic stent (REMS), instead of the nylon suture, the REMS was connected with the stainless steel thread. Under fluoroscopy the stainless steel thread of the shrinking body could be observed and was strong enough to retract the placed stent, then the stent could be removed by the stainless steel hook. We placed the REMS in the I.V.C. of canine, and removed them after one week placement, we could not remove them after two weeks placement. This study suggested that the REMS was considered to be useful and safe for clinical application.

Animals↗