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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 325 records · Page 18Linked to original sources

Concordant p53 and DCC alterations and allelic losses on chromosomes 13q and 14q associated with liver metastases of colorectal carcinoma.

To identify genetic alterations associated with acquisition of metastatic ability in colorectal carcinoma, 31 liver metastases and 40 primary tumors of colorectal carcinoma from 55 patients were analyzed for loss of chromosomal heterozygosity using 46 polymorphic DNA markers covering 15 chromosomes. Loss of heterozygosity (LOH) and/or rearrangement at the TP53 and DCC loci were detected in all liver metastases (10 of 10 at TP53 and 19 of 19 at DCC), and were observed in 59% (10 of 17) at TP53 and 75% (18 of 24) at DCC respectively in the primary tumors. Furthermore, the incidence of LOH on chromosomes 13q and 14q was higher than that on other chromosomes in liver metastasis, and it was higher in liver metastases than in primary tumors (20/30 vs. 18/39, p = 0.072 on chromosome 13q and 21/31 vs. 16/40, p = 0.018 on chromosome 14q). In 4 cases, LOH or rearrangement at loci on chromosomes 13q, 14q and 18q not detected in primary tumors was observed in liver metastases from the same patients. These results suggest that concordant p53 and DCC alterations and inactivation of several other tumor-suppressor genes, especially those on chromosomes 13q and 14q, play important roles in the acquisition of metastatic potential of colorectal carcinoma.

Alleles↗

Effects of mebendazole on Angiostrongylus costaricensis in mice, with special reference to the timing of treatment.

Mebendazole was given to mice infected with Angiostrongylus costaricensis at a single dose of 5 mg/kg at 6, 11, 16 or 21 days post-infection (p.i.) and in five successive doses at 5 mg/kg daily at 6, 11 or 16 days p.i. The effects were comparatively assessed by examining various parameters in host mice and worms. As a whole, the effects of mebendazole were caused more conspicuously by five successive treatments than by a single treatment. In both treatment modalities, the effects were more remarkable in earlier treatments, and nearly complete effects were caused by five successive treatments before 15 days p.i. These results suggest that the inhibition of egg formation and/or oviposition will inhibit the pathological changes caused in the disease by A. costaricensis, especially before the onset of the changes.

Angiostrongylus↗

A novel role in the removal of blood-borne foreign bodies for pulmonary capillaries in the guinea pig.

In certain mammals, the lung plays an important role in removing blood-borne foreign bodies by means of the numerous macrophages disposed in pulmonary capillaries. The present ultrastructural study demonstrates that in the guinea pig, the lung also plays a significant role in this respect, but that in this species, foreign body elimination takes place by another, hitherto undescribed process. In the guinea pig, the pulmonary capillaries are characterized by numerous neutrophils that adhere to endothelial cells even under normal conditions. At 30 min after intravenous injection of glutaraldehyde-fixed erythrocytes, large numbers of these foreign bodies were found to be ingested by these neutrophils. At 6 h after injection, the erythrocyte-carrying neutrophils had disappeared from the vascular lumen, but endothelial cells had begun vigorously to engulf the fixed erythrocytes by extending membranous processes which completely enwrapped them. Since endothelial cells lack lysosomes, there was no morphologic evidence of erythrocyte digestion within their cytoplasm. It is evident that the erythrocytes then passed through the endothelium, since by 48 h after injection, most of them were incorporated and digested by macrophages proliferating in the alveolar interstitium. The increase in macrophages was confirmed by acid phosphatase histochemistry. These observations indicate that in the guinea pig, the lung plays an important role in clearing blood-borne foreign bodies by the sequential involvement of intracapillary neutrophils, capillary endothelial cells and interstitial macrophages.

Acid Phosphatase↗

Electrophysiological study of dorsal column function in streptozocin-induced diabetic rats: comparison with 2,5-hexanedione intoxication.

Dorsal column function and peripheral motor and sensory conduction velocities (MCV, SCV) were evaluated in experimental diabetic rats and compared with those in 2,5-hexanedione (2,5-HD) intoxicated rats. Hyperglycemia was induced by a single injection of streptozocin, and electrophysiological studies were performed 4 and 12 weeks after the injection. For 8 weeks 2,5-HD was administered daily by drinking water to make the 2,5-HD neuropathy rats. Age-matched rats were used as control. In diabetic rats, gracile surface potentials evoked by electrical stimulation of the lumbosacral trunk remained normal during the experimental period, whereas the N and P waves of the evoked potentials were suppressed and the duration of the N wave was prolonged in the 2,5-HD rats. In 4-week diabetic rats, the antidromic compound action potentials of the gracile tract recorded at the most proximal site of lumbosacral trunk were normal. In 12-week diabetic rats, the gracile tract conduction velocity (GTCV) was decreased, although the duration of these potentials was normal. By contrast, the GTCV was decreased and the duration was markedly prolonged in 2,5-HD rats. These findings might indicate that temporal dispersion of incoming volleys in the gracile tract is increased in 2,5-HD rats, but not in diabetic rats. These results suggest that diabetic myelopathy exists that but the magnitude and progression of this condition are quite different from those of 2,5-HD intoxication, typical dying-back-type neuropathy and that the dorsal column is less vulnerable than the peripheral nerve in diabetes mellitus.

Animals↗

Complement-dependent virolysis of HIV-1 with monoclonal antibody NM-01.

Previous studies have described the isolation of monoclonal antibodies that neutralize human immunodeficiency virus type 1 (HIV-1). However, although certain antibodies are capable of blocking infection of CD4+ cells, the antibody-HIV-1 complex could potentially remain infectious and enter cells by an Fc receptor-mediated mechanism. Indeed, one goal of HIV-1 therapy with antibodies is the development of reagents capable of killing virus. The present studies with murine monoclonal antibody (MoAb) NM-01 demonstrate complement-mediated lysis of HIV-1. NM-01-dependent virolysis has been visualized by electron microscopy. Virus particles treated with NM-01 and rabbit or human complement undergo a process of outer envelope rupture and loss of the electron-dense core. The involvement of human complement in this process was confirmed by the presence of C9 in association with MoAb NM-01 immune complexes. In contrast, virolysis was not detectable with antibody or complement alone. Moreover, although MoAb NM-01 alone is capable of neutralizing HIV-1, the presence of rabbit complement was associated with over a 10-fold decrease in infectivity. Similar but less pronounced effects were observed with human complement. These findings support a potential role for antibody-dependent complement-mediated virolysis in HIV-1 therapy.

Amino Acid Sequence↗

Monoclonal antibodies against hst-1 gene product.

Four monoclonal antibodies (MAbs) against the hst-1 gene product (hst-1 protein) were obtained by a somatic cell hybridization technique. The recognition sites of these MAbs designated HS-131, HS-210, HS-233 and HS-276 on the hst-1 protein were evaluated by competitive binding assay with synthetic polypeptides. HS-131 MAb and HS-276 MAb recognize the epitope located within the 59-73 and the 197-206 amino acid sequences, respectively. The epitopes recognized by HS-210 and HS-233 MAbs could not be determined, but these MAbs showed neutralizing activity against hst-1 protein. Using HS-131 and HS-233 MAbs, a sensitive sandwich enzyme immunoassay (sandwich EIA) has been developed. The assay sensitivity was 1.2-2.5 pg/well of hst-1 protein. Acidic and basic fibroblast growth factors were not cross-reactive up to a concentration of 1 microgram/ml.

3T3 Cells↗

Helicobacter pylori may be transmitted through gastrofiberscope even after manual Hyamine washing.

Endoscopy is an effective diagnostic technique for gastric cancer, which is believed to be associated with Helicobacter pylori. Manual Hyamine washing is a widely used fiberscope cleaning method. Urease B gene of Helicobacter pylori was detected in 50% of the wash-out samples from the biopsy-suction channel of a fiberscope after manual Hyamine washing by nested polymerase chain reaction, and bacterial culture revealed viable Helicobacter pylori in 19%. However, Helicobacter pylori was not detected by either of the above methods in the biopsy-suction channel of the fiberscope after mechanical washing. These findings indicate that manual Hyamine washing of fiberscopes is insufficient to prevent iatrogenic Helicobacter pylori transmission, and that mechanical washing after manual Hyamine washing is essential.

Base Sequence↗

[Cyclosporine disposition in living related donor partial liver transplant recipients].

We studied the disposition of cyclosporine (CyA) in 8 living related donor partial liver transplant recipients (patient A-H). CyA blood levels were determined by fluorescence polarization immunoassay with specific monoclonal antibody (m-FPIA) and fluorescence polarization immunoassay with non-specific polyclonal antibody (p-FPIA). The ratio of the blood levels of CyA determined by p-FPIA to those by m-FPIA varied significantly, because the levels determined by p-FPIA were influenced by the function of graft liver. Thus, the levels of CyA determined by p-FPIA could not be used for the adjustment of CyA dose. The CyA dose ratios [DR; CyA blood level (mg/l)/dose (mg/kg)] of 3 in 8 patients were relatively large in 1-4 d after the transplant operation, however, it decreased within 2-5 d after the operation. CyA DR gradually increased from 5-8 d after the transplantation, and it reached to a maximum in 10-13 d in 5 patients to whom CyA was administered intravenously over 12 d after transplantation. The average ratio of DR in oral administration to that in intravenous one was about 43%. CyA bioavailability in the patient of living related partial liver transplantation was as usual as that in other organ transplant patient except for cadaveric liver transplant patients. The average DR of intravenous CyA administration in liver transplant recipients was 1.5 times larger than that in bone marrow transplant patients. CyA disposition had large inter-individual and intra-individual variation, and CyA blood level and DR varied in clinical time course at least within 1.5 month after operation. Therefore, it is necessary to measure CyA blood level frequently and to adjust CyA dose.

Administration, Oral↗

Amplified genes in cancer in upper digestive tract.

Gene amplification in stomach and oesophageal cancers was reviewed. In stomach cancers, two receptor type tyrosine kinases, c-erbB-2 and K-sam, are frequently amplified and overexpressed. c-erbB-2 seems to be preferentially amplified in well-differentiated, and K-sam in poorly-differentiated, gastric adenocarcinomas. 11q13 genes are amplified in about 50% of the oesophageal cancers. These genes include hst-1, int-2 and cyclin D/prad1, all of which are mapped to chromosome 11 at band q13. Although hst-1 and int-2 are usually not expressed despite amplification, elevated transcription of the cyclin D gene is accompanied by its amplification, suggesting a role of a G1 cyclin in oesophageal carcinogenesis.

ErbB Receptors↗

Effects of sensitization on efficacy of mebendazole in mice infected with adult Angiostrongylus costaricensis.

The relation between immunopotentiation and efficacy of mebendazole in sensitized mice infected with adult Angiostrongylus costaricensis was investigated. When compared with the non-treated control, the sensitized control showed better results in almost all parameters with a few mice being positive for the first-stage larvae in feces and eggs in the intestinal section. The results suggest development of protective immunity in the sensitized mice though it was not completely effective for inhibiting infection, worm growth and their functions. The immunity seemed to be developed by producing specific antibodies against the larvae by sensitization. Among 4 infected groups, the sensitized-treated group had the best results in all parameters especially in worm recovery and worm body length which referred that drug action was enhanced by the sensitization.

Angiostrongylus↗

[Pre and postoperative left ventricular volume and function in infants and children with total anomalous pulmonary venous return].

From January, 1989, to December, 1991, 36 consecutive patients with total anomalous pulmonary venous return (TAPVR) underwent intracardiac repair (ICR) in our institute. We studied the relationship between the size of atrial septal defect (ASD), age and preoperative left ventricular end-diastolic diameter (LVEDD) in 28 patients with regression analysis. There was no statistical relationship between the size of ASD, age and LVEDD. We measured LVEDD, RV to LV pressure ratio (RVP/LVP) and LV fractional shortening (LVFS) using two dimensional echocardiography in 15 patients, prior to and following ICR. LVEDD increased from 1.16 +/- 0.40 cm to 1.62 +/- 0.28 cm immediately following ICR, and then increased to 1.79 +/- 0.34 cm one month following ICR again. LVFS decreased from 38% to 35% immediately following ICR but still remained within normal range (normal range 28-45%). RVP/LVP decreased from 1.0 to 0.69 immediately following ICR, and to 0.39 one month following ICR. We concluded that the decrease of preoperative LV end-diastolic volume in TAPVR was not due to the decrease of LV preload but to anterior deviation of the ventricular septum caused by high RV pressure. There was significant increase of LV volume immediately following ICR, but LVFS maintained in normal range. This study suggested that small LV volume in patients with TAPVR did not influence the surgical results.

Echocardiography↗

[Helicobacter pylori infection in gastric cancer].

The relationship between Helicobacter pylori (H. pylori) infection and gastric cancer becomes the topics in the world, since some reports thereon in 1991. The purpose of this study was to know the prevalence of H. pylori infection in many patients with gastric cancer. We examined the H. pylori IgG antibody in 507 patients with gastric cancer resected surgically in our hospital from 1989 to 1991, retrospectively. For the test of H. pylori IgG antibody, HM-CAP EIA kit (Italy, ENTERIC PRODUCTS Co.) was used. The overall detection rate of H. pylori IgG antibody was 75% (378/507). H. pylori infection was significant significantly frequent in early cancer (80%, 231/288) than advanced cancer (67%, 147/219). But, the other clinicopathological features such as sex, age, histological type, location and the degree of intestinal metaplasia were not significantly correlated with H. pylori infection. To evaluate the risk of H. pylori infection for gastric cancer, we are going to plan a matched-pair case-control study.

Aged↗

[The limits for modified Fontan operations with AV valve regurgitation--the effect of AV valve regurgitation on the Fontan operation for single ventricle].

We performed a modified Fontan operation on 14 patients of single ventricle with AV valve regurgitation (single right ventricle: SRV 8, single left ventricle: SLV 6) until 1990. During the same period, 41 patients of single ventricle without AV valve regurgitation underwent the modified Fontan operation. To evaluate the effect of AV valve regurgitation on the Fontan operation, operative mortality, ventricular and pulmonary functions were compared between two groups. No significant differences were observed in operative mortality (7% vs 12%). There were also no significant differences of post-operative cardiac index (mean 2.6 L/min/m2 vs 2.6 L/min/m2), pulmonary vascular resistance (mean 2.3 U.m2 vs 2.2 U.m2) and preoperative ejection fraction (mean 54% vs 62%) between two groups. Therefore, the hemodynamic status of single ventricle following the Fontan operation remained almost unchanged irrespective of the presence of AV valve regurgitation. This suggested that AV valve regurgitation was not itself a contraindication of the Fontan operation, if the correct indices and time for operation were selected.

Heart Atria↗

Reconstitution of the RB gene suppresses the growth of small-cell lung carcinoma cells carrying multiple genetic alterations.

Multiple genetic alterations, including inactivation of the RB gene, occur commonly in small-cell lung carcinoma (SCLC). To assess a functional role of RB inactivation in the development of SCLC, an RB expression plasmid was introduced by stable transfection into SCLC cell lines, Lu-135 and N417, in which the RB gene was inactivated. Lu-135 and N417 cells transfected with the wild-type RB gene formed G418-resistant colonies twofold less efficiently than those with a mutated RB gene or with the control vector. Intact exogenous wild-type RB genes were detected only in approximately 20% of G418-resistant clones; three of 14 in Lu-135 and three of 16 in N417, respectively. Transcripts from the transfected RB gene were also detected in two of these three clones from Lu-135 and two of three from N417 but the amount of RB mRNA and protein was less than one fifth of that in normal fibroblast cells WI-38. Furthermore, clones with exogenous wild-type RB expression showed either reduced growth rates in culture or suppressed tumorigenicity in nude mice. These findings suggest that functional correction of the RB gene is sufficient to suppress the growth of SCLC cells, even though several other genetic alterations in the cells remain uncorrected.

Animals↗

[Surgical treatment of double orifice mitral valve in atrioventricular septal defect].

Ten patients with double orifice mitral valve and atrioventricular septal defect (AVSD) were examined. There were four cases with incomplete type, three with intermediate type and three with complete type AVSD. All patients with incomplete type AVSD were doing well after the mitral cleft repair, Leaving the accessory orifice untouched. Various valve repair procedures and prosthetic valve replacement were performed in the patients with intermediate and complete types of AVSD with left-sided atrioventricular valve regurgitation. There were three operative deaths, which included one patient with the intermediate type and two with the complete type. All of them were one-month old babies and were operated on emergency. Their general operative findings were hypoplasia of the common atrioventricular valve leaflets, abnormal attachment of the chorda tendineae and papillary muscle dysplasia. These findings increased the difficulty of the valve plasty to control mitral regurgitation.

Child↗

[Surgical repair in hearts with univentricular atrioventricular connection and subaortic stenosis].

Between 1986 and 1990, fourteen patients with univentricular atrioventricular connection and subaortic stenosis underwent surgical treatment. The patients consisted of 7 cases of double inlet left ventricle, 4 with double inlet right ventricle, 3 with tricuspid atresia. The palliative operation was performed in 6 infants ranging in age from 17 days to 6 months. Four patients with mild subaortic stenosis underwent pulmonary artery banding, in two patients this was combined with repair of coarctation of the aorta. Two patients with severe subaortic stenosis underwent the Norwood operation. There were no operative deaths. One of two patients who underwent the Fontan operation 2 years after the Norwood operation died later. The definitive operation was performed in 8 children ranging in age from 4 to 11 years. Five of these 8 patients had previous pulmonary artery banding. Five children with double inlet left ventricle underwent septation combined with enlargement of bulboventricular foramen. Postoperatively all remained in sinus rhythm and had no pressure gradient between Aorta and left ventricle. A Fontan operation combined with a Damus operation was performed in 2 children, 1 of double inlet right ventricle and 1 of tricuspid atresia. In both cases, postoperative angiogram showed no pulmonary incompetence. One patient underwent enlargement of bulboventricular foramen after a Fontan operation. All survived later. Young infants and neonates with severe subaortic stenosis can survive by the Norwood operation. Infants with mild subaortic stenosis, although can survive by pulmonary artery banding, should be closely followed for the development of subaortic stenosis. For relief of subaortic stenosis, enlargement of bulboventricular foramen may be effective in septation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aortic Coarctation↗

[Definitive repair for double inlet ventricle and common atrio-ventricular valve].

From 1982 through 1990, 13 patients with double inlet ventricle and common atrio-ventricular valve underwent definitive cardiac surgery. Nine patients simultaneously had anomalous systemic venous connection and 4 had anomalous pulmonary venous connection. One patient with double inlet left ventricle underwent a successful partition of ventricle and atrio-ventricular valve. All other 12 patients underwent a Fontan operation, which utilized different techniques to deal with various forms of anomalous systemic and pulmonary venous connection. Four patients with common atrioventricular valve regurgitation underwent a Fontan operation combined with a concomitant circular annuloplasty of atrio-ventricular valve. In all 4 patients, the degree of regurgitation decreased postoperatively. There was one operative death (mortality 7.7%). Most of patients with double inlet ventricle and common atrio-ventricular valve now are considered to be suitable not for partition but for the Fontan operation. Because of the complexity of anatomic variables, however, the repair of anomalous systemic or pulmonary venous connections in conjunction with the Fontan operation requires an individualised plan in each patient to provide unobstructed systemic and pulmonary venous pathways. We think that a circular annuloplasty could effectively decrease the degree of atrio-ventricular valve regurgitation in most cases.

Adolescent↗