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Biomedical subjects

M Terada

Publications and source records attributed to M Terada.

At least 289 records · Page 16Linked to original sources

[Reoperation for coarctation of the aorta and interrupted aortic arch].

This report presented four patients who underwent surgery for restenosis after repair of coarctation of the aorta (CoA) or interrupted aortic arch (IAA) at our institution between January 1980 and October 1994. Case #1 underwent primary repair for IAA, VSD, and PDA consisting of aortic arch reconstruction using a EPTFE (expanded polytetrafluoroethylene) graft of 10 mm in diameter at the age of four years. After 17 years, pressure gradient of 58 mmHg between the ascending aorta and the descending aorta prompted the reoperation. Case #2 underwent primary repair for CoA, VSD, and PDA consisting of a bypass between the ascending aorta and the descending aorta with an EPTFE graft of 11 mm in diameter at the age of three years. After 13 years, he had reoperation because of pressure gradient of 64 mmHg. Case #3 had pressure gradient of 20 mmHg between the upper and lower limb at the hospital discharge following patch angioplasty for CoA at five years of age. He underwent unsuccessful percutaneous transluminal balloon angioplasty at age 12 and had reoperation at age 15. Case #4 underwent subclavian flap angioplasty as the first stage operation for CoA, VSD, and PDA at 1 month after birth. About 9 months after the initial operation, the pressure gradient between the upper and lower limb had reached 40 to 50 mmHg, and the patient had reoperation at the age of 1 year. The reoperation method for cases #1, #2 and #3 consisted of bypass grafting from the left subclavian artery to the descending aorta under a simple cross clamping of the thoracic aorta.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[A modified Damus-Kaye-Stansel anastomosis for restrictive bulvoventricular foramen developed 5 years after Fontan procedure].

An one-year old girl, who had pulmonary artery (PA) banding and balloon atrioseptostomy done in the newborn period, underwent modified Fontan procedure on an emergency basis without cardiac catheterization, because of right heart failure. Echocardiogram showed no subaortic stenosis at Fontan procedure. Five years later, subaortic stenosis was documented with a 65 mmHg of ventricular-aortic pressure gradient at catheterization. A modified Damus-Kaye- Stansel (D-K-S) procedure was successfully performed using an end-to-end anastomosis of the distal aorta and a common stump, consisting of previously suture-closed main PA stump and the proximal aorta. At postoperative catheterization, the pulmonary valve was functioning well at LV outlet portion without regurgitation and stenosis. Significant subaortic stenosis may develop after Fontan procedure in patients with morphological narrowing without demonstrable pressure gradient. Such patients should have surgical intervention to the narrowing at the time of Fontan procedure. The modified D-K-S procedure can be an effective procedure to relieve subaortic stenosis after Fontan procedure.

Anastomosis, Surgical↗

Adenovirus-mediated transfer of the HST-1 (FGF4) gene induces increased levels of platelet count in vivo.

The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitogen for a variety of cell types of mesodermal and neuroectodermal origin, including fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells and tissue targets of HST-1 in vivo, adenovirus-mediated HST-1 gene transfer was performed. In nude mice, intraperitoneal injection of 3 x 10(9) plaque-forming units of adenoviruses carrying the HST-1 gene (Adex1HST-1L) caused an increase in the number of platelets in the peripheral blood. The number of platelets reached twice the pretreated level by 12 days after the virus injection and the increased level continued up to 20-30 days thereafter. Administration of recombinant HST-1 protein resulted in a transient increase in the platelet count. The number of megakaryocytes in the bone marrow and spleen of the animals with Adex1HST-1L was increased compared with the control animals. Other hematological changes attributed to HST-1 were not observed. Although the mechanisms involved in increased levels of platelet count by HST-1 protein remain to be elucidated, these findings also suggest that adenovirus with the HST-1 gene may be efficiently used for the treatment of thrombocytopenia in various diseases.

Adenoviridae↗

Highly efficient method for obtaining a subtracted genomic DNA library by the modified in-gel competitive reassociation method.

A highly efficient method to obtain a subtracted genomic DNA library using 1 microgram of target DNA was developed by modification of the previously reported in-gel competitive reassociation procedure. The modified method was based on polymerase chain reaction amplification after selective purification of a target-target reassociated molecule of subtracted DNA fragments to increase cloning efficiency. For a model experimental system, the subtracted DNA library was constructed after two cycles of subtractive reassociation between cervical cancer DNA fragments containing human papilloma virus DNA and the 100-fold excess of dephosphorylated normal tissue DNA fragments which were size-fractionated in agarose gel. Colony hybridization using human papilloma virus DNA as a probe revealed that a more than 500-fold enrichment of human papilloma virus DNA sequences in the subtracted DNA library could easily be obtained. This simple and efficient method will enable us to isolate an unknown foreign DNA fragment and an unknown amplified DNA fragment which might be present in cancer.

Base Sequence↗

Highly frequent homozygous deletion of the p16 gene in esophageal cancer cell lines.

To study the involvement of the p16 tumor suppressor gene in esophageal cancer development, we examined homozygous deletion of the p16 gene in 13 human esophageal cancer cell lines and 9 gastric cancer cell lines, in which some of genetic alterations have already been characterized. By Southern blot analysis, homozygous deletion was observed in 12 out of the 13 esophageal cancer cell lines (92%), in 2 out of a total of 9 gastric cancer cell lines (22%). It was also found that the p16 gene loss, cyclin D1 amplification and p53 gene mutations occurred independently in these cell lines. These findings suggest that loss or mutations of the p16 gene are involved in most esophageal cancers and that mutation of this gene plays a critical role in the development of esophageal cancer.

Blotting, Southern↗

A soluble form of K-sam/FGFR2 protein in the culture medium of human gastric cancer cells.

K-SAM/FGFR2 gene encodes a receptor tyrosine kinase which belongs to the fibroblast growth factor receptor family and is amplified and overexpressed in KATO-III gastric cancer cells. To characterize K-sam proteins in cancer cells, anti-K-sam rabbit polyclonal antibody PK1-2 was raised and used for the immunoprecipitation analysis. 135, 125, and 110-kDa transmembrane proteins were detected in KATO-III cell lysate, while a soluble truncated 85-kDa K-sam protein was found in the conditioned medium. The molecular size of the soluble K-sam protein does not match with those predicted from the secreted forms of the K-sam cDNA which have been cloned so far. The soluble K-sam protein was highly N-glycosylated like the transmembrane versions, and N-glycosylation appeared to be necessary for its release.

3T3 Cells↗

Angiogenic activity of the recombinant hst-1 protein.

The hst-1 transforming gene encodes a protein which belongs to the FGF family of growth factors. We showed previously that a human hst-1 protein produced in silkworm cells has in vitro mitogenic activity to vascular endothelial cells. Here we report effective synthesis of an unfused human hst-1 protein in E. coli and a potent in vivo angiogenic activity of this hst-1 protein by two in vivo assays for angiogenesis, chick chorioallantoic membrane assay and rat cornea assay. The NIH3T3 transformant transfected with the hst-1 gene appeared to develop a highly-vascularized tumor on nude mice. These data showed that the hst-1 protein has an angiogenic activity in vivo as well as in vitro.

Animals↗

Markedly increased amounts of messenger RNAs for vascular endothelial growth factor and placenta growth factor in renal cell carcinoma associated with angiogenesis.

The presence of mRNAs for vascular endothelial growth factor (VEGF) and a VEGF-related protein, placenta growth factor (PIGF) was examined in 29 cases of renal cell carcinoma tissues and adjacent normal kidney tissues and in 4 human renal cell carcinoma cell lines. Northern blot analysis showed that 26 of 27 hypervascular renal cell carcinoma tissues (96%) exhibited a markedly elevated level (3-13 fold) of VEGF mRNA compared to the adjacent normal kidney tissues. Even tumors of small size, whenever they were hypervascular, overexpressed VEGF mRNA. We also demonstrated that mRNA for PIGF was expressed in 21 of 23 hypervascular renal cell carcinoma tissues (91%) but was not detected in the adjacent normal kidney tissues. Two hypovascular carcinoma tissues neither overexpressed VEGF mRNA nor had PIGF mRNA. VEGF mRNA was detected in four human renal cell carcinoma cell lines, while PIGF mRNA was not. There was no difference in the level of basic fibroblast growth factor mRNA between tumor tissues and normal kidney tissue, although our previous study demonstrated elevated basic fibroblast growth factor protein in the serum of renal cell carcinoma patients (K. Fujimoto et al., Biochem. Biophys. Res. Commun., 180: 386-392, 1991). Taken together, these results suggest that VEGF, PIGF, and basic fibroblast growth factor are cooperatively working to increase the angiogenesis in renal cell carcinoma in vivo.

Angiogenesis Inducing Agents↗

Preferential alternative splicing in cancer generates a K-sam messenger RNA with higher transforming activity.

K-sam, also designated fibroblast growth factor receptor 2/BEK, was originally cloned from a stomach cancer cell line KATO-III. The gene is amplified and overexpressed preferentially in poorly differentiated types of stomach cancers. The major K-sam transcript in KATO-III cells encodes a receptor protein with a truncated carboxyl terminus and with a high-affinity binding site for keratinocyte growth factor. This truncated type is produced by an alternative splicing mechanism, and in normal tissues, the truncated type is far less prevalent than the untruncated form. The variant K-sam complementary DNA lacks tyrosine 769, which is a putative phospholipase C gamma 1 association site, and showed a higher transforming activity to NIH3T3 cells than the untruncated form, which is identical with the keratinocyte growth factor receptor.

3T3 Cells↗

Expression of fibroblast growth factor gene family and its receptor gene family in the human upper gastrointestinal tract.

All of 13 human esophageal cancer cell lines contained mRNAs for both basic fibroblast growth factor (bFGF) and its receptor, FGFR1/N-sam protein, while they did not have mRNAs for keratinocyte growth factor (KGF) despite the presence of mRNAs for the KGF receptor gene, K-sam. The results indicate that in human esophageal cancer, bFGF plays roles in an autocrine manner, while KGF acts as a paracrine mediator. In contrast, only one of seven human gastric cancer cell lines contained bFGF mRNAs, while three out of the seven had mRNAs for FGFR1/N-sam protein. The KGF gene was not expressed in any of the gastric cancer cell lines, while K-sam mRNAs were detected in six out of the seven. The results demonstrate that in most human gastric cancers, bFGF does not act as an autocrine mediator, while KGF acts as a paracrine factor. The mRNAs for the other four members of the fibroblast growth factor (FGF) family, including acidic FGF, int-2 protein, hst-1 protein, FGF5 protein and FGF6/hst-2 protein could not be detected in the esophageal and gastric cancer cell lines.

Adenocarcinoma↗

Preferential expression of the third immunoglobulin-like domain of K-sam product provides keratinocyte growth factor-dependent growth in carcinoma cell lines.

Previously, we identified an amplified gene in a stomach cancer cell line, KATO-III, and designated it K-sam. This gene was later found to be identical with a gene for a receptor tyrosine kinase, bek/FGFR2. One of the characteristics of the K-sam gene is structural diversity of its transcripts; K-sam complementary DNA (cDNA) cloned from human brain (K-sam-I) has a completely different sequence at the third extracellular immunoglobulin-like domain as compared to that of the K-sam cDNA derived from KATO-III cells (K-sam-II). Recent study has revealed that this difference signifies a differential ligand affinity; the receptor encoded by the K-sam-I cDNA has a high affinity for basic fibroblast growth factor (bFGF), while the K-sam-II cDNA corresponds to a receptor with the high affinity for keratinocyte growth factor (KGF). Reverse transcription-polymerase chain reaction and RNA blot analysis showed that the K-sam-II-type transcript was present in carcinoma cell lines but not in any of the sarcoma cell lines examined. The K-sam-I-type transcript was expressed in both carcinoma and sarcoma cell lines. Furthermore, KGF enhanced the DNA synthesis of the esophageal cancer cells, TE-1, in a dose-dependent manner, while the effect of bFGF was not substantial. In contrast, the glioblastoma cell line, A-172, that expressed the bFGF receptor showed a mitogenic response to bFGF but not to KGF. These data suggest that KGF is a growth factor used preferentially in cancer cells, and this preference is based on the presence of the K-sam-II-type receptor in carcinoma cells but not in sarcoma cells due to alternative splicing.

Base Sequence↗

Effects of gabergic anthelmintics at higher concentrations on the guanidine-induced twitch responses in isolated frog rectus preparations.

Effects of various gabergic anthelmintics on the guanidine-induced twitch responses in isolated frog rectus preparations were examined. All gabergic anthelmintics such as milbemycin oxime, milbemycin D, avermectin B1a, ivermectin, and diethylcarbamazine (DEC) showed stimulatory effects on the guanidine-induced twitch responses at their higher concentrations. Only piperazine caused inhibitory effects on the twitch responses, even at higher concentrations. The stimulation of the twitch responses by the gabergic anthelmintics was antagonized with tetrodotoxin, hemicholinium-3, d-tubocurarine, and strychnine. These results suggest that all gabergic anthelmintics except piperazine stimulate the release of acetylcholine from the nerve endings and that all of them, including piperazine, have different effects on the gabergic mechanism at lower concentrations and on the cholinergic mechanism at higher concentrations.

Acetylcholine↗

Effect of granulocyte colony-stimulating factor on neutropenia in liver transplant recipients with hypersplenism.

The authors present details of their initial experience with use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) for preventing neutropenia caused by hypersplenism, and, possibly, for reducing the risk of postoperative infections in pediatric liver transplant recipients. Seven patients with end-stage liver disease, three of whom had severe hypersplenism, underwent living related liver transplantation (LRLT). The rhG-CSF was administered to the latter three patients. Peripheral neutrophil counts decreased immediately after reperfusion (to 1500 +/- 300/microL) in the three patients, and returned to normal with use of rhG-CSF 3 to 10 days after transplantation. The dosage was adjusted to maintain peripheral leukocyte and granulocyte counts above 5,000/microL and 2,000/microL, respectively. This initial clinical trial showed that rhG-CSF administration restores the leukocyte counts of patients who have hypersplenism, without any significant adverse effects, and that rhG-CSF holds promise for reducing the risk of infections after liver transplantation.

Child↗

Ontogeny of gubernacular contraction and effect of calcitonin gene-related peptide in the mouse.

The mouse gubernaculum undergoes inguinoscrotal migration in the first postnatal week and also shows rhythmic contractions in organ culture in response to calcitonin gene-related peptide (CGRP). This study aimed to investigate the ontogeny of gubernacular contractile activity and effect of CGRP in organ culture in relation to the normal time of migration. Two hundred eighty gubernacula from male mice of 17 and 19 days' gestation, and of postnatal days 0,2,4,7, 10, and 14 were studied. Half were cultured with CGRP 714 nmol/L, and the other half were cultured without CGRP as controls. All were examined daily (for 7 days) for contractions. In the control group, the cumulative percentages of contractile gubernacula increased from 5% to 100% with age; in the CGRP group, these values ranged from 65% to 100%. There were significant differences between the two groups from prenatal day 17 to postnatal day 4 (P values ranged from less than .001 to less than 0.05, respectively). With increasing age in the CGRP group, the highest contractile rates were observed at the fewest number of days in culture. From prenatal day 17 to postnatal day 4, the gubernaculum had increasing endogenous contractility, but there was low endogenous contractility without exogenous CGRP. Contractility of gubernacula was enhanced strongly by exogenous CGRP, and the culture days of the peak contractile rates lined up in the reverse order. These results suggest that the days of optimal gubernacular contraction with CGRP in vitro are in keeping with the days of natural migration in vivo. This is consistent with the hypothesis that CGRP (released from the genitofemoral nerve) is important for gubernacular migration.

Animals↗

Metabolic effect of PGE1 analogue 01206.alpha CD on nerve Na(+)-K(+)-ATPase activity of rats with streptozocin-induced diabetes is mediated via cAMP: possible role of cAMP in diabetic neuropathy.

We investigated the dose-dependent effects of prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), on motor nerve conduction velocity (MNCV), nerve blood flow (NBF) and Na(+)-K(+)-ATPase (ATPase) activity in streptozocin-induced diabetic rats. At 10 micrograms/kg/day, OP ameliorated MNCV and NBF, but no ATPase activity, whereas at 30 micrograms/kg/day it increased MNCV and ATPase activity, but not NBF. These results suggested a possible direct metabolic effect of OP, at least at a certain dose, on ATPase activity independent of NBF. Since PGE1 exerts an effect on nerve cAMP content, we conducted an in vitro study to clarify the relationship of cAMP to the modulation of ATPase activity in diabetic nerves. We studied sciatic nerves isolated from 53 rats with streptozocin-induced diabetes that had exhibited hyperglycemia for 6 wk. OP increased the activity of ATPase and the accumulation of cAMP in a dose-dependent manner. Dibutyryl cAMP, a cAMP analogue, and aminophyline, which increases nerve cAMP content, enhanced ATPase activity in a dose-dependent manner. In addition, the increased activity of ATPase in diabetic nerves produced by OP was suppressed by a protein kinase inhibitor, H8. These results suggest that ATPase activity in diabetic nerves might be regulated or modified by cAMP and, possibly, by protein kinase A, a finding that is important for clarifying the pathogenesis of diabetic neuropathy and for developing new approaches to treatment.

Alprostadil↗

Calcitonin gene-related peptide receptors in the gubernaculum of normal rat and 2 models of cryptorchidism.

We investigated calcitonin gene-related peptide binding in the gubernaculum from a normal rat, a TS rat (congenitally cryptorchid from unknown causes) and a flutamide rat (cryptorchid secondary to prenatal antiandrogen treatment). Gubernacular sections from 2-day-old male pups were incubated with 125iodine-calcitonin gene-related peptide with various concentrations of unlabeled calcitonin gene-related peptide. After exposure to x-ray film, developed film was quantified by computerized densitometry. The binding analysis showed that concentrations of calcitonin gene-related peptide receptors were 22.9 +/- 2.12, 13.5 +/- 1.70 and 30.3 +/- 2.63 (mean plus or minus standard error of mean, fmol./mg. polymer) for each rat, respectively, and there were significant differences between the normal and TS rats (p < 0.01), and the normal and flutamide rats (p < 0.05). However, there was no significant difference in the dissociation constant among the 3 models. This result shows that deficiency and excess of calcitonin gene-related peptide binding in the gubernaculum are associated with cryptorchidism. Calcitonin gene-related peptide released from the genitofemoral nerve may regulate its own receptor concentration to control gubernacular motility in vivo.

Animals↗

Hormonal control of testicular descent and the cause of cryptorchidism.

This paper briefly reviews the literature on testicular descent and presents new observations from the authors' laboratory which suggest new ways of looking at old problems. There is now good evidence that testicular descent occurs in two morphologically and hormonally distinct phases. Relative 'transabdominal migration' of the testis compared with the ovary occurs at 10-15 weeks of gestation in the human and 'inguinoscrotal' migration occurs at 26-35 weeks of gestation. We have proposed previously that the first phase is controlled by Müllerian inhibiting substance although this remains controversial. The second phase is androgen dependent and is possibly mediated indirectly through the release from the genitofemoral nerve (GFN) of the neuropeptide calcitonin gene-related peptide (CGRP). Recently we have used three different rodent models of undescended testis to determine the involvement of the GNF and/or CGRP. The testicular feminization mouse with complete androgen resistance and the rat exposed prenatally to the antiandrogen flutamide have a deficiency of CGRP in the GFN. In contrast, the mutant trans-scrotal rat which has normal androgen levels has an excess of CGRP in the GFN. All cryptorchidism models, despite their different primary cause, have in common an abnormality of the GNF and/or CGRP which is consistent with the hypothesis that normal testicular descent in the rodent may be mediated by the GFN.

Abdomen↗