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Biomedical subjects

A Cho

Publications and source records attributed to A Cho.

32 records · Page 2Linked to original sources
PubMed1998

Endothelin-1-induced vasoconstriction causes a significant increase in portal pressure of rat liver: localized constrictive effect on the distal segment of preterminal portal venules as revealed by light and electron microscopy and serial reconstruction.

Intraportal infusion of endothelin-1 (ET-1), a potent vasoconstrictor, significantly elevates portal venous pressure. To determine the major site of vascular constriction in the intrahepatic porto-sinusoidal system, we performed an in situ perfusion of rat livers with 1 nmol/L ET-1 at a flow rate of 20 mL/min. Portal pressure rose from 22 cm H2O to 54 cm H2O within 25 minutes. Specimens were prepared for light-microscopic serial reconstruction and electron microscopy. The distal segment of preterminal portal venules (DS/PPV) with an inner diameter of 40 to 80 microm showed complete obliteration of the lumen over a 300-microm distance caused by the intense contraction of perivascular smooth muscle cells and protruding of endothelial cells into the lumen. The proximal segment of preterminal portal venules (PS/PPV) with a larger diameter up to 150 microm also underwent strong constriction, but still had luminal space for the flow, while the PS/PPV with a diameter of 150 to 400 microm showed moderate or mild constriction and retained a wide lumen. Neither terminal portal venules, inlet venules, sinusoids, nor central veins, however, exhibited demonstrable constriction. Liver parenchyma fed by the inlet venules that emerged from the PS/PPV exhibited a wide sinusoidal lumen and vacuolated hepatocytes caused by the influx of excess portal perfusate that escaped from the occlusive areas. The present study has revealed that the DS/PPV functions as a presinusoidal quasi-sphincter mechanism and is involved in the redistribution of intrahepatic portal flow under increased portal pressure.

Animals↗
PubMed1998

Eliminating arterial pulsatile strain by external banding induces medial but not neointimal atrophy and apoptosis in the rabbit.

We have examined the role of vessel pulsation and wall tension on remodeling and intimal proliferation in the rabbit infrarenal abdominal aorta. A rigid perivascular polyethylene cuff was used to reduce vessel systolic diameter by 25%, producing a region of reduced circumferential strain. At 6 weeks postoperatively, reduced circumferential strain caused medial atrophy, with 45% reduction of medial area and 30% loss of medial smooth muscle cells. Apoptotic cell death was indicated by DNA fragmentation, propidium iodide staining, and cell morphology. Cuffing the aorta after balloon denudation produced medial atrophy but did not inhibit neointimal growth. At 1 week postoperatively, intimal thickness was slightly decreased in regions with reduced strain; however, intimal thickening in regions of reduced strain was not different from control segments at 3 weeks postoperatively (intimal area was 0.37 +/- 0.05 mm2 with reduced strain and 0.50 +/- 0.08 for controls, mean +/- SEM). We conclude that circumferential strain is a major factor controlling medial structure and cell number, whereas growth of the neointima after injury is not significantly affected by either reduced strain or extensive medial cell death. Vessel cuffing represents a new model of blood vessel remodeling in vivo that involves extensive smooth muscle cell apoptosis.

Animals↗
PubMed1997

Suppressor and activator functions mediated by a repeated heptad sequence in the liver fatty acid-binding protein gene (Fabpl). Effects on renal, small intestinal, and colonic epithelial cell gene expression in transgenic mice.

A 35-nucleotide sequence in the liver fatty acid-binding protein gene (Fabpl) has been identified that interacts with nuclear proteins present in adult mouse liver, kidney, stomach, small intestine, and colon. The binding site consists of a direct heptad repeat (TTCTGNNTT) separated by five nucleotides. Both heptads are required for formation of stable complexes with nuclear proteins in gel mobility shift assays. The in vivo functions mediated by the repeats were determined by comparing the expression of four Fabpl/human growth hormone fusion genes in multiple pedigrees of adult transgenic mice. The transgenes contained (i) nucleotides -596 to +21 of Fabpl linked to the human growth hormone reporter, (ii) 4 additional copies of the 35-base pair element placed at nucleotide -596 of Fabpl, (iii) 4 additional copies of the sequence placed just upstream of its endogenous site at nucleotide -132, and (iv) a sequence identical to (iii) but with all heptad repeats mutated within each of the 4 additional copies of the 35-base pair element. Transgene expression was defined by RNA blot hybridizations and by light and electron microscopic immunohistochemistry. The heptad repeat functions to suppress expression in tubular epithelial cells of the proximal nephron, in hepatocytes, in the mucus-producing pit cells of the gastric epithelium, and in absorptive enterocytes located in the proximal small intestine. There is a gradient of escape from enterocytic suppression as one moves from the proximal to distal small intestine. This escape progresses to involve successively less differentiated cells located closer and closer to the stem cell zone in crypts of Lieberkühn. The heptad repeat activates gene expression in the colonic epithelium so that all proliferating and nonproliferating cells in colonic crypts distributed from the cecum to the rectum support transgene expression. The heptad has no obvious sequence similarities to known transcription factor binding sites, suggesting that mediators of its in vivo activities are likely to be novel. One candidate factor is a 90-kDa protein identified in Southwestern blots. The 90-kDa protein also binds to an element in the matrix metalloproteinase-2 gene that functions as an enhancer in renal cells, shares sequence homology with the heptad, and generates similar-sized complexes in gel mobility shift assays as the Fabpl repeat. The heptad repeat represents a target for identifying transcription factors that regulate gene expression between gut and renal epithelia and that also regulate the differentiation program of the intestine's principal epithelial lineage as a function of its location along the duodenal-colonic axis. Finally, the Fabpl regulatory elements described in this report should be useful for delivering a variety of gene products throughout the colonic epithelium of transgenic mice.

Animals↗
PubMed1997

Stomach-preserving gastric bypass for unresectable pancreatic cancer.

From 1992 to 1995, we treated 25 patients who had unresectable pancreatic cancer with a stomach-preserving gastric bypass (SPGB). After as much of the stomach as possible was preserved, it was bypassed to the jejunum by end-to-side anastomosis. During the same period, five patients underwent other types of bypasses while 47 similar patients did not undergo gastric bypass. Although the mean operative time for SPGB was significantly longer than for other types of bypass, the mean intraoperative blood loss was similar. Operative morbidity with SPGB was 28%, and there were no operative deaths. In patients undergoing SPGB, the incidence of delayed gastric emptying was high (24%), but the comfort index (ratio of duration of good palliation to duration of survival) exceeded 50% when metastases were either regional or systemic but limited. The comfort index of patients undergoing other types of bypass or not undergoing bypass was less than 40%. However, the patients with extensive systemic metastases survived less than 100 days and the comfort index was less than 30% for all treatment groups. Our results thus suggest that SPGB is safe and effective for patients with either regional metastases or limited systemic metastases.

Cholestasis↗
PubMed1997

Comparison of clinical features and survival in patients with hepatitis B and C virus-related hepatocellular carcinoma.

We analyzed the clinical characteristics and survival of 185 patients with hepatitis B virus-related hepatocellular carcinoma (HBV group) and 1033 with hepatitis C virus-related hepatocellular carcinoma (HCV group) by multi center study. The patients in the HBV group (mean age 52.1 yr) were about 10 years younger than those in the HCV group (mean age 62.9 yr). Liver function, as measured by indocyanine green retention at 15 min, was better in the HBV group (17.5%) than in the HCV group (25.4%). A higher proportion of the HBV group (55%) than the HCV group (44%) had clinical stage I, T-factor differed significantly between the groups: 53% of the HBV group were T3-4 compared with 41% of the HCV group. Furthermore, a higher proportion of the HBV group were graded 2-3 for tumor thrombus in the portal vein (20.3%) and had poorly differentiated hepatocellular carcinoma (7%) compared with the HCV group (7.1% and 5% respectively). Univariate analysis identified poor prognostic factors for hepatocellular carcinoma as HBV, age < or = 50 yr, clinical stage II-III, a high AFP level, higher number of tumors, larger tumor size, tumor thrombus in the portal vein 2-3 and in the hepatic vein 2-3. On multivariate analysis, poor prognostic factors were a high AFP level, higher number of tumors, tumor thrombus in the portal vein 2-3 and in the hepatic vein 2-3, but not HBV, age, clinical stage or tumor size. These results suggest that HBV itself is not a stronger prognostic factor than HCV.

Aged↗
PubMed1997

Effects of changes in blood flow rate on cell death and cell proliferation in carotid arteries of immature rabbits.

Spontaneous and experimental changes in arterial blood flow rates affect tissue accumulation in developing arteries. To examine whether cell proliferation and/or cell death are affected by alterations in blood flow, we ligated the left external carotid artery of 3-week-old rabbits, which reduces left common carotid blood flow by 71%. In control arteries and after 2 days of flow reduction, agarose gel electrophoresis of DNA extracted from all carotid arteries resolved multiple low molecular weight bands characteristic of apoptosis; however, DNA fragmentation in arteries carrying reduced blood flow was 2.5-fold higher than that of control arteries. The effect of reduced blood flow on cell death subsequently waned but remained significant at 7 days. Cell death in carotid arteries was also detected by in vivo uptake of propidium iodide, a DNA-binding fluorescent dye that labels the nuclei of nonviable cells. Both smooth muscle and endothelial cells exhibited large and statistically significant increases in labeling index in the flow-reduced artery. Propidium iodide-labeled cells were cleared from the vessel wall within 1 to 4 hours of labeling, and nuclear staining displayed condensation (clumping) of chromatin in all labeled cells at later time points. This time course and nuclear morphology and the rapid clearance of labeled cells are consistent with death via apoptosis. Many propidium iodide-positive cells did not display chromatin condensation immediately after labeling; however, this was also true of cultured endothelial cells that were driven into apoptosis with sphingomyelinase treatment and then double-labeled with propidium iodide and the apoptosis marker annexin V. We infer that propidium iodide can label apoptotic vascular cells before these cells display chromatin condensation that is detectable with fluorescence labeling of DNA. Replication rates of smooth muscle and endothelial cells, determined by 5-bromo-2'-deoxyuridine uptake, were inhibited by >75% with decreased blood flow. The inhibition of proliferation was unabated after 7 days of reduced flow. These findings indicate that the coordinated regulation of cell death and cell proliferation, in response to changes in arterial blood flow rates, contributes to arterial remodeling during development.

Animals↗
PubMed1996

A study on visual characteristics of binocular 3-D images.

To put the binocular 3-D image system into practical use, it is necessary to investigate the relationship between the system and human subjects in order to make an ergonomic evaluation of the system. In this study, a comparative analysis is made of the changes in the accommodation and pupil functions before and after observing binocular 3-D images as the visual distance varies. The results suggest that: (1) the discordance in the distance information on the accommodation and pupil functions when observing 3-D images is compensated by the miosis and altering the focal depth, (2) from the consideration of the effect of the visual distance condition on the visual functions, it is believed that the visual functions are stabilized at the dark focus in the sense that the changes in the contraction and relaxation after observing the 3-D images are minimized.

Accommodation, Ocular↗
PubMed1995

Apoptosis (programmed cell death) in arteries of the neonatal lamb.

We have examined whether cell death contributes to postnatal remodeling of arteries in lambs. First, abdominal aortic smooth muscle cell proliferation rates fell from 2.87 +/- 0.08% per day at 3 days of age to 1.75 +/- 0.15% per day at 21 days. These proliferation rates would yield a 50% increase in DNA content in the absence of cell death. No increase in DNA content was observed (P < .05 for predicted versus measured accumulation); therefore, significant cell death was inferred. The same analysis did not indicate high cell-death rates in the carotid, renal, or iliac arteries; however, cell death was detected in situ by end-labeling partially degraded DNA with terminal deoxynucleotidyl transferase or by nuclear labeling with propidium iodide, a fluorescent dye that permeates only nonviable cells. Nuclei were labeled in all arteries, although labeling was most frequent in the abdominal aorta, a vessel that regresses substantially after birth. Cell death was apoptotic because DNA extracted from arteries and end-labeled with [32P]dCTP produced a series of low molecular weight bands (DNA ladder) on an agarose gel, a hallmark of apoptosis. The ladder was strong for neonatal abdominal aorta but weak for other arteries. Only weak laddering was observed for fetal abdominal aortas in late gestation, confirming that high apoptosis rates in this vessel were initiated after birth. Intense DNA ladders and frequent in situ labeling indicated high rates of apoptosis in the postnatal intra-abdominal umbilical artery, another vessel that regresses after birth. We conclude that apoptosis contributes to postpartum arterial remodeling. This contribution is greatest in arteries that regress after birth.

Animals↗
PubMed1988

Molecular mechanisms of cell-cell interaction in Dictyostelium discoideum.

During development of the cellular slime mold Dictyostelium discoideum, cells migrate in response to cAMP to form aggregates, which give rise to fruiting bodies consisting of two major cell types: spores and stalk cells. Multicellularity is achieved by the expression of two types of cell-cell adhesion sites. The EDTA-sensitive binding sites are expressed at the initial stage of development. At the aggregation stage, cells acquire EDTA-resistant binding sites, which are mediated by a cell-surface glycoprotein of Mr80,000 (gp80). gp80 is preferentially associated with cell surface filopodia, which are probably involved in the initiation of contact formation between cells. Covaspheres conjugated with gp80 bind specifically to aggregation-stage cells. The binding can be inhibited by precoating cells with an anti-gp80 monoclonal antibody, thus suggesting that gp80 mediates cell-cell binding via homophilic interaction. The structure of gp80 predicted from its cDNA sequence can be divided into three major domains: a membrane anchor, a hinge, and a globular region. An analysis of fusion proteins containing different gp80 segments shows that the cell-binding activity resides in the globular region. In the postaggregation stages, gp80 is replaced by other surface glycoproteins in maintaining cell-cell adhesion. One of them has a Mr of 150,000 (gp150). Anti-gp150 antibodies have no effect on aggregation-stage cells, but they disrupt cell-cell adhesion at subsequent stages. It becomes evident that the complex phenomena of cell adhesion and tissue organization involve the participation of a number of surface glycoproteins.

Amino Acid Sequence↗
PubMed1987

The contact site A glycoprotein mediates cell-cell adhesion by homophilic binding in Dictyostelium discoideum.

Dictyostelium discoideum expresses a developmentally regulated cell surface glycoprotein of Mr 80,000 (gp80), which has been implicated in the formation of the EDTA-resistant contact sites A at the cell aggregation stage. To determine whether gp80 participates directly in cell binding and, if so, its mode of action, we conjugated purified gp80 to Covaspheres (Covalent Technology Corp., Ann Arbor, MI) and investigated their ability to bind to cells. The binding of gp80-Covaspheres was dependent on the developmental stage of the cells, with maximal interaction at the late aggregation stage. Scanning electron microscopic studies revealed the clustering of gp80-Covaspheres at the polar ends of these cells, similar to the pattern of gp80 distribution on the cell surface as reported earlier (Choi, A. H. C., and Siu, C.-H., 1987, J. Cell Biol., 104:1375-1387). Precoating cells with an adhesion-blocking anti-gp80 monoclonal antibody inhibited the binding of gp80-Covaspheres, suggesting that Covasphere-associated gp80 might undergo homophilic interaction with gp80 on the cell surface. Quantitative binding of 125I-labeled gp80 to intact cells gave an estimate of 1.5 X 10(5) binding sites per cell at the aggregation stage. Binding of soluble gp80 to cells was blocked by precoating cells with the anti-gp80 monoclonal antibody. The ability of gp80 to undergo homophilic interaction was further tested in a filter-binding assay, which showed that 125I-labeled gp80 was able to interact with gp80 bound on nitrocellulose in a dosage-dependent manner. In addition, reassociation of cells was significantly inhibited in the presence of soluble gp80, suggesting that gp80 has a single cell-binding site. These results are consistent with the notion that gp80 mediates cell-cell binding at the aggregation stage of development via homophilic interaction.

Cell Membrane↗
PubMed1987

Intestinal epithelial cells preferentially attach to a biomatrix derived from human intestinal mucosa.

Primary intestinal epithelial cells have a very short lifespan in vitro when cultured free of mucosal elements. Support of the basal plasma membrane by a more natural substrate may thus enhance the initiation of primary cell cultures. A cell free biomatrix consisting of native interstitial collagens, basement membrane fragments and microfibrils was extracted from the lamina propria of human intestinal mucosa. Immunofluorescence revealed the presence of collagens type III, IV, and VI and procollagens type I and III as well as fibronectin, laminin and undulin. Primary crypt cells of suckling mice displayed a significantly increased affinity to pepsin and collagenase solubilised intestinal biomatrix when compared with plastic and fibronectin. Colonies of primary crypt cells survived for up to four days and longer on pepsin solubilised biomatrix but only for 48 hours on fibronectin. The intestinal biomatrix preparation has proved to be a useful substrate for the initiation and prolongation of primary intestinal cell cultures.

Adult↗
PubMedDate not supplied

A case of glaucoma with choroidal hemangioma managed by nonpenetrating trabeculectomy.

BACKGROUND: Nonpenetrating trabeculectomy was used in a patient with glaucoma complicated by diffuse choroidal hemangioma. CASE: A 12-year-old boy suffered from glaucoma with choroidal hemangioma in the left eye. Intraocular pressure was 28 mm Hg and visual acuity was 0.04. Nonpenetrating trabeculectomy was then performed. OBSERVATIONS: Postoperative intraocular pressure was controlled at around 15 mm Hg with pilocarpine hydrochloride eye drops. Visual acuity and visual field were preserved over 19 months after the operation. CONCLUSIONS: An increase in aqueous outflow resistance was considered to be the major mechanism in the rise in intraocular pressure, based on distinct dilatation and tortuosity of the episcleral blood vessels and congestion of Schlemm's canal. Therefore, construction of aqueous drainage by nonpenetrating trabeculectomy was effective. Retaining the trabecular meshwork was also considered effective in controlling complications such as choroidal hemorrhage and postoperative flat anterior chamber.

Angiography↗