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S Hsu

Publications and source records attributed to S Hsu.

At least 109 records · Page 6Linked to original sources
PubMed1993

Compliance effects on small diameter polyurethane graft patency.

Microporous compliance matched and noncompliant grafts were compared in a dog carotid artery interposition model. We fabricated 4 mm diameter sponge type polyurethane (Biomer) tubes 5 cm in length with a 0.5 mm wall thickness. The luminal surface was covered with a 50 microns coating of cross-linked gelatin. Compliance was measured in vitro and in vivo by volume and vessel diameter changes. Over a mean arterial pressure range of 55-155 mm Hg, the diameter changes of grafts and stump arteries were measured in situ using an ultrasonic Hokanson device. Compliance matched grafts were found to have the same in vitro compliance values as the natural canine carotid at a mean arterial pressure of 100 mm Hg. Compliance matched and noncompliant grafts had values of 10.3 +/- 1.3 and 0.9 +/- 0.1 x 10(-2) mm Hg, respectively. End to end arterial anastomoses were constructed between the graft and the host arteries. The use of synthetic grafts with matched compliance to the adjacent natural vessels has been advocated as the ideal solution to circumvent the problems of graft failure. These studies indicate that compliance values for compliance matched grafts decreased immediately after implantation (from 10.3 to 6.5 x 10(-2) %/mm Hg) and within 6 weeks decreased to 3.6 x 10(-2) %/mm Hg. The compliance values for noncompliant grafts remained constant throughout the test period. At autopsy all grafts showed a tightly adhered tissue capsule. The thickness of the anastomotic hyperplasia at the distal sites of compliance matched grafts was significantly different (P < .05) than that of the adjacent artery. The patency for compliant and noncompliant grafts was 64% and 50%, respectively. Evidence for polyurethane graft degradation was obtained by Fourier transform infrared spectroscopy and gel permeation chromatography analysis of patent explants. Compliance mismatch alone does not contribute to graft failure, however, material degradation, suture technique and/or capsule formation can play a contributory role although these were not tested directly.

Animals↗
PubMed1992

Hypomethylation of beta-hydroxy-beta-methyl-glutaryl coenzyme A reductase gene and its expression during hepatocarcinogenesis in the rat.

Our earlier studies had demonstrated that inhibition of DNA methylation following carcinogen treatment potentiated initiation of the carcinogenic process in the rat liver system. The hepatic nodules developed by initiation-promotion protocols showed a characteristic hypomethylation in the cell-cycle-related genes c-fos, c-myc and c-Ha-ras. In the present study we have found that the gene for beta-hydroxy-beta-methyl glutaryl coenzyme A reductase, a major rate-limiting enzyme in the biogenesis of mevalonate, is also hypomethylated at both CCGG and GCGC sites and expressed in hepatic nodules. This gene, however, did not exhibit hypomethylation in CCGG sequences in non-nodular surrounding liver, livers from rats subjected to two-thirds partial hepatectomy, or exposed to initiator alone (1,2-dimethylhydrazine given 18 h after partial hepatectomy) or to diets containing 1% orotic acid alone (promoting regimen). The activity of the enzyme and mevalonate formation are positively correlated with DNA synthesis and cell proliferation--two key components of the carcinogenic process. Taken together, the results suggest that hypomethylation of specific genes occurs in the carcinogenic process and this altered pattern of DNA methylation may play a role in the growth of the nodules.

1,2-Dimethylhydrazine↗
PubMed1992

The hsp70 gene CCAAT-binding factor mediates transcriptional activation by the adenovirus E1a protein.

Expression of the human hsp70 gene is cell cycle regulated and is inducible by both serum and the adenovirus E1a protein (K. Milarski and R. Morimoto, Proc. Natl. Acad. Sci. USA 83:9517-9521, 1986; M. C. Simon, K. Kitchener, H.-T. Kao, E. Hickey, L. Weber, R. Voellmy, N. Heintz, and J. R. Nevins, Mol. Cell. Biol. 7:2884-2890, 1987; B. Wu, H. Hurst, N. Jones, and R. Morimoto, Mol. Cell. Biol. 6:2994-2999, 1986; B. Wu and R. Morimoto, Proc. Natl. Acad. Sci. USA 82:6070-6074, 1985). This regulated expression is predominantly controlled by the CCAAT element at position -70 relative to the transcriptional initiation site (G. Williams, T. McClanahan, and R. Morimoto, Mol. Cell. Biol. 9:2574-2587, 1989; B. Wu, H. Hurst, N. Jones, and R. Morimoto, Mol. Cell. Biol. 6:2994-2999, 1986). A corresponding CCAAT-binding factor (CBF) of 999 amino acids has recently been cloned and shown to stimulate transcription selectively from the hsp70 promoter in a CCAAT element-dependent manner (L. Lum, L. Sultzman, R. Kaufman, D. Linzer, and B. Wu, Mol. Cell. Biol. 10:6709-6717, 1990). We report here that the first 192 residues of CBF, when fused to the DNA-binding domain of the heterologous activator GAL-4, are necessary and sufficient to mediate E1a-dependent transcriptional activation. E1a and CBF exhibit complex formation in vitro, suggesting that an in vivo interaction between these proteins may be relevant to the well-characterized E1a-induced transcriptional activation of the hsp70 promoter.

Adenovirus Early Proteins↗
PubMed1992

Two roles for transforming growth factor beta 1 in colon enterocytic cell differentiation.

The role of transforming growth factor beta 1 (TGF-beta 1) in enterocytic differentiation was examined by treating two undifferentiated HT29 colon carcinoma sublines, U4 and U9, with hexamethylene bisacetamide to up-regulate their level of TGF-beta 1 mRNA expression. Although both lines after treatment secreted approximately equal levels of biologically active TGF-beta 1, only U4H cells were found to undergo enterocytic differentiation when cultured postconfluence on collagen I-coated transwells, forming polarized monolayer cells with an apical brush border, whereas U9H cells remained multilayered and undifferentiated. Enterocytic U4H cells exhibited four times as much cell surface expression of the collagen I-binding protein alpha 2-integrin, twice as much of the accessory collagen-binding protein carcinoembryonic antigen, and almost twice as much binding to collagen I films as undifferentiated U9H cells. TGF-beta 1 treatment doubled U4 cell collagen I binding, increased expression of alpha 2-integrin 4-fold, but increased carcinoembryonic antigen expression only marginally. U4H cells displayed cell cycle regulation by arresting reversibly at a restriction point in G1 when placed in the postconfluent culture conditions which initiated enterocytic differentiation. In contrast, undifferentiated U9H cells exhibited no restriction point but arrested throughout G1. TGF-beta 1 blocked synchronized U4H cells in G1, whereas it stimulated the growth of U9H cells. Thus, TGF-beta 1 has two roles in enterocytic differentiation: to increase levels of collagen I adhesion proteins and to block enterocytic cells in G1 so that they can differentiate.

Acetamides↗
PubMed1992

Transforming growth factor beta 1 (TGF-beta 1) inhibits retinoblastoma gene expression but not pRB phosphorylation in TGF-beta 1-growth stimulated colon carcinoma cells.

The response of the retinoblastoma (RB) gene and its product (pRB) to transforming growth factor beta 1 (TGF-beta 1) was studied in three types of colon carcinoma cells derived from the same parental line. TGF-beta 1 was a growth inhibitor for two enterocytic-differentiated lines, a growth stimulator for two undifferentiated lines, and had no effect on two goblet cell-differentiated lines. TGF-beta 1 treatment for 3 days decreased RB gene expression and pRB level two- to threefold in each responsive line. When treated with TGF-beta 1 beginning in early G1, enterocytic cells were arrested in G1 and pRB remained under-phosphorylated and in low abundance. Neither goblet cell line exhibited these responses to TGF-beta 1 because they were shown to lack TGF-beta 1 type I and II receptors. Thus during colonocyte differentiation goblet cells lose responsiveness to TGF-beta 1 by down-regulating TGF-beta 1 receptors, while enterocytic cells retain and exhibit responsiveness to TGF-beta 1 through modulations of pRB. Both of the undifferentiated lines exhibited mixed responses to TGF-beta 1: a decrease in total amount of RB mRNA and pRB protein yet an increase in pRB phosphorylation consistent with increased cell cycling. Therefore, TGF-beta 1 controls RB function by two separable mechanisms, the regulation of pRB phosphorylation and the control of RB mRNA and protein level.

Carcinoma↗
PubMed1990

Altered antigen expression predicts outcome in squamous cell carcinoma of the head and neck.

Monoclonal antibody UM-A9 identifies an antigen found on the basal surface of epithelial cells and expressed on all of the squamous cell carcinomas (SCC) that we have tested. In a previous study, we showed that cell lines from metastatic or recurrent SCC exhibit stronger expression of the A9 cell membrane antigen than cell lines from the primary tumor of the same donors, suggesting that this marker is associated with tumor progression. Loss of expression in tumor tissue of normal A, B, and H (ABH) blood group antigens has also been linked to clinical behavior in some epithelial cancers. To determine the prognostic significance of these antigen markers, we prospectively evaluated tissue specimens for expression of these markers in a group of 82 consecutive, previously untreated patients with SCC of the head and neck. Three patterns corresponding to strong (pattern 1), intermediate (pattern 2), or weak (pattern 3) A9 antigen expression were observed. Fifty-eight percent of the patients whose tumors had pattern 1 A9 antigen expression and 78% of the patients with loss of blood group antigen had early relapse, compared with only 34% of those with A9 antigen pattern 2 or 3 (P = .042) and 37% of those whose tumors expressed the mature ABH blood group antigen (P = .012). The combination of A9 pattern and ABH blood group antigen expression in tumor tissue was the variable most strongly associated with duration of disease-free survival, even after adjustment for the traditional prognostic factors of tumor site, stage, and TNM classification. Loss of blood group was the most significant single variable associated with early recurrence, but among patients whose tumors retained ABH blood group antigen expression, the A9 pattern distinguished good and poor prognostic groups. To our knowledge, our study is the first to demonstrate that differences in blood group antigen expression are significantly correlated with disease-free survival in SCC of the head and neck. We have initiated a study (a) to determine the relationship of the A9 antigen and the blood group antigens with clinical response of the tumors and (b) to determine whether these markers should be used as prognostic indicators.

ABO Blood-Group System↗
PubMed1990

Recognition of the product of a novel MHC TL region gene (27b) by a mouse gamma delta T cell receptor.

The gamma delta T cell receptor (TCR) derived from the mouse KN6 T cell hybridoma recognizes an autologous determinant encoded by a broadly expressed gene mapping in the TL region of the major histocompatibility complex (MHC). We have cloned the gene and demonstrated that it is a novel class I gene (designated 27b) belonging to a hitherto undescribed TL region gene cluster in strain C57BL/6. The BALB/c allele of 27b, gene T17c, is defective because it lacks an appropriate splice acceptor site, which explains the lack of recognition of BALB/c stimulator cells by the KN6 cells. We propose that gamma delta TCR and nonclassical MHC and MHC-related class I molecules have coevolved to recognize a conserved set of endogenous and foreign determinants.

Amino Acid Sequence↗
PubMed1990

Autoradiographic study of the attrition of migrating schistosomula in the skin of mice. II. Mice challenged with normal S. mansoni cercariae after immunization with highly irradiated cercariae.

The migratory pattern and attrition of 75Se-labelled S. mansoni challenge cercariae in CF1 mice immunized 0, 1, 3, or 5 times with 12kR- or 48kR-irradiated cercariae were investigated by compressed organ autoradiography. Mice were percutaneously inoculated with 500-1000 cercariae for each immunization and with a known count of approximately 90 cercariae at a different site for challenge. The skin, lungs, liver, other organs, and carcass were processed for autoradiography. Hepatic and mesenteric perfusions for worm collection were also sampled from day 19 through 34. In naive mice, 25% of challenge cercariae died in the skin. Skin attrition of challenge cercariae in mice immunized with 12kR-irradiated cercariae was 43% with 1 immunization, 54% with 3, and 58% with 5, whereas in mice immunized with 48kR-irradiated cercariae, skin attrition was 48% with 1, 63% with 3, and 76% with 5 immunizations. In all immunized mice, a high percentage of migrating schistosomula died in the skin within 24 hours of a challenge infection. Utilizing autoradiography, it was found that the silver foci created by single labelled worms were difficult to differentiate from those of paired worms. This study documents the induction of acquired resistance against a challenge infection in the skin by vaccination with highly irradiated cercariae, with the degree of attenuation of immunizing cercariae and the number of immunizations being closely related to the attrition rate in the skin. Finally, we discuss the contradictory views concerning the site of attrition of challenge cercariae.

Animals↗
PubMed1989

Characterization of human laryngeal primary and metastatic squamous cell carcinoma cell lines UM-SCC-17A and UM-SCC-17B.

The squamous cell carcinoma (SCC) cell lines UM-SCC-17A and -17B were derived, respectively, from the primary laryngeal cancer and a metastatic neck tumor of a patient who failed to respond to radiation therapy but achieved long-term remission after surgery. The karyotypes of both cell lines and a subline of 17A were pseudodiploid and stable in multiple in vitro passages. Several karyotypic abnormalities were common to all three cell lines and therefore represent mutations present in the tumor before the divergence of the metastatic and subline populations whereas those rearrangements observed only in one cell are more likely to be secondary. The shared mutations include: duplication of the short and proximal long arm of chromosome 2, isochromosome 3q, duplication 7, inversion 8, duplication of the distal long arm of 18, and monosomy 21 or ring 21. Each line had different rearrangements involving chromosome 7 that resulted in three copies of most of the short arm being present in both cell lines, except for high passages of 17B, in which one structurally normal 7 was replaced by a dicentric isochromosome, dic(7)(q11.22), resulting in four copies of 7p. The dic(7) may represent an in vitro mutation. An isochromosome 13q was noted in both the stemline and subline of UM-SCC-17A but not in UM-SCC-17B. A del(11p) and an iso(21q) were present only in the 17A subline. The cell lines expressed the membrane antigen phenotype characteristic of squamous cancers although the UM-SCC-17A subline differed with respect to three markers. Of these, the A9 and blood group antigen changes are thought to be associated with progression. The subline, which carried the del(11)(p13-p15.1), also failed to express the E7 antigen mapped to the band 11p13. It is possible that the two apparently normal 11s in this subline carry a point mutation or microscopically undetected deletion involving the E7 antigen locus.

Antigens, Neoplasm↗
PubMed1989

Both granulocyte-macrophage CSF and macrophage CSF control the proliferation and survival of the same subset of alveolar macrophages.

The effect of granulocyte-macrophage (GM)-CSF on the proliferation of murine pulmonary alveolar macrophages in vitro was investigated. About 20% of freshly isolated alveolar macrophages formed colonies in both liquid and soft agar cultures in the presence of GM-CSF. GM-CSF was also found to be capable of maintaining the survival of these colony-forming cells in vitro. Moreover, GM-CSF could substitute for CSF-1 in maintaining the survival of CSF-1-responding pulmonary alveolar macrophage colony-forming cells in the absence of CSF-1. The concentration of GM-CSF required for maintaining the survival of colony-forming cells without proliferation was much lower than that required for the proliferation of these cells in vitro. It also enhanced the CSF-1-dependent clonal growth of alveolar macrophages. These data suggest that the colony-forming cells that respond to GM-CSF are the same subset of macrophages that form colonies in the presence of CSF-1. GM-CSF did not inhibit the binding of 125I-CSF-1 to alveolar macrophages at 0 degrees C. However, the preincubation of macrophages with GM-CSF at 37 degrees C resulted in a transient down-regulation of CSF-1 binding activity.

Animals↗
PubMed1989

Biochemical mechanisms underlying the development of radioresistance by cultured peritoneal exudate macrophages.

We investigated changes in radiosensitivity of peritoneal exudate macrophage colony-forming cells (PE-CFC) when exudative peritoneal macrophages were cultured in vitro. The change in the shape of the dose-response curve of PE-CFC to ionizing irradiation was partly dependent on the concentration of oxygen in the gas phase of the incubators. When cells were incubated in an environment containing 20% oxygen, the value of both Dq and D0 for PE-CFC increased. The dose-response curve of PE-CFC cultured for 3 days resembled that of alveolar macrophage colony-forming cells (AL-CFC). The changes in radiosensitivity were accompanied by an increase in the level of three antioxidant enzymes: superoxide dismutase, catalase, and glutathione peroxidase. However, when they were cultured in a 6% oxygen environment, only the value of Dq increased. When alveolar macrophages were incubated in vitro, no significant change in the shape of the dose-response curve of AL-CFC was noted whether they were cultured in gas phase containing either 20 or 6% oxygen. It is concluded that the radiosensitivity of PE-CFC changes when they are cultured in vitro. The increase in D0 appears to be related to the intracellular level of antioxidant enzymes.

Animals↗