Biomedical subjects

E Wang

Publications and source records attributed to E Wang.

At least 289 records · Page 16Linked to original sources

PubMed1993

Regulation of phosphatidate phosphatase activity from the yeast Saccharomyces cerevisiae by sphingoid bases.

The regulation of Saccharomyces cerevisiae membrane-associated phosphatidate phosphatase (3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) activity by sphingoid bases was examined using Triton X-100/lipid-mixed micelles. Sphingosine, phytosphingosine, and sphinganine inhibited purified preparations of the 104- and 45-kDa forms of phosphatidate phosphatase in a dose-dependent manner. The structural requirements for the sphingoid base inhibition of phosphatidate phosphatase activity were a free amino group and a long chain hydrocarbon. A detailed kinetic analysis was performed to determine the mechanism of phosphatidate phosphatase inhibition by sphingoid bases. The phosphatidate phosphatase dependence on phosphatidate was cooperative (Hill numbers of approximately 2) in the absence and presence of sphingoid bases. Sphingosine, phytosphingosine, and sphinganine were parabolic competitive inhibitors of phosphatidate phosphatase activity. This indicated that more than one inhibitor molecule contributed to the exclusion of phosphatidate from the enzyme. The aKi values (inhibitor constants) for sphingosine, phytosphingosine, and sphinganine were 1.5, 0.4, and 0.2 mol %, respectively, and the Km value for phosphatidate was 2.2 mol %. The cellular concentrations of free phytosphingosine and sphinganine were 0.16 and 0.53 mol %, respectively, relative to the total phospholipids in S. cerevisiae. The cellular concentrations of phytosphingosine and sphinganine were in the range of the aKi values for these sphingoid bases. These results raised the suggestion that phosphatidate phosphatase activity may be regulated in vivo by sphingoid bases.

Amines↗

PubMed1993

Expression of terminin in the rat brain during neuronal differentiation.

Terminin is a cytoplasmic protein originally found in senescent cultured human fibroblasts. In the present study, we investigated terminin expression during development in three brain regions: the cerebral cortex, the neural retina and the cerebellum of the rat brain. By immunocytochemistry we found that terminin immunoreactivity in the brain is mainly localized in neurons. Immunoreactivity to terminin antibody was first noticed in the brain as early as embryonic day 15, and the staining intensity in the cerebral cortex reached maximum level at the first postnatal week, when the cerebral neurons become postmitotic and their synaptic connections with target cells are established. A similar pattern of terminin development was seen in the neural retinas of the same animals as well. Biochemical characterization shows that the anti-terminin antibody recognizes a 90 kDa (Tp90) and a 60 kDa (Tp60) polypeptide in immunoblots of the detergent insoluble fraction of rat brains, while Tp90 was found in the detergent-soluble fraction. Both the Tp90 and Tp60 polypeptides appeared at embryonic day 15 and reached highest levels at postnatal day 1. With the advance of further neural differentiation, however, Tp90 in the detergent-insoluble fraction diminished, and remained only in the detergent-soluble fraction. In the detergent insoluble fraction Tp60 became the predominant species during the first postnatal week. In the cerebellum, where neuronal differentiation is known to be relatively late, quantitative densitometric measurement of terminin abundance on the immunoblots showed that Tp60 in the detergent-insoluble fraction was the predominant form in the second week. Thus, the appearance of a predominant Tp60 coincided with terminal neuronal differentiation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Kinetic study of collagen fixation with polyepoxy fixatives.

A new biomaterial has been developed by fixing native collagen with a polyepoxy compound (PC) fixative. In this study, bovine internal thoracic arteries were fixed with PC under various conditions to help understand the kinetics of the collagen-PC reactions and optimize the fixation process. At predetermined time intervals, small samples were cut from the arteries to determine the quantities of the remaining unreacted amino acids in the collagen. Temperature, concentration, and solution pH were among the key parameters studied. The overall fixation rate was found to be reaction-rate controlled, as the rate of fixation was relatively slow compared with the rate of diffusion of PC. As might be expected, the reaction rate was favored by a higher temperature, concentration, and solution pH. A kinetic model, with a 2.5th reaction order with respect to the reactive functional groups of collagen and a first order with respect to PC, was developed that gave a good fit to the experimental data. Based on this model, the degree of fixation, X, as a function of time, t, is given by (1 - X)-1.5 = 1 + Kt, where K is a constant related to the initial concentrations and the reaction rate constant.

Amino Acids↗

PubMed1993

Retinomotor movements in isolated teleost retinal cone inner-outer segment preparations (CIS-COS): effects of light, dark and dopamine.

Teleost cone inner segments elongate and contract in response to light and circadian signals. Previous studies have shown that teleost cone contraction is triggered by light or dopamine, while cone elongation is triggered by darkness or experimental elevation of cAMP. We have developed procedures for isolating and purifying motile cone fragments consisting of inner and outer segments (CIS-COS) to permit more detailed analysis of light and dopamine regulation of cone retinomotor movements. When retinas are dissected from long-term dark-adapted fish, CIS-COS break off at the base of the ellipsoid and remain attached to the RPE. CIS-COS can be detached from the RPE by brief protease treatment, thereby generating a highly enriched CIS-COS suspension. CIS-COS retain normal morphology and extend new myoids when cultured in darkness or in light plus forskolin, an activator of adenylate cyclase. The microtubule and actin cytoskeletons of the new myoids resemble those of intact cone myoids in vivo. Light inhibits CIS-COS myoid elongation, suggesting that light reception by the outer segment can directly influence cone motility. In dark-cultured CIS-COS, myoid elongation is inhibited half-maximally by nanomolar concentrations of dopamine, suggesting that dopamine effects on motility are mediated by D2-family receptors present on the cone inner and/or outer segment. After dark-induced elongation in culture, CIS-COS myoids can be induced to contract by subsequent culture in the light or with dopamine. Thus isolated cone inner and outer segments possess sufficient cytoskeletal and regulatory machinery to exhibit light- and dopamine-regulation retinomotor movement similar to that observed in intact cones in situ.

Animals↗

PubMed1993

Alteration of tissue and serum sphinganine to sphingosine ratio: an early biomarker of exposure to fumonisin-containing feeds in pigs.

Fumonisins are a group of naturally occurring compounds produced by the fungus Fusarium moniliforme. They are believed to be the etiologic agent of several animal diseases associated with consumption of corn-based feeds including porcine pulmonary edema. Recently it was shown in vitro that fumonisins are specific inhibitors of sphingosine and sphinganine N-acyltransferases. Inhibition of these enzymes in cultured cells results in the accumulation of free long chain sphingoid bases, specifically sphingosine and sphinganine, and the depletion of complex sphingolipids. In this study, tissues and serum from male SPF pigs fed a nutritionally balanced diet containing corn or corn screenings naturally contaminated with fumonisins for up to 14 days were analyzed for free sphingoid bases and complex sphingolipids. Total fumonisins (B1 and B2) in the diets were analyzed at 0 (< 1), 5, 23, 39, 101, and 175 ppm. Pulmonary edema only occurred at 175 ppm, while histologic liver damage was present at > or = 23 ppm, and serum liver enzymes were significantly elevated at > or = 101 ppm. The results of this study show that free sphinganine is elevated in liver, lung, and kidney, from pigs consuming feeds containing fumonisins at total fumonisin concentrations of 23 ppm or greater. Sphingosine is also elevated in a dose-dependent manner, but to a lesser extent than sphinganine. The consequence of this differential inhibition is that the ratio of sphinganine to sphingosine increases, suggesting that sphinganine N-acyltransferase is the preferred target for fumonisins. Elevation of free sphinganine and free sphingosine in serum paralleled the increases in tissues. Statistically significant increases in the ratio were observed at feed concentrations as low as 5 ppm total fumonisins and in pigs (at higher concentrations) in which other serum biochemistry parameters and tissue morphology were not altered. Elevated ratios were also observed in serum from pigs fed pure fumonisin B1. The sensitivity of the ratio indicates that it could serve as an effective biomarker for consumption of fumonisin-containing feeds. In addition, the data supports the hypothesis that inhibition of sphingosine and sphinganine N-acyltransferase plays an important role in the pathogenesis of animal diseases associated with consumption of feed containing fumonisins.

Animal Feed↗

PubMed1993

A randomized, controlled trial of platelet transfusions in thrombocytopenic premature infants.

A multicenter prospective, randomized controlled trial was conducted to determine whether early use of platelet concentrates would reduce the incidence or extension of intracranial hemorrhage or both in sick preterm infants with thrombocytopenia. The effects on bleeding as reflected by the amount of blood product support administered and a shortened bleeding time were assessed as secondary outcomes. Premature infants with a platelet count < 150 x 10(9)/L within the first 72 hours of life were randomly assigned to receive either conventional therapy or conventional therapy plus platelet concentrates (10 ml/kg). The platelet count was maintained < 150 x 10(9)/L until day 7 of life by one to three platelet transfusions. In 22 (28%) of the 78 treated infants and 19 (26%) of the 74 control infants, either a new intracranial hemorrhage developed or an already-present one became more extensive (p = 0.73). Similar numbers of infants had each grade of intracranial hemorrhage on both initial and follow-up ultrasonography. Similar numbers of infants received fresh frozen plasma and packed red blood cells, but treated infants received less of both. The bleeding time was prolonged in the treated group before the infusion of platelet concentrates but subsequently shortened (mean difference, 79.0; 95% confidence interval, 73.1 to 84.9). Subanalysis of the control group showed that infants with platelet counts < 60 x 10(9)/L (n = 21) on at least one occasion received more fresh frozen plasma and packed red blood cells than did those with platelet counts > 60 x 10(9)/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Component Transfusion↗

PubMed1993

Structure-activity relationships of arylalkyl isothiocyanates for the inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone metabolism and the modulation of xenobiotic-metabolizing enzymes in rats and mice.

Many arylalkyl isothiocyanates are potent inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung tumorigenesis in rats and mice. In the mouse, 4-phenylbutyl isothiocyanate (PBITC) and 6-phenylhexyl isothiocyanate (PHITC) exhibited greater inhibition than benzyl isothiocyanate (BITC) and phenethyl isothiocyanate (PEITC). The present study was conducted to investigate the structure-activity relationships of these four arylalkyl isothiocyanates for their inhibition of NNK oxidation and effects on xenobiotic-metabolizing enzymes in rats and mice. A single dose (0.25 or 1.00 mmol/kg) of each isothiocyanate was given to F344 rats 6 or 24 h before death. The rates of NNK oxidation were decreased in microsomes from the liver, lung and nasal mucosa of rats. Generally, PEITC was more potent than BITC but less potent than PBITC and PHITC. The rates in rat liver microsomes were decreased at 6 h but recovered or increased at 24 h; the rates in rat lung microsomes were markedly decreased at both 6 and 24 h; and the rates in rat nasal mucosa microsomes were also significantly decreased. The same treatment decreased the rat liver N-nitrosodimethylamine demethylase activity dramatically and ethoxyresorufin O-dealkylase and erythromycin N-demethylase activities moderately. However, the rat liver microsomal pentoxy-resorufin O-dealkylase activity was decreased at 6 h but increased at 24 h, with PEITC showing the most marked induction. The rat liver NAD(P)H:quinone oxidoreductase activity was increased 1.4- to 3.3-fold, with PEITC being most effective; and the glutathione S-transferase activity was increased slightly. Similarly, at a single dose of 0.25 mmol/kg (5 mumol/mouse) 24 h before death, PEITC, PBITC, PHITC but not BITC, decreased NNK oxidation in mouse lung microsomes by 40-85%, with PBITC and PHITC showing greater inhibition. Furthermore, all four isothiocyanates extensively inhibited NNK oxidation in rat lung and nasal mucosa microsomes as well as mouse lung microsomes in vitro, with PEITC (IC50 of 120-300 nM) being more potent than BITC (IC50 of 500-1400 nM) but less potent than PBITC and PHITC (IC50 of 15-180 nM). PHITC was a very potent competitive inhibitor of NNK oxidation in mouse lung microsomes with apparent K(i) values of 11-16 nM. These results indicate that PBITC and PHITC are more potent inhibitors of NNK bioactivation in rats and mice than PEITC. In addition, these arylalkyl isothiocyanates could be effective in protecting against the actions of a broad spectrum of carcinogenic or toxic compounds.

Animals↗

PubMed1993

Leukocyte counts and colonization with Ureaplasma urealyticum in preterm neonates.

In this paper we review the literature, present previously unpublished case reports for a pair of twins, and provide data from two prospective cohort studies to determine whether nasopharyngeal and/or endotracheal colonization with Ureaplasma urealyticum in preterm neonates is associated with an elevated white blood cell (WBC) count. We observed an association between colonization of the respiratory tract and elevation in the WBC count caused by an increase in the number of mature and immature neutrophils. Such a response indicates that U. urealyticum is capable of eliciting an inflammatory reaction and may be a true pathogen in the neonate. If these increases in the WBC count are confirmed, the WBC count may be a useful marker in future trials of interventions directed at U. urealyticum.

Cohort Studies↗

PubMed1993

Cytokine production at the site of disease in human tuberculosis.

Clinical and immunologic evidence suggests that tuberculous pleuritis provides a model to understand protective immune mechanisms against Mycobacterium tuberculosis. We therefore evaluated the pattern of cytokine mRNA expression and cytokine production in pleural fluid and blood of patients with tuberculous pleuritis. RNA was extracted from mononuclear cells, reverse transcribed to cDNA, and amplified by polymerase chain reaction (PCR). After normalization for T-cell cDNA, cDNA from pleural fluid cells and peripheral blood mononuclear cells (PBMC) was amplified with cytokine-specific primers. PCR product was quantified by Southern blot. For the Th1 cytokines gamma interferon (IFN-gamma) and interleukin-2 (IL-2), PCR product was greater in pleural fluid than in blood, whereas PCR product for the Th2 cytokine IL-4 was decreased in pleural fluid compared with blood. Concentrations of IFN-gamma were elevated in pleural fluid compared with serum, but IL-2, IL-4, and IL-5 were not detectable. Mean concentrations of IFN-gamma and IL-2 in supernatants of M. tuberculosis-stimulated pleural fluid cells were significantly greater than corresponding concentrations in supernatants of stimulated PBMC. In situ hybridization showed that increased IFN-gamma production by pleural fluid cells was associated with a 20- to 60-fold increase in the frequency of antigen-reactive IFN-gamma-mRNA-expressing cells. Because IL-10 can be produced by T cells and macrophages, pleural fluid cells and PBMC were normalized for beta-actin cDNA content and then amplified by PCR with IL-10-specific primers. IL-10 mRNA was greater in pleural fluid cells than in PBMC and was expressed predominantly by macrophages. IL-10 concentrations were elevated in pleural fluid versus serum. These data provide strong evidence for compartmentalization of Th1 cytokines and IL-10 at the site of disease in humans with a resistant immune response to mycobacterial infection.

Cytokines↗

PubMed1993

Shift in S-layer protein expression responsible for antigenic variation in Campylobacter fetus.

Campylobacter fetus strains possess regular paracrystalline surface layers (S-layers) composed of high-molecular-weight proteins and can change the size and crystalline structure of the predominant protein expressed. Polyclonal antisera demonstrate antigenic cross-reactivity among these proteins but suggest differences in epitopes. Monoclonal antibodies to the 97-kDa S-layer protein of Campylobacter fetus subsp. fetus strain 82-40LP showed three different reactivities. Monoclonal antibody 1D1 recognized 97-kDa S-layer proteins from all C. fetus strains studied; reactivity of monoclonal antibody 6E4 was similar except for epitopes in S-layer proteins from reptile strains and strains with type B lipopolysaccharide. Monoclonal antibody 2E11 only recognized epitopes on S-layer proteins from strains with type A lipopolysaccharide regardless of size. In vitro shift from a 97-kDa S-layer protein to a 127-kDa S-layer protein resulted in different reactivity, indicating that size change was accompanied by antigenic variation. To examine in vivo variation, heifers were genetically challenged with Campylobacter fetus subsp. venerealis strains and the S-layer proteins from sequential isolates were characterized. Analysis with monoclonal antibodies showed that antigenic reactivities of the S-layer proteins were varied, indicating that these proteins represent a system for antigenic variation.

Animals↗

PubMed1993

Selective modulation of human natural killer cells in vivo after prolonged infusion of low dose recombinant interleukin 2.

The immunologic consequences of prolonged infusions of rIL-2 in doses that produce physiologic serum concentrations of this cytokine were investigated. rIL-2 in doses of 0.5-6.0 x 10(6) U/m2 per d (3.3-40 micrograms/m2 per d) was administered by continuous intravenous infusion for 90 consecutive days to patients with advanced cancer. IL-2 concentrations (25 +/- 25 and 77 +/- 64 pM, respectively) that selectively saturate high-affinity IL-2 receptors (IL-2R) were achieved in the serum of patients receiving rIL-2 infusions of 10 micrograms/m2 per d and 30 micrograms/m2 per d. A gradual, progressive expansion of natural killer (NK) cells was seen in the peripheral blood of these patients with no evidence of a plateau effect during the 3 mo of therapy. A preferential expansion of CD56bright NK cells was consistently evident. NK cytotoxicity against tumor targets was only slightly enhanced at these dose levels. However, brief incubation of these expanded NK cells with IL-2 in vitro induced potent lysis of NK-sensitive, NK-resistant, and antibody-coated targets. Infusions of rIL-2 at 40 micrograms/m2 per d produced serum IL-2 levels (345 +/- 381 pM) sufficient to engage intermediate affinity IL-2R p75, which is constitutively expressed by human NK cells. This did not result in greater NK cell expansion compared to the lower dose levels, but did produce in vivo activation of NK cytotoxicity, as evidenced by lysis of NK-resistant targets. There was no consistent change in the numbers of CD56- CD3+ T cells, CD56+ CD3+ MHC-unrestricted T cells, or B cells during infusions of rIL-2 at any of the dosages used. This study demonstrates that prolonged infusions of rIL-2 in doses that saturate only high affinity IL-2R can selectively expand human NK cells for an extended period of time with only minimal toxicity. Further activation of NK cytolytic activity can also be achieved in vivo, but it requires concentrations of IL-2 that bind intermediate affinity IL-2R p75. Clinical trials are underway attempting to exploit the differing effects of various concentrations of IL-2 on human NK cells in vivo.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1993

Localization of S1 and elongation factor-1 alpha mRNA in rat brain and liver by non-radioactive in situ hybridization.

Elongation factor-1 alpha (EF-1 alpha) is a ubiquitous, highly conserved protein that functions in peptide elongation during mRNA translation. We recently reported that, as do lower species, mammals also contain a second EF-1 alpha-like gene (S1). Unlike EF-1 alpha, which is present in all tissues, S1 mRNA is detected only in brain, heart, and muscle by Northern analysis and RNAse protection assays. In this report we present the identification of S1 and EF-1 alpha messages by non-radioactive in situ hybridization in brain and liver. We show that with this technique we can detected S1 mRNA only in certain cells in brain, mostly neurons; on the other hand, EF-1 alpha is present in all cell types that we have studied so far. We demonstrate that although EF-1 alpha mRNA can be detected in S1-negative cells it is also present in high abundance in S1-positive cells. The results presented here correlate with our previous finding that mammalian species contain a tissue-specific EF-1 alpha-like gene, S1. The presence of a second EF-1 alpha-like transcript within fully differentiated cells suggests a novel cell type-specific gene expression whose function may be related to the permanent growth-arrested state of cells in brain, heart, and muscle.

Animals↗

PubMed1993

Quiescent and cycling cell compartments in the senescent and Alzheimer-diseased human brain.

Statin is a 57-kd nuclear protein expressed exclusively in nonproliferating cells. In the present study, immunohistochemical localization of statin in normal, senescent human brain revealed that virtually all neurons, ependymal cells, vascular smooth muscle cells, and endothelial cells are statin-positive and, hence, postmitotic. As we previously demonstrated in rodents, an unexpectedly large fraction of neuroglial cells throughout the aging human brain is statin-negative (range, 41 to 45%), consistent with the substantial retention of neuroglial proliferative capacity well into the senium. In Alzheimer's disease, there is a significant increase in the proportion of statin-negative neuroglia (range, 51 to 58%). In all regions except cerebellum, loss of statin in Alzheimer neuroglia could be accounted for by changes involving the astrocyte subpopulation. These results provide evidence that reactive gliosis in this neurodegenerative disorder encompasses some degree of astrocyte hyperplasia in addition to astrocyte hypertrophy. Maintenance of normal compartments of cycling and quiescent neuroglia in the senescent human brain may serve to define neurologic well-being during the aging process. Conversely, deviations in neuroglial cytokinetics may indicate the presence and extent of intervening neuropathologic processes.

Aged↗

PubMed1993

Effects of feeding Fusarium moniliforme culture material, containing known levels of fumonisin B1, on the young broiler chick.

The effects of feeding Fusarium moniliforme culture material, containing known concentrations of fumonisin B1 (FB1), were studied in broiler chicks. Day-old chicks were allotted randomly to dietary treatments containing 0, 1.02, 2.04, 3.06, 4.08, 5.10, 6.12, and 7.14% fumonisin culture material (FCM). These levels of FCM supplied 0, 75, 150, 225, 300, 375, 450, and 525 mg of FB1/kg of feed. Each dietary treatment was fed to four pen replicates of six birds each for 21 days. Chicks fed FCM that supplied 450 and 525 mg FB1/kg diet had lower (P < .05) feed intakes and BW gains; increased (P < .05) liver and kidney weights; and increased (P < .05) mean cell hemoglobin, and mean cell hemoglobin concentrations. Compared with controls, chicks fed FCM had increased (P < .05) free sphinganine levels and sphinganine:sphingosine ratios. Treatment-associated histological lesions were only observed in the liver of chicks fed diets containing FCM that supplied 225 mg FB1/kg or higher. Diets containing FCM that supplied levels as low as 75 mg FB1/kg affected the physiology of chicks by increasing free sphinganine levels and sphinganine:sphingosine ratios. Because inhibition of sphingolipid biosynthesis has been hypothesized as the mechanism of action of FB1, this suggests that diets containing 75 mg FB1/kg FCM may be toxic to young broiler chicks.

Animal Feed↗

PubMed1993

Temporal relationships of statin and terminin expression in ventral lobe of rat prostate following castration.

The purpose of this study was to determine the temporal relationships, in the rat prostate following castration, the expressions of terminin, a cytoplasmic marker for senescence, and, statin, a nuclear marker for cell quiescence and senescence. The presence of these two proteins was determined at 0, 1, 2, 4, 8, 24 and 48 hours in the ventral lobe of the prostate following castration. Immunofluorescence techniques for double labelling were used and assessed with confocal microscopy. At 0 hour the mean % labelling index (LI) for terminin was 0% and 98% for statin. One hour following castration a complete reversal of expression of these two markers occurred indicating that the terminin marker is expressed at the start of programmed cell death or apoptosis. The mean % LI for terminin at 1, 2, 4, 8, 24 and 48 hours following castration were 54, 82, 63, 39, 44 and 41% respectively. The mean % labelling index of statin remained at zero during these time intervals. It is concluded that following castration, the prostatic ventral lobe exits from the quiescent phase to reenter cell cycle traverse. This is coupled by the loss of statin and the expression of the cytoplasmic marker terminin at the start of programmed cell death prior to the appearance of any histologic features of apoptosis.

Animals↗

PubMed1993

The differential expression of statin in the nuclei of human colonic crypts adjacent to a cancer: an immunohistochemical study.

Statin, a non-proliferation-specific nuclear antigen, was used here to assess the colonic crypt kinetics of the mucosa bordering a human colon cancer. Mucosal strips adjacent to a colon cancer obtained from operative specimens were immediately cut into five one cm segments and stored in liquid nitrogen. An immunohistological technique using the statin antibody as a nuclear marker was used to determine the labelling indices of the non-cycling compartment at the varying distances. Optical density measurements of the nuclear reaction product served to objectively identify the statin-positive nucleus. The results indicate that there is a statistically significant reduction (P < 0.0001) in the statin-positive labelling index in the entire crypt length for a distance of three cms. The division of the entire crypt into four levels (A, B, C and D) demonstrates that this effect is principally due to the upward extension of the statin-negative cell mass into levels B and C with a corresponding decrease in the labelling index of the statin-positive nuclei in these levels. The in vivo expression of nuclear statin demonstrates its usefulness in accurately determining the size of the non-proliferative compartment in the human colonic crypt adjacent to a colon cancer.

Cell Cycle↗

PubMed1993

Immunohistochemical expression of mutant p53 oncogene in transitional mucosa adjacent to human colon cancer.

The purpose of this study was to analyze the expression of a mutant (MUT) p53 oncogene protein in the mucosal crypts adjacent to a human colon cancer. Five 1-cm mucosal segments were taken from the surgical specimens over a 5-cm distance from the tumor. Immunohistochemistry was performed using a monoclonal antibody (Ab3) to the MUT p53 and examination by light microscopy. The mean % labelling index (LI) of 10 crypts/cm segment was determined by image analysis. The LI for the entire crypt length for the first cm segment was 33.51 +/- 4.2 and for the second cm segment was 29.26 +/- 5.4 (p < 0.02). Due to the unequal distribution of the label within the crypt length, it was divided into halves so that the LI of these levels could be determined. The LI for the upper and lower crypt levels for the first cm segment were 28.67 +/- 3.2 and 78.23 +/- 4.6 (p < 0.01); for the second segment, the LI were 22.0 +/- 5.1 and 68.66 +/- 4.7 (p < 0.01). No expression of MUT p53 nuclear protein was noted distally at 3-5 cm. The localization of MUT p53 protein product to the crypt stem cell nucleus supports the contention that a malignant field change exists in the transitional mucosa adjacent to a human colon cancer.

Antibodies, Monoclonal↗

PubMed1993

A compliant biological vascular prosthesis.

One requirement of the mechanical parameters for an acceptable vascular prosthesis is compliance. The compliance of a vascular prosthesis is defined as the fractional change in luminal volume per unit change in applied pressure. A compliant prosthesis has been correlated to prosthesis patency and long-term efficacy in an animal study. However, there have been very few reports on how to manufacture a compliant prosthesis. It is the objective of this study to research the processing methods to manufacture a reasonably compliant vascular prosthesis. A new fixative, polyepoxy compound, was used to fix an artery. The arteries were fixed under different degrees of longitudinal retraction. By locking in the collagen micro-structure at an overly relaxed state and then crosslinking said collagen, the resulting biological prosthesis exhibited extreme compliance and pliability. A prosthesis matching its arterial origin in tensile modulus was achieved by crosslinking an artery at its 45% retraction longitudinally. This flexible prosthesis showed a volumetric compliance index of 18.4 +/- 0.9 % delta/100 mmHg and a longitudinal tensile modulus of 942 grams/cm2. Our current study indicated that a prosthesis fixed with polyepoxy compounds has shown more pliability than that with glutaraldehyde. Further animal study to correlate prostheses patency to different degrees of compliance is needed to confirm this proposed manufacturing approach.

Bioprosthesis↗