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N Wang

Publications and source records attributed to N Wang.

At least 55 records · Page 3Linked to original sources
PubMed2001

CD150 is a member of a family of genes that encode glycoproteins on the surface of hematopoietic cells.

Human CD150 (SLAM) is a glycoprotein expressed on the surface of T, B, natural killer, and dendritic cells. The extracellular domain of CD150 is the receptor for measles virus and CD150 acts as a co-activator on T and B cells. We characterized the mouse and human CD150 genes, each of which comprises seven exons spanning approximately 32 kb. Mouse CD150 mRNA was detected in T cells and in most thymocyte subsets, except CD4-8- cells. Surprisingly, the CD4-8- thymocytes of CD3gammadeltanull mice, but not of Ragnull or severe combined immunodeficiency mice, expressed CD150. Whereas high levels of CD150 were found in Th1 cells, only small amounts were detectable in Th2 cells. CD150 expression was up-regulated upon in vitro activation of mouse T cells by anti-CD3. The complete mouse CD150 gene is highly homologous to its human orthologue in terms of nucleotide sequences and intron/exon organization. The human genomic sequences indicate that all isoforms detected so far have arisen from alternative splicing events. As judged by fluorescence in situ hybridization, mouse CD150 mapped to Chromosome (Chr) 1, band 1H2.2-2.3, and human CD150 was found on Chr 1q22. Human and mouse CD150 share sequence homologies with six other genes, five of which - CD84, CD229 (Ly-9), CD244 (2B4), CD48, and 19A - are localized in a 250-kb segment in close proximity to the human gene. Their location and their sequence similarities strongly suggest that the CD150 family of cell surface receptors arose via successive duplications of a common ancestral gene.

Amino Acid Sequence↗
PubMed2001

Suppression of tumorigenicity in human ovarian carcinoma cell line SKOV-3 by microcell-mediated transfer of chromosome 11.

To determine the pathogenic role of chromosomes 11 and 17 in the carcinogenesis of human ovarian cancers, neo(R)-tagged chromosome 11 or 17 was transferred from cell lines A9H11 or A9H17, respectively, into the ovarian carcinoma cell line SKOV-3 using microcell-mediated chromosome transfer. The chromosome transfer was verified by polymerase chain reaction detection of the neo(R) gene, fluorescence in situ hybridization detection of an extra chromosome 11, and microsatellite polymorphism detection of an exogeneous chromosome 11. Five SKOV-3/A9H11 hybrids and five SKOV-3/A9H17 hybrid clones were generated. For the chromosome 11 transfer, complete suppression of tumorigenicity was observed in four clones, (11)9-8 and 11(H)7-2, 11(H)8-3, and 11(H)7-2, 100 days post implantation. For the chromosome 17 transfer, no complete suppression of tumorigenicity was observed. However, an increased latency period ranging from 25 to 49 days in contrast to 7 days for the SKOV-3 parental line, and a significant reduction in tumor size was observed. There was no correlation between the in vitro growth rate and the tumorigenicity or length of latency period. Our results demonstrate functionally that chromosome 11 may carry a tumor suppressor gene(s) while chromosome 17 may carry a tumor growth-inhibitor gene(s) for the ovarian carcinoma cell line, SKOV-3.

Animals↗
PubMed2001

Determination of the anamorph of Cordyceps sinensis inferred from the analysis of the ribosomal DNA internal transcribed spacers and 5.8S rDNA.

The anamorph determination of Cordyceps sinensis remains problematic due to the lack of clear links between the sexual and conidial forms of the fungus. In this study, we applied molecular approaches to analyze the genetic variation of Cordyceps sinensis and its allies to identify the anamorph-teleomorph connection. The sequences of the internal transcribed spacers (ITS1 and ITS2) and 5.8S ribosomal RNA gene of Cordyceps sinensis (teleomorph) collected from Qingzang plateau (altitude over 4000m), Tibet and several related asexual conidial forms were determined. The sequence comparison showed that Cordyceps sinensis was most closely related to Hirsutella sinensis, and was clearly divergent from Paecilomyces sinensis, Stachybotrys sp. or Tolypocladium sp.; distance values, estimated according to Kimura two-parameter models between Cordyceps sinensis and Hirsutella sinensis, were extremely low (<0.02), whereas distance values between Cordyceps sinensis and Paecilomyces sinensis, Stachybotrys sp. and Tolypocladium sp. were 0.34, 0.21 and 0.25, respectively. Taken together, Hirsutella sinensis and Cordyceps sinensis are the different stages of the life cycle stages of the same organism. Hirsutella sinensis is therefore the anamorph of Cordyceps sinensis, rather than Paecilomyces sinensis or other species. The possible reasons as to why different taxa can be obtained when culturing Cordyceps sinensis are also discussed.

Journal Article↗
PubMed2001

Attenuated lapinized chinese strain of classical swine fever virus: complete nucleotide sequence and character of 3'-noncoding region.

The complete nucleotide sequence including precise 5'- and 3'-terminal non-coding regions (NCRs) of the attenuated lapinized Chinese strain (HCLV) of Classical Swine Fever Virus (CSFV) was determined from overlapping cDNA clones constructed by separated RT-PCR and rapid amplification of cDNA ends (RACE) methods. The genomic RNA of the HCLV strain consists of 12.310 nucleotides (nts) including 374 nts and 242nts in the 5'- and 3'-NCRs, respectively. It contains one large open reading frame (ORF) encoding a polyprotein of 3,898 amino acids with a calculated molecular weight of 437.6 kDa. There is one notable insertion of 12 continuous nts, CTTTTTTCTTTT in the 3'-NCR of HCLV genomic cDNA when compared with its parental virulent Shimen strain. Sequence alignment of partial 3'-NCR reveals two groups of CSFV vaccine strains carrying similar T-rich insertions at different positions in this region. Computer-predicted secondary structures suggest that T-rich insertion greatly change the structures and thus decrease the promoter functions of 3'-NCRs during the replications of these two groups of CSFV vaccine strains.

3' Untranslated Regions↗
PubMed2001

Bioassessment of streams using macroinvertebrates: are the chironomidae necessary?

We compared the sensitivity of commonly used bioassessment metrics to detect organic impairment of streams using data sets that varied only in the inclusion or exclusion of Chironomidae identified to genus. We evaluated situations in two contrasting ecoregions of Missouri, U.S.A., the Ozark ecoregion and the Prairie ecoregion where Chironomidae comprise an average of 32 and 42%, respectively, of the total number of individuals. The without-Chironomidae data showed either identical or greater sensitivity than with Chironomidae data in every case when using the metrics total taxa, biotic index. Shannon's diversity index, and % dominant taxon. We conclude that bioassessment programs employing commonly-used metrics that usually incorporate Chironomidae may become more efficient by eliminating Chironomidae from the protocols and using those resources for analyzing additional sites.

Animals↗
PubMed2001

Activation of a tissue-specific stress response in the aqueous outflow pathway of the eye defines the glaucoma disease phenotype.

The glaucomas are a group of optic neuropathies comprising the leading cause of irreversible blindness worldwide. Elevated intraocular pressure due to a reduction in normal aqueous outflow is a major causal risk factor. We found that endothelial leukocyte adhesion molecule-1 (ELAM-1), the earliest marker for the atherosclerotic plaque in the vasculature, was consistently present on trabecular meshwork (TM) cells in the outflow pathways of eyes with glaucomas of diverse etiology. We determined expression of ELAM-1 to be controlled by activation of an interleukin-1 (IL-1) autocrine feedback loop through transcription factor NF-kappaB, and activity of this signaling pathway was shown to protect TM cells against oxidative stress. These findings characterize a protective stress response specific to the eye's aqueous outflow pathways and provide the first known diagnostic indicator of glaucomatous TM cells. They further indicate that common mechanisms contribute to the pathophysiology of the glaucomas and vascular diseases.

Adolescent↗
PubMed2001

SAP controls T cell responses to virus and terminal differentiation of TH2 cells.

SH2D1A, which encodes signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), is altered in patients with X-linked lymphoproliferative disease (XLP), a primary immunodeficiency. SAP-deficient mice infected with lymphocytic choriomeningitis virus had greatly increased numbers of CD8+ and CD4+ interferon-gamma-producing spleen and liver cells compared to wild-type mice. The immune responses of SAP-deficient mice to infection with Leishmania major together with in vitro studies showed that activated SAP-deficient T cells had an impaired ability to differentiate into T helper 2 cells. The aberrant immune responses in SAP-deficient mice show that SAP controls several distinct key T cell signal transduction pathways, which explains in part the complexity of the XLP phenotypes.

Animals↗
PubMed2001

Angiotropic lymphoma: an immunophenotypically and clinically heterogeneous lymphoma.

Angiotropic lymphoma (AL) is an uncommon lymphoma often presenting with nonspecific clinical features and having a high mortality rate. Although not specifically recognized by the Revised European-American Classification of Lymphoid Neoplasms, it likely will appear as a subtype of diffuse large B-cell lymphoma in the upcoming WHO classification. Some authors may also consider it to be a subtype of cutaneous lymphomas. Recent studies have reported an immunophenotypic heterogeneity of AL, and in rare instances, an association with other NHL. To further characterize AL, we studied the immunophenotype by immunohistochemistry for CD5, CD10, CD20, bcl-2, and bcl-6 in 18 cases of B-cell AL identified at three medical centers in North America. Bcl-2 gene rearrangement status by polymerase chain reaction and Epstein Barr virus status by in situ hybridization also were evaluated. Eight men and 10 women were identified with AL (median age 71 years). Eleven patients were diagnosed in life and seven were diagnosed at autopsy. Neurologic symptoms were the most common presentation, seen in six patients. Skin was the most commonly biopsied site. All showed classic intravascular localization; in two cases, there was also a minor diffuse large cell lymphoma component observed in some organs. Most (89%) of the cases expressed bcl-2 protein; CD10, bcl-6 and CD5 were each expressed in 22% of cases. Based on CD5 and CD10 expression, three major groups were evident: CD5-, CD10- (11 cases); CD5+, CD10- (3 cases), and CD5-, CD10+ (3 cases). Even though a follicle center lymphoma preceded the AL in one patient, we did not detect bcl-2 gene rearrangement in any of these cases. All cases were negative for Epstein Barr virus. Of the five treated with chemotherapy, two achieved a complete remission. Based on these findings, we conclude that ALs are clinically and immunophenotypically heterogeneous and may represent more than one pathogenetic entity. In some instances AL may be preceded by another lymphoproliferative disorder, raising the possibility that some cases of AL may represent a transformation from another type of lymphoma. Cutaneous manifestations of AL are common; however, it appears to be a systemic lymphoma. Although often fatal, patients with AL who are diagnosed early and treated with chemotherapy may achieve remission.

Aged↗
PubMed2001

Role of protein kinase C in the reduction of infarct size by N-methyl-1-deoxynojirimycin, an alpha-1,6-glucosidase inhibitor.

Preischaemic treatment with N-methyl-1-deoxynojirimycin (MOR-14), an alpha-1,6-glucosidase inhibitor, attenuates glycogenolysis and lactate accumulation during ischaemia and markedly reduces infarct size in rabbit hearts. In the present study, we have investigated whether protein kinase C (PKC), a principal mediator of ischaemic preconditioning, is also involved in the cardioprotective effect of MOR-14. To assess the effect of PKC inhibition on infarct size in MOR-14-treated hearts, 38 rabbits were subjected to 30 min of ischaemia followed by 48 h of reperfusion. Infarct size, as a per cent of area at risk, was significantly smaller in rabbits administered 100 mg kg(-1) of MOR-14 10 min before ischaemia (17+/-2%, n=10), than in a control group (46+/-5%, n=10). This beneficial effect of MOR-14 was abolished when 5 mg kg(-1) of chelerythrine, a PKC inhibitor, was given 10 min prior to MOR-14 injection (39+/-4%, n=10), although chelerythrine alone did not alter infarct size (43+/-4%, n=8). Further, chelerythrine had no effect on MOR-14-induced attenuation of glycogen breakdown and lactate accumulation in hearts excised at 30 min of ischaemia. Immunoblot analysis of PKC in homogenates of Langendorff-perfused rabbit hearts revealed that MOR-14 significantly increased levels of PKC-epsilon in the particulate fraction at 20 and 30 min of ischaemia and in the cytosolic fraction at 30 min of ischaemia. Taken as a whole, our data suggest that PKC acts downstream of the inhibition of glycogenolysis by MOR-14 to reduce infarct size. Thus, activation of PKC is a more direct mediator of the cardioprotection afforded by MOR-14 than is inhibition of glycogenolysis.

1-Deoxynojirimycin↗
PubMed2001

Combination of miglitol, an anti-diabetic drug, and nicorandil markedly reduces myocardial infarct size through opening the mitochondrial K(ATP) channels in rabbits.

The anti-diabetic drug miglitol, an alpha-glucosidase inhibitor, which is currently used clinically, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart. Nicorandil, a K(ATP) channel opener with a nitrate-like effect, which is also currently used clinically, also reduces the infarct size. Therefore, we hypothesized that combination of nicorandil and submaximal dose of miglitol could markedly reduce myocardial infarct size more than miglitol or nicorandil alone, and investigated the mechanism for the infarct size-reducing effect. Japanese white rabbits without collateral circulation were subjected to 30 min coronary occlusion followed by 48 h reperfusion. Pre-ischaemic treatment with submaximal dose of miglitol (5 mg kg(-1), i.v.) and nicorandil alone (100 microg kg(-1) min(-1) 5 min) moderately reduced the infarct size as a percentage of area at risk (24+/-4 and 25+/-4%, respectively), and 10 mg kg(-1) of miglitol markedly reduced the infarct size (15+/-2%) compared with the controls (42+/-2%). Combination of 5 mg kg(-1) of miglitol and nicorandil (100 microg kg(-1) min(-1) 5 min), and 10 mg kg(-1) of miglitol and nicorandil (100 microg kg(-1) min(-1) 5 min) significantly reduced the infarct size (13+/-4 and 12+/-3%, respectively) more than miglitol or nicorandil alone. Pretreatment with 5HD completely abolished the infarct size-reducing effect of 10 mg kg(-1) of miglitol alone (36+/-7%) and that of combination of 5 mg kg(-1) of miglitol and nicorandil (46+/-2%). Combination of nicorandil and submaximal dose of miglitol markedly reduced the myocardial infarct size more than miglitol or nicorandil alone. This effect was suggested to be related to the opening of mitochondrial K(ATP) channels.

1-Deoxynojirimycin↗
PubMed2001

Y-chromosome SNP haplotypes suggest evidence of gene flow among caste, tribe, and the migrant Siddi populations of Andhra Pradesh, South India.

From observations of lack of haplotype sharing based on Y-chromosome specific short tandem repeat (STR) loci, previous reports suggested negligible gene flow among different geographic populations of India. Using Single Nucleotide Polymorphism (SNP) sites in combination with STRs, we observed evidence of haplotype sharing across caste-tribe boundaries in South India. We examined 27 SNPs in the non-recombining region of the Y chromosome to investigate gene flow in 204 individuals belonging to three caste groups (Vizag Brahmins, Peruru Brahmins, Kammas), three tribes (Bagata, Poroja, Valmiki) and an additional group (the Siddis) of African ancestry. Principal component and AMOVA analyses show that the between group component of variation is non-significant (P>0.05), while that among populations within the caste and tribal groups is significant (P<0.001). In particular, the Valmikis and Siddis are close to the caste groups. Of a total of 11 distinct SNP-haplotypes observed, the two tribal groups (Bagata and Poroja) lack the haplotypes H4, H4A, H5A and H16, which are seen in the caste groups. In contrast, all three tribal groups exhibit the Southeast Asian haplotype H11 that is absent in the caste populations. The presence of haplotypes H4, H5, H14, and H16 in the Siddis indicate that they have assimilated considerable non-African admixture. The evidence of haplotype sharing between castes and tribes is also found when the H14 lineage was further subdivided by five STR loci. We conclude that even though these SNP-based Y-haplotypes are able to distinguish the populations, gene flow in these South Indian populations is not as negligible as that inferred from other studies based on Y-specific short tandem repeat markers.

Alleles↗
PubMed2001

NEDD4L on human chromosome 18q21 has multiple forms of transcripts and is a homologue of the mouse Nedd4-2 gene.

The validation of full-length cDNA represents a crucial step in gene identification and subsequent functional analysis. In searching for candidate genes for bipolar disorder on chromosome 18q21, a novel gene homologous to NEDD4 (Neural precursor cells expressed developmentally down-regulated) was identified using exon trapping and cDNA cloning. This novel gene is termed NEDD4L (Human Gene Nomenclature Committee symbol). Typical NEDD4 orthologues that contain a C2 (Ca(2+)/lipid-binding) and a HECT (Homologous to the E6-AP Carboxyl Terminus) ubiquitin-protein ligase domain, and multiple WW domains have been shown to regulate the epithelial sodium channel (ENaC). In mice, Nedd4 has two distinct isoforms termed Nedd4-1 that belongs to the typical NEDD4 class, and Nedd4-2 that is homologous to Nedd4-1 but lacks the C2 domain. NEDD4L contains the WW and HECT domains seen in the NEDD4 gene family, but lacks the C2 domain in the N-terminus. BLAST database search showed that the deduced polypeptide of NEDD4L has 97 and 62% sequence identity to mouse Nedd4-2 and human NEDD4, respectively. Multiple forms of transcripts of NEDD4L have been isolated, which differ in transcription start and termination sites together with the presence or absence of an alternative spliced exon. Northern blot analysis showed a 3.4 kb mRNA species was specifically expressed in heart and skeletal muscle, while a 3.2 kb band and/or an additional 3.6 kb band is seen in other tissues tested. Striking homology of NEDD4L to mouse Nedd4-2 suggests it is the human homologue of mouse Nedd4-2. Its position in a region of linkage for autosomal dominant orthostatic hypotensive disorder and its potential role in regulating ENaC make NEDD4L a candidate gene for this disorder.

Alternative Splicing↗
PubMed2001

Treatment of MRL/lpr mice, a genetic autoimmune model, with the Ras inhibitor, farnesylthiosalicylate (FTS).

Activation and proliferation of lymphocytes requires the active signal transducer Ras. Activation of lymphocytes, associated with autoimmunity, may therefore be modified by S-farnesylthiosalicylic acid (FTS), a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. The MRL/lpr mouse is a genetic model of a generalized autoimmune disease sharing many features and organ pathology with systemic lupus erythematosus (SLE) and the primary antiphospholipid syndrome (APS). The objective of the present study was to examine the effect of FTS on laboratory and clinical pathology in the MRL/lpr mouse. Female MRL/lpr (n = 50) and MRL/++ control (n = 35) mice were treated intraperitoneally with either FTS (5 mg/kg/day) or saline between 6 and 18 weeks of age. The mice were weighed, tested for proteinuria and lymphadenopathy, lymphocyte proliferation, antibodies, grip strength and behaviour in an open field. FTS treatment resulted in a 50% decrease in splenocyte proliferation to ConA, LPS and a disease specific antigen, beta(2)-glycoprotein-I, and in a significant decrease in serum antibody levels against cardiolipin and dsDNA. Proteinuria and grip strength were normalized and lymphadenopathy and postmortem lymph node and spleen weights were significantly reduced in FTS treated MRL/lpr mice. These findings indicate that modulation of Ras activation has a significant impact on the MRL/lpr model and may represent a new therapeutic approach for the treatment of systemic autoimmune diseases such as SLE and APS.

Animals↗
PubMed2001

Role of protein kinase C, K(ATP) channels and DNA fragmentation in the infarct size-reducing effects of the free radical scavenger T-0970.

1. In the present study, we investigated the effect of 1-(3-tert-butyl-2-hydroxy-5-methoxyphenyl)-3-(3-pyridylmethyl) urea hydrocloride (T-0970), a novel water-soluble low-molecular weight free radical scavenger, on the generation of hydroxyl radicals in vivo and on myocardial infarct size in an in vivo model of myocardial infarction in rabbits. 2. T-0970 scavenged hydroxyl radicals generated in the myocardium during reperfusion, as assessed by using a microdialysis technique and HPLC in an in vivo model with 30 min coronary occlusion and 30 min reperfusion in rabbits. 3. Another group of rabbits was subjected to 30 min coronary occlusion and 48 h reperfusion. The control group (n = 10) was infused with saline for 190 min from 10 min before occlusion to 180 min after reperfusion. The treatment group (T-0970 group; n = 10) was injected with a bolus 2.5 mg/kg T-0970 and then infused with T-0970 for 190 min from 10 min before reperfusion to 180 min after reperfusion at a rate of 100 microg/kg per min. The T-0970 + CHE group (n = 5) was given chelerythrine (CHE; a selective inhibitor of protein kinase C (PKC); 5 mg/kg, i.v.) 10 min before the administration of T-0970. The T-0970 + 5-HD group (n = 5) was given 5-hydroxydecanoate (5-HD; an inhibitor of mitochondrial K(ATP) channels; 5 mg/kg, i.v.) 10 min before the administration of T-0970. The CHE and 5-HD groups were given CHE (5 mg/kg, i.v.) and 5-HD (5 mg/kg, i.v.) 20 min before reperfusion, respectively. After 48 h reperfusion, infarct size was measured histologically and expressed as a percentage of the area at risk (AAR). In another series of experiments, the control (n = 5) and T-0970 (n = 5) groups were killed 4 h after reperfusion following 30 min coronary occlusion and DNA fragmentation in myocytes was assessed using in situ dUTP nick end-labelling (TUNEL) at the light microscopic level. 4. Infarct size, as a percentage of AAR, in the T-0970 group was significantly reduced compared with the control group (21+/-4 vs 41+/-4%, respectively; P<0.05). This reduction of infarct size by T-0970 was abolished by pretreatment with CHE and 5-HD. Neither CHE nor 5-HD alone had any effect on infarct size. The percentage of infarcted myocytes with DNA fragmentation by TUNEL in the T-0970 group was significantly reduced compared with the number in the control group (4.0+/-1.5 vs 10.7+/-1.9%, respectively; P<0.05). 5. T-0970, a free radical scavenger, improved reperfusion injury. This effect seemed to be mediated by activation of PKC, the opening of mitochondrial K(ATP) channels and inhibition of DNA fragmentation.

ATP-Binding Cassette Transporters↗
PubMed2001

Latanoprost and matrix metalloproteinase-1 in human choroid organ cultures.

PURPOSE: Latanoprost, a prostaglandin F2a analogue and ocular hypotensive agent, alters extracellular matrix and matrix metalloproteinases (MMPs), including MMP-1, within tissues of the uveoscleral outflow pathway. In addition to these tissues, the anterior choroid also is exposed to fluid within the uveoscleral outflow pathway. The present study was undertaken to compare MMP-1 expression in the choroid with other uveoscleral pathway tissues and to determine the effect of latanoprost on MMP-1 expression in human choroid organ cultures. METHODS: Choroid tissue explant cultures were generated and incubated with PhXA85, the biologically active form of latanoprost, or vehicle for 12 or 18 hours. Explant cultures from iris and ciliary body also were generated and exposed to PhXA85. Protein extracts of theses cultures, as well as from fresh tissues, were then probed for MMP-1 by Western blotting. All samples were normalized for protein content and reletive expression was evaluated by densitometry. Also, total RNA was harvested from fresh tissues or from cultures treated with PhXA85. The amount of MMP-1 mRNA in these samples was measured using real time polymerase chain reaction. These results were normalized according to simultaneous measurements of glyceraldehyde-3-phosphate dehydrogenase mRNA within the same samples. RESULTS: Compared to the ciliary body, in which specific MMP-1 concentration (/total mg protein) was greatest, the specific MMP-1 concentrations within iris, anterior choroid, and posterior choroid were less by 24.7 +/- 0.69%, 40.7 +/- 1.04%, and 64.5 +/- 0.52%, respectively (mean +/- SD). The order of MMP-1 mRNA expression among these tissues from fresh eyes was ciliary body < anterior choroid < posterior choroid < iris. Treatment of ciliary body explant cultures with 200 nM PhXA85 for 12 hours increased MMP-1 protein content by 154 +/- 34% (P = 0.004, students t test, N = 3). In contrast, similar treatment of anterior choroid, posterior choroid, or iris explant cultures minimally changed MMP-1 protein content (23 +/- 22+/-, P = 0.124; 14 +/- 8%, P = 0.462; 27 +/- 16%, P = 0.037, respectively). Increased MMP-1 was observed in choroid cultures incubated for 18 hrs with 200 nM or 500 nM PhXA85. MMP-1 mRNA in 12 hour PhXA85-treated choroid cultures was the same or less than vehicle-treated cultures from 7 of 9 donors. In contrast, MMP-1 mRNA was increased in PhXA85-treated ciliary body cultures from 2 of 2 donors. CONCLUSIONS: These results suggest that the capacity for latanoprost-mediated induction of MMP-1 within the choroid is less than within the ciliary muscle. Hence, it is unlikely that induction of MMP-1 in choroid plays as important a role in uveoscleral outflow modulation as induction of MMP-1 in the ciliary muscle.

Adult↗
PubMed2001

Anatomical site-specific response to DNA damage is related to later tumor development in the rat azoxymethane colon carcinogenesis model.

There is now general agreement that the etiology of proximal and distal colon cancers may differ, thus prompting renewed interest in understanding anatomical site-specific molecular mechanisms of tumor development. Using a 2x2x2 factorial design with male Sprague-Dawley rats (corn oil, fish oil; pectin, cellulose; plus or minus azoxymethane injection) we found a greater than 2-fold difference (P < 0.001) in tumor incidence proximally versus distally (prox/dist ratio: corn oil, 2.25; fish oil, 2.61). The purpose of the present study was to determine if the higher degree of proximal versus distal tumors in our model system could be accounted for by differences between these two sites in initial DNA damage, response to that damage or an effect of diet at one site but not the other. DNA damage was assessed by quantitative immunohistochemistry of O(6)-methylguanine adducts; repair by measurement of O(6)-methylguanine-DNA alkyltransferase and removal was determined by measurement of targeted apoptosis. Although overall initial DNA damage was similar at both sites, in the distal colon there was a greater expression of repair protein (P < 0.001) and a greater degree of targeted apoptosis (P < 0.0001). There was also a reduction in DNA damage in the distal colon of rats consuming fish oil. Together, these results suggest that the lower tumor incidence in the distal colon may be a result of the capacity to deal with initial DNA damage by the distal colon, as compared with the proximal colon. Therefore, the determination of site-specific mechanisms in tumor development is important because distinct strategies may be required to protect against cancer at different sites.

Adenocarcinoma↗
PubMed2001

Celiac disease is highly prevalent in lymphocytic colitis.

A high frequency of celiac disease is reported in patients with collagenous colitis. Limited information is available on the frequency of celiac disease in lymphocytic colitis. The aim of our study was to determine the prevalence of celiac disease in microscopic colitis (collagenous and lymphocytic colitis). Patients were identified from a pathology registry of microscopic colitis from 1987 to 1999. Pathology reports and medical records were reviewed for previous small bowel biopsies and/or celiac serology. We identified 113 patients with microscopic colitis, and 46 patients underwent a small bowel biopsy and/or celiac serology. Of these, 27 patients had lymphocytic colitis (63% female; age, 58.6 +/- 16.2 years) and 19 patients had collagenous colitis (79% female; age, 61.8 +/- 13.6 years). Small bowel biopsy alone was performed in 28 of 46 patients, celiac serology alone was performed in 10, and both small bowel biopsy and celiac serology were performed in 8. Celiac disease was identified in 4 patients by small bowel histology; all had lymphocytic colitis (4 of 27 patients, 15%). This frequency of celiac disease is significantly higher than the highest reported U.S. prevalence of celiac disease (4/1,000 individuals; p < 0.01). There is a high frequency of celiac disease in patients with lymphocytic colitis. Given the importance of the early detection of celiac disease, it should be excluded in all patients with lymphocytic colitis, particularly if diarrhea does not respond to conventional treatment.

Celiac Disease↗