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At least 217 records · Page 12Linked to original sources
PubMed2002

Cyclin D1 expression in papillary superficial bladder cancer: its association with other cell cycle-associated proteins, cell proliferation and clinical outcome.

Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27(Kip1), p21(Waf1) and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (> or =25% positive nuclei) was significantly associated with p53 gene mutation (p = 0.012), low p21(Waf1) (p = 0.015) and high p27(Kip1) (p = 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (> or =10% positive nuclei) was significantly associated with high tumor grade (p = 0.001) and with DNA aneuploidy (p = 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p = 0.003). Both cyclin D1 (p = 0.027; RR = 1.898) and Ki67 (p = 0.047; RR = 1.932) protein expressions were independent predictors of reduced disease-free survival on a multivariate analysis that also included p27(Kip1) expression and tumor stage. The simultaneous presence of low cyclin D1, low p27(Kip1) and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.

Adult↗
PubMed1993

Avian integrin alpha v subunit associates with multiple beta subunits and shows tissue-specific variation in its association.

Integrins are heterodimeric cell surface receptors involved in cell adhesion to extracellular matrix proteins and in cell-cell interactions. RGD peptide-specific integrin subunit alpha v and its associated beta subunits were isolated by GRGDSPK-Sepharose affinity chromatography. Using Western blot and immunoprecipitation techniques, the nature of this integrin complexity in the avian system was studied in comparison with that of the human system. As found in human cell systems, in chicken embryo fibroblasts the integrin alpha v subunit is associated with both the 90-kDa beta 3 and the 110-kDa beta 1-like subunits with high specific binding to RGD peptides. Furthermore, immunoprecipitation studies revealed the presence of an unidentified 120-kDa subunit and an 85-kDa beta 5 subunit associated with the alpha v subunit in these cells. No qualitative differences were observed in the beta subunit profile associated with alpha v, as a function of the proliferating nonconfluent or nonproliferating confluent states of the embryonic fibroblast cultures. In adult chicken gizzard, a 110-kDa beta 1-like subunit and a 90-kDa subunit that does not cross-react with anti-H-beta 3 and anti-H-beta 5 are associated with the alpha v subunit. The structure of the novel 120-kDa subunit found in the embryonic fibroblasts and the 90-kDa subunit found in adult chicken gizzard and the ligand specificities of these novel combinations of alpha v are not known at present, but these integrins are RGD specific. It is hypothesized that embryonic fibroblasts, being the primordial proliferating cells, display a wider spectrum of alpha v-associated beta subunits, whose expression may progressively be restricted or highly reduced in favor of one or more beta subunits in subsequent progenies as differentiation progresses.

Amino Acid Sequence↗
PubMed1996

Self-Association of Phenothiazine Drugs: Influence of the Counterion on the Mode of Association

The association characteristics of the phenothiazine drug trimeprazine tartrate in water and aqueous electrolyte solution have been examined using static and dynamic light scattering techniques and compared with those reported for the structurally related drug promethazine hydrochloride, to identify differences in association pattern arising from differences in the counterions of the two drugs. The association of trimeprazine tartrate was micellar in water and in the presence of added electrolyte. A progressive increase of aggregation number and micellar radius was observed with increase of sodium chloride concentration over the range 0.05 to 0.60 M NaCl. This behavior is in contrast to that of promethazine hydrochloride which exhibits continuous association above the critical concentration in electrolyte of concentrations >/=0.2 M NaCl. Moreover, static light scattering curves for trimeprazine tartrate showed a single discontinuity corresponding to the onset of micellization, whereas the association behavior of promethazine hydrochloride (and other phenothiazine drugs with chloride counterions), in water and dilute electrolyte (0.05-0.1 M NaCl), is complex, with discontinuities in solution properties at several critical concentrations. The results of this study highlight the influence of the counterion on the association characteristics of this class of amphiphile.

Journal Article↗
PubMed1989

Immune cells associated with M cells in the follicle-associated epithelium of Peyer's patches in the rat. An electron- and immuno-electron-microscopic study.

Follicle-associated epithelium of Peyer's patches can be differentiated from nearby villous epithelium by the presence of M cells which are antigen-sampling epithelial cells, and by an increase in intraepithelial lymphocytes that are in close contact with M cells. The phenotype of the immune cells close to the M cells of the follicle-associated epithelium of rat Peyer's patches was determined by immunohistochemistry and compared with that of the intra-epithelial lymphocytes of the villous epithelium. Lymphoid T cells, predominantly of the cytotoxic/suppressor phenotype, were observed both in follicle-associated epithelium and in villous epithelium. Lymphoid B cells, mainly immunoblasts and plasma cells containing intracytoplasmic IgM, were present only in the follicle-associated epithelium, near M cells. Macrophages were also present, in contact with M cells, in follicle-associated epithelium, but not in villous epithelium. In addition, M cells bore Ia molecules on their apical membranes. These findings reinforce the concept of immune specialization of the follicle-associated epithelium, by demonstrating that this epithelium contains all the effector cells of immune responses.

Animals↗
PubMed2000

Coexpression of keratins 13 and 16 in human keratinocytes indicates association between hyperproliferation-associated and retinoid-induced differentiation.

In human skin, epidermal differentiation occurs in two ways: normal differentiation, characterized by keratin 10 expression, and alternative differentiation. Alternative differentiation can be hyperproliferation-associated differentiation (expression of keratin 16) or the reinduction of an embryonic type of differentiation (expression of keratin 13). This embryonic type of differentiation is also seen following treatment with retinoids. In the present study, the hypothesis that hyperproliferation-associated and retinoid-induced differentiation are separate processes was investigated. Two areas of normal skin were treated for 24 h with 0. 1% all-trans-retinoic acid. Subsequently, one of the areas was tape-stripped and treatment was continued for 48 h. Multiparameter flow cytometry permitted simultaneous measurement of two coexpressed differentiation markers (retinoid-induced and normal differentiation or retinoid-induced and hyperproliferation-associated differentiation) and the proliferation characteristics (cells in S/G(2)M phase). Concerning normal and retinoid-induced differentiation, the all-trans-retinoic acid-induced expression of keratin 13 was only seen in tape-stripped retinoid-treated skin and exclusively together with that of keratin 10. The assessment of hyperproliferation-associated and retinoid-induced differentiation showed slight expression of keratin 13 without expression of keratin 16 in tape-stripped skin. Coexpression of keratins 16 and 13 was exclusively seen in tape-stripped retinoid-treated skin. The finding that keratin 13 expression following treatment with all-trans-retinoic acid occurred exclusively in hyperproliferative skin suggests that retinoid-induced and hyperproliferation-associated differentiation are coupled. Coexpression of keratins 13 and 16 provides direct experimental evidence for this association.

Adhesives↗
PubMed2006

A complete genetic association scan of the 22q11 deletion region and functional evidence reveal an association between DGCR2 and schizophrenia.

Several lines of evidence have established the presence of an association between a 3-Mb deletion in chromosome 22q11 and schizophrenia. In this paper we present a complete high-density SNP scan of this segment using DNA pools, and demonstrate significant association between two distinct regions and schizophrenia in an Ashkenazi Jewish population. One of these regions contains the previously identified COMT gene. The pattern of association and linkage disequilibrium (LD) in the second region suggest that DGCR2, which encodes a putative adhesion receptor protein, is the susceptibility gene. We confirmed the association between DGCR2 and schizophrenia through individual genotyping of 1,400 subjects. In a gene expression analysis the risk allele of a coding SNP associated with schizophrenia was found to be associated with a reduced expression of DGCR2. Interestingly, the expression of DGCR2 was also found to be elevated in the dorsolateral prefrontal cortex of schizophrenic patients relative to matched controls. This increase is likely to be explained by exposure to antipsychotic drugs. To test that hypothesis, we looked at rats exposed to antipsychotic medication and found significantly elevated levels of DGCR2 transcripts. The genetic and functional evidences here reported suggest a possible role of the DGCR2 gene in the pathology of schizophrenia and also in the therapeutic effects of antipsychotic drugs.

Alleles↗
PubMed1995

Human herpesvirus type 6 and cytomegalovirus in AIDS-associated Kaposi's sarcoma: no evidence for an etiological association.

Epidemiological studies indicate that acquired immune deficiency syndrome (AIDS)-associated Kaposi's sarcoma (KS) may be caused by an infectious, preferentially sexually transmitted agent. Herpesviruses infections are common sexually transmitted diseases in homosexual men, who are also the main risk group for developing Kaposi's sarcoma. To evaluate a possible role of human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV) in the development of AIDS-associated KS, we investigated cutaneous AIDS-associated KS in 26 AIDS patients using the polymerase chain reaction (PCR) and immunohistochemistry (IHC) to detect the presence of HHV-6 and CMV. Human herpesvirus-6 was detected in nine of 26 Kaposi's sarcoma specimens (all cases were HHV-6 subtype B) and in eight of 27 normal skin specimens from human immunodeficiency virus (HIV) seropositive and HIV seronegative patients (one case was HHV-6 subtype A and seven cases were HHV-6 subtype B). In two of four patients showing HHV-6 in KS of the skin, the virus also was detected in other investigated tissues, such as heart, lung, liver, kidney, and adrenals. Cytomegalovirus was detected only in AIDS-associated KS (seven of 26 KS specimens) and not in normal skin tissues of HIV-seropositive and HIV-seronegative patients. Cytomegalovirus was detected in other organs of those patients showing CMV in Kaposi's sarcoma. Our data indicate that the presence of HHV-6 and CMV in AIDS-associated KS most likely reflects disseminated viral infection. Human herpesvirus-6 and CMV may be cofactors but not the only causative agents for the development of AIDS-associated KS.

AIDS-Related Opportunistic Infections↗
PubMed1990

Self-association of diisopropylphosphoryl-alpha-chymotrypsin: the involvement of active site of the enzyme in its self-association behaviour.

The self-association of diisopropylphosphoryl(DIP)-alpha-chymotrypsin is studied in order to find out whether the active site of the enzyme is involved in its self-association behaviour or not. Sedimentation coefficient as well as the weight-average (Archibald) molecular weight data are obtained as a function of concentration using an analytical ultracentrifugation technique. The analysis indicated that the experimental data fits the model of indefinite self-association. The comparison of the data with earlier data on alpha-chymotrypsin revealed that after the modification at the active site, the association constant for the self-association is reduced by about 47%, and the system deviated from ideality. Results showed further that Ser-195, at the active site, appears to be involved in the self-association behaviour of alpha-chymotrypsin; however, the participation of other groups at the active site is also implicated.

Binding Sites↗
PubMed1993

pH-dependent association of carbonic anhydrase (CA) with gastric light microsomal membranes isolated from bovine abomasum. Partial characterization of membrane-associated activity.

1. The effect of pH on the association of carbonic anhydrase (CA) with bovine gastric light microsomal membranes (LMMs) was investigated (a) by washing LMMs containing CA activity with solutions of different pHs; (b) by studying the adsorption at various pHs of soluble bovine erythrocyte CA to washed gastric LMMs. In both cases, the association of CA with gastric LMMs was dependent on pH, being lower at neutral or alkaline pH. 2. The amount of soluble CA associated with gastric LMMs at pHs 8.0 and 9.0 was reduced when 140 mM K+/10 mM Na+ was added to the incubation medium. 3. Two sources of CA activity in bovine gastric LMMs were assumed: a loosely- and a firmly-membrane-associated activity. Both CA activities were dose-dependently inhibited by acetazolamide (I50: 3.6 x 10(-9) and 8.4 x 10(-9) M, respectively) and by chloride, acetate, iodide, bromide and nitrate at 100 mM. Firmly-membrane-associated activity appeared to be less sensitive to inhibition by acetazolamide, chloride and iodide. 4. Both activities exhibited different behavior and stability following treatment with alkaline Triton X-100. 5. The possible importance of a membrane-associated CA activity in gastric LMMs related to gastric acid secretion is discussed.

Abomasum↗