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At least 379 records · Page 21Linked to original sources
PubMed2006

Method development and validation for zotarolimus concentration determination in stented swine arteries by liquid chromatography/tandem mass spectrometry detection.

Drug-eluting stents have attracted significant attention in the medical community and pharmaceutical industry due to their proven success in significantly reducing restenosis. Abbott Laboratories is developing a drug-eluting stent coated with zotarolimus and swine was recently used as an animal model for the pre-clinical study of stent implantation. In this article, we present a detailed experimental design and results for the validation and sample analysis of zotarolimus drug concentration in stented swine artery samples. Introduction of tissue quality control (QC) samples allows evaluation of the entire analytical process as well as the stability of the drug in both original tissue and homogenized tissue samples. In addition, a novel approach using 100% swine blood as the homogenization solution was developed for the consistency of the liquid-liquid extraction recovery and stability of the zotarolimus in tissue homogenates. Standards were prepared by spiking zotarolimus working solution in swine blood and tissue QC samples were used along with the artery samples during the sample analysis. The linear dynamic range of blood standard samples is from 0.61 to 333.20 ng/mL to accommodate the predicted artery homogenate concentrations. Overall tissue QC %CV during the method validation was from 4.4% to 8.6%. The overall %bias of tissue QC samples during the method validation was from -7.3% to 16.6%. The method was successfully applied for the analysis of swine artery samples. A similar approach for method validation and sample analysis has been successfully applied for the analysis of swine myocardium, kidney and liver tissue samples.

Animals↗
PubMed1990

Relationship between tumorigenicity, in vitro invasiveness, and plasminogen activator production of human breast cell lines.

Two human breast epithelial cell lines (HBL-100, HMT-3522) of non-malignant origin and six (MCF-7, T47-D, ZR-75-1, CAMA-1, BT-20, HMT-3909) of malignant origin have been studied to evaluate whether in vitro invasion and/or secretion of urokinase-type plasminogen activator are related to tumorigenicity in athymic nude mice. Only the six cell lines of malignant origin were tumorigenic. Two of these were invasive in the in vitro assay. These two cell lines were oestrogen receptor negative. Three of the other four cell lines of malignant origin contained oestrogen receptors. The two cell lines of non-malignant origin were neither tumorigenic nor invasive. Thus tumorigenicity was correlated to malignant origin of the cell line whereas invasiveness in vitro was a property of the most undifferentiated cell lines of tumor origin. Secretion of urokinase-type plasminogen activator was neither correlated to tumorigenicity nor to invasion in vitro nor to malignancy of tissue origin.

Animals↗
PubMed2006

CD4 and MHC-I downregulation are conserved in primary HIV-1 Nef alleles from brain and lymphoid tissues, but Pak2 activation is highly variable.

HIV-1 compartmentalization in the CNS has been demonstrated for gag, pol, and env genes. However, little is known about tissue compartmentalization of nef genes and their functional characteristics in brain. We have cloned 97 nef genes and characterized 10 Nef proteins from autopsy brain and lymphoid tissues from 2 patients with AIDS and HIV-1-associated dementia. Distinct compartmentalization of brain versus lymphoid nef genes was demonstrated within each patient. CD4 and MHC-I downregulation were conserved in all tissue-derived Nefs. However, MHC-I downregulation by brain-derived Nefs was weaker than downregulation by lymphoid-derived Nefs. The motifs KEEE- or EKEE- at the PACS-1 binding site represented brain-specific signature patterns in these 2 patients and contributed to the reduced MHC-I downregulation activity of brain-derived Nefs from these patients. Pak2 association was highly variable in Nefs from both patients. Three of 10 tissue-derived Nefs coimmunoprecipitated activated Pak2, with strong association demonstrated for only 2 Nefs. The ability of Nef to associate with activated Pak2 did not correlate with brain or lymphoid tissue origin. Nef genes from viruses isolated from brain by coculture with PBMC were not closely related to sequences amplified directly from brain tissue, suggesting that viral selection or adaptation occurred during coculture. This study of tissue-derived HIV-1 Nefs demonstrates that CD4 and MHC-I downregulation are highly conserved Nef functions, while Pak2 association is variable in late stage AIDS patients.

AIDS Dementia Complex↗
PubMed1993

Investigation of factors affecting fluorometric quantitation of cytosolic [Ca2+] in perfused hearts.

The goal of these studies was to examine the effects of several factors that may artifactually influence quantitation of cytosolic [Ca2+], [Ca2+]c, while using the fluorescent calcium indicator Indo-1. The following factors were investigated: 1) a possible fluorescence contribution from unhydrolized Indo-1/AM (by Mn2+ quenching), 2) Ca2+ buffering by Indo-1 (by varying [Indo-1]), 3) endothelial and mitochondrial Indo-1 loading (by bradykinin stimulation and calculations), and 4) effects of changing tissue fluorescence (predominantly NAD(P)H) on calculated [Ca2+]c during hypoxia (by a new method which allowed simultaneous determination of [Ca2+]c and changes in [NAD(P)H]). No significant contribution of Indo-1/AM was found. With increasing [Indo-1], calculated systolic [Ca2+]c fell significantly. Indo-1 incorporation (< 18%) into endothelial cells, caused a slight underestimation of systolic [Ca2+]c, while mitochondrial Indo-1 loading may cause overestimation of [Ca2+]c. With increased tissue fluorescence, during hypoxia, systolic [Ca2+]c may be underestimated by approximately 27% (for Indo-1 loading factors three to five times original tissue fluorescence). These studies suggest conditions in which experimental artifacts could be minimized to allow reliable quantitation of [Ca2+]c in intact perfused hearts using Indo-1 fluorometry. The major problem of obtaining reliable results depended on the ability to correct for changing NAD(P)H fluorescence while keeping [Indo-1] low.

Animals↗
PubMed2003

The chemically treated bovine ureter--clinical performance of a novel biological vascular prosthesis.

AIM: This paper describes the rationale, development and clinical performance of a novel small-diameter vascular prosthesis of non-vascular animal tissue origin. METHOD: Durable conduits suitable for coronary and peripheral arterial reconstruction are prepared for the first time from non-vascular animal tissue. Australian bovine ureters from young steers from protected herds are processed to form strong, bloodflow-compatible and non-immunogenic biologic grafts ('Flonova', Bionova International Pty Ltd, Melbourne). Fifty-six patients lacking suitable autogenous veins received 62 prostheses (32 bypasses were implanted above knee and 30 below knee). Determination of patency and function included Doppler ultrasound, duplex scanning and angiography. FINDINGS: The primary patency rate at 1, 2 and 5 years, respectively was 67, 59 and 52% and the secondary patency for the same time frames was 88, 73 and 61%. There were no occlusions as a result of intimal hyperplasia. Dilatation of the wall was diagnosed in one prosthesis at 3.5 years, and one at 7 years, and a false aneurysm of unknown aetiology occurred in another at 3 months. There were no primary graft infections. CONCLUSION: This evaluation shows the chemically treated bovine ureter (CTBU) is a viable medium-term alternative to the currently available artificial vascular prostheses for peripheral revascularisation.

Aged↗
PubMed2002

A tumor-specific kinase activity regulates the viral death protein Apoptin.

Apoptin, a chicken anemia virus-encoded protein, is thought to be activated by a general tumor-specific pathway, because it induces apoptosis in a large number of human tumor or transformed cells but not in their normal, healthy counterparts. Here, we show that Apoptin is phosphorylated robustly both in vitro and in vivo in tumor cells but negligibly in normal cells, and we map the site to threonine 108. A gain-of-function point mutation (T108E) conferred upon Apoptin the ability to accumulate in the nucleus and kill normal cells, implying that phosphorylation is a key regulator of the tumor-specific properties of Apoptin. An activity that could phosphorylate Apoptin on threonine 108 was found specifically in tumor and transformed cells from a variety of tissue origins, suggesting that activation of this kinase is generally associated with the cancerous or pre-cancerous state. Moreover, analyses of human tissue samples confirm that Apoptin kinase activity is detectable in primary malignancies but not in tissue derived from healthy individuals. Taken together, our results support a model whereby the dysregulation of the cellular pathway leading to the phosphorylation of Apoptin contributes to human tumorigenesis.

Amino Acid Sequence↗
PubMed2005

Serum CA 125 levels in patients with chronic lymphocytic leukemia.

Cancer antigen 125 (CA 125) is a glycoprotein expressed in normal tissues originally derived from celomic epithelia and its serum level is elevated in various benign and malignant conditions that involve stimulation of these tissues. Elevated levels have been reported in 40-43% of patients with non-Hodgkin's lymphoma (NHL) at diagnosis and were associated with parameters known to be associated with advanced and disseminated disease, and with event-free and overall survival. No difference in CA 125 level was found between indolent and aggressive lymphomas, and four of six patients with small lymphocytic lymphoma had elevated CA 125 levels. We therefore decided to measure serum CA 125 levels in chronic lymphocytic leukemia (CLL) patients, and evaluated them in 74 consecutive patients. The mean time from diagnosis to test was 74.5 months (range: 0-300). The mean serum CA 125 level was 16.3 U/ml (range: 3.7-133, normal value: <35 U/ml). CA 125 levels were elevated only in two patients (2.7%). To conclude, serum CA 125 levels are rarely elevated in CLL patients. It is possible that serum CA 125 levels can help differentiate between equivocal cases of small lymphocytic lymphoma and CLL.

Adult↗
PubMed2002

VLA-2 (alpha2beta1) integrin promotes rotavirus entry into cells but is not necessary for rotavirus attachment.

In an attempt to identify the rotavirus receptor, we tested 46 cell lines of different species and tissue origins for susceptibility to infection by three N-acetyl-neuraminic (sialic) acid (SA)-dependent and five SA-independent rotavirus strains. Susceptibility to SA-dependent or SA-independent rotavirus infection varied depending on the cell line tested and the multiplicity of infection (MOI) used. Cells of renal or intestinal origin and transformed cell lines derived from breast, stomach, bone, or lung were all susceptible to rotavirus infection, indicating a wider host tissue range than previously appreciated. Chinese hamster ovary (CHO), baby hamster kidney (BHK-21), guinea pig colon (GPC-16), rat small intestine (Rie1), and mouse duodenum (MODE-K) cells were found to support only limited rotavirus replication even at MOIs of 100 or 500, but delivery of rotavirus particles into the cytoplasm by lipofection resulted in efficient rotavirus replication. The rotavirus cell attachment protein, the outer capsid spike protein VP4, contains the sequence GDE(A) recognized by the VLA-2 (alpha2beta1) integrin, and to test if VLA-2 is involved in rotavirus attachment and entry, we measured infection in CHO cells that lack VLA-2 and CHO cells transfected with the human alpha2 subunit (CHOalpha2) or with both the human alpha2 and beta1 subunits (CHOalpha2beta1) of VLA-2. Infection by SA-dependent or SA-independent rotavirus strains was 2- to 10-fold more productive in VLA-2-expressing CHO cells than in parental CHO cells, and the increased susceptibility to infection was blocked with anti-VLA-2 antibody. However, the levels of binding of rotavirus to CHO, CHOalpha2, and CHOalpha2beta1 cells were equivalent and were not increased over binding to susceptible monkey kidney (MA104) cells or human colonic adenocarcinoma (Caco-2, HT-29, and T-84) cells, and binding was not blocked by antibody to the human alpha2 subunit. Although the VLA-2 integrin promotes rotavirus infection in CHO cells, it is clear that the VLA-2 integrin alone is not responsible for rotavirus cell attachment and entry. Therefore, VLA-2 is not involved in the initial attachment of rotavirus to cells but may play a role at a postattachment level.

Animals↗
PubMed2007

Differentiating primary human cells in rapid-throughput discovery applications.

Primary cultures of human cells provide an increasingly important alternative to using virally transformed or otherwise immortalized cell lines or to using cloned cell lines derived from human or animal tumors. Advances in primary cell culture techniques, media formulations, and other reagents have enabled routine culture of primary cells derived from human tissues for biomedical research and drug discovery approaches such as high content screening. That primary cells retain the phenotypic characteristics of the original tissue is one main advantage over immortalized cell lines. However, securing reliable supplies of primary cells on a large scale has been problematic. Here, two primary differentiating cell types, preadipocytes and preosteoclasts, are described to illustrate the utility of commercially produced cell systems in discovery research and rapid-throughput applications.

Adipocytes↗
PubMed1999

[Microdialysis. A method for measurement of local tissue metabolism].

Studies of pharmacological, immunological, and biochemical reactions in intact tissues have been hampered by the lack of appropriate techniques. The purpose of the review is to give a short introduction to the microdialysis technique which permits measurement of low molecular weight compounds in the extracellular water compartment in different tissue. Originally developed for use in animal brain, microdialysis is now being applied in humans for both clinical and experimental studies in different tissues, e.g. subcutaneous adipose tissue, brain, skin, and skeletal muscle. This review summarizes theoretical and practical aspects of microdialysis, and describes its main applications in humans.

Adipose Tissue↗
PubMed1988

[Tumorous and pseudotumorous cartilaginous lesions of the soft tissues of the hand].

The authors present several rare cartilaginous tumours and pseudotumours of the extraskeletal tissues in an unusual situation, the hand. They present three different varieties depending on the site and histogenesis of the tumour: 1) Intra-articular synovial chondromatosis. 2) Tenosynovial chondromatosis. 3) Soft tissue chondroma (extra-synovial). The authors also discuss the histogenesis of these lesions: synovial for the first two types and an extra-synovial connective tissue origin for the last type.

Chondroma↗
PubMedDate not supplied

Subcellular origin of the surface fluorescence of reduced nicotinamide nucleotides in the isolated perfused rat heart.

Surface fluorometric measurements and indicator metabolite determinations in the isolated perfused rat heart showed that the NADH + NADPH fluorescence of the intact tissue originates largely from the mitochondria. The redox potential of the lactate dehydrogenase system calculated from the endogenous lactate/pyruvate ratios was closely similar to that of the glycerol-3-phosphate dehydrogenase system calculated from the concentrations of glycerol-3-phosphate and dihydroxyacetone phosphate in the tissue. Thus, in contrast to the liver, the cytosolic redox state of the NADH/NAD+ system in isolated perfused heart oxidizing external glucose or fatty acid is not amenable to optical monitoring, but can be assessed from the state of the lactate dehydrogenase or glycerol-3-phosphate dehydrogenase systems.

Animals↗
PubMed1995

Adenylyl cyclase isoforms are differentially expressed in primary cultures of endothelial cells and whole tissue homogenates from various rat tissues.

The expression of five adenylyl cyclase isoforms (types II-VI) was studied with reverse transcription-polymerase chain reaction in whole tissue homogenates and in primary cultures of endothelial cells isolated from rat aorta, vena cava, heart, lung, adipose fat, brain, and adrenal medulla. It was found that: i) all endothelial cell types express all adenylyl cyclase isoforms studied, albeit at different levels depending on the tissue origin of the cells, and ii) the adenylyl cyclase isoform profile of isolated endothelial cells differs from that of homogenates of their parent tissues. Our data show a unique endothelial cell type specificity of AC isoform expression, which varies from that of the whole organ. These results support the idea that one of the factors mediating differential regulation of the cAMP cascade in EC in various locations within the vascular tree might be quantitative differences in the levels of AC isoforms expressed in each EC type.

Adenylyl Cyclases↗
PubMed2001

Possible applications of conditionally immortalized tissue cell lines with differentiation functions.

If all individual cell types of the body could be clonally isolated and stocked, similar to cDNA or genomic DNA libraries, they would be invaluable for studying the tissue and cellular functions. We developed a new method of establishing conditionally immortalized cell lines that retain differentiated cell functions similar to the original tissues, using temperature-sensitive (ts) simian virus 40 large tumor antigen gene transgenic animals. In this review the properties of such conditionally immortalized cell lines and their possible applications are discussed.

Animals↗
PubMed2003

Tissue microarray technology: validation in colorectal carcinoma and analysis of p53, hMLH1, and hMSH2 immunohistochemical expression.

Tissue microarray technology enables the analysis of hundreds of specimens by arranging numerous 0.6-mm tissue core biopsy specimens into a single paraffin block. Validation studies are necessary to evaluate the representativeness of small disks taken from the original tissue. We validated the tissue microarray technology in colorectal carcinoma by analyzing the immunohistochemical expression of proteins involved in the two main pathways of colorectal carcinogenesis: p53 protein for loss of heterozygosity tumors, hMLH1 and hMSH2 proteins for microsatellite instability (MSI) tumors. We compared in 30 colorectal carcinomas (15 MSI(-) and 15 MSI(+)), 8 microarrays disks, and the whole section of the block from which they were derived. Tumoral tissue was present in 95.7% of the microarray disks. The analysis of three disks per case was comparable to the analysis of the whole section in 99.6% (p53), 98.8% (hMLH1), and 99.2% (hMSH2) of cases. In the second part we applied the tissue microarray technology to 263 consecutive cases of colorectal carcinoma, sampled by three cores. We showed that 48.5% overexpressed p53 and 8.7% lost hMLH1 or hMSH2. Tissue microarray technology, validated in colorectal carcinoma, appears as a useful research tool for rapid analysis of the clinical interest of molecular alterations.

Adaptor Proteins, Signal Transducing↗
PubMed2002

The rho/rho-kinase pathway is involved in the progression of testicular germ cell tumour.

OBJECTIVE: To clarify the role of one of the downstream effectors of Rho (Rho-kinase) in testicular germ cell tumour (GCT) by quantifying mRNA expression for Rho-kinase in patients with this disease. MATERIALS AND METHODS: The mRNA levels of the RhoA and Rho-kinase genes were analysed in surgical specimens of testicular GCT tissues from 57 consecutive Japanese patients, and in the corresponding non-tumour tissue originating from the same patient, using the polymerase chain reaction after reverse transcription. The expression levels of these genes were compared between the tissues and the relationship between their expression levels evaluated within tumours and with tumour stage. The difference in the expression levels of the mRNAs of RhoA and Rho-kinase genes were also assessed between tumours that were seminoma only and mixed tumours of seminoma and nonseminoma. RESULTS: RhoA and Rho-kinase mRNAs were more abundant in tumour tissue than in non-tumour tissue (P < 0.01 and < 0.05, respectively). High RhoA and Rho-kinase mRNA expressions were related to tumour stage (P < 0.05 and < 0.01, respectively). The mRNA levels of RhoA and Rho-kinase in mixed tumours were higher than in tumours with seminoma only (P < 0.01 and < 0.05, respectively). There was a positive relationship between expression levels of mRNAs of RhoA and Rho-kinase in tumour tissues (P < 0.001). CONCLUSIONS: These findings suggest that the RhoA/Rho-kinase pathway is involved in the progression of testicular GCT. This pathway might be a molecular target for new treatment strategies for this disease.

Adolescent↗
PubMed1990

In vitro inhibition of hemopoietic cell line growth by hepatitis B virus.

The effects of hepatitis B virus (HBV) on established human cell lines of various tissue origins were evaluated by clonal or colorimetric assays in methylcellulose culture. HBV exposure inhibited the growth of six hemopoietic cell lines, while similar incubation did not affect the growth of seven nonhemopoietic carcinoma cell lines of breast, colon, liver, and stomach origin. The inhibition of hemopoietic cell line colony formation was dependent on the presence of intact viral (Dane) particles and the ratio of exposure of virions to cells and was reversible with antibodies to pre-S1, pre-S2, and S envelope protein epitopes. Purified HBV DNA, surface antigen pre-S antigens, and core antigen did not inhibit cell line growth. These results further demonstrate the tropism of HBV for cells of hemopoietic origin, confirming our previous findings on the effects of HBV on the growth of normal bone marrow progenitor cells in vitro. Established human tissue culture cell lines may be used to study the interactions of hemopoietic cells with HBV.

Cell Division↗
PubMed1989

Ewing's sarcoma of bone and soft tissues.

Ewing's sarcoma is a distinctive clinical and pathologic entity that may be intraosseous or of soft-tissue origin. In the facial bones, the incidence of the sarcoma is estimated at 2.5% of all Ewing's sarcoma of bone. The soft tissue of the head and neck account for 11% of extraskeletal sites of the neoplasm. Combined modality treatment has modified its high-grade malignancy.

Bone and Bones↗