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T Daly

Publications and source records attributed to T Daly.

At least 19 recordsLinked to original sources
PubMed2004

Observation of lymphatic vessels in orbital fat of patients with inflammatory conditions: a form fruste of lymphangiogenesis?

In the absence of antibodies specific for lymphatic vessels, analysis of lymphatic vessels within different tissues has been widely performed with light microscopic and, most importantly, electron microscopic techniques. In regard to lymphatic vessels in the ocular globe and the periocular structures, controversy remains about the specific distribution of lymphatic channels. It is postulated that bulbar and retrobulbar tissues are devoid of lymphatic vessels, but lymphatic vessels have been demonstrated in lacrimal gland and epibulbar conjunctiva. In this study, we analyzed orbital fat for the presence of lymphatic tissue using D2-40, a monoclonal antibody, specific for lymphatic vessels. We found lymphatic vessels present within bulbar conjunctiva extending to the level of the ciliary apparatus. No lymphatics were identified in healthy anterior orbital adipose tissue. In two cases of orbital mucor-mycosis and one case of panendophthalmitis, significant lymphovascular proliferation was present within granulation tissue associated with the acute inflammation. We conclude that lymph vessel proliferation may be induced in inflammatory conditions in tissues which are normally devoid of lymph channels.

Adipose Tissue↗
PubMed2004

Identification of lymphatic vessels in malignant, adenomatous and normal colonic mucosa using the novel immunostain D2-40.

Distribution of lymphatic vessels in normal and neoplastic colon has been previously analyzed with electron microscopic techniques, as reliable antibodies have not been available for selective lymph vessel staining. A novel monoclonal antibody, D2-40, is recently available to differentiate lymphatic vessels from blood vessels. In this study, we analyzed the distribution of lymphatic vessels in normal colon, adenomas with and without superficial stalk invasion and invasive carcinomas without identifiable polypoid precursor lesions. In contrast to previous studies, we found lymphatic vessels in superficially misplaced stalk stroma in adenomas, and closely associated with early invasive epithelial nests in invasive lesions. Lymphatic vessels were identified within the lamina propria of the in situ aspect of in invasive tumors. We conclude that lymphatic vessel structures are seen more superficially in adenomas and invasive carcinomas than previously described. Since intramucosal carcinomas in adenomas do not metastasize, these lymph vessels may be immature or not communicate with deeper lymphatics. Proliferation and distribution of lymphatic vessels may be related to prognosis and early metastasis.

Adenoma↗
PubMed2002

Supporting family carers through the use of information and communication technology--the EU project ACTION.

Assisting Carers Using Telematics Interventions to meet Older persons' Needs (ACTION) is an EU project designed to improve the quality of life of frail older and disabled people and their family carers by the use of information and communication technology. It involved Sweden, England, Northern Ireland, the Republic of Ireland and Portugal. This article provides an overview of the research and development process of the ACTION system and services. The focus is upon the evaluation results with regard to the quality of life of older people and their family carers, the usability of ACTION and cost considerations. Recommendations are made regarding user-focused technology such as ACTION.

Aged↗
PubMed2002

Increased functional expression of transgene in primary human lymphocytes using retroviral vectors modified with IRES and splicing motifs.

Genetic modification of human lymphocytes is being employed in strategies to correct enzyme deficiencies, encode cytokines and to redirect lymphocytes to antigenic targets other than those encoded by their endogenous T cell receptor. However, expression of transgenes in primary lymphocytes is generally low. Reasoning that vector modification may lead to increased transgene expression and subsequent increases in function, we have performed two retroviral vector modifications and report their effect on the functional expression in primary lymphocytes. A chimeric receptor specific for the colon carcinoma-associated antigen, EGP40, was initially incorporated into the retroviral vector LXSN. In this vector, receptor expression is driven by the Moloney murine leukemia virus LTR, and neomycin phosphotransferase expression driven by the SV40 promoter. Replacement of SV40 with an internal ribosomal entry site (IRES) increased the transgene activity of a mouse T cell line and human PBL as judged by increased cytokine release in response to antigen positive target cells. A further increase in transgene function was generated by the additional incorporation of a splice acceptor motif into the construct. Human PBL transduced with vector incorporating both IRES and intron were consistently more effective at lysing antigen positive colorectal carcinoma cells.

Adult↗
PubMed2001

CMV-beta-actin promoter directs higher expression from an adeno-associated viral vector in the liver than the cytomegalovirus or elongation factor 1 alpha promoter and results in therapeutic levels of human factor X in mice.

Although AAV vectors show promise for hepatic gene therapy, the optimal transcriptional regulatory elements have not yet been identified. In this study, we show that an AAV vector with the CMV enhancer/chicken beta-actin promoter results in 9.5-fold higher expression after portal vein injection than an AAV vector with the EF1 alpha promoter, and 137-fold higher expression than an AAV vector with the CMV promoter/enhancer. Although induction of the acute-phase response with the administration of lipopolysaccharide (LPS) activated the CMV promoter/enhancer from the context of an adenoviral vector in a previous study, LPS resulted in only a modest induction of this promoter from an AAV vector in vivo. An AAV vector with the CMV-beta-actin promoter upstream of the coagulation protein human factor X (hFX) was injected intravenously into neonatal mice. This resulted in expression of hFX at 548 ng/ml (6.8% of normal) for up to 1.2 years, and 0.6 copies of AAV vector per diploid genome in the liver at the time of sacrifice. Neonatal intramuscular injection resulted in expression of hFX at 248 ng/ml (3.1% of normal), which derived from both liver and muscle. We conclude that neonatal gene therapy with an AAV vector with the CMV-beta-actin promoter might correct hemophilia due to hFX deficiency.

Actins↗
PubMed2001

Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors.

Gene therapy using recombinant adeno-associated virus vectors (rAAV) is generally considered safe. During the course of a study designed to determine the long-term efficacy of rAAV-mediated gene therapy initiated in newborn mice with the lysosomal storage disease, mucopolysaccharidosis type VII (MPSVII), a significant incidence of hepatocellular carcinomas and angiosarcomas was discovered. A hepatocellular carcinoma was first detected in a 35-week-old mouse and by 72 weeks of age, three out of five rAAV-treated MPSVII mice had similar lesions. These types of tumors had not been seen previously in long-term studies of MPSVII mice using recombinant enzyme or bone marrow transplantation. In an attempt to ascertain whether mouse strain or GUSB expression confers susceptibility to tumor formation, we histopathologically examined untreated normal mice of the same strain, untreated MPSVII mice, and normal mice overexpressing human GUSB for the presence of tumors and increased hepatocyte replication. The results of these studies do not indicate that MPSVII mice or mice overexpressing human GUSB are susceptible to tumor formation; however, the number of animals examined is too small to draw definitive conclusions. Results from quantitative PCR performed on the tumor samples suggest that the tumors are probably not caused by an insertional mutagenesis event followed by the clonal expansion of a transformed cell. In a separate study, a relatively large group of mice injected with varying doses and types of rAAV vectors had no evidence of hepatic or vascular tumors. Although the mechanism of tumor formation is currently unknown, the tumorigenic potential of rAAV vectors must be rigorously determined in long-term in vivo studies.

Animals↗
PubMed2000

Recognition of human colon cancer by T cells transduced with a chimeric receptor gene.

Transduction with chimeric T-cell receptor genes can be used to redirect primary T lymphocytes to recognize specific antigens (Ags), including ovarian and breast cancer Ags. To extend this approach to colon cancer we report here redirection of T cells using a chimeric receptor recognizing the colon cancer-associated Ag EGP40. Chimeric T cell receptors were constructed by ligating single-chain genes of either of two EGP40-specific monoclonal antibodies (CO17.1 A, GA733) to the Fc receptor gamma-signaling chain. Retroviral vectors incorporating these constructs were used to transduce a murine T-cell line and human peripheral blood lymphocytes. These modified T cells were analyzed for specific recognition of colon cancer lines by measuring cytokine release and lytic activity against tumor targets. Murine lymphocytes transduced with the chimeric receptor based on GA733, but not CO17.1A, released cytokine specifically in response to EGP40-expressing colon cancer cell lines. Recognition of colon cancer targets by murine lymphocytes was blocked by the addition of GA733 antibody or soluble EGP40 Ag, confirming that colon cancer recognition is based on specific chimeric receptor-Ag interaction. Human lymphocytes transduced with chimeric GA733 specifically recognized colon carcinoma cells in cytokine release assays and lysed EGP40-expressing tumor cells. Genetic modification of T cells can be used to redirect T cells against EGP40-expressing tumor cells. The expression of chimeric GA733 in the autologous lymphocytes of patients may provide a source of tumor-reactive cells with therapeutic application against colon cancer.

3T3 Cells↗
PubMed1997

Cholesterol supplementation prevents necrosis and inflammation but enhances fibrosis in alcoholic liver disease in the rat.

Based on studies that show a role for the low-density lipoprotein (LDL)-receptor in arachidonic acid delivery and eicosanoid synthesis in macrophages, the present study investigated the effect of cholesterol supplementation on pathological changes and thromboxane (TX) synthesis in alcoholic liver injury. Male Wistar rats were intragastrically fed ethanol with either corn oil or fish oil for 1 month. Control rats received isocaloric amounts of dextrose instead of ethanol. An additional group of rats fed either ethanol or dextrose with fish oil or corn oil were supplemented with 1% cholesterol. At the time of killing, all rats had the following evaluated: liver histopathology, lipid peroxidation, liver and plasma thromboxane levels, plasma endotoxin and messenger RNA (mRNA) levels of LDL-receptor, tumor necrosis factor alpha (TNF-alpha), cyclooxygenase (Cox)-1 and -2, and transforming growth factor beta (TGF-beta). Rats fed ethanol with either fish oil or corn oil developed fatty liver, necrosis, inflammation, and central vein collagen deposition. Cholesterol supplementation enhanced the degree of fibrosis but prevented necrosis and inflammation. These alterations in pathological changes by cholesterol were accompanied by absent TNF-alpha and Cox-2 mRNAs, decreased thromboxane levels, decreased lipid peroxidation, and increased TGF-beta mRNA. Cholesterol enrichment of the diet thus decreases proinflammatory components, but enhances fibrosis in ethanol-fed rats.

Animals↗
PubMed1997

Dietary saturated fatty acids down-regulate cyclooxygenase-2 and tumor necrosis factor alfa and reverse fibrosis in alcohol-induced liver disease in the rat.

We investigated the potential of dietary saturated fatty acids to decrease endotoxemia and suppress expression of cyclooxygenase 2 (Cox-2) and tumor necrosis factor alpha (TNF-alpha) in established alcohol-induced liver injury. Six groups (five rats/group) of male Wistar rats were studied. Rats in group 1 were fed a fish oil-ethanol diet for 6 weeks. Rats in groups 2, 3, and 4 were fed fish oil and ethanol for 6 weeks. Ethanol administration was stopped at this time, and the rats were switched to isocaloric diets containing dextrose with fish oil (group 2), palm oil (group 3), or medium-chain triglycerides (group 4) as the source of fat for an additional 2 weeks. Rats in groups 5 and 6 were fed fish oil-ethanol and fish oil-dextrose, respectively, for 8 weeks. Liver samples were analyzed for histopathology, lipid peroxidation, and levels of messenger RNA (mRNA) for Cox-2 and TNF-alpha. Concentrations of endotoxin were determined in plasma. The most severe inflammation and fibrosis were detected in groups 1 and 5, as were the highest levels of endotoxin, lipid peroxidation, and mRNA for Cox-2 and TNF-alpha. After ethanol was discontinued, there was minimal histological improvement in group 2 but near normalization of the histology, including regression of fibrosis, in groups 3 and 4. Histological improvement was associated with decreased levels of endotoxin, lipid peroxidation, and reduced expression of Cox-2 and TNF-alpha. The data indicate that a diet enriched in saturated fatty acids (groups 3 and 4) effectively reverses alcohol-induced liver injury, including fibrosis. The therapeutic effects of saturated fatty acids may be explained, at least in part, by reduced endotoxemia and lipid peroxidation, which in turn result in decreased levels of TNF-alpha and Cox-2.

Animals↗
PubMed1994

Neural cyst of the ovary with central nervous system microvasculature.

A case of a monodermal teratoma of the ovary composed solely of mature neuroglial elements is described. The cyst lining comprised ependymal cells surrounded by white matter which itself was resting on mesothelial cells. Astrocytes, oligodendrocytes, microglia and neurofilament-positive fibres were seen, but no neuron cell bodies were present. Immunohistochemical stains showed positivity for glial fibrillary acidic protein in ependymal, subependymal and the white matter regions while S-100 protein positivity was restricted to the white matter. Vessels within neuroectodermal tissue, but not those within the mesodermal tissue, stained positively for anti-glucose transporter protein, a marker shown to be present in vessels with barrier functions. We conclude that this is a rare case of monodermal teratoma consisting of purely mature brain tissue with a microvasculature exhibiting blood-brain barrier characteristics.

Adult↗
PubMed1991

The lentivirus regulatory proteins REV and REX are site specific RNA binding proteins.

These studies demonstrate that HIV-1 REV and HTLV-1 REX are site specific RNA binding proteins. In addition, the REV protein studies indicate a protein domain essential for biological function that is not involved in RRE binding. Lentiviruses are unique among retroviruses in providing gene products to switch expression from early to late genes. Rather than transcriptional control, this is accomplished by regulating RNA transport. A further understanding of these lentiviral genes may identify means of inhibiting viruses responsible for insidious human disease.

Amino Acid Sequence↗
PubMed1987

Correlation of plasma beta-endorphin levels with mean arterial pressure and cardiac output in hypovolemic shock.

Recent studies have been conducted to evaluate the relationship between plasma beta-endorphin (END) levels and the hemodynamic changes that occur in severely stressed animals. Using our canine hypovolemic shock model, END levels were analyzed during the baseline period, at the beginning of treatment (after a period of fixed-pressure hypovolemic shock), and at the end of treatment. Mean arterial pressure (MAP) and cardiac output were also measured at these intervals. Animals were given iv 5 ml of 0.9% NaCl, 4 mg/kg of naloxone (NAL), 30 mg/kg of methylprednisolone (MP), or 4 mg/kg of NAL and 30 mg/kg of MP. A fifth group was composed of nonsteroid-treated animals. Scatterplots were generated and linear regression lines were drawn comparing END with cardiac output and MAP. In the nonsteroid-treated animals, a significant correlation was found between decreases in both MAP and cardiac output and increasing levels of END. The addition of MP did not seem to alter the relationship, suggesting that MP did not affect END release.

Animals↗
PubMed1987

Morphine sulfate depression of cardiac function is attenuated by opiate receptor antagonism with naloxone.

In previous work, morphine sulfate was shown to decrease heart rate (HR) and cardiac output (CO) in a dose-related fashion. It was hypothesized that this effect was mediated by opiate receptors located in the myocardium. The present study evaluated the effect of opiate receptor antagonism with naloxone using a modified Langendorff rat heart perfusion apparatus. Sixty-five rat hearts were excised and perfused with Krebs-Henseleit buffer (KHB) solution, to which morphine sulfate and naloxone (NAL) were added in different concentrations. In the initial studies, NAL (10(-5) M) was added to the perfusate prior to the incremental additions of morphine. This resulted in no antagonism of the previously described opiate agonist effects. Norepinephrine (NE; 10(-9) M) was then added to the perfusate prior to the NAL or morphine. The NE did not affect the dose-related decrease in HR and CO when morphine was added but did permit the attenuation of the morphine effect by the addition of increasing concentrations of NAL up to 10(-5) M. These results suggest that the agonist effect can be attenuated by opiate receptor antagonism with NAL; the data also suggest a possible interrelationship between opiate and catecholamine receptor activity in the myocardium.

Animals↗
PubMed1987

Myocardial opiate receptor activity is stereospecific, independent of muscarinic receptor antagonism, and may play a role in depressing cardiac function.

Earlier work has shown that morphine sulfate can produce a dose-related decrease in heart rate (HR) and cardiac output (CO) in isolated working rat hearts. This response is preventable with the use of the opiate receptor antagonist, naloxone hydrochloride. In this study, the stereospecificity of the opiate response was tested with the use of levorphanol tartrate and its d-isomer, dextrorphan, in our Langendorff rat heart model. The interaction of muscarinic receptor activity with the opiate response was tested by first adding bethanechol chloride to the perfusate in the presence and absence of atropine (5 X 10(-9) mmol/L). Our earlier studies with morphine sulfate were then repeated in the presence of the same concentration of atropine. At a concentration of 5 X 10(-6) mmol/L, levorphanol tartrate produced a significant decrease in CO (p less than 0.05), while a similar concentration of dextrorphan produced little change in either HR or CO. Bethanechol chloride, in a concentration of 3 X 10(-6) mmol/L, produced a significant decrease in HR and CO (p less than 0.05), which was prevented by atropine. When morphine sulfate was added to the standard perfusate (3 X 10(-4) mmol/L), HR and CO were significantly decreased (p less than 0.05). This change was not prevented by the addition of atropine. The opiate effect on myocardial function is mediated by a stereospecific opiate receptor, which acts independently of muscarinic receptor antagonism.

Animals↗