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Biomedical subjects

M Slater

Publications and source records attributed to M Slater.

At least 37 records · Page 2Linked to original sources
PubMed1999

Synthesis and biological evaluation of novel 2-deoxy-4-thio-imidazole nucleosides.

A study on the use of 3'-directing groups for the synthesis of imidazole 2'-deoxy-4'-thionucleosides led to varying alpha:beta ratios in the glycosylation reaction. The para-nitrobenzoyl group gave the optimum result in the glycosylation step; therefore, this protected thiosugar 10b was used for the synthesis of a series of novel 2'-deoxy-4'-thio-imidazole nucleosides which have been evaluated for antiviral activity in vitro.

Antiviral Agents↗
PubMed1999

Thrombospondin is sequentially expressed and then de-expressed during early pregnancy in the rat uterus.

The expression of thrombospondin on Day 1, Day 3 and Day 6 of pregnancy has been examined in the rat, using light microscopic immunoperoxidase and electron immunogold techniques. The glycoprotein was expressed in the apical, lateral and basal uterine epithelium on Days 1 and 3 but was then de-expressed at the time of implantation on Day 6. We propose that these data suggest a role for thrombospondin in remodellig the uterine epithelium during the plasma membrane transformation, but that it does not play a part in attachment and implantation.

Animals↗
PubMed1999

Detection of apoptotic DNA damage in prostate hyperplasia using tyramide-amplified avidin-HRP.

Avidin binds to damaged DNA with high specificity. Avidin conjugated to horseradish peroxidase may therefore be used to label apoptotic DNA damage, using standard immunohistochemical protocols. However, the resulting label may be too weak to visualise. We used tyramide signal amplification to enhance the avidin-peroxidase signal in a rat model of apoptotic damage in hyperplasic prostate tissue. After amplification, the difference between normal levels of apoptosis in the young rat prostate and the greatly reduced levels evident in aged rats was readily appreciated. The label was specific and the non-specific background was minimal. This method is particularly useful for the detection of weak apoptotic signals in tissue sections.

Aging↗
PubMed1998

Chronic Trypanosoma cruzi infection in dogs: 11 cases (1987-1996).

OBJECTIVE: To determine whether prevalence of naturally developing chronic infection with Trypanosoma cruzi in dogs in Texas changed between 1987 and 1996 and to characterize clinical aspects of the disease. DESIGN: Retrospective study. ANIMALS: 11 dogs with chronic infection with T cruzi. PROCEDURE: Number of positive serologic test results for T cruzi obtained between 1987 and 1996 were compared with the number of tests for T cruzi performed during the same period. Survival time, signalment, and clinical signs of dogs and results of thoracic radiography, electrocardiography, and echocardiography were evaluated. The Mann-Whitney test was used to assess the association between age at time of initial examination and survival time. RESULTS: The proportion of positive test results increased, compared with the number of tests submitted, during the 9-year period. Clinical signs in affected dogs were consistent with right-sided cardiac disease. Results of thoracic radiography were nonspecific. Conduction disturbances and supraventricular and ventricular arrhythmias were evident. Echocardiographic abnormalities, including chamber enlargement and functional impairment, were detected. Dogs were characterized on the basis of survival time; group-1 dogs (n = 6) survived 0 to 5 months, and group-2 dogs (5) survived 31 to 60 months. Age at time of initial examination was associated with survival time. CLINICAL IMPLICATIONS: Clinical course of disease varied. Electrocardiographic and echocardiographic changes may be detected. Clinicians should be aware of the potential for T cruzi infection in dogs with clinical signs of right-sided cardiac dysfunction and unexplained conduction disturbances and arrhythmias. Prevalence of this disease may be increasing in some regions of Texas.

Animals↗
PubMed1998

Oxidative damage to nucleic acids in motor neurons containing mercury.

Heavy metals have been implicated in the pathogenesis of sporadic motor neuron disease (MND). We were interested to see if inorganic mercury leads to oxidative damage in motor neurons since free radicals have been suspected to be involved in MND, so a method to examine oxidatively-damaged DNA in situ was used to examine individual motor neurons. Mice were exposed to 500 microg/m3 of mercury vapour for 2 h. Two, five, or ten days later sections from formalin-fixed, paraffin-embedded blocks of cervical spinal cord were incubated in avidin-FITC. Sections were examined under a fluorescence microscope and photographs of pairs of mercury-exposed and control spinal motor neurons were analysed semi-quantitatively for the amount of fluorescence using an image analysis program. Avidin fluorescence was seen in the perikaryon of both control and mercury-exposed motor neurons. In each control-mercury pair (four pairs per group) significantly more perikaryal fluorescence was seen in mercury-containing than in control motor neurons (Mann-Whitney testing). Mercury within the motor neuron perikaryon therefore leads to increased avidin binding, an indicator of oxidative damage to DNA. The findings support the hypothesis that an environmental toxin such as mercury can enter and damage motor neurons.

Animals↗
PubMed1998

Indolocarbazoles: potent and selective inhibitors of platelet-derived growth factor receptor autophosphorylation.

A quantitative assay for measuring the autophosphorylation of platelet-derived growth factor (PDGF) receptors in intact vascular smooth muscle cells has been developed and used to screen for novel tyrosine kinase (TK) inhibitors. Several novel inhibitors of PDGF receptor autophosphorylation have been identified from the indolocarbazole series, including the 3,9 dimethoxy derivative, 3744W (IC50 = 14.5+/-2 nM). Tested against a panel of tyrosine and serine/threonine kinases, 3744W is at least 1,000 fold selective for the PDGF receptor tyrosine kinase and was found to inhibit autophosphorylation of both the alpha and beta isoforms of the PDGF receptor in human smooth muscle cells. PDGF-BB-stimulated DNA synthesis in quiescent cultures of human smooth muscle cells was blocked in a concentration-dependent manner by 3744W, IC50 = 10 nM. Binding studies showed that 3744W did not block the binding of PDGF-BB to cell surface receptors on human airway smooth muscle cells. Furthermore, inhibition of bone marrow stem cell proliferation by 3744W was only observed at concentrations 100-1,000 times greater than those needed to block PDGF-driven DNA synthesis in human smooth muscle cells. 3744W represents a novel, potent and selective inhibitor of PDGF receptor autophosphorylation and a powerful biochemical probe for investigating PDGF-dependent responses in vitro.

Animals↗
PubMed1998

The Gateway program: ten-year lessons about outcomes and admission measures.

The Gateway to Higher Education is a comprehensive program that provides selected minority students from five New York public high schools with rigorous high school preparation for college and professional careers in medicine, science, engineering, and technology. In existence for over ten years, the program has begun to accumulate solid outcomes data. The authors briefly describe the Gateway program and discuss students' graduation rates, career plans, and other outcomes. They then describe the correlation they have established between students' scores on the Stanford mathematics test (a standardized test administered to all Gateway ninth-grade students) and their subsequent SAT scores. Given the correlation recently established by the Association of American Medical Colleges between SAT scores and MCAT scores, this information provides another useful--and early--predictor of the future success in medical school of underrepresented minority students.

Adolescent↗
PubMed1998

The influence of body movement on subjective presence in virtual environments.

We describe an experiment to assess the influence of body movements on presence in a virtual environment. In the experiment 20 participants were to walk through a virtual field of trees and count the trees with diseased leaves. A 2 x 2 between subjects design was used to assess the influence of two factors on presence: tree height variation and task complexity. The field with greater variation in tree height required participants to bend down and look up more than in the lower variation tree height field. In the higher complexity task participants were told to remember the distribution of diseased trees in the field as well as to count them. The results showed a significant positive association between reported presence and the amount of body movement in particular, head yaw--and the extent to which participants bent down and stood up. There was also a strong interaction effect between task complexity and gender: Women in the more-complex task reported a much lower sense of presence than in the simpler task. For applications in which presence is an important requirement, the research in this paper suggests that presence will be increased when interaction techniques are employed that permit the user to engage in whole-body movement.

Female↗
PubMed1997

Mutations at codon 184 in simian immunodeficiency virus reverse transcriptase confer resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine.

Variants of simian immunodeficiency virus (SIV) that display greater than 2,000-fold resistance to the (-) enantiomer of 2',3'-dideoxy-3'-thiacytidine (3TC) were generated through in vitro passage and drug selection. The polymerase regions of several of these resistant viruses were sequenced and were found to share either of two codon alterations at site 184 in reverse transcriptase (ATG to ATA [methionine to isoleucine] and ATG to GTA [methionine to valine]). The biological relevance of these substitutions for 3TC was confirmed by site-directed mutagenesis with the SIVmac239 infectious recombinant clone of SIV.

Anti-HIV Agents↗
PubMed1997

Saving for retirement.

In September, New Zealanders will take part in a referendum on a new, compulsory retirement savings scheme. This looks to be far less equitable than the present universal superannuation scheme.

Humans↗
PubMed1996

Dynamic interactions of the extracellular matrix.

The extracellular matrix (ECM) is a dynamic assemblage of interacting molecules that reorganise and regulate cell functions in response to endogenous and exogenous stimulii. Matrix components may affect cell behaviour directly or indirectly through growth factor sequestration and transmembrane signalling, by controlling the speed of various molecules through the ECM, and the access of growth factors, hormones and neurotransmitters to the cell surface.

Animals↗
PubMed1995

Thrombospondin co-localises with TGF beta and IGF-I in the extracellular matrix of human osteoblast-like cells and is modulated by 17 beta estradiol.

Thrombospondin (TSP) is a multifunctional glycoprotein which is synthesised by several cell types including osteoblasts, and incorporated into the extracellular matrix (ECM) of these cells. The function and regulation of TSP in bone is not clear. In this study, using a long term culture model of human osteoblast-like cells, we examined the distribution of TSP in the ECM and its modulation by added estradiol. In this model the osteoblast-like cells form a regular multilayer which continues to increase in depth up to 50 days post confluence. In the ECM of these cultures and in 19-week fetal bone, the bone markers osteocalcin and alkaline phosphatase were diffusely distributed in the matrix. In contrast, labelling for TSP was concentrated, confined to the banded collagen and its immediately adjacent ECM. This pattern of labelling resembled that of the growth factors transforming growth factor beta-I (TGF beta), and insulin-like growth factor-I (IGF-I), with which TSP label co-localised. Labelling intensities were comparable between fetal bone and the in vitro material for TSP, TGF beta and IGF-I. TSP label was present by 10 days post confluence, reached a maximum by 20 days, and declined slowly thereafter, a time course which was similar to that of IGF-I. Incubation of osteoblast-like cell cultures with 17 beta estradiol resulted in an increase in multilayer depth and a maximal 3-fold increase in TSP labeling at 30 days as well as approximately 2-fold increases for TGF beta and IGF-I. The dose-response relationship for these responses to estradiol treatment was biphasic with maximal increases at 10(-10) M-10(-11) M of added estradiol. Treatment with 17 alpha estradiol produced labelling intensities that were not significantly different from controls. Studies with other cell types have suggested that TSP may be involved in modulation of growth factor activity. The similarities between TSP, TGF beta and IGF-I, in terms of their distribution and regulation by 17 beta estradiol treatment, may indicate a role for TSP in modulating bone cell proliferation and function through interaction with local growth factors.

Alkaline Phosphatase↗
PubMed1995

Involvement of platelets in stimulating osteogenic activity.

Osteoblast-like cells have been shown to be sensitive to the proliferative action of a wide variety of growth factors. Many of these growth factors have been isolated from platelets and are thought to be released at local sites in response to injury. In this study, we tested whether human platelet concentrate, as a supplement to basic medium, would support the proliferative and functional activity of human fetal osteoblast-like cells in both short-term and long-term culture. In short-term studies, uptake of [3H]thymidine was increased in platelet-treated cultures by more than 4-fold compared with 10% serum-supplemented controls. When cultured for prolonged periods on coverslips, the cells formed multilayers, with a collagen-based matrix separating the layers. Long-term cultures that were treated with 1.5% (vol/vol) platelets in serum-supplemented medium showed increases in the depth of the multilayers of as much as 36-fold at 30 days after confluence, compared with the 10% serum-supplemented controls; this difference persisted until day 50. Incorporation of growth factor in the matrix was examined with the use of colloidal gold immunoelectron microscopy. Immunogold labeling intensities for transforming growth factor-beta 1 were significantly lower in the platelet-treated cultures at 20 days and then increased to a maximum level of 2.1-fold more than in the controls at 40 days. Labeling intensities for insulin-like growth factor-I and basic fibroblast growth factor were significantly lower in the platelet-treated cultures than in the controls at all stages of culture.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗