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Biomedical subjects

M Ward

Publications and source records attributed to M Ward.

At least 163 records · Page 9Linked to original sources

Bond strength of resin composite to air-abraded enamel.

Tensile bond strengths of a resin composite-dentinal bonding system to air-abraded enamel were determined. Several cutting variables available on an air-abrasion cavity preparation system were investigated. Two tip diameters, two abrasive powder flow rates, and two air pressures were selected, producing cutting actions that ranged from the most to the least aggressive of the air abrasion system. After enamel surfaces were air abraded, they were etched for 30 seconds with 37% phosphoric acid or not etched. Tensile bond strengths of resin composite to air-abraded, acid etched enamel were significantly greater than were those to air-abraded, unetched enamel. There was no statistically significant difference between any combination of tip diameter, powder flow rate, or air pressure.

Acid Etching, Dental↗

Suppression of two cloned smooth muscle-derived delayed rectifier potassium channels by cholinergic agonists and phorbol esters.

Functional coupling between muscarinic (m3) receptors and two voltage-gated K+ (Kv) channels (Kv1.2 and Kv1.5) cloned originally from canine colonic smooth muscle was studied using the Xenopus oocytes expression system and a mammalian cell line (COS cells). Oocytes were coinjected with cRNAs encoding the human m3 receptor and the Kv channel clones. COS cells were stably transfected with the hm3 cDNA and the cDNA encoding Kv1.5 channels. In oocytes coexpressing hm3 receptors and Kv channels, acetylcholine (ACh, 100 microM) decreased the whole-oocyte Kv channel current (IKv) by 72% over 20 min. ACh was equally effective at suppressing IKv1.2 as IKv1.5. In oocytes expressing only Kv channels phorbol esters (phorboldibutyrate) and phorbol dideconoate (10-30 nM) mimicked the action of ACh on IKv in oocytes coexpressing hm3 receptors. At the single-channel level, both ACh and phorbol dibutyrate applied to the extra-patch membrane reduced the open probability of Kv channels in the cell-attached patches without affecting single-channel conductance. In cotransfected COS cells, over a similar time course as in oocytes ACh suppressed whole-cell IKv1.5, but only by 30% and the effect was not reversible. These data indicate that stimulation of m3 receptors in cells that express Kv1.2 and Kv1.5 channels causes a poorly reversible decrease in the open probability of these channels.

Acetylcholine↗

Transfer and expression of the human multiple drug resistance gene in human CD34+ cells.

The human multiple-drug resistance (MDR1) gene has been transferred into human hematopoietic progenitors using retroviral gene transfer. Human bone marrow cells and isolated CD34+ cells isolated from marrow were exposed to growth factors interleukin-3 (IL-3), IL-6, and stem cell factor for 48 hours and then to two changes of MDR retroviral supernatants over the next 24 hours. Progenitor assays in methylcellulose at this time showed that 18% to 70% of BFU-E and 30% to 60% of CFU-GM contain the transferred MDR gene by polymerase chain reaction analysis. Up to 11.2% of the progeny of these cells express increased amounts of MDR glycoprotein on their surface by fluorescence-activated cell sorter (FACS) analysis. In addition, transduced cells are enriched in high MDR-expressing cells after exposure to taxol as assessed by FACS analysis, and by resistance of BFU-E to taxol (Bristol-Myers Squibb, Princeton, NJ). These studies indicate the feasibility of using MDR gene transfer as a means of enriching marrow for MDR-transduced cells. They also provide the basis of a phase 1 clinical protocol in patients with advanced cancers not involving the bone marrow for the use of MDR gene transfer as a means of protecting marrow cells, which normally express low levels of MDR, from the myelosuppressive effects of drugs like taxol.

Antigens, CD↗

Mouse fetal liver cells lack functional amphotropic retroviral receptors.

We have been transducing mouse hematopoietic cells with the human MDR1 (MDR) gene in retroviral vectors to determine the optimal conditions for retroviral gene transfer as a model system for potential human gene therapy. In these studies, we have demonstrated transduction and expression of the human MDR gene using ecotropic and amphotropic MDR-retroviral producer lines. To obtain more mouse hematopoietic cells for detailed study, mouse fetal liver cells (FLC) have been used for MDR transduction and expression, and to reconstitute the ablated marrows of live adult mice. FLC contain hematopoietic cells that have a reconstituting capacity comparable to that of adult mouse bone marrow cells. However, to our surprise, FLC can only be transduced with ecotropic retrovirus and not with amphotropic virus. This restriction of transduction of FLC cannot be overcome by higher titer virus. The resistance to amphotropic transduction by FLC may be part of a changing developmental program that results in a different antigen repertoire on FLC as compared with adult bone marrow cells.

Animals↗

Subdural grid recordings of distributed neocortical networks involved with somatosensory discrimination.

Previous studies suggest that evidence for the sub-second activation of distributed neural networks can be obtained by computing the covariance between segments of the scalp-recorded evoked potential. However, the cortical representation of such potentials is not known. Here we report a case study where the evoked potential covariance (EPC) measure was applied to data recorded from a 58-channel subdural grid implanted in an epilepsy patient. Recordings were made while the patient performed a task that required judging the somatosensory intensities of electrical stimuli and executing precise finger flexion responses in response to a subset of those stimuli. Post-stimulus EPC patterns involved covariances between somatosensory, motor, and temporal regions. Pre-stimulus EPC patterns involved these same regions, but only when it could be anticipated that the upcoming stimulus would likely require a response. The majority of the observed EPCs occurred with non-zero time-lags, and these EPCs often involved non-adjacent electrode pairs. Thus, the observed EPCs were unlikely to arise solely from volume conduction. Rather, they appeared to reflect the transient integration of activity across distinct cortical processing nodes.

Adult↗

The effect of a single oral dose of azithromycin on chlamydial infertility and oviduct ultrastructure in mice.

Azithromycin has been recommended for the treatment of human chlamydial genital tract infections because of the sustained, chlamydicidal levels of the antibiotic which can be achieved after a single dose. The effect of single dose azithromycin on the prevention or reversal of chlamydial-induced damage to the oviduct or to fertility was assessed in a mouse model of chlamydial salpingitis which closely mimics the human disease. C3H mice were treated with progesterone and then inoculated under the ovarian bursa with a human genital tract isolate of Chlamydia trachomatis, serovar F. Azithromycin at doses from 135-250 mg/kg was administered by oral intubation. Morphological damage to the oviduct lumen was assessed by scanning electron microscopy, while fertility was assessed by breeding experiments. Treatment of mice two or seven days after infection with 135 mg/kg azithromycin completely reversed chlamydial-induced ultrastructural changes and infertility. Treatment 12 or more days after infection, at doses as high as 250 mg/kg, failed to prevent infertility. The onset of fertility correlated with the loss of ciliated epithelia from the oviduct. However, the regeneration of ciliated epithelia following azithromycin treatment did not necessarily restore tubal patency. These results, if true for women also, indicate the need for rapid, effective antibiotic therapy for chlamydial salpingitis to prevent infertility and other sequelae of tubal damage.

Administration, Oral↗

Retrovirus-mediated transfer of the multidrug resistance gene into human haemopoietic progenitor cells.

We report the utilization of cord blood (CB) or bone marrow (BM) derived low density or purified CD34+ cells as a target for human multidrug resistance (MDR1) gene transfer. Cells were cocultivated for 48 h with an irradiated MDR1 retroviral producer line. Since some degree of MDR1 gene expression has been reported to occur in haemopoietic progenitor cells and in peripheral blood cells, efficiency of MDR1 gene transfer was assessed by: (1) Drug selection and culture in presence of 50 ng/ml doxorubicin, 10 ng/ml colchicine and 0.85 micrograms/ml taxol. In uninfected control, 1-2% of CFU-GM and CFU-GEMM were found to be drug-resistant, while 14-31% of original clonogenic activity was found after 2 weeks of culture of transduced cells. Efficiency of MDR1 transfer was significantly enhanced by prestimulation with cytokines, and found to be significantly superior in CB-derived compared to BM-derived progenitors. (2) Analysis of MDR1 gene expression by evaluating MDR1 mRNA through polymerase chain reaction. MDR1 expression was very low in cultures of uninfected controls, whereas, after drug selection, MDR1 mRNA levels in transduced cells was as high as in the MDR1 retroviral producer line (positive controls). (3) Flow cytometric analysis of the expression of CD34 and P-glycoprotein, the product of the MDR1 gene. After MDR1 transduction and 2 weeks of culture, membrane expression of P-glycoprotein was found on 17-25% of viable CD34+ cells. (4) Cytochemical localization by APAAP staining of P-glycoprotein. No specific localization was found in untransduced controls, whereas transduced and cultured CB-cells expressed P-glycoprotein on plasma and nuclei membrane. In conclusion, MDR1 gene transfer into CB- and BM-derived progenitor cells seems a feasible and attractive approach to generate a drug-resistant haemopoiesis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Anabolic steroids--the drugs that give and take away manhood. A case with an unusual physical sign.

A case is presented in which the abuse of anabolic steroids by a body builder led to an unusual physical sign. The case discusses the effects that anabolic steroid abuse can have upon manhood. The frequency of anabolic steroid misuse is increasing. The implications of this with respect to psychiatric illness and violent crime are discussed. It is well known that the use of anabolic steroids among young men, body builders in particular, is growing apace (Perry and Littlepage, 1992), and they may be aware of the risks of impurity and contamination. There is a wide range of anabolic steroids in use; they are often used in doses of greater than 1 mg/kg per day. As well as single use, the misuser may 'stack' (use more than one at a time) or 'pyramid' (use increasing doses of a given drug) the steroids (Kennedy, 1990). The physical and psychiatric effects of anabolic steroids are well known (Kashkin and Kleber, 1989; Brower, 1992; Pope and Katz, 1988). However, we describe a case with psychiatric symptoms, a violent outburst and a unique (?) physical sign.

Adult↗