PubMed Health⌕ Search

Biomedical subjects

N Mason

Publications and source records attributed to N Mason.

31 records · Page 2Linked to original sources
PubMed1990

Ancrod improves survival in murine systemic lupus erythematosus.

The effect of ancrod, a defibrinating agent, on murine lupus glomerulonephritis in the male BXSB mouse was studied to determine the relationship between macrophage procoagulant activity (PCA), fibrin deposition and glomerulonephritis. Marked renal disease and fibrin deposition were noted by three months of age in control mice, whereas little or no disease was seen in ancrod treated mice until five months of age. Similar high titers of anti-DNA antibodies and renal deposition of IgG were seen in both groups of mice. PCA rose with age in both ancrod treated and untreated mice, although it was significantly higher in control animals than in the ancrod treated group. Furthermore, ancrod therapy resulted in a decrease in plasma PCA inducing activity (PIF) and a decrease in the effectiveness of PIF to induce PCA in peritoneal macrophages in vitro. No mortality was observed in the 20 ancrod treated mice, whereas 10 of 20 control animals died. We conclude that defibrination with ancrod delays the development of renal fibrin deposition and glomerulonephritis and improves survival in BXSB mice. This was associated with a decrease in plasma PCA inducing activity and with an inhibitory effect on PCA induction. These results suggest that PCA contributes to injury in murine lupus glomerulonephritis by promoting fibrin deposition.

Ancrod↗
PubMed1988

Cyclosporin A metabolites suppress T-cell proliferation by concanavalin A and in a mixed lymphocyte reaction.

To ascertain if cyclosporine metabolites (CMs) have immunosuppressive activity, bile, whole blood and urine taken from patients after cholecystectomy and from a liver transplant recipient on cyclosporin A (CsA) were assayed to determine their effect on T-cell proliferation induced by concanavalin A (Con A) and in a two-way mixed-lymphocyte response. Bile and whole blood from the liver transplant patient completely suppressed Con A proliferation and the mixed lymphocyte response (MLR) at dilutions at which normal bile and whole blood have no suppressive activity, but no such activity was noted from the urine. The CMs were separated into six peaks (fractions) by high-pressure liquid chromatography (HPLC). Metabolites were identified by internal standards and HPLC/mass spectrophotometric analysis. Cyclosporine metabolite fractions 2 and 3 from bile and blood had immunosuppressive activity similar to parent CsA whereas fractions 5 and 6 demonstrated less but substantial immunosuppressive activity. Fractions 2, 3 and 5 demonstrated an ability to inhibit two-way MLR similar to parent CsA; the other metabolite fractions were able to inhibit the MLR but to a lesser extent. These results demonstrate that a number of CMs have immunosuppressive effects similar to those of the parent compound, and this may account for the lack of correlation between whole blood CsA levels and immunosuppressive activity.

Chromatography, High Pressure Liquid↗
PubMed1986

In vitro receptor specificity of the 5HT1A selective phenylpiperazine, LY165163.

LY165163, a ligand reported to be selective for the 5HT1A subtype of serotonin receptor, was examined for its ability to interact with 5HT2 receptors in the rat jugular vein and alpha-receptors in the rat aorta. In these smooth muscle preparations, no agonist activity of LY165163 occurred in concentrations up to 10(-5) M. However, LY165163 was an antagonist of serotonin-induced contractions in the jugular vein and of norepinephrine-induced contractions in the rat aorta. The dissociation constant calculated for LY165163 at 5HT2 receptors in the rat jugular vein was 10(-8) M and at alpha-receptors in the rat aorta was 2 X 10(-7) M. Thus, LY165163 is a relatively potent antagonist at vascular 5HT2 sites and possesses appreciable affinity at alpha-receptors. Based on these data, the multiple receptor interactions of LY165163 must be taken into consideration when utilizing this agent as a probe for the 5HT1A subtype of serotonin receptor.

Adrenergic alpha-Antagonists↗
PubMed1986

Effect of nitrendipine, diltiazem, trifluoperazine and pimozide on serotonin2 (5-HT2) receptor activation in the rat uterus and jugular vein.

The present study explored the calcium source used in serotonin (5-HT)-induced contractions mediated by 5-HT2 receptor activation in the rat uterus and jugular vein in vitro. In the rat uterus, the calcium channel antagonists, nitrendipine and diltiazem, and the neuroleptic agents, trifluoperazine (TFP) and pimozide, antagonized potently and noncompetitively 5-HT-induced contractions. These data are compatible with the contention that 5-HT-induced contractions in uterine smooth muscle require extracellular sources of calcium. In contrast, neither diltiazem nor nitrendipine inhibited the contractile response to 5-HT in the rat jugular vein although 5-HT-induced contractions in the jugular vein required the presence of extracellular calcium. This difference in sensitivity to calcium channel antagonists between the uterus and jugular vein was not related to differences in the receptor occupancy-response curves for 5-HT as these were similar in the rat uterus and jugular vein. Furthermore, in the jugular vein, neither diltiazem nor nitrendipine were markedly effective in blocking contractions produced by potassium chloride, an agent that activates voltage-dependent calcium channels, suggesting that this tissue lacks calcium channels susceptible to blockade by conventional calcium channel antagonists. Although responses to 5-HT in the jugular vein were only affected marginally by calcium channel antagonists, TFP and pimozide produced concentration-dependent rightward parallel shifts of 5-HT-induced contractions in the jugular vein. Furthermore, both TFP and pimozide showed high affinity at 5-HT2 binding sites in rat brain cortical membranes and the apparent dissociation constant at 5-HT2 receptors in the jugular vein was 38 and 31 nM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Phase I trial of carboplatin-cyclophosphamide and iproplatin-cyclophosphamide in advanced ovarian cancer: a Southwest Oncology Group study.

The Southwest Oncology Group has carried out a phase I clinical trial of carboplatin plus cyclophosphamide and iproplatin plus cyclophosphamide in 20 patients with stages III and IV ovarian cancer prior to initiating a phase III trial to compare these platinum analog-cyclophosphamide combinations with standard cisplatin-cyclophosphamide therapy. Myelosuppression proved the dose-limiting toxicity of both the carboplatin (300 mg/m2) plus cyclophosphamide (600 mg/m2) and iproplatin (180 mg/m2) plus cyclophosphamide (600 mg/m2) regimens. Evaluating up to six courses of therapy (repeated at 4-week intervals), the median nadir WBC and platelet counts associated with carboplatin-cyclophosphamide therapy were 1800 (range, 900-4000) and 69 000 per microliter, respectively, and those associated with iproplatin-cyclophosphamide therapy were 1400 (1100-1600) and 140 000 per microliter, respectively. Although the starting doses of carboplatin and iproplatin required a median decrease of 25%, the median doses of each administered through six courses of therapy were 300 and 180 mg/m2, respectively. Neither nephrotoxicity nor neuropathy were experienced by the patients, but mild to moderate nausea and vomiting occurred in more than 75% of those treated with either drug combination. Alopecia of mild to severe degree was observed in 40% of patients. Although the results of this phase I trial are still preliminary, we can recommend for future phase III trials 300 mg/m2 carboplatin and 180 mg/m2 iproplatin when combined with 600 mg/m2 cyclophosphamide repeated a 4-week intervals for six treatment courses.

Adult↗
PubMed1985

In vitro evaluation of anticancer drugs against ovarian cancer at concentrations achievable by intraperitoneal administration.

High-dose intraperitoneal chemotherapy is a current developmental approach in the treatment of advanced ovarian cancer. Considerable pharmacologic data have been obtained on the intraperitoneal X time product for a number of agents administered by this route. We used the human tumor cloning assay (HTCA) to compare the activities of both standard and experimental agents used for intraperitoneal treatment. In vitro dose-survival curves were constructed for each drug over a two-log range of concentrations using fresh ovarian cancers from more than 50 patients. The mean concentration X time product (CXT) achievable in the intraperitoneal space after high-dose intraperitoneal drug administration was divided by the corresponding ID50 value (concentration of drug in vitro associated with 50% survival of tumor colonies) for each agent to calculate in vivo CXT: in vitro ID50 ratios. Using this approach, the standard agents, melphalan, cisplatin, and 5-FU were predicted to have similar efficacies by intraperitoneal administration, but doxorubicin and mitomycin were significantly inferior. Of the drugs tested, the new agent mitoxantrone was associated with the most favorable CXT to ID50 ratio and is, therefore, predicted to be particularly promising for intraperitoneal administration.

Anthraquinones↗
PubMed1984

5HT2 receptors in the rat portal vein: desensitization following cumulative serotonin addition.

Contractile responses to serotonin were examined in vitro in the longitudinal portal vein to determine whether such responses were mediated by the interaction of serotonin with 5HT1 receptors (those that preferentially bind [3H]serotonin) or 5HT2 receptors (those that preferentially bind [3H]spiperone). Using eight serotonin receptor antagonists (spiperone, metergoline, LY53857, ketanserin, trazodone, benzoctamine, 1-(1-naphthyl)piperazine, and 1-meta-methoxyphenylpiperazine), we found a significant correlation between the affinity for serotonin receptors in the rat portal vein and the ability to bind to 5HT2, but not 5HT1 receptors in rat frontal cortical membranes. Thus, the receptors mediating vascular contraction to serotonin in the rat portal vein were similar to those receptors defined in other vascular beds from the rat (aorta, jugular vein,and caudal artery). Furthermore, contraction resulting from the cumulative addition of serotonin in the rat portal vein was associated with desensitization (higher ED50 value) relative to contractions produced by the non-cumulative addition of serotonin. Affinities of serotonin receptor antagonists were also lower when determined by antagonism of cumulative serotonin concentration-response curves compared to affinities obtained by antagonism of non-cumulative concentration-response curves. Thus, 5HT2 receptor affinities of antagonists in the rat portal vein are best determined by the shift of non-cumulative responses to serotonin.

Animals↗
PubMed1980

Antitumour activity and plasma kinetics of bleomycin by continuous and intermittent administration.

We have studied the cytotoxicity of bleomycin (4--10 u/kg/day for 6 days) given by continuous i.p. infusion (using an osmotic minipump) compared to daily i.p. bolus administration, against P388 leukaemic spleen colony-forming-units(LCFU-S). Continuous i.p. bleomycin at 8 u/kg/day caused a 0.5 log greater reduction of LCFU-S than did an identical dose given by intermittent bolus administration. The infusion minipump provided constant bleomycin plasma levels of 0.62 +/- 0.03 mu/ml and a total plasma AUC (area under the plasma decay curve) of 89.0 mu.h/ml for 6 days at 8 u/kg/day. Intermittent bolus bleomycin at 8 u.kg/day had a terminal-phase plasma t1/2 of 15 min and a total 6-day plasma AUC of 90.8mu.h/ml. These pharmacokinetic data validate the osmotic minipump as a constant drug-delivery system, and suggest that the two administration schedules resulted in equal total bleomycin dosages. Although high peak bleomycin plasma levels (i.e. 32 mu/ml) were achieved with the intermittent bolus administration, continuous-infusion bleomycin's greater inhibition of LCFU-S was probably related to the drug's schedule-dependent cell-killing characteristics. The results of this study provide further rationale for the continuing use of infusion bleomycin schedules in cancer patients.

Animals↗
PubMed1980

The transsexual dilemma: being a transsexual.

With few exceptions, a solution to any problem will bring new difficulties. These may or may not be worse than the original problem, and one must decide, not between problem and answer, but between degrees of difficulty. Is the new situation really going to be better than the last? This is undoubtedly the situation with the transsexual. It is undeniable that in the majority of cases the treated transsexual is an infinitely happier person than the one who has not undergone therapy, but as a result of this treatment there arises a host of new difficulties. Using personal experience, it is my intention to illustrate the problems which beset the transsexual before, during and after treatment. It will then be possible to ascertain whether or not, in spite of these difficulties, there is in fact a dilemma. Is there indeed any choice?

Attitude↗
PubMed1976

In vivo and in vitro evaluation of a microencapsulated narcotic antagonist.

Injectable microcapsules containing 75% (w/w) cyclazocine, a narcotic antagonist, were prepared with dl-poly(lactic acid) as the coating material. Capsule fractions falling between 105 and 295 mum released about 90% of their cyclazocine in 8 days of rotating-bottle extraction at 37 degrees in pH 7.4 phosphate buffer. Although larger capsules released the drug somewhat more slowly, all capsules released cyclazocine far more rapidly than an ideal capsule should. This rapid release is attributed to macroscopic defects located in the capsule walls. The ability of the capsules to block the action of morphine in vivo was assessed by injection of a sesame seed oil suspension into Holtzman rats. A hot-plate test procedure was used to evaluate animal behavior. Capsule doses of 100-250 mg/kg to rats caused significant antagonism of morphine's analgesic effect for 14 days after injection. By Day 17, no antagonism occurred, indicating that the capsules completely released the drug in vivo between 14 and 17 days after injection.

Animals↗