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Biomedical subjects

L Wilson

Publications and source records attributed to L Wilson.

At least 361 records · Page 20Linked to original sources
PubMed1983

Effects of estradiol and progesterone on uterine prostaglandin levels in the pregnant rat.

The purpose of this study was to delineate the effects of estradiol and progesterone treatment on uterine prostaglandin F (PGF), PGE, Thromboxane B2 (TxB2) and 6-Keto-PGF1 alpha (6KF) levels in the pregnant rat. Rats were ovariectomized on day 19 of pregnancy (sperm in vagina = day 0) and received the following treatments via silastic inserts placed s.c.: controls; estradiol (E); progesterone (P); estradiol + progesterone (EP). Twenty-four hours later (day 20 of pregnancy) uterine venous blood and uterine tissue were obtained and assayed for PGE, PGF, TxB2 and 6KF by radioimmunoassay. E treatment significantly enhanced (p less than .05) uterine PGF, TxB2 and PGE (4.5, 2.8 and 1.8 fold increase, respectively) but did not alter 6KF levels when compared to C. Concomitant administration of P with E (EP) blocked the stimulatory effects of estradiol. P treatment by itself was ineffective. Steroid treatment induced no significant alterations (p greater than .05) in uterine venous plasma PG levels. These results suggest that estradiol can provoke a dramatic increase in uterine PGF, TxB2 and PGE levels in the pregnant rat but has no effect on net production of 6KF. These data are compatible with the hypothesis that an increase in the ratio of E/P at the end of pregnancy in the rat contributes to enhanced uterine concentrations of PGF, TxB2 and PGE at term, but they do not explain the augmented 6KF concentrations reported at parturition.

Animals↗
PubMed1983

Effects of the fetal-placental unit on uterine prostaglandin levels at term in the pregnant rat.

Uterine prostaglandins (PGs) increase markedly at term in the pregnant rat. To assess the contribution of the fetal-placental unit (FPU) on uterine tissue and uterine venous blood PG concentrations, each uterine horn of 14 unilaterally pregnant rats at day 21 of pregnancy were compared. In addition, 7 bilaterally pregnant rats were studied. Uterine tissue and uterine venous plasma PGF, PGE, 6-Keto-PGF1 (6KF) and thromboxane B2 (TxB2) and systemic plasma progesterone, estradiol and estrone were determined by radioimmunoassay. Uterine concentrations of PGs (ng/mg DNA) were always greater on the pregnant side of unilaterally pregnant rats (p less than .05) although the PGF levels were elevated to a lesser extent than were PGE, TxB2 or 6KF. However, no differences were detected between uterine tissue from the pregnant side of unilaterally pregnant compared to bilaterally pregnant rats. In addition, no differences were found in uterine venous plasma PGs adjacent or opposite the pregnant uterine horn and in systemic plasma progesterone, estradiol and estrone levels in unilaterally vs bilaterally pregnant rats. These data suggest that the presence of the FPU is associated with an increased capacity of uterine tissue to produce PGE, TxB2 and 6KF, and to a lesser degree PGF, and thus may contribute to the increase in uterine PGs periparturition.

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Paradoxical response of malignant melanoma to methotrexate in vivo and in vitro.

Methotrexate (MTX) shows consistent cytotoxicity for melanoma cells in vitro but it is ineffective in clinical use at equivalent concentrations in vivo. This apparent paradox has been investigated by cell culture techniques and results quantified by cell number. In an in vitro model of high dose MTX therapy followed by leucovorin rescue (HD-MTX-LCR) there was survival of both melanoma and choriocarcinoma cell lines but not of an acute lymphocytic leukaemia cell line. The 70H metabolite of MTX was identified by HPLC in plasma samples of melanoma patients treated by HD-MTX-LCR, in which MTX concentrations approximately 10(-5) M were maintained for 24 h. However, metabolism per se is unlikely to account for the lack of response to MTX clinically. In vitro 70H MTX (10(-7) - 10(-6) M) was two orders of magnitude less cytotoxic for melanoma than MTX (10(-9) - 10(-8) M). The cellular accumulation of [3H]-MTX, using a rapid gradient centrifuge technique for separation of melanoma cells from medium, was reduced in the presence of 70H-MTX. The results suggest that reduced cellular uptake of MTX combined with biochemical rescue of tumour cells may partially explain the paradoxical lack of clinical response of melanoma to the drug.

Animals↗
PubMed1983

Alterations in plasma and tissue prostaglandin levels in rabbits during luteal regression.

To determine if ovarian as well as uterine prostaglandin production was associated with luteal regression, tissue and plasma concentrations of prostaglandin F (PGF), prostaglandin E (PGE), 6-keto-PGF1 alpha (6-keto-PGF), and thromboxane B2 (TxB) were measured by radioimmunoassay in uterus, corpora lutea, nonluteal tissue, uterine venous plasma and ovarian venous plasma on Days 8, 12 and 15 of pseudopregnancy in the rabbit. Total prostaglandin levels (PGF + PGE + 6-keto-PGF + TxB) were 4-fold greater in the uterus compared to nonluteal tissue and 8-fold greater than in corpora lutea. Both PGF and PGE levels were increased in uterine tissue on Day 15 compared to Days 8 or 12 (P less than 0.01). The ratio of PGF:PGE was also elevated on Day 15 compared to Days 8 or 12 (P less than 0.05) which suggests that the luteolytic effect of PGF predominates over the possible luteotropic effect of PGE. There were no significant changes in the concentration of TxB or 6-keto-PGF or the ratio of TxB:6-keto-PGF in uterine tissue on any day studied. In nonluteal tissue, PGE was the only PG to vary significantly; PGE levels were elevated (P less than 0.05) on Day 8 of pseudopregnancy compared to Days 12 or 15. Although corpora lutea contain significant quantities of PGF, PGE, TxB and 6-keto-PGF, no alterations in the levels of any of these substances were observed between Days 8, 12 or 15 of pseudopregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1983

Inhibition of bovine brain microtubule assembly in vitro by stypoldione.

Stypolidione, an orthoquinone derived from the brown seaweed Stypopodium zonale, inhibited the polymerization of three-cycle-purified bovine brain microtubule protein in vitro in a concentration-dependent manner. Fifty per cent inhibition of the extent of polymerization beginning under initiating conditions occurred at a stypoldione concentration of approximately 25 microM, and 50% inhibition of tubulin addition to the assembly ends of microtubules at steady state occurred at a concentration of approximately 8 microM. Only slight structural abnormalities could be detected by negative stain electron microscopy in some of the microtubules that did assemble in the presence of the drug, and no aberrant structural forms of microtubule protein were detected. Stypoldione inhibited the binding of [3H]colchicine to tubulin, with 50% inhibition of colchicine binding activity occurring at a stypoldione concentration of 12-15 microM. Inhibition of colchicine binding activity appeared noncompetitive and was at least partially reversible, suggesting that stypoldione and colchicine bind at separate sites. By assuming that the inhibition constant for the ability of stypoldione to prevent the binding of colchicine to tubulin was equivalent to the dissociation constant for the binding of stypoldione to tubulin, we calculated that approximately 62% of the tubulin present free in solution under initiating conditions and 35-37% of the soluble tubulin under steady-state conditions was complexed with stypoldione when polymerization was inhibited by 50%. These data are consistent with a mechanism in which stypoldione interacts with soluble tubulin and inactivates the tubulin so that it is unable to add to microtubule ends, although a colchicine-like mechanism involving an action of stypoldione at microtubule ends has not been eliminated.

Animals↗
PubMed1983

Evaluation of problems and needs of veteran lower-limb amputees in the San Francisco Bay Area during the period 1977-1980.

From 1977 through 1980, 251 veterans from the San Francisco Bay Area received permanent lower-extremity prostheses at the two local Veterans Administration hospitals. For a survey, 213 of the 251 were contacted and 179 of them (84%) responded to written or telephone questionnaires concerning their prosthetic problems and complaints and their recommendations regarding prosthetic care. Seventy-four percent of the patients were traumatic amputees and 23 percent were dysvascular amputees. Eighty-six percent of the traumatic amputees said they wore their limbs all day, compared with only 51 percent of the dysvascular group. Seventy-one percent of traumatic and 43 percent of dysvascular amputees engaged in some form of recreational activity. There was a high incidence of complaints of pain in the residual limb: 55 percent among the dysvascular group and 44 percent among the traumatic group. Half of the patients had socket problems. Fifty-four of the 178 patients received a physical examination, a prosthetic evaluation, and a gait analysis. Among this group, 59 percent of the below-knee prostheses and 78 percent of the above-knee prostheses had inadequate socket fitting. Improper shaping of socket margins was the most frequently observed deficiency. Moreover, 41 percent of below-knee and 22 percent of above-knee amputees had mechanical skin irritation or skin breakdown in the examined residual limbs. Faulty suspension and alignment in addition to improper socket fit and construction contributed to this problem. Excessive stiffness of SACH foot heel cushions was the most common prosthetic foot problem and contributed to gait abnormalities.

Activities of Daily Living↗
PubMed1982

Effect of colchicine binding on the reversible dissociation of the tubulin dimer.

The reversible subunit-dissociation equilibria of the tubulin alpha beta dimer and of the colchicine-tubulin dimer complex have been examined by equilibrium ultracentrifugation at 4.6 degrees C. The dissociation constants (KD) of tubulin from bovine brain and from flagellar outer-doublet microtubules of the sea urchin Strongylocentrotus purpuratus were 7.4 x 10(-7) M and 15.2 x 10(-7) M, respectively. In contrast, both brain and outer-doublet colchicine-tubulin complexes dissociated less readily into their alpha- and beta-tubulin monomers; KD = 2.7 x 10(-7) M for the brain complex and KD = 5.0 x 10(-7) M for the outer-doublet colchicine-tubulin species. Podophyllotoxin (2 x 10(-4) M), tropolone (10(-4) M), or both podophyllotoxin and tropolone (2 x 10(-4) and 5 x 10(-4) M, respectively) had no effect on the dissociation constant of brain tubulin. Under these experimental conditions, the initial colchicine-binding capacities of brain and flagellar tubulins were 0.87 +/- 0.05 and 0.70 +/- 0.07 mol/mol, respectively. The colchicine-binding activities of free tubulins decayed at 4 degrees C according to first-order kinetics with half-times of 37 h for brain tubulin and 26 h for flagellar tubulin. However, colchicine-tubulin complexes (brain or flagellar) showed no decay of binding activity when stored at 4 degrees C for periods up to 4 days. These results strongly support the following conclusions: (1) colchicine binding induces or stabilizes a conformational isomer of tubulin that dissociates into its alpha and beta monomers less readily than free tubulin; (2) the conformational change in tubulin is specific for binding of the intact colchicine molecule and does not occur when ligands specific for the trimethoxyphenyl subdomain (i.e., podophyllotoxin) or tropolone subdomain of the colchicine-binding site bind singly or simultaneously to tubulin; and (3) bound colchicine stabilizes tubulin against loss of colchicine-binding activity at 4 degrees C. This altered conformation of tubulin may be involved in the substoichiometric poisoning of microtubule assembly produced by the addition of colchicine-tubulin complexes to the ends of microtubules.

Animals↗
PubMed1982

Two different monoclonal antibodies to alpha-tubulin inhibit the bending of reactivated sea urchin spermatozoa.

Two monoclonal antibodies reactive for alpha-tubulin but not for beta-tubulin have been prepared, characterized in terms of their relative binding to tubulins from different sources by a solid-phase binding assay, immunoautoradiography, and indirect immunofluorescence, and utilized to study flagellar motility. Our results demonstrate that alpha-tubulins from different species, and even from different tissues of the same species, are nonidentical. Especially interesting was the observation that one of the antibodies, Ab2, immunofluorescently stained microtubules of chick embryo fibroblast cells, but was completely unreactive for microtubules of rat kangaroo (PtK2) fibroblasts; a different antibody, Ab1, stained both cell types. Results of these and additional experiments clearly show that Ab1 and Ab2 recognize discrete and different epitopes on alpha-tubulin. Monoclonal antitubulins Ab1 and Ab2 each inhibited the bend amplitude of reactivated sea urchin spermatozoa without affecting beat frequencies or the ability of the outer doublet microtubules to slide past each other in elastase-digested models. These results, together with those obtained previously using rabbit polyclonal antitubulin antibodies [Asai and Brokaw, 1980], demonstrate that inhibition of bend amplitude is a common property of antitubulin antibodies and is not due to the binding of antibodies to one specific site on the axoneme. Our results suggest that tubulin subunit conformational changes may occur on the outer doublet lattice and may be integrally involved in the mechanism and control of flagellar bending.

Animals↗
PubMed1982

Alterations in uterine and placental prostaglandin F and E with gestational age in the rat.

Experiments were designed to determine the chronological alterations in placental and uterine prostaglandin F and E (PGF and PGE) during pregnancy in the rat. Pregnant rats (sperm in the vagina = day 0) were sacrificed at days 15, 18, 19, 20, 21 and delivery (day 21 1/2) and placental and uterine tissues assayed (RIA) for PGF and PGE immediately ("in vivo") or after 1 hour incubation ("in vitro"). Uterine content of PGF and PGE in vivo (ng Pg/mg DNA) was increased significantly by day 19 and further increases were seen through delivery. Incubation of uterine tissue resulted in enhanced net production of PGF and PGE (p less than .05) per mg DNA (as judged by tissue content and release into the incubation medium) by day 18 of pregnancy vs. day 15. Net production in vitro peaked around the time of delivery thus paralleling the alterations in tissue content in vivo. By contrast, no differences with gestational age were found in placental content of PGF and PGE in vivo, the concentrations throughout late gestation remaining in the range of uterine PGs at day 15. However, production of PGs per mg placental DNA increased markedly during incubation in vitro with significant enhancement detected by day 19 vs. 15, achieving levels even greater than the uterus in vitro. The in vivo and in vitro findings for the uterus are consistent with the hypothesis that increases in uterine PGs levels at the end of pregnancy may play an important role in parturition. The in vitro experiences with placental tissue suggest that the potential for PG production per placental cell may also increase in late gestation and thereby contribute to the augmented intrauterine availability of PGs at that time.

Animals↗
PubMed1982

Neurotensin inhibition of gastric exocrine secretions in the cat.

The gastric exocrine inhibitory activities of neurotensin were characterized in conscious cats prepared with gastric fistulae. Neurotensin was a potent inhibitor of pentagastrin-stimulated pepsin secretion (ID50, approx. 0.3 mumol . kg-1 . h-1) but was approximately 60 times less potent against acid secretion. Neurotensin did not significantly reduce submaximal histamine-stimulated acid or pepsin secretions. the total 2 h acid and pepsin outputs in response to insulin-hypoglycaemia were not reduced by neurotensin, although the peak 15-min outputs were reduced. The reduction in peak secretion was possibly related to neurotensin antagonism of the ability of insulin to lower blood glucose concentrations. Neurotensin alone was not hyperglycaemic when given as an intravenous infusion. Two C-terminal fragments of neurotensin, the dodecapeptide and nonapeptide, inhibited pentagastrin-stimulated pepsin secretion, but were less potent than neurotensin. The observations with the C-terminal fragments indicate that the major determinants of gastric exocrine inhibitory activity of neurotensin reside in its C-terminal; this agrees with observations on other biological activities of neurotensin. The reduced potency of the dodecapeptide indicates the importance of the N-terminal pyroglutamyl residue for full gastric exocrine inhibitory activity.

Animals↗