Search PubMed⌕ Search

Biomedical subjects

D Lawson

Publications and source records attributed to D Lawson.

At least 91 records · Page 5Linked to original sources
PubMed1991

Fibrin(ogen) degradation product peptide 6A increases femoral artery blood flow in dogs.

To determine the effects of peptide 6A (a fibrinogen-degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50 mumoles) caused a short-lasting dose-dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 mumoles min-1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 +/- 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A-induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6-keto-PGF1 alpha in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A-induced relaxation was abolished by de-endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium-derived relaxing factor. PGI2 release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Valsalva maneuver in obstetrics: the influence of peripheral circulatory changes on function of the pulse oximeter.

Strenuous expulsive efforts involving sequential Valsalva maneuvers may result in maternal hypoxemia during the second stage of labor. Pulse oximetry has been used to assess oxygen saturation in laboring parturients, and this study was undertaken to evaluate the performance of the pulse oximeter (Nellcor) during the Valsalva maneuver. In both pregnant patients and nonpregnant volunteers, there were consistent interruptions in the transmission of oxygen saturation data during the Valsalva maneuver. To determine the physiologic events associated with this monitoring interruption, occlusive venous impedance plethysmographs and pulse volume amplitude recordings were obtained in volunteers performing the Valsalva maneuver. A marked decrease in pulse volume amplitude was noted, which adversely affected the oximeter's ability to distinguish physiologic arterial pulsations from background noise. Each Valsalva maneuver was associated with abrupt and transient changes in peripheral vascular volumes, thus presenting the oximeter with a rapidly changing signal for analysis that violated predetermined software criteria for pulse uniformity and caused an interruption in data transmission. The authors conclude that the Valsalva maneuver interferes with the ability of pulse oximeter technology to provide useful oxygen saturation data.

Adult↗
PubMed1991

Bioactivity of plasma prolactin in ovariectomized, diethylstilbestrol-treated Long-Evans and Holtzman rats after thyrotropin-releasing hormone or bromocriptine administration.

The objective of this study was to determine the effects of thyrotropin-releasing hormone (TRH) and bromocriptine on plasma levels of biologically active prolactin in ovariectomized, diethylstilbestrol (DES)-treated rats. Female Long-Evans and Holtzman rats were ovariectomized and each was given a subcutaneous implant of diethylstilbestrol (DES). One week later, groups of DES-treated rats were fitted with indwelling intra-atrial catheters, and 2 days later blood samples were withdrawn before and at 1, 2, 5, 10, and 20 min after intravenous administration of TRH (250, 500, or 1000 ng/rat). Blood samples were obtained from other groups at 4 weeks of DES treatment by orbital sinus puncture under ether anesthesia before and at 30, 60, and 120 min after bromocriptine administration (2.5 mg/rat sc). Plasma was assayed for prolactin by conventional radioimmunoassay (RIA) and by Nb2 lymphoma bioassay (BA). Holtzman rats released significantly more prolactin following TRH than did Long-Evans rats when the RIA was used to measure prolactin. However, when the BA was used to assay prolactin in the same samples, the Long-Evans rats released more prolactin than did the Holtzman rats. In addition, the ratio of the BA to RIA values was significantly increased in both strains following TRH, but the greatest increase was observed in the Long-Evans rats, in which the ratio was 4.5 at the peak of the TRH-induced rise in plasma prolactin. Gel filtration chromatography of plasma obtained at 5 min after TRH treatment in Long-Evans rats revealed large molecular forms of prolactin with BA to RIA ratios of 4-5. In addition, monomeric prolactin had a BA to RIA ratio of 2. Bromocriptine treatment reduced prolactin levels in both strains, but the effect was more rapid in Holtzman than in Long-Evans rats. In addition, bromocriptine treatment of Holtzman, but not Long-Evans, rats significantly reduced the BA to RIA ratio of plasma prolactin. The results indicate that TRH and bromocriptine affect the release of biologically active prolactin to a greater extent than prolactin detected by antibody in the RIA, and that Long-Evans and Holtzman rats respond to these secretagogues differently with regard to BA to RIA comparisons.

Animals↗
PubMed1991

A comparison of plasma prolactin levels in young female Long-Evans and Holtzman rats as measured by Nb2 lymphoma bioassay and radioimmunoassay.

This study was conducted to determine the plasma levels of prolactin in prepubertal and young, postpubertal, proestrus rats of mammary tumor-susceptible (Sprague-Dawley) and tumor-resistant (Long-Evans) strains using a sensitive bioassay-Nb2 lymphoma cell replication. Prepubertal Long-Evans rats had significantly higher levels of prolactin than did Holtzman Sprague-Dawley rats of the same age. Likewise, Long-Evans rats secreted significantly more prolactin into the blood on the afternoon and evening of proestrus than did Holtzman rats. Finally, ovariectomized Long-Evans rats released more prolactin into the blood at 1 day, but not at 8 or 15 days, of treatment with diethylstilbestrol. Prolactin levels determined by conventional radioimmunoassay and by bioassay were similar except on the afternoon of proestrus, when, in both strains of rats, the bioassay to radioimmunoassay ratio increased significantly above 1.0 during the late evening. In addition, the ratio was significantly less than 1.0 in the early and late afternoon in the Holtzman rats, but not Long-Evans rats. These data indicate that a strain of rats that is resistant to experimentally induced mammary cancer has higher prolactin levels in the blood than does a strain that is susceptible to mammary cancer at a time when mammary gland growth is rapid. Furthermore, there are times during the proestrus prolactin surge when the bioassay yielded higher and lower values of prolactin than radioimmunoassay of the same samples, suggesting functional heterogeneity of prolactin that may impact on mammary gland or other target tissue function.

Animals↗
PubMed1991

The cytoskeletal architecture of Trypanosoma brucei.

The cytoskeleton of Trypanosoma brucei has been analyzed by the high-resolution technique of quick-freeze deep-etch rotary-shadowing electron microscopy. The study provides detailed structural information on the subpellicular array of microtubules, the flagellum, and the interaction of these 2 major structures of the trypanosomal cytoskeleton with each other. The subpellicular microtubules closely interact both with the cell membrane and with each other. At the anterior tip of the cell they converge into a tightly closed structure, whereas at the posterior end the microtubular array remains open ended. The microtubular array is involved also in forming the opening of the flagellar pocket. The microtubular array interacts with the paraflagellar rod of the flagellum through a dense meshwork of fibers that are anchored on the microtubular surface with one end and within the paraflagellar rod structure with the other. The highly ordered, 3-dimensional network of the paraflagellar rod itself is connected tightly to the microtubular axoneme of the flagellum through a regular array of fleur-de-lis-shaped linking structures.

Animals↗
PubMed1991

Response of rat thoracic aortic rings to thromboxane mimetic U-46,619: roles of endothelium-derived relaxing factor and thromboxane A2 release.

Studies were designed to test the role of the endothelium and endogenous release of thromboxane (Tx) A2 in the contractile response of rat thoracic aortic rings to the TxA2/prostaglandin (PG) H2 mimetic, U-46,619. U-46,619 caused a dose-dependent contraction of rings with endothelium (mean ED50 = 6.54 +/- 3.02 x 10(-9) M; n = 13) which was abolished by the TxA2/PGH2 receptor antagonist, SQ-29,548. Removal of endothelium greatly potentiated (P less than .05) the contractile response to U-46,619 (ED50 = 4.78 +/- 2.14 x 10(-10) M; n = 14). On addition to the organ bath, oxyhemoglobin (10(-6) M), an inhibitor of endothelium-derived relaxing factor, increased vascular smooth muscle contraction in response to U-46,619 and abolished the difference in response between rings with endothelium (ED50 = 6.63 +/- 0.38 x 10(-11) M) and those without (ED50 = 5.13 +/- 0.18 x 10(-11) M). Vascular contraction with U-46,619 (10(-7] was associated with release of immunoreactive TxB2 and 6-keto PGF1 alpha as well as increased conversion of [14C]arachidonate to [14C]TxB2 and 6-keto-[14C]PGF1 alpha. To test the role of endogenous TxA2 in response to U-46,619, the TxA2 synthetase inhibitor UK-38,485 (10(-6) M) was added directly to the organ bath; this diminished (P less than .05) the contractile responses to U-46,619 of rings with and without endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

A polypeptide of 59 kDa is associated with bundles of cytoplasmic filaments in Neurospora crassa.

Complex arrangements of filamentous structures have been isolated from vegetative cells of the fungus Neurospora crassa. They were enriched by differential centrifugation and purified by permeation chromatography. The filamentous structures are made up of units of 8-10 nm diameter and were isolated in bundles of up to six to nine units. The main constituent of these structures is a polypeptide with an apparent molecular mass of 59 kDa (P59Nc), which represents 4-5% of the total N. crassa proteins. The filamentous structures are cold-stable and are not affected by high-ionic-strength solutions or by the presence of 10 mM-EDTA or 1% (w/v) Triton X-100; they were disassembled by raising the pH of the solution or by using Tris-based buffers. The disassembled form assembled into structures sedimentable at 105,000 g after dialysis against the isolation buffer. The sedimentable structures were organized in the form of regular aggregates of 42-45 nm polypeptides and reacted weakly with anti-IFA, a monoclonal antibody which recognizes an epitope common to many of the higher-eukaryote intermediate-filament polypeptides. Immunofluorescence examination of wall-digested hyphae of N. crassa using affinity-purified antibodies prepared against P59Nc showed immunostaining of abundant filamentous and dot-shaped structures distributed in the cytoplasm.

Cytoskeleton↗
PubMed1990

Effects of androgen withdrawal on the stem cell composition of the Shionogi carcinoma.

The parent Shionogi mouse mammary carcinoma is androgen dependent but cells that survive hormone withdrawal progress and give rise to an androgen-independent tumor. To determine whether renewed growth might be attributed to the persistence or partial recovery of an androgenic stimulus, we compared the amount of dihydrotestosterone and nuclear androgen receptor in parent and recurrent tumors. The whole tissue concentration of dihydrotestosterone in the parent tumor before castration was 1.40 +/- 0.46 (SE) as compared with 0.22 +/- 0.10 pmol/mg of DNA in the recurrent tumor. The initial concentration of nuclear androgen receptor in the parent was 0.65 +/- 0.12 pmol/mg of DNA; this was reduced to zero within 24 h after castration. Also in keeping with the androgen independence, no receptor was detected in the nuclear fraction of the recurrent carcinoma. In an attempt to relate malignant potential to nonhormonal factors associated with progression, we compared the proportions of androgen-dependent and -independent tumorigenic (stem) cells in parent and recurrent tumors using an in vivo limiting dilution assay. The difference observed, i.e., one stem cell per 4000 tumor cells in the parent versus one stem cell per 200 tumor cells in the recurrent carcinoma, was consistent with a marked enrichment of stem cells in the latter. The proportion of androgen-independent stem cells was also determined by assaying tumor takes in female hosts. The difference, i.e., one stem cell per 370,000 tumor cells in the parent versus one stem cell per 800 tumor cells in the recurrent carcinoma, demonstrated a striking 500-fold increase in androgen-independent stem cells resulting from androgen withdrawal. Unexpectedly, no enrichment of androgen-independent stem cells was evident in regressing parent tumors; rather, the proportion of such cells was very small, i.e., one androgen-independent stem cell per 2,200,000 regressing parent cells. This finding implies that the androgen-independent state of cells which survive androgen withdrawal may result from the ability of a small number of initially androgen-dependent stem cells to adapt to an altered hormone environment.

Androgens↗
PubMed1990

A medical information networking system between practitioners and academia.

This paper reports on a one-year experience with an information networking system (MIS) between 47 rural practitioners and an academic center. Physicians were invited to phone in non-emergency clinical questions specific to daily practice needs to a telephone answering service located in the medical school library. Two-hundred-forty questions triggered by patient visits, colleagues, local rounds, allied health or local professionals, and on-site administrative meetings were forwarded to the MIS. All inquiries were classified according to the International Classification of Disease-9th Revision-Clinical Modification, and categorized into three areas of practice: diagnostic/investigative, general treatment, and pharmacology (therapeutics). The paper outlines how specific practice questions are being screened and adopted for decisions relating to four current activities which assist the ongoing maintenance of competence: 1) CME program planning, 2) residency/undergraduate curriculum development, 3) individualized CME for specific practitioners and sites, and 4) future CME research. The physician inquiries represent true needs in rural medical practice and as such should be given high priority in programs and assessments addressing the maintenance of competence.

Academic Medical Centers↗
PubMed1990

Effects of calcium channel-blocking agents on platelet-osteogenic sarcoma interaction: platelet aggregation and electron microscopic findings.

A variety of tumors stimulate platelet activation. Because platelet activation may, in part, require calcium channel mobilization, we evaluated whether calcium channel blocking agents inhibit osteogenic sarcoma induced platelet aggregation. Platelet rich plasma (PRP) from normal subjects was incubated with one of four calcium channel-blocking agents: nifedipine, diltiazem, verapamil, or amlodopine, all 0-25 micrograms/ml, or diluent. Osteogenic sarcoma cells (2 or 4 x 10(6)/ml) were then added. Platelet aggregation was monitored by light transmission through PRP, and residual PRP was processed for electron microscopy. MG63 cells caused aggregation of PRP in most subjects (mean, 36 +/- 3%). Calcium channel-blocking agents (nifedipine greater than diltiazem greater than amlodopine greater than verapamil) caused partial inhibition of osteogenic sarcoma-induced platelet aggregation, at high concentrations only. Electron microscopy showed platelets aggregating to each other and to tumor cell membranes within 1-5 minutes. Changes in pattern of platelet clumping around tumor cells occurred when PRP was incubated with high concentration of diltiazem (50 micrograms). This study shows that calcium channel-blocking agents inhibit osteogenic sarcoma-induced platelet aggregation when used in high doses.

Blood Platelets↗
PubMed1990

The Cytoskeleton of trypanosomes.

From the concept of cells as mere bags full of enzymes, cell biology has come a long way towards understanding the highly complex structural organization of eukaryotic cells. The cytoskeleton, ie. the complex of fibrous elements that are crucial for cell shape, motility and the structural organization of cytoplasm and cell membranes, is now recognized as vital for supporting many critical functions in eukaryotic cells. Surprisingly, this subject, which has provided scores of cell biologists with excitement and fascination, has been largely overlooked with respect to parasitic protozoa. A notable change of perception has taken place over the past few years as the cytoskeleton of parasitic protozoa has been increasingly recognized as a potential target for antiparasitic intervention. The following article by Thomas Seebeck, Andrew Hemphill and Durward Lawson highlights some recent developments in the analysis of what is presently the best-studied parasite cytoskeleton, that of the trypanosome.

Journal Article↗
PubMed1990

Nitrous oxide effects on isolated myocardium: a reexamination in vitro.

This study examined in vitro myocardial depression by 50% N2O. Maximal isometric contractions of guinea pig right ventricular papillary muscles were studied in Tyrode's superfusate at 37 degrees C within a gas-tight chamber. Superfusate (pH at 7.45) and chamber were equilibrated with 95% O2/5% CO2. After control measurements in 95% O2, muscles were studied with 50% N2 and 50% N2O (45% O2/5% CO2) in random order with an intervening and final recovery in oxygen. Muscles were field stimulated after rest and at 0.1-3 Hz. At 37 degrees C, muscle performance deteriorated over time with exposure to reduced oxygen; therefore, identical experiments were performed at 30 degrees C in which no systematic deterioration occurred. Peak tension and maximum rate of tension development (dT/dtmax) were compared for each stimulation rate. At both temperatures, N2O caused a 10-15% depression of contractility as compared to that observed with nitrogen. In a second protocol, muscles were studied at 37 degrees C in 26 mM K+ Tyrode's solution with 0.10 microM isoproterenol to study enhanced contractions mediated by slow (Ca2(+)-channel-dependent) action potentials. Rested-state double stimulations were used (stimulus interval, 250-600 ms) resulting in a first rested-state contraction followed by a second contraction (C2) with rapid initial tension development. The muscles were exposed to nitrogen and N2O as in the force-frequency experiments and did not deteriorate over time. In this setting, N2O also caused a 10-15% depression of C2 contractility as compared with nitrogen. Another set of muscles was studied in 95% O2 to which 0.5% halothane or 1% isoflurane was added before exposure to nitrogen and N2O. The combined depressant action of N2O with either halothane or isoflurane did not differ from that predicted by the simple addition of independent effects; there was no evidence of synergism. Furthermore, N2O (50%) alone depressed dT/dtmax in a manner similar to that of 0.5% halothane and different from that of 1.0% isoflurane. Experiments conducted in iso-osmolar 40 mM Na+ Tyrode's solution, in which activator Ca2+ arose from the sarcoplasmic reticulum Ca2+, also showed greater depression by N2O than nitrogen. N2O (50%) is a myocardial depressant independent of concurrent hypoxic effects with a pattern and magnitude of contractile depression similar to that of 0.5% halothane.

Action Potentials↗
PubMed1990

An unusual intracerebral foreign body associated with eye trauma.

A case report is presented of penetrating orbital trauma in the driver of a motor vehicle which collided with a kangaroo. A tooth fragment from the kangaroo traversed the orbit, lodging intracranially. Management of the case is described and appropriate choice of antibiotic regime discussed.

Accidents, Traffic↗