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Biomedical subjects

L Clark

Publications and source records attributed to L Clark.

At least 145 records · Page 8Linked to original sources

Evaluation of triacontanol-containing compounds as anti-inflammatory agents using guinea pig models.

A mixture of the aliphatic alcohol, triacontanol, and other chemically associated naturally occurring alcohols was applied to the denuded dorsal cutaneous surface of guinea pigs to evaluate anti-inflammatory activity. In the setting of a chemical irritation with 2% croton oil and in an allergic dermatitis created with dinitrochlorobenzene sensitization and challenge, the triacontanol-containing preparation was significantly more effective than vehicle alone (DHL skin cream) but not as effective as 0.05% Diprolene ointment. Lymphocyte stimulation was studied by tritiated thymidine uptake and morphologic examination for blast transformation. When triacontanol-containing compounds were solubilized in aqueous media, effects on lymphocytes were insignificant. When solubilized in ethanol, there was a marked effect on thymidine uptake but not on blast transformation when compared to parallel controls.

Animals↗

The role of sequence-specific DNA-binding proteins in adenovirus DNA replication.

In prokaryotes it is well established that proteins which recognise defined DNA sequences are involved in the control of gene expression and replication. Cellular proteins in eukaryotes which may perform a similar function have been identified by their interactions with control regions of the human adenovirus genome. Immediately after infection a small region (E1a) at the left end of the adenovirus genome is expressed. Proteins coded by the E1a region transcriptionally activate the viral early genes. The products of a number of these early genes are directly involved in replication of the viral DNA. DNA sequences which are required for efficient E1a transcription and for the initiation of DNA replication have been identified by mutational analysis. Cellular proteins which recognise these sequences were detected using a sensitive gel retention assay. The basis of this assay is that during electrophoresis DNA-protein complexes migrate more slowly through a polyacrylamide gel than free DNA. In this way a cellular protein which binds to a conserved sequence in the adenovirus enhancer has been identified and partially purified. Cellular proteins which bind to adenovirus type 2 and 4 origins of replication have also been fractionated from nuclear extracts of uninfected HeLa cells. The roles of these proteins in adenovirus replication will be discussed.

Adenoviridae↗

Methylation of chromatin in vitro.

The endogenous DNA methylase in nuclei isolated from growing mouse cells preferentially methylates DNA in micrococcal nuclease-resistant regions probably as a result of the location in these regions of the preponderance of hemimethylated sites. Added mouse ascites cell DNA methylase catalyses the methylation of exposed, nuclease-sensitive DNA in chromatin from growing or non-growing mouse or insect cells. The poor acceptor ability of nuclease-resistant regions in this situation is due to the presence of histone proteins which block de novo methylation. Transcriptionally active regions of chromatin are selectively methylated in vitro by either endogenous or added DNA methylase.

Animals↗

Olfactory responses of aquatic and terrestrial tiger salamanders to airborne and waterborne stimuli.

Electro-olfactograms (EOGs) were used to assess olfactory responding by aquatic larval and terrestrial adult tiger salamanders (Ambystoma tigrinum) to airborne volatile compounds, and volatile and non-volatile compounds in aqueous solution. Both forms of salamander showed saturation effects to presentations of airborne stimuli (Fig. 2). Saturation was not observed, however, to stimulus presentations in aqueous solution (Figs. 2, 3). When threshold values and concentration-response curve parameters were compared, non-volatile amino acids in solution were more potent stimuli for larvae while airborne volatiles were more potent stimuli for adults (Tables 1, 2). We infer that metamorphosis in the tiger salamander is accompanied by changes in olfactory response characteristics, due possibly to changes in receptor population, changes in perireceptor properties (e.g. mucus) or to changes in stimulus access.

Ambystoma↗

Behavioral determinants of 24-hour blood pressure patterns in borderline hypertension.

Borderline hypertension is a heterogeneous condition; only a minority of patients will progress to fixed essential hypertension or suffer cardiovascular damage. Ambulatory blood pressure monitoring can detect the subgroup of borderlines with sustained blood pressure elevation outside the office setting and can also provide a measure of blood pressure variability. Patients in the former group may be at greatest risk for cardiovascular complications while the latter have been theorized to be at risk for progression to fixed hypertension. Evidence we have gathered utilizing ambulatory monitoring does not support the contention that there is a subgroup of borderline hypertensives with excessive blood pressure variability in natural settings. Such recordings have been of benefit in identifying patients with excessive pressor responses to office visits. Future studies employing ambulatory monitoring may be useful in the detection of clinically important subgroups of borderline hypertension.

Behavior↗

A monoclonal antibody detecting a possible public specificity of the HLA-C locus.

An IgM monoclonal antibody (CC-Cl 11) was produced by fusing myeloma cell line SP2/08 with lymphocytes of a Balb/c mouse previously immunized with peripheral blood lymphocytes of an A2, Bw44, B27, Cw1, Cw7, DR5 donor. Reactivity of CC-Cl 11 on a lymphocyte panel of 172 unrelated donors and lysostripping and absorption experiments have shown that CC-Cl 11 recognizes an antigenic determinant common to HLA-Cw1 and Cw3 positive lymphocytes.

Antibodies, Monoclonal↗

Demographic and personality characteristics of couples undergoing in vitro fertilisation.

Two hundred and fifty-eight (258) couples requesting in vitro fertilisation (IVF) were interviewed by a social worker prior to commencing treatment. At the time of admission to hospital 147 women and 134 men completed a questionnaire which incorporated the Eysenck Personality Inventory and the Spielberger State-Trait Anxiety Inventory. Forty-three women conceived and 26 couples (14.2%) required extra counselling or support after their involvement in the programme. Couples seeking IVF did not differ significantly from the rest of the population with respect to occupation, education, alcohol, cigarette and medication use. The personality characteristics of couples seeking IVF did not differ significantly from a local comparison group. Personality and psychosocial characteristics did not identify those couples who were more likely to become pregnant by IVF. However, couples who required extra counselling were more likely to have required similar help in the past. Women requiring counselling also scored significantly higher on the Eysenck neuroticism scale and the Spielberger State-Trait anxiety scales compared to those women who did not require extra counselling or support. The male partners scored significantly lower on the Eysenck scale of extroversion compared to male partners of couples who did not require support or counselling. We conclude that these inventories may be of value in identifying certain couples who require extra care during attempted conception by IVF.

Adult↗

Effect of topical indomethacin and timolol maleate on intraocular pressure in normal subjects.

In a prospective randomized double-masked crossover study in ten healthy volunteers, conducted to determine if the intraocular hypotensive effect of timolol eyedrops was significantly affected by the concomitant use of the topically administered prostaglandin inhibitor, indomethacin, we found that significant ocular hypotension was achieved with timolol alone. This was not changed by the concurrent administration of indomethacin. The results provide further evidence that prostaglandins are not involved in the control of normal intraocular pressure.

Double-Blind Method↗

Reduction of aspirin-induced fecal blood loss with low-dose misoprostol tablets in man.

Misoprostol (SC-29333), a synthetic prostaglandin E1 methyl ester analog, was given simultaneously with acetylsalicylic acid in a double-blind, placebo-controlled randomized prospective study of 32 healthy human male subjects. Fecal blood loss was measured for eight days using the 51Cr-labeled red blood cell technique. Aspirin (650 mg qid) and misoprostol (25 micrograms qid) or placebo were given during days 3, 4, and 5. There was a significant (P less than 0.05) increase in median blood loss (modified Friedman test) from 0.81 to 6.05 ml/day in the aspirin with placebo group (N = 16). Median blood loss was increased (from 0.75 to 3.75 ml/day) in the aspirin with misoprostol group (N = 16), but this was significantly less (Mann-Whitney U test, P less than 0.01) than the placebo group. Mean serum salicylate concentrations in the placebo and misoprostol groups were similar (7.8 and 6.8 micrograms/ml, respectively). There were no significant changes in laboratory values in any of the subjects studied, nor were any major side-effects encountered. This study demonstrates that oral misoprostol reduces aspirin-induced gastrointestinal bleeding even when administered simultaneously and at a dose level below its threshold for significant acid inhibition. This indicates a potential role for misoprostol in the prevention of gastric mucosal damage in selected patients.

Adult↗

Protection against aspirin-induced antral and duodenal damage with enprostil. A double-blind endoscopic study.

Prostaglandins protect against aspirin-induced damage to the gastrointestinal tract. This study tested the ability of enprostil, a synthetic analog of prostaglandin E2, given concurrently to prevent gastroduodenal injury. Twenty-four healthy subjects were randomly assigned to one of three groups. All received aspirin 650 mg q.i.d. for 5 days. One group received placebo and the other groups were given either 7 or 70 micrograms of enprostil b.i.d. for 5 days. Upper endoscopy was performed at entry and 2 h after the final dose of aspirin. Enprostil 70 micrograms b.i.d. afforded significant protection of both the antral and duodenal mucosa. The 7-micrograms dose protected only the antral mucosa. Side effects were not observed with the lower dose of enprostil. Serum salicylate levels did not differ significantly between the groups.

Adolescent↗

Cigarette smoking reduces human gastric luminal prostaglandin E2.

The effect of smoking three cigarettes on the release of prostaglandin E2 (PGE2) by the gastric mucosa was studied in seven healthy smokers. Smoking caused the expected increases in pulse rate, blood pressure, plasma glucose, and carboxyhaemoglobin. In addition, smoking resulted in a significant (p less than 0.05) reduction in the volume of pentagastrin stimulated gastric juice from 76.1 +/- 4.4 to 54.1 +/- 4.6 ml/15 min and PGE2 output from 22.8 +/- 4.9 to 12.2 +/- 3.8 ng/15 min but did not alter acid output. It is concluded that smoking reduces the amount of PGE2 in the gastric lumen and that this may explain why it is a risk factor for peptic ulcer.

Adult↗

Phagocytosis and killing of Gardnerella vaginalis by human neutrophils.

Gardnerella vaginalis was ingested and killed by neutrophils in the presence of normal human serum. Heat inactivation of the serum inhibited these processes. The opsonisation of some but not all G vaginalis strains was enhanced by immune rabbit serum. Immune serum did not, however, enhance intracellular killing. Blockade of the classical pathway of complement activation had no effect on the opsonic activity of human serum. These results suggest that the opsonisation, phagocytosis, and killing of G vaginalis by human serum and neutrophils is primarily mediated by complement activated by the alternative pathway. Serum without neutrophils has little effect on the viability of G vaginalis.

Animals↗

Risk factors for prematurity and premature rupture of membranes: a prospective study of the vaginal flora in pregnancy.

Prematurity remains a major cause of perinatal mortality in the United States. Some research has indicated that infectious agents play a role in either initiating preterm labor, causing premature rupture of the membranes, or preventing tocolysis. This study attempted to determine if the presence of various vaginal pathogens in early pregnancy was associated with the subsequent development of premature rupture of membranes or preterm labor. We found that among 233 evaluable patients those with Trichomonas vaginalis were significantly more likely to have premature rupture of the membranes (p less than 0.03), and those with Bacteroides sp. were more likely to be delivered of their infants before 37 weeks (p less than 0.03) and to have infants weighing less than 2500 gm (p less than 0.05). Those with Ureaplasma urealyticum more frequently began preterm labor (p less than 0.05). Preterm premature rupture of the membranes was found significantly more often among patients with Bacteroides sp. Stepwise multiple logistic regression analysis indicated that those associations were not related to the number of previous abortions, deliveries, or preterm deliveries or to maternal age. We conclude that microbiologic screening in early pregnancy may aid in the assessment of patient risk for preterm delivery.

Adolescent↗