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Biomedical subjects

S Farrell

Publications and source records attributed to S Farrell.

At least 37 records · Page 2Linked to original sources
PubMed1997

Cerebral blood flow during hypoxemia and hemodilution in rabbits: different roles for nitric oxide?

Hypoxemia and anemia are associated with increased CBF, but the mechanisms that link the changes in PaO2 or arterial O2 content (CaO2) with CBF are unclear. These experiments were intended to examine the contribution of nitric oxide. CaO2 in pentobarbital-anesthetized rabbits was reduced to approximately 6.5 mL O2/dL by hypoxemia (PaO2 approximately 24 to 26 mm Hg) or hemodilution with hetastarch (hematocrit approximately 14% to 15%). Animals with normal CaO2 (approximately 17.5 to 18 mL O2/dL) served as controls. In part I, each animal was given 3, 10, and 30 mg/kg N omega-nitro-L-arginine methyl ester (L-NAME) intravenously (total 43 mg/kg) to inhibit production of nitric oxide. Forebrain CBF was measured with radioactive microspheres approximately 15 to 20 minutes after each dose. Baseline CBF was greater in hypoxemic rabbits (111 +/- 31 mL x 100 g-1 x min-1, mean +/- SD) than in hemodiluted (70 +/- 22 mL x 100 g-1 min-1) or control animals (39 +/- 12 mL x 100 g-1 min-1). L-NAME (which reduced brain tissue nitric oxide synthase activity by approximately 65%) reduced CBF in hypoxemic animals to 80 +/- 23 mL x 100 g-1 x min-1 (P < 0.0001), but had no significant effect on CBF in either anemic or control animals. In four additional rabbits, further hemodilution to a CaO2 of approximately 3.5 mL O2/dL increased baseline CBF to 126 +/- 21 mL x 100 g-1 min-1, but again there was no effect of L-NAME. In part II, animals were anesthetized as above, and a close cranial window was prepared. The cyclic GMP (cGMP) content of the artificial CSF superfusate was measured under baseline conditions, and then after the reduction of CaO2 to approximately 6.5 mL O2/dL by either hypoxemia or hemodilution. Concentrations of cGMP did not change during either control conditions or after hemodilution. However, cGMP increased significantly with the induction of hypoxemia. The cGMP increase in hypoxemic animals could be blocked with L-NAME. These results suggest that nitric oxide plays some role in hypoxemic vasodilation, but not during hemodilution.

Animals↗
PubMed1997

Diagnostic laparoscopy for chronic right iliac fossa pain: a pilot study.

BACKGROUND: The aim of this study was to determine the value of diagnostic laparoscopy in patients with chronic right iliac fossa pain. METHODS: A retrospective study at Echuca Hospital involving case-note review and telephone questionnaire of patients who had undergone diagnostic laparoscopy for chronic right iliac fossa pain at least 12 months earlier (September 1992 to August 1995) was carried out. RESULTS: Forty-one cases were identified and followed up 12-40 months postoperatively (median 21 months). Eleven cases had positive findings at laparoscopy, of whom eight obtained lasting relief after treatment. Of the remaining 30 patients 17 had a normal-looking appendix removed and 12 were cured; these were younger patients with episodic symptoms and localized signs. Of eight patients who had adhesions divided, four with adhesions beneath old scars obtained relief. Altogether 32 of the 41 patients considered the laparoscopy worthwhile even though in some cases it did not relieve their chronic pain. CONCLUSIONS: Diagnostic laparoscopy is worthwhile for patients with chronic right iliac fossa pain. Concurrent appendicectomy should be considered in young patients with episodic, well-localized symptoms associated with systemic malaise while adhesiolysis may be beneficial for viscero-parietal adhesions beneath abdominal wall scars.

Abdominal Pain↗
PubMed1996

Gene activation by recruitment of the RNA polymerase II holoenzyme.

The single amino acid "P" (potentiator) mutation in the holoenzyme component GAL11 creates an interaction between that protein and the dimerization region of GAL4. That interaction triggers strong gene activation when the GAL4 fragment is tethered to DNA. Here we show that, among a series of variants of the GAL4 dimerization region and different GAL11P alleles, the strength of the interaction as quantitated in vitro correlates with the degree of activation in vivo; swapping the protein fragments bearing the GAL4 dimerization region and the GAL11P mutation such that the latter is tethered to DNA and the former is attached to the holoenzyme does not diminish gene activation; gene activation in this system is squelched by overproduction of either a fragment bearing the GAL4 dimerization region or a fragment of GAL11 bearing a P mutation; and neither GAL11 nor GAL11P is a target of an acidic activating region. These results argue that the GAL4-GAL11P interaction triggers gene activation simply by recruiting the holoenzyme to DNA. Consistent with this view, we also show that fusion of LexA to another holoenzyme component, SRB2, creates an activator, and that an SRB2 mutant predicted on genetic grounds to interact especially efficiently with a holoenzyme containing a specific mutant form of polymerase also activates more efficiently when tethered to DNA.

Bacterial Proteins↗
PubMed1996

Regional localization of an X-linked mental retardation gene to Xp21.1-Xp22.13 (MRX38).

A gene responsible for X-linked mental retardation with macrocephaly and seizures (MRX38) in a family with five affected males in three generations was localized to Xp21.1-p22.13 by linkage analysis. Recombination events placed the gene between DXS1226 distally and DXS1238 proximally, defining an interval of approximately 14 cM. A peak lod score of 2.71 was found with several loci in Xp21.1 (DXS992, DXS1236, DXS997, and DXS1036) at a recombination fraction of zero. The map intervals of 5 X-linked mental retardation loci, MRX2 (Xp22.1-p22.2), MRX19 (Xp22), MRX21 (Xp21.1-p22.3), MRX29 (Xp21.2-p22.1), and MRX32 (Xp21.2-p22.1), and two syndromal mental retardation loci, Partington syndrome (PRTS; Xp22) and Coffin-Lowry syndrome (CLS; Xp22.13-p22.2), overlap this region. As none of these display the same phenotype seen in the family reported here, this X-linked mental retardation locus may represent a new entity.

Adolescent↗
PubMed1996

The effect of chronically elevated intraocular pressure on the rat optic nerve head extracellular matrix.

The extracellular matrix of the optic nerve head is altered in both human glaucoma and in experimental primate models of this disease. However, the relationship of this change to glaucomatous optic nerve degeneration is unknown. This report describes similar matrix alterations in rats with unilateral elevated intraocular pressure. Brown Norway rats received episcleral vein injections of hypertonic saline to produce prolonged elevations of intraocular pressure. After up to 6 months of pressure elevation, optic nerve head sections from the rats were evaluated by light microscopic immunohistochemistry using antibodies to collagens I, III, IV and VI, laminin, elastin and chondroitin and dermatan sulfate proteoglycans. In experimental eyes with 11 days or more of pressure elevation, depositions of collagen IV, collagen VI and laminin were found within regions of the optic nerve head that, in normal eyes, are occupied solely by nerve bundles. Collagen I and III deposition appeared to be more dependent on the level and duration of the pressure rise. Eyes with lower mean intraocular pressures showed deposits of interstitial collagens primarily at the level of the sclera, while eyes with higher mean pressure elevations had depositions in the neck regions as well. Chondroitin and dermatan sulfate proteoglycans were deposited in a pattern similar to that of collagen I. No extracellular matrix deposition was seen in the orbital optic nerve in any experimental eye. These extracellular matrix changes in rats replicate previous findings in human glaucomatous eyes and monkey eyes with experimentally elevated pressures. They also suggest a sequence of extracellular matrix protein deposition in response to pressure elevation. The optic nerve head deposition of matrix materials in response to elevated intraocular pressures may affect the susceptibility of remaining axons to pressure by changing the physical properties of their support tissues, by affecting the support functions of astrocytes and by changing the microenvironment of injured axons. This model may be useful for studying these and other aspects of the process of axonal injury resulting from elevated intraocular pressure.

Animals↗
PubMed1996

Beta-adrenergic receptor activation promotes process outgrowth in an embryonic rat basal forebrain cell line and in primary neurons.

A clonal cell line, AS583-8.E4.22, from the embryonic day 15 rat basal forebrain was established using retrovirus-mediated transduction of a temperature-sensitive mutant of the simian virus 40 (SV40) large tumour antigen. The cell line expresses cytoskeletal and neurotransmitter features indicative of neuronal commitment. In response to agents that increase intracellular cAMP, including forskolin and catecholamines, the cell line exhibits rapid process outgrowth and growth cone formation that does not require new gene expression or protein synthesis. The neurite outgrowth induced by catecholamines is mediated by beta 2-adrenergic receptors and is characterized by a rapid, reversible redistribution of filamentous actin. Neurons from primary cultures of embryonic day 15 basal forebrain were also found to respond to beta-adrenergic receptor agonists by enhancing growth cone formation. These results suggest that catecholamines provide cues that induce cytoskeletal rearrangements leading to neuronal process outgrowth and growth cone formation in the developing basal forebrain and possibly other neuronal progenitor cell populations. The neuronal basal forebrain cell line provides an ideal model to study the signalling mechanisms underlying the catecholamine-induced process outgrowth.

Adrenergic beta-Agonists↗
PubMed1995

Contact with a component of the polymerase II holoenzyme suffices for gene activation.

In yeast strains bearing the point mutation called GAL11P (for potentiator), certain GAL4 derivatives lacking any classical activating region work as strong activators. The P mutation confers upon GAL11, a component of the RNA polymerase II holoenzyme, the ability to interact with a portion of the dimerization region of GAL4. The region of GAL11 affected by the P mutation is evidently functionally inert in ordinary cells, suggesting that this mutation is of no functional significance beyond creating an artificial target for the GAL4 dimerization fragment. From these observations and further analyses of GAL11, we propose that a single activator-holoenzyme contact can trigger gene activation simply by recruiting the latter to DNA.

DNA, Fungal↗
PubMed1995

Structure and composition of the rodent lamina cribrosa.

To define the architecture and extracellular matrix composition of the lamina cribrosa in rodents, normal, adult pigmented rat and guinea pig eyes were frozen and sectioned for light microscopic immunohistochemistry. Antibodies specific for collagens I, III, IV and VI, laminin, elastin, and chondroitin and dermatan sulfate proteoglycans were exposed to longitudinal and cross-sections of optic nerve heads and their binding distributions observed with the avidin-biotin-peroxidase complex technique. Cross-sections of the intraocular portion of the rat optic nerve head revealed a horizontally oval shape with distinct, vertically oriented, laminar beams. The guinea pig optic nervehead cross-section was circular, with randomly oriented beams. In both animals, collagens I, III and VI were found throughout the laminar beams, along with elastin fibrils. Collagen IV and laminin antibodies deposited along laminar beam margins and within the beams, representing astrocytic and vascular endothelial cell basement membranes. Both animals showed evidence for dermatan and chondroitin sulfate-containing proteoglycans in all connective tissue structures of the nerve head. In the rat, chondroitin-4 sulfate proteoglycans appeared localized to the sclera and laminar beams. The rat and the guinea pig optic nerve head possess an identifiable lamina cribrosa with structural proteins nearly identical to that of the primate. Both animals may provide affordable alternative animal models for in vivo studies on the role of the lamina cribrosa in glaucomatous optic nerve damage.

Animals↗
PubMed1994

Disruption of a putative working memory task and selective expression of brain c-fos following microwave-induced hyperthermia.

To discern the effects of hyperthermia on working memory, we recorded the ability of rats to discriminate between objects following microwave radiation exposure. Memory changes were evaluated by measuring relative exploration time of a familiar vs. a new stimulus object. A subject that extensively reexplores a stimulus with which it has previous experience is presumed to exhibit memory loss associated with that object. Between training and testing, rats were exposed to various doses of microwave radiation, were sham irradiated, or remained in their home cage. Brain (dural) and rectal temperatures were recorded. To discern brain regions activated or possibly damaged by microwave exposure, we also used immunocytochemistry techniques to identify sites of c-fos protein expression in the brains of several irradiated/sham-irradiated subjects. Rats exposed to > 5 W/kg exhibited hyperthermia when compared to nonirradiated controls. Normothermic control subjects (sham-irradiated rats and rats exposed to 0.1 W/kg) showed a distinct preference for the new object although other microwave-exposed rats (1, 5, 8.5, 9.3, 10 W/kg) did not. Microwave hyperthermia evoked prominent c-fos expression in periventricular strata, hypothalamic nuclei, amygdala, and several areas of the cortex. These data suggest that performance on a putative working memory task may be disrupted by a sufficiently intense microwave-induced hyperthermia. The pattern of expression of the early proto-oncogene c-fos may suggest candidate brain nuclei that mediate the behavioral changes we observed.

Animals↗
PubMed1994

Adenoviral vector-mediated gene transfer into sheep arteries using a double-balloon catheter.

The potential for catheter-based in vivo delivery of genetic material to the arterial wall is incompletely explored. We evaluated the level of recombinant protein production as well as the anatomic distribution and duration of gene expression following adenoviral vector-mediated gene transfer into sheep arteries via a double balloon catheter. Catheters were positioned in the carotid or femoral arteries of 20 sheep via a combined percutaneous and surgical approach, and virions infused over a 30-min period. Three days later, recombinant gene expression was identified in approximately 30% (range 0-80%) of the luminal endothelial cells within the targeted area of the artery. Persistent recombinant protein expression was identified histochemically for up to 4 weeks, although the number of positive cells decreased steadily. High levels of both beta-galactosidase (beta-Gal) activity and protein (mean 20 mU and 44 ng per vessel) were measured in vessel extracts 3 days after gene transfer, again decreasing significantly over a 4-week period. Transgene expression was limited almost entirely to the intima and adventitia; adventitial gene transfer occurred virtually exclusively along the vasa vasorum. In comparison to previous studies of catheter-based gene transfer, adenoviral vectors delivered by double balloon catheter resulted in a particularly high efficiency of endothelial cell gene transfer. The efficiency and amount of recombinant gene expression achieved in this study suggest that catheter-based gene delivery may eventually be applicable to the treatment of focal human arterial disease.

Adenoviridae↗
PubMed1990

Treatment of myofascial pain-dysfunction syndrome with occlusal equilibration.

Fifty-three patients with a diagnosis of chronic myofascial pain-dysfunction syndrome were treated with occlusal equilibration to establish complete anterior guidance. In approximately 5 to 7 days after treatment, most myofascial pain dysfunction symptoms disappeared and complete symptom resolution was usually attained within 3 weeks. The common symptoms all patients had were (1) pain and fatigue in the masseter and temporal muscles, (2) nocturnal bruxism, (3) jaw tension on waking up, and (4) difficulty chewing some foods. All patients had an absence of true anterior guidance with molar interferences in all excursive movements. Many patients had previously undergone orthodontic therapy and had "ideal" vertical tooth relationships. Treatment consisted of occlusal equilibration to remove all posterior interferences and establish anterior guidance. Three appointments, 1 week apart, were alloted for treatment. Major symptom reduction occurred after the first appointment. Four-year follow-ups reveal no recurrence of chronic symptoms after treatment completion.

Adolescent↗
PubMed1990

Contribution of women dentists to general practice.

The number of women general dental practitioners has increased in the last few years as the number of women graduating from UK dental schools has also increased. The increase in women practitioners from 1975 to 1985 is of the order of 10 per cent, although only 23 per cent of the total owned their own practices either alone or in partnership. The paper describes the author's own experiences in setting up a thriving practice and the problems she encountered as a woman. Also described are the author's observations in striving for greater goals for general dental practitioners in terms of continuing education and vocational training.

Dentists, Women↗
PubMed1989

Policy alternatives for alcohol-impaired driving.

This article summarizes current scientific evidence about the impact of public policy measures on alcohol-related motor vehicle crashes. The public policy measures considered are (1) minimum drinking age laws, (2) taxation of alcoholic beverages, (3) drinking and driving laws, (4) laws and regulations governing the physical availability of alcoholic beverages, and (5) server intervention programs. It is concluded that certain public policy measures reduce alcohol-related crashes. These measures include higher taxes on alcoholic beverages and at least some laws and regulations governing the physical availability of alcohol (as well as the minimum drinking age). The article suggests that strengthening drinking and driving laws without also adopting these other measures may have less than optimum (and possibly disappointing) effects.

Age Factors↗
PubMed1987

Phase I and pharmacokinetic study of high volume intraperitoneal aclacinomycin-A (Aclarubicin).

Aclacinomycin-A (Aclarubicin) is a relatively new anthracycline antibiotic with potential activity against ovarian cancer. Eight patients with various malignancies (4 ovary, 1 breast and ovary, 1 breast, 1 colon, 1 leiomyosarcoma) and intraperitoneal disease were treated in a Phase I trial with escalating doses of intraperitoneal Aclacinomycin. Drug treatments were administered through a peritoneal catheter in a 2 liter fluid volume (1.5% Dianeal). Seventeen cycles were administered with doses ranging from 25 to 75 mg of Aclacinomycin. Pharmacokinetic studies were carried out in 7 patients. Although high concentrations of Aclacinomycin could be obtained in the peritoneal cavity no drug was detected in the plasma. The major dose-limiting toxicity was chemical peritonitis. Two patients had reduction in the amount of ascites. The recommended dose for Phase II trials is Aclacinomycin 50 mg in 2 liters given every 2 weeks.

Aclarubicin↗