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Biomedical subjects

A Farrell

Publications and source records attributed to A Farrell.

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

Release of atrial natriuretic factor prohormone peptides 1-30, 31-67 and 99-126 from freshwater- and seawater-acclimated perfused trout (Oncorhynchus mykiss) hearts

Atrial natriuretic factor (ANF), a 28-amino-acid peptide hormone produced in the heart, circulates in both freshwater and seawater rainbow trout. In mammals, two other peptide hormones, proANF 1-30 and proANF 31-67, derived from the same 126-amino-acid prohormone as ANF (amino acids 99&shyp;126), circulate and have natriuretic and diuretic properties. It has never been determined whether these peptides circulate in fish. The present investigation was designed to determine (1) whether proANF 1-30 and/or proANF 31-67 circulate in perfused hearts from freshwater- and seawater-acclimated rainbow trout (Oncorhynchus mykiss) in situ, and (2) if they do, to determine whether increasing the filling pressure of the heart causes their release in trout as it does in mammals. High-performance gel-permeation chromatography of fish plasma revealed that both proANF 1-30 and 31-67 circulate in freshwater- and seawater-acclimated trout plasma at threefold higher concentrations than does ANF. The basal rates of release of ANF and proANF 1-30 and 31-67 were similar in both freshwater and seawater trout, with the rate of release of proANF 1-30 being 10 times higher and that of proANF 31-67 20 times higher than that of ANF. When the filling pressure was increased to the peak of the Starling curve (max), the rate of release of ANF and proANFs 1-30 and 31-67 increased fivefold for each peptide in the freshwater trout, while in seawater trout the rates of release increased six- to ninefold. We conclude that proANF 1-30 and 31-67, as well as ANF, circulate in both freshwater-and seawater-acclimated trout and do so at concentrations higher than that of ANF. Increasing the filling pressure to the trout heart was found to cause a similar increase in the release rates for each of these peptides, but the maximal increase was higher in the seawater-acclimated trout, apparently because they showed a larger increase in cardiac output.

Journal Article↗
PubMed1996

A cyclin-dependent kinase-activating kinase (CAK) in budding yeast unrelated to vertebrate CAK.

Progress through the cell cycle is governed by the cyclin-dependent kinases (CDKs), the activation of which requires phosphorylation by the CDK-activating kinase (CAK). In vertebrates, CAK is a trimeric enzyme containing CDK7, cyclin H, and MAT1. CAK from the budding yeast Saccharomyces cerevisiae was identified as an unusual 44-kilodalton protein kinase, Cak1, that is only distantly related to CDKs. Cak1 accounted for most CAK activity in yeast cell lysates, and its activity was constant throughout the cell cycle. The CAK1 gene was essential for cell viability. Thus, the major CAK in S. cerevisiae is distinct from the vertebrate enzyme, suggesting that budding yeast and vertebrates may have evolved different mechanisms of CDK activation.

Amino Acid Sequence↗
PubMed1996

Isolation and analysis of cDNAs encoding tomato cysteine proteases expressed during leaf senescence.

Several cDNAs for mRNAs that change in abundance during tomato leaf senescence were isolated. In this paper we report molecular cloning and expression analysis of two cysteine proteases. SENU2 is identical to the cDNA C14 which encodes a cysteine protease previously shown to be expressed in response to extremes of temperature in tomato fruit [43]. SENU3 cDNA clone was 1.2 kb in length and hybridized to a transcript of 1.4 kb which suggested that the clone was not full-length. The missing 5' end was isolated using rapid amplification of cDNA ends (RACE). Southern blot analysis of tomato genomic DNA indicates that SENU3 is encoded by a single or low copy gene. SENU3 was also shown to have significant homology with known cysteine proteases. These two senescence-associated cysteine proteases are also expressed during other developmental processes, including seed germination, consistent with a role in protein turnover. SENU2 and SENU3 mRNAs were detectable in young fully expanded leaves and increased in abundance with leaf age, reaching a maximum during the later stages of visible leaf senescence. Such a pattern of expression suggests that the onset of leaf senescence is a gradual event. Analysis of senescence in transgenic plants deficient in ethylene biosynthesis, in which leaf senescence is delayed, indicated that enhanced accumulation of SENU2 and SENU3 mRNA was similarly delayed but not prevented.

Aging↗
PubMed1996

Genetic complementation of radiation response by 3' untranslated regions (UTR) of RNA.

The molecular basis of radiosensitivity was studied using a cDNA complementation approach to correct radiosensitivity in cells. Four cDNAs of sizes 1.6, 2.0, 2.2 and 2.5 kb were isolated that corrected several aspects of the phenotype of cells from patients with the human genetic disorder ataxia-telangiectasia, characterized by hypersensitivity to ionizing radiation. The criteria used to assess correction included cell viability, induced chromosome aberrations, G2 phase delay and induction of p53 after exposure to radiation. One cDNA (2.5 kb) was identified as the complete sequence of the RNA helicase p68, which was capable of correcting radiosensitivity based on two of the above four criteria, with p53 induction post irradiation being partially corrected. The 2.2 kb cDNA was shown to correspond to the complete sequence of arginyl tRNA synthetase and the other two cDNAs were identical to the 3' untranslated regions (UTR) of the transcription factor TFIIS (1.6 kb) and phospholipase A2 (2.0 kb) respectively. Additional transfections with the 3'UTR (198 nucleotides) of p68 RNA helicase and its inverse sequence revealed that the 3'UTR had the same complementation capacity as the full-length cDNA, whereas the inverse construct failed to complement radiosensitivity. These data provide additional support for a novel role for 3'UTRs in the regulation of gene expression.

Ataxia Telangiectasia↗
PubMed1996

Maximum cardiac performance of rainbow trout (Oncorhynchus mykiss) at temperatures approaching their upper lethal limit

Numerous studies have examined the effect of temperature on in vivo and in situ cardiovascular function in trout. However, little information exists on cardiac function at temperatures near the trout's upper lethal limit. This study measured routine and maximum in situ cardiac performance in rainbow trout (Oncorhynchus mykiss) following acclimation to 15, 18 and 22 °C, under conditions of tonic (30 nmol l-1), intermediate (60 nmol l-1) and maximal (200 nmol l-1) adrenergic stimulation. Heart rate increased significantly with both temperature and adrenaline concentration. The Q10 values for heart rate ranged from 1.28 at 30 nmol l-1 adrenaline to 1.36 at 200 nmol l-1 adrenaline. In contrast to heart rate, maximum stroke volume declined by approximately 20 % (from 1.0 to 0.8 ml kg-1) as temperature increased from 15 to 22 °C. This decrease was not alleviated by maximally stimulating the heart with 200 nmol l-1 adrenaline. Because of the equal and opposite effects of increasing temperature on heart rate and stroke volume, maximum cardiac output did not increase between 15 and 22 °C. Maximum power output decreased (by approximately 10-15 %) at all adrenaline concentrations as temperature increased. This reduction reflected a poorer pressure-generating ability at temperatures above 15 °C. These results, in combination with earlier work, suggest (1) that peak cardiac performance occurs around the trout's preferred temperature and well below its upper lethal limit; (2) that the diminished cardiac function concomitant with acclimation to high temperatures was associated with inotropic failure; (3) that Q10 values for cardiac rate functions, other than heart rate per se, have a limited predictive value at temperatures above the trout's preferred temperature; and (4) that heart rate is a poor indicator of cardiac function at temperatures above 15 °C.

Journal Article↗
PubMed1995

Cdc37 is required for association of the protein kinase Cdc28 with G1 and mitotic cyclins.

Studies of the temperature-sensitive cdc37-1 mutant of Saccharomyces cerevisiae suggest that Cdc37 is required for passage through the G1 phase of the cell cycle, but its precise function is not known. We have investigated the role of Cdc37 in the regulation of the cyclin-dependent protein kinase Cdc28. We find that G1 arrest in the cdc37-1 mutant is accompanied by a decrease in the Cdc28 activity associated with the G1 cyclin Cln2. This defect appears to be caused by a decrease in the binding of Cdc28 and Cln2. cdc37-1 mutants also exhibit a defect in the binding and activation of Cdc28 by the mitotic cyclin Clb2. Thus Cdc37 may be a regulator that is required for the association of Cdc28 with multiple cyclins.

Base Sequence↗
PubMed1995

The influence of contralateral carotid stenosis and occlusion on cerebral oxygen saturation during carotid artery surgery.

OBJECTIVES: To study the effect of contralateral carotid stenosis on oxygen saturation (CsO2) of both cerebral hemispheres monitored by reflective near-infrared spectroscopy (NIRS) during carotid surgery. METHODS: NIRS was compared to ipsilateral transcranial Doppler ultrasonography (TCD) of the middle cerebral artery and jugular bulb venous oxygen saturation (JvSO2) in 54 patients undergoing carotid endarterectomy. RESULTS: Median operated side and contralateral CsO2 were 68(54-88)% and 69(55-85)% before carotid clamping falling to 63(44-80)% and 69(55-84)% respectively on clamping the carotid (p < 0.0001 and p = NS). JvSO2 fell from 78(38-98)% to 72(30-97)% on carotid clamping with a percentage fall in peak TCD of -28(0 to -100)% (p < 0.0001). Patients with a contralateral carotid artery occlusion experienced falls in ipsi and contralateral CsO2 of -8(-4 to -10)% and -3(2 to -7)% compared to -4(0 to -14)% and 0(-5 to 4)% in those with a lesser stenosis (p < 0.05). On declamping, median ipsilateral and contralateral CsO2 rose from 65(46-82)% and 67(52-87)% to 68(53-84)% respectively (p < 0.0001 and p = NS). JvSO2 increased from 75(33-95)% to 79(42-95)% (p < 0.0001) with an increase in median peak TCD of 35(-34 to 506)%. CONCLUSIONS: The greatest changes in CsO2 occurred in the operated side cerebral hemispheres in those with a contralateral carotid artery occlusion. However, a contralateral carotid artery occlusion does not reliably predict the need for a shunt and cerebral monitoring remains essential; although is only required on the operated side.

Brain↗
PubMed1995

Acute graft-versus-host disease with unusual cutaneous intracellular vacuolation in an infant with severe combined immunodeficiency.

We report an infant with severe combined immunodeficiency (SCID) who had cutaneous manifestations of acute graft-versus-host disease (GVHD) due to maternofetal lymphocyte engraftment. Histologic and ultrastructural examinations of the skin revealed intracellular vacuoles resembling lipid droplets in the epidermis and dermis, which is not a recognized feature of acute GVHD or SCID.

Acute Disease↗
PubMed1995

Anetoderma of Jadassohn-Pellizzari.

Anetoderma (derived from the Greek anetos, meaning slack) is a term used to describe localized increased laxity of the skin with herniation or outpouching, resulting from abnormal dermal elastic tissue. Primary anetoderma is distinctly rare. We describe a case where we suspect an auto-immune aetiology.

Adult↗
PubMed1994

Identification of a potentially radiosensitive subgroup among patients with breast cancer.

BACKGROUND: The description of genes and genetic syndromes, such as ataxia-telangiectasia, that predispose some women to breast cancer will provide greater insight into the genetic basis of cancer susceptibility. PURPOSE: Our goal was to establish cell lines from patients with breast and bladder cancers, to screen for enhanced levels of radiation-induced arrest in the G2 phase of the cell cycle such as is observed in ataxia-telangiectasia heterozygotes, and to correlate G2 arrest with other prognostic indicators of these cancers and in vivo radiosensitivity. METHODS: Epstein-Barr virus-transformed lymphoblastoid cells were established from 108 female patients with breast cancer and 24 age-matched female control subjects, and from 45 patients with bladder cancer and 18 age-matched control subjects. Cells were exposed to 3 Gy of gamma radiation, and the percentages of cells in G1 and G2 phases were determined at 18 and 24 hours after irradiation by fluorescence-activated cell sorter analysis. Postirradiation delay in G2 phase was determined by calculating the percentage of cells in G2 and by using the ratio G2/G1. RESULTS: When we determined the percentage of cells in G2 phase at 18 hours after irradiation in 108 lymphoblastoid cells from breast cancer patients, we observed an increase of between 3% and 38% in the number of cells in G2 phase in comparison with cells that were not irradiated. Comparison with previous G2-phase arrest data for ataxia-telangiectasia heterozygotes using a cutoff point at 29% delay demonstrated that 20% and 8% of the breast cancer cell lines of the case patients and control subjects, respectively, fell into that category (P < .001). At the same time after irradiation, it was not possible to distinguish between bladder cancer cell lines (7%) and those of the corresponding control group (6%). Assessment of radiation effects by G2/G1 ratio showed that 18% of the breast cancer patients and 8% of the control subjects were in the high range. When G2 arrest was correlated with other prognostic factors, we found that case patients with a greater G2 block were more likely to have had a family history of breast cancer (P < .006) and more aggressive tumors when assessed by number of involved lymph nodes (P < .002) and tumor size (P < .05). Furthermore, an adverse response to radiotherapy was observed in a group of patients with high G2 arrest. IMPLICATIONS: While the postirradiation increase in G2-phase arrest in cells from breast cancer patients observed in this study may indicate genetic heterozygosity for ataxia-telangiectasia, it might also reflect other genetic abnormalities important to breast cancer.

Adult↗
PubMed1994

Iron deficiency anaemia in infants.

AIM: To determine the prevalence of iron deficiency anaemia in infants presenting to their general practitioner in a socially deprived, ethnically mixed suburb. METHODS: A total of 43 infants between 6 and 36 months of age were tested for iron deficiency anaemia. The blood tests were collected opportunistically over a 10 month period. Infants with other than trivial illness were excluded. Parents of infants with evidence of iron deficiency were offered dietary counselling, and infants with iron deficiency anaemia were treated with oral iron therapy. Follow up blood tests for iron deficient infants were performed after approximately three months of treatment with oral iron therapy. RESULTS: 42% (18) of infants tested were Pacific Island, 35% (15) were Maori, 16% (7) were European and 7% (3) belonged to other ethnic groups. 23.2% (10) of those tested had iron deficiency anaemia (haemoglobin less than 110 g/L and mean cell volume less than 70 fL). Six of the 10 were followed up and all six found to have improved haematological indices following oral iron therapy. CONCLUSION: Given the known adverse effects of iron deficiency anaemia in infancy primary health care providers in socially disadvantaged areas should consider screening all infants for iron deficiency anaemia.

Anemia, Hypochromic↗
PubMed1994

Cerebral oxygen saturation, transcranial Doppler ultrasonography and stump pressure in carotid surgery.

Transcranial Doppler ultrasonography (TCD) of the middle cerebral artery (MCA), light-reflective cerebral oximetry and measurement of internal carotid artery stump pressure were compared as methods of monitoring cerebral perfusion during carotid surgery in 33 patients. Median cerebral oxygen saturation was 70 (range 62-85) per cent and TCD-measured mean blood velocity 42 (range 19-91) cm/s before carotid cross-clamping, falling to 68 (53-83) per cent and 16 (0-50) cm/s respectively on application of the clamps (P < 0.001). Stump pressure correlated closely with MCA blood velocity 30 s after the start of cross-clamping (rs = 0.58, P < 0.001), but not with cerebral oxygen saturation. A fall of 5 per cent or more in cerebral oxygen saturation following cross-clamp application was predicted by a decrease in mean MCA blood velocity of at least 60 per cent. Changes in cerebral oxygen saturation correlated significantly with systolic blood pressure throughout the perioperative period (rs = 0.41, P < 0.001). Significant falls in cerebral oxygenation were not predicted by low stump pressure but were associated with large reductions in the mean MCA blood velocity measured by TCD.

Blood Flow Velocity↗
PubMed1994

Light-reflective cerebral oximetry and jugular bulb venous oxygen saturation during carotid endarterectomy.

A novel instrument using reflected near-infra-red light spectroscopy to measure cerebral oxygen saturation non-invasively was evaluated during carotid endarterectomy; cerebral perfusion was compared with jugular bulb venous oxygen saturation and transcranial Doppler ultrasonographic measurements. Initially, oximetry sensors with light source-detector separation distances of 10 and 27 mm were positioned over the frontal area, while a cannula positioned in the jugular bulb permitted sampling for jugular bulb venous oxygen saturation. To increase cerebral oxygen saturation sensitivity, modified sensors with light source-detector separation distances of 30 and 40 mm were relocated over the middle cerebral artery territory. The changes in cerebral and jugular bulb venous oxygen saturation, and in peak blood flow velocity before and 30 s after carotid clamping and declamping were recorded. The modified cerebral perfusion system achieved improved correlations between cerebral and jugular bulb venous oxygen saturation changes during carotid clamping and declamping (r = 0.92, P < 0.001). The correlation between change in cerebral oxygen saturation and the percentage change in peak flow velocity on both cross-clamping and declamping was equally strong (r = 0.90, P < 0.001). Near-infra-red cerebral spectroscopy reliably detects changes in cerebral oxygen saturation during carotid endarterectomy and may have wide applications in monitoring brain perfusion during neurosurgery and cardiopulmonary bypass surgery, and in closed head injury.

Blood Flow Velocity↗
PubMed1994

Comparison of measurement of stump pressure and transcranial measurement of flow velocity in the middle cerebral artery in carotid surgery.

Transcranial Doppler ultrasound measurement of the velocity of blood flow in the middle cerebral artery (MCA) was performed in 24 consecutive patients undergoing carotid endarterectomy. Measurements were performed preoperatively at rest, following common carotid artery compression, and continuously during surgery. In addition, internal carotid artery stump pressures were measured and a subjective assessment of back flow was made. No relationship between MCA flow velocity and stump pressure following carotid clamping was demonstrated. Peak and mean MCA flow velocity was significantly lower in patients with stump pressures < 30 mm Hg (p < 0.03) and those with poor back flow (p < 0.02).

Blood Flow Velocity↗
PubMed1994

Comparative study of radiation-induced G2 phase delay and chromatid damage in families with ataxia-telangiectasia.

Two assay systems, radiation-induced chromosome aberrations and flow cytometry, were compared for the detection of ataxia-telangiectasia (A-T) heterozygotes. In three A-T families, the frequencies of chromatid aberrations in phytohemagglutinin-stimulated blood lymphocytes after 1 Gy of gamma-irradiation were twofold higher in A-T homozygotes than in obligate A-T heterozygotes, which were in turn approximately twofold higher than in normal control cells. Other consanguineous relatives of A-T patients had intermediate levels of induced chromatid aberrations, suggesting that they were carriers of the gene. Matched Epstein-Barr virus-transformed lymphoblastoid cell lines from A-T homozygotes showed a greater radiation-induced accumulation in the G2 phase of the cell cycle than did control cells. In family B, both obligate heterozygotes had increased G2 delay, as did the one heterozygote available for family C, and two of the grandparents in that family were in the high range for G2 delay. Neither parent in family A had high G2 phase delay after irradiation although the induced chromatid aberrations were in the heterozygote valve range. These results show a good concordance between the two assay systems for A-T heterozygotes, with the chromatid aberrations somewhat more consistent.

Adult↗
PubMed1994

MECHANICAL PERFORMANCE OF AN IN SITU PERFUSED HEART FROM THE TURTLE CHRYSEMYS SCRIPTA DURING NORMOXIA AND ANOXIA AT 5 C AND 15 C

We developed an in situ perfused turtle (Chrysemys scripta) heart preparation to study its intrinsic mechanical properties at 5&deg;C and 15&deg;C using normoxic and anoxic perfusion conditions. The in situ preparation proved durable and stable. At 15&deg;C and a spontaneous heart rate of 23.4 beats min-1, maximum stroke volume was 2.54 ml kg-1 body mass, maximum cardiac output was 62.5 ml min-1 kg-1 and maximum cardiac myocardial power output was 1.50 mW g-1 ventricular mass. There was good agreement between these values and those previously obtained in vivo. Furthermore, since the maximum stroke volume observed here was numerically equivalent to that observed in ventilating C. scripta in vivo, it seems likely that C. scripta has little scope to increase stroke volume to a level much beyond that observed in the resting animal through intrinsic mechanisms alone. The ability of the perfused turtle heart to maintain stroke volume when diastolic afterload was raised (homeometric regulation) was relatively poor. At 5&deg;C, the spontaneous heart rate (8.1 beats min-1) was threefold lower and homeometric regulation was impaired, but maximum stroke volume (2.25 ml kg-1) was not significantly reduced compared with the value at 15&deg;C. The significantly lower maximum values for cardiac output (18.9 ml min-1 kg-1) and power output (0.39 mW g-1 ventricular mass) at 5&deg;C were largely related to pronounced negative chronotropy with only a relatively small negative inotropy. Anoxia had weak negative chronotropic effects and marked negative inotropic effects at both temperatures. Negative inotropy affected pressure development to a greater degree than maximum flow and this difference was more pronounced at 5&deg;C than at 15&deg;C. The maximum anoxic cardiac power output value at 15&deg;C (0.77 mW g-1 ventricular mass) was not that different from values previously obtained for the performance of anoxic rainbow trout and hagfish hearts. In view of this, we conclude that the ability of turtles to overwinter under anoxic conditions depends more on their ability to reduce cardiac work to a level that can be supported through glycolysis than on their cardiac glycolytic potential being exceptional.

Journal Article↗
PubMed1994

LOCALIZATION OF ANGIOTENSIN II RESPONSES IN THE TROUT CARDIOVASCULAR SYSTEM

The renin/angiotensin system (RAS) is a tonic anti-drop regulator of arterial blood pressure in many teleosts. In trout, angiotensin II (ANG II) has no direct constrictor effect on large arteries or veins and the identity of specific cardiovascular pressor effectors is unknown. Potential targets of angiotensin activation were examined in the present experiments using perfused organs and isolated tissues from the rainbow trout Oncorhynchus mykiss. Perfused gill (arches 2 and 3), perfused skeletal muscle-kidney (via the dorsal aorta; PDA) and perfused splanchnic (via the celiacomesenteric; PCM) circulations vasoconstrict in response to salmonid ANG II in a dose-dependent manner. ANG II was significantly (P&frac34;0.05) more potent in the PCM than in the PDA, and both preparations were more responsive than the gills: pD2=8.0&plusmn;0.20 (10) for PCM; pD2=7.5&plusmn;0.07 (13) for PDA; pD2=6.9 &plusmn;0.21 (8) for gill arch 3; pD2=6.7&plusmn;0.23 (8) for gill arch 2; mean &plusmn; s.e.m. (N), respectively. Salmonid angiotensin I (ANG I) also produced a dose-dependent constriction of the PDA and PCM. Angiotensin converting enzyme (ACE) activated nearly 100 % of ANG I to ANG II in a single pass through the PDA, whereas PCM conversion was estimated to be less than 10 %. Inhibitors of adrenergic constriction partially prevented ANG II responses in the PDA but did not affect PCM responses. ANG II did not affect paced rings of ventricular muscle in the presence of high or low [Ca2+] or epinephrine concentrations, nor did it have any inotropic or chronotropic effects in the in situ perfused heart. Red blood cell swelling was unaffected by ANG II. Similarly, the effects of ANG II on gut, urinary bladder and gall bladder smooth muscle were negligible or non-existent; thus, an increase in splanchnic resistance due to extravascular compression can be discounted. These results indicate that, in trout, the systemic microcirculation is the major cardiovascular effector of angiotensin-mediated pressor responses. In addition, the RAS has little direct effect on non-vascular smooth muscle or the heart. From an evolutionary perspective, the initial site of direct systemic RAS action appears to be the vascular microcirculation.

Journal Article↗