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Biomedical subjects

K Kirkpatrick

Publications and source records attributed to K Kirkpatrick.

At least 19 recordsLinked to original sources
PubMed2002

Telomerase activity and Bcl-2 expression in human breast cancer.

AIMS: Telomerase is a ribonucleoprotein that synthesizes telomeres and plays an important role in cellular immortalization. Bcl-2 gene encodes for a mitochondrial protein thought to prevent apoptosis of normal cells. We previously reported telomerase activity in 74% of human invasive breast cancers and detected a significant association between telomerase activity and prognostic parameters such as nodal status, tumour size and cellular proliferation. We hypothesized that telomerase reactivation in human breast cancer was associated with increased immunohistochemical expression of Bcl-2. METHODS: Bcl-2 immunohistochemical expression was determined in 25 infiltrating breast carcinomas with known telomerase activity (17 telomerase-positive and 8 telomerase-negative). The percentage of strongly and moderately stained tumour cells for Bcl-2 was determined by a breast pathologist who was blinded to telomerase data. Fisher's exact test was used to examine the association between telomerase activity and Bcl-2 expression. RESULTS: The median percentage of strongly stained tumour cells was 50% for telomerase-positive tumours (range, 0--100%) and 45% for telomerase-negative tumours (range, 0--100%). Twelve (70%) of 17 telomerase-positive tumours expressed strong or moderate Bcl-2 staining in >50% of tumour cells compared with six (75%) of eight telomerase-negative tumours (P=1.0). CONCLUSION: Telomerase reactivation seems to be independent of Bcl-2 protein expression in human breast cancer.

Adult↗
PubMed2002

HER-2/neu expression in germ cell tumours.

AIMS: To determine the rate of HER-2/neu positivity of germ cell tumours by immunohistochemistry (IHC) and by fluorescence in situ hybridisation (FISH). PATIENTS/METHODS: Ninety six archival, paraffin wax embedded pathology specimens were chosen from four groups of germ cell tumours. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the INFORM assay and confirmed with a centromere 17 probe. RESULTS: Twenty two of 96 specimens overexpressed the HER-2/neu protein when measured by IHC. Only three specimens showed HER-2/neu gene amplification by FISH. There was no correlation between the results obtained by IHC and FISH. CONCLUSIONS: The lack of concordance between IHC and FISH makes it unlikely that overexpression of the HER-2/neu protein in germ cell tumours is of prognostic or therapeutic relevance. Because of the low rate of HER-2/neu gene amplification in germ cell tumours, a clinical trial of trastuzumab treatment in patients with germ cell tumours is not warranted.

Gene Expression↗
PubMed2000

Stimulus and temporal cues in classical conditioning.

In 2 experiments, separate groups of rats were given stimulus conditioning, temporal conditioning, untreated control and (in Experiment 2) learned irrelevance control procedures, followed by a compound with both stimulus and temporal cues. Stimulus conditioning consisted of a random 15-s duration conditioned stimulus (CS) followed by food; temporal conditioning consisted of food-food intervals of fixed 90 s (Experiment 1) or fixed 75 + random 15 s (Experiment 2). The stimulus group abruptly increased responding after CS onset, and the temporal group gradually increased responding over the food-food interval. When the food-food interval was fixed 90 s, the temporal cue exerted stronger control in the compound, whereas when the food-food interval was fixed 75 + random 15 s, the stimulus cue exerted stronger control. The strength of conditioning, temporal gradients of responding, and cue competition effects appear to reflect simultaneous timing of multiple intervals.

Animals↗
PubMed1998

Extrinsic modulation of spike afterpotentials in rat hypothalamoneurohypophysial neurons.

1. Magnocellular neurosecretory cells (MNCs) in the rat hypothalamus adopt a phasic pattern of spike discharge under conditions demanding enhanced vasopressin release, such as during dehydration or hemorrhage. The emergence of phasic firing minimizes the occurrence of secretory fatigue from the axon terminals of MNCs, thereby maximizing vasopressin release from the neurohypophysis. 2. Intracellular and whole-cell recordings from hypothalamic slices or explants in vitro have shown that phasic firing is supported by the presence of a plateau potential which arises from the summation of spike depolarizing afterpotentials (DAPs). Modulatory actions of neurotransmitters on the amplitude of the DAP, therefore, represent possible mechanisms by which the expression of phasic firing may be regulated in vivo. 3. Here we review the basis for phasic firing in MNCs of the rat supraoptic nucleus and present recent findings concerning the direct and indirect mechanisms through which selected neurotransmitters have been found to regulate the amplitude of DAPs.

Action Potentials↗
PubMed1996

Activity dependence and functional role of the apamin-sensitive K+ current in rat supraoptic neurones in vitro.

1. Intracellular recordings were obtained from seventy-two magnocellular neurosecretory cells (MNCs) in superfused explants of rat hypothalamus. The current underlying the after-hyperpolarization (IAHP) following spike-evoked trains of action potentials was characterized using the hybrid-clamp technique. The activity-dependent requirements for the genesis of the AHP were determined. The functional role of the conductance was investigated using saturating concentrations (50-300 nM) of apamin, a selective blocker of the AHP in MNCs. 2. IAHP was reversibly abolished by the removal of extracellular Ca2+. The amplitude of IAHP varied linearly as a function of voltage and reversed at -100 +/- 3 mV in 3 mM external K+. Changes in the concentration of extracellular K+ resulted in shifts of the reversal potential consistent with Nernst equation predictions for a K+-selective conductance. 3. Action potentials triggered by brief depolarizing pulses elicited an AHP during trains evoked at frequencies > 1 Hz. Onset of the AHP progressed exponentially, reaching a maximum after the first fifteen to twenty impulses. The steady-state amplitude of the AHP increased logarithmically between 1 and 20 Hz. 4. Switching to voltage clamp during periods of continuous cell activity (firing rate > 4 Hz) confirmed the presence of an apamin-sensitive Ca2(+)-dependent K+ current. 5. Application of apamin produced a threefold increase in the mean firing rate of spontaneously active cells, but was without effect when applied to silent cells (firing rate < 0.5 Hz). 6. Apamin did not affect the ability of MNCs to fire in a phasic manner but caused a dramatic increase in the mean intraburst firing rate. Moreover, inhibition of IAHP by apamin strongly attenuated spike accommodation normally seen at the onset of phasic bursts. 7. While apamin did not enhance the amplitude of depolarizing after-potentials following single spikes, post-train plateau potentials and associated after-discharges were enhanced. 8. The possible consequences of IAHP modulation are discussed in the context of the regulation of firing rate and pattern in MNCs.

Action Potentials↗
PubMed1995

Effects of neurotensin on rat supraoptic nucleus neurones in vitro.

1. The electrophysiological actions of neurotensin on magnocellular neurosecretory cells (MNCs) were examined during intracellular recording from seventy-three supraoptic nucleus neurones in superfused explants of rat hypothalamus. 2. Application of neurotensin tridecapeptide (NT(1-13); 1 nM to 3 microM) caused a membrane depolarization and reversibly attenuated the after-hyperpolarization (AHP) which followed current-evoked spike trains. This effect was accompanied by increased firing frequency during depolarizing current pulses evoked from a fixed potential. 3. The effects of neurotensin could be mimicked by the C-terminal fragment, NT(8-13), but not by the N-terminal fragment, NT(1-8). 4. Depolarizing responses to NT(1-13) or NT(8-13), retained during K+ channel blockade with internal Cs+, were accompanied by increased membrane conductance. Current- and voltage-clamp analyses revealed that neurotensin-evoked depolarizations result partly from the activation of a non-selective cationic conductance reversing near -34 mV. 5. Depolarizing responses to neurotensin were retained in the presence of TTX or in Ca(2+)-free solutions, indicating the involvement of receptors located on the plasma membrane of MNCs themselves. 6. Through these effects endogenously released neurotensin may modulate excitability, activity patterns and secretion from the hypothalamo-neurohypophysial axis.

Animals↗
PubMed1991

Dual role for calcium in the control of spike duration in rat supraoptic neuroendocrine cells.

Magnocellular neurosecretory cells (MNCs) display activity-dependent changes in spike duration to modulate Ca2+ influx both in their somata, and in their axon terminals in the neurohypophysis. This study reveals (i) that Ca2+ influx is required to mediate the expression of spike broadening, and (ii) that internal Ca2+ activates a delayed component of spike repolarization in MNCs of the rat supraoptic nucleus. This mechanism provides a rapid feedback control of spike-mediated Ca2+ influx in these neuroendocrine cells.

Action Potentials↗
PubMed1991

Hospital-based case management for medically fragile infants: program design.

A hospital-based multidisciplinary team is demonstrating services for medically fragile infants which facilitate transition from the hospital to the community and home. The team provides education and counseling for communities and families to overcome barriers to services. With individualized case management, the team facilitates family access to the community services they need in infant health, infant development and family functioning. The team plans the infant's discharge from the hospital and collaborates on the initial Individualized Family Service Plan (IFSP) with the family and local community providers. The initial IFSP details potential outcomes in the areas of infant health, infant development and family functioning for the first year the infant is home. Systematic home visits with the team's nurse or developmental consultant, the family and the local provider continue the education and counseling process during the infant's first year of life. This describes the educational aspect of case management services for medically fragile infants.

Aftercare↗
PubMed1991

Hospital-based case management for medically fragile infants: results of a randomized trial.

A recent federal law has expanded the eligibility for multidisciplinary evaluation and assessment of infants suspected of developmental delay. At the same time, modern neonatal care has increased infant survival. These two developments have created a need for family education regarding the need for health and developmental intervention, as well as counseling to maintain family participation in these services. This study compares the education and counseling services of a hospital-based case management team with the traditional discharge and follow-up services of a neonatal intensive care unit (NICU). Subjects were the 10% most medically severe infants discharged from a neonatal intensive care unit over a 16-month period. Preliminary data suggests a significantly greater number of families accessed community-based, coordinated, comprehensive health and developmental services when they received case management services. The data suggest that hospital professionals generally refer the most medically severe 3% of this group for services under a traditional model. However, the additional 7% referred under the transition model showed greater developmental benefits from the services during the first 6 months of life. These data support current federal initiatives for early intervention services which are family-centered, community-based and coordinated.

Aftercare↗
PubMed1988

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: a possible new mechanism for hypoxia-induced vasodilatation of the rat heart.

In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.

Animals↗
PubMed1988

Direct evidence for concomitant release of noradrenaline, adenosine 5'-triphosphate and neuropeptide Y from sympathetic nerve supplying the guinea-pig vas deferens.

Concomitant release of noradrenaline (NA) (using tritium labelling), adenosine 5'-triphosphate (ATP) (using the luciferin-luciferase firefly technique) and neuropeptide Y (using the enzyme-linked immunosorbant assay) during electrical stimulation of the guinea-pig vas deferens has been demonstrated. In addition it has been shown: (1) that release of NA and ATP is unaffected following selective desensitization of the P2 (ATP)-purinoceptor by alpha, beta-methylene ATP and (2) that total block of contractile responses of the vas deferens to nerve stimulation by a combination of prazosin and alpha, beta-methylene ATP does not reduce the release of NA and ATP. These results are consistent with the hypothesis that NA, ATP and neuropeptide Y are released as co-transmitters or modulators in sympathetic nerves supplying the vas deferens.

Adenosine Triphosphate↗
PubMed1988

Efficacy of perioperative cefamandole with postoperative cephalexin in the primary outpatient treatment of open wounds of the hand.

Eighty-seven patients participated in a prospective, double-blind, clinical study to determine the efficacy of preventive antibiotics in the management of common open traumatic hand wounds ranging in severity from single nail bed injuries with open fractures to moderately contaminated wounds involving tendon, bone, joint, and neurovascular structures. Under current medical practice, these wounds would be treated with antibiotics. Thirty-nine patients received intravenous cefamandole and oral cephalexin and 48 received intravenously and orally administered placebo. With an overall infection rate of 1.1%, there were no infections in the antibiotics group and only one (2.1%) infection in the placebo group. Aerobic cultures from 97 similar wounds were 53.6% positive predebridement and 50.5% positive postdebridement. There was no significant difference in rates of infection or imperfect wound healing between the two groups. The preventive antibiotics administered were not necessary in treating these wounds when accompanied by debridement, irrigation, and rapid primary repair in an operating room environment.

Adolescent↗
PubMed1987

Sympathetic nerve-mediated release of ATP from the guinea-pig vas deferens is unaffected by reserpine.

The release of ATP from the guinea-pig vas deferens was measured using the luciferin-luciferase assay. The effects of reserpine, tetrodotoxin, 6-hydroxydopamine and guanethidine on this efflux were investigated. Reserpine, which produced extensive loss of noradrenaline (NA) (about 99%) and eliminated the second phase of the nerve-mediated contraction, failed to impair either ATP release from the vas deferens or the concomitant 'twitch' contraction; in fact both were increased. Therefore the neurotransmitter mediating the twitch cannot be NA, thus excluding the gamma-receptor hypothesis. Furthermore, since the release of ATP is unaffected by reserpine, it is unlikely that ATP is being released from smooth muscle as a consequence of the post-junctional actions of NA. Tetrodotoxin, 6-hydroxydopamine and guanethidine substantially reduced or abolished the release of ATP and both phases of the nerve-mediated response. To conclude, in the guinea-pig vas deferens, ATP co-released with NA from sympathetic nerves, mediates the twitch phase of the contraction and its underlying electrical events.

Adenosine Triphosphate↗
PubMed1986

Actions of alpha, beta-methylene ATP and 6-hydroxydopamine on sympathetic neurotransmission in the vas deferens of the guinea-pig, rat and mouse: support for cotransmission.

alpha-Adrenoceptor antagonists (prazosin or phentolamine) reduced the contractile response to field stimulation of the isolated vasa deferentia of guinea-pig, rat and mouse. alpha, beta-Methylene ATP (alpha, beta-MeATP) reduced that portion of the contraction which was resistant to alpha-adrenoceptor blockade. alpha, beta-MeATP (1-800 microM) did not affect action potential conduction in the guinea-pig vas deferens nerves, and (up to 10 microM) did not reduce the stimulation-evoked overflow of [3H]-noradrenaline from this tissue. Spontaneous excitatory junction potentials (s.e.j.ps) in the majority of cells of guinea-pig, rat, and mouse vasa were abolished by alpha, beta-MeATP (0.1-10 microM). In a small number of cells s.e.j.ps were resistant to the actions of alpha, beta-MeATP (10 microM). Excitatory junction potentials (e.j.ps) in the majority of cells in vasa of all species studied were abolished by alpha, beta-MeATP (1-10 microM). E.j.ps elicited in some 'resistant' cells demonstrated marked facilitation characteristics. It is concluded that alpha, beta-MeATP inhibits s.e.j.ps and e.j.ps by a postjunctional action. In all species pretreatment of animals with 6-hydroxydopamine produced a marked reduction in noradrenaline (NA) content (as determined by fluorescence histochemistry) and abolished e.j.ps, findings which suggest that e.j.ps originated from sympathetic nerves. The results support the hypothesis that NA and ATP are co-transmitters in the sympathetic nerves of rodent vasa.

Action Potentials↗