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C Kennedy

Publications and source records attributed to C Kennedy.

At least 163 records · Page 9Linked to original sources

Characterization of P2-purinoceptors in the smooth muscle of the rat tail artery: a comparison between contractile and electrophysiological responses.

1. The electrophysiological actions of the P2-purinoceptor agonists, adenosine 5'-triphosphate (ATP), 2-methylthioATP (2-meSATP), alpha, beta-methyleneATP (alpha, beta-meATP) and uridine 5'-triphosphate (UTP) were studied under concentration and voltage-clamp conditions in acutely dissociated rat tail artery smooth muscle cells. For comparison, their actions as vasoconstrictors were studied in intact ring preparations. 2. Rapid application of ATP (100 nM-1 microM) via a U-tube superfusion system activated concentration-dependent inward currents with a latency to onset of less than 3 ms. The inward current decayed by more than 95% during a 2 s application of 300 nM and 1 microM ATP. 3. 2-meSATP (100 mM-1 microM) and alpha, beta-meATP (100 nM-1 microM) also evoked transient inward currents. The agonist order of potency was ATP = 2-meSATP > or = alpha, beta-meATP. UTP (300 nM-1 microM) did not produce a change in the holding current. 4. A second application of ATP (300 nM and 1 microM) 10 min after the first, evoked currents which were one third of the initial amplitude. This decline was dependent upon activation of the P2-purinoceptor. Similar results were seen with 2-meSATP and alpha, beta-meATP (both 300 nM and 1 microM). Cross-desensitization was seen between ATP and 2-meSATP or alpha, beta-meATP. 5. Inward currents evoked by ATP, 2-meSATP and alpha, beta-meATP (all 1 microM) were abolished by the P2-purinoceptor antagonist suramin (100 microM). 6. Alpha, beta-meATP (100 nM-30 micro M), 2-meSATP (3 micro M- 100 micro M), ATP (3 micro M-I mM) and UTP (3 ELM-I mM)produced concentration-dependent contractions of rat tail artery rings. When measured at a level equal to 50% of the maximum response to noradrenaline, the rank order of agonist potency was alpha,beta-meATP>>2-meSATP >UTP >ATP.7. This study shows that the rank order of agonist potency at the P2X-purinoceptor which mediates contractions of the rat isolated tail artery is very different from the potency order for evoking the inward current which initiates the contractions. It is concluded that this difference may be due to the relative absence of breakdown of some of the agonists in the single cell system compared with artery rings.

Adenosine Triphosphate↗

An interstitial deletion of chromosome 7(q35).

We describe a patient with developmental delay, mild dysmorphic features, and monosomy of 7q35. Only one other patient with an interstitial deletion of this band has been previously reported. A review of clinical features of these two children did not show similarities in dysmorphic features. Reports of patients with other 7q interstitial deletions are listed.

Child↗

Increases in local cerebral blood flow associated with somatosensory activation are not mediated by NO.

Effects of inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-NAME) on the increases in local cerebral blood flow (LCBF) produced in the whisker-to-barrel sensory pathway by vibrissal stimulation were studied in conscious rats with the autoradiographic iodo[14C]antipyrine method. Unilateral whisker stroking increased LCBF in the ipsilateral trigeminal spinal and principal sensory nuclei, contralateral ventral posteromedial thalamic nucleus, and contralateral somatosensory barrel cortex. Intravenous L-NAME (30 mg/kg) lowered baseline LCBF without altering the percent increases due to stimulation. Intracisternal infusions of L-NAME in doses about 10 times the molar content of free arginine in brain inhibited brain NO synthesis activity by 88%, but the percent augmentations of LCBF by stimulation remained unchanged. Chronic treatment with L-NAME (50 mg/kg ip twice daily for 4 days) inhibited NO synthase activity in brain by 84% but also failed to reduce the percent increases in LCBF due to stimulation. These results indicate that NO does not mediate the increases in LCBF associated with functional activation.

Amino Acid Oxidoreductases↗

Case management and nursing practice.

Does adopting a case management model alter nursing practice? The authors examine the effect case management has on nurse-client relationships and nurse-colleague relationships and explore how nurses are using case management as a vehicle to achieve professionalism. The article is based on a literature review of case management for community-dwelling elderly residents and interviews with 17 community-based nurses practicing as case managers in Canada.

Canada↗

Non-acute casemix in the Illawarra.

There are problems associated with the use of acute care diagnosis-related groups for prospective payment for rehabilitation medicine services. As a preliminary effort to assist in the development of the National Non-Acute Inpatient Casemix Project, a modified costing study was done in the rehabilitation and geriatrics ward of the Illawarra Regional Hospital; its aim was to assess the validity of the functional independence measure (FIM) and the resource utilization group (RUG) system as predictors of staff time involvement in inpatient rehabilitation services. Data collected on 51 patients over 3 months showed that in a standard Australian rehabilitation unit the costs of staff involvement varied depending on the type of functional impairment and severity of carer burden. The FIM alone was not predictive of rehabilitation costs and the RUG 2 instrument was not comprehensively predictive of cost. The RUG 3 instrument developed in the USA did not allocated weightings appropriate to Australian costs. If, however, functional impairment groups were combined with one of these measures of carer burden, then costs did fall into categories reflective of staff time involvement. An Australian system which incorporates an instrument measuring functional capacity may be useful for resource allocation in rehabilitation care.

Activities of Daily Living↗

Effects of physostigmine on local cerebral glucose utilization in the central components of the rat visual system.

The effects of intravenous administration of physostigmine at doses of 0.03, 0.095, or 0.3 mg/kg on local cerebral glucose utilization (LCGU) were determined in 3 structures of the visual system of the rat brain by means of the quantitative 2-[14C]deoxyglucose method. LCGU was increased in the superior colliculus (superficial gray layer), but unchanged in the visual cortex and the lateral geniculate body. To determine whether the observed effect of physostigmine on the superior colliculus depended on input from the retina, the highest dose of physostigmine was administered to rats which had previously been enucleated bilaterally. Enucleation decreased LCGU in the superior colliculus of the animals not treated with physostigmine and blocked the effect of physostigmine on LCGU. The effect of physostigmine in the superior colliculus appears, therefore, to depend on input from the retina.

Animals↗

The effects of pharmacologic doses of 2-deoxy-D-glucose on local cerebral blood flow in the awake, unrestrained rat.

Previous studies on the effects of acute insulin-induced hypoglycemia on cerebral blood flow (CBF) have resulted in conflicting results. An alternate approach to the study of glucoprivation is the administration of pharmacologic doses of the glucose analogue, 2-deoxy-D-glucose (2-DG). 2-DG is transported across the blood-brain barrier into brain tissue where it is phosphorylated to 2-deoxy-D-glucose-6-phosphate (2-DG-6-P) but not metabolized further. The 2-DG-6-P accumulates and inhibits the conversion of glucose-6-phosphate to fructose-6-phosphate, thus blocking glycolysis and glucose metabolism. In the present study we have employed the [14C]iodoantipyrine method to examine the effects of a pharmacologic dose (500 mg/kg) of 2-DG on local cerebral blood flow (lCBF) in 29 regions of the brain in conscious, unrestrained, adult male rats. The 2-DG treatment raised arterial plasma glucose levels from 8 to 17 mM without affecting arterial blood pO2, pCO2, or pH but increased lCBF in most brain regions examined. The largest increases were in the cerebral cortex, basal ganglia, and thalamic nuclei (+65 to +157%). Smaller increases were found in most structures of the limbic system, brainstem, and white matter, and no changes in lCBF were seen in the cerebellar cortex and ventral medial hypothalamus. The results indicate that cerebral glucoprivation produced by pharmacological doses of 2-deoxyglucose is accompanied by substantial increase in blood flow in most regions of the brain.

Animals↗

Sequence and molecular analysis of the nifL gene of Azotobacter vinelandii.

In both Klebsiella pneumoniae and Azotobacter vinelandii the nifL gene, which encodes a negative regulator of nitrogen fixation, lies immediately upstream of nifA. We have sequenced the A. vinelandii nifL gene and found that it is more homologous in its C-terminal domain to the histidine protein kinases (HPKs) than is K. pneumoniae NifL. In particular A. vinelandii NifL contains a conserved histidine at a position shown to be phosphorylated in other systems. Both NifL proteins are homologous in their N-termini to a part of the Halobacterium halobium bat gene product; Bat is involved in regulation of bacterio-opsin, the expression of which is oxygen sensitive. The same region showed homology to the haem-binding N-terminal domain of the Rhizobium meliloti fixL gene product, an oxygen-sensing protein. Like K. pneumoniae NifL, A. vinelandii NifL is shown here to prevent expression of nif genes in the presence of NH+4 or oxygen. The sequences found homologous in the C-terminal regions of NifL, FixL and Bat might therefore be involved in oxygen binding or sensing. An in-frame deletion mutation in the nifL coding region resulted in loss of repression by NH+4 and the mutant excreted high amounts of ammonia during nitrogen fixation, thus confirming a phenotype reported earlier for an insertion mutation. In addition, nifLA are cotranscribed in A. vinelandii as in K. pneumoniae, but expression from the A. vinelandii promoter requires neither RpoN nor NtrC.

Amino Acid Sequence↗

Muscle glucose uptake during and after exercise is normal in insulin-resistant rats.

It is not generally known whether impaired stimulation of muscle glucose metabolism in insulin-resistant states is specific to insulin stimulation. Our aim was to examine whether glucose uptake responded normally to exercise and postexercise recovery in insulin-resistant high-fat-fed (HFF) rats. Three-week HFF or Chow-fed [control (Con)] adult rats were studied 5 days after cannulation. Before, during, or immediately after (recovery) 50 min of treadmill exercise, bolus 2-deoxy-[3H]glucose and [14C]glucose were administered to estimate muscle glucose uptake (R'g) and glycogen incorporation rates. Mean exercise and recovery plasma glucose levels were similar in HFF and Con rats. In hindlimb muscles sampled, exercise and recovery R'g were similar in HFF and Con (e.g., red quadriceps exercise 104 +/- 13 vs. 113 +/- 8, recovery 45.3 +/- 3.9 vs. 47.7 +/- 4.5 mumol.100 g-1.min-1, respectively). Moreover, muscle glucose transporter (GLUT-4) content was not reduced in HFF rats. Glycogen resynthesis accounted almost entirely for R'g during recovery and was equivalent between groups. We conclude that impaired muscle glucose uptake and glycogen synthesis in HFF rats are characteristic of insulin but not of exercise or postexercise stimulation.

Analysis of Variance↗

Generation and characterization of an anti-idiotypic antibody specific for intercellular adhesion molecule-1.

Intercellular adhesion molecule-1 (ICAM-1) is an inducible ligand for the LFA-1/MAC-1 family of leukocyte adhesion molecules. The results reported herein show that a mouse monoclonal anti-idiotypic antibody, CA3, specific for R6.5 anti-ICAM-1 mAb, shares conformational homology with the original epitope bound by R6.5. The CA3 bound specifically to R6.5 F(ab) fragments and blocked the binding of R6.5 to its ICAM-1 epitope; no CA3 binding was detected to a second anti-ICAM-1 mAb F(ab) fragment nor to control mouse IgG F(ab) fragments. Similarly, the interaction of CA3 with R6.5 was inhibited by sICAM-1. However, CA3 was ineffective in inhibiting CD18-dependent cell aggregation. A rabbit anti-CA3 response (Ab3) further indicated that CA3 is of the Ab2 beta type. Significant binding of anti-CA3 to sICAM-1 was demonstrated and anti-CA3 competed with R6.5 for binding to sICAM-1. Anti-CA3 bound to both soluble and cell-surface-associated ICAM-1. However, unlike R6.5, significant binding both to reduced sICAM-1 and to native sICAM-1 was exhibited by anti-CA3, whereas the binding of R6.5 to reduced sICAM-1 was undetectable.

Animals↗

Light reflection rheography: a simple noninvasive screening test for deep vein thrombosis.

PURPOSE: The clinical diagnosis of deep vein thrombosis (DVT) is unreliable. Contrast phlebography (CP) continues to be the gold standard, but it is invasive. Although duplex ultrasonography is an accurate, noninvasive alternative, it is expensive, technically demanding, and time-consuming. We postulated that light reflection rheography (LRR), a noninvasive method of assessing the quantity and rate of venous emptying, might be a reliable and inexpensive bedside approach to screening patients with clinically suspected DVT. METHODS: With LRR, infrared light is beamed onto the skin, and the amount of backscattered rays are detected, which indirectly measures the amount of blood present in a volume of the epidermis beneath the LRR probe. Applied to the calf muscle pump, LRR can provide a noninvasive method of assessing blood volume changes in the sample area of skin, in response to venous hemodynamic changes in the lower limb. RESULTS: Sixty-nine limbs in 61 patients undergoing CP for clinically suspected DVT over a period of 12 months also underwent LRR, either just before or within 24 hours of undergoing phlebography. The criteria for diagnosing DVT on CP were presence of filling defect or nonfilling of a venous segment. The result of LRR was considered positive for DVT if the rate of venous emptying was 0.35 or less. With these criteria a sensitivity of 96.4% and specificity of 82.9 were obtained. This resulted in a positive predictive value of 79% and a negative predictive value of 97.1%. CONCLUSIONS: LRR is a simple, inexpensive, and noninvasive bedside test that takes 10 minutes to perform. It is highly sensitive with a high negative predictive value, detecting most cases of DVT, reliably ruling out DVT, and eliminating the need for more time-consuming and costly studies. Therefore it seems to be an appropriate screening test in patients with clinically suspected DVT.

Adult↗

Visually guided reaching with the forelimb contralateral to a "blind" hemisphere: a metabolic mapping study in monkeys.

The 2-14C-deoxyglucose method was used to map local cerebral metabolic activity in monkeys performing a unimanual task requiring visually guided arm reaching and key pressing. The study was carried out with monkeys that either had intact brains or had one hemisphere deprived of visual input by unilateral optic tract section combined in some cases with forebrain commissurotomy. The metabolic mapping revealed activation of sensorimotor cortex only in the hemisphere contralateral to the moving forelimb, irrespective of whether this hemisphere was intact or visually deafferented. These results suggest that visually guided reaching with the forelimb contralateral to the "blind" hemisphere is subserved by that hemisphere's sensorimotor cortex and not by the cortex of the ipsilateral, "seeing" hemisphere. Other areas that were more active metabolically in the "blind" than in the "seeing" hemisphere included the supplementary motor, the secondary somatosensory, and certain posterior parietal cortical areas, intraparietal lateral 5 (lateral 5-ip), 7a, and intraparietal 7 (7-ip). It is suggested that the "blind" hemisphere utilizes at least two distinct pieces of information to guide forelimb movements to visual targets: (1) information about the location of the visual target derived from head and eye movements made to this target and mediated via the inferior parietal cortical areas 7a and 7-ip, and (2) information about the instantaneous upper extremity position derived from forelimb proprioceptive mechanisms and mediated via the somatosensory cortex and thereafter via the superior parietal cortical area, lateral 5-ip.

Animals↗

Properties of the nuclear P1 protein, a mammalian homologue of the yeast Mcm3 replication protein.

Polyclonal antibodies were raised against a multiprotein 'holoenzyme' form of calf thymus DNA polymerase alpha-primase and used to probe a human cDNA-protein expression library constructed in the lambda gt11 vector. The probe identified a series of cDNA clones derived from a 3.2 kb mRNA which encodes a novel 105 kDa polypeptide, the P1 protein. In intact cells, the P1 protein was specifically associated with the nucleus, and in cell extracts, it was associated with complex forms of DNA polymerase alpha-primase. The synthesis of human P1-specific mRNA was stimulated upon addition of fresh serum to growth-arrested cells, and RNA blot analyses with the human P1-cDNA probe indicated that P1 is encoded by a strictly conserved mammalian gene. The amino acid sequence deduced from a 240-codon open reading frame resident in the largest human P1-cDNA (0.84 kb) displayed greater than 96% identity with that deduced from the equivalent segment of a 795-codon open reading frame of a larger mouse P1-cDNA (2.8 kb). Throughout its length, the primary structure of mammalian P1 displayed strong homology with that of Mcm3, a 125 kDa yeast protein thought to be involved in the initiation of DNA replication (Gibson et al. 1990. Mol. Cell. Biol. 10: 5707-5720). The P1-Mcm3 homology, the strong conservation of P1 among mammals, its nuclear localization, and its association with the replication-specific DNA polymerase alpha strongly suggest an important role of the P1 protein in the replication of mammalian DNA.

Amino Acid Sequence↗

Sensory testing in human immunodeficiency virus type 1-infected men. HIV Neurobehavioral Research Center Group.

Patients with acquired immunodeficiency syndrome frequently suffer peripheral neuropathy. We investigated its prevalence and relationship to clinical stage of human immunodeficiency virus (HIV) infection using quantitative sensory testing and nerve conduction testing. Vibratory threshold was determined in the right great toe and index finger of 179 men seropositive for HIV (28 with acquired immunodeficiency syndrome [AIDS] or AIDS-related complex [ARC], 151 asymptomatic) and 32 HIV-seronegative controls. None had clinical peripheral neuropathy. Abnormal threshold was control mean plus 2.5 SDs. In the toe, 10 (36%) of 28 subjects with AIDS or ARC had abnormal vibratory thresholds, compared with seven (5%) of 151 asymptomatic seropositive subjects and none of 32 controls. A subgroup of 168 seropositive subjects underwent nerve conduction testing. Abnormality rates were similar, but abnormalities of nerve conduction coincided with quantitative sensory testing abnormalities in only half the cases. Mean (+/-SD) vibratory threshold was significantly greater in subjects with AIDS or ARC (3.00 +/- 0.51 vibratory units) than in asymptomatic subjects (1.56 +/- 0.27 vibratory units) and controls (1.63 +/- 0.54 vibratory units). Finger abnormality rates did not differ, although subjects with AIDS or ARC had greater mean vibratory threshold. Subclinical peripheral neuropathy is thus related to stage of HIV infection and is present by quantitative sensory testing in 36% of patients with AIDS or ARC.

AIDS-Related Complex↗