Search PubMed⌕ Search

Biomedical subjects

G Campbell

Publications and source records attributed to G Campbell.

249 records · Page 14Linked to original sources

Apoptosis occurs in a new model of thermal brain injury.

Apoptosis has been implicated recently as a prominent response of the brain to a variety of insults, such as ischemia and trauma. In this study, we demonstrate that apoptosis is a prominent part of the brain's response to a thermal insult. To examine the brain's response to a thermal insult, a new model of thermal brain injury in the laboratory rat was developed. Water heated to 60 degrees C was passed over an area of thinned calvarium for 1 min. This resulted in an actual brain temperature of 47-48 degrees C. A uniform area of 2,3,5-triphenyl-tetrazolium chloride pallor was demonstrated and pyknotic neurons were seen in the area of injury by hematoxylin-eosin staining. Apoptosis was demonstrated by the characteristic DNA fragmentation seen by agarose gel electrophoresis, ApopTag in situ staining and electron microscopy. The findings of apoptosis were localized to the area of thermal injury and were time dependent, starting 6 h after the insult and peaking approximately 18 h after the insult. This represents one of the first demonstrations that apoptosis occurs in the brain in response to a thermal injury.

Animals↗

Effects of untreated bed nets on the transmission of Plasmodium falciparum, P. vivax and Wuchereria bancrofti in Papua New Guinea.

The impact of untreated bed nets on the transmission of human malaria and filariasis in a village in a hyperendemic area of Papua New Guinea was studied. In anopheline mosquitoes, the Plasmodium falciparum sporozoite antigen positivity rate, filarial infection rates and human blood indices dropped significantly after bed nets were introduced. This reduction in human-vector contact did not affect mosquito density as no significant difference in either landing rates or indoor resting catches was found. The number of bed nets in a house and ownership of dogs were factors significantly associated with a reduction in the number of indoor resting mosquitoes. However, the reduction in the P. falciparum sporozoite antigen rate in mosquitoes was not accompanied by a reduction in either malaria parasite or antibody prevalences or titres against the P. falciparum circumsporozoite protein.

Adolescent↗

Relationships between nitric oxide synthase, vasoactive intestinal peptide and substance P immunoreactivities in neurons of the amphibian intestine.

Nitric oxide synthase (NOS)-containing neurons (localized using NADPH diaphorase histochemistry or NOS immunoreactivity) and vasoactive intestinal peptide-immunoreactive (VIP-IR) neurons were found in the myenteric plexus of the gastrointestinal tract of the amphibian, Bufo marinus. Only limited co-localization of the two substances was observed in nerve cell bodies, about 11% of the NOS-containing neurons were also labelled by VIP-IR and about 37% of VIP-IR nerve cell bodies contained NOS. The relationship between VIP, NOS and SP-IR in nerve fibres in the circular muscle was examined. There was partial co-localization of VIP and NOS, but no co-localization of NOS or VIP with substance P. Of fibres that were immunoreactive for VIP or NOS, fewer than 10% contained VIP alone.

Amino Acid Oxidoreductases↗

Projections of nitric oxide synthase- and peptide-containing neurons in the small and large intestines of the toad (Bufo marinus).

The projections of galanin (GAL)- and vasoactive intestinal peptide (VIP)-immunoreactive (IR) and nitric oxide synthase (NOS)-containing neurons in the small and large intestines of the amphibian Bufo marinus were investigated by their reactions to surgical interruption (myotomy). In the small intestine, myotomy caused accumulation of GAL- and VIP-IR and of NADPH diaphorase reaction product (revealing NOS) in cut axons on the oral side of the operation site. On the anal side there was loss of GAL-IR axons from the circular muscle and myenteric plexus and long, anally directed processes could be traced from GAL-IR nerve cell bodies. There was no significant loss of VIP-IR or NADPH diaphorase from nerve fibres in the myenteric plexus or circular muscle layer, although anally-directed axons could be traced from nerve cell bodies on the anal side of the operation sites. In the large intestine, myotomy caused accumulation of VIP-IR and of NADPH diaphorase reaction product in cut axons on the oral side of the operation site. Anal to the cut, although there was no significant loss of these fibres from the muscle or myenteric plexus, anally directed axons could be traced from nerve cell bodies. GAL-IR fibres in the large intestine are of two types: a few contain GAL-IR alone and are thought to arise from enteric neurons; many contain both GAL- and SOM-IR and are thought to arise from nerve cell bodies in the hindgut. Myotomy caused an accumulation of GAL/SOM-IR material in fibres on the anal side of the cut and a substantial decrease in the number of fibres on the oral side. There was no detectable effect of myotomy on the GAL-IR fibres, although an abnormally high density of GAL-IR nerve cell bodies was found oral to the cut. These results indicate that VIP-IR and NOS-containing enteric neurons project in an oral to anal direction in the toad small and large intestines. Some of the neurons have short anal projections to the circular muscle. GAL-IR enteric neurons have similar projections in the small intestine, but their projections could not be determined in the large intestine. GAL/SOM-IR axons in the large intestine project from anal to oral. Myotomy in the large intestine appears to induce an increased or de novo expression of GAL-IR in enteric neurons oral to the cut.

Amino Acid Oxidoreductases↗

Attenuation of isoproterenol-mediated myocardial injury in rat by an inhibitor of polyamine synthesis.

OBJECTIVE: Ornithine decarboxylase (ODC) is an initial rate-limiting enzyme in the synthesis of polyamines (putrescine, spermidine, and spermine) that play a role in cell growth and differentiation. Recent studies have shown that spermidine and spermine cause injury to a variety of cells including myocytes in vitro. In this investigation, we used alpha-difluoromethylornithine (DFMO), a specific and irreversible inhibitor of ODC activity and polyamine synthesis to test the hypothesis that polyamines contribute to myocardial injury in rat. METHODS: Male Sprague Dawley rats were treated with (i) saline (0.2 ml/day, s.c.), (ii) isoproterenol (ISO) (5 mg/kg/day for 8 days, s.c.) to produce necrotizing myocardial injury, or with (iii) DFMO + ISO. DFMO was started 2 days before the initiation of ISO and both ISO and DFMO were continued until the end of the experimental period. Myocardial injury was assessed by determining the increased release of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) into the plasma, and by morphometric analysis of the lesion area in heart sections stained with Gomori trichrome. RESULTS: ISO induced the release of CPK and LDH by 6 hr and 24 hr, respectively, and produced subendocardial necrosis, which was both acute and resolving following 8 days of ISO. DFMO treatment inhibited ISO-induced increases in (i) ODC activity and putrescine and spermidine levels in heart, (ii) CPK and LDH activity in plasma, and (iii) the area of subendocardial lesions. CONCLUSIONS: These observations suggest that polyamines are one of the intracellular factors that contribute to ISO-mediated cardiac injury in the rat.

Adrenergic beta-Agonists↗

Dendritic development of retinal ganglion cells after prenatal intracranial infusion of tetrodotoxin.

The dendritic form of a cell may be established by many factors both intrinsic and environmental. Blockade of action potentials along the course of axons and in their postsynaptic targets dramatically alters the development of axonal morphology. The extent to which blockade of target cell activity retrogradely alters the dendritic morphology of the presynaptic cells is unknown. To determine whether the establishment of dendritic form by developing retinal ganglion cells depends on activity within their targets, the sodium channel blocker, tetrodotoxin (TTX), was administered via minipumps to the diencephalon of cat fetuses from embryonic day 43 (E43) to E57. At E57 retinae were removed and living retinal ganglion cells injected in vitro with Lucifer yellow to reveal their dendritic morphology. In the TTX-treated animals both alpha and beta types of retinal ganglion cells were present, as were putative gamma cells. Overall, the dendrites of retinal ganglion cells in TTX-treated animals appeared qualitatively and quantitatively similar to those of untreated animals. The only significant change in the TTX-treated cases was a small increase in the number of dendritic spines on the non-beta cells. These results indicate that the acquisition of basic dendritic form of developing ganglion cells is not influenced by the action potential activity within their targets, and that it is also independent of the terminal branching patterns of their axons.

Action Potentials↗

Global cerebral glucose utilization is independent of brain size: a PET Study.

Cerebral glucose metabolic rates were measured in 80 normal volunteers by studying the uptake of [18F]deoxyglucose with positron emission tomography (PET), using three PET scanners. A brain size index was determined from the PET images using either length-width or area measurements of the brain at a standard level. There was a significant negative correlation between glucose metabolism per unit volume and brain size that was well described by an inverse functional relationship, implying that the total glucose consumption of the brain is approximately constant. Analyses of men versus women revealed no sex differences in total brain glucose consumption, although there were differences in brain size and in glucose metabolism per unit volume. Similarly there was no significant correlation of total brain glucose consumption with age. The variation with brain size accounted for 46% of the logarithmic intersubject metabolic variance. When comparing global metabolic rates in different subjects, multiplying the rates by a brain size index has the dual advantage of correcting for differences related to brain size and correcting for differences in cerebrospinal fluid volume.

Adolescent↗

Percutaneous nephrolithotomy in the dog. An experimental study.

Percutaneous nephrostomies (PN) were created with teflon fascial dilators under fluoroscopic guidance, to implant stones bilaterally into the renal pelves of five dogs weighing 7 to 35 kg. Between one and seven stones of 0.25 to 1.00 cm diameter were implanted into each renal pelvis. Two to 4 weeks later, PN tracts were recreated, and the implanted renal stones were successfully removed under fluoroscopic and endoscopic visualization. Results of gross and histopathologic evaluation of the kidneys 2, 7, 14, 30, and 90 days after stone removal showed minimal, localized renal parenchymal trauma. Complications, although infrequent, included proximal ureteral tears and hemorrhage. Difficulty was encountered in maneuvering equipment around large or numerous stones. Canine percutaneous nephrolithotomy was successful despite great variation in kidney size, as well as variations in the number, size, and shape of stones in the upper urinary tract.

Animals↗

Serotonin stimulates protein tyrosyl phosphorylation and vascular contraction via tyrosine kinase.

Serotonin (5-HT, 5-hydroxytryptamine) is a mitogen in vascular smooth muscle and vascular reactivity to 5-HT is significantly enhanced in hypertension and atherosclerosis. We have tested the hypothesis that tyrosine kinases, enzymes important for mitogenesis, may play a role in 5-HT-induced vascular smooth muscle contractility. Helical strips of rat carotid artery and aorta denuded of endothelium were mounted in tissue baths for measurement of contractile force. The tyrosine kinase inhibitor genistein (5 x 10(-6) M) decreased the potency of 5-HT approximately 4-fold and reduced maximal contraction to 5-HT in carotid arterial strips denuded of endothelium (58% control). Genistein's inactive congener daidzein (5 x 10(-6) M) did not reduce maximal contraction to 5-HT in carotid arteries but did shift the 5-HT concentration response curve 3-fold to the right. Tyrphostin 23 (5 x 10(-5) M), another tyrosine kinase inhibitor, decreased the potency of 5-HT 4-fold and reduced the maximal contraction to 5-HT in the carotid artery (10% control). Contractions induced by phorbol-12,13-dibutyrate (10(-9) to 10(-5) M) were not reduced or shifted by either tyrosine kinase inhibitor, indicating that phorbolester-sensitive protein kinase C isoforms were not affected. KCl-induced contraction was shifted 2-fold and the maximum significantly inhibited by tyrphostin 23 (38.6% control) but not genistein or daidzein, indicating that tyrphostin 23 but not genistein may inhibit voltage-gated calcium channels to reduce contractility. Western blot analysis using antiphosphotyrosine antibody confirmed that 5-HT produced a time- and concentration-dependent increase in the phosphotyrosine immunoreactivity of a 42-kD protein in cultured aortic smooth muscle cells. Lysate immunoprecipitation with an antimitogen-activated-protein (MAP)-kinase antibody indicated that the 42-kD protein was most likely a MAP kinase. 5-HT (10(-5) M) stimulated contraction and increased antiphosphotyrosine immunoreactivity in whole aorta mounted in tissue baths. Importantly, aortic contraction to 5-HT was shifted (5-fold rightward) and reduced (69% control) by genistein but not daidzein. These findings demonstrate that (1) tyrosine kinase activation may partially mediate contractility to 5-HT in arterial smooth muscle, (2) tyrphostin 23 is somewhat nonselective and (3) 5-HT stimulates tyrosine kinase as documented by increased tyrosyl phosphorylation of proteins in cultured aortic smooth muscle cells and aortic tissue in active contraction of 5-HT. These findings have significant implications not only in understanding a novel pathway of 5-HT signal transduction but also in vascular diseases in which growth and/or contractility to 5-HT is increased (e.g. hypertension, atherosclerosis).

Animals↗

Posterior shoulder laxity in asymptomatic athletes.

We evaluated the frequency of posterior subluxations on physical examination of athletes who had no symptoms of shoulder injuries and correlated the findings with other measures of joint laxity. During routine sports physical examinations, 356 shoulders in 178 athletes were examined for posterior subluxation and graded as either positive or negative for subluxation. Sulcus signs were performed and graded as I (< 1.0 cm), II (1.0 to 1.5 cm), or III (> 1.5 cm). Standard hyperlaxity tests of other joints were used to measure general ligamentous laxity. Statistical analysis included the Student's t-test and chi-square analysis (P < 0.05). Overall, 55% of the shoulders could be subluxated posteriorly. More female shoulders (65%) than male shoulders (51%) could be subluxated posteriorly. Ten percent of the athletes had asymmetrical posterior shoulder laxity. Men had statistically significant less inferior translation (sulcus signs of grade I, 49%; grade II, 46%; grade III, 3%) than women (grade I, 36%; grade II, 54%; grade III, 9%). Five percent of the shoulders had posterior subluxation and a grade III sulcus sign. Asymptomatic posterior subluxation present at physical examination may represent normal laxity and may not indicate pathologic instability.

Adolescent↗

Measurement systems in physical therapy.

Many physical therapists lack an understanding of the prociples and applications of objective measurement methods in the clinical environment. This paper presents a working definition of the parameters of motor performance (analyzed in terms of outcome or process) as well as an explanation of measurement systems, particularly those related to measurements of position and motion (goniometers and photography), force (dynamometers and force gauges), and muscle activity (electromyography).

Documentation↗

An optimal mounting frame to reduce flexural stresses of bioprosthetic heart valves.

Recent studies suggest that sharp bending of valve leaflets during the opening phase may be the reason for much of the mechanical failure of bovine pericardial bioprostheses. Sharp bending of the valve leaflets is promoted by the rigid, non expanding stents upon which the leaflets are mounted. We hypothesized that sharp bends and the associated flexural stresses could be significantly reduced by incorporating a stent that expands with the recipient aorta during systolic valve opening. We therefore modeled the opening and closing sequence of a trileaflet bovine pericardial valve with such an expanding supporting stent using our own finite element analysis software. Six different degrees of expansion were simulated, ranging from 2% to 25% expansion measured at the level of the stent post tips. Our results show that a 15% expansion is optimal, for the analyzed valve, because it eliminates the compressive flexural stresses at the commissures. Expansions below 15% were not sufficient to reduce flexural stresses, whereas expansions greater than 20% induced excessive tension in the valve cusps.

Animals↗

Multiple sclerosis lesions: relationship between MR enhancement pattern and magnetization transfer effect.

PURPOSE: To investigate the relationship between the enhancement pattern of a multiple sclerosis lesion and its magnetization transfer effect. METHODS: Fifty-four lesions were chosen from 29 patients with multiple sclerosis on the basis of enhancement pattern on contrast-enhanced T1-weighted MR images. They included 14 homogeneously enhancing lesions, 26 nonenhancing lesions, and 14 ring-enhancing lesions. Magnetization transfer ratios of the homogeneously enhancing lesions, nonenhancing lesions, and central portion of the ring-enhancing lesions were measured. Means were calculated and compared. RESULTS: The magnetization transfer ratios for homogeneously enhancing lesions were higher (mean, 32.2%; SD, 3.4%) than those for nonenhancing lesions (mean 29.4%; SD, 4.3%) and for the central portion of ring-enhancing lesions (mean, 24.5%; SD, 4.0%). Significant differences were found between the ring-enhancing lesions and the homogeneously enhancing lesions and between the ring-enhancing lesions and the nonenhancing lesions. CONCLUSION: We found a relationship between decreased magnetization transfer ratios and those enhancement patterns in which myelin is known to be decreased histopathologically. Thus, use of the magnetization transfer technique may increase the specificity of MR imaging in assessing the extent of residual myelination in multiple sclerosis lesions.

Blood-Brain Barrier↗

Reproducibility of proton MR spectroscopic imaging findings.

PURPOSE: To study the intraindividual, interindividual, and intraregional reproducibility of multisection proton MR spectroscopic imaging in healthy adults. METHODS: Six subjects were studied three times with proton MR spectroscopic imaging. Multisection long-echo-time proton MR spectroscopic imaging permits simultaneous acquisition of N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine plus phosphocreatine (Cr) signal intensities from four 15-mm-thick sections divided into 0.84-mL single-volume elements. Regions of interest were the frontal cortex, the occipital cortex, the parietal cortex, the insular cortex, the cingulate gyrus, the centrum semiovale, the thalamus, and the caudate. Statistical evaluation was performed by analyses of variance and components of variance method. RESULTS: The ratio NAA/Cr showed the lowest overall coefficient of variation (CV, %) in most of the regions of interest (range, 8.9 to 26.1). Interregional differences in the overall CV were present. Interindividual CVs ranged from 4.2 to 8.7 for NAA/Cr, from 6.8 to 17.4 for NAA/Cho, and from 5.0 to 13.6 for Cho/Cr. Intraindividual CVs ranged from 8.2 to 22.2 for NAA/Cr, from 12.8 to 25.8 for NAA/Cho, and from 4.5 to 21.0 for Cho/Cr. Intraregional CVs ranged from 12.3 to 21.2 for NAA/Cr, from 13.0 to 20.4 for NAA/Cho, and from 12.2 to 18.9 for Cho/Cr. CONCLUSIONS: Proton MR spectroscopic imaging showed good overall reproducibility. The finding of interregional variations of CV indicates that care is needed when using this imaging technique for follow-up studies.

Adult↗