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Biomedical subjects

J Grayson

Publications and source records attributed to J Grayson.

At least 19 recordsLinked to original sources
PubMed2002

Attitudes of suburban Western Australians to proposed cat control legislation.

OBJECTIVE: To determine the knowledge, attitudes and practices of cat-owners and non-owners in suburban Perth, Western Australia, on issues relating to proposed local government regulation of cat-ownership. DESIGN: The 1,261 respondents to a mailed survey were ranked on issues regarding restrictions on cat-ownership and cat roaming (control scale), attitudes to wildlife in suburbia and putative impacts of cats on wildlife (wildlife scale), knowledge of cat behaviour and husbandry (knowledge scale) and attitudes and practices regarding cat sterilisation (sterilisation scale). Age, gender and cat-ownership status of the survey respondents were explored to see if any of these factors influenced the position of respondents on the scales. RESULTS: Cat-owners, particularly female owners, scored significantly higher on the knowledge scale than non-owners, whilst non-owners scored significantly higher than cat-owners on the control and wildlife scales. Women were more likely to favour compulsory sterilisation of pet cats than men, but men were more willing to implement controls on cat-ownership. Age was also a significant factor, with older people more willing to implement controls. Analysis of specific questions showed that both cat-owners and non-owners agreed that there was a need for cat control legislation and supported measures such as compulsory sterilisation, registering of cats, restricting cats' ability to roam and stipulating a maximum number of cats per property. Nevertheless, both groups rejected the idea that local governments should enforce cat-free zones. CONCLUSION: Cat legislation that avoids or educates about the contentious issue of cat-free zones should receive solid community support.

Adolescent↗
PubMed2000

Respiration and heart rate at the surface between dives in northern elephant seals.

All underwater activities of diving mammals are constrained by the need for surface gas exchange. Our aim was to measure respiratory rate (fb) and heart rate (fh) at the surface between dives in free-ranging northern elephant seals Mirounga angustirostris. We recorded fb and fh acoustically in six translocated juveniles, 1.8-2. 4 years old, and three migrating adult males from the rookery at Año Nuevo, California, USA. To each seal, we attached a diving instrument to record the diving pattern, a satellite tag to track movements and location, a digital audio tape recorder or acoustic datalogger with an external hydrophone to record the sounds of respiration and fh at the surface, and a VHF transmitter to facilitate recovery. During surface intervals averaging 2.2+/-0.4 min, adult males breathed a mean of 32.7+/-5.4 times at a rate of 15. 3+/-1.8 breaths min(-)(1) (means +/- s.d., N=57). Mean fh at the surface was 84+/-3 beats min(-)(1). The fb of juveniles was 26 % faster than that of adult males, averaging 19.2+/-2.2 breaths min(-)(1) for a mean total of 41.2+/-5.0 breaths during surface intervals lasting 2.6+/-0.31 min. Mean fh at the surface was 106+/-3 beats min(-)(1). fb and fh did not change significantly over the course of surface intervals. Surface fb and fh were not clearly associated with levels of exertion, such as rapid horizontal transit or apparent foraging, or with measures of immediately previous or subsequent diving performance, such as diving duration, diving depth or swimming speed. Together, surface respiration rate and the duration of the preceding dive were significant predictors of surface interval duration. This implies that elephant seals minimize surface time spent loading oxygen depending on rates of oxygen uptake and previous depletion of stores.

Animals↗
PubMed1998

Collaborative interactions between MEF-2 and Sp1 in muscle-specific gene regulation.

Previous investigations have demonstrated synergistic interactions in vivo between CCAC and A/T-rich nucleotide sequence motifs as functional components of muscle-specific transcriptional enhancers. Using CCAC and A/T-rich elements from the myoglobin and muscle creatine kinase (MCK) gene enhancers, Sp1 and myocyte-specific enhancer factor-2 (MEF-2) were identified as cognate binding proteins that recognize these sites. Physical interactions between Sp1 and MEF-2 were demonstrated by immunological detection of both proteins in DNA binding complexes formed in vitro by nuclear extracts in the presence of only the A/T sequence motif, by coprecipitation of recombinant MEF-2 in the presence of a glutathione-S-transferase-Sp1 fusion protein bound to glutathione beads, and by a two-hybrid assay in Saccharomyces cerevisiae. The interaction with Sp1 in vitro and in vivo is specific for MEF-2 and was not observed with serum response factor, a related MADS domain protein. Forced expression of Sp1 and MEF-2 in insect cells otherwise lacking these factors promotes synergistic transcriptional activation of a promoter containing binding sites for both proteins. These data expand the repertoire of functional and physical interactions between lineage-restricted (MEF-2) and ubiquitous (Sp1) transcription factors that may be important for myogenic differentiation.

Animals↗
PubMed1997

Peroxynitrite inhibits leukocyte-endothelial cell interactions and protects against ischemia-reperfusion injury in rats.

Peroxynitrite (ONOO-) anion, formed by the interaction of superoxide with nitric oxide (NO), has previously been implicated as a cytotoxic agent. However, the effects of this free radical species on neutrophil (PMN)-endothelial cell interactions is largely unknown. We investigated the direct actions of ONOO- on PMN adhesion to endothelial cells in vitro and in vivo, as well as the effects of ONOO- on PMN-mediated myocardial ischemia-reperfusion injury. In vitro, peroxynitrite (100-1,000 nM) inhibited the adhesion of rat PMNs to the endothelium of isolated thrombin- or H2O2-stimulated rat mesenteric artery (P < 0.01 vs. thrombin or H2O2 alone). In vivo, in the rat mesentery, thrombin (0.5 U/ml) or N(G)-nitro-L-arginine-methyl ester (50 microM) significantly increased venular leukocyte rolling and adherence, which were also significantly (P < 0.01) attenuated by ONOO (800 nM) accompanied by reduced P-selectin expression on the endothelial cell surface. Isolated perfused rat hearts were subjected to global ischemia and reperfusion with rat PMNs (10(8) cells), which resulted in profound cardiac depression (i.e., a marked reduction in left ventricular developed pressure and maximal rate of development of left ventricular pressure). Infusion of ONOO- reversed the myocardial contractile dysfunction of ischemic-reperfused rat hearts to near baseline levels, and markedly attenuated the accumulation of PMNs in the postischemic heart. The present study provides strong evidence that nanomolar concentrations of ONOO- both inhibit leukocyte-endothelial cell interactions and exert cytoprotective effects in myocardial ischemia-reperfusion injury. Furthermore, our results suggest that the inhibition of P-selectin expression by peroxynitrite is a key mechanism of the modulatory actions of ONOO- on leukocyte-endothelial cell interactions.

Animals↗
PubMed1996

Postnatal development and plasticity of specialized muscle fiber characteristics in the hindlimb.

Recent progress in defining molecular components of pathways controlling early stages of myogenesis has been substantial, but regulatory factors that govern the striking functional specialization of adult skeletal muscle fibers in vertebrate organisms have not yet been identified. A more detailed understanding of the temporal and spatial patterns by which specialized fiber characteristics arise may provide clues to the identity of the relevant regulatory factors. In this study, we used immunohistochemical, in situ hybridization, and Northern blot analyses to examine the time course and spatial characteristics of expression of myoglobin protein and mRNA during development of the distal hindlimb in the mouse. In adult animals, myoglobin is expressed selectively in oxidative, mitochondria-rich, fatigue-resistant myofibers, and it provides a convenient marker for this particular subset of specialized fibers. We observed only minimal expression of myoglobin in the hindlimb prior to the second day after birth, but a rapid and large (50-fold) induction of this gene in the ensuing neonatal period. Myoglobin expression was limited, however, to fibers located centrally within the limb which coexpress myosin isoforms characteristic of type I, IIA, and IIX fibers. This induction of myoglobin expression within the early postnatal period was accompanied by increased expression of nuclear genes encoding mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial proteins, and exhibited a time course similar to the upregulation of myoglobin and mitochondrial protein expression that can be induced in adult muscle fibers by continuous motor nerve stimulation. This comparison suggests that progressive locomotor activity of neonatal animals may provide signals which trigger the development of the specialized features of oxidative, fatigue-resistant skeletal muscle fibers.

Animals↗
PubMed1995

Synergistic interactions between heterologous upstream activation elements and specific TATA sequences in a muscle-specific promoter.

Previous investigations have defined three upstream activation elements--CCAC, A/T, and TATA sequences--necessary for muscle-specific transcription of the myoglobin gene. In the present study, we demonstrate that these three sequences elements, prepared as synthetic oligonucleotide cassettes, function synergistically to constitute a cell-type-specific transcription unit. Previously, cognate binding factors that recognize the CCAC and TATA elements were identified. In this study we determine that the A/T element binds two nuclear factors, including myocyte enhancer factor-2 (MEF-2) and an apparently unknown factor we provisionally termed ATF35 (A/T-binding factor, 35 kDa). Mutations that alter in vitro binding of either MEF-2 or ATF35 to this site diminish promoter function in vivo. Functional synergism between factors binding the CCAC and A/T elements is sensitive to subtle mutations in the TATA sequence, recapitulating the unusual preference for specific TATA variants exhibited by the native myoglobin promoter. These results provide new insights into mechanisms that underlie the distinctive pattern of myoglobin gene regulation in mammalian muscle development and lay a foundation for further studies to elucidate general principles of transcriptional control of complex mammalian promoters through combinatorial actions of heterologous transcriptional factors.

Animals↗
PubMed1994

The significance of blood levels of IgM, IgA, IgG and IgG subclasses in Sudanese visceral leishmaniasis patients.

We developed an ELISA test using leishmania antigenic extracts to detect antigen-specific antibody responses, including subclass and isotype analysis, in visceral leishmaniasis (VL) patients from the Sudan. A total of 92 parasitologically proven patients were compared with cutaneous leishmaniasis, schistosomiasis, malaria, onchocerciasis and tuberculosis patients, as well as with healthy endemic and non-endemic controls. Some VL patients were examined before and after chemotherapy. VL patients showed significantly higher IgG responses compared with all other groups (93.4% sensitivity, 93.7% specificity), and higher (but not significantly) IgM responses. All groups showed low IgA levels. All IgG subclasses, IgG1, 2, 3, and 4, showed higher levels in patients than all other groups, with IgG1 and IgG3 levels being significantly reduced following treatment. The rank order for specificity and sensitivity for IgG subclasses was IgG3 > IgG1 > IgG2 > IgG4.

Adolescent↗
PubMed1993

Sequence elements required for transcriptional activity of the human myoglobin promoter in intact myocardium.

To define sequence elements required for myoglobin gene transcription in the intact heart, we examined the expression of a reporter gene under the control of a 380-bp upstream segment (-373 to +7) from the human myoglobin gene in transgenic mouse embryos and after gene transfer into left ventricular myocardium of adult rats. This proximal upstream region was sufficient to direct expression of luciferase selectively in cardiac and skeletal muscle of mouse embryos and to recapitulate the pattern of expression of the endogenous mouse myoglobin gene. This same upstream region was transcriptionally active after injection of plasmid DNA into the left ventricular wall of adult rats. Point mutations within two evolutionarily conserved sequence elements--a cytosine-rich (CCAC-box) motif and an A+T-rich (A/T) motif--severely impaired transcription within the intact heart. Nuclear extracts from neonatal cardiomyocytes contain protein factors that bind to each of these elements in a sequence-specific manner. We conclude that combinatorial interactions between the cognate DNA binding factors that recognize these motifs are necessary for transcriptional activity of the myoglobin upstream region in cardiac muscle.

Animals↗
PubMed1992

Rhabdomyosarcoma. A new classification scheme related to prognosis.

We classified 159 cases of rhabdomyosarcoma (RMS) according to the conventional scheme adopted by the World Health Organization and a modified conventional scheme established at the National Cancer Institute (NCI), Bethesda, Md. The major modification in the NCI scheme was the inclusion of compact round-cell RMS with scant myogenesis in the group of alveolar RMS despite lack of an alveolar architecture. These tumors were previously considered to be embryonal RMS, but their cytologic features are quite different from those seen in embryonal RMS and are indistinguishable from those encountered in alveolar RMS. These tumors are referred to as "solid alveolar RMS." Survival curves were constructed with the method of Kaplan-Meier and compared with the unstratified and stratified methods of Mantel-Haenszel (with stratification factors being stage, site, and age) and with the Cox regression analysis. Both histologic schemes showed a statistically significant prognostic value in unstratified analyses, but the NCI scheme demonstrated prognostic value even in stratified analyses and in the Cox regression analysis in our series of cases. The data indicate that the NCI scheme can serve as a highly predictive, independent prognostic factor in RMS and that the alveolar category should be expanded to include the solid round-cell RMS, even in the absence of a classic alveolar architecture.

Adolescent↗
PubMed1990

Primary malignant extragonadal germ cell tumors. An analysis of the effect of the effect of radiotherapy.

A retrospective analysis was performed on all patients diagnosed with biopsy-proven extragonadal germ cell tumors at the University of Virginia (Charlottesville, VA), The Medical University of South Carolina (Charleston, SC), the Bethesda Naval Hospital (Bethesda, MD), and The Medical College of Virginia (Richmond, VA) for the time period of January 1965 to December 1984. A total of 54 patients were treated with the initial sites of presentation observed: mediastinum, 26; central nervous system, 14; retroperitoneum, eight; and sacrococcygeal region, six. Megavoltage irradiation was used in 44 patients with a dose range of 2400 to 5580 cGy (mean, 4213 cGy). With a minimum follow-up of 4.0 years and a mean follow-up of 10.8 years, the 5-year actuarial survival for the entire population was 57.8%. Local control was achieved in 26 of 44 (59%) of the irradiated population. Factors of prognostic significance included histologic type at presentation, site of presentation, and radiation doses greater than or equal to 4000 cGy. Radiotherapy appears to be an effective modality in patients with extragonadal seminomas; however, the nonseminomatous tumors do not appear to be as radioresponsive.

Adolescent↗
PubMed1990

Neurologic, computed cranial tomographic, and magnetic resonance imaging abnormalities in patients with small-cell lung cancer: further follow-up of 6- to 13-year survivors.

To determine the subsequent evolution of neurologic, neuropsychologic, and intracranial anatomic findings in long-term survivors of small-cell cancer, we repeated an evaluation done 4 years previously in patients 6 to 13 years after treatment. Fifteen patients were reevaluated with a history and physical examination, mental status examination, neuropsychologic testing, computed cranial tomographic (CCT) scans, and magnetic resonance imaging (MRI). All but one was ambulatory and none were institutionalized. Thirteen of 15 had neurologic complaints, 10 of 15 had an abnormal neurologic examination, seven of 14 had an abnormal mental status examination, 12 of 14 had abnormal neuropsychologic testing, 12 of 15 had abnormal CCT scans, and seven of 15 had white-matter abnormalities on MRI scans. No dramatic decline in performance status, functional status, neurologic symptoms, or neurologic examination occurred in these patients with 4 years of additional follow-up. More patients showed a decline in mental status examinations and neuropsychologic testing than demonstrated improvement. Anatomic studies showed no dramatic changes in the CCT scans and MRI confirmed these findings. From these data we conclude that there is a slow decline in neuropsychologic function in some of the patients surviving more than 6 years from a diagnosis of small-cell lung cancer. The anatomic abnormalities documented by CCT scans and MRI are more frequent in patients with abnormal neuropsychologic function.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation.

We evaluated the 10- to 15-year outcome of 252 patients with small-cell lung cancer entered into therapeutic clinical trials with or without chest and cranial irradiation. Thirty-two patients (13%) survived free of cancer for 2 or more years. Twelve patients (5%) survived at least 10 years free of cancer, and 10 patients are currently alive and free of cancer beyond 10 years. Six of these 10 patients currently function at a level comparable with that before diagnosis. The other 22 patients who were cancer-free at 2 years have died. Nine patients died from recurrent small-cell lung cancer 2 to 6.2 years after initiation of chemotherapy. Five died from non-small-cell lung cancer, three died of other malignancies, and five died of causes other than cancer. A small fraction of patients with small-cell lung cancer are cured of their original malignancy, but these patients remain at high risk for second cancers and death from other causes.

Actuarial Analysis↗
PubMed1987

Right hemicolectomy and ileal resection with primary reanastomosis for irradiation injury of the terminal ileum.

Injury to the small intestine from pelvic irradiation increases in frequency when extended treatment fields are utilized and when radiation therapy follows a major abdominal operation. Recommended surgical correction of such injury has been intestinal bypass to avoid the excessive morbidity and mortality from anastamotic leaks associated with primary resection and anastomosis. Since 1980, eight patients with extensive ileal injury secondary to irradiation have been seen at the Naval Hospital Bethesda, Maryland. All patients had previously undergone an abdominal operation and three patients had irradiation utilizing extended fields. In all cases, right hemicolectomy and extended ileal resection were performed with primary anastamosis of the ileum to the ascending colon or the transverse colon. Operating time averaged 4 1/2 hr utilizing hand closure anastomoses and 2 1/2 hr with stapled anastomoses. All patients received postoperative hyperalimentation and six of eight patients received preoperative hyperalimentation. One operative death occurred in a patient with intestinal perforation who required multiple resections. The remaining seven patients experienced no serious complications and had rapid return of bowel function. Our experience indicates that wide ileal resection with right hemicolectomy and primary reanastomosis is an acceptable alternative to intestinal bypass for the treatment of severe irradiation injury, especially when performed with gastrointestinal stapling devices.

Colectomy↗
PubMed1987

Primary malignant mediastinal germ-cell tumors and the contribution of radiotherapy: a southeastern multi-institutional study.

A retrospective review was performed by a multi-institutional study group to determine the contribution of radiotherapy to the management of primary malignant mediastinal germ-cell tumors. Twenty-seven patients diagnosed with a primary mediastinal germ-cell tumor between January 1965 and July 1985 form the basis of this study. Twenty-five of the 27 patients were male. Thirteen patients' tumors were diagnosed as seminoma and the remaining 14 patients' tumors had other germ-cell histologies. The single most important prognostic factor was histology, with a 5-year actuarial survival of 100% for the seminomas and only 8.8% for the remaining germ-cell varieties. If total surgical extirpation is not possible, biopsy may be adequate. Of the patients with seminoma, 11 of 12 had local control, and 3 of the 12 patients were treated with doses between 3,000 and 3,100 cGy. High doses for this variety of mediastinal germ-cell tumor might not be required. For the germ-cell tumors other than seminoma, no patient had local control with doses over the range of 3,000-4,750 cGy.

Adolescent↗
PubMed1985

Functional and morphological changes in the microcirculation of the dog following acute coronary artery ligation.

Acute ligation of the anterior descending coronary artery in the dog had little immediate effect on heat clearance but immediately lowered heat production, which fell to its minimum level in 1/2 hr, after which it began to recover; recovery was complete in 6 hr. After 1/2 hr heat clearance also began to fall and reached a minimum level in 1 1/2 hr. Ligation increased oxygen extraction but reduced oxygen consumption markedly though temporarily. Complete recovery followed. After 3 months, there was full recovery in flow, oxygen extraction ratio, and oxygen consumption mVO2. In morphological studies using Microfil injections soon after ligation, capillaries failed to fill retrogradely, though network vessels were perfused. After 1 hr of acute artery ligation, capillaries still did not perfuse but by 3 hr there was some reperfusion. After 6 hr there was marked capillary reperfusion. In dogs kept for 3 months after ligation the microcirculation was normal. These studies confirm that immediate circulatory failure occurred in capillaries (probably critical closure) which accounts for the immediate fall in venous outflow, heat production, and mVO2. Flow continued in network vessels which traversed the ischemic zone without perfusing capillaries. These results are contrasted with the findings of some other workers who found a continued functional decline leading to infarction. The present results were accounted for by closure and reopening to capillaries.

Animals↗
PubMed1985

Effect of nicotine on blood flow, oxygen consumption and glucose uptake in the canine small intestine.

Resting blood flow, arterio-venous glucose and oxygen (A-V)O2 differences, glucose uptake and oxygen consumption by a segment of the upper jejunum were measured in anaesthetized dogs. Systemic arterial pressure was also measured. The effect of nicotine infusion (25 micrograms kg-1 i.v., over 10 min) on these measurements was recorded in untreated dogs, in dogs treated with propranolol (0.5 mg kg-1) to produce beta-adrenoceptor blockade and in dogs after alpha 1-adrenoceptor blockade with prazosin (0.2 mg kg-1). Nicotine cause a significant pressor response during infusion and a hypotensive response during the post infusion period. Propranolol did not significantly affect these results. Jejunal blood flow increased in the first half of nicotine infusion in both the untreated and beta-blocked animals. Vascular resistance was reduced during nicotine infusion and the decrease persisted post infusion in the beta-blocked group. In the untreated group (A-V)O2 was significantly reduced during the first 5 min of nicotine infusion, thereafter it returned to control levels, then rose significantly above control level, post infusion. beta-Adrenoceptor blockade had little effect on these responses to nicotine. When oxygen consumption was calculated it was found that nicotine had little effect during or after infusion. Nicotine caused significant hyperglycaemia during and for about 1 h after infusion. Tissue release of glucose was occasionally observed following the infusion. beta-Adrenoceptor blockade reduced the hyperglycaemia caused by nicotine. beta-Blockade alone increased uptake and nicotine caused a further three to four fold increase. Prazosin abolished the effects that were observed in the untreated and the alpha-blocked animals. 6 The present findings, related to our previous observations on the effects of catecholamines on glucose uptake by the bowel, are consistent with the hypothesis that nicotine has its action on bowel glucose uptake or release through its well-established action in releasing catecholamines and in activating beta-adrenoceptors. The responses are not related to oxygen utilization.

Animals↗