Search PubMedSearch

Biomedical subjects

J Atkinson

Publications and source records attributed to J Atkinson.

At least 55 records · Page 3Linked to original sources

Chronic treatment with naftidrofuryl attenuates the development of vascular hypersensitivity to serotonin in the spontaneously hypertensive rat.

Three-month-old spontaneously hypertensive rats were treated for 1, 2, or 3 months with daily intraperitoneal injections of naftidrofuryl (30 mg/kg). Systolic arterial pressure was measured. Tail arteries were removed and perfused at a constant flow rate of 2 ml/min. A concentration-response curve for serotonin was prepared. A second curve was then constructed in the presence of naftidrofuryl. Chronic treatment with naftidrofuryl had no effect on blood pressure but produced a decrease in the maximal vasoconstrictor response and the sensitivity to serotonin in vitro. The in vitro sensitivity to naftidrofuryl was unchanged. These studies suggest that chronic treatment with a dose of naftidrofuryl that does not modify blood pressure attenuates the in vitro vascular sensitivity to serotonin.

Animals

Hemopoietic progenitor cell binding to the stromal microenvironment in vitro.

Primitive clonogenic progenitor cells in human bone marrow bind to preformed marrow-derived stromal layers in vitro and generate colonies of blast cells. The binding interaction does not require calcium or magnesium ions and occurs equally well in serum-free and serum-supplemented culture medium. It does not appear to involve known cell adhesion molecules (CAMs) for which monoclonal antibodies are available (integrins, N-CAM, LFA-1, and ICAM-1), and we were unable to demonstrate a role for the progenitor cell antigen CD34 in progenitor cell adhesion to cultured stroma. The CAM expressed by the blast colony-forming cells may exist in transmembrane or phosphatidylinositol (PI)-linked forms because it is only partially degraded by exposure to trypsin or to PI-specific phospholipase C. However, binding of these cells to stroma is not prevented in the presence of monoclonal antibodies reacting with known PI-linked structures (Thy-1, CD14, and CD16). It is either masked by neuraminidase-sensitive residues or is no longer expressed as cells mature, respectively, along the granulocytic or erythroid lineages. The properties of the hemopoietic progenitor CAM are discussed with reference to the properties of other CAMs and of hemopoietic progenitor cell markers.

Antibodies, Monoclonal

'Where' and 'what' in visual search.

A line segment target can be detected among distractors of a different orientation by a fast 'preattentive' process. One view is that this depends on detection of a 'feature gradient', which enables subjects to locate where the target is without necessarily identifying what it is. An alternative view is that a target can be identified as distinctive in a particular 'feature map' without subjects knowing where it is in that map. Experiments are reported in which briefly exposed arrays of line segments were followed by a pattern mask, and the threshold stimulus-mask interval determined for three tasks: 'what'--subjects reported whether the target was vertical or horizontal among oblique distractors; 'coarse where'--subjects reported whether the target was in the upper or lower half of the array; 'fine where'--subjects reported whether or not the target was in a set of four particular array positions. The threshold interval was significantly lower for the 'coarse where' than for the 'what' task, indicating that, even though localization in this task depends on the target's orientation difference, this localization is possible without absolute identification of target orientation. However, for the 'fine where' task, intervals as long as or longer than those for the 'what' task were required. It appears either that different localization processes work at different levels of resolution, or that a single localization process, independent of identification, can increase its resolution at the expense of processing speed. These possibilities are discussed in terms of distinct neural representations of the visual field and fixed or variable localization processes acting upon them.

Attention

Congenital central hypoventilation syndrome associated with multiple ganglioneuromas.

A five-year-old girl had congenital central hypoventilation syndrome and mediastinal and adrenal tumors. The mediastinal mass was though to be present, retrospectively, for at least four years prior to surgery. Pathology of the excised tumors revealed benign ganglioneuromas. This is the first case reported of an association between CCHS and multiple ganglioneuromas. This suggests that CCHS, like neural crest tumors, may result from maldevelopment of the embryonic neural crest.

Adrenal Gland Neoplasms

Serial electrocardiographic changes in idiopathic dilated cardiomyopathy confirmed at necropsy.

Serial electrocardiographic changes in necropsy-proven idiopathic dilated cardiomyopathy are evaluated and a method of predicting heart weight using QRS amplitudes is described. In 34 patients with multiple electrocardiograms (mean 3/patient) progressive prolongation of PR interval (0.18 +/- 0.03 to 0.21 +/- 0.03, p less than 0.001) and QRS duration (0.10 +/- 0.02 to 0.13 +/- 0.03, p less than 0.0001) was noted. Progressive conduction abnormalities were common (82%). QTc interval and QRS- and T-wave axes did not change. In 50 patients with electrocardiograms within 60 days of death, total 12-lead QRS and V1 through V6 QRS amplitude correlated better with heart weight (r = 0.51, p less than 0.0001 and r = 0.55, p less than 0.0001) than the Estes-Romhilt score did. The mean total 12-lead QRS amplitude was 138 mm with a mean of 106 for V1 through V6. In 31 patients cardiac mass index was calculated and showed significant correlation with 12-lead and V1 through V6 QRS amplitudes (r = 0.68, p less than 0.0001 and r = 0.75, p less than 0.0001, respectively). The QRS amplitudes remained constant during the illness. By using total 12-lead QRS or frontal plane QRS amplitude, heart weight can be predicted as early as 2 years before death. Use of body surface area and QRS amplitude criteria increases the accuracy of heart weight prediction. Thus, progressive electrocardiographic changes are common in patients with idiopathic dilated cardiomyopathy and QRS amplitude criteria are more accurate in the prediction of left ventricular hypertrophy than standard criteria.

Adolescent

Greater vasodepressor sensitivity to nicardipine in spontaneously hypertensive rats (SHR) compared to normotensive rats.

Differences in the degree of attenuation by the calcium entry blocker, nicardipine, of the pressor responses to alpha-1 (phenylephrine) and alpha-2 (UK 14.304) adrenoceptor agonists was investigated in pentobarbital-anesthetized, normotensive Sprague-Dawley (SD) or Wistar Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR), treated with the ganglionic blocking agent, pentolinium. Following administration of the ganglionic blocking agent, pentolinium, nicardipine produced a significant fall in blood pressure in SHR but not in SD or WKY rats. Nicardipine had no effect on the basal blood pressure of pithed SHR. In rats treated with the ganglionic blocking agent, pentolinium, nicardipine produced parallel shifts to the right in the dose-response curves for phenylephrine but had no effect on maximal responses to phenylephrine. The decrease in the ED50 of phenylephrine was greater in the SHR than in normotensive rats. Nicardipine produced a decrease in both the ED50 and the maximal response to the alpha-2 adrenoceptor agonist, UK 14.304. The decrease in the maximal response was greater in SHR than in WKY normotensive rats but the change in ED50 for UK 14.304 was greater in WKY than in SHR. SD normotensive rats gave intermediate results. We conclude that the inhibition of alpha-adrenoceptor-mediated pressor responses by nicardipine is generally more pronounced in SHR than in normotensive rats. This suggests that hypertension may be accompanied by an increase in the sensitivity of peripheral resistance beds to calcium entry blockers.

Animals

Alpha-1 and alpha-2 adrenoceptor agonists induce vasoconstriction of the normotensive rat caudal artery in vitro by stimulation of a heterogeneous population of alpha-1 adrenoceptors.

Although alpha-2 adrenoceptor agonists rapidly induce arterial vasoconstriction in vivo, such responses have proven difficult to obtain in vitro. We have investigated the vasoconstrictor effects of various alpha-1 and alpha-2 adrenoceptor agonists in the perfused superfused caudal artery of the normotensive rat. Intrinsic activities were; methoxamine; 1, phenylephrine; 0.94, noradrenaline; 0.93, guanfacine; 0.88, clonidine; 0.47, UK 14,304 [5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline tartrate]: 0.10, azepexole; 0. Antagonism by the selective alpha-1 agent, prazosin of the vasoconstrictor responses provoked by methoxamine, guanfacine or clonidine, showed a high affinity with--log KB values in the range of 8.5 to 9.4. There were no significant differences between the KB values obtained with the three agonists. Antagonism by the selective alpha-2 antagonist, yohimbine showed a low affinity with KB values between 6.7 to 7.6 for the three agonists. The calcium entry blocker, nicardipine, antagonized responses to clonidine at nanomolar concentrations and those to phenylephrine at micromolar concentrations. We conclude that vasoconstrictor responses in this isolated tail artery preparation are primarily mediated via an alpha adrenoceptor which can be classified, on the basis of the results with specific antagonists, as being of the alpha-1 type. The results obtained with nicardipine suggest that the population of alpha adrenoceptors is not, however, homogeneous.

Adrenergic alpha-Agonists

Biochemical evidence that brainstem adrenaline-containing neurons are activated during clonidine withdrawal in the spontaneously hypertensive rat.

We have investigated the effects of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.1 mg/kg/day for 7 or 10 days) and of withdrawal of such treatment on brainstem noradrenaline and adrenaline metabolism in the adult spontaneously hypertensive rat (SHR). After a seven day treatment with clonidine, noradrenaline and adrenaline turnovers were unchanged both in the A2-C2 and A1-C1 regions. During withdrawal, the noradrenaline turnover was also unchanged in these regions. However, the adrenaline turnover was significantly increased 16 h after withdrawal (p less than 0.01) in the A2-C2 region and 16 h (p less than 0.01) and 40 h (p less than 0.05) after withdrawal in the A1-C1 region. These results show that noradrenaline metabolism is unchanged both during clonidine treatment and during its withdrawal in the brainstem catecholaminergic regions analyzed. In contrast, the increases in adrenaline turnover found in the A2-C2 and A1-C1 regions suggest that the adrenergic neurons of the brainstem could be activated during clonidine withdrawal. As the adrenergic C1 neurons are a key element of the sympathetic vasopressor system, the increase in adrenaline turnover observed during withdrawal could be at the origin of the sympathetic hyperactivity found after cessation of prolonged treatment with clonidine.

Animals

Cerebroretinal vasculopathy. A new hereditary syndrome.

A new hereditary syndrome characterized by a frontoparietal lobe pseudotumor and retinal capillary abnormalities is described. A pedigree is presented in which characteristic ophthalmic findings have been found in ten family members and are suspected in eight additional family members spanning a total of four generations. Typical retinal findings include perifoveal capillary obliteration, peripheral focal capillary occlusion, and microvascular abnormalities, particularly involving the posterior pole. Eight patients spanning three generations had a central nervous system pseudotumor with identical histopathology. Histopathologic analysis of brain tissue shows a characteristic pattern of an unusual vasculopathy without vasculitis characterized by fibrinoid necrosis and resulting in necrosis of white matter with sparing of cortical brain tissue. The pedigree shows an apparent autosomal dominant pattern of inheritance with delayed expression of abnormalities. Of note, two patients unrelated to the pedigree having similar neuropathologic and retinal findings also have been seen at the authors' institution.

Adult