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Biomedical subjects

R J Adams

Publications and source records attributed to R J Adams.

195 records · Page 11Linked to original sources

Propulsion of organelles isolated from Acanthamoeba along actin filaments by myosin-I.

Eukaryotic cells are dependent on their ability to translocate membraneous elements about the cytoplasm. In many cells long translocations of organelles are associated with microtubules. In other cases, such as the rapid cytoplasmic streaming in some algae, organelles appear to be propelled along actin filaments. It has been assumed, but not proven, that myosin produces these movements. We have tested vesicles from another eukaryotic cell for their ability to move on the exposed actin bundles of Nitella as an indiction that actin-based organelle movements may be a general property of cells. We found that organelles from Acanthamoeba castellanii can move along Nitella actin filaments. Here, we report two different experiments indicating that the single-headed non-polymerizable myosin isozyme myosin-I is responsible for this organelle motility. First, monoclonal antibodies to myosin-I inhibit movement, but antibodies that inhibit double-headed myosin-II do not. Second, approximately 20% of the myosin-I in homogenates co-migrates with motile vesicles during Percoll density-gradient ultracentrifugation. This is the first indication of a role for myosin-I within the cell and supports the suggestion of Albanesi et al. that myosin-I moves vesicles in this way.

Actin Cytoskeleton↗

Canine mesenteric artery Na+,K+-ATPase: vasopressor receptor for digitalis?

Localization and characterization studies of Na+,K+-ATPase in canine superior mesenteric artery were undertaken to examine the role of the Na+-K+ pump in the vasopressor response of cardiac glycosides. The enzymatic component of the membrane-bound Na+-K+ pump, Na+,K+-ATPase, was found by histochemical and cell fractionation techniques to be localized primarily in the sarcolemma of the smooth muscle cell in superior mesenteric artery. The enzyme could be enriched in microsomal and partially purified sarcolemma preparations of superior mesenteric artery and first-order arterial side branches. Binding of [3H]ouabain to arterial microsomes followed pseudo-first-order reaction kinetics. In the presence of magnesium plus ATP, sodium stimulates and potassium inhibits the rate of binding. Scatchard analysis indicated a single class of [3H]ouabain binding sites with a KD of 2-9 nM and a Bmax of 2.3-3.5 pmol/mg protein. Although the characteristics of [3H]ouabain binding to mesenteric artery microsomes resemble the characteristics of [3H]ouabain binding to purified Na+,K+-ATPase, the density or total number of Na+-K+ pump sites in mesenteric artery is small compared with either heart muscle or kidney parenchyma. In isolated mesenteric arterial strips, more than 80% of a 2.5 microM ouabain-induced contraction could be inhibited or reversed by alpha-adrenoceptor blockade with 1 microM phentolamine. These data indicate that although cardiac glycosides interact with specific receptor sites in smooth muscle of canine superior mesenteric artery, the direct vasoconstrictor effect, which may be related to this digitalis-smooth muscle Na+,K+-ATPase interaction, is meager and may be a reflection of the low density of Na+-K+ pump sites.

Animals↗

Internal carotid artery occlusion in a child with sickle cell disease: case report and immunohistochemical study.

PURPOSE: The purpose of this report is to describe the clinical and pathologic features of a patient with acute thrombosis of both internal carotid arteries leading to death. METHODS: This is a case report of special interest because of extensive brain vessel pathologic examination. RESULTS: The analysis of this case showed that the brain had suffered massive infarction and cerebral edema. The internal carotid arteries (ICAs) were occluded by acute thrombus. The arterial wall of the left ICA, studied at its distal segment, showed a small amount of intimal hyperplasia which did not cause encroachment on the lumen. Immunohistochemical stains indicated that this lesion was formed by proliferative vascular smooth muscle rather than incremental thrombus formation. CONCLUSION: Acute thrombus formation can occur in the large cerebral arteries of children with sickle cell disease in the presence of only minimal intimal hyperplasia. The intimal hyperplasia which forms the sickle related vasculopathy seen on angiography or detected by Transcranial Doppler may be more related to stimulation of smooth muscle cells than dysregulation of thromboregulation at the endothelial surface. Implications for preventive treatment are discussed.

Acute Disease↗

Multicenter comparison of magnetic resonance imaging and transcranial Doppler ultrasonography in the evaluation of the central nervous system in children with sickle cell disease.

PURPOSE: To compare the results of standardized magnetic resonance imaging (MRI) of the brain and transcranial Doppler (TCD) ultrasonography of cerebral arteries in school-aged children with sickle cell disease to determine the correlation between these two different neurodiagnostic tests. PATIENTS AND METHODS: Data were analyzed from 78 children with sickle cell disease (mean age 11 yrs) who participated in both the Cooperative Study of Sickle Cell Disease (CSSCD) and the Stroke Prevention Trial in Sickle Cell Anemia (STOP). Patients who had experienced an overt stroke were excluded. MRI findings were classified as normal or "silent infarct." Results of TCD were classified as normal, conditional, or abnormal, based on the time-averaged maximum mean flow velocity in the proximal middle cerebral and distal internal carotid arteries. RESULTS: Of 61 patients who had a normal MRI examination, 11 (18%) had either conditional (5 patients) or abnormal (6 patients) TCD results. Among 17 patients in whom silent infarction was seen on MRI, only 5 (29%) had a conditional (1 patient) or abnormal (4 patients) TCD velocity. Thus, discordant results were seen in 23 patients: 12 in which the TCD result was normal and the MRI abnormal; 11 in which the TCD velocity was elevated and the MRI normal. CONCLUSIONS: Abnormal TCD and MRI examinations reveal different aspects of the pathophysiology of central nervous system (CNS) injury in sickle cell disease and are often discordant. Although TCD abnormality is predictive of overt stroke, the lack of concordance between TCD and MRI findings suggests a need to develop more sensitive and specific indicators of early CNS pathology, such as neuropsychometric testing and positron-emission tomography (PET) scans, and to obtain more information about microvascular pathologic processes that may affect CNS function.

Adolescent↗

Early activation of PBMC and appearance of antiviral CD8+ cells influence the prognosis of SIV-induced disease in rhesus macaques.

We studied 15 macaques inoculated with SIV and identified three phases of infection. Phase 1 was characterized by activated lymphocytes in blood and infected cells in the CSF. In phase 2, activated cells were not detected but virus was recovered from mitogen-stimulated PBMC, while in phase 3, virus was recovered from mitogen-stimulated PBMC only after depletion of CD8+ lymphocytes, indicating effective control of the virus in peripheral blood. Early development of phase 3 status correlated with a longer period of clinical normalcy.

Animals↗

Decrease in Na+,K+-ATPase activity and [3H]ouabain binding sites in sarcolemma prepared from hearts of spontaneously hypertensive rats.

Na+,K+-ATPase activity, phosphorylation, and [3H]ouabain binding in sarcolemma isolated from spontaneously hypertensive rat (SHR) hearts were compared to the same parameters in sarcolemma from normotensive rat (WKY) hearts. Sarcolemma prepared from SHR heart contained significantly less ouabain-inhibitable ATPase activity than sarcolemma from WKY heart. No significant differences in sarcolemmal protein content or recovery were noted between the two groups. The numbers of phosphorylation sites and ouabain binding sites were lower for SHR hearts than for WKY hearts. The KD values for ouabain binding were the same (0.30 muM) in cardiac sarcolemma of SHR and WKY. The I50 values for inhibition by ouabain of Na+,K+-ATPase were also the same for both groups (SHR = 49 microM; WKY = 44 microM). These data suggest that the decrease of cardiac sarcolemmal Na+,K+-ATPase activity in SHR hearts is due to a decrease in the number of active sites.

Animals↗

Graded neurologic scale for use in acute hemispheric stroke treatment protocols.

A standardized neurologic assessment scoring instrument was developed and tested for use in a multicenter trial of hypervolemic hemodilution in acute hemispheric stroke. Components of the neurologic examination pertinent to hemispheric stroke syndromes were emphasized. The scale was evaluated using 16 acute stroke patients for concurrent validity (Pearson coefficient r = 0.89 compared with global assessments by neurologists or neurosurgeons) and interobserver reliability (r = 0.95 interobserver reliability estimate). Such a scale should prove useful in quantifying neurologic deficits in hemispheric stroke and in following changes in neurologic status during multicenter acute treatment protocols.

Acute Disease↗

Assessment of visual acuity in children with severe neurological impairments.

We used the Teller Acuity Cards to assess visual acuity in children with severe neurological handicaps (N = 12), all of whom had been previously untestable. With every child we were able to obtain at least one estimate of visual acuity, even with those described as likely having little or no visual function. However, in all cases, performance was poorer than that of unimpaired children of the same age. Our results confirm that the test is useful for assessing visual acuity in populations who, because of significant cognitive, linguistic, and motor deficits, cannot be assessed by more traditional techniques.

Adolescent↗

MR and CT investigation of cerebrovascular disease in sickle cell patients.

Stroke is a common complication of sickle cell disease. Using MR and CT, we studied 10 patients with sickle cell disease and a history of stroke and compared these findings with those of 10 sickle cell patients without stroke. The purpose was to determine if MR could visualize the large vessel vasculopathy previously seen on angiography and to estimate the incidence of asymptomatic abnormalities in the nonstroke group. MR consistently demonstrated the major intracranial arteries and showed three cases with occlusion and three with stenosis of either the internal carotid or middle cerebral arteries. Infarctions were better delineated on MR but were also seen on CT. Seven cases with and two without stroke had high-signal white matter lesions on MR. Further research using cranial MR to develop noninvasive means of identifying sickle cell patients at risk for stroke is warranted.

Adolescent↗

Modified CT techniques in the evaluation of temporal lobe epilepsy prior to lobectomy.

The outcome of temporal lobectomy performed for seizure control is improved by preoperative identification of structural lesions. We used cranial CT, modified to improve visualization of mesial temporal structures, as a means of preoperative evaluation in 48 patients with partial complex seizures. The axial views, parallel to the temporal fossa, improved visualization of five lesions, including two that were not diagnosed by routine cranial CT. In 12 patients, intrathecal metrizamide was used; the rest received intravenous contrast. These modified techniques could not reliably predict mesial temporal herniation; however, modified axial CT with intravenous contrast is recommended for evaluation of suspected temporal lobe pathology.

Brain Neoplasms↗