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Biomedical subjects

A W Clark

Publications and source records attributed to A W Clark.

At least 55 records · Page 3Linked to original sources

Cortical degeneration with swollen chromatolytic neurons: its relationship to Pick's disease.

We report two cases of dementia in which cortical degeneration with widespread swollen chromatolytic neurons (SCN) was the dominant pathologic feature. Each patient had received the diagnosis of Alzheimer's disease on the basis of clinical findings. There was no deficit of cortical choline acetyltransferase activity, assayed in one case, or lesions of the nucleus basalis of Meynert. The brains had moderate to marked frontal atrophy. Comparison of SCN with several other cerebral degenerative disorders indicates a similarity with certain features of the transmissible spongiform encephalopathies and with corticodentatonigral degeneration. The pathologic features of our cases are those of a number of other cases reported as "Pick's disease," and may represent an earlier stage in the pathogenetic process than the severe, sharply circumscribed atrophy with "nonspecific" cell loss and gliosis as the only microscopic residuals. Our findings re-emphasize the need to search for pathogenetically distinct subgroups which have been wholly or partially subsumed into the concept of Pick's disease.

Acetylcholine↗

Nonbacterial thrombotic endocarditis in bone marrow transplant patients.

We reviewed the findings in 2381 consecutive autopsies, a series containing 91 bone marrow transplant (BMT) patients, and found 45 cases of nonbacterial thrombotic endocarditis (NBTE). The overall prevalence of NBTE was 1.9%. NBTE was present in seven BMT patients, for a prevalence of 7.7%. The rate of NBTE in BMT patients was significantly greater than the rate of NBTE in the general autopsy population (P less than 0.001). The frequency of NBTE was not increased in patients with the individual underlying diseases for which BMT was a possible treatment (the BMT candidate diseases [BMTCD]). When rates of NBTE were compared in patients with BMTCD, there was a significantly higher rate in patients who had received BMT than in those who had not (P less than 0.02). These findings indicate that NBTE occurs with greater frequency in BMT patients and that there may be features of the BMT regimen that predispose patients to develop NBTE. Although several factors related to BMT are discussed as potential contributors to the increased prevalence of NBTE, we were not able to demonstrate an association between NBTE and any single factor. Since NBTE is an important cause of arterial embolization, an awareness of the increased frequency of NBTE in BMT patients is important for clinicians who must interpret neurologic and other abnormalities in BMT recipients.

Adolescent↗

Brainstem findings in Huntington's disease. Possible mechanisms for slow vertical saccades.

Quantitative, morphometric studies of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) were performed on the brains of four patients with Huntington's disease (HD) who had shown slow vertical saccades, and on the brains of three control subjects. Only one HD brain showed a statistically significant decrease in the number of larger neurons in the riMLF though all four brains showed non-specific gliosis. Taken with results from physiological and other clinical studies, the present data suggest that slow vertical saccades in HD are due, at least in part, to disordered inputs to the riMLF.

Adult↗

Outbreak of Pseudomonas aeruginosa following endoscopic retrograde cholangiopancreatography.

In a 12 week period five patients developed gentamicin-resistant Pseudomonas aeruginosa infection after endoscopic retrograde cholangiopancreatography with the same endoscope. The organism was subsequently cultured from the endoscopic apparatus. The cases are discussed and the importance of adequate disinfection of endoscopes is re-iterated.

Cholangiopancreatography, Endoscopic Retrograde↗

Neurologic complications of bone marrow transplantation.

Among 78 patients who died after bone marrow transplantation, neurologic complications were present in 55 (70%) and were the cause of death in 5 (6%). Metabolic encephalopathy occurred in 29 patients (37%). CNS infections included aspergillosis (3), herpes simplex encephalitis (2), and Listeria monocytogenes meningitis (1). Six additional patients had neuropathologic changes possibly due to cytomegalovirus infection. Cerebrovascular complications occurred in five patients (two hemorrhages and three infarcts). All infarcts were associated with endocarditis. The rate of nonbacterial thrombotic endocarditis was significantly higher (p less than 0.001) than in the general autopsy population. CNS leukemia and therapy-induced injury were rare. There was no evidence of graft-versus-host disease involving the CNS.

Adolescent↗

Alzheimer's disease and related dementias: selective involvement of specific neuronal systems.

The brains of individuals with dementia due to Alzheimer's disease (AD), Parkinson's disease (PD), and Down's syndrome (DS) exhibit similar neuropathological features, including neuritic plaques, neurofibrillary tangles, and the loss of specific populations of neurons. In addition, these brains show similar transmitter-specific neurochemical alterations. Recent evidence indicates that several pathological and neurochemical changes are related to diseases involving projection systems innervating the telencephalon. At least two transmitter-specific circuits, cholinergic neurons in the basal forebrain and noradrenergic neurons in the locus coeruleus, are selectively affected in many patients with these disorders. This review focuses on these systems because they provide particularly useful examples of the ways in which multidisciplinary studies can provide new clinical-pathological-chemical correlations. Strategies used in these studies are applicable to a wide variety of other neurodegenerative diseases affecting specific populations of neurons. Modern neuropathological approaches to these diseases should eventually allow investigators to directly relate pathogenic processes involving transmitter-specific neuronal populations, whose projections, physiological properties, and functions are known, with the clinical manifestations occurring in human disorders of behavior and cognition.

Aging↗

Reconstitution of (Na+ + K+)-ATPase proteoliposomes having the same turnover rate as the membranous enzyme.

Membranous (Na+ + K+)-ATPase from the electric eel was solubilized with 3-[3-cholamidopropyl)-dimethylammonio)-1-propanesulfonate (Chaps). 50 to 70% of the solubilized enzyme was reconstituted in egg phospholipid liposomes containing cholesterol by using Chaps. The obtained proteoliposomes consisted of large vesicles with a diameter of 134 +/- 24 nm as the major component, and their protein/lipid ratio was 1.25 +/- 0.07 g protein/mol phospholipid. The intravesicular volume of these proteoliposomes is too small to consistently sustain the intravesicular concentrations of ligands, especially K+, during the assay. The decrease in K+ concentration was cancelled by the addition of 20 microM valinomycin in the assay medium. The low value of the protein/lipid ratio suggests that these proteoliposomes contain one Na+/K+-pump particle with a molecular mass of 280 kDa per one vesicle as the major component. In these proteoliposomes, the specific activity of the (Na+ + K+)-ATPase reaction was 10 mumol Pi/mg protein per min, and the turnover rate of the ATP-hydrolysis was 3500 min-1, the same as the original enzyme under the same assay condition. The ratio of transported Na+ to hydrolyzed ATP was 3, the same as that in the red cell. The proteoliposomes could be disintegrated by 40-50 mM Chaps without any significant inactivation. This disintegration of proteoliposomes nearly tripled the ATPase activity compared to the original ones and doubled the specific ATPase activity compared to the membranous enzyme, but the turnover rate was the same as the original proteoliposomes and the membranous enzyme. This disintegration of proteoliposomes by Chaps suggests the selective incorporation of the (Na+ + K+)-ATPase particle into the liposomes and the asymmetric orientation of the (Na+ + K+)-ATPase particle in the vesicle.

Adenosine Triphosphate↗

Neurofilamentous axonal swellings as a normal finding in the spinal anterior horn of man and other primates.

To define the nature and extent of axonal swellings in the normal spinal anterior horn, we studied the spinal cords of patients five days to 83 years of age from a general autopsy population. Axonal swellings were routinely found in the anterior horn of the cervical and lumbosacral spinal cord. The swellings measure 5-50 micron in diameter and are most numerous at the anterior edge of the anterior horn. They first appear about five months of age and appear to increase in number until about 20 years of age, with no increment thereafter. Ultrastructurally, they are filled with neurofilaments and surrounded by a thin myelin sheath. Most are probably aberrant components of motor axons. Identical axonal swellings, in the same anatomical site, were found in the spinal cords of cynomolgus and rhesus monkeys. On the basis of their natural history and morphologic features, they should be distinguished from the neuroaxonal dystrophy of aging. The largest of them resemble the neurofilamentous axonal swellings of early onset motor neuron disease but occur in much smaller numbers. Moreover, location on the proximal axon could not be demonstrated for any of these swellings. An awareness of this normal phenonemon is essential for the interpretation of axonal swellings in the spinal cord.

Adolescent↗

Doxorubicin intoxication: neurofilamentous axonal changes with subacute neuronal death.

Neurofilamentous axonal swellings occur in various chronic neuronal degenerations in man and animals. The pathogenesis of these swellings in the setting of neuronal degeneration remains unclear. A toxic model of neuronal degeneration can be produced by doxorubicin. This agent impairs DNA-dependent RNA synthesis and produces subacute neuronal death. The aim of the present study was to investigate whether neurofilamentous axonal swellings occur in association with neuronal nuclear derangement and subacute neuronal death produced by doxorubicin. We investigated the evolution of changes seen in retinal ganglion cells and their axons after an intravitreous injection of doxorubicin in rats. The earliest changes were in the nuclei of the retinal ganglion cells. Later, transient axonal swellings filled with neurofilaments were prominent. These neurofilamentous swellings preceded the subacute neuronal cell death. To determine whether these changes represent a direct effect of the agent on the axon, we injected doxorubicin directly into the sciatic nerve. This local injection did not produce similar changes in the axons. These results suggest that in this model neurofilamentous axonal swellings precede neuronal cell death and may be due to a primary insult to the nerve cell body.

Animals↗

Postinfectious leukoencephalitis complicating Mycoplasma pneumoniae infection.

Neuropathological findings in a patient with fatal neurological complications due to infection with Mycoplasma pneumoniae were similar to those seen in postinfectious encephalitis and acute hemorrhagic leukoencephalitis. This case supports the hypothesis that immune mechanisms play a role in the pathogenesis of neurological symptoms during mycoplasmal infections.

Electroencephalography↗

Ocular clinicopathologic correlation of Hallervorden-Spatz syndrome with acanthocytosis and pigmentary retinopathy.

We studied the eyes of a 10-year-old girl with retinal degeneration, acanthocytosis, and normal betalipoprotein levels. The ophthalmoscopic pattern was characterized initially by a flecked retina and later by bone-spicule formation and "bull's-eye" annular maculopathy. On ultrastructural study, the retinal pigment epithelium varied in size and contained large, round single-membrane-bound aggregates composed of complex melanolipofuscin granules. Cells that had migrated into the outer retinal layers contained similar melanolipofuscin aggregates; these cells were identified as macrophages and correlated with the flecks and macular annulus seen on ophthalmoscopy. The cells around the retinal blood vessels contained normal melanin pigment, were identified as retinal pigment epithelial cells, and correlated with the bone spicule pigmentation found on ophthalmoscopic examination.

Basal Ganglia Diseases↗

The nucleus basalis in Huntington's disease.

The nucleus basalis of Meynert (nbM) provides most of the cholinergic input to the cerebral cortex. The loss of cortical choline acetyltransferase (CAT) activity in Alzheimer's disease (AD) and senile dementia of the Alzheimer's type (SDAT) appears to be related to a severe depopulation of the nbM in this dementia. In Huntington's disease (HD), by contrast, there is no loss of cortical CAT activity. The present quantitative study indicates that (1) there is no significant loss of neurons from the nbM in HD, and (2) that the previously described cytologic changes in the neurons of this nucleus in HD patients do not differ significantly from controls. These findings are consistent with the working hypothesis that the types of dementia associated with reductions of neocortical CAT activity are characterized by dysfunction or death of neurons in the nbM, but dementing disorders with normal neocortical CAT activity manifest no major abnormalities in this cholinergic nucleus of the basal forebrain.

Aged↗

Downbeat nystagmus. A case report of herpetic brain stem encephalitis.

A 35-year-old man with aplastic anemia developed prominent downbeat nystagmus 80 days after receiving an allogeneic bone marrow transplant. A diagnosis of herpes simplex encephalitis was made which was confirmed by positive virus cultures at autopsy 1 week later. Routine pathologic examination of the brain stem revealed no lesions which would explain the downbeat nystagmus. Immunoperoxidase studies, however, revealed virus-infected neurones throughout the brain stem including the nuclei of the basis pontis, the superior olive, and nuclei of the spinal tracts of 5 and 10. The significance of "negative" pathologic brain stem findings in cases of downbeat nystagmus is discussed.

Adult↗

Structural changes in murine cancer associated with hyperthermia and lidocaine.

Hyperthermia alone and hyperthermia with lidocaine cause changes in the fine structure of the CA755 tumor cell as well as the breakdown of the tumor vasculature. The first structural change, observed immediately after termination of hyperthermia of 43.5 degrees for 1 hr, is the vesiculation of the Golgi apparatus. Other structural changes occur later but with variable times of onset. The changes appear to be unrelated to the presence of lidocaine. Vascular breakdown results in hemorrhaging within the tumor, and its onset and intensity appear to vary directly with the size of the tumor. Breakdown of the tumor cell plasmalemma and degenerative changes of the cytoplasm and nucleoplasm are seen more frequently in large tumors and in the interior of small tumors at any given time after the end of hyperthermia. The vesiculation of the Golgi persists in treated cells for as long as 30 hr. This modification may represent an intensification in the function of the Golgi apparatus; however, it closely corresponds to that found in a variety of other cells treated with a class of compounds, including lidocaine, that specifically inhibits the function of the Golgi apparatus. The effect of these compounds is rapidly reversible, unlike hyperthermia. Since the Golgi apparatus probably is crucial in repairing any deleterious effects of hyperthermia, any impairment of its normal function would place most treated tumor cells in a difficult position. The rate of tumor destruction may ultimately depend on the breakdown of the tumor vasculature following hyperthermia and lidocaine.

Adenocarcinoma↗

A longitudinal study of interests of medical technologists: comparisons between medical technology and other allied health fields.

Three good reasons to improve allied health student selection can be suggested: There are often more applicants than spaces; there is often high attrition within programs; and it is often difficult for a student to transfer in or out of a program without cost in time and/or money. Although college grade point average (GPA) has been the best single predictor of continuing academic success in an allied health major, this GPA is not available for entering freshmen. Also, students' curriculum or career choices are often uninformed. It seemed worthwhile, therefore, to consider what could be added to evaluation of high school achievement and expressed interest to improve the selective admission of students to allied health programs. This study evaluated the use of the Strong Vocational Interest Blank (SVIB) and the Strong-Campbell Interest Inventory (SCII) as a selection technique for medical technology students. Results of the two interest inventories appeared to be similar in comparable areas. Our findings did not support the use of either test as a selection device for medical technology students, primarily because of the lack of discrimination within allied health professions. The graduates' scores on the basic interest and occupational scales of the SVIB-SCII did show shared interests and similarity with other allied health professions. This suggests that these tests could be of value in more general counseling of students interested in the allied health professions.

Achievement↗

Differential sensitivity of AKR murine leukemia and normal bone marrow cells to hyperthermia.

To determine if there is a differential effect of hyperthermia on AKR murine leukemia and AKR normal bone marrow cells incubated in vitro, the fractional survival of leukemic and of normal cells with proliferative potential as a function of heating exposure was estimated by evaluating spleen colony formation. Normal bone marrow colony-forming units were assayed in lethally irradiated (750 centigrays) mice; leukemic colony-forming units were assayed in nonirradiated mice. Electron micrographic studies of leukemic cells treated with 41.8 degrees hyperthermia found that structural damage to the cell, i.e., changes in the Golgi apparatus, was associated with the lack of ability to form colonies. AKR leukemia cells were more sensitive than normal cells to hyperthermic killing at 41.8 degrees and at 42.5 degrees. This differential was found whether cells of each type were heated separately or when mixed together. This model system demonstrates an inherently greater sensitivity of neoplastic cells, as compared to normal syngeneic stem cells, to thermal killing. This finding may have relevance to autologous bone marrow transplantation in humans.

Animals↗