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Biomedical subjects

W R Markesbery

Publications and source records attributed to W R Markesbery.

At least 163 records · Page 9Linked to original sources
PubMed1985

Laminar organization of cholinergic circuits in human frontal cortex in Alzheimer's disease and aging.

Cholinergic enzyme activity (choline acetyltransferase, CAT; acetylcholinesterase, AChE) and muscarinic cholinergic receptor density were measured in frontal cortex (Brodmann's area 9) of normal patients over the life span and in brains of patients with Alzheimer's disease (AD). CAT, but not AChE activity, declined with normal aging. Significant loss of CAT and AChE activity occurred in the AD brains, but later onset AD was associated with less severe loss of frontal cortex CAT activity. The majority of normal CAT activity resided in lamina I, II, and upper lamina III; CAT loss in AD resulted in large losses from all depths, most notably the upper cortical layers. AChE did not precisely correspond to the localization of CAT; loss of AChE in AD was consistent across all six laminae. No differences were seen in muscarinic cholinergic receptor binding between AD and age-matched controls; the distribution of binding was equal in all layers of normal frontal cortex, and no laminar differences were detected in distribution of cholinergic receptors between normal and AD samples.

Acetylcholinesterase↗
PubMed1985

Brain biopsy in cases of neonatal herpes simplex encephalitis.

Neonatal herpes simplex encephalitis (HSE) can represent a difficult diagnostic problem when it occurs without concomitant mucocutaneus lesions and usually requires brain biopsy for diagnosis. Asymptomatic for the initial 2 to 4 weeks of life, the three infants we describe with localized HSE came to medical attention only because they developed persistent seizures and other nonspecific symptoms. Lumbar spinal fluid obtained from these children at clinical presentation showed an encephalitic pattern. Radionuclide brain scans revealed focal uptake of isotope in a variety of cortical areas, and electroencephalograms (EEGs) demonstrated repetitive, high amplitude, polyphasic sharp waves arising from analogous regions. Computed tomography (CT) showed nonspecific ill-defined areas of low density or contrast enhancement that did not correlate well with radionuclide, EEG, or clinical findings in two neonates. No infant had predominant temporal lobe involvement. Because these data suggested a multifocal, encephalitic process, all three infants underwent brain biopsy. A widespread infiltration of leukocytes and macrophages was observed in each specimen, and abundant intranuclear inclusions were present. Electron microscopy revealed abundant herpesvirus particles, and herpes simplex virus (HSV) was subsequently isolated from each sample. From our observations and our review of the literature, we propose the following criteria as indications for brain biopsy: Brain biopsy is warranted to rule out HSE when a neonate presents with seizures, cerebrospinal fluid mononuclear pleocytosis with a negative gram stain, and focal, cortical disease on EEG and radionuclide scan.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1985

Influence of serotonin on the immune response.

The present study investigates the influence of pharmacological agents known to regulate biosynthesis of the neurotransmitter, serotonin (5-hydroxytryptamine, 5-HT) on the primary antibody response to sheep red blood cells (SRBC) in the CBA mouse. Systemic administration of 5-HT (4-100 mg/kg) or its precursor, 5-hydroxytryptophan (5-HTP, 50-400 mg/kg), 30-60 min before immunization resulted in dose-dependent suppression of both the IgM and IgG plaque-forming cell (PFC) response to SRBC. Conversely, para-chlorophenylalanine (PCPA, 250 mg/kg), which inhibits the rate-limiting enzyme (tryptophan hydroxylase) in 5-HT biosynthesis, markedly enhanced IgM and IgG antibody production when injected 48 hr prior to antigen. Effects of these drugs on immune processes appeared independent of observed changes in plasma corticosterone levels. Further, immune function was preserved following selective depletion of brain serotonin through intracisternal injection of the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) in mice pretreated with desmethylimipramine (DMI). Thus, immunomodulation by serotonin appears to be mediated via peripheral mechanism(s).

5,7-Dihydroxytryptamine↗
PubMed1984

Brain trace elements in Pick's disease.

The trace element content of the brain of two patients with Pick's disease examined postmortem was studied using instrumental neutron activation analysis. Results showed significant increases in chlorine, iron, manganese, sodium, and phosphorus and significant decreases in chromium, cesium, rubidium, and selenium and in the mean freeze-dried to wet-weight ratio for patients with Pick's disease compared with control patients. Brain zinc content was not elevated in the two patients, a finding that fails to support the hypothesis that elevated zinc levels play a role in the pathogenesis of Pick's disease.

Aged↗
PubMed1984

Neuromodulation of lymphocyte reactivity in aged rats.

Numerous reports indicate that both central nervous system (CNS) and immune system functions decline with age. We have previously shown that the CNS can modulate both mitogen-induced spleen cell proliferation and NK activity in young Fischer 344 rats. In the present study we have determined the effects of AHT lesions on the lymphocyte reactivity of aged Fischer 344 rats. These data show that lesions in the AHT of aged rats cannot modulate splenic mitogen responsiveness, however, NK activity is impaired. This differential effect may be due to multiple factors including enhanced splenic suppressor cell activity, the inability of the brain to send modulatory signals following lesioning, or the failure of the immune system to receive a neural signal and react to it.

Animals↗
PubMed1984

Brain trace element concentrations in aging.

Trace element concentrations were determined in various human brain regions over the complete life span using instrumental neutron activation analysis. Several different patterns of trace element alteration were observed with age. Brain Al, Cl and Na concentrations increase with advancing age, while K, P and Rb decline. Ag, Co, Fe, Sb and Sc concentrations increase up to the 40 to 79 age range then decline. Br, Se and Zn remain relatively constant throughout adult life. Hg, Mn and Cs show no consistent trend with age. In infant brains Br and Cl increase and Al, Cr, Cs, Fe, Mn, P, Rb, Sc, Se and Zn decrease compared to adults. The essential elements that remain within narrow concentration limits throughout adult life suggest the presence of an efficient homeostatic mechanism for their regulation in the brain, while those that are altered with age suggest modifications in control mechanisms or altered relationships with other elements. Increased concentrations of non-essential elements may reflect accumulation from our environment, impaired removal or altered balance with other elements.

Adult↗
PubMed1984

Brain manganese concentrations in human aging and Alzheimer's disease.

Manganese levels have been measured in various brain regions in Alzheimer's disease (AD) and aging using instrumental neutron activation analysis. Mn grand mean for all regions was 0.261 micrograms/g for adult controls and 0.245 micrograms/g for AD and the differences were not statistically significant (p less than 0.05). Highest Mn levels were found in the basal ganglia in controls and AD. No significant alterations in Mn were found with advancing age suggesting that the brain has an efficient homeostatic mechanism regulating Mn concentrations. Mn exhibited a significant positive correlation with Fe. Infants had a significantly lower brain Mn level compared to adults.

Adult↗
PubMed1984

Hypothalamic-immune interactions: neuromodulation of natural killer activity by lesioning of the anterior hypothalamus.

Placement of bilateral electrolytic lesions in the preoptic-anterior hypothalamic area (AHT) of Fischer 344 rats results in decreased splenic NK activity as compared to control and normal animals. Animals with AHT lesions have a decrease in NK activity 4 and 7 days after lesion placement, with a return to normal activity by day 14. Fractionation of spleen cells on glass bead columns results in nonadherent and adherent cell fractions with NK activity. AHT lesions affect NK activity only in the adherent cell fraction. The removal of macrophages from this cell fraction did not restore NK activity. Moreover, this NK activity is not the result of cytotoxic macrophages. Hypophysectomy decreases NK activity in lesioned and non-lesioned animals, suggesting the influence of pituitary factors. These data indicate that the anterior hypothalamus is capable of modulating the cytotoxic activity of NK cells. Thus, neuroimmunomodulation may be a potential factor in susceptibility to some disease states such as viral infections and neoplasia.

Animals↗
PubMed1983

Spin labeling studies of membrane proteins in erythrocyte ghosts from patients with Huntington's disease.

Previous electron spin resonance (ESR) studies employing a protein-specific spin label have suggested an alteration in membrane proteins in erythrocytes in Huntington's disease (HD). Recently, Beverstock and Pearson [4] have published the results of an ESR study not confirming our findings. In the present communication, we show that with correct use of the statistical technique of the Dixon test to determine if extreme values can be eliminated, one of the data points of these authors can be rejected. Recalculation of their results suggests a significant difference in the physical state of membrane proteins in HD erythrocytes, confirming our findings.

Electron Spin Resonance Spectroscopy↗
PubMed1983

Hypothalamic astrocytoma. Syndrome of hyperphagia, obesity, and disturbances of behavior and endocrine and autonomic function.

A 26-year-old woman had hyperphagia, obesity, aggressive behavior, visual hallucinations, reversal of wake-sleep patterns, hypothermia, hypothyroidism, and amenorrhea. She died of pancreatitis, probably secondary to hypothermia. Autopsy revealed a low-grade astrocytoma in the third ventricle and medial anterior and mid hypothalamus, primarily on the right. Although she exhibited thyroid and ovarian hypofunction, the patient had intact median eminence and pituitary function, suggesting end-organ failure, possibly of an autoimmune nature.

Adult↗
PubMed1982

Neuroimmunomodulation: neural anatomical basis for impairment and facilitation.

Rats with bilateral electrolytic lesions of specific limbic nuclei show alterations in lymphoid cell number and in lymphocyte activation induced in vitro by concanavalin A (Con A). The number of splenocytes decreases after lesioning in the anterior hypothalamus (p less than 0.001), ventromedial hypothalamus (p less than .0.2), and mamillary bodies (p less than. 0.001). The number of thymocytes decreases after lesioning of the anterior hypothalamus (p less than 0.001) and increases after hippocampal lesioning (p less than 0.001). Spleen cell responsiveness to con A decreases subsequent to lesioning of the anterior hypothalamus, whereas reactivity was enhanced after lesion placement in the mamillary bodies (p less than 0.002), hippocampus (p less than 0.001), and amygdaloid complex (p less than 0.001). Thymocyte mitogen reactivity is increased by lesions of the hippocampus (p less than 0.001) and amygdaloid complex (p less than 0.001). These effects manifest themselves maximally 4 days after lesioning, with a return to normal by day 14. These preliminary data indicated that quantitative and qualitative lymphocyte functions are altered by ablation of selected brain nuclei, thereby suggesting the presence of neural modulation of immune function.

Amygdala↗
PubMed1982

Hypothalamic-immune interactions. Effect of hypophysectomy on neuroimmunomodulation.

Electrolyte destruction of certain nuclei of the brain cause specific structural and functional changes in the immune system. Lesions in the preoptic-anterior hypothalamic area result in thymic involution and a decrease in the number and blastogenic reactivity of splenocytes. In contrast, lesions in the hippocampus increase thymic and splenic mitogenic responsiveness and cellularity. Hypophysectomy abrogates all changes in splenocyte number and function induced by hypothalamic and limbic lesions. The effects of ablating the hippocampus and amygdaloid complex on thymocyte number and function also are abolished. Hypothalamic lesions in hypophysectomized animals result in an increase in the number of thymocytes but suppressed mitogenic activity. These data indicated that neuroimmunomodulation is mediated predominantly but not exclusively by the pituitary gland.

Animals↗
PubMed1982

Spin label studies of human erythrocyte membranes in aging.

Spin-labeling studies of erythrocyte membranes from people more than 65 years of age and those less than 25 years of age have been performed. No statistically significant alteration in lipid fluidity in ghost membranes from older persons could be demonstrated. However, use of a protein-specific, covalently bound spin label demonstrated a highly significant alteration in electron spin resonance spectra of the probe in erythrocyte ghost membranes in aging, suggesting that the physical state of membrane proteins is altered in senescence. These results suggest a possible role of membrane proteins in the molecular biology of aging.

Adult↗
PubMed1982

SV-40 virus-induced neoplastic transformation of hamster brain cells in vitro. Studies with scanning and transmission electron microscopy.

Neoplastic transformation of one-day-old hamster brain cells was produced by infection with SV-40 virus and verified by phase contrast microscopy, growth in semisolid media, and intracranial tumor production after inoculation of the cells into other one-day-old hamsters. Transformed cells were studied by transmission and scanning electron microscopy. The numerous alterations in cell surface structure and in nuclear and cytoplasmic organization suggest a marked increase in cell metabolism and in the rate of mitosis and cell division. Cilia with a nine-to-zero pattern of microtubule doublets were present in cells with intermediate size filaments which stained for glial fibrillary acidic protein. The findings indicate that infection of one-day-old hamster brain cells in culture by SV-40 virus results in their transformation to a neoplastic state and the transformed cells are differentiating neoplastic astrocytes.

Animals↗
PubMed1982

Santavuori disease: diagnosis by leukocyte ultrastructure.

Since Santavuori's 1973 description of infantile neuronal ceroid lipofuscinosis, 46 of the 58 reported cases have been Finnish. We recognized the disorder in three children from two different American families by leukocyte ultrastructure and clinical picture. These patients had the cardinal features of early developmental deterioration, retinal blindness, microcephaly, and seizures. Ultrastructural study of buffy coats revealed compact, granular, osmiophilic membrane-bound cytoplasmic inclusions in approximately 15 to 21% of lymphocytes and larger mononuclear cells. Similar cytoplasmic inclusions were seen in neurons, astrocytes, macrophages, and endothelial cells of a frontal lobe biopsy from one patient. The use of leukocyte ultrastructure combined with an awareness of the characteristic clinical picture should lead to the increased recognition of this disorder in American children.

Biopsy↗
PubMed1982

Hypothalamic-immune interactions. II. The effect of hypothalamic lesions on the ability of adherent spleen cells to limit lymphocyte blastogenesis.

Animals with electrolytic pre-optic and anterior hypothalamic (AHT) lesions show impaired mitogen-induced lymphocyte blastogenesis which is restored by removal of a population of spleen cells with macrophage-like properties. Although suppressor macrophages are detectable in normal and control rats, substantially more activity is present following AHT destruction. Abrogation of lymphocyte activation does not result from increased numbers of splenic macrophages. These data indicate that one mechanism by which neuroimmunomodulation occurs is by induction of a qualitative alteration in the function of naturally occurring suppressor macrophages.

Animals↗