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Biomedical subjects

A Anthony

Publications and source records attributed to A Anthony.

At least 73 records · Page 4Linked to original sources
PubMed1991

A follow-up of female delinquents: maternal contributions to the perpetuation of deviance.

Twenty-one female delinquents, neuropsychiatrically evaluated while in a juvenile correctional facility, were followed up to 7 to 12 years later. Compared with a matched sample of male delinquents, they committed fewer and less violent offenses. Unlike the males, early biopsychosocial variables were not predictive of adult criminality; however, most females were seriously impaired neuropsychiatrically. Mortality rates were high. Having come from abusive households, the female delinquents became suicidal, alcoholic, drug addicted, enmeshed in violent relationships, and unable to care for their children.

Adolescent↗
PubMed1989

Neuronal RNA in Pick's and Alzheimer's diseases. Comparison of disease-susceptible and disease-resistant cortical areas.

Comparative neuronal RNA analyses were conducted in disease-prone (frontal association, Brodmann's area 9) vs relatively disease-resistant (primary visual, occipital area 17) cortex of patients with autopsy-proved Pick's disease (PD) and Alzheimer's disease (AD). Azure B-RNA staining and scanning-integrating microdensitometry were used to determine total RNA contents of pyramidal neurons in layers 3 and 5. In both PD and AD (1) significant (15% to 47%) RNA loss was detected in neurons of both cortical areas and layers relative to those of aged, nondemented controls, and (2) RNA loss was not markedly enhanced in the damaged frontal cortex relative to that in the preserved occipital cortex. Neuronal RNA depletion was generally more marked in PD than AD. However, this impairment does not appear to be related to the formation of classic neuropathological abnormalities in either disease.

Aged↗
PubMed1989

Cytophotometric assessment of T-2 toxin induced alterations in azure B-RNA and Coomassie-protein in supraoptic-magnocellular neurons of rat hypothalami.

Quantitative cytophotometry was used to monitor T-2 toxin-induced alterations in azure B-RNA and Coomassie-total cell protein in supraoptic-magnocellular neurons of rat hypothalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.00 and 1.50 x LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric azure B-RNA and Coomassie-protein staining of brain sections, scanning-integrating microdensitometry was used to quantify toxin-induced alterations in these well established indices of neuronal toxicity. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in azure B-RNA reactivity were observed in the 0.75, 1.00 and 1.50 x LD50 groups (i.e. 11%, 13% and 8%, respectively); no differences in RNA levels were observed between controls and the 0.50 x LD50 group. In addition, a decrease in Coomassie-total cell protein was seen in animals receiving 0.50, 0.75 and 1.50 x LD50 T-2 toxin (i.e. 33%, 21% and 12%, respectively); however, toxin administration did not alter protein levels in the 1.00 x LD50 group. Furthermore, a dose-dependent decrease in systolic blood pressure was observed at 8 hr. post-injections (i.e., approximately -39%, -52%, -66% and -64% for the 0.50, 0.75, 1.00 and 1.50 x LD50 groups, respectively). Additional observations include pronounced polydipsia, ascites, abdominal and subdural hemorrhage, and horripilation (piloerection) in experimental groups. It is postulated that the T-2 toxin-induced reductions in azure B-RNA and Coomassie-protein represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is advanced that the supraoptic-magnocellular compartment represents an important site in T-2 toxin mycotoxicosis. Moreover, these findings support previous claims that T-2 toxin intoxication may critically impair the vasopressinergic response to toxin-induced cardiovascular collapse.

Animals↗
PubMed1989

Cytophotometric analysis of T-2 toxin induced alterations in chromatin condensation and neuronal nuclear volume of rat supraoptic-magnocellular neurons.

Quantitative cytophotometry and ocular filar micrometry were used to monitor T-2 toxin induced alterations in chromatin and neuronal nuclear volume in supraoptic-magnocellular neurons of rat hypo-thalami. Thirty male Sprague-Dawley rats (200-220g) were given a single i.p. injection of T-2 toxin (0.5, 0.75, 1.0 and 1.5 X LD50), a trichothecene mycotoxin; rats were decapitated 8 hours post-dosing. After stoichiometric Feulgen-DNA staining of brain sections, scanning-integrating microdensitometry was used to quantify changes in the susceptibility of chromatin to Feulgen acid hydrolysis. Changes in neuronal nuclear volumes were also determined histometrically. Within the magnocellular neurons of the supraoptic nuclei, significant reductions in F-DNA reactivity were observed in the 0.5, 0.75, and 1.0 X LD50 groups (i.e. 3.7%, 4.4% and 2.5%, respectively); however, rats receiving 1.5 X LD50 T-2 toxin showed no difference in F-DNA reactivity compared to controls. In addition, ocular filar micrometry demonstrated increased neuronal nuclear volumes in all groups receiving T-2 toxin, and following an inverse trend to that seen with F-DNA stainability. Additional observations included pronounced polydipsia, polyphagia and horripilation in the experimental groups, independent of the dosages employed; these changes were evident within 1 hour post-injection. It is postulated that the T-2 toxin induced reduction in the susceptibility of chromatin to Feulgen acid hydrolysis and concomitant increases in neuronal nuclear volumes represent an early indication of impaired metabolic activity. Since these neurons are important sites of vasopressin (antidiuretic hormone) synthesis, these data suggest an impaired osmoregulatory ability. The pronounced polydipsia which occurred shortly after intoxication is further evidence of this impairment. Although these findings do not provide insight relating to the mechanism of osmoregulatory disruption, it is evident that an impaired ability to osmoregulate is among the earliest indications of acute T-2 toxin mycotoxicosis.

Animals↗
PubMed1989

Evaluation and characterization of the hypothyroid hyt/hyt mouse. I: Somatic and behavioral studies.

Mice homozygous for the autosomal-recessive gene hypothyroid (hyt) had congenital hypothyroidism of fetal onset after 15 days postconception. Neonatal hyt/hyt mice had reduced serum thyroxine ranging from 1/5 to 1/6 of normal as well as significantly delayed somatic and behavioral development. Delayed somatic development included retarded eye opening and ear raising, and reduced body length and body weight. The hyt/hyt animals compared to their normal littermates demonstrated delayed reflexive behavior and abnormal motor and adaptive behavior. The somatic and behavioral measures clearly distinguished hyt/hyt animals from their normal littermates even without T4 determination. The somatic and reflexive behavioral abnormalities in the hyt/hyt mouse were similar to other rodent models of human congenital hypothyroidism. The hyt/hyt mouse provided an ideal model for exploring the effect of severe primary inherited hypothyroidism related to deficient autonomous fetal thyroid function and was consistent with the hypothesis that thyroid hormone deficit in utero and in the early neonatal period significantly altered functional development.

Animals↗
PubMed1988

Neuronal RNA in relation to Alz-50 immunoreactivity in Alzheimer's disease.

Both defective nucleic acid metabolism/protein synthesis and the expression of an abnormal antigen recognized by the Alz-50 antibody may be involved in the neuronal degeneration of Alzheimer's disease (AD). A multiparametric analysis involving Alz-50 immunocytochemistry and azure B--RNA microdensitometry was developed to compare nucleic acid alterations in Alz-50-positive neurons to those in Alz-50-negative neurons of the brain of AD patients. Alz-50-immunoreactive neurons of the hippocampal endplate (Rose's H3-H5 fields) and the subiculum exhibited significantly lower (by approximately 30%) total RNA contents than negative neurons of the corresponding region. The mean RNA content of Alz-50-positive neurons of the AD brain was also reduced in comparison to that of Alz-50-negative neurons of age-matched, nondemented controls, whereas there were no significant differences between negative neurons of AD patients and controls. The hippocampus of nondemented controls was also found to contain Alz-50-immunoreactive neurons, although 20- to 30-fold fewer than the hippocampus of AD patients. In the controls, there was also a tendency toward reduced RNA levels in Alz-50-positive versus -negative neurons. These data suggest a relationship between Alz-50 immunoreactivity and defective nucleic acid metabolism in the AD brain.

Alzheimer Disease↗
PubMed1988

Astrocyte RNA in relation to neuronal RNA depletion in Alzheimer's disease.

A new double-staining procedure, in which the techniques of immunocytochemistry of glial fibrillary acidic protein (GFAP) and quantitative microdensitometry of azure B-RNA were combined, was used to study nucleic acid alterations in fibrous astrocytes in Alzheimer's disease (AD). RNA contents of GFAP-positive cells of the hippocampal endplate (Rose's H3-H5 fields) and the dentate gyrus molecular layer were determined in ten autopsy-proven AD patients (ages 51-88) and ten age-matched, non-demented controls. In addition, RNA contents of pyramidal neurons of the endplate were examined. While there were no differences in RNA contents of astrocytes of either region between AD patients and controls, neuronal RNA was markedly depleted. These data suggest that astrocytes maintain protein synthetic capabilities in AD and that RNA loss is limited to the neuronal compartment.

Aged↗
PubMed1988

Effects of oxotremorine on neuronal RNA and chromatin in thalamic cholinoceptive sites.

Neuronal nucleic acid responses were examined within the rat thalamic ventrobasal nuclear complex (VBC) and nucleus reticularis (NR) following single intraperitoneal injections of the central muscarinic-cholinergic (M2) receptor agonist oxotremorine (0.1, 0.7, or 1.0 mg/kg). After stoichiometric azure B and Feulgen staining of brain sections, scanning-integrating cytophotometry was used to quantify azure B-ribonucleic acid (RNA) content, Feulgen-DNA levels, and changes in the susceptibility of chromatin to Feulgen acid hydrolysis (F-DNA yield) of neurons on an individual basis. Changes in neuronal nucleolar volume were also determined histometrically. Within the VBC, oxotremorine produced marked dose-dependent elevations in neuronal RNA content and nucleolar volume with increased F-DNA yield (chromatin activation) in a proportion of VBC neurons. In contrast, within the NR, oxotremorine elicited reductions in RNA levels, F-DNA yield and nucleolar volume. The data demonstrate that oxotremorine-induced central muscarinic receptor stimulation is associated with metabolic correlates of thalamic VBC neuroexcitation and NR neuron depression. The overall study lends further credence to the hypothesis that muscarinic-cholinergic mechanisms are operative within the mammalian thalamus.

Animals↗
PubMed1988

Cytophotometric assessment of granulosa cell protein and nucleic acid levels during the estrous cycle in rats treated with T-2 toxin.

Female Sprague-Dawley rats (160-180g.) with normal estrous cyclicity established by vaginal smears, were injected intraperitoneally with 0.45 mg/kg (low dose) or 0.68 mg/kg (high dose) of T-2 toxin, a trichothecene with potent protein inhibitory abilities. Control animals were injected with only the 100% ethanol vehicle. All animals were decapitated at 8 hours post-exposure, and their ovaries removed and processed for paraffin sectioning. Coomassie, Feulgen, and azure B/DNase staining procedures were used to show granulosa cell protein levels, F-DNA stainability, and basophilia/RNA levels, respectively. Quantification of these parameters was accomplished using scanning-integrating microdensitometry. T-2 toxin treatment groups had granulosa cell protein levels significantly lower than those of the control animals. However, rats exposed to the lower dose of T-2 toxin generally showed a more marked suppression of protein levels than the high dose group, regardless of the stage of the estrous cycle. In addition, rats that received lower doses of T-2 toxin had impaired translation and template activity in response to injury, when compared with the rats in the high dose group. These results are attributed to the lesser degree of circulatory impairment in the low T-2 toxin dosage group, which allows a higher amount of T-2 toxin to interact with the cells.

Animals↗
PubMed1987

Metabolism of estragole in rat and mouse and influence of dose size on excretion of the proximate carcinogen 1'-hydroxyestragole.

The major metabolic pathways of estragole have been established in rats and mice, and in both species the relative importance of the different pathways has been shown to be dose related. At low doses, estragole mainly undergoes detoxication reactions, notably O-demethylation and side-chain cleavage, but as the dose is increased, the extent of O-demethylation falls and other pathways, notably l'-hydroxylation, come into prominence. The disproportionate relationship between dose size and the elimination of the proximate carcinogenic metabolite l'-hydroxyestragole may influence the relationship between dose size and tumour incidence. These findings may have important implications for the safety assessment of this food flavouring, since the dose levels used in carcinogenicity studies have been very much larger than the estimated human daily intake. Moreover the percentage of an administered dose of estragole eliminated as 1-hydroxyestragole glucuronide in human urine is much lower than that found with even the lowest doses examined in rats in this study.

Allylbenzene Derivatives↗
PubMed1987

Neuronal RNA in relation to neuronal loss and neurofibrillary pathology in the hippocampus in Alzheimer's disease.

Topographic analyses were performed on the distribution of neuronal RNA loss in relation to local neuronal loss and neurofibrillary degeneration in the hippocampal region of brains of patients with Alzheimer's disease (AD). Compared to age-matched controls, pyramidal neuronal RNA was depressed (p less than 0.0001) in all areas of the hippocampus examined in AD, viz., the endplate (33%), Rose's H2 field (30%), Rose's H1 field (37%) and the subiculum (46%). Significant neuronal loss was observed in Rose's H1 field and the subiculum but not in the endplate or Rose's H2 field. The frequency of neurofibrillary tangle-bearing neurons was enhanced in all four regions of AD brains, the number of involved neurons being markedly greater in Rose's H1 field and the subiculum than in the endplate and Rose's H2 field. Overall, the data indicate the existence of a generalized disturbance in RNA metabolism within pyramidal neurons in the hippocampus in AD, occurring in regions of minimal (endplate, Rose's H2 field) as well as those of extensive (Rose's H1 field, subiculum) pathological alterations. Although there is focal accentuation of RNA depletion in the latter, the marked RNA depletion in regions of minimal pathologic change suggests that this effect is largely unrelated to local neuronal loss or neurofibrillary degeneration.

Aged↗
PubMed1987

In situ analysis of neostriatal RNA and chromatin in Alzheimer's disease.

Scanning-integrating microdensitometry of azure B-RNA- and Feulgen-Schiff-stained tissue sections was used to measure neostriatal neuronal RNA levels and susceptibility of neuronal and oligodendrocyte chromatin to acid hydrolysis in Alzheimer's disease (AD) patients and controls. AD was associated with neuronal RNA depletion (17 to 23%) in both caudate nucleus and putamen. While neuronal chromatin was found to be more acid-labile than that of the oligodendrocytes, there were no differences in either cell type between AD and controls. These data support the existence of a macromolecular disturbance (RNA loss) occurring within neostriatal neurons, perhaps related to the extrapyramidal dysfunction of AD, but fail to demonstrate that an alteration in chromatin is responsible for this effect.

Aged↗
PubMed1987

The metabolic disposition of [methoxy-14C]-labelled trans-anethole, estragole and p-propylanisole in human volunteers.

1. The metabolic fates of the naturally occurring food flavours trans-anethole and estragole, and their synthetic congener p-propylanisole, have been investigated in human volunteers using the [methoxy-14C]-labelled compounds. The doses used were close to those encountered in the diet, 1 mg, 100 micrograms and 100 micrograms respectively. 2. In each case, the major routes of elimination of 14C were in the urine and in the expired air as 14CO2. 3. Urinary metabolites were separated by solvent extraction, t.l.c. and h.p.l.c., and characterized by comparison of chromatographic mobilities with standards and by radioisotope dilution. Nine 14C urinary metabolites were found after trans-anethole administration, four after p-propylanisole and five after estragole. All were products of side chain oxidations. 4. The principal metabolites of p-propylanisole were 4-methoxyhippuric acid (12%) and 1-(4'-methoxyphenyl)propan-1-ol (2%) and -2-ol (8%). 5. The major metabolite of trans-anethole was 4-methoxyhippuric acid (56% of dose), accompanied by much smaller amounts of the two isomers of 1-(4'-methoxyphenyl)propane-1,2-diol (together 3%). 6. After estragole administration, the two volunteers eliminated 0.2 and 0.4% of the dose respectively as 1'-hydroxyestragole. 7. The human metabolic data is discussed with reference to the comparative metabolic disposition of these compounds in the mouse and rat, species commonly used in their safety assessment.

Adult↗
PubMed1986

Scanning cytophotometric analysis of brain neuronal nuclear chromatin changes in acute T-2 toxin-treated rats.

Male Sprague-Dawley rats (200 g) were injected intraperitoneally with T-2 toxin, a trichothecene mycotoxin protein synthesis inhibitor, at dosages of 0.75, 1.0, 1.5, and 6.0 mg/kg (1 LD50 = 0.9 mg/kg) before decapitation at 8-hr postexposure. Correlative data were obtained on changes in physicochemical properties of nuclear chromatin, chromatin dispersion, and nuclear volume of cerebrocortical (layer III) and striatal neurons using Feulgen-DNA (F-DNA) cytophotometry and ocular filar micrometry. Decreased lability of neurons to F-DNA acid hydrolysis (reduced F-DNA yield), nuclear shrinkage, and chromatin aggregation (decreased chromophore area) were used as indices of suppression of genomic template activity, i.e., neuronal nuclear functioning. Conversely, increased F-DNA yield, chromophore area, and nuclear volume signify enhanced neuronal activation. At 8 hr following T-2 toxin exposure, cerebrocortical and striatal neurons exhibited a dose-dependent decrease in F-DNA hydrolyzability, i.e., impaired chromatin activity, and increases in both chromatin dispersion and nuclear volume. Microscopic observation revealed no gross evidence of T-2 induced neurotoxicity. These data indicate that T-2 toxin elicits both neurochemical injury and adaptive or compensatory processes simultaneously. The toxicological importance of observed nuclear alterations and the role of impairments in central nervous system metabolism in acute T-2 toxicity remain to be ascertained.

Animals↗
PubMed1986

Brain neuronal chromatin responses in acute soman intoxicated rats.

Male Sprague-Dawley rats (200 g) were injected subcutaneously with soman, a potent neuronal acetylcholinesterase (AChE) inhibitor, at doses of 0.5, 0.8 and 1.0 LD50 (1 LD50 = 135 micrograms/kg) before decapitation at 1 and 24 h post-exposure. Correlative data were obtained on the severity of brain AChE inactivation and physicochemical changes in nuclear chromatin of cerebrocortical (layer V) and striatal neurons using Feulgen-DNA (F-DNA) cytophotometry and ocular filar micrometry. Decreased lability of neurons to F-DNA acid hydrolysis (reduced F-DNA yield), nuclear shrinkage and chromatin aggregation (decreased chromophore area) were used as indices of suppression of genomic template activity; conversely, increases in F-DNA yield and chromophore area signify enhanced neuroexcitation. At 1 hr post-soman there was a dose-dependent inactivation of AChE with a moderate increase in chromatin activation, i.e., nuclear hypertrophy and chromatin dispersion. At 24 hr post-soman there was a partial restoration of AChE activity, notably in striatal neurons, with a suppression in chromatin template activity. These data indicate that actions of soman on neuronal functioning are time-dependent. The absence of any dose-related neuronal chromatin changes may signify existence of non-cholinergic mediated events.

Acetylcholinesterase↗
PubMed1986

Quantitative cytophotometric analysis of brain neuronal RNA and protein changes in acute T-2 mycotoxin poisoned rats.

Male Sprague-Dawley rats (200 g) injected intraperitoneally with T-2 toxin, a trichothecene mycotoxin protein synthesis inhibitor, at dosages of 0.75, 1.0, 1.5 and 6.0 mg/kg (1 LD50 = 0.9 mg/kg) were decapitated at 8 hr post-exposure. Data were obtained on changes in neuronal (perikaryal) RNA levels, protein contents and nucleolar volumes in cerebrocortical (layer III) and striatal (caudate-putamen) brain regions using quantitative azure B-RNA and Coomassie-protein cytophotometry and ocular filar micrometry. Correlative observations were made on changes in brain cytomorphology. Reductions in neuronal RNA/protein contents and nucleolar volume were used as indices of impaired perikaryal functioning. At 8 hr after T-2 toxin poisoning the following results were obtained in cerebrocortical and striatal brain compartments: neuronal RNA contents were generally maintained at control values in both brain regions, however, moderate RNA depletion was evidenced in the cerebral cortex with 1.5 mg/kg T-2 and in the striatum with a 6.0 mg/kg dose; neuronal protein levels were suppressed in a dose-dependent fashion within the cerebrocortex, while in the striatum there was no direct correspondence between protein loss and T-2 dosage; neuronal nucleolar volumes were typically maintained at control levels in both neuronal compartments. Microscopic observations revealed no gross evidence of T-2-induced brain cytopathology. These data indicate that T-2 toxin does not elicit direct cytopathic actions in these two brain regions, thus indicating that cerebrocortical and striatal compartments do not represent primary target sites of T-2 toxicant action.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Cytophotometric analysis of neuronal chromatin and RNA changes in oxotremorine-treated rats.

Neuronal nucleic acid responses were examined within the rat striatum and sensorimotor cortex (layer V) following single intraperitoneal injections of the central cholinergic-muscarinic agonist oxotremorine (0.1, 0.7, or 1.0 mg/kg). After stoichiometric Feulgen and azure B staining of brain sections, scanning-integrating microdensitometry was used to quantify Feulgen-deoxyribonucleic acid levels, changes in the susceptibility of chromatin to Feulgen acid hydrolysis (F-DNA yield) and azure B-ribonucleic acid (RNA) content of neurons on an individual basis. Changes in neuronal nuclear and nucleolar volumes were also determined histometrically. Within the striatum and sensorimotor cortex, oxotremorine produced marked dose-dependent elevations in both F-DNA yield and RNA content. These metabolic increases were typically paralleled by elevations in nuclear and nucleolar volumes. The data demonstrate that the oxotremorine-induced central muscarinic activation is associated with dose-related enhancements in neuronal chromatin template activity, RNA content, and protein synthetic capacity.

Animals↗