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Mammoth albumin.

Serum albumin was detected immunologically in muscle from a mammoth that died about 40,000 years ago. Rabbits injected with ground mammoth muscle produced antibodies that react strongly with elephant albumin, weakly with sea cow albumin, and still more weakly or not at all with other mammalian albumins. Since elephant albumin elicited antibodies with the same specificity, some of the surviving mammoth albumin molecules evidently have antigenic sites identical to those on native elephant albumin. Much of the mammoth albumin has, however, undergone postmortem change. The small amount of soluble albumin extractable from mammoth muscle is heterogeneous in size, charge, and antigenic properties.

Animals↗

Interpreting bruises at necropsy.

The accurate interpretation of bruising at necropsy is essential to understanding how a victim has been injured and assists the pathologist in a reliable reconstruction of the events leading to death. It is essential not only to assess the mechanism of production of a bruise, taking into account the type of impacting surface and the magnitude of force used, but also to estimate when the injury was caused. An account is given of the various methods used in the examination of bruises, particularly with respect to aging, as well as the factors that may affect their appearance. Differentiation from artefacts resulting from postmortem changes is also discussed in some detail.

Artifacts↗

Clinical and pathological features of dilated cardiomyopathy in Holstein-Friesian cattle.

Dilated cardiomyopathy is a primary disease of the heart muscle that has been reported in Holstein-Friesian cattle worldwide in the past 20 years. Nine cases of the condition were compared in terms of their clinical and pathological characteristics with nine unaffected animals matched for age, sex and breed. Their clinical signs included right-sided heart failure with severe subcutaneous oedema, ascites and/or hydrothorax and distended jugular veins. There were no characteristic biochemical or haematological changes. Postmortem, the affected hearts were enlarged with all the chambers dilated and walls of variable thickness. In most cases the kidneys were pale with a pitted surface. Histologically there was marked perimysial and endomysial fibrosis, extensive loss of cardiomyocytes by coagulative or colliquative necrosis, increased variation in the cross-sectional area of the myocardial fibres, and multifocal disarray and vacuolation of myocytes. Scanning electron microscopy showed that in all cases there was a mild myocardial inflammatory infiltrate, either diffuse or multifocal, which was identified by immunohistochemical labelling as T cells.

Age Factors↗

A potential artifact in use of a new technique for rapid brain removal.

New techniques are are continuously being developed to obtain animal brain tissue that is as close as possible to its in vivo status. The brain-blowing technique provides a swift freezing of brain tissue (within 1 s) in which postmortem changes have been said to be minimal. Higher concentrations of glucose were present in brain samples removed by this method than have previously been found when the brain was frozen in situ, but at the same time the plasma levels of glucose were higher. It is suggested that, although the procedure did not appear to involve any stress, the hyperglycemia was stress related. Modifications of the procedure are described, by which these changes in blood glucose have been minimized.

Animals↗

Spondyloarthropathy in progressive ankylosis mice: ultrastructural features of the intervertebral disk.

Progressive ankylosis mice (ank/ank) spontaneously develop a joint disorder characterized by calcium hydroxyapatite deposition and bony ankylosis of the joints of the axial and the appendicular skeleton. Mice in this study were used to determine the extent of mineralization of the intervertebral disks and to determine their suitability as a model for ankylosing spondyloarthropathies. Intervertebral disks taken from affected mice from 4 to 18 weeks of age were studied by electron-microscopic, electron energy-dispersive X-ray microanalysis and selected-area electron diffraction techniques. Necrotic foci seen in light microscope studies were found to be massive accumulations of calcium hydroxyapatite crystals deposited within the extracellular matrix. Chondrocytes of older animals demonstrated what appeared to be postmortem changes and contained numerous large vacuoles.

Animals↗

Hibernating myocardium: chronically adapted to ischemia but vulnerable to sudden death.

The inability to reproduce spontaneous ventricular fibrillation in an animal model of chronic coronary artery disease has limited advances in understanding mechanisms of sudden cardiac death (SCD). Swine with hibernating myocardium arising from a chronic left anterior descending coronary artery (LAD) occlusion have a high rate of SCD that parallels the poor clinical survival of medically treated patients with hibernating myocardium. Kaplan-Meier analysis (n=426) demonstrated a cumulative mortality of 49% after 5 months that was almost entirely attributable to spontaneous SCD. Using implantable loop recorders, ventricular fibrillation was documented as the arrhythmic mechanism of death in all animals (n=10) and was usually preceded by ventricular tachycardia (n=8). Physiological studies before SCD (n=7) demonstrated total LAD occlusion and collateral-dependent myocardium (n=5), excluding acute occlusion as a major trigger of arrhythmia. The physiological substrate of hibernating myocardium was present before SCD, with reductions in LAD perfusion (SCD 0.79+/-0.13 versus 0.80+/-0.08 mL/min per g) and wall thickening (SCD 28+/-3% versus 22+/-3%) that were similar to survivors (n=14). Triphenyltetrazolium chloride infarcts among animals with SCD were infrequent (4 of 32) and small, averaging 4.6% of LV mass. Histology (n=4) showed postmortem changes but no acute inflammation nor contraction band necrosis. These data support the notion that hibernating myocardium is a pathophysiological substrate at high risk of SCD. This is independent of changes in functional stenosis severity, acute myocardial necrosis, or fibrotic scar. Thus, regional adaptations that promote myocyte survival in the setting of chronic repetitive ischemia result in a substrate with enhanced vulnerability to lethal arrhythmias and SCD.

Adaptation, Physiological↗

Abnormalities in airway smooth muscle in fatal asthma. A comparison between trachea and bronchus.

Tracheal smooth muscle from seven cases of fatal asthma demonstrated an increased contractile response to histamine, acetylcholine, and electrical stimulation of intrinsic cholinergic nerves; impaired relaxation to isoproterenol, and possibly theophylline, was also evident (1). Fourth generation bronchial spirals from the same patients were also studied, and these results were compared with those of the trachea and normal bronchi (n = 5). In contrast to trachea, contractile responses in asthmatic bronchi to acetylcholine, histamine, and cholinergic nerve stimulation were similar to those in control bronchi. The potency of isoprenaline (IC50) was reduced 9.4-fold (p less than 0.003), similar to trachea (4.5-fold), whereas theophylline responses were normal. The discrepant results obtained may reflect differences in the disease process, including rates of postmortem change, at the two anatomic sites.

Acetylcholine↗

Exercise in paleo-otolaryngology: head and neck examination of two Egyptian mummies.

Two Ptolemaic period mummies underwent head and neck examination including high-resolution tomography and endoscopic rhinoscopy and cranioscopy. The anatomy demonstrated characteristic laryngeal calcification and sexual dimorphism. Pathologic findings consisted of severe dental disease and possible chronic ear disease. Postmortem changes revealed the entrance of the embalmers into the cranial cavity, but raised interesting speculation regarding the method of brain removal.

Dentition↗

The estimation of tooth age from attrition of the occlusal surface.

Age estimation in unidentified bodies is inaccurate. Usually only a broad range of ages, such as 20-30 years or 30-50 years, can be given, especially when postmortem change has occurred. Thus there is a real need in routine forensic practice for greater accuracy. Takei (1970, 1981), looked at the relationship between teeth and age by using the 'Theory of Quantification'. Song and Jia (1987), extended the use of this technique, adding multiple stepwise regression analysis, to the statistical examination of data derived from the study of attrition of the occlusal surfaces of teeth. The computer model thus derived provides a basis for an accurate assessment of age from qualitative material. This paper discusses the technique and is based upon the findings made during a study of the degree of occlusal attrition in 880 people, living in rural and urban areas of the Liaoning province of the People's Republic of China.

Adolescent↗

Experimental Clostridium perfringens type D enterotoxemia in goats.

The effects of intraduodenal administration of Clostridium perfringens cultures and culture products in goats were evaluated to develop a reliable experimental model of enterotoxemia in this species. Five conventionally reared, 11-16-week-old Angora goat kids were dosed intraduodenally with whole cultures of C. perfringens type D; five similar animals were dosed with C. perfringens type D filtered culture supernatant; and a third group of five kids was dosed with C. perfringens type D washed cells. Two kids were used as controls and received sterile, nontoxic culture medium intraduodenally. All animals received starch solution into the abomasum. All five kids inoculated with whole culture and three of five dosed with culture supernatant and with washed cells developed central nervous system signs. Diarrhea was observed in two of five kids inoculated with whole culture, in all five of those dosed with culture supernatant, and in three of five of those that received washed cells. The most striking postmortem findings consisted of lung edema, necrotizing pseudomembranous colitis, and cerebral vasogenic edema. The protocol thus provided a reasonable model of naturally occurring enterotoxemia in goats, producing a range of clinical signs and postmortem changes similar to those observed in the natural disease.

Abomasum↗

An autosomal recessive, lethal, neurologic disease of Gordon Setter puppies.

This report details clinical, necropsy, and pedigree data on an inherited, lethal, neurologic disease of young Gordon Setters. This disorder is characterized by an early age of onset, gait and postural abnormalities, progressive weakness, and recumbency by 5-6 weeks of age. Although clinically distinctive, postmortem changes in affected pups were minimal. Gross lesions were not observed. Microscopic changes were subtle and consisted of astrocyte swelling, primarily in the cerebrocortical and cerebellar white matter, and white matter tracts of the brainstem. Immunohistochemistry for glial fibrillary acidic protein revealed a marked increase in the number and staining intensity of astrocyte cytoplasmic processes in affected pups compared with age-matched controls. Neither cerebral inflammation nor neuronal necrosis was identified. Pedigree analysis of affected litters demonstrated an autosomal recessive mode of inheritance. A diagnosis of this heritable disease should be based on the early age of onset (3-4 weeks of age), characteristic clinical signs, rapid progression to recumbency by 5-6 weeks of age, identification of swollen astrocytes primarily in the cerebellar and cerebrocortical white matter and white matter tracts of the brainstem, and the exclusion of other disease processes.

Animals↗

The pathology of peracute experimental Clostridium perfringens type D enterotoxemia in sheep.

The pathological findings in sheep with peracute experimental Clostridium perfringens type D enterotoxemia are described. Of 16 animals inoculated intraduodenally with a whole culture of this microorganism and a starch solution in the abomasum, 12 developed clinical signs including increased respiratory efforts, recumbency, paddling, bleating, convulsions, blindness, and opisthotonus. Diarrhea was not observed in any of the animals. The time lapse between the beginning of intraduodenal infusion and onset of clinical signs varied between 30 minutes and 26 hours, and the clinical course varied between 1 and 9 hours. Gross postmortem changes were observed in these 12 animals and included pulmonary edema; excess pericardial, peritoneal, or pleural fluid with or without strands of fibrin; liquid small intestinal contents; leptomeningeal edema; cerebellar coning; and subcapsular petechiae on kidneys. Histological changes consisted of severe edema of pleura and interlobular septa and around blood vessels and airways and acidophilic, homogeneous, proteinaceous perivascular edema in the brain. Five of 12 animals (42%) with clinical signs consistent with enterotoxemia lacked specific histological lesions in the brain. None of the intoxicated or control animals developed nephrosis. Glucose was detected in the urine of 3 of 6 animals that were tested for this analyte. These results stress the importance of the use of histological examination of the brain, coupled with epsilon toxin detection, for a definitive diagnosis of C. perfringens type D enterotoxemia in sheep.

Animals↗

Monitoring immediate-early gene expression through firefly luciferase imaging of HRS/J hairless mice.

BACKGROUND: Gene promoters fused to the firefly luciferase gene (luc) are useful for examining gene regulation in live transgenic mice and they provide unique views of functioning organs. The dynamics of gene expression in cells and tissues expressing luciferase can be observed by imaging this enzyme's bioluminescent oxidation of luciferin. Neural pathways involved in specific behaviors have been identified by localizing expression of immediate-early genes such as c-fos. A transgenic mouse line with luc controlled by the human c-fos promoter (fos::luc) has enabled gene expression imaging in brain slice cultures. To optimize imaging of immediate-early gene expression throughout intact mice, the present study examined fos::luc mice and a second transgenic mouse containing luc controlled by the human cytomegalovirus immediate-early gene 1 promoter and enhancer (CMV::luc). Because skin pigments and hair can significantly scatter light from underlying structures, the two transgenic lines were crossed with a hairless albino mouse (HRS/J) to explore which deep structures could be imaged. Furthermore, live anesthetized mice were compared with overdosed mice. RESULTS: Bioluminescence imaging of anesthetized mice over several weeks corresponded with expression patterns in mice imaged rapidly after a lethal overdose. Both fos::luc and CMV::luc mice showed quantifiable bright bioluminescence in ear, nose, paws, and tail whether they were anesthetized or overdosed. CMV::luc and fos::luc neonates had bioluminescence patterns similar to those of adults, although intensity was significantly higher in neonates. CMV::luc mice crossed with HRS/J mice had high expression in bone, claws, head, pancreas, and skeletal muscle, but less in extremities than haired CMV::luc mice. Imaging of brain bioluminescence through the neonatal skull was also practical. By imaging luciferin autofluorescence it was clear that substrate distribution did not restrict bioluminescence imaging to capillaries after injection. Luciferin treatment and anesthesia during imaging did not adversely affect circadian rhythms in locomotor activity. CONCLUSIONS: Imaging of gene expression patterns with luciferase can be extended from studies of live animals to rapid imaging of mice following a pentobarbital overdose before significant effects from postmortem changes occurs. Bioluminescent transgenic mice crossed with HRS/J mice are valuable for examining gene expression in deep tissues.

Animals↗

Measurement and prediction of functional capacity in Alzheimer's disease.

Functional loss in Alzheimer's disease is difficult to measure or predict. The Blessed Dementia Rating Scale (Part 1) correlates well with postmortem changes but is not an effective antemortem index of functional change since disparate behavioral domains are assessed. We performed a factor analysis of the Blessed items in 187 patients with clinically diagnosed Alzheimer's disease and identified 4 independent factors: (I) cognitive, (II) personality, (III) apathy, and (IV) basic self-care. An endpoint, consisting of a score indicative of moderate disability, was determined for each factor. We then used life table analyses to compare the probability of reaching these endpoints over time in longitudinally followed patients. Patients with extrapyramidal signs at their initial visit reached the factor IV endpoint sooner, and those with psychosis or no family history of dementia also reached the factor I endpoint faster. These data illustrate the utility of a multifactorial approach to the assessment of functional capacity in Alzheimer's disease, and also indicate that extrapyramidal symptoms and psychosis are powerful predictors of the rate of decline in basic self-care activities and cognition.

Aged↗

Inhibition of acetylcholinesterase activity in human brain tissue and erythrocytes by galanthamine, physostigmine and tacrine.

Galanthamine, physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (tacrine) were evaluated as inhibitors of human acetylcholinesterase activity from samples of postmortem human brain, fresh brain cortex biopsies and human erythrocytes. Acetylcholinesterase activity was most effectively inhibited in all tissues by physostigmine, followed by tacrine and galanthamine. The respective inhibitor concentrations exerting a half maximal effect (IC50) on acetylcholinesterase in postmortem human brain frontal cortex were 14 nmol/l, 1.0 mumol/l and 3.2 mumol/l versus 15 nmol/l, 1.1 mumol/l and 2.8 mumol/l in the hippocampus region. In addition, the inhibition of acetylcholinesterase by galanthamine was similar in postmortem brain and brain cortical biopsies from patients submitted to brain-tumour removal, indicating that postmortem changes up to 28 h after death probably did not influence the measurement of acetylcholinesterase inhibition. While physostigmine and tacrine acted equally on acetylcholinesterase from different sources, galanthamine was 10-fold less potent in inhibiting the enzyme activity from human brain that from human erythrocytes. Comparison with issues from mice revealed that galanthamine was selectively more potent in suppressing acetylcholinesterase in human erythrocytes. The results are discussed in the light of pharmacokinetic data, and conclusions are drawn for further clinical studies.

Acetylcholinesterase↗

Phosphorus-31 nuclear magnetic resonance study of energy metabolism in intact slow- and fast-twitch muscles of rats.

The time course of the catabolism of phosphorylated metabolites was studied by phosphorus-31 NMR(31P NMR) spectroscopy over a 6-h period after the isolation of rat slow- and fast-twitch muscles, the soleus and the extensor digitorum longus (EDL), respectively, obtained without any muscle damage. In both muscles, rapid depletion of creatine phosphate was followed by a decrease in ATP. These high-energy phosphates disappeared earlier in the soleus than in the EDL. In both muscles, inorganic phosphate (Pi) largely increased in a biphasic pattern, and sugar phosphates (SP) also showed considerable increase. The NMR-visible total phosphates (NTP) increased significantly in the soleus during the latter stage of observation. This increase in NTP was attributed to an increase in Pi. Although the two muscles showed the same initial (7.21) and final (approximately 5.9) intracellular pH (pHi), the pattern of pHi decline differed between these muscles. The rapid fall of pHi in the soleus in the early stage suggests that nonlactic acid acidosis plays a significant role in postmortem changes.

Animals↗

Sex-related reduced weight gains in growing swine fed diets containing deoxynivalenol.

A 5-wk feeding trial was conducted with 30 castrated male and 28 female, 5-wk-old crossbred piglets. Three different deoxynivalenol (DON) and zearalenone (Z)-contaminated diets were fed: .7, 3.1 and 5.8 ppm DON and 0, .05, and .1 ppm Z, respectively. The animals were fed their respective diets for 4 wk followed by the .7:0-ppm diet during wk 5. Feed intake and weight gain varied in a manner reciprocal to the levels of DON-Z in the diets during the first 4 wk (P less than .05). The castrated males had an overall lower weight gain compared with the females receiving the same diet (P less than .05). Gross postmortem changes were not different in either sex and tended to be most prominent in the pigs fed the lower DON:Z-contaminated diets after the first week, although they were seen in pigs fed the higher DON:Z diets after 4 wk of feeding. Lesions included mild to moderated reddening of the fundic mucosa of the stomach, reddening of the mucosa of the small intestine, and mild to moderate enlargement and edema of the mesenteric lymph nodes. Similarly, the severity of histologic changes tended to vary inversely with the concentrations of DON:Z in the diets after the first week but varied with the concentrations of DON:Z after 4 wk. They consisted of vascular congestion with mild to moderate multifocal erosions and degeneration of the mucosa in the stomach and small intestine. Mild to moderate lymphoid degeneration and depletion were also observed in the Peyer's patches of the intestines, bronchial and mesenteric lymph nodes, spleen, tonsil and thymus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗