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PubMedDate not supplied

Autolytic changes in blood cells of human cadavers. II. Morphological studies.

The morphology of various types of cells in the peripheral blood of human cadavers was investigated. The material comprised 123 medicolegal autopsy cases with post-mortem (p.m.) times ranging fro 1.7 to 270.4 hours. The corpses were kept at +4 degrees C. The haematocrit values of the blood increased rapidly after death. The haematocrit-corrected red cell count, and the total white cell and platelet counts remained quite stable during the whole p.m. time range. Red cells were quite rapidly transformed from a discoid configuration to crumbled discs, echinocytes and spherocytes, but no debris or burst cell configurations were seen. Rapid deterioration of the staining properties and marked morphological changes in many leucocytes occurred quite rapidly after death. Lymphocytes seemed to be the most resistant and basophils the least resistant to the effects of autolysis. Morphologically altered platelets and aggregates of them were seen in each cadaver. The present morphological observations and the quantitative results suggest that various cellular elements of the blood seem to be quite resistant to autolytic effects, and many cells apparently retain their viability for longer periods of time in the blood of cadavers kept at reduced temperature.

Adolescent↗

PubMed1978

The Golgi rapid method in clinical neuropathology: the morphologic consequences of suboptimal fixation.

Cytologic changes in neurons of the neocortex of mice consequent to suboptimal fixation have been investigated systematically in Golgi-rapid preparations. With few exceptions, there is no alteration in cellular morphology if the brain is refrigerated after death, and fixed by immersion within 3 hours. With latencies of fixation of 6 hours or more, autolytic changes supervene which modify the general histologic appearance and the morphology of individual cells. In general, the degree of tissue and cellular change is proportional to the latency between death and tissue fixation. Similar alterations in cellular morphology and general tissue appearance are found in Golgi-rapid impregnations of human brains obtained at autopsy. However, the degree of tissue autolysis in the human specimens bears a less predictable relationship to the latency of fixation after death. The duration of preterminal metabolic encephalopathy appears to be equally decisive as a determinant of tissue preservation.

Adolescent↗

PubMed1977

[On the enzymatic breakdown of tripolyphosphate and diphosphate in minced meat. V. Change in the diphosphatase activity of muscle post mortem (author's transl)].

The diphosphatase (DPase) activity of minced bovine muscle decreased during storage of the intact muscle post mortem (p.m.) but there was only little change after development of rigor mortis. The drop in pH p.m. seems to be not the only reason for the decrease in DPase activity. In the postrigor muscle the DPase activity, measured at pH greater than 6, increased during the breakdown of DP. The rise of activity was the slower the longer the muscle was stored. The result of a mathematical regression analysis, developed for the kinetic study of this anomaly in the breakdown of DP, indicates that a certain mechanism of activation of the initially inactive DPase in muscle exists.

Abattoirs↗

PubMedDate not supplied

[The survivability time of central nervous system cells].

Our investigations show that vital functions of some neurons and glial cells may survive for 4-8 hours after death and disappear in parallel with destructive changes in cells. Up-to-date morphological techniques demonstrate that neurons and other cells of the CNS preserve biological activity not for several minutes as believed so far but up to 4-8 hours. It is too early to judge about functional importance of this phenomenon and further investigations into this problem are necessary. Temporal parameters of RNA synthesis in the brain cells give additional knowledge about CNS cells survival and this may be of interest for reanimatology and transplantology.

Autopsy↗

PubMed1975

Changes in phospholipids of ram spermatozoa during migration through the epididymis and possible origin of prostaglandin F2alpha in testicular and epididymal fluid.

A study of the lipid composition of ram testicular and ejaculated spermatozoa was made in an attempt to resolve conflicting results in the literature. Testicular spermatozoa were found to contain more than double the amount of phospholipid present in ejaculated spermatozoa. Most phohpholipid components, including choline plasmalogen, decrease substantially in concentration during migration of the spermatozoa through the male reproductive tract. Phosphatidylserine, ethanolamine phosphoglycerides and cardiolipin components accounted for the greatest relative decreases in concentration, the former decreasing by approximately nine tenths. Of the phospholipid-bound fatty acids the most pronounced change occurs in palmitic during migration of spermatozoa through the reproductive tract. There is a net loss of approx. 500 mug of palmitic acid for every 10-9 spermatozoa. The loss of arachidonic acid was particularly interesting, and prompted a study of the prostaglandin content of testicular and epididymal fluids, since arachidonic acid can act as a precursor of prostaglandin. The concentration of prostaglandin F2alpha found in the testicular and epididymal fluid is considerably in excess of that found in venous plasma of the ram.

Animals↗

PubMed2006

Bodies recovered from wells, sewerage systems and pits: what is the cause of death?

INTRODUCTION: The aim of this study was to determine the problems encountered during investigations into causes of death in corpses found in wells, sewer systems and pits, and to seek solutions to the problems. In fact, wells, sewer systems and pits have some common characteristics which may cause the problems. They contain water, have a hypoxic/anoxic environment and prevent corpses from being recognised. MATERIALS AND METHODS: Based on the data obtained from the 1st Specialization Board of the Council of Forensic Medicine, affiliated with the Ministry of Justice, we retrospectively reviewed 69 corpses found in wells, sewer systems and pits between 1 January 1992 and 31 December 2002. Data on age, sex, crime scene and causes of death were obtained and evaluated using the SPSS 11.0 package programme. RESULTS: Of 69 cases, 69.1% were male and 33.4% were aged 0 to 10 years. Fifty-eight per cent and 13.1% of the cases were found in wells and sewer systems respectively. Forty-three (62.3%) cases were found in a place with water. However, 34.9% of them had not drowned. The most frequent cause of death was drowning (40.6%). The cause of death was unknown in 18.8% of the cases. 15.9% of the corpses were exhumed to determine the cause of death. Twenty-six cases (37.7%) had signs of putrefaction and the cause of death was not determined in 9 cases. Diatom was investigated in 42.0% of the cases (29 cases), but 17 cases did not have diatom. CONCLUSION: It is a complicated process to determine the causes of death in bodies recovered from wells, pits, water supplies and sewer systems, etc. Thorough forensic investigations are required because death may result from a wide variety of factors, and lesions on the corpses may undergo some changes quickly or can be covered in wells, pits and water supplies. A complete crime scene investigation, a thorough autopsy and histopathological, toxicological and biochemical examinations would prevent potential problems in determining the causes of death in bodies recovered from wells, sewer systems and pits. Almost one-third of the bodies recovered from wells, sewer systems and pits were aged 10 years or younger, which indicates a public health problem. Extra safety precautions will help to solve this problem.

Adolescent↗

PubMed2002

Genotype-related differences of hippocampal apolipoprotein E levels only in early stages of neuropathological changes in Alzheimer's disease.

Inheritance of the epsilon4 allele of apolipoprotein E (APOE, gene; apoE, protein) represents the most common genetic risk factor for developing Alzheimer's disease (AD), but the role of apoE in AD pathogenesis is yet to be clarified. A number of studies investigating apoE expression and protein levels in AD brain in correlation to its genetic polymorphism has yielded controversial results. We designed our approach based on neuropathological characteristics of AD to investigate apoE levels in relation to the APOE genotype and AD-related neurofibrillary changes, and amyloid deposits. We determined hippocampal apoE levels by reducing sodium dodecylsulfate-polyacrylamide gel electrophoresis and immunoblotting in 70 Braak-staged and APOE-genotyped autopsy brains. In our stage-, age- and gender-matched case sample, we found a significant increase of hippocampal apoE in the APOE epsilon3 homozygotes with beginning AD-related pathology (Braak stages I and II) compared with brain samples free of neurofibrillary changes and amyloid deposits. In the APOE epsilon4 allele carriers no such increase was found. In both genotype groups, severely affected brain samples with widespread neurofibrillary changes (Braak stages V and VI) and amyloid deposits (Braak stage C) showed low apoE levels comparable to those found in unaffected brain samples (Braak stage 0). Our data suggests that the isoform-specific impact of apoE on the development of AD may be of crucial importance only in the early stages of the disease. These stages are believed to represent phases of the disease in which the beginning neurodegeneration can be compensated by plastic reorganization.

Aged↗

PubMed1988

Change from aerobic to anaerobic metabolism after brain death, and reversal following triiodothyronine therapy.

Brain-dead organ donors are depleted of circulating triiodothyronine (T3) and show features suggestive generally of anaerobic metabolism at the tissue level, accompanied by deteriorating hemodynamic function. The principle of single-bolus kinetics with labeled carbon compounds (14C-R), with subsequent measurement of both plasma activity and of exhaled 14C O2 has therefore been used to study glucose, pyruvate, and palmitate utilization under conditions of (1) sedation, (2) brain death, and (3) brain death with T3 therapy in the baboon. Serum lactate and plasma-free fatty acid concentrations were also measured. There was a major change in metabolic oxidative processes following brain death. The rate of glucose, pyruvate, and palmitate utilization was markedly reduced, and there was an accumulation of lactate and free fatty acids in the plasma, indicating a general change from aerobic to anaerobic metabolism. The administration of T3 to the brain-dead baboon resulted in a dramatic increase in the rate of metabolite utilization, and a reduction in the plasma concentrations of plasma lactate and free fatty acids, indicating an apparent reversal from tissue anaerobic to aerobic metabolism. We suggest that T3 should be administered to all brain-dead potential organ donors to correct and maintain a more physiologic metabolic status and thus to improve organ function.

Aerobiosis↗

PubMed2005

Elevated levels of the NR2C subunit of the NMDA receptor in the locus coeruleus in depression.

Low levels of the intracellular mediator of glutamate receptor activation, neuronal nitric oxide synthase (nNOS) were previously observed in locus coeruleus (LC) from subjects diagnosed with major depression. This finding implicates abnormalities in glutamate signaling in depression. Receptors responding to glutamate in the LC include ionotropic N-methyl-D-aspartate receptors (NMDARs). The functional NMDAR is a hetero-oligomeric structure composed of NR1 and NR2 (A-D) subunits. Tissue containing the LC and a nonlimbic LC projection area (cerebellum) was obtained from 13 and 9 matched pairs, respectively, of depressed subjects and control subjects lacking major psychiatric diagnoses. NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively. In contrast to NRI and NR2C, very weak immunoreactivity of NR2A and NR2B subunits was observed in the LC. Possible changes in concentrations of NR1 and NR2C that might occur in depression were assessed in the LC and cerebellum. The overall amount of NR1 immunoreactivity was normal in the LC and cerebellum in depressed subjects. Amounts of NR2C protein were significantly higher (+ 61%, p = 0.003) in the LC and modestly, but not significantly, elevated in the cerebellum (+ 35%) of depressives as compared to matched controls. Higher levels of NR2C subunit implicate altered glutamatergic input to the LC in depressive disorders.

Adult↗

PubMed2004

A laboratory incubation method for determining the rate of microbiological degradation of skeletal muscle tissue in soil.

A controlled laboratory experiment is described, in principle and practice, which can be used for the of determination the rate of tissue decomposition in soil. By way of example, an experiment was conducted to determine the effect of temperature (12 degrees, 22 degrees C) on the aerobic decomposition of skeletal muscle tissue (Organic Texel x Suffolk lamb (Ovis aries)) in a sandy loam soil. Measurements of decomposition processes included muscle tissue mass loss, microbial CO2 respiration, and muscle tissue carbon (C) and nitrogen (N). Muscle tissue mass loss at 22 degrees C always was greater than at 12 degrees C (p < 0.001). Microbial respiration was greater in samples incubated at 22 degrees C for the initial 21 days of burial (p < 0.01). All buried muscle tissue samples demonstrated changes in C and N content at the end of the experiment. A significant correlation (p < 0.001) was demonstrated between the loss of muscle tissue-derived C (Ct) and microbially-respired C (Cm) demonstrating CO2 respiration may be used to predict mass loss and hence biodegradation. In this experiment Q10 (12 degrees C-22 degrees C) = 2.0. This method is recommended as a useful tool in determing the effect of environmental variables on the rate of decomposition of various tissues and associated materials.

Animals↗

PubMed2006

Dermal lesions after post mortem petrol-exposure.

The effect of post mortem contact of the skin with petrol was investigated in 18 corpses with exposure times between 10 min and 24 h. The earliest onset of skin changes was observed within 2 h of exposure. They consisted of swelling and wrinkling with detachment of the upper layers of the skin (positive Nikolski's sign). Histologically the lesions appeared as non-vital acantholyses located in the prickle-cell layer with formation of intra-epidermal bullae. An influence of age and sex could be excluded, the earlier onset of lesions at 22 degrees C than at 4 degrees C was not statistically significant. These findings prove that post mortem petrol exposure may lead to dermal lesions.

Adult↗

PubMed1990

Effects of transient forebrain ischemia and pargyline on extracellular concentrations of dopamine, serotonin, and their metabolites in the rat striatum as determined by in vivo microdialysis.

Striatal microdialysis was performed in rats subjected to 20 min of transient forebrain ischemia produced by occlusion of the carotid arteries during hemorrhagic hypotension. Extracellular changes of dopamine, serotonin, and their metabolites were monitored before, during, and after the ischemic insult at 10-min intervals by on-line HPLC analysis. During ischemia, extracellular dopamine increased dramatically (156 times baseline), as did 3-methoxytyramine (3-MT), whereas 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) decreased (15-25% of baseline). Upon reperfusion, dopamine was cleared from the extracellular fluid within 40 min and reached a stable level (70% of baseline). DOPAC and HVA increased (250-330%) transiently and reached their maximum 1 h following reperfusion, whereas 3-MT decreased to undetectable levels within 20 min. Although baseline levels of serotonin were not detectable, serotonin and 5-hydroxyindoleacetic acid showed a qualitatively similar temporal pattern to dopamine and its acid metabolites. Killing rats by cervical dislocation produced changes in extracellular dopamine, serotonin, and their metabolites that were almost identical to those seen during ischemia. Pargyline pretreatment 2 h before ischemia had marginal effects on the postischemic clearing of dopamine. The pargyline pretreatment, however, did increase the survival rate of rats subjected to ischemia, and this protective effect might be due to the pargyline-induced blockade of the post-ischemic monoamine oxidase-mediated increase in dopamine metabolism and the concurrent production of the potentially neurotoxic molecule, hydrogen peroxide.

Animals↗

PubMed1998

Loss of inositol 1,4,5-trisphosphate receptor sites and decreased PKC levels correlate with staging of Alzheimer's disease neurofibrillary pathology.

Inositol 1,4,5-trisphosphate (IP3), inositol 1,3,4,5-tetrakisphosphate (IP4) and protein kinase C (PKC) play important roles in the phosphoinositide hydrolysis signal transducing pathway. Several studies have shown severe deficits in both IP3 receptor levels and PKC levels and activity in Alzheimer's disease brain, although the relationship of these changes to disease pathology is poorly understood. In the present study, we determined the autoradiographic localization of [3H]IP3 and [3H]IP4 binding to their calcium mobilizing receptor sites and [3H]phorbol 12,13-dibutyrate ([3H]PDBu) binding to PKC in sections of entorhinal cortex/hippocampal formation and cerebellum from 24 cases that had been staged for Alzheimer's disease-related neurofibrillary changes and amyloid deposition according to Braak and Braak [Acta Neuropathol. Berl., 82 (1991) 239-259]. Results indicated that [3H]IP3 binding showed a trend towards a decline with staging for neurofibrillary changes in the entorhinal region (0.05 < P < 0.10, ANOVA) and subiculum (0.05 < P < 0.10). In the former region, [3H]IP3 binding showed a significant decline with staging for amyloid deposition (P < 0.05). [3H]IP3 binding in the CA1 region showed statistically significant declines with respect to both neurofibrillary changes and amyloid staging (P < 0.05). [3H]IP3 binding levels in the other hippocampal subregions were too low to quantify accurately. The binding of [3H]IP4 showed no significant changes with either neurofibrillary changes or amyloid staging in any of the regions investigated. In contrast, [3H]PDBu binding showed significant declines with neurofibrillary staging in the entorhinal region (P < 0.01), subiculum (P < 0.001), CA1 (P < 0.001), CA2 (P < 0.001), CA3 (P < 0.001) and CA4 (P < 0.0001) regions and the dentate gyrus (P < 0.0001). Of these regions, only the subiculum showed a significant decline of [3H]PDBu binding with amyloid staging. There were no significant neurofibrillary or amyloid stage-related changes in either [3H]IP3, [3H]IP4 or [3H]PDBu binding in the molecular layer of the cerebellum. These findings suggest that reduced IP3 receptor and PKC levels in the entorhinal cortex/hippocampal formation reflect and may be important for the progression of Alzheimer's disease neurofibrillary pathology. The data also suggests that hippocampal IP3 receptor loss is related to the extent of amyloid deposition.

Adult↗

PubMed1984

Post-mortem analyses of neuropeptides in brains from sudden infant death victims.

The causative factors underlying SIDS are still unknown, but in recent years much interest has been focused on the central ventilatory control system. In this study, peptides which are known to affect respiration were examined in brains from SIDS victims and controls. The levels of Met-enkephalin and substance P were measured in cortex, medulla oblongata, pons and hypothalamus. Substance P1-7, substance P C-terminal fragments, Met-enkephalin-Lys6 and neuropeptide Y (NPY) were estimated in medulla oblongata. The substance P levels in the medulla oblongata from the SIDS victims were significantly elevated compared with the controls. No change, however, was observed in the Met-enkephalin levels, but a tendency to higher levels in the youngest infants was noticed. As substance P and enkephalins have opposite effects on respiration, their relative concentrations were calculated in each individual sample. The ratio was significantly higher in the medulla oblongata from the SIDS victims. The levels of NPY, substance P1-7, C-terminal fragments of substance P and Met-enkephalin-Lys6 were similar in both groups. A significant correlation between the NPY levels and age was observed, however.

Age Factors↗

PubMed1992

Variations of monoamines and their metabolites in the human brain putamen.

The levels of the monoamines dopamine (DA), serotonin (5-HT) and norepinephrine (NE) and the monoaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured with HPLC-ECD in 42 samples from human brain putamen. The influence of gender and of age was investigated and correlations between the monoamines were established. The DAergic system shows a significant difference between males and females, with females having lower DA and higher DOPAC levels and a higher DOPAC/DA ratio than males. No gender-related differences of 5-HT and its metabolites were observed, nor of NE. Three different age groups (group 1: 0-9.9 years: group 2: 10-59.9 years; group 3: 60 years and older) were defined according to previous studies on ontogenesis and senescence in human brain. An increase in 5-HT levels, decrease in 5-HIAA levels and a decrease in the 5-HIAA/5-HT ratio were observed after the first decade of life. Changes in the DAergic system were seen in senescence, with decreasing DA levels and an increase in the HVA/DA ratio. DOPAC, HVA and the DOPAC/DA ratio are unaffected. NE is similar in all age groups. The analysis of the relation of the levels of the three monoamines proved a strong correlation between the DAergic and 5-HTergic systems. The nature of this relationship might have an impact on neuro-psychiatric disorders and brain function.

Adolescent↗

PubMed2006

Distinctive profiles of gene expression in the human nucleus accumbens associated with cocaine and heroin abuse.

Drug abuse is thought to induce long-term cellular and behavioral adaptations as a result of alterations in gene expression. Understanding the molecular consequences of addiction may contribute to the development of better treatment strategies. This study utilized high-throughput Affymetrix microarrays to identify gene expression changes in the post-mortem nucleus accumbens of chronic heroin abusers. These data were analyzed independently and in relation to our previously reported data involving human cocaine abusers, in order to determine which expression changes were drug specific and which may be common to the phenomenon of addiction. A significant decrease in the expression of numerous genes encoding proteins involved in presynaptic release of neurotransmitter was seen in heroin abusers, a finding not seen in the cocaine-abusing cohort. Conversely, the striking decrease in myelin-related genes observed in cocaine abusers was not evident in our cohort of heroin subjects. Overall, little overlap in gene expression profiles was seen between the two drug-abusing cohorts: out of the approximately 39,000 transcripts investigated, the abundance of only 25 was significantly changed in both cocaine and heroin abusers, with nearly one-half of these being altered in opposite directions. These data suggest that the profiles of nucleus accumbens gene expression associated with chronic heroin or cocaine abuse are largely unique, despite what are thought to be common effects of these drugs on dopamine neurotransmission in this brain region. A re-examination of our current assumptions about the commonality of molecular mechanisms associated with substance abuse seems warranted.

Adult↗

PubMed1999

A case study of selected medical findings among plutonium injectees.

Available medical records of plutonium injectees exposed in experimental studies of plutonium biokinetics under Manhattan Engineer District auspices have been reviewed for subsequent medical findings potentially related to the plutonium exposures. Five subjects who had been injected with approximately 11 kBq 239Pu, and one injected with 3.5 kBq 238Pu, had useful follow-up medical data. Bone lesions dominated the findings: none of six subjects with follow-up for bone conditions lacked bone lesions clearly or potentially caused, or worsened, by plutonium. Roentgenograms of three subjects, read by a radiologist experienced reading films of radium cases, demonstrated possible to likely plutonium effects. Two cases of osteoporosis or non-specific degenerative changes were seen, associated with a hip fracture and vertebral fractures. Areas of increased bone density were seen, as well as numerous dystopic calcifications and one unusual case of widespread pathologic calcification on bone surfaces probably due to a plutonium-related calciphylactic reaction. Non-skeletal findings include labyrinthitis with inflammatory mastoid changes, conduction deafness, and a benign neurofibroma directly adjacent to bone. The radium literature contains similar observed findings, but interpretation of these limited clinical observations is hampered by lack of quantitative data on humans exposed to radium with respect to prevalence of non-specific ear, mastoid, and skeletal symptomatologies or x-ray findings, or cumulative incidence rates of bone fractures or of other physical disabilities related to ear, mastoid, or bone damage. Disability and invalidism late in life can be risk factors for earlier mortality.

Adolescent↗

PubMed1990

Circadian rhythms of human pineal melatonin, related indoles, and beta adrenoreceptors: post-mortem evaluation.

Human pineal glands obtained from 77 post-mortem sources from various age groups and times of death were used to examine the 24-hour cycle of serotonin (5-HT), melatonin, N-acetylserotonin (NAS), and beta adrenoceptor density. Pineal glands were divided sagittally and a single half was used to measure 5-HT, NAS, and melatonin concentrations, while the remaining half from the same gland was employed to assess changes in the density of beta adrenoceptors on partially purified membranes. The results show that density of pineal beta adrenoceptors was relatively constant between midnight and 18.00 h and became significantly higher between 18.00 and 20.00 h as measured by ligand saturation binding experiments using (125-I) iodocyanopindolol. The receptor affinity of all of the samples assayed remained in relatively narrow range near 58 pM and only changes in the relative receptor density were apparent. The up-regulation of receptors coincided with an increase in the concentration of 5-HT that began to rise between 16.00 and 20.00 h and became maximal between 20.00 and midnight. NAS, the immediate precursor of melatonin, was also at maximal levels between 20.00 h and midnight. Both 5-HT and NAS began declining after midnight and this change corresponded to the maximal pineal gland concentration of melatonin between midnight and 4.00 h. It is therefore suggested that the up-regulation of beta adrenoceptors noted during the late afternoon and early evening hours corresponds to the increased synthesis of 5-HT and the subsequent conversion to NAS. These events are followed by the highest accumulation of melatonin after midnight and represent the synthesis of melatonin from its precursor NAS in a sequential pattern.

Adolescent↗