A comparative analysis of the distribution of prosomatostatin-derived peptides in human and monkey neocortex.

Comparative analyses were made of the immunohistochemical and biochemical distributions of three prosomatostatin-derived peptides (PSDP) in human, perfused monkey, and unperfused monkey neocortex. The PSDP we examined were the tetradecapeptide somatostatin 14 (SS14); the N-terminal extension of this peptide, somatostatin 28 (SS28); and somatostatin 28(1-12) (SS28(1-12)). In immunohistochemical experiments, numerous SS28-immunoreactive perikarya were located in both superficial and deep layers of perfused monkey cortex, but none were present in the cerebral cortex from unperfused monkey or autopsied human brains. In contrast, the number of SS28(1-12)-immunoreactive neurons was five times greater in the superficial cortical layers of unperfused monkey than of perfused monkey brain. Moreover, unperfused monkey and human cortex contained notably more SS14-immunoreactive processes than perfused monkey cortex. These data suggested that SS28 may have been converted into SS14 and SS28(1-12) in unperfused tissue during the post-mortem interval. This hypothesis was examined biochemically by measuring the levels of immunoreactivity of SS14, SS28, and SS28(1-12) in samples of unperfused monkey cortex frozen at different time intervals after removal from the brain. Samples frozen 10 minutes or longer after removal contained only 10-20% the level of SS28 immunoreactivity measured in samples frozen immediately or 1 minute after removal. The levels of SS14 and SS28(1-12) immunoreactivity did not demonstrate such reductions, and may instead have increased at early time points. To further characterize post-mortem effects on PSDP and to explore for species differences, we performed a detailed comparison of the regional, laminar, and cellular distribution of SS28(1-12) immunoreactivity under the three conditions. A progressive loss of immunoreactivity, particularly in radial fibers, was found at increasing post-mortem intervals in unperfused monkey neocortex, indicating that differences in density and distribution of immunoreactive fibers between human and perfused monkey may result from post-mortem peptide degradation in unperfused tissue. In contrast, the larger size of SS28(1-12)-immunoreactive white matter neurons in humans as compared to monkeys appeared partially due to a post-mortem effect but also reflected a species difference. In addition, the density of white matter neurons was found to be significantly greater in human than in perfused or unperfused monkey. These data indicate that any study of human autopsy material must be assessed in light of possible post-mortem effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Up-regulation of adenosine A1 receptors in frontal cortex from Pick's disease cases

The adenosine A₁ receptor (A₁R)–adenylyl cyclase (AC) pathway was studied in post-mortem human frontal and occipital cortex from Pick's disease (PiD) cases and age-matched nondemented controls. In frontal cortex, the main brain area affected in PiD, A₁Rs, determined by radioligand binding, Western blotting and real-time PCR assays, were significantly increased in PiD samples, suggesting up-regulation of this receptor. AC activity was determined in basal and stimulated conditions via stimulatory guanine nucleotide binding proteins (Gs) using GTP, or directly with forskolin. Basal AC activity was reduced in brains from PiD cases. This agrees with the decrease in AC type I (AC I) level detected by Western blotting. However, inhibition of forskolin-stimulated AC activity by a selective A₁R agonist was significantly increased in brains from PiD. In occipital cortex, adenosine A₁R numbers were similar in control and PiD cases, and no significant differences were found in A₁R-mediated AC inhibition. These results show that the adenosine A₁R–AC transduction pathway is specifically up-regulated and sensitized in frontal cortex brain in PiD.     

Normal ascent of the conus medullaris: a post-mortem foetal MRI study

Abstract

Objectives: The position of the conus medullaris is considered abnormal if it ends below lumbar vertebrae three (L3) at birth. We used magnetic resonance imaging (MRI) to measure the position of the conus in post-mortem foetuses, to investigate the timing of normal ascent.

Methods: The position of the conus in 84 post-mortem foetuses (mean gestation 26.3 weeks; range 14–41 weeks) was identified using 3D MRI datasets. A numerical scale was used for vertebral levels, from 1 (S2) to 15 (T12).

Results: There was significant ascent of the conus medullaris with increasing gestation. At 20 weeks gestation, an estimated 84.2% (95% confidence interval (CI): 72.9, 93.2%) of foetuses have a conus position of L4/5 or higher, but only 22.8% (95% CI 11.7, 34.9%) at L3 or higher. By 26 weeks, an estimated 50.7% (95% CI 34.1, 67.5) will have reached L3, and 94.8% (95% CI 87.0, 98.5%) reach L3 by 40 weeks.

Conclusion: There is regular ascent of the conus throughout foetal life. Although growth for each individual foetus may be non-linear, most foetuses have a conus level within the normal adult range by 33 weeks gestation.     

Ultra structure of pre-synaptic input to motor neurons in Onuf''s nucleus: controls and motor neuron disease

Ultrastructural analyses of sphincteric motoneurons in Onuf's nucleus at S2 were undertaken in human spinal cord obtained 3-6 h post-mortem from three subjects with no neurological disease ('controls') and five in which death was due to motor neuron disease (MND). Neurons in specified locations within Onuf's nucleus of control subjects ranged between 17.8 and 71.7 microns diameter (mean 38.6 microns). Analyses of synaptology revealed five ultrastructural classes of presynaptic terminal synapsing with the neuronal surface membrane. When classified by size, vesicle morphology, and synaptic site structure these conformed to the S, F, T, M and C-terminals defining somatic motoneurons. No terminals characteristic of autonomic motoneurons were found. In MND subjects, neurons in Onuf's nucleus at S2 were preserved despite a paucity of neurons in medial and lateral motor nuclei and were of similar size range to those in control subjects. The morphological classes of pre-synaptic terminal found in controls, also characterized sphincteric motoneurons in MND subjects, including the C-type terminal. The presence of C-terminals indicates (i) that sphincteric motoneurons are somatic alpha-motoneurons, and (ii) that hypotheses explaining the survival of sphincteric motoneurons in MND on the basis of Onuf's nucleus being an extension of the pre-ganglionic parasympathetic nucleus, or having intrinsic autonomic properties are incorrect.     

Post-mortem sperm retrieval in new European Union countries: case report

This paper describes post-mortem sperm retrieval from a man who had given prior written consent to the retrieval and use of his sperm in assisted reproduction before his accidental death. The case illustrates some of the complex ethical and legal issues occurring in a new European Union (EU) country and the need for prior preparation by the medical teams involved. We also discuss a questionnaire sent to Centres of Assisted Reproduction in other new EU countries, which reveals a dearth of both legislation and guidelines for post-mortem sperm retrieval. If this method becomes more requested in these culturally diverse countries in the future, the situation demands public debate first of all at the national level.     

Significant and potentially overlooked causes of unexpected death outside the cardiovascular and central nervous system

Most post-mortem examinations in the United Kingdom (UK) are currently performed at the request of the Coroner to differentiate between natural and unnatural causes of death on balance of probabilities. This has curtailed the remit of the practicing pathologist to only include additional investigations where the results of which would directly influence the cause of death given. The current review discusses sudden unexpected causes of death where additional investigations are required to make the correct diagnosis in certain circumstances. It is focused at pathologists working within Coronial systems and on causes of death outside the cardiovascular and central nervous systems. Specifically, we discuss the utility of cultures in sepsis, histology in unexpected tumours and special investigations in pneumothorax, asthma, anaphylaxis, diabetes mellitus, insulin-overdose, acute pancreatitis, acute liver failure and acute kidney injury.     

Exchanging information: current United Kingdom developments in the infrastructure to support post-mortem imaging

Through joint working across the Home Office, Ministry of Justice and Department of Health the United Kingdom (UK) has developed a single programme of research and development in the field of less invasive autopsy, forensic and mass fatality imaging. By supporting research and development within these fields the UK has developed an outline for a national core training programme in this field along with the development of the National Forensic Image Management System (FiMag). This symposium paper is a brief overview of this development.