Biomedical subjects

P F Atkinson

Publications and source records attributed to P F Atkinson.

8 recordsLinked to original sources

PubMed2004

Microstructural observations of villous and membrane histology in monochorionic triplet placenta after in vitro fertilization.

The frequency of triplet gestation is low in humans, estimated at 1:6400 deliveries. Monochorionic gestations represent a subpopulation of approximately 10% of these triplet pregnancies. Hypertensive complications are known to occur with greater frequency in the context of multiple gestation. In this report we describe microscopic placental changes associated with pre-eclampsia and proteinuria in the setting of an uncommon monochorionic-triamniotic triplet pregnancy achieved via in vitro fertilization. Histologic features observed in this case include placental stromal fibrosis and increased syncytial nodularity (Tenney-Parker change). In this triplet delivery resulting from two consecutive fissions of a single embryo, chorion and amnion configuration are also characterized with a review of the literature discussing the potential relationship between in vitro culture conditions and monozygotic multiple gestation.

Adult↗

PubMed1997

Tau protein in the glial cytoplasmic inclusions of multiple system atrophy can be distinguished from abnormal tau in Alzheimer's disease.

The glial cytoplasmic inclusion (GCI) is a histological hallmark for multiple system atrophy (MSA). These inclusions are in oligodendrocytes, contain microtubular structures of 20-30 nm diameter, and can be labelled immunohistochemically with antibodies to ubiquitin, alphaB-crystallin, alpha- and beta-tubulin, and the microtubule-associated protein tau. GCIs have been compared with neuronal inclusions in other neurodegenerative disorders including the neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD), which also contain tau protein. In order to determine whether the tau protein of GCIs in MSA is similar to that observed in AD we used a panel of antibodies to phosphorylation-independent (SMI51, TP007, TP70), dephosphorylation-dependent (Tau.1), and phosphorylation-dependent antibodies to tau and neurofilaments (AT8, AT180, AT270, SMI31, SMI34, RT97, BF10, 8D8). Immunohistochemistry was performed on paraffin wax-embedded brain tissue of the cerebellum, brainstem, and frontal lobes (Brodmann areas 4/6) of ten clinically and neuropathologically well-characterised cases of MSA, two cases of AD, and two normal controls. The NFTs of the AD cases were labelled with all the phosphorylation-dependent and phosphorylation-independent antibodies and with Tau.1 only after treatment with alkaline phosphatase. In contrast, GCIs were immunolabelled by the phosphorylation-independent antibodies and Tau.1, but not by the phosphorylation-dependent antibodies. These data demonstrate that the tau in GCIs is different from the abnormally phosphorylated tau found in AD and is similar to normal adult tau. The mechanism causing the abnormal accumulation of tau in GCIs remains to be elucidated.

Adult↗

PubMed1997

Presenilin-1 intron 8 polymorphism is not associated with autopsy-confirmed late-onset Alzheimer's disease.

Mutations in the presenilin-1 (PS-1) gene may account for the majority of familial early-onset Alzheimer's disease (EOAD) cases. However, there is controversy as to whether the bi-allelic intron 8 PS-1 polymorphism plays a role in late-onset AD (LOAD). As previous association studies with this polymorphism have all investigated clinically diagnosed LOAD cases, we have analysed the frequency of the PS-1 intronic polymorphism in a series of autopsy-confirmed early- (n = 54) and late-onset (n = 199) cases and a large control population of non-demented, aged individuals (n = 215). Our sample size should have had the power to reveal effects of the size previously reported for the PS-1 polymorphism, but we detected no significant increase in the 1/1 risk genotype distribution in EOAD or LOAD cases. Thus, we have been unable to find an association between the PS-1 intronic polymorphism and early- or late-onset AD within this autopsy-confirmed population.

Age of Onset↗

PubMed1997

Apolipoprotein E e4 allele frequency in patients with multiple system atrophy.

The glial cytoplasmic inclusion provides a histological hallmark for multiple system atrophy, a group of neurodegenerative disorders including: striatonigral degeneration, olivopontocerebellar atrophy, and Shy-Drager syndrome. Apolipoprotein E (APOE) genotype was determined by the polymerase chain reaction and restriction digestion of DNA extracted from frozen brain tissue from 22 patients (64.9 +/- 2.2 years) with clinically and neuropathologically verified multiple system atrophy (MSA). In addition, brain tissue from 36 age- and sex-matched patients who died with Alzheimer's disease (68.8 +/- 1.6 years) and 66 neurologically and psychiatrically normal subjects (66.6 +/- 1.8 years) was genotyped. The APOE e4 allele frequency in the Alzheimer's disease subjects was significantly increased (0.44, P < 0.001), as has been reported previously. The APOE e4 allele frequency of the MSA cases (0.11) was not significantly different from that of the control subjects (0.12). These data indicate that the APOE e4 allele is not a risk factor for multiple system atrophy.

Aged↗

PubMed1993

Immunoelectronmicroscopical demonstration of major histocompatibility class II antigen: expression on endothelial and perivascular cells but not Schwann cells in human neuropathy.

A pre-embedding technique for identifying major histocompatibility (MHC) class II antigen with monoclonal antibody LN3 at the electron microscope level by immunogold silver enhancement was applied to sections from 12 human nerve biopsies. Many perivascular mononuclear cells in the epineurium, perineurium and endoneurium expressed MHC class II antigen and had the morphological appearance of macrophages. Cell processes expressing MHC class II antigen extended throughout the endoneurium, often close to Schwann cells. No MHC class II expression was identified on myelinating or non-myelinating Schwann cells. The endothelial cells of epineurial blood vessels expressed MHC class II antigen on their luminal surfaces more often and more strongly than those of the endoneurial vessels. These observations indicate that perivascular cells in both the endoneurium and perineurium commonly express the molecules necessary to present antigen to CD4+ T lymphocytes, but Schwann cells do not.

Adult↗

PubMed1992

Motor nerve biopsy in severe Guillain-Barré syndrome.

We undertook a biopsy of a terminal branch of the musculocutaneous nerve in a man with severe Guillain-Barré syndrome and very small distally evoked action potentials. The biopsy showed pronounced subperineurial edema, macrophage infiltration, and many axons that had been completely demyelinated, some associated with intratubal macrophages. The biopsy unequivocally identified the pathological process as primary demyelination, not axonal degeneration, and was more informative than previous reports of sural nerve biopsies in patients with Guillain-Barré syndrome.

Axons↗

PubMed1987

Major histocompatibility antigens and lymphocyte subsets during experimental allergic neuritis in the Lewis rat.

Major histocompatibility antigens were identified in frozen sections of normal Lewis rat peripheral nerve tissue with monoclonal antibodies and an avidin-biotin-peroxidase complex system. Class I antigen is normally required for cytotoxic/suppressor T lymphocyte function and class II antigen for activation of helper T lymphocytes. In the sciatic nerves class I antigen was expressed diffusely by most endoneurial and perineurial cells but class II antigen only by a minority. In the cauda equina class I antigen was expressed by all arachnoid and some endoneurial cells, while class II antigen was expressed by a smaller proportion of arachnoid cells in the endoneurium of spinal roots and interstitial cells surrounding dorsal root ganglion neurons. The endothelium of endoneurial, perineurial and meningeal vessels uniformly expressed class I but not class II antigen. Experimental allergic neuritis was induced in Lewis rats by immunisation with bovine intradural root myelin. Early lesions consisted of multifocal infiltration of the nerve roots by cells expressing leucocyte common antigen. Surrounding endoneurial cells showed markedly increased expression of major histocompatibility antigens. In inflammatory lesions about 10% of the cells were stained with pan T cell antibodies. T lymphocyte subsets were identified with antibody W3/25 for helper cells and MRC OX-8 for cytotoxic/suppressor cells. The W3/25 positive cells were usually slightly in excess of OX-8 positive cells and their relative proportions did not alter during the disease. The presence of class I antigen on normal endothelium and its increased expression on endoneurial cells in the early phase of inflammation suggest an important role for class I restricted lymphocytes in the pathogenesis of the early stages of experimental allergic neuritis.

Animals↗

PubMedDate not supplied

Chronic experimental allergic neuritis in Lewis rats.

An experimental chronic relapsing demyelinating neuropathy was produced by immunizing adult Lewis rats with bovine myelin in low (2.5 mg) and high (5 mg) doses, with and without Mycobacterium tuberculosis in the adjuvant. Each regime produced a similar disease course: acute severe hind limb weakness was followed by apparent recovery and then reappearance of mild neurological deficit with occasional spontaneous exacerbations. The partially recovered animals were relatively resistant to reimmunization with myelin. Immunization of four-week-old rats with myelin in complete adjuvant produced disease with a similar course. Subsequent immunization of these juvenile rats with adjuvant alone precipitated exacerbations. In the late stages, the prominent changes in peripheral nerves and nerve roots were axon loss, axonal regeneration and remyelination while inflammatory cell infiltration was confined to occasional foci. Onion bulb formation was extremely common in the dorsal root ganglia and affected in particular the nerve fibres close to the dorsal root ganglion cells. The cells forming the onion bulbs resembled the satellite cells surrounding the axon hillocks. Onion bulb formation also occurred in the portion of the ventral roots adjacent to the dorsal root ganglion but was rare elsewhere. Immunocytochemistry revealed only occasional lymphocyte infiltration but there was increased Class I and Class II MHC antigen expression throughout the peripheral nervous system. The results are relevant to the interpretation of biopsies from patients with chronic demyelinating neuropathy of possible inflammatory or autoimmune origin.

Animals↗