Search PubMed⌕ Search

Biomedical subjects

J E Bell

Publications and source records attributed to J E Bell.

At least 91 records · Page 5Linked to original sources
PubMed1993

Sudden death in HIV-infected drug users. Presumptive overdose in an HIV-positive narcotic addict.

We report the case of an HIV-positive drug user who was found dead in a room in which were discovered tablets of dihydrocodeine and amitriptyline. There had been past episodes of drug overdose which was suspected of being the cause of death on this occasion. However toxicology analysis did not support this diagnosis and necropsy revealed a severe desquamative interstitial pneumonitis and HIV encephalitis. The need to investigate thoroughly the cause of sudden death in all HIV-positive drug users is emphasised.

Adult↗
PubMed1993

Human immunodeficiency virus and the brain: investigation of virus load and neuropathologic changes in pre-AIDS subjects.

Brain tissue was examined for evidence of human immunodeficiency virus (HIV) infection in 23 intravenous drug users who died suddenly some years after seroconversion but while still in presymptomatic stages of infection. None showed giant cell encephalitis, but 14 showed T cell lymphocytic leptomeningitis and 3 showed other significant neuropathologic features. Quantitative polymerase chain reaction for HIV was applied to 13 of the 23 with negative results in 6 and very low positive results in the other 7, a finding consistent with contamination by residual infected blood in the brain tissue. This contrasted with findings in AIDS-infected tissue, in which substantial amounts of provirus were found. It is concluded that significant infection in brain tissue does not occur in presymptomatic stages of HIV infection and that invasion of the central nervous system may be delayed until the transition to symptomatic AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Neuropathology of spongiform encephalopathies in humans.

The historical aspects and classification of human spongiform encephalopathies are reviewed and the newer concept of 'prion dementias' is explored. Guidelines for safe laboratory and autopsy handling of spongiform encephalopathy tissues are outlined: this includes an update on strategies which are currently thought to be effective in decontamination. A wide ranging review of the pathology of the various human spongiform encephalopathies includes newly emerging data on microglia, and cell-specific and neurodegenerative proteins. A large section of this chapter is devoted to the methodology of immunocytochemical demonstration of PrP in tissue sections, and the dilemmas inherent in interpretation. Clinicopathological correlations are provided for classical cases of spongiform encephalopathy, together with the newly recognised atypical dementias associated with PrP gene mutations. The pathology of iatrogenic cases of CJD is described. The chapter concludes with problems in differential diagnosis, and discussion of the histopathological features which help to resolve diagnostic dilemmas.

Cerebellum↗
PubMed1993

Zn-binding globulin in human fetal brain and liver: a marker for passive blood/CSF transfer of protein.

The presence of Zn-binding globulin (ZnbG) during human fetal development was studied in cerebrospinal fluid (CSF) and plasma with immunodiffusion methods and in brain, CSF, plasma and liver using immunocytochemical methods. At the earliest stages examined with immunocytochemistry (5-6 weeks gestation) no staining for ZnbG was visible in liver, plasma, CSF or brain. However, the primitive mesenchyme exhibited a prominent staining reaction. In late embryonic and early fetal stages, staining for the protein was most prominent in the spinal cord, brain stem and diencephalon and in the choroid plexuses and marginal and subplate zones in the telencephalon. At the cellular level, synaptic strata and territories were most strongly stained. The distribution of ZnbG in the early developing central nervous system suggests that this protein may be involved in the initial establishment of CNS circuitry. Embryonic brain was positive for ZnbG well before the protein could be detected in CSF, plasma or liver. The early occurrence of ZnbG in brain tissue prior to its presence in liver or plasma also suggests that the protein is synthesized in early fetal brain. At the time when CSF first became positive (17 weeks gestation), the brain staining had largely disappeared. ZnbG in plasma increased throughout gestation to reach 2.6 +/- 0.4 mg/100 ml at term and subsequently increased to an adult value of 6.8 +/- 1.5 mg/100 ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Ubiquitin immunocytochemistry in human spongiform encephalopathies.

The distribution of ubiquitin was studied by immunocytochemistry in eight cases of human spongiform encephalopathy and compared with the findings in seven age- and sex-matched cases of Alzheimer's disease and six non-demented control cases. The results were also compared with the immunocytochemical distribution of prion protein and the lysosomal aspartic protease cathepsin D. In the human spongiform encephalopathies, ubiquitin immunoreactivity was found in a punctate distribution at the periphery of prion protein amyloid plaques and in a finely granular pattern in the neuropil around and within areas of spongiform change. Cortical nerve cells contained scanty ubiquitinated dot-like inclusions, and occasional microglia around the areas of spongiform change also gave a positive staining reaction for ubiquitin, as did multiple irregular thread-like structures in the neuropil and white matter. The ubiquitin-containing structures at the plaque periphery in human spongiform encephalopathies resemble the neuritic processes at the periphery of the senile plaque in Alzheimer's disease. The granular positivity for ubiquitin associated with areas of spongiform change closely resembles the pattern of immunostaining seen with the antibodies to the prion protein and cathepsin D, consistent with the reported accumulation of ubiquitinated proteins and prion protein in lysosomes in the murine scrapie model. Further studies are required to investigate the role of lysosomes in this group of disorders, and to study the localization of other cell stress proteins and prion protein in spongiform encephalopathies.

Adult↗
PubMed1993

Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes.

Using an antibody raised against the catalytic subunit of glucose-6-phosphatase, this enzyme was immunolocalized in many astrocytes in 20 normal human brains. Double immunofluorescence studies showed co-localization of glial fibrillary acidic protein (GFAP) with glucose-6-phosphatase in astrocytes. However, not all GFAP-positive cells were also glucose-6-phosphatase positive, indicating that some astrocytes do not contain demonstrable expression of this enzyme. Reactive astrocytes in a variety of abnormal brains were strongly glucose-6-phosphatase positive, but neoplastic astrocytes were often only weakly positive. Expression of the enzyme could not be demonstrated in radial glia, neurons or oligodendroglia. Astrocytes normally contain glycogen and the demonstration that some astrocytes also contain glucose-6-phosphatase indicates that they are competent for both glycogenolysis and gluconeogenesis, which may be critical for neuronal welfare.

Adult↗
PubMed1993

Plasma protein levels in normal human fetuses: 13 to 41 weeks' gestation.

OBJECTIVES: To establish reference ranges for the levels of alpha-fetoprotein, albumin, prealbumin (transthyretin) alpha-1-antitrypsin, transferrin, ceruloplasmin and total protein in the plasma of normal human fetuses and newborn babies. DESIGN: Prospective study of individual normal cases to fulfil objectives. SETTING: Pathology laboratories of the University of Edinburgh and the biochemistry laboratories of the University of Keele. SUBJECTS: Twenty-two normal fetuses 13 to 22 weeks of gestation and 66 babies born between 24 and 41 weeks gestation. RESULTS: Albumin is the predominant plasma protein throughout gestation. The levels of alpha-fetoprotein and prealbumin fell significantly with increasing gestation, whereas the concentrations of the other proteins studied increased. The ratios of individual proteins to total protein demonstrated similar trends. CONCLUSIONS: This study provides developmental profiles of normal human fetal plasma proteins to serve as possible reference data for abnormal fetuses. Declining levels of prealbumin (transthyretin) were unexpected and suggest a functional role for this protein in early pregnancy.

Blood Proteins↗
PubMed1993

Effect of whole saliva components on enamel demineralization in vitro.

The aim of the present study was to use an in vitro enamel demineralization model (1) to confirm that whole saliva pretreatment conferred acid resistance to dental enamel and (2) to determine whether this phenomenon was attributable to specific salivary proteins, minerals, lipids, or some combination of these. Crowns of human teeth, each with one exposed window, were prepared in groups of ten. They were each pretreated by immersion individually in 4 ml of either (1) clarified whole saliva for 18, 72, or 168 h, (2) dialyzed saliva (3500 MWCO membrane), (3) the "flow-through" fraction from a DEAE separation of whole saliva (neutral and basic proteins), (4) the "eluted" fraction of a DEAE separation of whole saliva (anionic proteins), or (5) a combination of salivary lipids and the DEAE "flow-through" fraction of whole saliva (neutral and basic proteins). Control groups were group 6 with no pretreatment, group 7 pretreated for 168 h in a borate buffer (5 mmol/l), and group 8 pretreated in a mineral solution containing calcium (0.7 mmol/l) and phosphate (2.6 mmol/l). The crowns were then demineralized for 7 d in vitro (0.1 mol/l acetate, 1 mmol/l Ca and phosphate, pH 5.0) to produce artificial caries-like lesions. Lesions were assessed by cross-sectional microhardness profiles, and mineral loss (delta Z, micron x vol% mineral) calculated. Mineral loss (delta Z) values decreased linearly with the square root of time of pretreatment by whole saliva, confirming a time-dependent protective effect of salivary pellicle against demineralization of enamel.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗
PubMed1992

Western blotting analysis in patients with MS using human brain vessels as antigen.

Serum samples from patients suffering from multiple sclerosis, other neurological diseases and normal controls were screened by "western blotting" for antibody directed against proteins of human brain vessels purified from a post mortem brain. A small number of sera contained autoantibodies against some of the proteins of the brain vessels, particularly in patients suffering from MS, epilepsy and migraine. The significance of these results is discussed.

Antibody Specificity↗
PubMed1991

The partial amino acid sequence of the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum: implications for the evolution and structural basis of coenzyme specificity.

The amino acid sequence is reported for CNBr and tryptic peptide fragments of the NAD(+)-dependent glutamate dehydrogenase of Clostridium symbiosum. Together with the N-terminal sequence, these make up about 75% of the total sequence. The sequence shows extensive similarity with that of the NADP(+)-dependent glutamate dehydrogenase of Escherichia coli (52% identical residues out of the 332 compared) allowing confident placing of the peptide fragments within the overall sequence. This demonstrated sequence similarity with the E. coli enzyme, despite different coenzyme specificity, is much greater than the similarity (31% identities) between the GDH's of C. symbiosum and Peptostreptococcus asaccharolyticus, both NAD(+)-linked. The evolutionary implications are discussed. In the 'fingerprint' region of the nucleotide binding fold the sequence Gly X Gly X X Ala is found, rather than Gly X Gly X X Gly. The sequence found here has previously been associated with NADP+ specificity and its finding in a strictly NAD(+)-dependent enzyme requires closer examination of the function of this structural motif.

Amino Acid Sequence↗
PubMed1991

Developmental profile of plasma proteins in human fetal cerebrospinal fluid and blood.

Total protein, alphafetoprotein, albumin, prealbumin, alpha-1-antitrypsin, transferrin and ceruloplasmin levels were measured in samples of human fetal and neonatal cerebrospinal fluid (CSF) (97 cases), obtained between 12 and 41 weeks of gestation. In 39 of these cases (13 to 40 weeks gestation) plasma was also available for comparative analysis. CSF was collected from lateral ventricles in the first half of gestation and from the lumbar region in the second. Since these CSF samples were obtained from different sites, the protein levels in the lateral ventricle (early) samples could not be compared directly with those in the lumbar (later) samples. However, the mean protein levels in the lumbar samples were lower than those in the ventricular samples, which is in accord with the decline in CSF protein levels described in maturing animal fetuses. Despite a wide scatter of results, particularly in the first half of gestation, significant decline in the level of CSF alphafetoprotein was demonstrated during both first and second halves of gestation, and of albumin and prealbumin in the second half. No sex differences were found except for ceruloplasmin in lumbar CSF later in gestation, when males had higher levels than females. In fetal plasma, protein levels increased with increasing gestation apart from alphafetoprotein and prealbumin which both declined progressively. CSF/plasma ratios were dissimilar for different proteins, and changed with increasing gestation. These findings support the concept that the human fetal blood brain barrier matures early.

Blood Proteins↗
PubMed1990

Dehydrogenase binding by tiazofurin anabolites.

Thiazole-4-carboxamide adenine dinucleotide (TAD) is the active anabolite of the new antitumor agent tiazofurin (NSC 286193). TAD is an analogue of NAD in which the nicotinamide ring has been replaced by a thiazole-4-carboxamide heterocycle. TAD putatively acts by inhibition of inosine monophosphate dehydrogenase (IMPd). In this study it is shown that TAD is a competitive inhibitor, with respect to NAD, of mammalian glutamate, alcohol, lactate, and malate dehydrogenases. TAD binds to these enzymes with 1-2 orders of magnitude less affinity than it binds to IMPd. Computer modeling studies suggest that dehydrogenase binding by TAD occurs at the regular cofactor site, the thiazole-4-carboxamide group mimicking the steric and hydrogen-bonding properties of the nicotinamide ring. Noncompetitive kinetics of TAD inhibition of the target enzyme IMPd are potentially due to a reverse order of addition of substrate and cofactor from that observed in the dehydrogenases studied here. The weaker binding of TAD to these dehydrogenases may be due to their inability to preserve a close sulfur-oxygen contact in the bound inhibitor.

Adenine Nucleotides↗
PubMed1990

Glial and neuronal differentiation in the human fetal brain 9-23 weeks of gestation.

Nineteen human fetal brains ranging from 9-23 weeks of gestation were examined immunocytochemically for evidence of glial and neuronal differentiation. Radial glia were positive for vimentin and glial fibrillary acidic protein (GFAP) throughout the age range. S100-positive cells which were presumed to be astrocytes were present from 9 weeks; they were always more widespread in the cerebrum and the brainstem than GFAP-positive mature astrocytes, which could be detected with certainty only at 14 weeks. Carbonic anhydrase II (CA II)-positive oligodendrocytes were present in the brainstem in small numbers from 17 weeks. Neuronal fibre tracts in the cerebrum were positive for 160 kD phosphorylated neurofilament protein (BF10) from 9 weeks, but negative for 200 kD phosphorylated neurofilament protein (RT97) and for 70 and 200 kD non-phosphorylated neurofilament protein (NFP) whereas most tracts in the brainstem were positive for BF10 from 9 weeks and positive for the other neurofilament proteins from 14 weeks. Corticospinal tracts differed in remaining negative for neurofilament proteins other than BF10, which showed positive reaction throughout. Perikarya of differentiated neurons in all areas of the brain were neurofilament-negative but neuron specific enolase (NSE)-positive. Germinal eminence cells were focally vimentin-positive from 15 weeks, focally GFAP-positive from 17 weeks, and negative for all NFP and for NSE. The value of a short fixation time and pretreatment with trypsin in the immunocytochemical demonstration of GFAP is stressed.

Brain↗
PubMed1990

Glutathione S-transferase in human brain.

The glutathione S-transferases are a complex group of multifunctional enzymes which may detoxify a wide range of toxic substances including drugs and carcinogens. Different isoenzymes vary in substrate specificity, tissue distribution and level of expression during development. Following reports of cell-specific and age-dependent expression in rat brain we have studied, immunohistochemically, expression of the Pi and Alpha class isoenzymes in 10 adult and 21 human fetal brains. Whilst Alpha isoenzyme is expressed only in adult brain, and then only focally, Pi isoenzyme is strongly expressed from as early as 12 weeks gestation. In the adult, expression is localized to choroid plexus, vascular endothelium, ventricular lining cells, pia-arachnoid and astrocytes. In fetal brain, expression is also strong in cells with the morphology of tanycytes and in the cell bodies of radial glia. Neurons are consistently negative. Pi isoenzyme thus localizes to the sites of the blood-CSF barrier, blood-brain barrier, CSF-brain barrier and pia-arachnoid-brain barrier. It is ideally placed to regulate neuronal exposure to potentially toxic substances derived from blood or cerebrospinal fluid. Expression so early in gestation is of significance and may imply a role in protection of the developing human brain.

Adult↗
PubMed1989

Hepatic microsomal glucose-6-phosphatase system and sudden infant death syndrome.

Microassay techniques and monospecific antibodies were used to study the hepatic glucose-6-phosphatase system in liver samples from 55 infants who had died suddenly and unexpectedly, including 38 victims of sudden infant death syndrome (SIDS). Raised hepatic glycogen was found in 10, all of whom had a diagnosis of SIDS, and in 1 other infant who was already known to have type 1b glycogen storage disease (deficiency of transport protein T1). Of the 10 infants with raised hepatic glycogen who had a diagnosis of SIDS, 8 had glucose-6-phosphatase deficiency (type 1a glycogen storage disease), and 2 had transport protein T2 deficiency (type 1c glycogen storage disease).

Glucose-6-Phosphatase↗