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J Lowe

Publications and source records attributed to J Lowe.

At least 37 records · Page 2Linked to original sources
PubMed1995

Immunohistochemical localization of ubiquitin cross-reactive protein in human tissues.

Ubiquitin cross-reactive protein (UCRP) is an interferon-inducible ubiquitin homologue which is constitutively present in cells and can be conjugated to other proteins. Using a characterized polyclonal antiserum to UCRP, immunohistochemical localization of UCRP was performed on paraffin-processed normal human tissues and in human tissues known to contain ubiquitinated intracellular inclusions. The antibody to UCRP immunostained lymphoid cells, striated and smooth muscle, several epithelia, and neurons. The level of staining varied greatly between tissues but was in a consistent punctate pattern. Localization to neuromuscular junctions and striations is similar to that described for antisera to ubiquitin-protein conjugates. Inclusion bodies characterized by immunoreactivity to anti-ubiquitin were not detected by the antibody to UCRP. Importantly, because UCRP may also be detected by antisera to conjugated ubiquitin, future studies on the distribution of ubiquitin in tissue sections must now take account of possible cross-reactivity with UCRP.

Cross Reactions↗
PubMed1995

Parkinsonism in motor neuron disease: case report and literature review.

This report describes a patient who had clinical features of both motor neuron disease and Parkinson's disease. Neuropathological examination and immunocytochemical studies showed that he had motor neuron disease of the progressive muscular atrophy type, and Lewy body Parkinson's disease, with intracytoplasmic inclusion bodies characteristic of both conditions. This is the first detailed description of these two diseases occurring concurrently in the same patient. A review of all previously reported cases of combined motor neuron disease and parkinsonism has led to the following conclusions: (1) that these two neuropathologically defined diseases occur together very infrequently, but (2) that parkinsonism and substantia nigra degeneration are not uncommon as part of the multi-system disease process underlying motor neuron disease.

Aged↗
PubMed1995

Discriminative stimulus effects of CP 55,940 and structurally dissimilar cannabinoids in rats.

CP 55,940 is a potent synthetic bicyclic cannabinoid analog that has been used in a number of studies as a radioligand for the cannabinoid receptor. This compound shares behavioral and biochemical properties with naturally occurring cannabinoids such as delta 9-THC. The purpose of the present study was 3-fold: to establish the ability of CP 55,940 to serve as a discriminative stimulus, to determine whether this discriminative stimulus is identical to that of delta 9-THC, and to examine whether a newly developed cannabinoid antagonist, SR141716A, would antagonize the discriminative stimulus effects of CP 55,940. Rats were trained to discriminate 0.1 mg/kg CP 55,940 from vehicle in standard 2-lever operant conditioning chambers. CP 55,940 produced dose-dependent generalization from the training dose in dose-effect determinations conducted before and after testing with other drugs. The effects of the training dose of CP 55,940 were dose-dependently antagonized by co-administration of SR141716A. Results of substitution tests showed that delta 9-THC, WIN 55,212-2, and cannabinol substituted completely for CP 55,940 in a dose-dependent manner; however, CP 55,940 was approx 10-fold more potent than any of the other drugs in producing CP 55,940-like discriminative stimulus effects. Several drugs with CNS depressant properties (phencyclidine, haloperidol and diazepam) failed to produce reliable substitution for CP 55,940. These results demonstrate that CP 55,940 has discriminative stimulus effects and that it shares these effects with structurally dissimilar compounds that, like CP 55,940, bind to the cannabinoid receptor. Further, these effects are blocked by SR141716A, a cannabinoid receptor antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesics↗
PubMed1995

An anatomical, histological and magnetic resonance imaging study of the nasal septum.

Considerable variations are present in the thickness of the normal nasal septum. These were studied and measured in cadavers and from MRI scans. In addition, a histological analysis was performed to determine whether cavernous tissue is present at any point in the septum. The nasal septum reaches maximum thickness antero-superiorly where the mucosa may be as thick a 5.0 mm (average 3.5 mm) and the minimum thickness lies inferiorly where the mucosa is often thinner than 0.5 mm. The area of maximum septal thickness lies at the region of the nasal valve and its contribution towards nasal airway resistance must be significant. No cavernous tissue was identified in the nasal septum.

Adult↗
PubMed1995

The cortical neuritic pathology of Huntington's disease.

We have studied the brains of 10 patients with clinically and pathologically defined Huntington's disease and graded the degree of striatal pathology according to the Vonsattel grading system. Sections from nine cerebral cortical areas (Brodmann areas 8, 10, 24, 33, 28, 38, 7, 39, 18), the cerebellum, hypothalamus, medulla and caudate nucleus were stained with antibodies to ubiquitin and ubiquitin C-terminal hydrolase (PGP 9.5). Dystrophic neurites, immunoreactive with ubiquitin and PGP 9.5 were detected in all cortical areas, in layers 3, 5 and 6, of all brains studied. No dystrophic neurites were found in subcortical areas or cerebellum. Sections from cortical areas 8 and 24 from the two brains with the most and least ubiquitin-immunoreactive neurites were stained with antibodies to beta-amyloid precursor protein, tau, glial fibrillary acidic protein, neurofilament protein, alpha B crystallin, GABA, cholecystokinin and somatostatin. The dystrophic neurites were found to also react with beta-amyloid precursor protein. Electron microscopy showed the abnormal neurites to contain granulofilamentous material. Granular deposits with a diameter of 40-100 nm were interspersed between randomly orientated 'fuzzy' or coated, straight or slightly curved filaments measuring 10-15 nm in diameter. These structures have not been seen in control brain and differ from age-related neuritic degeneration and neurites associated with amyloid. Immunohistochemically these structures most resemble CA 2/3 neurites seen in Lewy body disease, and, ultrastructurally, the intraneuronal filamentous inclusions in motor neuron disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Osmotic activation of a Na(+)-dependent Cl-/HCO3- exchanger.

In many systems, osmotically induced cell shrinkage activates the Na+/H+ exchanger. To assess the role of H(+)-extruding transporters in the response to osmotic shrinkage in vascular smooth muscle (VSM) and Chinese hamster ovary (CHO) cells, intracellular pH (pHi) was measured with 2',7'-bis(carboxy-ethyl)-5(6)- carboxyfluorescein-acetoxymethyl ester (BCECF-AM) after exposing cells to hypertonic medium. In nominally HCO(3-)-free medium, addition of 200 mM sucrose caused pHi to increase 0.33 pH unit on average in VSM cells but only 0.13 pH unit in CHO cells. Permeant solutes failed to increase pHi significantly. Cytochalasin B (1-20 microM), colchicine (1-10 microM), Ca2+ removal, and downregulation of protein kinase C activity did not affect osmotic activation of H+ extrusion in either cell type. Additional work was carried out to determine why osmotic activation of H+ extrusion was less in CHO than in VSM cells. In CHO cells, the osmotically induced delta pHi was only weakly sensitive to amiloride, suggesting that osmotic forces may activate an H+ transport system other than Na+/H+ exchange. In the presence of 10 mM HCO3-, osmotically induced delta pHi decreased by 60% in VSM cells but increased by 50% in CHO cells compared with the delta pHi in HCO(3-)-free medium. Lastly, removal of extracellular Cl- did not affect osmotically induced delta pHi in VSM cells but completely abolished the response in CHO cells. We conclude that in VSM cells osmotically induced changes in pHi are mediated by Na+/H+ exchange, whereas in CHO cells they are most likely mediated by a Na(+)-dependent Cl-/HCO3- exchanger.

Amiloride↗
PubMed1995

Skeletal muscle lymphocytic vasculitis in systemic lupus erythematosus: relation to disease activity.

Lymphocytic vasculitis (LV) characterises systemic lupus erythematosus (SLE) and this potentially reversible lesion, which may be subclinical, may imply overt systemic disease activity. Needle quadriceps muscle biopsy was performed in 26 unselected patients with SLE and the presence of LV in these muscle specimens was compared with SLE disease activity scored using the British Isles Lupus Assessment Group Index (BILAG). Ten of the 22 patients with active disease showed evidence of LV compared with none of the four patients with inactive disease. In the patient group with LV, significantly higher ESR and urine neopterin values were found with P = 0.002 and P = 0.02, respectively compared with patients without LV. Features of vasculitis (as defined by BILAG) were also significantly more common in these patients (P = 0.005). None of the other parameters, including creatine kinase, were significantly different between the two patient subgroups. Thus, LV in needle quadriceps muscle biopsy specimens is a further valuable marker of disease activity in patients with SLE and might provide histological evidence of a systemic vasculitic process in a group of patients with diverse clinical manifestations.

Adult↗
PubMed1995

Chicken B cells undergo discrete developmental changes in surface carbohydrate structure that appear to play a role in directing lymphocyte migration during embryogenesis.

The migration of progenitor cells to specific microenvironments is essential for the development of complex organisms. Avian species possess a unique primary lymphoid organ, the bursa of Fabricius, that plays a central role in the development of B cells. B cell progenitors, however, arise outside the bursa of Fabricius and, during embryonic development, must migrate through the vasculature to the bursa of Fabricius. In this report, we demonstrate that these progenitor B cells express the sialyl Lewis x carbohydrate structure previously shown to be a ligand for the selectin family of vascular adhesion receptors. Soon after migration to the bursa of Fabricius, B cell progenitors are induced to undergo a developmental switch and terminate the expression of sialyl Lewis x in a temporal pattern that correlates with the developmental decline in the ability of these cells to home to the bursa of Fabricius upon transplantation. The induction of the developmental switch in the glycosylation pattern of developing B cells requires the bursal environment. In addition, sialyl Lewis x carbohydrate determinants or structurally similar determinants on the surface of immortalized bursal lymphoid stem cells participate in the adherence of these cells to the vascular regions of the bursal microenvironment. These data demonstrate that the carbohydrate structure sialyl Lewis x is developmentally regulated during chicken B cell development and may facilitate the migration of B cell progenitors to the bursal microenvironment by serving as a ligand for a lectin-like adhesion receptor.

Animals↗
PubMed1995

Follicular fluid levels of midazolam, fentanyl, and alfentanil during transvaginal oocyte retrieval.

OBJECTIVE: To investigate the time course of changes in follicular fluid (FF) concentrations of midazolam (Roche Products Ltd., Welwyn Garden City, United Kingdom), fentanyl (Janssen Pharmaceuticals Ltd., Wantage, United Kingdom), and alfentanil (Janssen Pharmaceuticals Ltd.) during ultrasound-guided transvaginal oocyte collection. STUDY DESIGN: Forty-five patients with tubal infertility were randomized to receive a bolus IV dose of midazolam, fentanyl, or alfentanil for sedation during ultrasound-guided transvaginal oocyte collection. Paracervical block with lignocaine was given for analgesia. Simultaneous blood and FF samples were drawn at 5-minute intervals after the bolus dose for analysis of drug levels. RESULTS: Data were obtained on 15 women receiving midazolam and fentanyl and on 13 women receiving alfentanil. Plasma levels of all agents rose to a peak and then fell in an exponential fashion as was expected. The FF levels of the agents continued to rise significantly to 25 minutes after the bolus dose, although the absolute level was low when compared with the blood level. There were no significant differences in fertilization or pregnancy rates in the three groups, but patient numbers were small. CONCLUSION: We conclude that midazolam, fentanyl, and alfentanil are found in FF after a single IV dose, but further investigation needs to be undertaken to investigate any potential influence on fertilization and implantation rates.

Adult↗
PubMed1994

Human monoclonal anti-D secreting heterohybridomas from peripheral B lymphocytes expanded in the CD40 system.

Peripheral human B lymphocytes isolated from four immunised anti-D donors have been cultured in the CD40 system (Banchereau et al., 1991), prior to fusion to murine X63Ag8.653 plasmacytoma cells. High fusion efficiency was noted in all cases and immunoglobulin (IgG and IgM) was detected in nearly all heterohybrid containing wells. Only fusions using boosted donor lymphocytes generated specific anti-D secreting hybrids. A short period of culture of committed B cell precursors in the CD40 system before fusion appears to be both adequate and efficient in permitting generation of specific antibody-secreting hybrids.

Animals↗
PubMed1994

A novel bioactivity assay for monoclonal antibodies directed against IgE.

A novel bioactivity assay has been developed to quantitate the biological activity of a humanized, monoclonal anti-IgE antibody (rhuMAbE25) in human whole blood. Heparinized blood specimens from prescreened healthy donors were sensitized for 2 h with a constant amount of human plasma containing IgE specific for ragweed and then challenged with ragweed allergen. Histamine was released in a dose-dependent fashion and reached plateau levels after 30 min. As expected, the release of histamine by ragweed allergen was time, temperature and Ca2+ dependent, and could be enhanced by the presence of 33% deuterium oxide. Allergen-triggered release could be inhibited by rhuMAbE25 with an effective dose range from 0.1 to 1 microgram/ml. Preincubation with other humanized MAbs, which exhibit 95% homology to rhuMAbE25 but differ in epitope specificity, failed to inhibit the ragweed-induced histamine release. Overall, this bioactivity assay has a low interassay variability (%CV) of 17% (n = 23) and can be readily modified to determine if rhuMAbE25 or other anti-allergy therapeutics are capable of blocking histamine release elicited by other allergens. Moreover, the assay can be used to confirm IgE-mediated allergic responses and to provide early information regarding safety and potential efficacy of therapeutics aimed at blocking IgE dependent responses.

Adult↗
PubMed1994

Alpha-B crystallin in the normal human myocardium and cardiac conducting system.

The alpha crystallins are major protein components of the ocular lens and show both structural and functional homology with the family of small heat shock proteins. alpha B crystallin is also present in various extra-lenticular tissues, with a high concentration in cardiac muscle. In this study, the myocardium and conducting system from 15 adult and 25 fetal and infant hearts were examined by immunohistochemistry using a previously characterized antiserum to alpha B crystallin. Contractile myocardium showed moderate staining, with particular localization to Z bands and intercalated discs. Fibres of the sino-atrial and atrio-ventricular nodes and His bundle showed less intense staining than contractile fibres, whereas fibres of the left and right bundle branches showed more intense staining. This distribution is similar to that previously demonstrated for the intermediate filament desmin. This observation, together with currently available evidence, suggests that cardiac alpha B crystallin may play a role in protecting the cytoskeleton during cell stress. For practical purposes, immunostaining with alpha B crystallin greatly facilitates the identification of cardiac conducting fibres.

Adult↗
PubMed1994

The expression of alpha B-crystallin in epithelial tumours: a useful tumour marker?

Alpha B-crystallin is a lens protein showing homology with small heat-shock proteins. We have previously demonstrated its expression in non-lenticular normal and diseased human tissues by immunostaining with a polyclonal antibody. In view of the expression seen in normal renal tubular epithelium, we have assessed the immunoreactivity of a variety of epithelial tumours, to determine the usefulness of alpha B-crystallin as a specific renal tumour marker. Carcinomas arising from tissues which normally express alpha B-crystallin, such as colo-rectal and thyroid carcinomas, showed a varying pattern and degree of immunoreactivity. The most consistently positive tumours, however, with typically strong cytoplasmic and cell membrane staining, were renal cell carcinomas, 90 per cent of which showed positive immunoreactivity. This pattern of staining, while not absolutely specific, is a useful aid to the diagnosis of renal carcinoma. When a metastic deposit or a small biopsy is being assessed, anti-alpha B-crystallin may be included in a panel of antibodies, the pattern of staining of which may direct the search for the primary site of the tumour.

Biomarkers, Tumor↗
PubMed1994

New pathological findings in amyotrophic lateral sclerosis.

There have been recent developments in the pathology of sporadic ALS. A new filamentous neuronal inclusion body in ALS detected by immunohistochemical localisation of the protein ubiquitin has been characterised at the light microscopic and ultrastructural level and appears specific for the disease. The molecular composition of underlying filaments remains unresolved but the quest for this is a major aim in ALS research. Despite being a progressive degenerative process which primarily affects motor systems, ALS is now recognised to involve several non-motor systems and in long survivors affects many subcortical structures. There is also accumulating evidence that the neurodegenerative process underlying ALS may present as a non-motor clinical syndrome, particularly as a frontal lobe dementia with characteristic inclusions present in the non-motor cortex. Considering ALS as a multisystem disease rather than simply a disease of motor neurones has major implications for research into pathogenesis.

Amyotrophic Lateral Sclerosis↗
PubMed1994

Endosome-lysosomes and neurodegeneration.

A number of the major human and animal neurodegenerative diseases, such as Alzheimer's disease and sheep scrapie, are characterised by deposits of amyloid, arising through incomplete breakdown of membrane proteins. Although our knowledge concerning these diseases is increasing, they remain largely untreatable. Recently, attention has focussed on the mechanisms of production of different types of amyloid and the likely involvement within cells of acid compartments called endosome-lysosomes. These organelles may be 'bioreactor' sites for the unfolding and partial degradation of membrane proteins to generate the amyloid materials. These subsequently become expelled from the cell, or are released from dead cells, and accumulate as pathological entities. Common features of the disease processes give new direction to therapeutic intervention.

Alzheimer Disease↗
PubMed1994

Muscle biopsy abnormalities in systemic lupus erythematosus: correlation with clinical and laboratory parameters.

OBJECTIVES: To investigate the incidence and significance of Type II fibre atrophy, vessel wall thickening, lymphocytic vasculitis and myositis in needle quadriceps muscle biopsies from patients with systemic lupus erythematosus (SLE) and their correlations with clinical and laboratory parameters. METHODS: Needle quadriceps muscle biopsies from 55 patients with SLE and 26 controls were prospectively examined. Clinical and laboratory parameters recorded at the time of muscle biopsy included arthralgia, arthritis, myalgia, proximal weakness, vasculitic rashes, Schirmer test, ENA antibodies, ESR, serum creatine kinase (CK) and plasma C3 degradation products. RESULTS: Abnormal muscle biopsies were significantly more frequent in patients with SLE compared with controls (P < 0.005). None of the controls had lymphocytic vasculitis and/or myositis. The difference in incidence between patients with SLE and controls for lymphocytic vasculitis was significant at P < 0.005. Due to the small number of SLE patients with myositis, the difference in incidence for this abnormal finding reached only P = 0.09. In the SLE patient group, lymphocytic vasculitis was associated with significantly higher ESR values (P = 0.007) and higher incidence of arthritis (P = 0.01); and appears to characterise a subset of patients with positive Schirmer tests, anti-Ro and/or anti-La antibodies. Raised serum CK was found to correspond with underlying myositis in patients with SLE and these patients also had an increased incidence of symptoms of proximal weakness and/or anti-RNP antibodies. In contrast, both Type II fibre atrophy and vessel wall thickening failed to correlate with any of the clinical and laboratory parameters studied and appear to be non-specific findings. CONCLUSIONS: Abnormal muscle biopsies are common in patients with SLE and the presence of lymphocytic vasculitis and/or myositis signify pathology in these patients. Histopathological abnormalities in needle quadriceps muscle biopsies are further valuable parameters in the assessment of patients with SLE.

Adult↗