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Biomedical subjects

M E Beard

Publications and source records attributed to M E Beard.

At least 55 records · Page 3Linked to original sources
PubMed1987

Peroxisomes in wild-type and rosy mutant Drosophila melanogaster.

This study shows that peroxisomes are abundant in the Malpighian tubule and gut of wild-type Oregon R Drosophila melanogaster and that the peroxisomal population of the rosy-506 eye-color mutant differs from that of the wild type. Catalase activity in wild-type flies is demonstrable in bodies of appearance and centrifugal behavior comparable to the peroxisomes of vertebrate tissues. Xanthine oxidase (xanthine:oxygen oxidoreductase, EC 1.1.3.22) activity of the Malpighian tubule of wild-type flies is demonstrable cytochemically in bodies like those containing catalase. The rosy-506 mutant flies, with a deletion in the structural gene for xanthine dehydrogenase (xanthine:NAD+ oxidoreductase, EC 1.1.1.204), lack cytochemically demonstrable peroxisomal xanthine oxidase activity. In addition, peroxisomes in the rosy-506 mutants show less intense cytochemical staining for catalase than those in wild-type flies, and biochemical assays indicate that catalase in the rosy mutant is much more accessible to substrate in the absence of detergent than in the wild type. Thus, the rosy-506 mutation appears to affect peroxisomes and may mimic aspects of the defects of peroxisomes in some human metabolic disorders.

Animals↗
PubMed1987

Functional analysis of a clonal expansion of Leu 11 positive NK active lymphoid cells.

A female patient with an unusual lymphoproliferative disease associated with marked neutropenia has been observed for 36 months. The expanded cell population consists of large lymphocytes, many of which contain large azurophilic granules with acid phosphatase activity. These cells were T3, T8, T11 and Leu 11 positive but lacked the M1, T10, IL-2 receptor and HLA.DR antigens. The majority of these cells (60-70%) were also Leu 7 (HNK-1) positive. Strong natural killer (NK) activity was found in both the Leu 7 positive and negative cell populations. This cytotoxic activity was inhibited by monoclonal antibodies known to inhibit NK activity but was unaffected by antibodies which block T cell and T/NK cell cytotoxicity. Further functional analysis indicated that these cells suppressed normal T cell responses to mitogens, MLC responses and PWM induced B cell immunoglobulin synthesis. No effect on bone marrow progenitor cell growth was demonstrated. Antibody dependent cellular cytotoxic (ADCC) activity was barely detectable despite the presence of the Leu 11 antigen. Southern blot DNA analysis demonstrated clonal rearrangement of the T cell receptor beta gene thereby confirming that this variant of T gamma lymphoproliferative disease was a neoplastic condition.

Adult↗
PubMed1987

Ph-negative chronic myeloid leukaemia.

An analysis of five patients with Philadelphia chromosome (Ph) negative chronic myeloid leukaemia (CML) revealed that two were clinically and haematologically identical to Ph-positive CML whereas three should be reclassified as chronic myelomonocytic leukaemia (CMML). At a molecular level the first two patients showed the same juxtaposition of c-abl and bcr genes as is seen in Ph-positive CML. These genomic changes were not seen in the other three patients. Observations on these five patients suggest that the clinical course and prognosis of the rare patient who carries the Ph 'molecular defect' but lacks the Philadelphia chromosome is no different from Ph-positive CML.

Adult↗
PubMed1986

B cell lymphoma presenting as carcinoma of the lung.

A patient presented with superior vena caval obstruction caused by a tumour which resembled carcinoma of the lung both clinically and histologically. However, immunologic and cytogenetic analyses carried out on the mediastinal biopsy and on pleural fluid revealed that the tumour was of B cell origin, Burkitt-like in sub-type, and had the t(8;14) translocation. The nature of many poorly differentiated tumours may be more clearly identified with the help of immunological and cytogenetic analyses.

Antigens, Neoplasm↗
PubMed1986

Allogeneic bone marrow transplantation at Christchurch 1979-1985.

Twelve bone marrow transplants have been carried out at Christchurch since 1979 in five patients with aplastic anaemia and seven with acute leukaemia. Five patients are currently alive at 77, 69, 63, 45, and seven months post-transplant. Acute and chronic graft versus host disease have been major problems and its clinical features and management are described. Long term follow-up data is presented on the four patients currently alive at between three to six years post-transplant. The practical problems we have experienced by carrying out bone marrow transplants without special funding have been considerable and the implications of this are discussed.

Adolescent↗
PubMed1986

Peroxisomes in infantile phytanic acid storage disease: a cytochemical study of skin fibroblasts.

Cultured skin fibroblasts from six patients demonstrating clinical signs and biochemical characteristics of infantile phytanic acid storage disease (IPSD) were examined by electron microscopy, using cytochemical procedures for the demonstration of peroxisomal catalase activity. In four of the six fibroblast cell lines peroxisomes strongly reactive for catalase were present in numbers similar to those found in normal fibroblasts. Liver biopsy tissue from one of these patients showed no typical hepatic peroxisomes, but did show small, marginally reactive bodies. In two other IPSD fibroblast cell lines peroxisomes with appreciable cytochemical reactivity were rare or absent. It seems, therefore, that infantile phytanic acid storage disease is heterogeneous with respect to the presence of cytochemically recognizable peroxisomes, at least in the cases studied here. Furthermore, peroxisomes may be markedly affected in one cell type - liver - and yet not affected in another - skin fibroblasts - within a single individual.

Catalase↗
PubMed1986

The inheritance of abnormal sialoglycoproteins found in a Gerbich negative individual.

The Gerbich blood group antigens are probably expressed on one or more of the minor erythrocyte (beta, beta 1, or gamma) sialoglycoproteins which are lacking in some rare individuals having the Gerbich negative phenotype. A monoclonal antibody, CMRF-10, which recognises a trypsin-sensitive site on both the beta and beta 1 sialoglycoproteins, was tested for binding to erythrocytes from a Gerbich negative individual, OM. Erythrocytes from OM bound CMRF-10 in similar amounts to normal erythrocytes even though membranes from OM were shown by sodium dodecyl sulphate-polyacrylamide gel electrophoresis to lack both the beta and gamma sialoglycoproteins found in normal red blood cells. Instead, abnormal sialoglycoproteins which migrated as two bands with apparent molecular weights within the range 29,500-32,500 daltons were identified and purified using CMRF-10. Subsequent electrophoretic analysis of OM's two children failed to reveal any abnormal sialoglycoproteins. This suggests that in this instance the Gerbich negative phenotype may result from other mechanisms, possibly defective glycosylation, rather than a crossover involving the gene coding for the primary protein structure of the sialoglycoproteins.

Aged↗
PubMed1985

Peroxisomes in the nervous system of Aplysia californica: a cytochemical study.

We have studied the distribution of peroxisomes in the abdominal ganglion of Aplysia californica using electron microscopic cytochemical methods. Reaction product for catalase was observed in small ovoid or dumb-bell-shaped bodies in the perikarya of many of the neurons. The abundance of these catalase-reactive peroxisomes is considerably greater than is the case in vertebrate neurons. While the non-neuronal cells of the Aplysia abdominal ganglion do contain appreciable peroxisome populations, there were few peroxisomes in glial cytoplasm directly adjacent to the perikarya, again contrasting with vertebrate ganglia in which the satellite cells are a principal site of peroxisomes. Peroxisomes are present throughout the perikaryal cytoplasm. In the regions in which lipochrome granules abound, peroxisomes are frequently seen closely associated with these granules; glycogen is abundant nearby. The association of peroxisomes, lipochrome granules and glycogen is interesting in view of the propinquities of peroxisomes to lipid droplets and lipofuscin granules reported for non-neuronal vertebrate tissues, and in view of the growing evidence indicating that some of the roles of peroxisomes are in lipid metabolism and in gluconeogenesis. Some of the lipochrome granules themselves show reaction product in ganglia incubated to demonstrate catalase activity and some react in tissue incubated to demonstrate acid phosphatase activity. Such observations suggest that the enzymatic capacities of the lipochrome granules merit further studies, and that the granules may be of complex or heterogeneous nature.

Acid Phosphatase↗
PubMed1985

Severe hypertension and raised haematocrit: unusual presentation of Guillain-Barré syndrome.

A 36 year old man presented with headache, polyuria, thirst and weakness of the lower limbs. Hypertension and a high haematocrit were striking features on initial assessment. Subsequently the full picture of Guillain-Barré syndrome developed. Hormone measurement revealed marked sympathetic nervous system and renin-angiotensin system activation with a return to normal of both blood pressure and hormones with neurological recovery.

Adult↗
PubMed1985

Peroxisomes in fibroblasts from skin of Refsum's disease patients.

Skin fibroblasts were cultured from young adult patients with Refsum's disease, an inherited metabolic disorder characterized by a deficiency in oxidation of phytanic acid and by increased serum and tissue concentrations of this fatty acid. These cultures were compared to cultures of normal fibroblasts in terms of the number and distribution of peroxisomes demonstrable cytochemically in preparations incubated for catalase activity. Refsum's fibroblasts were found to contain 1-10 peroxisome profiles per 100 micron 2 of cytoplasm; the controls contained 1-2 profiles per 100 micron 2. The peroxisomes in normal fibroblasts were found in all regions of the cytoplasm. In the Refsum's material they were relatively scarce in the perinuclear region, where many of the cells showed numerous large inclusions containing lipid-like material and myelin figures. Our findings indicate that in the adult form of Refsum's disease, which is the more thoroughly studied variety, peroxisomes in fibroblasts are not diminished in number. This contrasts with a recent report concerning a case of what is thought to be an infantile form of the disorder, in which no peroxisomes were detected in a liver biopsy. If phytanic acid accumulations in the adult form are a consequence of peroxisomal defects, the defects presumably are at the level of specific enzymatic deficiencies and do not involve a generalized absence of peroxisomes.

Adult↗
PubMed1985

Oxidation of oxalate and polyamines by rat peroxisomes.

During renal failure, polyamines and oxalate levels are elevated in the serum and the glomerular filtrate and are dumped by the kidney. Both of these compounds can be catabolized by oxidative reactions. We have, therefore, investigated the intracellular distribution of oxalate oxidase and of a polyamine oxidase in normal female rat kidney and liver. Polyamine oxidase was demonstrable, using spermidine as substrate in the cerous peroxyhydrate procedure of Briggs et al., in peroxisomes of kidney tubule cells and of hepatocytes. Oxalate oxidase could not be studied with this technique due to precipitation of cerium oxalate in the incubation medium. To demonstrate oxalate oxidase, and to confirm the polyamine oxidase localization, we incubated aldehyde-fixed tissue in a diaminobenzidine medium at pH 8, following the approach of Veenhuis et al., in which oxidases are demonstrated by virtue of their production of H2O2, which then serves as a substrate for endogenous catalase. Using oxalate or spermidine as substrate with this approach, we found reaction product in typical renal peroxisomes; we also found reaction product, with the polyamine substrate, in hepatocyte peroxisomes. To strengthen the conclusion that the oxidases themselves are present in peroxisomes, we used a light microscopic method, based on the tetrazolium procedures of Allen and Beard to demonstrate polyamine and oxalate oxidase activities in bodies with the distribution of renal peroxisomes.

Animals↗
PubMed1984

Ovarian failure following cytotoxic therapy.

Evidence of ovarian failure was sought in 18 premenopausal women who were being treated with cytotoxic drugs for malignant disease. Ten had symptoms and signs of ovarian failure although only two had conveyed these problems to us. Ovarian failure was more frequently observed in patients over 25 and in those on continuous low doses of alkylating agents such as busulphan. Oestrogen/progesterone replacement therapy together with appropriate counselling was given to eight women and brought great benefit to them all. Provided there is no danger of activating the tumour, cytotoxic induced ovarian failure should be treated promptly with replacement therapy even if life expectation is short.

Adolescent↗