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Biomedical subjects

A J Yates

Publications and source records attributed to A J Yates.

At least 145 records · Page 8Linked to original sources
PubMed1987

Biochemical and histological evidence that carcinoma of the prostate is associated with increased bone resorption.

We have investigated the hypothesis that carcinoma of the prostate with skeletal metastases is associated with increased bone resorption. In 54 affected patients a close correlation was observed between serum activity of alkaline phosphatase and urinary excretion of hydroxyproline (r = +0.818; P less than 0.001), comparable to that seen in Paget's disease of bone. The administration of synthetic salmon calcitonin (100 U subcutaneously) induced a significant fall in serum calcium and urinary excretion of hydroxyproline, proportional to the prevailing rate of bone turnover, as assessed by serum alkaline phosphatase or hydroxyprolinuria. Administration of the diphosphonate, etidronate, also decreased hydroxyprolinuria, suggesting that urinary hydroxyproline reflected increased rates of bone resorption in this disorder. Histology of bone in sites adjacent to and distant from skeletal metastases showed increased histological indices of bone resorption. These results suggest that the skeletal disease associated with prostatic carcinoma is characterized by generalized increases in bone resorption as well as focal increases in bone formation.

Aged↗
PubMed1986

Effects of lectin activation on sialyltransferase activities in human lymphocytes.

The effects of phytohemagglutinin (PHA) stimulation on the activities of sialyltransferase 1 (SAT-1), and sialyltransferase 3 (SAT-3), in human lymphocytes were investigated in vitro. For SAT-1 and SAT-3, respectively, the apparent Km values with variable CMP-NeuAc concentrations were 0.19 and 0.015 mM and with variable LacCer were 0.075 and 0.17 mM. Progressive increases in the activities of SAT-1 and SAT-3 were detected in lymphocytes stimulated with PHA, whereas no increase was observed in control lymphocytes incubated in culture medium alone. These increased activities occurred within 18-36 h of incubation and preceded optimum lymphocyte proliferation. Intact lymphocytes were needed for the lectin-stimulated increase of sialyltransferase activities because neither concanavalin A nor phytohemagglutinin added to the broken cell preparation modulated SAT-1 activity. The glycolipid products formed as a result of these enzymatic reactions in the presence of endogenous and exogenous acceptors were tentatively identified by thin-layer chromatography and autofluorography. The addition of exogenous LacCer to the SAT-1 assay resulted in the radiolabeling of a small amount of ganglioside GM1b (3.4%), but GM3 was the major labeled product (96%). When GgOse4Cer was added to the SAT-3 assay, 32% GM3 and 24.6% GM1b were detected while 44% consisted of glycolipids not labeled in assays performed without exogenous acceptors. Of the radioactivity transferred to endogenous acceptors, 81.3% was in GM3 and 14.6% in GM1b. These results demonstrate that the modulation of sialyltransferase activity occurs earlier than cellular activation.

Cells, Cultured↗
PubMed1986

Effective short term treatment of Paget's disease with oral etidronate.

Twelve patients with Paget's disease of bone were treated with high doses of disodium etidronate for one month and compared with patients given treatments for longer periods. The effects of treatment for one month with etidronate 20 mg/kg daily were indistinguishable from six months' continuous treatment with the same dose but significantly better than treatment with 5 mg/kg daily in suppressing biochemical indices of disease activity. Treatment for one month was associated with transient osteomalacia but sustained suppression of bone resorption. Short term treatments with high doses of disodium etidronate may maximise suppression of disease activity but decrease exposure to unwanted effects.

Administration, Oral↗
PubMed1986

Does infarction of the medullary pyramid lead to spasticity?

A 60-year-old patient developed leg weakness leading to spasticity, secondary to a sharply localized infarction of the medullary pyramids. Within a month, spasticity had replaced the initial flaccidity. Several years later, rupture of an atherosclerotic aneurysm of the basilar artery led to subarachnoid hemorrhage and eventual death.

Brain↗
PubMed1986

Gangliosides in the nervous system during development and regeneration.

Gangliosides are present in nervous tissues of echinoderms and chordates, but the amounts and patterns differ widely. There are changes in the ganglioside contents of nervous tissues during development in most animals studied. To a large extent, regional differences and changes with development and degeneration in ganglioside composition reflect changing and different proportions of cellular types and subcellular organelles within the tissue. GM1 and GM4 are enriched in myelin; GD1a may be a marker for dendritic arborization. During regeneration of fish optic nerve and rat sciatic nerve there is an increased amount of ganglioside proximal to the regenerating axon tips, which may largely be a result of accumulation. This could provide a relatively large reservoir of ganglioside to become incorporated into the sprouting axolemma. Gangliosides added exogenously to growth medium can induce neuritogenesis of several types of neurons. The mechanisms of this action are unknown but may be related to nerve growth factor, microskeletal organization, membrane fluidity, and other factors. Gangliosides injected into young animals affect brain development, but further studies are required to determine these effects more specifically. Ganglioside administration increases the number of sprouts in regenerating peripheral nerves, but does not seem to accelerate axonal elongation. Parenterally administered gangliosides alter the recovery of brain tissue from a variety of types of lesions, and clinical trials are in progress to determine if they are of benefit in human neurological disorders. The biochemical mechanisms of these in vivo ganglioside effects are poorly understood, but may involve modulation of several enzyme systems as well as other properties of neural membranes, such as fluidity. It is possible that gangliosides may play similar roles and operate through some of the same mechanisms in developing and regenerating nervous tissues.

Animals↗
PubMed1986

DNA excision repair in spontaneously diabetic BB Wistar rats.

BB Wistar rats develop a syndrome characterized by spontaneous diabetes mellitus as well as a wide variety of autoimmune, neoplastic, and degenerative disorders which do not occur in the outbred Wistar strain from which they were derived. This syndrome also includes elements of premature ageing (i.e., a markedly shortened lifespan and premature occurrence of diseases associated with ageing). Excision DNA repair capacity which has been reported to be directly proportional to maximal achievable life span was estimated in neonatal BB Wistar and outbred Wistar rats. Excision repair was assayed autoradiographically by determining unscheduled DNA synthesis following UV radiation of passage 3 cultured skin fibroblasts. No difference in excision repair capacity could be demonstrated between the two strains.

Animals↗
PubMed1986

Steroid-induced remission in primary malignant lymphoma of the central nervous system.

A case of primary malignant lymphoma of the central nervous system is described in which lesions seen on computed tomography scans disappeared, and clinical remissions occurred with the administration of corticosteroids. The tumor affected the region of the fourth ventricle and parietal and frontal lobes. In our patient, three remissions occurred over a span of 24 months, each in conjunction with corticosteroid administration. This supports other observations that steroids alter the natural history of primary malignant lymphoma of the central nervous system, leading to both radiologic and clinical remissions.

Adrenal Cortex Hormones↗
PubMed1986

A study of intracellular orthophosphate concentration in human muscle and erythrocytes by 31P nuclear magnetic resonance spectroscopy and selective chemical assay.

In order to study the relationship between extracellular and intracellular concentrations of orthophosphate (Pi), phosphorus nuclear magnetic resonance spectra were recorded, at rest, from the flexor digitorum superficialis muscle of hypophosphataemic patients with vitamin D-resistant rickets, and patients with Paget's disease of bone before and after they had been made hyperphosphataemic by treatment with the drug ethylidene-1-hydroxy-1,1-bisphosphonate. Changes in intramuscular P1 were estimated from the ratio of the areas of the Pi to adenosine 5'-triphosphate peaks. Even though the plasma Pi concentration in these patients spanned a fourfold range (0.5-2.0 mmol/l) the corresponding intramuscular Pi concentration increased by only 70%. A similar effect was observed in erythrocytes, from patients with these disorders, which were incubated in autologous plasma at 37 degrees C, under an atmosphere of O2 + CO2 (95:5, v/v). However, chloride ions, which are transported passively across the cell membrane, showed no change in distribution between cells and plasma, indicating that there was no general effect on passive anion distribution. When erythrocytes from normal subjects were incubated in autologous plasma (1.0 mmol of Pi/l) and in plasma supplemented with Pi (2.3 mmol of Pi/l), the Pi concentration in the cells, at steady state, increased only from 0.57 to 0.78 mmol/l cells, suggesting that the effect was not an artifact of disease or drug therapy. It is concluded that, in human skeletal myocytes and erythrocytes, the percentage change in the concentration of cytoplasmic Pi is lower than that in plasma. This implies that these cells can buffer or regulate cytoplasmic Pi when the extracellular concentration is disturbed.

Adult↗
PubMed1985

Mechanism of malignant hypercalcaemia in carcinoma of the breast.

To investigate the mechanisms of hypercalcaemia in carcinoma of the breast, 22 patients with hypercalcaemia due to metastatic carcinoma were studied and the findings compared with those obtained in normal subjects and patients with benign and malignant breast disease without hypercalcaemia. As expected, patients with metastases of bone showed biochemical evidence of increased bone resorption. Whereas all patients with hypercalcaemia had skeletal metastases, not all patients with skeletal metastases had hypercalcaemia despite considerable degrees of bone resorption. The presence of hypercalcaemia was associated with a significant increase in renal tubular reabsorption of calcium (p less than 0.001) and decreased reabsorption of phosphate (p less than 0.001) despite adequate rehydration of patients. These studies suggest that increased renal tubular reabsorption of calcium, possibly mediated by a humoral factor with activity similar to that of parathyroid hormone, contributes appreciably to the hypercalcaemia of malignant breast disease.

Absorption↗
PubMed1985

Intravenous clodronate in the treatment and retreatment of Paget's disease of bone.

The effects of short courses (5 days) of intravenous clodronate 300 mg daily were studied in 31 patients with active Paget's disease of bone. The diphosphonate induced a striking reduction in biochemical indices of disease activity, which was sustained for at least 6 months after withdrawal of treatment. Apparent resistance to further treatment in patients previously treated for Paget's disease was an artefact due to incomplete relapse before retreatment. There was no significant difference in the degree of suppression of alkaline phosphatase activity between patients given intravenous clodronate and 45 patients given clodronate 1.6 g daily by mouth for 6 months. Short-term intravenous clodronate provides a useful alternative strategy for the treatment of patients with Paget's disease.

Administration, Oral↗
PubMed1985

Brainstem immaturity in sudden infant death syndrome: a quantitative rapid Golgi study of dendritic spines in 95 infants.

Quantitative analysis of reticular dendritic spines was performed on rapid Golgi impregnated neurons in 7 brainstem areas from 61 sudden infant death syndrome (SIDS) and 34 control infants. Throughout the first postnatal year, mean spine density in SIDS was significantly greater than the mean density in controls (P less than 0.0001). There were significantly higher values of spine density in SIDS compared to controls (P less than 0.0001) in both term and preterm infants. Within the SIDS brainstem itself, the density of dendritic spines was significantly different (P less than 0.05) between two medullary regions and between reticular and non-reticular formation areas. Among these brainstem areas in controls, there was no significant difference. Our findings indicate an immature developmental pattern of increased dendritic spine density in the SIDS brainstem which may be responsible for abnormal central respiratory and arousal control. These significant quantitative differences in spine density are considered in the present study to represent an anatomical substrate of brainstem immaturity in the multifactorial pathogenesis of SIDS.

Brain Stem↗
PubMed1985

Polyneuropathy and IgM monoclonal gammopathy: studies on the pathogenetic role of anti-myelin-associated glycoprotein antibody.

Attention has recently been directed toward patients having a polyneuropathy and a monoclonal IgM anti-myelin-associated glycoprotein (anti-MAG) antibody. The possibility of a pathogenetic role for the anti-MAG antibody in the evolution of the polyneuropathy and in the development of central nervous system signs, including tremor and ataxia, remains unresolved. In 5 patients with this syndrome whose clinical courses were followed closely, in 1 of whom a complete postmortem examination of the nervous system was performed, we made the following observations: the anti-MAG antibody did not localize to the compact layer of the myelin sheath in affected nerves, but did localize to areas of myelin splitting; anti-MAG antibody present in the sural nerve of an affected individual for 7 years was not associated with progressive pathology; anti-MAG antibody was not deposited in the central nervous system of an affected individual, although the antibody did bind to these same tissues in vitro; deposition of anti-MAG antibody observed at postmortem examination did not correlate with the degree of pathological change; and study of the peripheral nervous system favored a primary axonal neuropathy with secondary demyelination.

Adult↗
PubMed1985

Natural killer activity against cultured human neural tumor and fetal brain cells.

Ten human neural tumor lines and three established from normal human brain were analyzed for sensitivities to natural killer (NK) cytolysis. Compared to MOLT-4, fetal brain cells were sensitive, but those from adult brain and eight of ten neural tumor cell lines demonstrated marked NK resistance. The frequencies of target-binding cells (TBC) and single-cell lysis of glioma cells bound within tumor cell conjugates demonstrated that the resistance of two lines was explained either by a decrease in the frequencies of TBC or reduced ability of bound NK cells to lyse the tumor cell conjugates. A third resistant line demonstrated decreases in both TBC and tumor cell conjugate lysis. Two glioma lines with less NK resistance had greater frequencies of TBC or conjugate lysis than the resistant lines. Thus, NK resistance can result from decreased recognition of targets, diminished NK lysis of bound targets, or a combination of both.

Astrocytoma↗
PubMed1985

The patterns of brain gangliosides of Rana catesbeiana during metamorphosis and in the adult.

Ganglioside patterns were quantitated for brains of bullfrog (Rana catesbeiana) at three stages of metamorphosis and adult. At each stage nine gangliosides were identified by mobility on silica gel thin-layer chromatograms, and quantitated on the basis of sialic acid content. A single band with chromatographic mobility close to that of GD2, and doublets close to GT1b and GQ were quantitatively the major ones (over 16% each). Doublets close to GM1 and GD1b and a single band slightly behind GD1a made up 5-10% each. A doublet comigrating with GM3, and bands close to GM2 (trace) and GD3 were present in smaller amounts. The only developmental trend was a slight increase in the proportion of the band close to GD3 from 2.4% (early prometamorphic phase) to 9.1% (adult). This suggests that changes in the regenerative capacity of frog nervous tissues during metamorphosis are due to changes other than ganglioside composition.

Animals↗