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Biomedical subjects

R Cameron

Publications and source records attributed to R Cameron.

At least 91 records · Page 5Linked to original sources

Synapsins in the vertebrate retina: absence from ribbon synapses and heterogeneous distribution among conventional synapses.

The vertebrate retina contains two ultrastructurally distinct types of vesicle-containing synapses: conventional synapses, made predominantly by amacrine cells, and ribbon synapses, formed by photoreceptor and bipolar cells. To identify molecular differences between these synapse types, we have compared the distribution of the synapsins, a family of nerve terminal phosphoproteins, with that of synaptophysin (p38) and SV2, two intrinsic membrane proteins of synaptic vesicles. We report an absence of synapsin I and II immunoreactivity from all ribbon-containing nerve terminals. These include terminals of rod cells in developing and adult rat retina, rod and cone cells in monkey and salamander retinas, and rat bipolar cells. Furthermore, we show that synapsins I and II are differentially distributed among conventional synapses of amacrine cells. The absence of the synapsins from ribbon synapses suggests that vesicle clustering and mobilization in these terminals differ from that in conventional synapses.

Aging↗

Elevated liver enzymes and thrombocytopenia in the third trimester of pregnancy: an unusual case report and a review of the literature.

A woman presented in the third trimester of pregnancy with epigastric pain, elevated liver enzymes, and thrombocytopenia. The frozen-section liver biopsy findings were compatible with acute fatty liver of pregnancy. The light and electron microscopic findings were those of preeclampsia. All clinical and laboratory abnormalities resolved before delivery.

Acute Disease↗

Biochemical and clinical response of fulminant viral hepatitis to administration of prostaglandin E. A preliminary report.

The effect of PG on patients with fulminant and subfulminant viral hepatitis (FHF) was studied. 17 patients presented with FHF secondary to hepatitis A (n = 3), hepatitis B (n = 6), and non-A, non-B (NANB) hepatitis (n = 8). 14 of the 17 patients had stage III or IV hepatic encephalopathy (HE). At presentation the mean aspartate transaminase (AST) was 1,844 +/- 1,246 U/liter, bilirubin 232 +/- 135 mumol/liter, prothrombin time (PT) 34 +/- 18, partial thromboplastin time (PTT) 73 +/- 26 s, and coagulation Factors V and VII 8 +/- 4 and 9 +/- 5%, respectively. Intravenous PGE1 was initiated 24-48 h later after a rise in AST (2,195 +/- 1,810), bilirubin (341 +/- 148), PT (36 +/- 15), and PTT (75 +/- 18). 12 of 17 responded rapidly with a decrease in AST from 1,540 +/- 833 to 188 +/- 324 U/liter. Improvement in hepatic synthetic function was indicated by a decrease in PT from 27 +/- 7 to 12 +/- 1 s and PTT from 61 +/- 10 to 31 +/- 2 s, and an increase in Factor V from 9 +/- 4 to 69 +/- 18% and Factor VII from 11 +/- 5 to 71 +/- 20%. Five responders with NANB hepatitis relapsed upon discontinuation of therapy, with recurrence of HE and increases in AST and PT, and improvement was observed upon retreatment. After 4 wk of intravenous therapy oral PGE2 was substituted. Two patients with NANB hepatitis recovered completely and remained in remission 6 and 12 mo after cessation of therapy. Two additional patients continued in remission after 2 and 6 mo of PGE2. No relapses were seen in the patients with hepatitis A virus and hepatitis B virus infection. Liver biopsies in all 12 surviving patients returned to normal. In the five nonresponders an improvement in hepatic function was indicated by a fall in AST (3,767 +/- 2,611 to 2,142 +/- 2,040 U/liter), PT (52 +/- 25 to 33 +/- 18 s), and PTT (103 +/- 29 to 77 +/- 44 s), but all deteriorated and died of cerebral edema (n = 3) or underwent liver transplantation (n = 2). These results suggest efficacy of PGE for FHF, and further investigation is warranted.

Adolescent↗

The problem of longterm disability payments and litigation in primary fibromyalgia: the Canadian perspective.

The determination of disability in fibromyalgia syndrome is problematic because of its perceived subjective nature and the absence of well defined criteria for diagnosis. This, together with an unclear idea of the natural history, creates problems in litigation and determination of rehabilitation costs. Lawyers and third party payers must cooperate with physicians to determine the "hidden costs" of fibromyalgia so that a fairer estimate of longterm disability is achieved.

Canada↗

Glomerular epithelial detachment, not reduced charge density, correlates with proteinuria in adriamycin and puromycin nephrosis.

To identify the structural change coincident with increased glomerular permeability in both adriamycin (ADR) and puromycin-aminonucleoside (PAN) nephrosis, we explored the temporal correlation between developing proteinuria, the reduction in glomerular polyanions, and the detachment of epithelium from glomerular basement membrane (GBM). Sprague-Dawley rats received a single tail-vein injection of PAN (150 mg/kg), ADR (7.5 mg/kg) or saline. Nephrotic-range proteinuria appeared between days 2 to 5 in the PAN-treated and days 5 to 10 in the ADR-treated rats. The GBM heparan sulfate charge density and epithelial membrane sialic acid (SA) content were determined before, during and after the rise in proteinuria. Polyethyleneimine was used to detect heparan sulfate and the number staining of renal cortical slices was used to detect heparin sulfate and the number of sites/microns GBM in the lamina rara externa were counted on electron micrographs (magnification x60,000). Controls had a regular distribution of polyethyleneimine 20.19 +/- 1.72 sites/microns (X + SD). In ADR rats, the polyethyleneimine density decreased by day 5, 18.61 +/- 1.79 sites/microns (p less than 0.05) which persisted to day 15, 17.38 +/- 1.27 sites/microns (p less than 0.02). PAN rats, by day 1, had significant reduction, 14.94 +/- 1.47 sites/microns (p less than 0.05), which persisted to day 20. The total membrane-bound SA content of isolated glomeruli was analyzed with a modified Warren's method. The SA content in control glomeruli was 46.8 +/- 8.0 nmol/mg glomerular protein (X +/- SD). In ADR rats, there was significant decrease in SA content to 84 +/- 3% of control (p less than 0.01) at day 15. In PAN rats, by day 2, the SA content was decreased to 73 +/- 18% of control (p less than 0.05). In both models, scanning and transmission electron microscopy revealed epithelial foot process fusion, loss of slit diaphragms, and vacuolization before increased proteinuria. Epithelial detachment from the GBM and rupture of vacuoles occurred coincidently with rapid development of nephrotic proteinuria in both models. In summary, reduced GBM heparan sulfate and epithelial SA content do not correlate with the onset of altered glomerular permeability, whereas epithelial detachment is coincident with the development of massive proteinuria in both ADR and PAN nephrosis.

Animals↗

Hepatotoxicity to dogs of horse meat contaminated with indospicine.

An outbreak of liver disease which killed more than 30 dogs at Alice Springs was associated with feeding meat from horses, some of which had developed Indigofera linnaei poisoning (Birdsville horse disease). Affected livers were small, nodular and yellow. There was associated jaundice, ascites, elevation of alanine aminotransferase levels in serum, a tendency to bleed, and signs of hepatic encephalopathy. Histologically, livers showed periacinar necrosis, collapse and haemorrhage, with severe swelling, vacuolation and cholestasis in remaining hepatocytes. Indospicine, a toxic amino acid found in the genus Indigofera, was detected in samples of suspect horsemeat. Experimental feeding of horsemeat containing 16 mg indospicine/kg for 32 days produced periacinar necrosis and hepatocellular swelling in 2 dogs, although neither died nor showed clinical illness. In another experiment, intakes of as little as 0.13 mg indospicine/kg bodyweight/day for 70 days produced periacinar liver lesions, and indospicine concentrations in serum, muscle and liver rose during this period to 3.9, 7.9 and 17.5 mg/kg, respectively. It was concluded that meat from horses grazing I. linnaei can be hepatotoxic for dogs, and that this toxicity may be related to its indospicine content.

Amino Acids↗

Imaging studies and the prognostic value of serum calcitonin in staging small-cell lung cancer.

The controversial prognostic significance of serum calcitonin in small-cell lung cancer (SCC) prompted this retrospective study relating serum levels to (1) stage of disease [limited disease (LD) vs. extensive disease (ED)], (2) imaging studies of metastases to bone, liver, and brain, and (3) survival. Of the 127 previously untreated patients with SCC presenting from 1979 to 1984, calcitonin levels could be compared to the stage of the disease in 69 patients (25 LD and 44 ED) and to various staging procedures including 99mTc methylene diphosphonate bone scans (63 patients), 99mTc sulfur colloid liver-spleen scans (64 patients), computed tomography of the head (63 patients) and serum calcium (61 patients). 71% (49/69) of patients had elevated calcitonin of whom 65% (32/49) had ED. 29% (20/69) had normal levels of whom 60% (12/20) had ED. 40% (18/45) of patients with raised calcitonin had liver metastases. 100% (19/19) with normal calcitonin had no liver involvement. Two patients with hypercalcemia and increased calcitonin had extensive bony metastases. The survival experiences of patients with normal and elevated serum calcitonin levels were analyzed. No significant differences were found within each stage or in the group overall. The positive correlation of serum calcitonin to liver metastases was statistically significant. No such relationship could be demonstrated with stage of disease, bone metastases, brain metastases, or survival.

Calcitonin↗

Protein production and secretion in exocrine cells.

Acinar cells of exocrine glands are highly specialized for producing, storing, and discharging secretory proteins for use on surfaces that represent interfaces between the organism and the surrounding environment. These functions are achieved through the secretory pathway that includes a series of functionally distinct intracellular compartments--the endoplasmic reticulum, subcompartments of the Golgi complex, and the secretion granule in which exportable macromolecules are stored at high concentrations. Most secretion occurs by granule exocytosis in response to external hormonal or neural stimuli. Although these processes have been traced in a variety of morphological and biochemical studies, very little is known about the mechanisms involved in facilitating and maintaining secretory storage, orchestrating discharge at the apical cell surface, and in ensuring conservation and re-internalization of the granule membrane. Recent studies initiated on cell fractions obtained from the rat parotid gland have provided significant insight into the protein storage conditions that prevail in the granule interior and the components of the granule membrane that are likely to be involved in general secretory function such as exocytosis.

Animals↗

Pleomorphic adenoma in the breast of a human female. Aspiration biopsy findings and receptor determinations. Case report.

A case of multiple pleomorphic adenomas ("mixed" tumour of salivary gland type) of the breast is reported. This rare benign tumour can be misinterpreted as a malignant tumour both clinically and radiologically. The aspiration biopsy findings suggested cystosarcoma phyllodes. Oestrogen and progesterone receptor determinations revealed medium high levels, comparable to carcinoma of the breast.

Adenoma, Pleomorphic↗

Delineation of two defects responsible for T-cell hyporesponsiveness to concanavalin A in MRL congenic mice.

MRL-lpr mice and their congenic counterparts MRL-+ spontaneously develop an autoimmune disease that resembles systemic lupus erythematosus in humans. The two strains, although congenic, differ by a considerable number of disease parameters, reflecting the expression of the lpr autosomal recessive gene. One paradox that has developed out of the work utilizing the congenic mice is that the gene responsible for lymphoproliferation also appears to be responsible for the inability of T cells to respond to proliferative signals in vitro. In this paper we investigated a possible lpr gene-encoded macrophage defect in these mice. It was found, however, that both the MRL-+ and MRL-lpr mice failed to divide in response to Con A, the lack of division correlating with an inability to secrete the growth promoter interleukin-2. In MRL-+ mice and young MRL-lpr mice this non-responsiveness was corrected by the addition of normal CBA PEC. The defect could not be explained by a failure of MRL-+ or MRL-lpr peritoneal exudate cells to quantitatively or qualitatively provide a source of interleukin-1 to Con A-activated T cells or by the possibility that the peritoneal exudate cells were blocked in their function by the presence of sera-derived autoantibodies and/or immune complexes on their membranes. We postulate that the inability of T cells to proliferate in MRL congenic mice can be explained by two defects: the failure of antigen-presenting cells in MRL-+ and MRL-lpr to provide the necessary signals to immunocompetent T cells, this defect not being associated with the lpr gene, and the lpr gene controlled outgrowth of a unique T-cell population that cannot respond in our assay system.

Animals↗

Radiosensitization effects of nicotinamide on malignant and normal mouse tissue.

Inhibitors of the chromatin-associated enzyme adenosine diphosphate ribosyltransferase have been found to inhibit DNA strand rejoining and to potentiate lethality of DNA-damaging agents both in vivo and in vitro. We have in this work examined the radiosensitizing potential of one such inhibitor, nicotinamide, on tumor tissue by using transplanted C3H mouse mammary adenocarcinomas and on normal tissue in a tail-stunting experiment using BALB/cA mice. Our data indicate a radiosensitizing effect of nicotinamide on tumor cells as well as on normal tissue. The data indicate a possible role of adenosine diphosphate ribosyltransferase inhibitors as a sensitizing agent in the radiotherapy of malignant tumors.

Animals↗

The effects of education and group discussion in the post myocardial infarction patient.

An education and group discussion program administered to a randomly selected group of post myocardial infarction subjects failed to produce any differences in a large number of behavioral and psychological measures. These included smoking behavior, health status, social and recreational status, family and marital life and vocational activities, as well as measures of anxiety, depression, and health locus of control. Treated subjects were slower to return to work than controls and were less likely to have returned to work by the end of the study. More individuals in the treatment group were receiving compensation and this may have been a factor in delaying return to work. Since the majority of our subjects had a very optimistic attitude toward their eventual recovery, there was limited room for improvement. We suggest that cardiac rehabilitation be directed only at those patients with "negative" attitudes, and with more than usual anxiety and depression.

Adaptation, Psychological↗

Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections.

Synapsin I (formerly referred to as protein I) is the collective name for two almost identical phosphoproteins, synapsin Ia and synapsin Ib (protein Ia and protein Ib), present in the nervous system. Synapsin I has previously been shown by immunoperoxidase studies (De Camilli, P., T. Ueda, F. E. Bloom, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA, 76:5977-5981; Bloom, F. E., T. Ueda, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA 76:5982-5986) to be a neuron-specific protein, present in both the central and peripheral nervous systems and concentrated in the synaptic region of nerve cells. In those preliminary studies, the occurrence of synapsin I could be demonstrated in only a portion of synapses. We have now carried out a detailed examination of the distribution of synapsin I immunoreactivity in the central and peripheral nervous systems. In this study we have attempted to maximize the level of resolution of immunohistochemical light microscopy images in order to estimate the proportion of immunoreactive synapses and to establish their precise distribution. Optimal results were obtained by the use of immunofluorescence in semithin sections (approximately 1 micron) prepared from Epon-embedded nonosmicated tissues after the Epon had been removed. Our results confirm the previous observations on the specific localization of synapsin I in nerve cells and synapses. In addition, the results strongly suggest that, with a few possible exceptions involving highly specialized neurons, all synapses contain synapsin I. Finally, immunocytochemical experiments indicate that synapsin I appearance in the various regions of the developing nervous system correlates topographically and temporally with the appearance of synapses. In two accompanying papers (De Camilli, P., S. M. Harris, Jr., W. B. Huttner, and P. Greengard, and Huttner, W. B., W. Schiebler, P. Greengard, and P. De Camilli, 1983, J. Cell Biol. 96:1355-1373 and 1374-1388, respectively), evidence is presented that synapsin I is specifically associated with synaptic vesicles in nerve endings.

Animals↗