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S Cameron

Publications and source records attributed to S Cameron.

At least 109 records · Page 6Linked to original sources

Clinical, biochemical and immunoelectron microscopical evidence of dual hormone production in a mammosomatotroph cell adenoma.

This paper reports the occurrence of a rare, yet distinct pituitary adenoma which was surgically removed from a 42-year-old male with both clinical and biochemical evidence of acromegaly and mild hyperprolactinaemia. The monomorphic adenoma consisted of mature cells which were ultrastructurally indistinguishable from those of a prolactinoma. Electron immunocytochemistry, including a series of double-labelling techniques using selected colloidal gold particles as markers, indicated the presence of a pituitary adenoma in which the cells were capable of simultaneously producing growth hormone and prolactin and packaging them within the same secretory granule. This is thought to represent a mammosomatotroph cell adenoma.

Adenoma↗

Surveillance and sentinel systems.

The research committee of the RACGP has urged authorities in each State to introduce sentinel practice schemes in order to provide information on selected conditions not normally notifiable to public health agencies. To date not all States have taken up the request. In this article the history and role of such schemes are examined. Special attention is paid to the sentinel system that has operated in South Australia since 1983.

Data Collection↗

Purification and characterization of C1, the catalytic subunit of Saccharomyces cerevisiae cAMP-dependent protein kinase encoded by TPK1.

In the yeast Saccharomyces cerevisiae, three genes TPK1, TPK2, and TPK3 encode catalytic subunits of cAMP-dependent protein kinase. We have purified and characterized the catalytic subunit, C1, encoded by the TPK1 gene. In order to purify C1 completely free of C2 and C3, a strain was constructed that contained only the TPK1 gene and genetic disruptions of the other two TPK genes. The cellular level of C1 was increased by expressing the genes for C1 (TPK1) and yeast regulatory subunit (BCY1) on multiple copy plasmids within this strain. Purification was accomplished by a two-column procedure in which holoenzyme was chromatographed on Sephacryl-200, then bound to an anti-regulatory subunit immunoaffinity column. Pure C1 was released from the antibody column by addition of cAMP. The protein migrated on a sodium dodecyl sulfate-polyacrylamide gel with an Mr of 52,000. Kinetic analysis showed that the apparent Km for ATP and Leu-Arg-Arg-Ala-Ser-Leu-Gly was 33 and 101 microM, respectively. The kcat was determined to be 640 min-1. The protein weakly autophosphorylated, incorporating less than 0.1 mol of phosphate/mol of catalytic subunit. NH2-terminal sequencing revealed that the protein was blocked.

Carrier Proteins↗

cAMP-independent control of sporulation, glycogen metabolism, and heat shock resistance in S. cerevisiae.

Genes encoding the regulatory (BCY1) and catalytic (TPK1, TPK2, and TPK3) subunits of the cAMP-dependent protein kinase (cAPK) are found in S. cerevisiae. bcy1- yeast strains do not respond properly to nutrient conditions. Unlike wild type, bcy1- strains do not accumulate glycogen, form spores, or become resistant to heat shock when nutrient limited. We have isolated mutant TPK genes that suppress all of the bcy1- defects. The mutant TPK genes appear to encode functionally attenuated catalytic subunits of the cAPK. bcy1- yeast strains containing the mutant TPK genes respond appropriately to nutrient conditions, even in the absence of CDC25, both RAS genes, or CYR1. Together, these genes encode the known components of the cAMP-generating machinery. The results indicate that cAMP-independent mechanisms must exist for regulating glycogen accumulation, sporulation, and the acquisition of thermotolerance in S. cerevisiae.

Alleles↗

A mutation in the catalytic subunit of cAMP-dependent protein kinase that disrupts regulation.

A mutant catalytic subunit of adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase has been isolated from Saccharomyces cerevisiae that is no longer subject to regulation yet retains its catalytic activity. Biochemical analysis of the mutant subunit indicates a 100-fold decreased affinity for the regulatory subunit. The mutant catalytic subunit exhibits approximately a threefold increase in Michaelis constant for adenosine triphosphate and peptide cosubstrates, and is essentially unchanged in its catalytic rate. The nucleotide sequence of the mutant gene contains a single nucleotide change resulting in a threonine-to-alanine substitution at amino acid 241. This residue is conserved in other serine-threonine protein kinases. These results identify this threonine as an important contact between catalytic and regulatory subunits but only a minor contact in substrate recognition.

Amino Acid Sequence↗

Neuropathy in multiple symmetric lipomatosis. Madelung's disease.

With increasing age, peripheral neuropathy becomes more common in multiple symmetric lipomatosis (MSL) and the principal cause of severe disability. High alcohol consumption is frequently associated and the peripheral neuropathy of MSL is often attributed to alcoholism. In this study, sural nerve biopsies from MSL patients revealed an absence of acute axonal degeneration, a significant shift to the left of myelinated fibre diameter distributions, reduced indices of axonal and nerve fibre circularity, and an increase in myelin periodicity. This pathology supports the view that the neuropathy of MSL is not alcohol-induced but that a chronic distal axonopathy is an integral part of the MSL syndrome. Biochemical observations suggest a defect in catecholamine-stimulated lipolysis in MSL at a membrane level, possibly in the amount or function of Gs membrane protein or in the catalytic unit of adenylate cyclase. Evidence is presented that the frequent association of MSL with alcoholism is on the basis of an additional ethanol-induced membrane lesion involving beta-adrenergic receptors.

Adult↗

SCH9, a gene of Saccharomyces cerevisiae that encodes a protein distinct from, but functionally and structurally related to, cAMP-dependent protein kinase catalytic subunits.

A new gene, SCH9, was isolated from Saccharomyces cerevisiae by its ability to complement a cdc25ts mutation. Sequence analysis indicates that it encodes a 90,000-dalton protein with a carboxy-terminal domain homologous to yeast and mammalian cAMP-dependent protein kinase catalytic subunits. In addition to suppressing loss of CDC25 function, multicopy plasmids containing SCH9 suppress the growth defects of strains lacking the RAS genes, the CYR1 gene, which encodes adenylyl cyclase, and the TPK genes, which encode the cAMP-dependent protein kinase catalytic subunits. Cells lacking SCH9 grow slowly and have a prolonged G1 phase of the cell cycle. This defect is suppressed by activation of the cAMP effector pathway. We propose that SCH9 encodes a protein kinase that is part of a growth control pathway which is at least partially redundant with the cAMP pathway.

Amino Acid Sequence↗

Seronegative blood products prevent primary cytomegalovirus infection after bone marrow transplantation.

Seventy one patients underwent bone marrow transplantation for aplastic anaemia or haematological malignancy, 39 as allografts and 32 as autografts. All patients who were seronegative to cytomegalovirus received blood product support exclusively from seronegative community blood donors; seropositive patients received unscreened products. In no patients was there any attempt to reduce cytomegalovirus (CMV) infection by giving prophylaxis with immunoglobulin, and granulocyte transfusions were not given. The incidence of cytomegalovirus infection in the seronegative recipients (22 allograft, 15 autograft) was 0%; in the seropositive recipients 16 (63%) in allografts and 17 (18%) in autografts. These results suggest that provision of exclusively seronegative blood products is an important contribution for seronegative transplant recipients, but make little impact in autologous transplantation where the incidence of infection is low.

Adolescent↗

Peripheral neuropathy in elderly CBA mice.

A late-onset peripheral neuropathy in a mouse with a wider progressive neurological disorder is morphologically characterized for comparison with late life human neuropathies. Preliminary studies indicate the presence of a proximal, predominantly motor, axonopathy in the mouse model.

Age Factors↗

Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase.

We have isolated three genes (TPK1, TPK2, and TPK3) from the yeast S. cerevisiae that encode the catalytic subunits of the cAMP-dependent protein kinase. Gene disruption experiments demonstrated that no two of the three genes are essential by themselves but at least one TPK gene is required for a cell to grow normally. Comparison of the predicted amino acid sequences of the TPK genes indicates conserved and variable domains. The carboxy-terminal 320 amino acid residues have more than 75% homology to each other and more than 50% homology to the bovine catalytic subunit. The amino-terminal regions show no homology to each other and are heterogeneous in length. The TPK1 gene carried on a multicopy plasmid can suppress both a temperature-sensitive ras2 gene and adenylate cyclase gene.

Amino Acid Sequence↗

Expression in Escherichia coli of BCY1, the regulatory subunit of cyclic AMP-dependent protein kinase from Saccharomyces cerevisiae. Purification and characterization.

The regulatory (R) subunit of cAMP-dependent protein kinase from the yeast Saccharomyces cerevisiae was expressed in Escherichia coli by engineering the gene for yeast R, BCY1, into an E. coli expression vector that contained a promoter from phage T7. Oligonucleotide-directed mutagenesis was used to create an NdeI restriction site at the natural ATG of the yeast R. This facilitated construction of the T7 expression vector so that the sequence of the protein produced was identical to the natural R subunit. Yeast R was highly expressed in a soluble form. 20 mg of purified yeast R was obtained from 4 liters of E. coli. N-terminal amino acid sequencing revealed that the expressed protein began with the natural sequence. 60% of the molecules contained an N-terminal methionine, and 40% initiated with valine, the second amino acid of yeast R. The protein produced in E. coli migrated on a sodium dodecyl sulfate-polyacrylamide gel with an Mr of 52,000. The yeast R bound 2 mol of cAMP/mol of R monomer with a Kd of 76 nM. The protein was treated with urea to remove bound cAMP. Sedimentation values before and after the urea treatment were identical (s20,w = 5.1). Addition of purified R subunit to a preparation of yeast C subunit (TPK1) rendered catalytic activity cAMP-dependent with an activity ratio of 4.6. The yeast R was autophosphorylated by yeast C to a level of 0.8 mol of phosphate/mol of R monomer. By these criteria, the R subunit produced in E. coli was structurally and functionally identical to the natural yeast R subunit and similar to mammalian type II R subunits.

Base Sequence↗

Selective attention in young children: the relations between visual search, filtering, and priming.

Previous studies of visual attention in children have used a wide variety of tasks to demonstrate that visual selectivity improves with age. A guiding assumption (often implicit) of this work is the existence of a single attentional resource that increases in capacity with development. The present study examined the relations between three components of tasks that are often used in developmental studies of attention: search, filtering, and priming. Additive factors logic was applied to a simple speeded classification task performed by subjects aged 4, 7, and 24 years. The results showed (1) improvements with age occurred in each of the three task components, (2) visual search was unrelated to filtering and priming, and (3) filtering and priming were related to one another in a capacity-sharing fashion. Implications of these results for developmental studies of attention and for theories of attention are discussed.

Adolescent↗

Rigorous feedback control of cAMP levels in Saccharomyces cerevisiae.

We have isolated and characterized normal and mutant alleles of many of the genes of the RAS/adenylyl cyclase pathway of the yeast Saccharomyces cerevisiae. Manipulation of those genes has revealed a system for feedback control that can modulate cAMP levels over at least a 10,000-fold range. The feedback control depends upon the activity of the cAMP-dependent protein kinases and requires the presence of the CDC25 and RAS proteins. The capacity for such dramatic control of cAMP levels raises fundamental questions about the normal mechanism of action of the cAMP signaling system in yeast.

Adenylyl Cyclases↗

Cloning and characterization of BCY1, a locus encoding a regulatory subunit of the cyclic AMP-dependent protein kinase in Saccharomyces cerevisiae.

We have cloned a gene (BCY1) from the yeast Saccharomyces cerevisiae that encodes a regulatory subunit of the cyclic AMP-dependent protein kinase. The encoded protein has a structural organization similar to that of the RI and RII regulatory subunits of the mammalian cyclic AMP-dependent protein kinase. Strains of S. cerevisiae with disrupted BCY1 genes do not display a cyclic AMP-dependent protein kinase in vitro, fail to grow on many carbon sources, and are exquisitely sensitive to heat shock and starvation.

Amino Acid Sequence↗

The ultrastructural pathology of congenital murine toxoplasmic retinochoroiditis. Part I: The localization and morphology of Toxoplasma cysts in the retina.

This study describes the ultrastructural characteristics of retinal parasitization by Toxoplasma gondii in a congenital mouse model. Forty-two eyes from infected mice, 18-22-weeks-old, and 24 control eyes were initially studied by light microscopy of semithin sections. Twenty-six eyes from infected animals and six from the controls were further investigated by transmission electron microscopy. A total of 13 Toxoplasma cysts was found in samples of the retinas of six eyes from five infected animals. These were located in the inner retina, particularly the ganglion-cell layer, but in no other ocular tissue. The cyst wall interdigitated with the host cell which in most cases was probably glial in origin (Müller cell). Two cysts showed evidence of parasitization of neural cells. The individual Toxoplasma cystozoites demonstrated characteristic ultrastructural features. There was no evidence of morphological changes indicative of toxicity to surrounding retinal tissues, and the associated inflammatory cell reaction (described in Dutton, McMenamin, Hay and Cameron, 1986b) was remote from the parasite. There was no morphological evidence of rupture or degeneration of cysts. No free parasites (endozoites) or pseudocysts were observed.

Animals↗

The ultrastructural pathology of congenital murine toxoplasmic retinochoroiditis. Part II: The morphology of the inflammatory changes.

A congenital murine model of toxoplasmic retinochoroiditis was employed to study the ultrastructural pathology of retinal parasitization by Toxoplasma gondii. Forty-two eyes from infected mice (18-22-weeks-old) and 24 eyes from control animals were studied by light microscopy (semithin sections). Twenty-six of the eyes from infected animals and six from the control group were subsequently selected for transmission electron microscopy. Control tissues showed no significant abnormality. The pathological changes in diseased tissues ranged in severity from low-grade mononuclear cell infiltration in the subretinal space to complete destruction of the outer retina, the retinal pigment epithelium and the choroid in the presence of a granulomatous inflammatory reaction. Phagocytosis of photoreceptor outer segments by macrophages was observed. Both macrophages and lymphocytes appeared to mediate photoreceptor lysis in eyes which were moderately affected by the disease. Severely affected eyes exhibited vasculitis and inflammatory cell invasion into the vitreous. A lymphoplasmacytoid cell infiltrate was present in the outer retina and choroid in these eyes. There was no evidence that Toxoplasma cysts provided foci for inflammatory cell attack.

Animals↗