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Biomedical subjects

P Cameron

Publications and source records attributed to P Cameron.

At least 55 records · Page 3Linked to original sources
PubMed1995

Patterns of injury from major trauma in Victoria.

Basic demographic and injury data were collected on all major trauma patients (ISS > 15) presenting to 25 Victorian hospitals over a 1 year period (March 1992-February 1993). A total of 1076 patients were identified with an Injury Severity Score (ISS) > 15. Of these, 957 resulted from blunt trauma, 68 from penetrating trauma and 51 from burns. Most serious blunt injury was transport-related (n = 652) but falls made up a significant proportion (n = 206). The pattern of injury in blunt trauma demonstrated in this study showed a preponderance of serious head, thoracic and limb injuries with less frequent occurrences of abdominal, spine and facial injuries. In major penetrating trauma, serious injuries of the thorax and abdomen were more frequent. Head injury is the most common cause of morbidity in major trauma patients. Motor vehicle accidents caused the majority of head injuries but, proportionately, head injury was more common in pedal cycle, pedestrian, motorcycle injuries and falls. The low frequency of major abdominal trauma has important implications for surgical training and resource allocation. In Victoria, various injury prevention interventions have been introduced such as compulsory wearing of bicycle helmets, a safer home environment and behavioral modifications through advertising. Injury prevention strategies must continue to target the populations at risk and assess the impact of interventions by accurate injury surveillance.

Accidents, Home↗
PubMed1995

Microbial Demethylation of Immunosuppressant FK-506: Isolation of 31-O-FK-506-Specific Demethylase Showing Cytochrome P-450 Characteristics from Streptomyces rimosus MA187.

As a result of an extensive screening program for the microbial modification of the immunosuppressant FK-506, one culture, Streptomyces rimosus MA187, which specifically catalyzed the C-31 demethylation of FK-506 was identified. Treatment of the biotransforming culture with FK-506 increased demethylase activity 2.4-fold and stabilized the cytochrome P-450 protein. The enzyme responsible for this demethylation (31-O-FK-506 demethylase) was isolated and shown to be a soluble cytoplasmic protein which is constitutively expressed in the cells, which requires NADPH, ferredoxin-NADP(sup+)-reductase, and ferredoxin for activity, and which shows a cytochrome P-450 light absorption characteristic. Carbon monoxide saturation of the enzyme preparation and known mammalian cytochrome P-450 inhibitors such as quinidine HCl, ketoconazole, troleandomycin, and sulfaphenazole abolish the demethylating activity extensively. The purified enzyme is a monomeric protein with a molecular mass of 42 kDa and shows its maximal activity at a pH of 7.4 and an incubation temperature of 34(deg)C. The first 19 N-terminal amino acids in the sequence of the purified protein have been determined, with no cytochrome P-450 match found in the OWL and Swiss-Prot 23 databases. The isolated demethylase is therefore a cytochrome P-450 protein that can be used as a catalyst for the synthesis of 31-O-desmethylFK-506, an important immunosuppressant and a known metabolite of FK-506 metabolism by human liver microsomes.

Journal Article↗
PubMed1995

Does incest cause homosexuality?

A random sample of 5,182 adults from 6 U.S. metropolitan areas were questioned about incestuous sexual relationships during childhood. Incest was disproportionately reported by both male and female bisexuals and homosexuals. 148 gays (7.7% of the sample) reported 14 (50%) of same-sex, and 7 (22%) of opposite-sex incestuous experiences, and 20 (69%) of same-sex and 2 (3%) of opposite-sex sexual experiences with other relatives. 88 lesbians (3% of the sample) reported 2 (33%) of same-sex incest and 7 (9%) of opposite-sex incest and 1 (17%) of same-sex and 10 (13%) of opposite-sex sexual experiences with other relatives. 12% of 98 male homosexuals vs 0.8% of 1,224 male heterosexuals with a brother reported brother-brother incest. These findings are consonant with those of other studies in which disproportionately more incest by homosexuals was reported. As opposed to an evolutionary genetic hypothesis, these data support the alternative that homosexuality may be learned, since homosexuals do not produce children at sustainable levels and the incidence of homosexuality varies as a function of various social factors. Incest cannot be excluded as a significant basis for homosexuality.

Adolescent↗
PubMed1994

A mutant human histocompatibility leukocyte antigen DR molecule associated with invariant chain peptides.

From a human histocompatibility leukocyte antigen (HLA)-DR/DQ hemizygous, B lymphoblastoid progenitor, we isolated a cell line, 10.24.6, with a DR alpha missense mutation (96P-->96S), which results in an N-linked carbohydrate addition at position 94 in the DR alpha 2 domain. Several features of 10.24.6 cells suggest that the mutation disrupts normal intracellular formation of peptide/DR complexes. The mutant HLA-DR dimers, though expressed at the cell surface, lack the conformation of the mature, peptide-loaded class II molecules of the progenitor cell, as assessed by their loss of binding of certain antibodies and by the lack of stability in detergent (sodium dodecyl sulfate) solution. In addition, presentation of endocytosed antigen to HLA-DR-restricted T cells is defective in the mutant, but can be restored by transfection of a wild type DRA gene. Assays with synthetic peptides indicate that the 10.24.6 phenotype is not due to an intrinsic inability of the mutant DR molecules to bind peptides. Therefore, to directly evaluate peptide occupancy of the mutant molecules, we analyzed acid-eluted, HLA-DR-associated peptides. The predominant species from the 10.24.6 mutant is a nested set of invariant chain (Ii)-derived peptides that are undetectable in the DR eluate from progenitor cells. The region of DR alpha altered in the mutant molecules is thus implicated in normal formation of peptide/DR complexes. Further, the same set of Ii peptides associated with the DR molecules is present in the eluate from an antigen presentation mutant with a defect in an major histocompatibility complex (MHC)-linked gene. These results suggest that DR molecules in 10.24.6 and in certain presentation mutants are affected at the same or related steps in class II molecule biosynthesis, raising the possibility that class II molecules interact with an MHC-encoded accessory molecule during antigen presentation.

Amino Acid Sequence↗
PubMed1993

Efficacy of low doses of the polyethylene glycol derivative of interleukin-2 in modulating the immune response of patients with human immunodeficiency virus type 1 infection.

Interleukin-2 (IL-2) is a key cytokine in cellular immunity. Human immunodeficiency virus type 1 (HIV-1)-infected individuals lack IL-2 because of low CD4+ T lymphocyte numbers. In an attempt to enhance cellular immunity, low-dose recombinant human (rh) IL-2 at 10 micrograms or 180,000 units or its polyethylene glycol (PEG) derivative at 9 micrograms or 36,000 units was given by intracutaneous injection to 8 HIV-1-infected men for 30 days. Participants had no evidence of opportunistic infection and received concurrent zidovudine. IL-2 treatment was nontoxic and elicited a local cellular response resembling classic delayed-type hypersensitivity (DTH) with local interferon-gamma production, even in anergic patients. Systemic responses included enhanced DTH responses to recall antigens, improved in vitro proliferative responses to mitogen, and enhanced NK cell activity. Peripheral leukocyte phenotype and virus titers were unchanged. Long-term studies of low-dose IL-2 are warranted to determine whether immunoenhancing effects can be sustained and if they are associated with improved clinical course.

Adult↗
PubMed1993

Intravenous aminophylline confers no benefit in acute asthma treated with intravenous steroids and inhaled bronchodilators.

BACKGROUND: The role of intravenous aminophylline in acute asthma is unclear despite meta-analysis of many studies comparing aminophylline with other bronchodilator therapies. AIMS: The aim of this study is to determine whether continuous aminophylline infusion confers any benefit in acute severe asthmatics treated with intravenous steroids and inhaled bronchodilators. METHODS: The study was randomised, double-blind and placebo-controlled. All patients received nebulised salbutamol (1 mL of 0.5%) and ipratropium bromide (1 mL of 0.025%) with glycol diluent (1 mL) at 0, two, four, six, eight and 12 hours, and six-hourly thereafter. In addition all patients were given intravenous hydrocortisone 250 mg six-hourly and oxygen to maintain normoxia. Aminophylline infusions were adjusted to maintain therapeutic levels. Peak expiratory flow rate (PEFR) was measured before and after nebulised bronchodilator on a two-hourly basis in the Emergency Department (ED) and six-hourly on the inpatient wards. RESULTS: Thirty-one patients were clinically sufficiently improved within 12 hours to be discharged home from the ED. The remaining 28 patients were admitted to the inpatient ward for a total trial duration of 48 hours. No significant difference was found between the placebo and treatment groups for measurements of PEFR, or for the duration of stay of the patients in hospital. The power of the study was 80% for a 25% to 33% difference at a 5% level of significance. Presentation values of PEFR and arterial blood gases did not predict which patients would require inpatient admission and which could be safely discharged home from the ED.

Acute Disease↗
PubMed1993

Traffic of synaptic vesicle proteins in polarized and nonpolarized cells.

Neurons have at least two pathways of regulated secretion, which involve two classes of secretory organelles: typical synaptic vesicles (SVs) and large dense-core vesicles. Large dense-core vesicles store and secrete peptide neurotransmitters and amines, and may be seen as the neuronal counterpart of secretory granules of endocrine cells. SVs are highly specialized secretory organelles, which store and secrete non-peptide hormones and play a dominant role in the fast, point-to-point signalling typical of the nervous system. Microvesicles that share a variety of biochemical and functional similarities with SVs (synaptic-like microvesicles) have recently been described in endocrine cells. SVs and synaptic-like microvesicles are closely related to vesicular carriers of the receptor-mediated recycling pathway. They undergo repeated cycles of exo-endocytosis, which are thought to involve endosomal intermediates. In mature neurons, SVs are concentrated in axon endings. To gain insight into the mechanisms responsible for SV targeting, we have studied the traffic of SV proteins in both endocrine cells and developing hippocampal neurons in primary culture at different stages of differentiation. Additionally, the distribution of the SV protein synaptophysin, when expressed by transfection in fibroblastic cells or in polarized epithelial cells (MDCK cells), was investigated. SV proteins are already present in developing neurons at stages preceding the establishment of neuronal polarity. As axons and dendrites form, SV proteins are found in both types of processes, although they become progressively more concentrated in the axon. Throughout these developmental stages SVs undergo active exo-endocytotic recycling.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The challenge of predicting response to stabilising lithium treatment. The importance of patient selection.

Lithium treatment, an approach with well documented efficacy, has recently been losing its treatment value. Lithium continues working, however, for those patients for whom it was proven efficacious; that is, most patients with primary episodic affective disorders. Such responders to lithium prophylaxis can be reliably identified beforehand by a comprehensive clinical assessment. The explanation for the paradox of lithium's lost efficacy lies mostly in the educational bias against a comprehensive patient assessment, and in the shift in diagnostic fashion favouring affective disorders and the treatment methods associated with them in the clinicians' minds.

Depressive Disorder↗
PubMed1992

Production, purification and characterization of canine prostromelysin.

One of the best studied animal models of osteoarthritis is a dog model in which the anterior cruciate ligament of the hind limb stifle joint is transected (Pond-Nuki model). To determine whether stromelysin might play a role in this model, it was necessary to purify the enzyme for production of suitable probes. In the present study, dog synovial fibroblasts were stimulated to express a metalloproteinase that was demonstrated to be canine prostromelysin by Northern blot, protein purification and amino-terminal sequence analyses. Unlike rabbit synoviocytes, passaged dog synoviocytes did not express stromelysin mRNA in response to recombinant human IL-1, but expressed stromelysin mRNA only upon treatment with dog monocyte-conditioned medium (dMCM). The aminophenylmercuric acetate (APMA)-activatable metalloproteinase present in the culture supernatants of stimulated dog synoviocytes was purified using a combination of ion-exchange and dye matrix affinity chromatography. The purified canine metalloproteinase co-migrated on reducing SDS-PAGE with recombinant human prostromelysin-1 as a doublet with apparent molecular masses of 54 and 56 kDa. Similar to APMA-activated human prostromelysin-1, the APMA-activated canine metalloproteinase was inhibited by 1,10-phenanthroline or recombinant human tissue inhibitor of metalloproteinase (TIMP). The amino-terminal sequences of the canine pro- and APMA-activated enzymes were compared with those of human, rabbit and rat stromelysin. The striking homologies among the sequences demonstrated that the purified canine metalloproteinase was indeed canine prostromelysin. A rabbit anti-canine prostromelysin polyclonal antiserum was generated and used to localize the enzyme within cultured dog synoviocytes and articular cartilage stimulated with dMCM. The reagents developed in this study should be useful for examining the expression and distribution of prostromelysin in canine models of osteoarthritis.

Amino Acid Sequence↗
PubMed1991

AIDS--intervention works; "education" is questionable.

A decrease in or leveling off of new cases of transfusion-related AIDS coupled with continued increases in homosexual and IV drug cases suggests that intervention by barring contaminated blood has worked and "education" has worked less well, if at all. Current evidence suggests that the blood-bar resulted in the change in new AIDS cases among children within 3 years and among adults within 3 1/2 years.

Acquired Immunodeficiency Syndrome↗
PubMed1991

The distribution of synapsin I and synaptophysin in hippocampal neurons developing in culture.

As a first step toward elucidating mechanisms involved in the sorting of synaptic vesicle proteins in neurons, we have used immunofluorescence microscopy to determine the distribution of two synaptic vesicle proteins, synapsin I and synaptophysin, in hippocampal neurons developing in culture. In mature cultures, synapsin I and synaptophysin immunoreactivity was concentrated in puncta that were restricted to sites where axons contacted neuronal cell bodies or dendrites. Electron-microscopic immunocytochemistry demonstrated that these puncta corresponded to vesicle-filled axonal varicosities that were exclusively presynaptic. At early stages of development, before cell-cell contact, both synapsin I and synaptophysin were preferentially localized in axons, where they were particularly concentrated in the distal axon and growth cone. In axons that did not contact other cells, immunostaining for these two proteins had a granular appearance, which persisted for at least 7 d, but focal accumulations of vesicles comparable to those seen at sites of synaptic contact were not observed. When neurons contacted one another, numerous puncta of synapsin I and synaptophysin formed within the first week in culture. Double-label immunofluorescence demonstrated that the two vesicle antigens were closely codistributed throughout these stages of development. These observations demonstrate that synaptic vesicle proteins assume a polarized distribution within nerve cells beginning early in development, as soon as the axon can be identified. In contrast, differences in microtubule polarity orientation that distinguish mature axons and dendrites, and that have been proposed to account for the selective sorting of some materials in nerve cells, first appear at a subsequent stage of development. The selective distribution of synaptic vesicle proteins to the axon occurs in isolated cells, independent of interactions with other cells. In contrast, the formation of large clusters of vesicles typical of presynaptic specializations requires contact with an appropriate postsynaptic target. Thus, in cultured hippocampal neurons, the localization of synaptic vesicles in presynaptic specializations is the result of sorting mechanisms intrinsic to individual neurons as well as to mechanisms mediated by cell-cell contact.

Animals↗
PubMed1989

Identification of a monocyte specific pre-interleukin 1 beta convertase activity.

Interleukin 1 (IL-1) is a lymphokine secreted by monocytes in response to a variety of inflammatory stimuli. IL-1 beta, the predominant form of IL-1 produced by human monocytes, is synthesized as an inactive precursor of 31 kDa and is cleaved at Asp116-Ala117 to yield a 17.5-kDa extracellular form. The exact cellular site of cleavage and mechanism of secretion is at present unknown. We have prepared cell-free postnuclear extracts from freshly isolated human monocytes as well as THP.1 cells, a human monocyte-like cell line, and various blood lymphocytes and fibroblast cell lines. Using pre-IL-1 beta synthesized by in vitro transcription and translation, we have shown that only extracts derived from human monocytes and THP.1 cells were capable of cleaving precursor IL-1 beta to authentic mature IL-1 beta. Subcellular fractionation of the extracts suggested that the processing activity is found in the cytosol of monocytes or monocyte-like cell lines. The cleavage product of this protease is identical to authentic IL-1 beta as shown by mobility on SDS/PAGE and amino acid sequence analysis of the [3H]leucine-labeled product. The cleavage product is also capable of binding to the IL-1 receptor found on fibroblast membranes. Finally, mutation of Asp116----Ala116 rendered the IL-1 beta precursor resistant to cleavage by the processing activity. We conclude that a protease activity found only in monocytes will specifically process IL-1 beta to an active form.

Caspase 1↗
PubMed1989

Effect of homosexuality upon public health and social order.

Are homosexuals "not dangers to society" and is homosexuality "compatible with full health"? To answer these questions 4,340 adult respondents drawn via area probability sampling from 5 metropolitan areas of the USA self-administered an extensive sexuality/public order questionnaire of over 500 items. Bisexuals and homosexuals (about 4% of the sample) as compared to heterosexuals: (1) more frequently exposed themselves to biological hazards (e.g., sadomasochism, fisting, bestiality, ingestion of feces); (2) exposed themselves sexually to more different bodies (e.g., more frequently admitted to participating in orgies, reported considerably larger numbers of sexual partners); (3) more frequently reported participating in socially disruptive sex (e.g., deliberate infection of others, cheating in marriage, making obscene phone calls); and (4) more frequently reported engaging in socially disruptive activities (e.g., criminality, shoplifting, tax cheating). From the standpoints of individual health, public health and social order, participating in homosexual activity could be viewed as dangerous to society and incompatible with full health.

Adult↗
PubMed1989

Enhanced recency effects with changing-state and primary-linguistic stimuli.

A number of explanations for the modality effect in immediate serial recall have been proposed. The auditory advantage for recall of recency items has been explained in terms of (1) the contributions of precategorical acoustic storage (PAS), (2) an advantage of changing-state over static stimuli, and (3) an advantage of primary-linguistic coding. Four experiments were conducted to evaluate these hypotheses. In the first, subjects viewed seven consecutive rectangles of different colors on a computer monitor. A small recency effect was obtained when the task was to recall the colors of the rectangles in order, with the size of the effect being independent of whether the rectangles remained stationary on the screen or moved in one of four directions. However, when the task was to recall the direction of movement of the rectangles, a larger recency effect was found. This pattern of results was interpreted as suggesting that recency effects are enhanced by changing-state stimulus information, but only when the changing-state information serves to identify the stimulus. Experiments 2 and 3 provided converging evidence by demonstrating an analogous recency advantage for changing-state visual stimuli that were somewhat different from those of Experiment 1. Experiment 4 demonstrated recency effects with synthesized speech stimuli that were substantially greater than were those found with the changing-state visual stimuli of the first three experiments. Implications of the results for the PAS, changing-state, and primary-linguistic hypotheses, as well as temporal-distinctiveness theories of recency, are discussed.

Color Perception↗