PubMed Health⌕ Search

Biomedical subjects

C Malcolm

Publications and source records attributed to C Malcolm.

10 recordsLinked to original sources

The unique mutation in ace-1 giving high insecticide resistance is easily detectable in mosquito vectors.

High insecticide resistance resulting from insensitive acetylcholinesterase (AChE) has emerged in mosquitoes. A single mutation (G119S of the ace-1 gene) explains this high resistance in Culex pipiens and in Anopheles gambiae. In order to provide better documentation of the ace-1 gene and the effect of the G119S mutation, we present a three-dimension structure model of AChE, showing that this unique substitution is localized in the oxyanion hole, explaining the insecticide insensitivity and its interference with the enzyme catalytic functions. As the G119S creates a restriction site, a simple PCR test was devised to detect its presence in both A. gambiae and C. pipiens, two mosquito species belonging to different subfamilies (Culicinae and Anophelinae). It is possibile that this mutation also explains the high resistance found in other mosquitoes, and the present results indicate that the PCR test detects the G119S mutation in the malaria vector A. albimanus. The G119S has thus occurred independently at least four times in mosquitoes and this PCR test is probably of broad applicability within the Culicidae family.

Acetylcholinesterase↗

Childhood H. pylori: disappearing disease or chronic infection?

Helicobacter pylori is one of the commonest chronic bacterial infections worldwide. It is acquired during childhood and its persistence has implications for health in later life. In adults, it is the principle cause of duodenal ulcer disease and there is evidence of an association between H. pylori and gastric cancer. However, most colonized people are asymptomatic. The prevalence of H. pylori increases with age but there is a striking difference between the rates in developed and developing countries. As no significant non-human or environmental source for this infection has been identified, person to person spread is almost certainly the main mode of transmission. Community nurses should be aware of this micro-organism as a potential cause of illness in children, and that they can play a role in promoting hygiene practices and educating families so that the risk of acquisition may be reduced. This review discusses the clinical features, prevalence, risk factors for transmission, diagnosis and treatment of H. pylori.

Age Distribution↗

Association of c-fos mRNA expression and excitotoxicity in primary cultures of mouse neocortical and cerebellar neurons.

The effect of excitatory amino acids (EAAs) on c-fos mRNA expression was studied in primary cultures of mouse cerebellar granule cells and in neocortical neurons after 2 and 7 days in vitro (div). In cultured granule cells at 2 and 7 div, and in cortical neurons at 2 div, exposure to low levels (< or = 10 microM) of a variety of EAAs (viz. glutamate [Glu], S-sulpho-L-cysteine [SC], N-methyl-D-aspartate [NMDA], alpha-amino-3-hydroxy-5-methyl-4-isoxazole [AMPA], and kainate [KA]) resulted in a transient increase in the level of c-fos mRNA which peaked at 30 min but returned to a basal level by 120 min. However, exposure of granule cells (7 div) to high levels (250 microM) of Glu, NMDA, KA, SC and of cortical neurons (7 div) to high levels (250 microM) of Glu, NMDA, KA, SC, or AMPA and to low levels (< or = 10 microM) of Glu and AMPA resulted in a delay in c-fos mRNA induction but a subsequent, progressive increase that was sustained for at least 240 min. Furthermore, this effect was accompanied by a dose-related increase in the release of the cytosolic enzyme, lactate dehydrogenase, used as an indicator of excitotoxicity. A ratio (Q240/30) for the steady-state levels of c-fos mRNA after 30 min and 240 min of exposure to EAAs was determined which showed that Q240/30 >2 correlated reproducibly with excitotoxic cell death, whereas a ratio of < or = 1 correlated with a nonexcitotoxic event. In both cell types at 7 div, coadministration of the selective NMDA receptor antagonist, DL(+/-)-2-amino-5-phosphonopentanoic acid (APV) with cytotoxic levels of Glu 1) protected against EAA-induced neurotoxicity and 2) exhibited a transient c-fos mRNA expression (Q240/30 values approximately 1). In contrast, the AMPA/KA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), provided no protection against excitotoxicity and had no significant effect on the Glu-induced delay in c-fos mRNA expression. These results suggest that the Q240/30 c-fos mRNA ratio may 1) be used as a predictive index for excitotoxic neuronal death, 2) provide information on the identity of the receptor subtype mediating excitotoxicity in different brain cell types, and 3) aid in establishing the role of excitotoxicity during the development of neurons in vitro.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

NMDA receptor-mediated cGMP synthesis in primary cultures of mouse cerebellar granule cells appears to involve neuron-astrocyte communication with NO operating as the intercellular messenger.

The possibility that neuron-astrocyte communication may be responsible for glutamate (Glu)-stimulated cGMP formation even in relatively homogeneous primary cultures of mouse cerebellar granule cells (7 days in vitro) was investigated. Pharmacological analysis using selective excitatory amino acid (EAA) receptor antagonists showed that cGMP production, stimulated in these cultures by Glu and a variety of endogenous EAAs structurally-related to Glu (namely, L-aspartate, L-cysteine sulphinate, L-homocysteate, S-sulpho-L-cysteine), was mediated wholly by N-methyl-D-aspartate (NMDA) receptor activation. Moreover, EAA-induced responses were dependent on the presence of extracellular calcium but unaffected by addition of the L-type voltage-sensitive calcium channel blockers nifedipine (10 microM) or verapamil (5 microM). The mode of calcium entry was also shown to be important since the calcium ionophore, A23187 (10 microM), was unable to stimulate cGMP levels above basal. cGMP formation was blocked by the competitive nitric oxide synthase inhibitor, L-NG-nitroarginine (100 microM), consistent with a role of nitric oxide (NO) in this signalling pathway. In the presence of added haemoglobin (1 microM), acting as a membrane-impermeable NO scavenger, Glu-stimulated cGMP formation was abolished implying that NO must act as an intercellular messenger. When the neuronal population was destroyed following a 24 hr exposure to the excitotoxin, S-sulpho-L-cysteine (200 microM), Glu-stimulated cGMP formation was abolished; whereas responses to the NO donor, sodium nitroprusside (SNP), although markedly reduced were still double that stimulated by Glu in the absence of the excitotoxin, suggesting the presence of non-neuronal cells that can generate cGMP if supplied directly with NO. Consistent with this suggestion, low levels of the glial specific enzyme, glutamine synthetase, were detected in granule cell cultures. Furthermore, omission or delayed addition of the antimitotic agent, cytosine arabinoside (20 microM), to the growth medium caused a significant increase in the level of Glu-stimulated cGMP formation.

Animals↗

Community occupational therapists and volunteers: a survey of utilization and satisfaction.

Current estimates lead us to believe that approximately 16% of the population works in some capacity on a volunteer basis. In spite of the size of this valuable human resource, occupational therapists often remark that they are unable to find suitable volunteers to assist with patient-related activities. The present study is an attempt to explore this topic, looking specifically at how community occupational therapists use volunteers, and how satisfied they are with the services provided. A descriptive survey was carried out in two parts: a questionnaire was distributed to all therapists associated with Community Occupational Therapy Associates (COTA) in Toronto; and, a structured interview was conducted with a sample of therapists who indicated they were dissatisfied with volunteer services. The survey revealed three problems: non-availability of appropriate volunteers to do specific patient-related activities; poor communication between therapists and volunteers; and general negative feelings about the reliability and accountability of volunteers. Based on identified problems and in consultation with the literature, a program was set up at COTA to enhance the effective utilization of volunteers within the agency.

Analysis of Variance↗

Breakpoint distribution in male-linked translocations in Anopheles stephensi Liston.

A series of translocations involving the male chromosome and chromosome 3 was analyzed in Anopheles stephensi. Using three genetic markers in 3R, namely sp, dp, and Bl, the recombination distance between the breakpoint and each of the three markers was assessed. On the basis of control recombination it was possible to assign the breakpoint to the chromosome relative to the three markers. It was shown that the majority of breakpoints were located in the vicinity of dp-Bl and translocations were identified that showed complete linkage with each of the markers. The results are compared with the published data on radiation-induced breakage and used to interpret the difficulties that have been experienced in producing a genetic sexing system in this species.

Animals↗