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Biomedical subjects

C Lamont

Publications and source records attributed to C Lamont.

At least 19 recordsLinked to original sources
PubMed2004

A chronic disease management programme can reduce days in hospital for patients with chronic obstructive pulmonary disease.

BACKGROUND: A steady increase in chronic obstructive pulmonary disease (COPD) admissions was addressed by enhancing primary care to provide intensive chronic disease management. AIM: To compare the effect of a disease management programme, including a COPD management guideline, a patient-specific care plan and collaboration between patients, general practitioners, practice nurses, hospital physicians and nurse specialists with conventional care, on hospital admissions and quality of life. METHODS: One hundred and thirty-five patients with a clinical diagnosis of moderate to severe COPD were identified from hospital admission data and general practice records. General practices were randomized to either conventional care (CON), or the intervention (INT). Pre- and post-study assessment included spirometry, Shuttle Walk Test, Short Form-36, and the Chronic Respiratory Questionnaire (CRQ). Admission data were compared for 12 months prior to and during the trial. RESULTS: For respiratory conditions, mean hospital bed days per patient per year for the INT group were reduced from 2.8 to 1.1, whereas those for the CON group increased from 3.5 to 4.0 (group difference, P = 0.030) The INT group also showed an improvement for two dimensions of the CRQ, fatigue (P = 0.010) and mastery (P = 0.007). CONCLUSIONS: A chronic disease management programme for COPD patients that incorporated a variety of interventions, including pulmonary rehabilitation and implemented by primary care, reduced admissions and hospital bed days. Key elements were patient participation and information sharing among healthcare providers.

Adult↗
PubMed2001

Adrenergic stimulation of rat resistance arteries affects Ca(2+) sparks, Ca(2+) waves, and Ca(2+) oscillations.

Confocal laser scanning microscopy and fluo 4 were used to visualize local and whole cell Ca(2+) transients within individual smooth muscle cells (SMC) of intact, pressurized rat mesenteric small arteries during activation of alpha1-adrenoceptors. A method was developed to record the Ca(2+) transients within individual SMC during the changes in arterial diameter. Three distinct types of "Ca(2+) signals" were influenced by adrenergic activation (agonist: phenylephrine). First, asynchronous Ca(2+) transients were elicited by low levels of adrenergic stimulation. These propagated from a point of origin and then filled the cell. Second, synchronous, spatially uniform Ca(2+) transients, not reported previously, occurred at higher levels of adrenergic stimulation and continued for long periods during oscillatory vasomotion. Finally, Ca(2+) sparks slowly decreased in frequency of occurrence during exposure to adrenergic agonists. Thus adrenergic activation causes a decrease in the frequency of Ca(2+) sparks and an increase in the frequency of asynchronous wavelike Ca(2+) transients, both of which should tend to decrease arterial diameter. Oscillatory vasomotion is associated with spatially uniform synchronous oscillations of cellular [Ca(2+)] and may have a different mechanism than the asynchronous, propagating Ca(2+) transients.

Animals↗
PubMed1999

Prescription and nonprescription drug use among at-risk community-dwelling seniors in Ottawa-Carleton.

BACKGROUND: The Council on Aging Ottawa-Carleton conducted an evaluation study aimed at reducing the inappropriate use of medication by community-dwelling seniors. During a 17-month period from 1990 to 1992, 278 of 415 seniors consented to participate. All were new referrals to home care, all were 65 years of age or older and all were taking a minimum of six prescription medications. OBJECTIVE: To describe the patterns of prescription and nonprescription drug use among high risk elderly people living in the Ottawa-Carleton region. ANALYSIS: Descriptive statistics and logistic regression were used to explore relationships between the numbers of drugs (prescription and nonprescription), drug classes and drug subclasses, and sex, age and number of prescribing physicians. RESULTS: The top 10 prescription or nonprescription drugs taken by study participants were consistent among diseases and health problems most commonly found among the elderly. Comparisons by rank for subclasses of drugs indicated that eye, ear, nose and throat (EENT), and respiratory drugs were considerably more prevalent among males than females, while women took more hormones and anxiolytics, sedatives and hypnotics. Age also appeared to have an effect; the proportions of respiratory drugs and hormones decreased with age. In contrast, vitamins and EENT drugs were most prevalent among the oldest seniors. These findings were supported by the results of multivariate analyses. Having three or more prescribing doctors was positively associated with the use of laxatives. Findings from multivariate analyses indicated that for prescription drugs, the youngest age group was about four times more likely than the oldest age group to be taking at least eight drugs. For nonprescription drugs, the only statistically significant finding was that those with three or more doctors were twice as likely as those with one or two doctors to take at least one nonprescription drug.

Aged↗
PubMed1998

Intercellular Ca2+ waves in rat heart muscle.

1. Confocal laser scanning microscopy was used to visualize intercellular transmission of Ca2+ waves in intact rat ventricular trabeculae micro-injected with the calcium indicator fluo-3. 2. Ca2+ waves usually failed to be transmitted from cell to cell. At identified individual end-to-end cell contacts, successful transmission interspersed with failure, which sometimes occurred despite an apparent small spritz of Ca2+ between cells. The probability of cell to cell transmission (Ptran) was 0.13. 3. Ca2+ waves arose preferentially near junctions of connected cells, where connexin-43 was found, but randomly in enzymatically disconnected heart cells. 4. beta-Adrenergic stimulation significantly increased Ptran (to 0.22) and heptanol, an uncoupler of gap junction channels, significantly decreased it (to 0.045). 5. In regions of high [Ca2+]i due to damage, wave frequency decreased markedly with each cell-cell junction passed. 6. The Ca2+ permeability of cardiac gap junctions may be regulated, and the low ability of cardiac gap junctions to transmit Ca2+ may help control the spread of Ca2+ from damaged regions.

Adrenergic beta-Agonists↗
PubMed1998

Intracellular Na+ measurements in smooth muscle using SBFI--changes in [Na+], Ca2+ and force in normal and Na(+)-loaded ureter.

Our understanding of the control and effects of intracellular [Na+] ([Na+]i) in intact smooth muscle is limited by the lack of data concerning [Na+]i. The initial aim of this work was therefore to investigate the suitability of using the Na+-sensitive fluorophore SBFI in intact smooth muscle. We find this to be a good method for measuring [Na+]i in ureteric smooth muscle. Resting [Na+]i was found to be around 10 mM and rose to 25 mM when the Na+-K+-ATPase was inhibited by ouabain. This relatively low [Na+]i in the absence of Na+-K+-ATPase suggests that other cellular processes, such as Na+-Ca2+ exchange, play a role in maintaining [Na+]i under these conditions. Simultaneous measurements of [Na+]i or [Ca2+] i and force showed that Na+-Ca2+ exchange can play a functional role in ureteric smooth muscle. We found that the greater the driving force for Na+ exit and hence Ca2+ entry, the larger the contraction. In addition the Na+-Ca2+ exchanger activity under these conditions was found to be pH sensitive: acidification reduced the contraction and concomitant changes in [Ca2+] and [Na+]i. We conclude that SBFI is a useful method for monitoring [Na] in smooth muscle and that Na+-Ca2+ exchange may play a functional role in the ureter.

Animals↗
PubMed1997

Radioprotection of bone marrow stem cell subsets by interleukin-1 and kit-ligand: implications for CFU-S as the responsible target cell population.

Various cytokines have been reported to have radioprotective effects on the bone marrow. Of these, c-kit-ligand (KL) and interleukin-1 (IL-1) have the most dramatic effect when given prior to total body irradiation (TBI). Given simultaneously, KL and IL-1 demonstrated a strong effect on increasing the LD50/30 of mice. In this case the LD50/30 of C57BL/6 mice was 1.25 (1.14-1.38) times higher (10.08 Gy [confidence interval (c.i.): 9.62-10.56] vs. 8.05 Gy [c.i.: 7.64-8.42]) when KL (120 micrograms/kg) and IL-1 (40 micrograms/kg) were injected subcutaneously at 20 hours before TBI. It was also investigated whether the combined effects of KL and IL-1 resulted in changes in the intrinsic radiation sensitivity of different bone marrow subsets. Therefore, mice were irradiated and the survival of bone marrow subsets was determined at 4-6 hours after TBI by using the CFU-S assay and the competitive repopulation assay. The CFU-S subset displayed an increased Dzero value in KL and IL-1-treated mice (0.88 Gy vs. 0.72 Gy) and the protection factor was 1.22, close to the factor found for the hemopoietic syndrome (LD50/30). It may therefore be concluded that CFU-S are the target cell population involved in hemopoietic death. Additional protection of the more primitive stem cell subset with long-term repopulation ability (LTRA) could not be shown from the data we obtained with the competitive repopulation assay. Both Dzero and the extrapolation number (n) were increased, but not significantly. These data suggest that radioprotection by cytokines is caused mainly by the decreased radiation sensitivity of the CFU-S subset, although earlier subsets may also be protected (but to a lesser extent).

Animals↗
PubMed1996

B7-1 is superior to B7-2 costimulation in the induction and maintenance of T cell-mediated antileukemia immunity. Further evidence that B7-1 and B7-2 are functionally distinct.

Although intact, viable tumor cells rarely induce a clinically significant immune response in vivo, immunogenicity can be elicited by irradiated tumor cells that protect against subsequent challenge with wild-type intact viable tumor cells. Genetic modification of murine tumor cells, by transfection of cDNAs encoding either cytokines, MHC molecules, or costimulatory molecules, has been capable of inducing antitumor immunity. We and others have previously demonstrated that expression of the B7-1 costimulatory molecule, in either immunogenic or nonimmunogenic tumors, can protect against subsequent challenge with wild-type tumor cells. In this work, using a murine model of acute myeloid leukemia, we demonstrate that the B7-1 costimulatory molecule is superior to the B7-2 molecule in its capacity to protect against wild-type tumor challenge and eradicate minimal residual disease. These results provide compelling evidence that the B7-1 and B7-2 costimulatory signals are functionally distinct, thus resulting in clinically significant differences in the induction of antitumor immunity in vivo.

Animals↗
PubMed1996

The sarcolemmal mechanisms involved in the control of diastolic intracellular calcium in isolated rat cardiac trabeculae.

We performed experiments using the calcium indicator Indo-1 to determine the relative roles of the sarcolemmal mechanisms involved in the regulation of diastolic intracellular calcium concentration ([Ca2+]i) in trabeculae from the rat heart. Ryanodine was used to eliminate sarcoplasmic reticulum (SR) function. In the functional absence of the SR, 76.8 +/- 3.9% of the calcium was extruded by the Na-Ca exchange carrier in the [Ca2+]i range of diastolic concentration +/- 200-400 nM. This was assessed by measuring the recovery of [Ca2+]i from small perturbations in the presence and absence of extracellular sodium. The steady-state relationship between [Ca2+]o and [Ca2+]i was linear over the range of 1-40 mM, a 20-fold increase of [Ca2+]o produced a 1.97-fold +/- 0.13-fold increase in [Ca2+]i (n = 5). In the absence of extracellular sodium raising [Ca2+]o had a variable effect. In some preparations there was little change of [Ca2+]i while in others the response was almost as large as in control conditions. We conclude that the Na-Ca exchanger contributes approximately 77% of sarcolemmal calcium extrusion following small perturbations in [Ca2+]i and that this fraction does not diminish as the [Ca2+]i declines. In addition we have shown a sodium-independent entry of calcium into quiescent cardiac muscle under resting conditions.

Animals↗
PubMed1995

Hematopoietic stem cells in the blood after stem cell factor and interleukin-11 administration: evidence for different mechanisms of mobilization.

Peripheral blood stem cells and progenitor cells, collected during recovery from exposure to cytotoxic agents or after cytokine administration, are being increasingly used in clinical bone marrow transplantation. To determine factors important for mobilization of both primitive stem cells and progenitor cells to the blood, we studied the blood and splenic and marrow compartments of intact and splenectomized mice after administration of recombinant human interleukin-11 (rhlL-11), recombinant rat stem cell factor (rrSCF), and IL-11 + SCF. IL-11 administration increased the number of spleen colony-forming units (CFU-S) in both the spleen and blood, but did not increase blood long-term marrow-repopulating ability (LTRA) in intact or splenectomized mice. SCF administration increased the number of CFU-S in both the spleen and blood and did not increase the blood or splenic LTRA of intact mice, but did increase blood LTRA to normal marrow levels in splenectomized mice. The combination of lL-11 + SCF syngeristically enhanced mobilization of long-term marrow-repopulating cells from the marrow to the spleen of intact mice and from the marrow to the blood of splenectomized mice. These data, combined with those of prior studies showing granulocyte colony-stimulating factor mobilization of long-term marrow repopulating cells from the marrow to the blood of mice with intact spleens, suggest different cytokine-induced pathways for mobilization of primitive stem cells.

Animals↗
PubMed1995

Role of B7-1 in mediating an immune response to myeloid leukemia cells.

A costimulatory signal from B7-1 (CD80) to its counter-receptor CD28 is required for T-cell activation. Many tumors, including most human leukemias, lack expression of B7-1, and this has been suggested to contribute to the failure of immune recognition of these diseases. A murine leukemia model system was developed to assess the potential role of B7-1 in the induction immunity to leukemia cells. The nonleukemic 32Dc13 myeloid cell line was transformed by transfection of the BCR/ABL gene, generating a subline (32Dp210/clone 26) that was leukemic and rapidly lethal to syngeneic, immunocompetent C3H/HeJ mice or T-cell-deficient nude mice. B7-1-modified leukemic cells remained lethal in nude mice, but caused only a transient, nonlethal leukemia in C3H/HeJ mice. After a single exposure to live, nonirradiated B7-1-modified leukemic cells, C3H/HeJ mice developed protective immunity against subsequent challenge with B7-1(-) leukemic cells. Further, hyperimmunization with B7-1(+) leukemic cells prolonged the survival of mice previously injected with a lethal number of B7-1(-) leukemic cells. These results indicate that myeloid leukemic cells may be attractive candidates for B7-1 gene transfer.

Acute Disease↗
PubMed1993

High affinity binding of TAR RNA by the human immunodeficiency virus type-1 tat protein requires base-pairs in the RNA stem and amino acid residues flanking the basic region.

The binding site for tat protein on TAR RNA has been defined in quantitative terms using an extensive series of mutations. The relative dissociation constants for the mutant TAR RNAs were measured using a dual-label competition filter binding assay in which 35S-labelled wild-type TAR RNA (K1) was competed against 3H-labelled mutant TAR RNA (K2). The error in the self-competition experiment was usually less than 10% (e.g. K2/K1 = 1.07 +/- 0.05, n = 19) and the experimental data accurately matched theoretical curves calculated with fitted dissociation constants. Mutations in U23, a critical residue in the U-rich "bulge" sequence, or in either of the two base-pairs immediately above the "bulge", G26.C39 and A27.U38 reduced that affinity by 8- to 20-fold. Significant contributions to tat binding affinity were also made by the base-pairs located immediately below the bulge. For example, mutation of A22.U40 to U.A reduced tat affinity 5-fold, and mutation of G21.C41 to C.G reduced tat affinity 4-fold. The binding of a series of peptides spanning the basic "arginine-rich" sequence of tat was examined using both filter-binding and gel mobility shift assays. Each of the peptides showed significantly reduced affinities for wild-type TAR RNA compared to the tat protein. The ADP-2 (residues 43 to 72), ADP-3 (residues 48 to 72) and ADP-5 (residues 49 to 86) peptides were unable to discriminate between wild-type TAR RNA and TAR RNA mutants with the same fidelity as the tat protein. For example, these peptides showed no more than 3-fold reductions in affinity relative to wild-type TAR RNA for the U23-->C mutation in the bulge, or G26.G39-->C.G mutation in the stem of TAR RNA. By contrast, the ADP-I (residues 37 to 72), ADP-4 (residues 32 to 62) and ADP-6 (residues 32 to 72) peptides, which each carry amino acid residues from the "core" region of the tat protein have binding specificities that more closely resemble the protein. The ADP-4 and ADP-6 peptides showed between 4- and 7-fold reductions in affinity for the U23-->C or G26.C39-->C.G mutations. The ADP-1 peptide most closely resembles the protein in its binding specificity and showed 9-fold and 14-fold reductions in affinity for the two mutants, respectively. Chemical-modification interference assays using diethylpyrocarbonate (DEPC) and ethylnitrosourea (ENU) were also used to compare the binding properties of the tat protein and the tat-derived peptides.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗
PubMed1992

Calcium sensitizing action of carnosine and other endogenous imidazoles in chemically skinned striated muscle.

1. The imidazole-containing compounds carnosine and homocarnosine, endogenous to skeletal and cardiac muscle, have been tested for effect on the contractile behaviour of chemically skinned (saponin or Triton X-100) skeletal and cardiac muscle. 2. Carnosine, at millimolar concentrations which are near physiological for many skeletal fibres, and in a concentration-dependent fashion, shifts the curve relating [Ca2+] to steady-state tension to lower [Ca2+] in both skeletal (frog but not crab) and cardiac (rat) muscle preparations. 3. Of other imidazoles endogenous to heart, homocarnosine is somewhat more effective, while N-acetyl L-histidine is much less so. 4. The maximum level of Ca(2+)-activated force is increased significantly by homocarnosine in cardiac trabeculae. 5. We propose that the cellular imidazoles related to carnosine are natural 'Ca2+ sensitizers' in striated muscle. Alterations in their levels as a result of disease or training, and between different fibre types, may contribute to differences in contractile performance of the intact tissues.

Animals↗
PubMed1992

Identification of the Rev transactivation and Rev-responsive elements of feline immunodeficiency virus.

Spliced messages encoded by two distinct strains of feline immunodeficiency virus (FIV) were identified. Two of the cDNA clones represented mRNAs with bicistronic capacity. The first coding exon contained a short open reading frame (orf) of unknown function, designated orf 2. After a translational stop, this exon contained the L region of the env orf. The L region resides 5' to the predicted leader sequence of env. The second coding exon contained the H orf, which began 3' to env and extended into the U3 region of the long terminal repeat. The in-frame splicing of the L and H orfs created the FIV rev gene. Site-directed antibodies to the L orf recognized a 23-kDa protein in infected cells. Immunofluorescence studies localized Rev to the nucleoli of infected cells. The Rev-responsive element (RRE) of FIV was initially identified by computer analysis. Three independent isolates of FIV were searched in their entirety for regions with unusual RNA-folding properties. An unusual RNA-folding region was not found at the Su-TM junction but instead was located at the end of env. Minimal-energy foldings of this region revealed a structure that was highly conserved among the three isolates. Transient expression assays demonstrated that both the Rev and RRE components of FIV were necessary for efficient reporter gene expression. Cells stably transfected with rev-deleted proviruses produced virion-associated reverse transcriptase activity only when FIV Rev was supplied in trans. Thus, FIV is dependent on a fully functional Rev protein and an RRE for productive infection.

Amino Acid Sequence↗
PubMed1991

Characterization of endogenous and recombinant proviral elements of a highly tumorigenic AKR cell line.

As an approach to evaluating the contribution of classes of endogenous viral sequences to leukemogenesis, a genomic library was prepared from the highly tumorigenic AKR SL12.3 cell line and screened for env-containing proviruses. An extensive battery of virus-derived probes and specific oligonucleotide probes were used to segregate 83 positive clones into related groups. The nonecotropic endogenous retroviruses were identified as members of the polytropic, modified polytropic, or xenotropic groups. At least three unique xenotropic proviruses were detected that differed from the published xenotropic sequence within a variable region of the 5' portion of env. Changes among the xenotropic proviruses included relative insertions and/or deletions that maintain an open reading frame and hence the potential to encode viable envelope gene products. Several recombinant viruses were also detected. Recombination was not random and primarily involved the formation of mink cell focus-inducing class I retroviruses via recombination between polytropic elements and ecotropic virus. One other recombinant was detected which contained ecotropic virus sequences in the 5' region encoding p15 of an otherwise xenotropic provirus. An interesting observation was the finding that certain clones contained more than one provirus within the average 20-kb cloned insert. This would not be expected if integration were totally random. The de novo recombinant proviruses identified here provide a series of potential candidates to be evaluated for their contribution to the tumorigencity of the SL12.3 cell line.

Base Sequence↗