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Biomedical subjects

C M Lloyd

Publications and source records attributed to C M Lloyd.

At least 37 records · Page 2Linked to original sources
PubMed1996

Eosinophil recruitment to the lung in a murine model of allergic inflammation. The role of T cells, chemokines, and adhesion receptors.

Eosinophil accumulation is a distinctive feature of lung allergic inflammation. Here, we have used a mouse model of OVA (ovalbumin)-induced pulmonary eosinophilia to study the cellular and molecular mechanisms for this selective recruitment of eosinophils to the airways. In this model there was an early accumulation of infiltrating monocytes/macrophages in the lung during the OVA treatment, whereas the increase in infiltrating T-lymphocytes paralleled the accumulation of eosinophils. The kinetics of accumulation of these three leukocyte subtypes correlated with the levels of mRNA expression of the chemokines monocyte chemotactic peptide-1/JE, eotaxin, and RANTES (regulated upon activation in normal T cells expressed and secreted), suggesting their involvement in the recruitment of these leukocytes. Furthermore, blockade of eotaxin with specific antibodies in vivo reduced the accumulation of eosinophils in the lung in response to OVA by half. Mature CD4+ T-lymphocytes were absolutely required for OVA-induced eosinophil accumulation since lung eosinophilia was prevented in CD4+-deficient mice. However, these cells were neither the main producers of the major eosinophilic chemokines eotaxin, RANTES, or MIP-1alpha, nor did they regulate the expression of these chemokines. Rather, the presence of CD4+ T cells was necessary for enhancement of VCAM-1 (vascular cell adhesion molecule-1) expression in the lung during allergic inflammation induced by the OVA treatment. In support of this, mice genetically deficient for VCAM-1 and intercellular adhesion molecule-1 failed to develop pulmonary eosinophilia. Selective eosinophilic recruitment during lung allergic inflammation results from a sequential accumulation of certain leukocyte types, particularly T cells, and relies on the presence of both eosinophilic chemoattractants and adhesion receptors.

Animals↗
PubMed1996

Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron disease.

BACKGROUND: Variants of the apolipoprotein E (APOE) gene influence the age of onset of Alzheimer's disease. APOE may influence the presentation of other neurological diseases. We investigated the relationship between the allelic variants of apolipoprotein E and clinical presentation in motor neuron disease. METHODS: 123 patients with motor neuron disease and 121 controls were studied. Diagnosis, location of onset and date of onset were recorded prospectively. Genotyping was performed blind to clinical information. FINDINGS: Possession of at least one epsilon 4 allele was significantly more common in patients with bulbar onset motor neuron disease (14/33, 42%) than in limb onset patients (20/90, 22%) and controls (26/121, 21%) (chi 2 = 4.93, p = 0.026 and chi 2 = 5.91, p = 0.015, respectively). INTERPRETATION: These results suggest that the apolipoprotein E epsilon 4 allele may influence the pattern of motor neuron loss in motor neuron disease and that it may affect neuronal function in ways unrelated to the deposition of beta-amyloid or accumulation of neurofibrillary tangles.

Age of Onset↗
PubMed1996

Frontal lobe dysfunction in amyotrophic lateral sclerosis. A PET study.

PET measurements of regional cerebral blood flow (rCBF) were used to explore frontal lobe dysfunction in amyotrophic lateral sclerosis (ALS). An activation paradigm of executive frontal lobe function (verbal fluency), which contrasted rCBF during word generation and word repetition, was used. Two groups of ALS patients, defined by the presence or absence of cognitive impairment (ALSi) (impaired, n = 6: ALSu unimpaired, n = 6) were compared with healthy age-matched controls (n = 6). Patient selection was based on prior performance on a written test of verbal fluency. Additional neuropsychological assessment of the patients revealed evidence of executive and memory dysfunction in the ALSi group only, with marked deficits in tests of intrinsic generation. The ALSi patients displayed significantly (P < 0.001) impaired activation in cortical and subcortical regions including the dorsolateral prefrontal cortex (DLPFC; areas 46 and 9), lateral premotor cortex (areas 8 and 6), medial prefrontal and premotor cortices (areas 8 and 9), insular cortex bilaterally and the anterior thalamic nuclear complex. Although the three groups showed matched word generation performance on the scanning paradigm, the ALSu group displayed a relatively unimpaired pattern of activation. These results support the presence of extra-motor neuronal involvement, particularly along a thalamo-frontal association pathway, in some non-demented ALS patients. In addition, this study suggests dysfunction of DLPFC in some ALS patients with associated cognitive impairments.

Aged↗
PubMed1996

Integument and sensillum auriforme of the opisthosoma of Rhipicephalus appendiculatus (Acari:Ixodidae).

The opisthosomal integument and sensilla auriformia of Rhipicephalus appendiculatus Neumann larvae, nymphs, females and males, both unfed, fed, and during molt, were examined by light and electron microscopy in relation to semiochemical production. The integument consists of epidermis, endocuticle, exocuticle, epicuticle, a superficial wax layer and a variable additional deposit. The integument of immature instars and females grows greatly during feeding. The integument is traversed by pore canals from the epidermis to the outer wax canals. The epidermis can secrete material to the exterior by way of the pore canals and wax canals. The sensillum auriforme is a common disk-shaped organ, with a complex internal chamber open to the exterior by way of a pore. It has no apparent secretory capacity and is of presumed sensory function. It is located in the integument of scutum and alloscutum of all instars.

Animals↗
PubMed1996

Integumental glands of the tick Rhipicephalus appendiculatus (Acari:Ixodidae) as potential producers of semiochemicals.

The opisthosomal integument and associated secretory organs of Rhipicephalus appendiculatus Neumann larvae, nymphs, females and males, both unfed and fed were examined by light and electron microscopy. Type 1 dermal glands were found on the alloscutum and scutum of all ticks. They were undeveloped in unfed ticks and reached full development in engorging ticks. They produced secretory granules from 2 glandular cells but without accumulation of a reservoir of secreted material. Type 2 dermal glands were found in all ticks, with pores on the alloscutum, edge of scutum, and on anal plates. These glands produced secretion during feeding and accumulated large reservoirs of secreted material that were present in engorging, recently detached and questing ticks. Spiracular glands were found in all ticks below the spiracle plate. They produced small amounts of secretion and had pores to the exterior by way of spiracle goblets. No obvious cycle of secretory activity was recorded. Foveal glands were present and produced secretions in nymphs, females, and males. They were largest in females with an accumulation of secretory vesicles in feeding ticks. The potential function of these glands is discussed in the context of the chemical ecology of this tick.

Animals↗
PubMed1995

Expression and tissue localization of donor-specific complement C3 synthesized in human renal allografts.

Recent evidence suggests that the third component of complement, C3, is synthesized in renal tissue, and that increased C3 synthesis occurs in allograft rejection and immune complex-mediated nephritis. However, it is unclear whether intrinsic renal cells or migratory cells in the inflammatory infiltrate, possibly of recipient bone marrow origin, are the source of the C3 detected. This was investigated by determining the C3 allotypes of mRNA and protein produced by transplanted human kidney. Twenty donor-recipient pairs were examined, of which nine pairs had C3 allotypes that were informatively mismatched at the C3 F/S locus. Reverse transcriptase polymerase chain reaction (RT-PCR) followed by amplification refractory mutation system analysis showed intracellular donor-specific mRNA expression in six of these nine cases, at up to 61 days post-transplantation. Nested PCR reactions and the size of PCR products excluded contamination by genomic DNA. Allotype-specific staining of frozen sections of renal cortex demonstrated donor-derived C3 protein in both glomeruli and tubules of all biopsies examined, in a predominantly tubular distribution. These results imply that at least some of the pro-inflammatory effects of complement arise from intrinsic tissue synthesis of donor C3, and that this may represent a previously unrecognized source of tissue injury. The occurrence of local synthesis of C3 of donor allotype may have functional implications related to C3 allotype, and may also be relevant to strategies to inhibit intrarenal complement-mediated injury.

Alleles↗
PubMed1995

A positron emission tomography study of frontal lobe function (verbal fluency) in amyotrophic lateral sclerosis.

Positron emission tomography (PET) was used to investigate the location of cerebral cortical and subcortical abnormalities in non-demented patients with amyotrophic lateral sclerosis (ALS). Involvement of the frontal lobes was investigated with a task of executive frontal lobe function (verbal fluency/word generation), using a PET activation paradigm. Two groups of ALS patients defined by the presence or absence of cognitive impairment were tested. ALS patients who had cognitive impairments showed a region of cortical and subcortical dysfunction which extended across a wide area of the frontal lobes, and included the insular cortex and thalamic nuclear complex. These findings support the notion that extra-motor involvement is relatively common in ALS and broadens concepts of selective vulnerability in ALS.

Amyotrophic Lateral Sclerosis↗
PubMed1995

Salivary glands and saliva of Amblyomma variegatum ticks: comparison of immatures and adults in relation to the pathogenesis of dermatophilosis.

Salivary glands from immature and adult Amblyomma variegatum were compared for differences in potential components responsible for the systemic aggravation by adult ticks of the skin disease dermatophilosis. Whole salivary glands from adult, nymphal and larval A. variegatum ticks were compared for structural differences by light microscopy and for protein content by gel electrophoresis. Type-2 salivary gland acini from adult ticks at the second stage of feeding contained significantly greater (P < 0.01) proportions of c1 secretory granules than those from either of the immature instars. There was also significantly more area occupied with e secretory granules in the type-3 salivary gland acini from adult ticks compared with larval ticks. Electrophoresis of whole salivary glands showed seven bands present only in the adult material; of these, three were dense bands at 37, 35 and 31 kDA. Electrophoresis of saliva from adult and nymphal A. variegatum obtained by artificial stimulation showed that nine bands were unique to the saliva produced by adults; of these nine bands one was a dense band at 67 kDa. It was concluded that adult salivary material was different from that of immature ticks and that further studies on the relationship between the feeding of adult A. variegatum and dermatophilosis should investigate these components unique to the adults.

Actinomycosis↗
PubMed1994

Development of a community breast screening promotion program using baseline data.

The process of developing a comprehensive community-based breast screening program for the Breast Screening Program Project is presented in this article. Behavior change theories were used to develop a program effects model which served as the conceptual foundation for a comprehensive breast screening program. This program would enlist professional and lay resources to promote breast screening through public and physician education and through improved access to mammography. Baseline survey data were used to focus program components on educational needs of women ages 40 and older for participating in regular mammography, clinical breast exam, and breast self-exam. The program effects model was also used as an evaluation framework to specify the intermediate changes that will be accomplished to reach a hypothesized 15% increase in screening participation between a study area receiving the program and two comparison areas. Results of this study will be of immediate value to other communities planning breast screening promotion programs.

Adult↗
PubMed1994

Evidence for a mounting sex pheromone in the brown ear tick Rhipicephalus appendiculatus, Neuman 1901 (Acari: Ixodidae).

The presence of a mounting sex pheromone was demonstrated on the surface of fed female Rhipicephalus appeniculatus. This pheromone, which is present on the female cuticle, allows the male to recognise the female. The pheromone was removed by cleaning the female in hexane, resulting in the loss of male mating behaviour in in vitro experiments. Male mating behaviour was resumed when extract made from fed female cuticle was replaced on cleaned females. When the extract was transferred to inanimate objects typical male mating behaviour was released. Preliminary chemical analyses indicated that the active component of the extract was contained in the sterol ester fraction of the extract.

Animals↗
PubMed1994

Characterization and pathological significance of monoclonal DNA-binding antibodies from mice with experimental malaria infection.

Malaria infection is accompanied by the production of a number of autoantibodies, including some that react with DNA. Epidemiological evidence implicates these in the nephritides that arise in human quartan malaria and in experimental malaria infections in mice. Through parallels with the involvement of DNA-reactive antibodies in the autoimmune syndrome systemic lupus erythematosus, a role for DNA-reactive antibodies in forming phlogistic immune deposits in the kidneys is implied. To more fully understand the relationship between antibodies of this specificity made in malaria and systemic lupus erythematosus, we prepared monoclonal DNA-reactive antibodies from BALB/c mice infected with Plasmodium berghei (clone RC) and compared their properties with those of other antibodies previously isolated from lupous MRL/Mp lpr/lpr and (NZB x NZW)F1 mice. Antibodies from malarial mice were all immunoglobulin M class and bound to single-stranded but not double-stranded DNA in an enzyme-linked immunosorbent assay. They also reacted with synthetic polyribonucleotides in the enzyme-linked immunosorbent assay and with parasitized erythrocytes and parasite pigment in kidney sections. None of the antibodies from lupous mice had identical specificities. The potential involvement of the DNA-reactive antibodies in malarial nephritis was demonstrated, by use of immunocytochemical methods, on the basis of their binding to existing immune deposits in kidney sections from malarial mice, a similar property having been previously demonstrated for antibodies from lupous mice. Furthermore, antibodies from malarial mice expressed public idiotypes, notably Id.V-88, which is a member of the Id.16/6 family, commonly found on DNA-reactive antibodies in lupus and other infectious and connective tissue diseases. This study indicates that DNA-reactive antibodies in malaria have immunochemical properties similar but not identical to those of such antibodies in systemic lupus erythematosus and that they have the potential to participate in the formation of immune deposits in nephritic malarial kidneys.

Animals↗
PubMed1993

The local effect of hypersensitive or inflammatory reactions to nymphal Amblyomma variegatum on simultaneous infections with Dermatophilus congolensis.

Amblyomma variegatum nymphs were applied to sites infected with Dermatophilus congolensis on eight rabbits. Four rabbits were previously sensitized to the feeding of nymphal A. variegatum to produce hypersensitive reactions to the tick feeding; the remaining four rabbits had no previous exposure to nymphal A. variegatum and produced inflammatory reactions to the tick feeding. The resulting dermatophilosis infections were assessed for three weeks and there was a correlation between the position of the inflammatory tick attachment sites and the foci of infection. There was a significant increase in the lesions at sites with inflammatory reactions to the ticks, compared with sites not exposed to tick feeding; these differences appeared to be due to individual variation in the host response and were not sustained throughout the assessment.

Actinomycetales Infections↗
PubMed1993

The effect of inflammatory and hypersensitive reactions, in response to the feeding of the tick Amblyomma variegatum, on the progression of experimental dermatophilosis infections.

Initial infestations of Amblyomma variegatum larvae and nymphs, on rabbits and sheep respectively, produced inflammatory reactions in the host's skin; repeated infestations resulted in an increase in development of delayed type hypersensitive reactions. Dermatophilus congolensis cocci were applied in titrated doses to hosts at sites of inflammatory or hypersensitive reactions to ticks, and to control hosts with no exposure to ticks. We assessed the resulting infections for three weeks and found no significant difference between the infections on the three groups. We conclude that the local effects of the feeding of immature stages of this tick do not influence the pathogenesis of dermatophilosis.

Actinomycetales Infections↗
PubMed1993

Experiments on the relationship between feeding of the tick Amblyomma variegatum (Acari: Ixodidae) and dermatophilosis skin disease in sheep.

Experiments on the systemic effect of feeding adult Amblyomma variegatum (F.) on dermatophilosis caused by Dermatophilus congolenis in six sheep were performed by feeding ticks at sites separate from sites of experimental infection with D. congolensis. Comparisons were made with D. congolensis infections on six control sheep without ticks. Tick-infested sheep developed chronic dermatophilosis lesions; tick-free sheep healed rapidly. On two tick-infested and two control sheep a chronological sequence of D. congolensis infection sites were made for histological comparisons. Dermatophilosis lesions on tick-infested sheep were characterized by chronic cellular infiltration and accumulation of plasma cells. Lesions on control sheep healed in association with transient cellular infiltration including plasma cells. In neither test nor control sheep was there evidence of effective phagocytosis of D. congolensis. It was concluded that feeding of these ticks had a systemic effect on the host such that dermatophilosis was aggravated via an effect on immunological reactions in the skin. Control of dermatophilosis by tick control is advocated.

Actinomycetales Infections↗
PubMed1993

Cell-mediated pathology during murine malaria-associated nephritis.

We have studied the cellular mechanisms involved in the development of nephritis during acute and chronic murine malaria infections induced by Plasmodium vinckei petteri and P. berghei respectively. Albuminuria and uraemia were observed during the early stages of both types of infection, and were associated with glomerular and interstitial hypercellularity. There was a gradual increase in numbers of CD45+ cells from the early stages of both infections onwards. These infiltrates contained CD4+ and CD8+ cells and mononuclear phagocytes. The interstitial and glomerular hypercellularity was due to an influx of inflammatory cells rather than an increase in renal cell division. These findings indicate the importance of cell-mediated immune mechanisms in the development of nephritis during murine malaria and illustrate an example of naturally occurring infection-induced nephritis.

Acute Disease↗
PubMed1993

The systemic effect of adult and immature Amblyomma variegatum ticks on the pathogenesis of dermatophilosis.

The systemic effect of adult and nymphal Amblyomma variegatum on the pathogenesis of experimental infections of Dermatophilus congolensis was investigated. Three groups of four sheep were used with all 12 sheep being infected with identical titrated doses of D. congolensis One group of sheep was simultaneously infested with adult A. variegatum the second with nymphal A. variegatum and the third group were the controls, with no exposure to ticks. Assessment of the resulting infections indicate that the systemic effect of this tick is confined to the adults. Skin and serological tests using foreign antigens showed significantly reduced cell mediated and humoral immune response only in the sheep infested with adult A. variegatum.

Actinomycetales Infections↗