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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Analysis of allergens in rat fur and saliva.

BACKGROUND: The fur is an important source of allergens in many mammal species, but this source has not been extensively studied in rats. Rat room dust contains high-molecular-weight allergens that have been found to cross-react with fur and its presumed salivary contaminants. The role of rat fur and saliva as a source of respiratory allergens merits further investigation. The objective was to describe the allergens present in the fur and saliva of male rats. METHODS: Allergen extracts were prepared from the saliva and fur of the pelts from adult male rats. Immunoblotting was used to describe the allergens present in rat fur and saliva with serum from 76 and 25 individuals, respectively. RESULTS: There was considerable variation between the individuals in the binding of IgE to the separated fur and saliva allergens. Immunoblot analysis identified 23 allergens in rat fur. "Major" allergens were found at the "origin", and at 55, 51, 19, and 17 kDa, and "intermediate" allergens at 74, 67 (probably albumin), and 21.5 (diffuse) kDa. Seventeen salivary allergens were described with "major" allergens at 21.5, 19.5, 19, 18, and 17.5 kDa. Many subjects had IgE to the 67 kDa (56%) and 43 kDa (64%) allergens but the density of staining was weak. CONCLUSION: Rat fur and saliva are the sources of many allergens. Fur contained five "major" allergens and was a complex source of allergens of relatively high molecular weight (>22 kDa). The most important salivary allergens have molecular weights of less than 22 kDa. Fur is the most probable source of the high-molecular-weight allergens found in rat room dust.

Allergens↗
PubMed2001

Identification of some rabbit allergens as lipocalins.

Rabbits are frequently used as laboratory animals or kept as domestic pets. Rabbit serum albumin and a 17-kDa protein referred to as Ory c 1 have previously been reported as allergens. Several other allergenic proteins have been recognized by crossed immuno-electrophoresis but have not been characterized. The aim of this study was to characterize the allergenic proteins present in rabbit saliva, urine and fur on the basis of molecular size and, where possible, to determine their amino acid sequences. Extracts from the male New Zealand white rabbit were used for developing specific direct RAST and RAST inhibition assays. Proteins in the extracts were separated by SDS-PAGE and the individual allergens identified by immunoblotting with serum from rabbit-allergic individuals. The N-termini of four allergens were sequenced. Saliva was the most potent extract. In total, 26 protein bands were recognized as allergens in the three extracts: 12 in saliva, seven in urine and seven in fur. Their molecular weights ranged from an 8-kDa species in saliva to an 80-kDa protein in urine. The N terminal sequences of an 18 kDa and a 21-kDa species in saliva, were identified as lipocalins with sequence similarity to a recently described odourant binding protein. This is the first evidence that allergens from the rabbit are members of the lipocalin superfamily of proteins, suggesting that similar mechanisms may be involved in eliciting the allergic response to rabbits. The 18 kDa allergen from saliva may be the previously named rabbit allergen, Ory c 1.

Allergens↗
PubMed2001

The use of human CD68 transcriptional regulatory sequences to direct high-level expression of class A scavenger receptor in macrophages in vitro and in vivo.

Macrophages (Mphi) play a key role in innate and acquired immunity. The study of Mphi biology has been hampered by the absence of suitable gene regulatory sequences for the overexpression of heterologous genes in Mphi. The human CD68 gene encodes a glycoprotein that is expressed in monocytes and Mphi, and therefore represents an attractive candidate gene for the generation of a Mphi-specific gene-targeting vector. A transgene expression cassette that combines 2.9 kb of CD68 5' flanking sequence with the 83-bp first intron (IVS-1) of the CD68 gene, directed high-level, long-lasting expression of class A human scavenger receptor (hSR-A) isoforms in the murine Mphi cell line, RAW-264. By using this CD68 expression cassette to generate Mphi cell lines that overexpress a soluble secreted form of the extracellular portion of type I human SR-A, we were able to purify significant quantities of this protein and show its ability to inhibit SR-A-mediated endocytosis. Analysis of two independent lines of transgenic mice that expressed type III human SR-A under the control of the CD68 gene sequences revealed transgene mRNA expression in elicited Mphi populations and in mouse tissues in a pattern that was consistent with Mphi-specific gene targeting. These data show that CD68 transcriptional regulatory sequences can be used to direct high-level transgene expression in Mphi in vitro and in vivo.

Animals↗
PubMed2001

Meeting the needs of consumers in the community: a working partnership in mental health in New Zealand.

AIM: The aim was to evaluate whether the services community mental health nurses provide are meeting the needs of consumers in the community. RATIONALE: The role of the mental health nurse in the community is changing as a result of deinstitutionalization, the consumer movement and the market model of health care delivery. In this context it is important for mental health nurses to evaluate whether the service they are currently providing is meeting the needs of consumers. DESIGN: This was a joint project between nurses and consumers. It was a service-specific descriptive research project utilizing qualitative methods of data collection and analysis that provides a model for working in partnership. FINDINGS: The results of this research identify collaboration in planning care and sharing information as two areas of concern but generally the consumers were very satisfied with the care provided by community mental health nurses. The analysis of the data suggests that consumers value nursing care because nurses provide support in their own home; they help consumers develop strategies for coping with their illness and their life; they provide practical assistance when it is required; they are vigilant about any deterioration or improvement; and they are available and accessible. CONCLUSION: The results of this study have demonstrated that nurses will remain critical to the success of community-based care because of their ability and willingness to be flexible to the demands of their own organization and the users of services.

Adult↗
PubMed2001

Elimination of mouse allergens in the working environment: assessment of individually ventilated cage systems and ventilated cabinets in the containment of mouse allergens.

BACKGROUND: Laboratory animal allergy is an important occupational disease that is preventable by reduction of exposure to mammalian allergens. OBJECTIVE: The purpose of this investigation was to assess the efficacy of safety equipment in containing mouse urinary protein (MUP)--specifically, individually ventilated cage (IVC) systems and class I--type and class II ventilated cabinets. METHODS: Six IVC systems (which are used to house rodents) were operated at positive and negative pressure. Air samples (2 L/min) were collected at the cage front, cage back, air inlet, and air outlet, and the MUP was quantified by immunoassay. The background MUP of the IVC study room was compared with that of rooms where mice were housed conventionally or in isolators. Class I--type cabinets (n = 2) were tested during the disposal of soiled litter. Air samples were positioned on and behind the operator and inside the cabinet (n = 2). Personal samples were collected while scientific procedures were performed in a class II cabinet and in the open. RESULTS: All of the IVC systems contained MUP effectively (>250-fold) when operated at negative pressure. At positive pressure, the "unsealed" IVC racks leaked MUP (1- to 25-fold reduction) but the "sealed" IVC system did not. Class I--type cabinets reduced (10-fold) but did not eliminate exposure during "cleaning out." No MUP was detected when procedures were performed in class II cabinets (protection factor, >10-fold). CONCLUSION: Safety equipment can substantially reduce exposure to mouse allergen. Allergen exposure in holding rooms will be minimized if mice are housed in IVC systems operated at negative pressure or in "sealed" IVC systems at positive pressure. Respiratory protection should be used whenever "unsealed" IVC systems are operated at positive pressure or during "cleaning out" in class I--type cabinets.

Allergens↗
PubMed2001

Binding properties of the mannose receptor.

A comprehensive approach to the study of mannose receptor (MR) biology has unveiled an unexpected level of complexity and stresses the importance of post-translational modifications and gene regulation in the analysis of protein function. The existence of endogenous tissue ligands for the MR highlights the need to reduce MR expression in antigen presenting cells and/or to regulate T cell stimulation after presentation of MR ligands, in order to avoid autoimmunity. This regulation might be achieved by down modulation of the antigen presenting cell stimulatory capacity upon MR ligation. In macrophages there are conflicting evidence regarding the outcome of MR recognition. These results are not unexpected if endogenous mannosylated and sulphated self-antigens, that need to be shielded from the immune system, are being eliminated through this receptor. The presence of counter receptors for the cysteine rich (CR) domain of the MR in specialized myeloid cells in lymphoid organs adds a new dimension to this system. It opens the possibility for a delivery pathway for MR carbohydrate recognition domains (CRDs) ligands that needs to be investigated further.

Animals↗
PubMed2001

Laboratory animal allergy: a British perspective on a global problem.

In the United Kingdom, laboratory animal allergy (LAA) has been recognized as an important occupational disease for nearly 25 years. However, introduction of health and safety legislation (e.g., the Control of Substances Hazardous to Health Regulations of 1988) and an increasing knowledge of the factors that contribute to the etiology of this disease have had surprisingly little impact on the prevalence and incidence of LAA over the last 10 to 20 yr. Studies of the relation between exposure to animal allergens and the development of LAA reveal that the risk of disease increases with increasing intensity of exposure. Current evidence suggests that animal allergens are very potent, and substantial decreases in allergen exposure are therefore necessary before a reduction in symptoms will be observed. In the United Kingdom, it is unlikely that an Occupational Exposure Limit will be set for animal allergens in the near future, partly because an adequately standardized assay for quantifying exposure is not yet available. Prevention of LAA in the future will probably be driven by the needs of the industry and will most likely rely on the adoption of guidelines describing " best practise" which incorporate sophisticated engineering methods of controlling exposure to animal allergens.

Allergens↗
PubMed2001

Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea-predominant irritable bowel syndrome.

OBJECTIVES: Bowel urgency is one of the most bothersome symptoms for nonconstipated IBS patients. The efficacy of alosetron in control of bowel urgency and Global Improvement of IBS symptoms were evaluated in a multicenter double-blind, randomized, placebo-controlled study. METHODS: Female IBS patients with lack of satisfactory control of bowel urgency were randomized 2:1 to alosetron 1 mg twice daily or placebo treatment groups. The primary endpoint was the proportion of days with satisfactory control of bowel urgency during the 12-wk treatment period and 2-wk follow-up period. Secondary endpoints included IBS Global Improvement (responder defined as patient-reported moderate or substantial improvement in IBS symptoms) and improvements in bowel function (stool frequency, consistency, and sensation of incomplete evacuation). RESULTS: A total of 801 women were randomized to the alosetron (n = 532) or placebo groups (n = 269). Physicians classified 98% of patients with diarrhea-predominant IBS. Patients treated with alosetron had a significantly greater proportion of days with satisfactory control of urgency compared to placebo for the treatment period (73% vs 57%, p < 0.001). A significantly greater number of patients treated with alosetron were IBS Global Improvement responders compared to placebo at week 12 (76% vs 44%, p < 0.001). IBS Global Improvement responders had more days with satisfactory control of urgency at week 12 (88% vs 48%) as well as firmer stools, fewer stools/day, and fewer days with incomplete evacuation compared with nonresponders. Alosetron-treated patients showed improvements in bowel functions compared to placebo-treated patients. Constipation was the most commonly reported adverse event.

Carbolines↗
PubMed2001

Species-specific PCR for identification of common contaminant mollicutes in cell culture.

Mycoplasma arginini, M. fermentans, M. hyorhinis, M. orale, and Acholeplasma laidlawii are the members of the class Mollicutes most commonly found in contaminated cell cultures. Previous studies have shown that the published PCR primer pairs designed to detect mollicutes in cell cultures are not entirely specific. The 16S rRNA gene, the 16S-23S rRNA intergenic spacer region, and the 5' end of the 23S rRNA gene, as a whole, are promising targets for design of mollicute species-specific primer pairs. We analyzed the 16S rRNA genes, the 16S-23S rRNA intergenic spacer regions, and the 5' end of the 23S rRNA genes of these mollicutes and developed PCR methods for species identification based on these regions. Using high melting temperatures, we developed a rapid-cycle PCR for detection and identification of contaminant mollicutes. Previously published, putative mollicute-specific primers amplified DNA from 73 contaminated cell lines, but the presence of mollicutes was confirmed by species-specific PCR in only 60. Sequences of the remaining 13 amplicons were identified as those of gram-positive bacterial species. Species-specific PCR primers are needed to confirm the presence of mollicutes in specimens and for identification, if required.

Cell Line↗
PubMed2001

Case of synovitis potentially caused by Dolosigranulum pigrum.

We report a case of synovitis in a 64-year-old man who developed the infection while on steroid therapy for rheumatoid arthritis. Dolosigranulum pigrum, a gram-positive catalase-negative coccus, was isolated from two sets of blood cultures prior to antibiotic therapy. The patient was treated with 4 weeks of appropriate antibiotics, and the synovial inflammation resolved. Although synovial aspirates were never positive for any bacteria or fungi, the timing of positive blood cultures and absence of other pathogens suggest the possible etiology as D. pigrum.

Blood↗
PubMed2001

Linked chromosome 16q13 chemokines, macrophage-derived chemokine, fractalkine, and thymus- and activation-regulated chemokine, are expressed in human atherosclerotic lesions.

Chemokines are important mediators of macrophage and T-cell recruitment in a number of inflammatory pathologies, and chemokines expressed in atherosclerotic lesions may play an important role in mononuclear cell recruitment and macrophage differentiation. We have analyzed the expression of the linked chromosome 16q13 genes that encode macrophage-derived chemokine (MDC/CCL22), thymus- and activation-regulated chemokine (TARC/CCL17), and the CX(3)C chemokine fractalkine (CX(3)CL1) in primary macrophages and human atherosclerotic lesions by reverse transcription-polymerase chain reaction and immunohistochemistry. We show that macrophage expression of the chemokines MDC, fractalkine, and TARC is upregulated by treatment with the Th2-type cytokines interleukin-4 and interleukin-13. High levels of MDC, TARC, and fractalkine mRNA expression are seen in some, but not all, human arteries with advanced atherosclerotic lesions. Immunohistochemistry shows that MDC, fractalkine, and TARC are expressed by a subset of macrophages within regions of plaques that contain plaque microvessels. We conclude that MDC, fractalkine, and TARC, which are chromosome 16q13 chemokines, could play a role in mononuclear cell recruitment into atherosclerotic lesions and influence the subsequent inflammatory response. Macrophage-expressed chemokines upregulated by interleukin-4 may be useful surrogate markers for the presence of Th2-type immune responses in human atherosclerotic lesions.

Adolescent↗
PubMed2001

Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal.

Our best pharmacologic agents for osteoporosis treatment prevent no more than 40-60% of osteoporotic fractures in patients at highest risk. Thus, there is a need for agents that can further augment bone mass and reduce fracture risk more substantially. To this end, we investigated the utility of parathyroid hormone (PTH) in combination with established hormone-replacement therapy (HRT) in women with osteoporosis. Fifty-two women who had been on HRT for at least 2 years were enrolled in this trial in which 25 were assigned randomly to remain on HRT alone and 27 were assigned to remain on HRT and also receive daily subcutaneous PTH(1-34) 400 U (25 microg) per day for 3 years. Bone mineral density (BMD) measurements at the spine, hip, and total body as well as biochemical determinations of bone turnover and calcium homeostasis were obtained every 6 months. Lateral thoracic and lumbar spine X-rays were obtained at baseline and annually. Subjects also had measurements of bone density and biochemical indices of bone turnover 1 year after discontinuation of PTH, while HRT was continued. In the group receiving HRT alone, bone density and biochemical variables of bone turnover remained stable throughout the 3-year treatment trial and 1-year follow-up. In the PTH + HRT group, biochemical variables of bone formation and resorption peaked at 6 months and subsequently remained elevated until 30 months at which time levels were indistinguishable from baseline. Subjects in the PTH + HRT group increased bone mass by 13.4+/-1.4% in the spine, 4.4+/-1.0% in the total hip, and 3.7+/-1.4% in the total body. Bone density measurements remained stable 1 year after discontinuation of PTH without any significant loss while women continued HRT. Biochemical variables did not change significantly after cessation of PTH through the 1-year follow-up period. PTH + HRT reduced the percent of women who had vertebral fractures from 37.5% to 8.3% (using a 15% height reduction criterion) and from 25% to 0% (using a 20% height reduction criterion) compared with women receiving HRT alone (p < 0.02 for both). We conclude that ongoing HRT maintains almost all of the PTH-induced bone mass increment for 1 year after discontinuation of PTH. Furthermore, PTH in combination with hormone therapy is an effective means of increasing bone mass throughout the skeleton and specifically reducing vertebral fracture occurrence by 75-100%, compared with HRT alone.

Bone Density↗