Biomedical subjects

T J Williams

Publications and source records attributed to T J Williams.

At least 109 records · Page 6Linked to original sources

PubMed1998

Central sleep apnoea in congestive heart failure despite vagal denervation after bilateral lung transplantation.

Nonhypercapnic central sleep apnoea is a disorder of respiratory control characterized by hyperventilation previously attributed to the stimulation of either pulmonary vagal afferent nerve fibres or respiratory chemoreceptors. This report describes central sleep apnoea in a patient with congestive heart failure following bilateral lung transplant in whom pulmonary vagal afferent nerve activity was absent.

Heart Failure↗

PubMed1998

The effect of physiologic and mechanical aging on the performance of peak flowmeters.

PURPOSE: To investigate the effects of physiologic and mechanical aging on peak flowmeters. MATERIALS AND METHODS: Eight each of MiniWright (MW; Clement Clark; Harlow, UK), Personal-Best (PB; HealthScan Products; Cedar Grove, NJ), Vitalograph (V; Vitalograph Ltd; Buckingham, UK), and Breath-Taker (BT; Medical Development Australia; Melbourne, Australia) peak flowmeters were assessed for accuracy and repeatability before and after aging using a computer-driven syringe to deliver peak flows from 100 to 700 L/min. Four of each type of flowmeter were physiologically aged by normal subjects performing up to six peak flows daily for 1 year. The remaining four of each flowmeter were mechanically aged using an accelerated aging device to deliver 2,000 exponential waveforms with a peak flow of 600 L/min over a period of 3 h. RESULTS: The V and BT flowmeters were linear and accurate over the range 100 to 700 L/min, while the PB overread at high flows. The MW was alinear throughout. The SD of the difference between readings before and after aging ranged from 8.6 to 40.6 L/min (mean, 9.2). Comparing the slopes of the relationship of actual against reference peak expiratory flow (PEF) showed that 16 flowmeters--5 BTs, 6 MWs, 4 PBs, and 1 V had no significant change in slope after aging. Mechanical aging caused a consistent underreading in PEF at high flow rates. Physiologic aging showed a more variable pattern both within and between flowmeter types. The MW was the most affected by physiologic aging, producing overestimates of PEF by as much as 100 L/min at 500 L/min. CONCLUSIONS: We conclude that the effects of physiologic and mechanical aging are different, and that while mechanical aging may provide a guide to the effects of aging, studies using physiologic aging would be more appropriate.

Equipment Failure↗

PubMed1997

Lung volume reduction surgery for emphysema.

OBJECTIVE: To report the results of lung volume reduction surgery (LVRS) for severe emphysema in Australia. SETTING: A tertiary teaching hospital. DESIGN: A prospective study of a consecutive case series. PARTICIPANTS: 20 patients (mean age, 56 years) with severe emphysema--mean forced expiratory volume in one second (FEV1), 0.72 L (28% of predicted) and severe gas trapping (mean residual volume, 286% of predicted). INTERVENTION: Bilateral apical LVRS was performed via a median sternotomy with a linear stapler; bovine pericardial strips were used to reinforce the staple line. RESULTS: There was a 95% survival, and a mean (range) inpatient stay of 17 (8-45) days. No complications occurred in nine patients; a further six patients had only minor complications. Five patients had major complications (sputum retention requiring reintubation, persistent air leak requiring reoperation, duodenal perforation, and epidural haemorrhage); one patient died from multiorgan failure at 28 days. Intercostal drainage was left in situ for a mean of eight days. The results of FEV1, Medical Research Council (MRC) Dyspnoea Score and six-minute walk test improved in more than 90% of patients. FEV1 improved an average of 0.35 L (54% over baseline) (P < 0.001). Mean MRC Dyspnoea Score decreased from 3.4 to 2.1 (P < 0.001). Mean distance for the six-minute walk test increased from 306 to 431 metres (P < 0.001). CONCLUSION: Our experience confirms that LVRS produces worthwhile early outcomes for a subgroup of patients with severe emphysema. The clinical, economic and ethical questions raised by this new therapy will need to be assessed.

Adult↗

PubMed1997

Angiogenic and HIV-inhibitory functions of KSHV-encoded chemokines.

Unique among known human herpesviruses, Kaposi's sarcoma-associated herpesvirus (KSHV or HHV-8) encodes chemokine-like proteins (vMIP-I and vMIP-II). vMIP-II was shown to block infection of human immunodeficiency virus-type 1 (HIV-1) on a CD4-positive cell line expressing CCR3 and to a lesser extent on one expressing CCR5, whereas both vMIP-I and vMIP-II partially inhibited HIV infection of peripheral blood mononuclear cells. Like eotaxin, vMIP-II activated and chemoattracted human eosinophils by way of CCR3. vMIP-I and vMIP-II, but not cellular MIP-1alpha or RANTES, were highly angiogenic in the chorioallantoic assay, suggesting a possible pathogenic role in Kaposi's sarcoma.

Animals↗

PubMed1997

Chemokine-induced eosinophil recruitment. Evidence of a role for endogenous eotaxin in an in vivo allergy model in mouse skin.

Selective eosinophil recruitment into tissues is a characteristic feature of allergic diseases. Chemokines are effective leukocyte chemoattractants and may play an important role in mediating eosinophil recruitment in various allergic conditions in man. Here, we describe a novel mouse model of eosinophil recruitment in which we have compared the in vivo chemoattractant activity of different C-C chemokines. Furthermore, we describe the use of antibodies to chemokines and receptor blockade to address the endogenous mechanisms involved in eosinophil recruitment in a late-phase allergic reaction in mouse skin. Intradermal injection of mEotaxin and mMIP-1alpha, but not mMCP-1, mRANTES, mMCP-5, or mMIP-1beta, induced significant 111In-eosinophil recruitment in mouse skin. Significant 111In-eosinophil recruitment was also observed in an active cutaneous anaphylactic reaction. Pretreatment of skin sites with antieotaxin antiserum, but not an antiMIP-1alpha antibody, suppressed 111In-eosinophil recruitment in this delayed-onset allergic reaction. Similarly, desensitization of the eosinophil eotaxin receptor CCR3 with mEotaxin, or blockade of the receptor with metRANTES, significantly inhibited 111In-eosinophil recruitment in the allergic reaction. These results demonstrate an important role for endogenous eotaxin in mediating the 111In-eosinophil recruitment in allergic inflammation, and suggest that blockade of the CCR3 receptor is a valid strategy to inhibit eosinophil migration in vivo.

Anaphylaxis↗

PubMed1997

Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo.

Challenge of the airways of sensitized guinea pigs with aerosolized ovalbumin resulted in an early phase of microvascular protein leakage and a delayed phase of eosinophil accumulation in the airway lumen, as measured using bronchoalveolar lavage (BAL). Immunoreactive eotaxin levels rose in airway tissue and BAL fluid to a peak at 6 h falling to low levels by 12 h. Eosinophil numbers in the tissue correlated with eotaxin levels until 6 h but eosinophils persisted until the last measurement time point at 24 h. In contrast, few eosinophils appeared in BAL over the first 12 h, major trafficking through the airway epithelium occurring at 12-24 h when eotaxin levels were low. Constitutive eotaxin was present in BAL fluid. Both constitutive and allergen-induced eosinophil chemoattractant activity in BAL fluid was neutralized by an antibody to eotaxin. Allergen-induced eotaxin appeared to be mainly in airway epithelium and macrophages, as detected by immunostaining. Allergen challenge of the lung resulted in a rapid release of bone marrow eosinophils into the blood. An antibody to IL-5 suppressed bone marrow eosinophil release and lung eosinophilia, without affecting lung eotaxin levels. Thus, IL-5 and eotaxin appear to cooperate in mediating a rapid transfer of eosinophils from the bone marrow to the lung in response to allergen challenge.

Animals↗

PubMed1997

N-arylpiperazinyl-N'-propylamino derivatives of heteroaryl amides as functional uroselective alpha 1-adrenoceptor antagonists.

Novel arylpiperazines were identified as alpha 1-adrenoceptor (AR) subtype-selective antagonists by functional in vitro screening. 3-[4-(ortho-Substituted phenyl)piperazin-1-yl]propylamines were derivatized with N,N-dimethyl anthranilamides, nicotinamides, as well as carboxamides of quinoline, 1,8-naphthyridine, pyrazolo[3,4-b]pyridine, isoxazolo[3,4-b]pyridine, imidazo[4,5-b]pyridine, and pyrazolo[1,5-a]pyrimidines. Strips of rabbit bladder neck were employed as a predictive assay for antagonism in the human lower tract. Rings of rat aorta were used as a "negative screen" for the test antagonists. Binding to alpha 1-ARs was relatively sensitive to size and electronic features of the arylpiperazine portion of the antagonists and permissive to these features on the heteroaryl carboxamide side. These structure-affinity findings were exploited to produce nicotinamides (e.g. 13ii and 25x) and pyrazolo[3,4-b]pyridines (e.g. 37f and 37y) ligands with nanomolar affinity at the alpha 1-AR subtype prevalent in the human lower urinary tract(pA2 values: 8.8, 10.7, 9.3, and 9.9, respectively) and displaying 2-3 orders of magnitude selectivity over the alpha 1D-AR.

Adolescent↗

PubMed1997

Chemoattractant cross-desensitization of the human neutrophil IL-8 receptor involves receptor internalization and differential receptor subtype regulation.

Human neutrophils undergo rapid homologous receptor desensitization following repeated stimulation with chemoattractants such as IL-8, C5a, and FMLP. It has also been demonstrated that cross-desensitization among these chemoattractant receptors occurs. We investigated the mechanisms underlying the cross-desensitization of responses to IL-8 induced by pretreatment with FMLP or C5a. In [125I]-labeled IL-8 binding studies we found that the cross-desensitization induced by FMLP or C5a was associated with a subsequent reduction in IL-8 binding to neutrophils. There was no recovery of [125I]-labeled IL-8 binding on removal of the C5a or FMLP pretreatment. FACS analysis using mAbs specific for the two IL-8R subtypes showed differential regulation of IL-8R A and IL-8R B cell surface expression after chemoattractant pretreatment. Homologous desensitization by IL-8 resulted in internalization of IL-8R A and IL-8R B, but only IL-8R A was completely re-expressed after removal of agonist. FMLP stimulation led to a substantial loss of IL-8R B from the cell surface, whereas C5a stimulation induced only a partial loss. In both cases there was no re-expression of IL-8R B on removal of the chemoattractant stimulation. C5a and FMLP did not affect IL-8R A expression. Calcium mobilization studies using melanoma growth stimulatory activity and IL-8 suggest that a sustained loss of IL-8R B may play a part in maintaining FMLP-induced IL-8R cross-desensitization. Chemoattractant-induced cross-desensitization of neutrophils may be of importance in regulating neutrophil accumulation during the inflammatory response in vivo.

Antigens, CD↗

PubMed1997

Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells.

Eotaxin is a newly discovered C-C chemokine which preferentially attracts and activates eosinophil leukocytes by acting specifically on its receptor CCR3. The airway inflammation characteristic of asthma is believed to be, at least in part, the result of eosinophil-dependent tissue injury. This study was designed to determine whether there is increased expression of eotaxin and CCR3 in the bronchial mucosa of asthmatics and whether this is associated with disease severity. The major sources of eotaxin and CCR3 mRNA were determined by co-localization experiments. Bronchial mucosal biopsy samples were obtained from atopic asthmatics and normal non-atopic controls. Eotaxin and CCR3 mRNA were identified in tissue sections by in situ hybridization (ISH) using radiolabeled riboprobes and their protein product visualized by immunohistochemistry (IHC). Co-localization experiments were performed by double ISH/IHC. Eotaxin and CCR3 (mRNA and protein) were significantly elevated in atopic asthmatics compared with normal controls. In the asthmatics there was a highly significant inverse correlation between eotaxin mRNA+ cells and the histamine provocative concentration causing a 20% fall in FEV1 (PC20). Cytokeratin-positive epithelial cells and CD31+ endothelial cells were the major source of eotaxin mRNA whereas CCR3 co-localized predominantly to eosinophils. These data are consistent with the hypothesis that damage to the bronchial mucosa in asthma involves secretion of eotaxin by epithelial and endothelial cells resulting in eosinophil infiltration mediated via CCR3. Since selective (eotaxin) and non-selective C-C chemokines such as RANTES, MCP-3 and MCP-4 all stimulate eosinophils via CCR3, this receptor is potentially a prime therapeutic target in the spectrum of diseases involving eosinophil-mediated tissue damage.

Adult↗

PubMed1997

Animal models of asthma: role of chemokines.

In studies of disease processes, increasing knowledge leads to an increased awareness of the complexity of the underlying mechanisms. The intense research activity in the chemokine field has made this acutely manifest. Numerous chemokines have been discovered through the use of (1) bioassay of in vitro cell culture supernatants and in vivo exudates from animal models of inflammation and (2) molecular biology techniques. Any one chemokine can often be produced by a number of different cell types and exert its effects on different target cells. This has been interpreted by some as implying a high degree of redundancy. Although this is understandable, in disease processes parallel and sequential mechanisms are possible, and potentially important therapeutic targets have emerged. There is compelling evidence from animal and clinical studies that eosinophils are important effector cells in asthma, but this relationship is as yet unproven in the human disease. Two possible targets to prevent eosinophil recruitment to the lung are IL-5 and its receptor, which are important in several aspects of eosinophil biology, and eotaxin and its receptor, CCR3. The eotaxin receptor is particularly attractive as a target as it is expressed in high numbers on eosinophils, but not other leukocytes, and appears to be the major detector of the eosinophil for eotaxin and other chemokines such as MCP-4. Eotaxin and CCR3 knockout mice are being developed, and animal models will continue to be invaluable when antagonists are available. In the shape of receptor antagonists, the chemokine field may yet provide the final proof of concept for the long-established eosinophil theory of asthma in humans.

Amino Acid Sequence↗

PubMed1997

Role of nitric oxide in the dilator actions of capsaicin-sensitive nerves in the rabbit coronary circulation.

Perivascular sensory nerves release calcitonin gene-related peptide (CGRP) and substance P, the dilator actions of which can be regulated by nitric oxide (NO). This study investigated the role of NO in the vasodilation caused by sensory nerve stimulation, by capsaicin, or exogenous CGRP and substance P in the isolated perfused coronary circulation of the rabbit. Coronary perfusion pressure (CPP) was raised in order to observe vasodilator responses, using the thromboxane mimetic, U46619. Capsaicin (3 x 10(-6) moles), alpha CGRP (3 x 10(-11) moles) and substance P (3 x 10(-12) moles) caused comparable reductions in CCP. At these concentrations, responses to capsaicin and CGRP were inhibited by the antagonist CGRP(8-37) but unaffected by the neurokinin-1 receptor antagonist, CP 96,345. The nitric oxide synthase inhibitor, NG nitro L-arginine methyl ester inhibited the effects of substance P and capsaicin but not CGRP. These results suggest that CGRP release following capsaicin-induced sensory nerve activation is modulated by NO.

Animals↗

PubMed1997

Early and long-term functional outcomes in unilateral, bilateral, and living-related transplant recipients.

Lung transplantation offers the possibility of improved quality of life and survival in patients with severe pulmonary and pulmonary vascular disease. Since the first human lung allotransplantation in 1963, survival has moved from hours or days into the present era of long-term (years) survival in many recipients. Measurement of outcome has now extended to measurement of exercise capacity and quality of life. A substantial improvement in quality of life is seen; however, exercise capacity remains moderately impaired in spite of the return (in many) of near normal cardiopulmonary function, suggesting peripheral limitation to exercise. Recently, fiber type changes and abnormal oxidative metabolism have been shown in the skeletal muscle of stable lung transplant recipients. This suggests a persistence of a pretransplant skeletal muscle injury and/ or the effects of post-transplant immunosuppression (particularly Cyclosporin A and corticosteroids).

Exercise Test↗

PubMed1997

Comparison of the reversed passive Arthus and local Shwartzman reactions of rabbit skin: effects of the long-acting PAF antagonist UK-74,505.

1. By using the selective, potent and long acting platelet-activating factor (PAF) antagonist, UK-74,505, we investigated the role of PAF in a local Shwartzman reaction (LSR) and a reversed passive Arthus (RPA) reaction in rabbit skin. For comparison, we also studied the effect of the PAF antagonist on neutrophil aggregation in vitro and on acute inflammatory responses induced by intradermally (i.d.) injected lipopolysaccharide (LPS), PAF, bradykinin and zymosan-activated plasma. 2. Neutrophil aggregation was assessed photometrically. Haemorrhage, oedema formation, platelet deposition and neutrophil accumulation were quantified in rabbit skin by measuring the accumulation of i.v. injected 51Cr-labelled red blood cells (RBC), 125I-labelled human serum albumin, 111In-labelled platelets and 111In-labelled neutrophils respectively. 3. UK-74,505 inhibited in vitro neutrophil aggregation induced by PAF but not by leukotriene B4. When injected i.v. into rabbits UK-74,505 suppressed oedema formation in response to i.d. PAF for up to 4 h but had no effect on oedema induced by bradykinin or zymosan-activated plasma. 4. Oedema formation, but not neutrophil accumulation, produced during the RPA reaction was significantly inhibited by i.v. UK-74,505. The PAF antagonist also suppressed 111In-platelet but not 111In-neutrophil accumulation in response to i.d. LPS. UK-74,505 did not affect haemorrhage or oedema formation produced during the LPS-mediated LSR. 5. The results demonstrate that PAF is an important mediator of oedema formation, but not neutrophil accumulation, in the immune-complex mediated RPA reaction in rabbit skin. PAF also appears to be required for platelet, but not neutrophil, accumulation in response to locally injected LPS. Our studies do not suggest a role for PAF in the LPS-mediated LSR.

Animals↗

PubMed1997

Menstrual cycle phase and running economy.

To further elucidate the relationship between RE and menstrual cycle phase, eight eumenorrheic moderately-trained female runners were studied throughout their menstrual cycles, which were divided into five phases: early follicular (EF), late follicular (LF), early luteal (EL), mid-luteal (ML), and late luteal (LL). Subjects were studied at rest and while running at speeds initially corresponding to 55% and 80% maximal oxygen consumption (VO2max). Ventilation (L x min-1) was significantly (P < 0.05) higher in ML compared with EF during all three conditions (mean +/- SE) (rest: 12.4 +/- 0.7 vs 10.3 +/- 0.8; 55% VO2max: 46.2 +/- 0.9 vs 42.2 +/- 1.4; and 80% VO2max: 68.8 +/- 3.0 vs 63.3 +/- 2.0 L x min-1, respectively). Resting VO2 (mL x kg-1 x min-1) was significantly (P < 0.05) hi gher in ML (4.8 +/- 0.1) compared with EF (3.9 +/- 0.2). Profile of Mood States (POMS) total mood disturbance (TMD) and three subscale (depression, fatigue, and confusion) scores were also significantly higher during ML compared with EF; TMD: 127 +/- 6.0 vs 104 +/- 6.0; depression: 6 +/- 1.4 vs 3 +/- 1.4; fatigue: 9 +/- 1.0 vs 4 +/- 0.9; and confusion: 7 +/- 0.9 vs 5 +/- 1.2, respectively. The POMS vigor subscale score was significantly lower during ML (11 +/- 1.5) when compared with EF (19 +/- 0.7). RE at speeds corresponding to 55% VO2max was not significantly different between phases of the menstrual cycle. RE at speeds corresponding to 80% VO2max was, however, significantly less (higher VO2) during ML (41.4 +/- 0.8 mL x kg-1 x min-1) than EF (40.2 +/- 0.5 mL x kg-1 x min-1). It was concluded that RE at speeds corresponding to 80% VO2max in moderately-trained female runners covaries independently with ventilatory drive changes and with fluctuations in mood state which occur throughout the menstrual cycle.

Affect↗

PubMed1997

Role of tear fluid in the growth of gram-negative bacteria on contact lenses.

Incidents of CLARE (contact lens induced acute red eye) are associated with high numbers of Gram-negative bacteria on the lens surface. This study found that most strains of bacteria implicated in CLARE adhere poorly to the lens surface regardless of whether the lens surface was clean or had been worn in the eye. The high numbers of bacteria on the lens surface result from bacterial growth on the lens surface after adhesion has occurred. Using an artificial tear formulation and real tears, this study demonstrated that the tear fluid provides the necessary nutrients required for bacterial growth.

Bacterial Adhesion↗

PubMed1997

Immunopathological changes in the airways of stable lung transplant recipients.

BACKGROUND: Pathological obliterative bronchiolitis, characterised by inflammation and occlusion of airways, is a serious complication of lung transplantation. Endobronchial biopsy (EBB) provides a means of examining transplanted airways. This study aimed to investigate the role of EBB samples in revealing early signals of airway injury. METHODS: In 18 stable lung transplant recipients with close to maximal lung function (median FEV1, best after transplantation 100%, interquartile range 98-100%) EBB samples were taken simultaneously with transbronchial biopsy samples and bronchoalveolar lavage (BAL) fluid (median 195 days after transplantation). OCT embedded specimens were snap frozen on an isopentane slurry made with liquid nitrogen and 7 microns sections were stained with monoclonal antibodies using a three stage immunoperoxidase method. RESULTS: Compared with nine non-transplanted control subjects, EBB specimens from the stable transplant group had significantly increased CD8 positivity (median 53 versus 27 cells/mm basement membrane, p = 0.04; 95% CI for the difference 1 to 46)) and increased HLA-DR positivity (median 84 versus 26 cells/mm basement membrane, 95% CI for the difference 6 to 115). There was an increase in CD68 positive cells in the EBB specimens from transplant recipients of borderline significance (median 92 versus 68, p = 0.08, 95% CI for the difference 1 to 84). CD3, CD4, and CD25 counts were similar in the two groups. EBB findings were not influenced by age, sex, indication for transplant, immunosuppression doses or levels, nor the presence of airway commensals in the BAL fluid. CONCLUSIONS: EBB is practicable in a transplant setting and provides information about bronchial inflammatory changes. It is likely that there is ongoing inflammation, possibly rejection mediated, even in healthy lung transplant recipients despite triple immunosuppression.

Adult↗

PubMed1997

Bronchial hyperresponsiveness in lung transplant recipients: lack of correlation with airway inflammation.

BACKGROUND: Bronchial hyperresponsiveness (BHR) to methacholine has been reported to occur in most lung transplant recipients. BHR to physical stimuli such as exercise and non-isotonic aerosols has not been as extensively studied in this subject population. This report aims to assess the presence and degree of BHR to methacholine and hypertonic saline in stable lung transplant recipients and to relate it to the presence of airway inflammation. METHODS: Ten patients undergoing bilateral sequential lung transplantation and six heart-lung transplant recipients, all with stable lung function, were recruited 66-1167 days following transplantation. Subjects underwent a methacholine challenge and bronchoscopy for sampling of bronchoalveolar lavage fluid, transbronchial and endobronchial biopsy tissues. Hypertonic saline challenge was performed six days later. RESULTS: Nine of the 16 transplant recipients had positive methacholine challenges (geometric mean PD20 0.18 mg, interquartile range 0.058-0.509) and three of these subjects also had positive hypertonic saline challenges (PD15 = 2.3, 33.0, and 51.5 ml). No clear relationship was found between BHR to either methacholine or hypertonic saline and levels of mast cells, eosinophils or lymphocytes in samples of biopsy tissue or lavage fluid. CONCLUSIONS: Most of the lung transplant recipients studied were responsive to methacholine and unresponsive to hypertonic saline. BHR was not clearly related to airway inflammation, suggesting an alternative mechanism for BHR following lung transplantation from that usually assumed in asthma.

Adult↗

PubMed1997

RANTES in human allergen-induced rhinitis: cellular source and relation to tissue eosinophilia.

Human allergen-induced rhinitis is associated with recruitment and activation of CD4+ T lymphocytes and eosinophils. RANTES is a novel CC chemokine that is a potent chemoattractant for both memory T cells and eosinophils. We therefore investigated RANTES in the nasal mucosa after local allergen provocation. Nasal lavage was performed, and biopsies from the inferior nasal turbinate were taken from 14 atopic, seasonal rhinitic patients and seven normal subjects for as long as 6 h after challenge with a grass pollen extract and after a control (allergen diluent) challenge. In five of seven rhinitics tested, radioimmunoassay of nasal fluid demonstrated increases in RANTES at 2 to 4 h (p < 0.05). Nasal allergen challenge provoked significant increases in RANTES mRNA (p = 0.0015) and protein (p = 0.01) containing cells in the nasal submucosa at 6 h. No changes were observed in normal subjects. Increases in RANTES mRNA+ cells correlated with the associated increases in eosinophils (r = 0.78, p = 0.001). Colocalization studies revealed that the majority of RANTES mRNA+ cells were macrophages (51%) followed by eosinophils (15%), T lymphocytes (11%), and mast cells (3%). Our results demonstrate that allergen-induced rhinitis is associated with release of RANTES and upregulation of RANTES mRNA and protein+ cells, predominantly macrophages, in the nasal mucosa. RANTES synthesis, release, or receptor antagonism may represent a potential target for antiallergy treatment.

Adult↗