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Biomedical subjects

P Burke

Publications and source records attributed to P Burke.

At least 19 recordsLinked to original sources

Cholecystokinin (CCK) secretion in patients with severe short bowel syndrome (SSBS).

This study examined the effects of a liquid meal on cholecystokinin (CCK) secretion in patients with severe short bowel syndrome (SSBS) receiving home total parenteral nutrition (TPN) support for 5-19 years after massive small bowel resection. Five patients with SSBS due to superior mesenteric artery or vein thrombosis were included. Five healthy volunteers served as controls. Blood was drawn before and 1 hr following consumption of 250 ml of a liquid diet containing 232 kcal with 8 g fat and 8 g protein. Plasma CCK activity was evaluated by amylase bioassay. All patients had stable weight with a normal BMI and serum albumin level, although there were mild abnormalities in their liver function tests. CCK secretion after stimulation was significantly decreased in patients. These results suggest that reduction in intestinal length influences CCK secretion in response to meal stimulation in SSBS patients.

Adult↗

Quantitative analysis of angiogenesis using confocal laser scanning microscopy.

Angiogenesis is essential for tumor growth and metastasis. Angiogenesis is commonly quantified by measuring microvessel density (MVD) within tumors. In this report, we compared light microscopy with confocal laser scanning microscopy (CLSM) in the qualitative and quantitative analysis of angiogenesis. MVDs were determined manually in a lung tumor xenograft and a normal skeletal muscle using CD31 immunohistochemical staining and light microscopy. Area of three-dimensional representation of microvessels, detected as CD31 immunofluorescence, was measured automatically using computer-assisted CLSM. By manual counting under light microscopy, the relative level of MVD of the lung tumor vs. skeletal muscle was 0.8. However, the corresponding relative level of microvessels was 3.4 as determined by computer-assisted CLSM. Furthermore, the architecture of microvessels was better delineated with CLSM than with light microscopy. We have applied this CLSM method for analyzing the antiangiogenic effect of an anticancer drug, paclitaxel, in the lung tumor xenograft model. We conclude that CLSM is an appropriate method for quantitative and qualitative analysis of microvasculature in normal and tumor tissues.

Angiogenesis Inhibitors↗

Regulation of epidermal growth factor receptor signaling by endocytosis and intracellular trafficking.

Ligand activation of the epidermal growth factor receptor (EGFR) leads to its rapid internalization and eventual delivery to lysosomes. This process is thought to be a mechanism to attenuate signaling, but signals could potentially be generated after endocytosis. To directly evaluate EGFR signaling during receptor trafficking, we developed a technique to rapidly and selectively isolate internalized EGFR and associated molecules with the use of reversibly biotinylated anti-EGFR antibodies. In addition, we developed antibodies specific to tyrosine-phosphorylated EGFR. With the use of a combination of fluorescence imaging and affinity precipitation approaches, we evaluated the state of EGFR activation and substrate association during trafficking in epithelial cells. We found that after internalization, EGFR remained active in the early endosomes. However, receptors were inactivated before degradation, apparently due to ligand removal from endosomes. Adapter molecules, such as Shc, were associated with EGFR both at the cell surface and within endosomes. Some molecules, such as Grb2, were primarily found associated with surface EGFR, whereas others, such as Eps8, were found only with intracellular receptors. During the inactivation phase, c-Cbl became EGFR associated, consistent with its postulated role in receptor attenuation. We conclude that the association of the EGFR with different proteins is compartment specific. In addition, ligand loss is the proximal cause of EGFR inactivation. Thus, regulated trafficking could potentially influence the pattern as well as the duration of signal transduction.

Adaptor Proteins, Signal Transducing↗

Incidence, prognosis, and etiology of end-stage liver disease in patients receiving home total parenteral nutrition.

BACKGROUND: Elevations in liver function tests have been reported in patients receiving total parenteral nutrition (TPN). The clinical aspects of end-stage liver disease (ESLD) associated with the prolonged use of home TPN have not been fully clarified. In previous series patients with duodenocolostomies appeared to be at higher risk than persons with some jejunum or ileum remaining in situ. METHODS: The records of 42 patients treated with home TPN for more than 1 year were examined. This constituted 283 person-years of home TPN. Patients with duodenocolostomies were examined as a separate group on the basis of the literature experience. RESULTS: Six of 42 patients who received chronic home TPN had ESLD with 100% subsequent mortality, at an average of 10.8 +/- 7.1 months after the initial bilirubin elevation. Thirteen of 42 patients had superior mesenteric artery or vein thrombosis (SMT) leading to duodenocolostomy. In 8 of these 13 patients with SMT and underlying inflammatory or malignant disorder, 2 had ESLD. The remaining 5 SMT patients who had only minimal liver enzyme elevation over 13.6 +/- 6.7 (range 3 to 19) years of home TPN were significantly younger (36 +/- 7 years vs 64 +/- 13 years) and did not have underlying inflammation either by clinical diagnosis or as reflected in the high normal serum albumin level (> or = 4.0 g/dL). Despite their extreme short bowel syndrome and long exposure to home TPN, ESLD did not develop. CONCLUSIONS: Approximately 15% of patients who receive prolonged TPN have ESLD with a high rate of morbidity and mortality. The combination of chronic inflammation and the short bowel syndrome appears to be necessary for the development of ESLD with prolonged home TPN.

Adult↗

Colonization with broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units during a nonoutbreak period: prevalence, risk factors, and rate of infection.

OBJECTIVE: To define the epidemiology of broad-spectrum cephalosporin-resistant gram-negative bacilli in intensive care units (ICUs) during a nonoutbreak period, including the prevalence, the risk factors for colonization, the frequency of acquisition, and the rate of infection. DESIGN: Prospective cohort study. SETTING: Tertiary care hospital. PATIENTS: Consecutive patients admitted to two surgical ICUs. MAIN OUTCOME MEASUREMENTS: Serial patient surveillance cultures screened for ceftazidime (CAZ) resistance, antibiotic and hospital exposure, and infections. RESULTS: Of the 333 patients enrolled, 60 (18%) were colonized with CAZ-resistant gram-negative bacilli (CAZ-RGN) at admission. Clinical cultures detected CAZ-RGN in only 5% (3/60) of these patients. By using logistic regression, CAZ-RGN colonization was associated with duration of exposure to cefazolin (odds ratio, 10.3; p < or = .006) and to broad-spectrum cephalosporins/penicillins (odds ratio, 2; p < or = .03), Acute Physiology and Chronic Health Evaluation III score (odds ratio, 1.2; p < or = .008), and previous hospitalization (odds ratio, 3.1; p < or = .006). Of the 100 patients who remained in the surgical ICU for > or = 3 days, 26% acquired a CAZ-RGN. Of the 14 infections caused by CAZ-RGN, 11 (79%) were attributable to the same species present in surveillance cultures at admission to the surgical ICU. CONCLUSIONS: Colonization with CAZ-RGN was common and was usually not recognized by clinical cultures. Most patients colonized or infected with CAZ-RGN had positive surveillance cultures at the time of admission to the surgical ICU, suggesting that acquisition frequently occurred in other wards and institutions. Patients exposed to first-generation cephalosporins, as well as broad-spectrum cephalosporins/penicillins, were at high risk of colonization with CAZ-RGN. Empirical treatment of nosocomial gram-negative infections with broad-spectrum cephalosporins, especially in the critically ill patient, should be reconsidered.

Aged↗

[Ultrasonography contrast media Levovist and power Doppler in the study of the breast. Methodology, vascular morphology and automatic enhancement quantification with wash-in and wash-out curves].

PURPOSE: To define the technique for contrast-enhanced power Doppler US studies of breast lesions and to identify possible clinical applications. MATERIAL AND METHODS: We studied 51 breast lesions detected at mammography and confirmed at cytology and/or surgical biopsy; 15 were benign lesions and 36 carcinomas, namely 14 T1ab, 29 T1c and 8 T2. We found 14 masses with regular margins, 28 with irregular margins, 1 asymmetric density, 2 architectural distortions and 6 clustered calcifications. US studies were performed with an AU5 Harmonic unit (Esaote Biomedica, Genoa, Italy) equipped with a software for online image storage, analysis and automatic quantification of US signal intensity changes after contrast agent injection, namely wash-in and wash-out contrast enhancement curves. The echocontrast agent Levovist (Schering AG, Berlin, Germany), 4.0 g preparation, was administered by i.v. injection (cubital vein) in two times at a concentration of 400 mg/mL. The first 4 mL of Levovist suspension were injected as a bolus at approximately .5 mL/s to evaluate lesion vascularization and choose the best scanning plane for wash-in and wash-out quantification. The remaining 6 mL of Levovist suspension were injected at approximately 1.0 mL/s and dedicated to wash-in and wash-out recording. RESULTS: The region of interest could not be identified in 2 of 6 calcifications. After Levovist administration, signal enhancement was seen in 36 lesions. Nonsignificant curves were obtained in 7 fibroadenomas, 1 fibrocystic mastopathy and 5 carcinomas. Pathology diagnosed an in situ component around the lesion core (true positives) in 12 carcinomas with perilesional vessels and also 3 more carcinomas with perilesional foci in situ missed at contrast-enhanced US (false negatives). The wash-in/wash-out curves of 30 carcinomas differed from those of the 6 fibroadenomas, in that the former had faster wash-in and an earlier enhancement peak, as well as longer enhancement than the latter. Moreover, fibroadenoma curves are regularly increasing, with moderate variations. As for wash-out, carcinomas exhibited three main patterns, namely a monophasic, a polyphasic and a plateau pattern. DISCUSSION: The pattern of enhancement curves in fibroadenomas is related to straight and regular vessels, while arteriovenous shunts in carcinomas cause early signal intensity peaks. Wash-out is longer in carcinomas than in fibroadenomas because the former present anarchic and tortuous vessels with slow flows. CONCLUSIONS: Levovist enhanced US is a complementary test to study known breast lesions which permits the differential diagnosis of carcinomas and fibroadenomas. Our results justify a larger clinical trial to assess the role of this technique for diagnosis, prognosis and staging purposes.

Adult↗

[Breast carcinoma diagnosed in mammographic screening incidentally. Research on the radiologic signs in prior mammograms].

PURPOSE: To determine how many cancers screen-detected at subsequent rounds were already visible on previous screening mammograms, and to study their radiological features. MATERIALS AND METHODS: The previous screening mammograms of 100 women who had cancers screen-detected at subsequent rounds (group A), and the negative screening mammograms of 200 women (group B) who had a further negative screening test two years later, were mixed for a new reading. The two groups were similar for age and year of examination. These films were blindly reviewed by 5 radiologists. Then, mammograms were reviewed retrospectively, with knowledge of subsequent diagnostic results. Finally the A group findings were classified as: 1) true negative: no radiological signs; 2) minimal sign: a nonspecific abnormality is retrospectively visible at the site of subsequent cancer; 3) false negative: "she should have been recalled"; 4) misdiagnosis at assessment: the woman had been recalled, but the cancer was missed after the assessment procedures. RESULTS: 60% of cases were true negatives, 29% were minimal signs, 9% were false negative and 2% were misdiagnosed at assessment. The most common radiological sign found among false negative cases was an architectural distortion: opacities and calcifications were more frequent among minimal signs. Only 10 of 40 cancers retrospectively visible on previous mammograms had reached stage II at diagnosis. At blinded review, the radiologists found false abnormalities in a considerable number of healthy women (average: 29%). DISCUSSION AND CONCLUSIONS: Our study shows that mammography sensitivity can be improved. Cancer radiological signs may go undetected due to difficult interpretation (opacities, calcifications) or perception (architectural distortions). The use of a low threshold of suspicion (as in a reading test) in real screening might permit to detect more cancers (most of them, however, would not reach advanced stages at subsequent rounds), but might also lead to many unnecessary assessments and, probably, to some benign biopsies in healthy women. In conclusion, an attempt at improving mammography sensitivity by lowering the threshold of suspicion can not be directly recommended due to the considerable negative effects related to a loss in specificity. A reading test similar to the one presented in our study would be a useful training procedure for radiologists who are involved in a screening program.

Breast Neoplasms↗

Effects of human recombinant growth hormone (rhGH) on inflammatory responses in patients undergoing abdominal aortic aneurysm repair.

BACKGROUND: Human recombinant growth hormone (rhGH) has been shown to increase skeletal muscle protein synthesis and improve nitrogen balance in critically ill patients and those undergoing surgery. rhGH effects on hepatic protein turnover in critically ill patients are less clearly understood. OBJECTIVE: To examine rhGH effects on hepatic acute phase protein responses and inflammatory cytokine release in patients undergoing major surgery. DESIGN: Prospective double blind randomised trial. SETTING: Tertiary referral university teaching hospital. PATIENTS: Patients undergoing elective abdominal aortic aneurysm repair. INTERVENTION: Patients received rhGH (Genotropin, 0.3 IU/kg per day, n = 8) or placebo (n = 10) for 6 days prior to surgery. RESULTS: Blood levels of growth hormone (GH) and insulin-like growth factor (IGF-1) were measured following rhGH treatment and C-reactive protein (CRP), serum amyloid A (SAA) and the cytokines interleukin-6 (IL-6) and the IL-1 receptor antagonist (IL-1ra) were measured for up to 24 h following surgery. Significant increases in plasma rhGH (0.84 +/- 0.3, mean (sem) versus 52 +/- 20 mU/l, p < 0.0008) and IGF-1 levels (119 +/- 13 versus 644 +/- 110 ng/ml, p < 0.0001) were seen prior to surgery following rhGH administration. No differences in acute phase protein or cytokine levels were seen following surgery in patients receiving rhGH. CONCLUSIONS: These results indicate that pre-operative administration of rhGH does not alter acute phase protein or inflammatory cytokine release in response to major surgery.

Aged↗

A group treatment approach to failure to toilet train: the case of Max.

Toilet training is a major developmental milestone for children and parents. Accurate statistics on the prevalence of toilet-training failure do not exist; however, it is estimated that approximately 4% of 4-year-olds are not bowel trained. A number of biopsychosocial and developmental factors can interfere with toilet training. Frequently, a cycle of withholding and constipation with painful bowel movements and/or overflow incontinence ensues. A case study of a 4-year-old boy with encopresis and pervasive developmental disorder will highlight an interdisciplinary team's approach to helping children (4-6 years old) toilet train. Along with individual patient care management, parents and children attended (separately) a six-session medical and psychoeducational group called "Toilet School." This group model employs the principles of behavior modification, the concepts of children's preoperational thinking, and a philosophy of care that values collaborative relationships between caregivers and families.

Autistic Disorder↗

Bcl-2 and c-myc expression, cell cycle kinetics and apoptosis during the progression of chronic myelogenous leukemia from diagnosis to blastic phase.

Chronic myelogenous leukemia (CML) has a progressive course but little is known about the biologic characteristics of disease progression. This study was designed to assess the changes in cell proliferative characteristics, apoptosis, the expression of the bcl-2 and c-myc genes between the time of initial diagnosis and entrance into the blastic phase of the disease. We observed that the rate of cell proliferation decreased and the cell death rate did not significantly change as the disease accelerated. The level of bcl-2 expression was significantly higher in accelerated/blastic phase cells than in the chronic phase cells in the population as a whole, however, the bcl-2 expression level did not change in blast cell subpopulation. c-myc Expression was significantly higher in the blast cell subpopulation of accelerated/blastic phase than in that of earlier phases of the disease. In conclusion, the characteristics of CML cells, namely proliferation rate, c-myc and bcl-2 change during the course of the disease. It is possible that the change in c-myc expression plays a causative role in evolution of the blastic phase from the chronic phase.

Adult↗

Safety and immunogenicity of a bivalent Haemophilus influenzae type b/hepatitis B vaccine in healthy infants. Hib-HB Vaccine Study Group.

OBJECTIVE: To assess the safety, tolerability and immunogenicity of COMVAX, a liquid, bivalent Haemophilus influenzae type b-hepatitis B vaccine, containing the polyribosylribitol phosphate (PRP)-Neisseria meningitidis outer membrane protein complex conjugate used in the Hib vaccine, PedvaxHIB, and the yeast-derived hepatitis B surface antigen (HBsAg) used in the HB vaccine, RECOMBIVAX HB. DESIGN: Eight hundred eighty-two healthy infants, approximately 2 months of age, were enrolled in an open, multicenter (n = 11) clinical trial and randomized to receive either COMVAX (7.5 micrograms of PRP/5 micrograms of HBsAg in 0.5 ml) or concurrent injections of the liquid formulation of PedvaxHIB (P) (7.5 micrograms of PRP in 0.5 ml) and RECOMBIVAX HB (R) (5 micrograms of HBsAg in 0.5 ml) at 2, 4 and 12 or 15 months of age. Safety and tolerability were monitored after each injection. The serum concentrations of anti-PRP and anti-HBs were determined at the time of each vaccination, 2 months after the second vaccination and 1 month after the third vaccination. RESULTS: COMVAX was well-tolerated and proved to be immunologically comparable with a series of concomitant P+R injections. There were no serious adverse experiences attributable to the study vaccines. The most commonly reported nonserious adverse experiences were all events prelisted on diary cards given to parents. These included generally mild and transient signs of inflammation at the injection site (pain/ soreness, erythema, swelling/induration), somnolence and irritability. Because children are at peak risk of invasive Hib disease during the first year of life, 6 months of age (2 months after the second dose of vaccine) was designated the time of primary interest with regard to the development of anti-PRP. At that time 94.8% of the infants given COMVAX had > 0.15 microgram/ml of anti-PRP and 72.4% had > 1.0 microgram/ ml, with a geometric mean concentration (GMC) of 2.5 micrograms/ml, compared with 95.2%, 76.3% and 2.8 micrograms/ml, respectively, in recipients of P+R. The third injection given at 12 or 15 months of age induced a secondary rise in antibody. The proportions with > 0.15 microgram/ml and > 1.0 microgram/ml of anti-PRP increased to 99.3 and 92.6%, respectively, and the GMC rose to 9.5 micrograms/ml among COMVAX recipients, compared with 98.9%, 92.3% and 10.2 micrograms/ml in children given concurrent injections of P+R. In contrast to Hib few infants in countries with low endemicity of HBV infection are at near term risk of exposure to virus. Consequently the anti-HBs response after the last dose of vaccine was designated the outcome of primary interest. At 13 to 16 months of age (1 month after the third dose of vaccine) 98.4% of children given COMVAX had a protective anti-HBs concentration of > or = 10 mIU/ml with a GMC of 4468 mIU/ml, compared with 100% and a GMC of 6944 mIU/ml among children given P+R. CONCLUSIONS: COMVAX is well-tolerated by healthy infants and can induce immunity against invasive Hib disease and HBV infection using only three injections compared with six injections if separate courses of monovalent PedvaxHIB and RECOMBIVAX HB are given.

Antibodies, Bacterial↗

Immunological and physiological responses to aortic surgery: effect of reperfusion on neutrophil and monocyte activation and pulmonary function.

BACKGROUND: The aims of this study were to evaluate the effects of aortic clamping and unclamping on neutrophil and monocyte activation and release of plasma mediators in 20 patients undergoing elective aortic aneurysm surgery, and to correlate these findings with pulmonary haemodynamics and gas exchange. METHODS: Simultaneous arterial and mixed venous samples were obtained during and after aortic clamping and unclamping. RESULTS: Neutrophil respiratory burst activity in mixed venous samples increased significantly during the period of aortic clamping. An initial increase in neutrophil CD11b expression in venous blood 5 min after clamp removal was followed by a significant decrease in level of expression. Plasma tumour necrosis factor levels increased at the end of the cross-clamp period and reached a maximum 60 min following reperfusion. There was a significant and sustained rise in plasma thromboxane B2 levels following clamp removal. This increase correlated with the development of increased pulmonary vascular resistance. CONCLUSION: This study confirms the central role played by activated neutrophils in the early stages of reperfusion injury and also suggests a role for plasma mediators in mediating cardiopulmonary dysfunction during major vascular surgery.

Aged↗

Nitric oxide attenuates interleukin 2-induced lung injury.

BACKGROUND: The pathogenesis of interleukin (IL) 2-induced vascular leak syndrome may be related to neutrophil-mediated endothelial injury. Nitric oxide inhibits neutrophil superoxide anion synthesis and adherence to endothelial cells. The role of systemic nitric oxide in preventing IL-2-induced lung injury was studied in an experimental model. METHODS: Sprague-Dawley rats (seven per group) were randomized to control, IL-2 treatment (1 x 10(6) units), and IL-2 with sodium nitroprusside 0.2 mg/kg. Lung injury was measured by estimation of extravascular lung water (wet:dry weight) and bronchoalveolar lavage (BAL) protein concentration, and by histological findings. Neutrophil infiltration was evaluated by measuring myeloperoxidase activity and BAL neutrophil concentration. RESULTS: IL-2 produced significant lung damage characterized by leucocyte sequestration (increased myeloperoxidase and BAL neutrophil concentrations), pulmonary congestion and microvascular protein leakage (increased wet:dry weight ratio and BAL protein concentration). This injury was reduced significantly by the addition of sodium nitroprusside, the nitric oxide donor. CONCLUSION: Nitric oxide reduces IL-2-induced lung injury.

Animals↗

The economic impact on families of children's participation in junior sport.

The study investigated the socio-economic consequences for families of participation in junior sport. Two hundred and twenty families in Queensland and Victoria were surveyed from the sports of cricket, Australian football, gymnastics, hockey, netball and tennis and twenty seven of these interviewed. The study showed that parents make a substantial contribution in terms of financial support to their children's participation in junior sport. Each of the sports mode different financial demands on families depending on the yearly cycle of training and competition, distance from facilities and coaching, costs associated with coaching, equipment and uniforms, and representative level. It is concluded that family income and structure are the key factors in determining the likelihood of a child's involvement in junior sport, and that for many Australian children, financial factors may be barriers to their participation in junior sport.

Adolescent↗

Glyceryl trinitrate prevents neutrophil activation but not thromboxane release following ischaemia-reperfusion injury.

The aim of this study was to determine whether glyceryl trinitrate (GTN) has a protective effect on neutrophil-mediated lung injury in a model of aortic occlusion (30 min) and reperfusion (120 min). Sprague-Dawley rats were randomized into control (n = 11), ischaemia-reperfusion (IR) (n = 12), and IR treated with GTN (2 micrograms kg-1 min-1) during reperfusion (n = 10). Myeloperoxidase (MPO) activity measured pulmonary neutrophil influx. Pulmonary endothelial permeability was measured by wet:dry weight ratio, bronchoalveolar lavage (BAL) protein and neutrophil counts. Neutrophil superoxide release was measured by flow cytometry in a further IR versus GTN experiment (n = 6 in each group). The significant increase in MPO activity produced by IR to a level of 7.99 units g-1 was prevented by GTN which reduced the level to 4.73 units g-1. The increase in pulmonary microvascular leakage after reperfusion was also prevented by GTN: BAL protein without GTN was 992 micrograms ml-1 and with GTN 579 micrograms ml-1; BAL neutrophil count without GTN was 3219 cells mm-3 and with GTN 820 cells mm-3; the wet:dry lung weight ratio without GTN was 3.8 and with GTN 3.3. Neutrophil superoxide release increased significantly after 40 min of reperfusion in the untreated IR group (P < 0.05). This increase was prevented in the GTN-treated group. GTN administration had no effect on plasma thromboxane production during revascularization. These data suggest that GTN administration during the reperfusion phase has the potential to decrease pulmonary microvascular injury.

Animals↗

Systemic cytokine administration alters the histology of the eruption of lymphocyte recovery.

The eruption of lymphocyte recovery occurs after marrow ablative antineoplastic chemotherapy, with the earliest reappearance of lymphocytes in the peripheral circulation. The typical histopathologic findings are not specific, consisting of a perivascular lymphocytic infiltrate in the upper dermis with mild overlying epidermal changes. Since the initial report, 21 additional biopsy specimens from eruptions of lymphocyte recovery were obtained at our institution. Of these specimens, 18 displayed the expected findings while 3 specimens contained a relatively heavy lymphocytic infiltrate with nuclear pleomorphism and hyperchromasia. The majority of lymphocytes from the heavily inflamed tissues expressed CD3 and CD4; rare CD8+ cells were observed. The cells with large irregular nuclear contours displayed an "activated" phenotype, consisting of CD30, HLA-DR, and CD25, accounting for roughly 50% of the total infiltrate. The three patients from whom these specimens were obtained had received human recombinant cytokines in pharmacologic doses (2 granulocyte-macrophage colony stimulating factor, 1 interleukin-3). Three patients in this series also received human recombinant cytokines, but developed eruptions with the typical scant infiltrate of small lymphocytes. These findings extend the histologic spectrum of the eruption of lymphocyte recovery and suggest that the administration of human recombinant cytokines prior to marrow recovery may alter the appearance and phenotype of lymphocytes migrating into the skin.

Adult↗