The Impact of Varying Nipple Properties on Infant Feeding Physiology and Performance Throughout Ontogeny in a Validated Animal Model.

Infant feeding requires successful interactions between infant physiology and the maternal (or bottle) nipple. Within artificial nipples, there is variation in both nipple stiffness and flow rates, as well as variation in infant physiology as they grow and mature. However, we have little understanding into how infants interact with variable nipple properties to generate suction and successfully feed. We designed nipples with two different stiffnesses and hole sizes and measured infant feeding performance through ontogeny using a pig model. We evaluated their response to nipple properties using high-speed X-Ray videofluoroscopy. Nipple properties substantially impacted sucking physiology and performance. Hole size had the most profound impact on the number of sucks infants took per swallow. Pressure generation generally increased with age, especially in nipples where milk acquisition was more difficult. However, most strikingly, in nipples with lower flow rates the relationship between suction generation and milk acquisition was disrupted. In order to design effective interventions for infants with feeding difficulties, we must consider how variation in nipple properties impacts infant physiology in a targeted manner. While reducing flow rate may reduce the frequency an infant aspirates, it may impair systems involved in sensorimotor integration.

The contractile patterns, anatomy and physiology of the hyoid musculature change longitudinally through infancy.

All mammalian infants suckle, a fundamentally different process than drinking in adults. Infant mammal oropharyngeal anatomy is also anteroposteriorly compressed and becomes more elongate postnatally. While suckling and drinking require different patterns of muscle use and kinematics, little insight exists into how the neuromotor and anatomical systems change through the time that infants suckle. We measured the orientation, activity and contractile patterns of five muscles active during infant feeding from early infancy until weaning using a pig model. Muscles not aligned with the long axis of the body became less mediolaterally orientated with age. However, the timing of activation and the contractile patterns of those muscles exhibited little change, although variation was larger in younger infants than older infants. At both ages, there were differences in contractile patterns within muscles active during both sucking and swallowing, as well as variation among muscles during swallowing. The changes in anatomy, coupled with less variation closer to weaning and little change in muscle firing and shortening patterns suggest that the neuromotor system may be optimized to transition to solid foods. The lesser consequences of aspiration during feeding on an all-liquid diet may not necessitate the evolution of variation in neuromotor function through infancy.

Biopsychosocial factors associated with depression and anxiety in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Depression and anxiety are amongst the most prevalent mental health disorders in the older population with intellectual disability (ID). There is a paucity of research that pertains to associative biopsychosocial factors for depression and anxiety in this population. The aim of this study is to determine the biopsychosocial factors associated with depression and anxiety in a population of older adults with ID in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. Depressive symptoms were assessed using the Glasgow Depression Scale for people with a Learning Disability. Anxiety symptoms were measured using the Glasgow Anxiety Scale for people with a Learning Disability. The cross-sectional associations of depression and anxiety with biopsychosocial parameters were measured using a variety of self-report and proxy-completed questionnaires. RESULTS: For the study population, 9.97% met the criteria for depression, and 15.12% met the criteria for an anxiety disorder. Participants meeting criteria for depression were more likely to be taking regular mood stabiliser medications and to exhibit aggressive challenging behaviour. Participants meeting criteria for anxiety were more likely to have sleep difficulties and report loneliness. Participants meeting criteria for either/both depression and anxiety were more likely to report loneliness. CONCLUSIONS: This study identified both treatable and modifiable, as well as unmodifiable, biopsychosocial factors associated with depression and/or anxiety in older adults with ID. A longitudinal study follow-up will further develop our knowledge on the causality and direction of associated biopsychosocial factors with depression and anxiety in older adults with ID and better inform management strategies, prevention policies and funding of services.

The association of life events and mental ill health in older adults with intellectual disability: results of the wave 3 Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing.

BACKGROUND: Exposures to life events are associated with emotional, psychological and behavioural problems in those with intellectual disability (ID). Older adults with ID may experience different life events given differences in living circumstances, cognitive decline, greater dependency on others and less autonomy. This study examines the relationship of life events and mental ill health in an older ID population in Ireland. METHODS: The study was part of 'The Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing'. The frequency of life events was assessed using a 20-item checklist, and the level of stress experienced was assessed using a three-point Likert scale measuring the burden of the life event. The associations of life events with factors associated with mental ill health were measured using a variety of self-report and proxy completed questionnaires. RESULTS: For the study population, 88.1% had been exposed to at least one life event in the preceding 12 months and 64.5% to two or more life events. Frequency and burden of life events were significantly higher in individuals living in institutional settings and in individuals with any current psychiatric condition, increased depressive and anxiety symptoms, challenging behaviour and reported poorer self-rated mental and physical health. More life events were significantly associated with new psychiatric diagnoses as well as initiation and increased dosage of mood stabilising, hypnotic and sedative medications. CONCLUSIONS: Life events are significantly associated with mental ill health in the older ID population. Service providers must focus on limiting the exposure to these events and, in situations where they cannot be avoided, should support and manage individuals compassionately and effectively, prioritising their mental and physical well-being.

Impact of a national audit on child and adolescent psychiatrists' prescribing practices.

BACKGROUND: A look back review of South Kerry Child and Adolescent Mental Health Services (CAMHS) in Ireland, known as the 'Maskey report' (MR), highlighted substandard prescribing practices. The aim of this 'Maskey Impact Study' (MIS) was to explore changes to child and adolescent psychiatrists' prescribing practices following the MR. METHOD: The study was cross-sectional and mixed method. A study specific questionnaire was distributed electronically to psychiatrists working in CAMHS (n = 160). RESULTS: 102 psychiatrists participated in the study (response rate 63.8%). Perceived improvement in prescribing practices included improved medical record keeping (63.7%), consent documentation (53.9%), medication information provision (41.2%) and physical health monitoring (60.8%). However, 43.1% of psychiatrists reported a reluctance to prescribe medication even when clinically indicated and 50% were more likely to avoid off-label use. Most respondents reported increased stress levels (80.4%) with higher stress being significantly associated with reticence in prescribing (χ2 = 11.746, p < .001) and avoiding off-label use (χ2 = 15.392, p < 0.001). Thematic analysis highlighted increased medication hesitancy, enforced 'meaningless' bureaucracy and medication mistrust among families. DISCUSSION: Although improvements reported are welcomed, the increased hesitancy of medication use, avoidance of prescribing more than one medication, and avoidance of off-label use, is of concern with potential unintended adverse consequences. Reluctance in prescribing may deprive youth of access to evidence-based treatments and limit exposure of NCHDs to the safe practice of consultant-initiated psychopharmacology. Further research will be important to determine if this impacts clinical care. Continued education in psychopharmacology is essential along with increased public awareness of the evidence for medication, to help restore public confidence and trust in psychopharmacology.

A qualitative study exploring the challenges for a national police force as first responders to children and young people presenting with mental health crises: perspectives of emergency department professionals.

INTRODUCTION: The difficulties in accessing Child and Adolescent Mental Health Services (CAMHS) and the lack of out-of-hours and crises services have resulted in Ireland's national police force, An Garda Síochána (GS), becoming increasingly involved as first responders to children and young people (CYP) who are experiencing potential mental health crises. AIMS: To outline challenges faced by members of GS and emergency department (ED) professionals in such cases. METHOD: Qualitative study design with semi-structured interviews conducted with a convenience sample of medical and mental health professionals (n = 11) from a paediatric ED who are frequently involved with the interface between GS and CYP experiencing potential mental health crises. Thematic analysis was conducted on transcribed interviews using the software package MaxQDA to systematically organise and code transcriptions. RESULTS: Participants highlighted a lack of appropriate clinical settings within the ED for CYP who attend with a mental health crisis through GS. Whilst participants described positive rapport between GS and ED staff, interactions between GS and patients were identified as challenging. Knowledge gaps amongst members of GS in Mental Health Act (MHA) legislation and restraint were also identified as contributory stressors for GS and emergency department professionals. CONCLUSION: The increased prevalence of CYP mental health issues and psychosocial stressors in conjunction with difficulty in accessing CAMHS means that challenges faced by GS as first responders are likely to continue. Research is needed to quantify the adverse personal impacts on GS along with the potential negative impact on youth. Access to emergency mental health review for youth is essential to optimise the experience of both groups.

Sleep problems in children and adolescents in an attention deficit hyperactivity disorder service.

OBJECTIVES: Sleep problems are common amongst children and adolescents with attention deficit hyperactivity disorder (ADHD). The purpose of this study was to investigate sleep problems in children and adolescents attending a specialist ADHD service. METHODS: This was a cross-sectional online survey combined with a retrospective chart review, conducted in the ADHD Assessment, Diagnosis, Management, initiation, Research and Education (ADMiRE) service, the first public specialist ADHD service for young people in Ireland. Participants were caregivers of children and adolescents with ADHD attending ADMiRE. Sleep was assessed using The Children's Sleep Habits Questionnaire (CSHQ) and ADHD symptoms were assessed using an abbreviated version of the Swanson, Nolan and Pelham Teacher and Parent Rating Scale (SNAP-IV). Details regarding patient demographics, co-morbidities and medication were collected from patient records. RESULTS: Eighty-four percent of young people scored above the clinical cut-off for a sleep disorder. The most frequently reported sleep problems were related to sleep onset and sleep duration, and 64% of respondents met the criteria for two or more sleep problems. ADHD severity was associated with greater sleep problems. Co-morbid physical, neurodevelopmental, and mental health disorders as well as stimulant use were not associated with greater sleep problems. CONCLUSION: Sleep problems are very common amongst children and adolescents with ADHD. This study has demonstrated an association between more sleep problems and ADHD severity. These findings highlight the need for both effective ADHD treatment to ensure optional sleep in young people as well as effective interventions for sleep problems to prevent worsening of ADHD symptoms.

The Function of the Mammal Extrinsic Tongue Musculature in the Transition from Suckling to Drinking.

The transition from suckling to drinking is a developmental pathway that all mammals take. In both behaviors, the tongue is the primary structure involved in acquiring, transporting, and swallowing the liquid. However, the two processes are fundamentally different: during suckling, the tongue must function as a pump to generate suction to move milk, whereas during drinking, the tongue moves backwards and forwards through the mouth to acquire and move water. Despite these fundamental differences, we have little understanding of how tongues role varies between these behaviors. We used an infant pig model to investigate the relationships between anatomy, physiology, and function of the tongue to examine how lingual function is modulated in the transition from infancy to adulthood. We found that while some muscles were proportionally largest at birth, others were proportionally larger at the time of weaning. Furthermore, we found variation in tongue movements between suckling and drinking along both the mediolateral and anteroposterior axes, resulting in differences in tongue deformation between the two behaviors. The extrinsic tongue muscles also changed in function differently between drinking and suckling. Genioglossus increased its activity and turned on and off earlier in the cycle during drinking, whereas hyoglossus fired at lower amplitudes during drinking, and turned on and off later in the cycle. Together, the data highlight the significant need for high neuroplasticity in the control of the tongue at a young age in mammals and suggest that the ability to do so is key in the ontogeny and evolution of feeding in these animals.

Regional Variation in Contractile Patterns and Muscle Activity in Infant Pig Feeding.

At the level of the whole muscle, contractile patterns during activity are a critical and necessary source of variation in function. Understanding if a muscle is actively lengthening, shorting, or remaining isometric has implications for how it is working to power a given behavior. When feeding, the muscles associated with the tongue, jaws, pharynx, and hyoid act together to transport food through the oral cavity and into the esophagus. These muscles have highly coordinated firing patterns, yet also exhibit high levels of regional heterogeneity in both their timing of activity and their contractile characteristics when active. These high levels of variation make investigations into function challenging, especially in systems where muscles power multiple behaviors. We used infant pigs as a model system to systematically evaluate variation in muscle firing patterns in two muscles (mylohyoid and genioglossus) during two activities (sucking and swallowing). We also evaluated the contractile characteristics of mylohyoid during activity in the anterior and posterior regions of the muscle. We found that the posterior regions of both muscles had different patterns of activity during sucking versus swallowing, whereas the anterior regions of the muscles did not. Furthermore, the anterior portion of mylohyoid exhibited concentric contractions when active during sucking, whereas the posterior portion was isometric during sucking and swallowing. This difference suggests that the anterior portion of mylohyoid in infant pigs is functioning in concert with the tongue and jaws to generate suction, whereas the posterior portion is likely acting as a hyoid stabilizer during sucking and swallowing. Our results demonstrate the need to evaluate both the contractile characteristics and activity patterns of a muscle in order to understand its function, especially in cases where there is potential for variation in either factor within a single muscle.

Implementation of ironXS: a study of the acceptability and feasibility of genetic screening for hereditary hemochromatosis in high schools.

Hereditary hemochromatosis (HH), most often due to HFE C282Y homozygosity, is an iron overload disorder that can result in severe morbidity including hepatic cirrhosis. Predisposition to HH is easily diagnosed and morbidity is preventable by maintaining normal body iron and thus calls have been made to introduce community screening. The current study has been designed to assess the acceptability and feasibility of HH screening in high schools. Students (mostly 15-16 years of age) watched a purpose-designed DVD for education about HH. Those with parental consent were then offered cheek-brush screening for C282Y. Students completed a questionnaire prior to screening. The program was offered to 9187 students at 32 schools and 3489 (38%) had screening. Nineteen C282Y homozygotes (1 in 183) and 376 heterozygotes (1 in 9.3) were identified. More than 90% of students answered each of five knowledge questions correctly. Eight homozygotes (42%) had elevated transferrin saturation, but only two (10.5%) had marginally elevated serum ferritin (SF). We have shown that genetic screening for HH can successfully be offered in the high school setting. Ongoing research in this study will answer questions about the impact of high school students learning that they are at risk of HH.

Preterm Birth Impacts the Timing and Excursion of Oropharyngeal Structures during Infant Feeding.

Swallowing in mammals requires the precise coordination of multiple oropharyngeal structures, including the palatopharyngeal arch. During a typical swallow, the activity of the palatopharyngeus muscle produces pharyngeal shortening to assist in producing pressure required to swallow and may initiate epiglottal flipping to protect the airway. Most research on the role of the palatopharyngeal arch in swallowing has used pharyngeal manometry, which measures the relative pressures in the oropharynx, but does not quantify the movements of the structures involved in swallowing. In this study, we assessed palatopharyngeal arch and soft palate function by comparing their movements in a healthy population to a pathophysiological population longitudinally through infancy (term versus preterm pigs). In doing so, we test the impact of birth status, postnatal maturation, and their interaction on swallowing. We tracked the three-dimensional (3D) movements of radiopaque beads implanted into relevant anatomical structures and recorded feeding via biplanar high-speed videofluoroscopy. We then calculated the total 3D excursion of the arch and soft palate, the orientation of arch movement, and the timing of maximal arch constriction during each swallow. Soft palate excursion was greater in term infants at both 7 and 17 days postnatal, whereas arch excursion was largely unaffected by birth status. Maximal arch constriction occurred much earlier in preterm pigs relative to term pigs, a result that was consistent across age. There was no effect of postnatal age on arch or soft palate excursion. Preterm and term infants differed in their orientation of arch movement, which most likely reflects both differences in anatomy and differences in feeding posture. Our results suggest that the timing and coordination of oropharyngeal movements may be more important to feeding performance than the movements of isolated structures, and that differences in the neural control of swallowing and its maturation in preterm and term infants may explain preterm swallowing deficits.

Correction of CD18-deficient lymphocytes by retrovirus-mediated gene transfer.

Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function caused by derangements in CD18 expression. The genetic and functional abnormalities in a lymphocyte cell line from a patient with LAD have been corrected by retrovirus-mediated transduction of a functional CD18 gene. Lymphocytes from patients with LAD were exposed to CD18-expressing retrovirus and enriched for cells that express CD11a and CD18 (LFA-1) on the cell surface. Molecular and functional analyses of these cells revealed (i) one copy of proviral sequence per cell, (ii) viral-directed CD18 RNA that exceeded normal endogenous levels, (iii) normal quantities of CD11a and CD18 protein on the cell surface, and (iv) reconstitution of LFA-1-dependent adhesive function.

Attaining the age threshold for adolescent mental health services: factors associated with transition of care in the independent sector in Ireland.

OBJECTIVES: The transition from adolescent to adult mental health services (AMHS) is associated with disengagement, poor continuity of care and patient dissatisfaction. The aim of this retrospective and descriptive study was to describe the 'care pathways' in an independent mental health service when adolescents reach age 18 and to investigate the level of engagement of those who transitioned to independent AMHS. METHODS: This is a retrospective, naturalistic and descriptive study in design. All patients discharged from the St Patrick's Adolescent Mental Health Service aged 17 years and 6 months and older, during a 3-year period between January 2014 and December 2016, were included. Electronic records were used to collect socio-demographic and clinical details and to determine engagement rates in adolescents who transferred to independent adult services. RESULTS: A total of 180 patients aged over 17 years and 6 months were discharged from the adolescent service. Of these, 45.6% were discharged to their GP, 28.9% to public mental health services and 25.6% to independent mental health services. The majority who transitioned to independent AMHS went to a Young Adult Service, which had high engagement rates at 3 and 12 months post-transition. CONCLUSIONS: In this independent mental health service, less than half of adolescents who reach the transition age are referred onto AMHS. Engagement rates were found to be high among those referred on to a specialised young adult service.

No need for nanny.

The term "nanny state" is regularly used to attack health groups or governments, especially by interest groups bereft of arguments and journalists in search of a cliché. It has become a special favourite of tobacco companies and their supporters. In the present work we argue that the term should be retired in favour of genuine debate on substantive issues.

Immunogenicity of a Staphylococcus aureus-cholera toxin A2/B vaccine for bovine mastitis.

Staphylococcus aureus causes a chronic, contagious disease of the udder, or mastitis, in dairy cows. This infection is often refractory to antibiotic treatment, and has a significant economic impact on milk production worldwide. An effective vaccine to prevent S. aureus mastitis would improve animal health, reduce antibiotic dependence and inform human vaccine approaches. The iron-regulated surface determinant A (IsdA) and clumping factor A (ClfA) are conserved S. aureus extracellular-matrix adhesins and target vaccine antigens. Here we report the results of two bovine immunogenicity trials using purified IsdA and ClfA-cholera toxin A2/B chimeras (IsdA-CTA2/B and ClfA-CTA2/B). Cows were intranasally inoculated with IsdA-CTA2/B + ClfA-CTA2/B at dry off and followed for 70 days. Trial 1 utilized three groups with one or two booster doses at a total concentration of 600 or 900 µg. Trial 2 utilized two groups with one booster at a total concentration of 1200 µg. Humoral immune responses in serum and milk were examined by ELISA. Responses in serum were significant between groups and provide evidence of antigen-specific IgG induction after vaccination in both trials. Cellular proliferation was detected by flow cytometry using antigen-stimulated PBMCs from day 60 of Trial 2 and revealed an increase in CD4+ T cells from vaccinated cows. IsdA and ClfA stimulation induced IL-4 expression, but not IFN-γ or IL-17, in PBMCs from day 60 as determined by cytokine expression analysis. Opsonophagocytosis of S. aureus confirmed the functional in vitro activity of anti-IsdA antibodies from Trial 2 serum and milk. The vaccine was well tolerated and safe, and results support the potential of mucosally-delivered CTA2/B chimeras to protect cows from mastitis caused by S. aureus.

An in vivo animal model of gene therapy for leukocyte adhesion deficiency.

Leukocyte adhesion deficiency (LAD) is an inherited disorder of leukocyte function that is caused by defects in the CD18 gene and is associated with diminished cell surface expression of CD11/CD18 proteins. We have developed an in vivo model for gene therapy of LAD. Recombinant retroviruses were used to transduce a functional human CD18 gene into murine bone marrow cells which were transplanted into lethally irradiated syngeneic recipients. A reliable flow cytometric assay for human CD18 in transplant recipients was developed based on: (a) the availability of human specific CD18 monoclonal antibodies and (b) the observation that human CD18 can form chimeric heterodimers with murine CD11a on the cell surface. Human CD18 was detected on leukocytes in a substantial number of transplant recipients for at least 6 mo suggesting that the gene had been transduced into stem cells. Expression was demonstrated in several lineages of a variety of hematopoietic tissues, but was consistently highest and most frequent in granulocytes. Murine granulocytes demonstrated appropriate posttranscriptional regulation of human CD18 in response to activation of protein kinase C. No apparent untoward effects of human CD18 expression were noted in transplant recipients. These studies suggest a specific strategy for LAD gene therapy that may be effective and safe.

Intra-operative navigation of a 3-dimensional needle localization system for precision of irreversible electroporation needles in locally advanced pancreatic cancer.

INTRODUCTION: Irreversible electroporation (IRE) uses multiple needles and a series of electrical pulses to create pores in cell membranes and cause cell apoptosis. One of the demands of IRE is the precise needle spacing required. Two-dimensional intraoperative ultrasound (2-D iUS) is currently used to measure inter-needle distances but requires significant expertise. This study evaluates the potential of three-dimensional (3-D) image guidance for placing IRE needles and calculating needle spacing. PATIENTS AND METHODS: A prospective clinical evaluation of a 3-D needle localization system (Explorer™) was evaluated in consecutive patients from April 2012 through June 2013 for unresectable pancreatic adenocarcinoma. 3-D reconstructions of patients' anatomy were generated from preoperative CT images, which were aligned to the intraoperative space. RESULTS: Thirty consecutive patients with locally advanced pancreatic cancer were treated with IRE. The needle localization system setup added an average of 6.5 min to each procedure. The 3-D needle localization system increased surgeon confidence and ultimately reduced needle placement time. CONCLUSION: IRE treatment efficacy is highly dependent on accurate needle spacing. The needle localization system evaluated in this study aims to mitigate these issues by providing the surgeon with additional visualization and data in 3-D. The Explorer™ system provides valuable guidance information and inter-needle distance calculations.

Partial purification and properties of the fatty acid elongation systems in the outer and inner membranes of beef liver mitochondria.

Purified outer membrane of beef liver mitochondria was found to elongate medium chain fatty acyl-CoA primer by the incorporation of [1-14C]acetyl-CoA. This enzymic activity, extracted by Triton X-100, was purified 8-fold by ammonium sulfate fractionation followed by chromatography on a Sephadex column. Purified inner membrane, when processed through an identical purification procedure, yielded a second enzyme system which incorporated [1-14C]acetyl-CoA into long chain fatty acids in the presence of medium chain fatty acyl-CoA primer. This enzyme preparation was about four times as active as the preparation from the outer membrane, and used NADH as the reductant for the synthesis. The molecular weights of the inner and the outer membrane enzyme systems, estimated by gel filtration as well as sucrose density gradient centrifugation, were approx. 57 000 and 126 000, respectively. The partially purified outer membrane enzyme system required NADH and a medium chain acyl-CoA primer for the incorporation of [1-14C]acetyl-CoA into long chain fatty acids. KNC stimulated the reaction. NADPH could substitute for NADH only to a limited extent. Malonyl-CoA was ineffective as a substrate in this reaction. The optimum pH of the reaction was 7.2-7.6 in 0.1 M potassium phosphate buffer. Dithiothreitol, beta-mercaptoethanol, N-ethylmaleimide and high concentrations of ATP and acyl-CoA primer inhibited the reaction. The specificity for the acyl-CoA primer in the reaction was very broad. All the primers tested, C8 to C16, incorporated acetyl-CoA significantly. However, maximum incorporation was observed with dodecanoyl-CoA. Decanoyl-CoA was the best primer for the enzyme system isolated from the inner membrane. About 42% of the radioactivity in the fatty acids synthesized by the outer membrane enzyme system, from myristoyl-CoA and [1-C14]acetyl-CoA, was in palmitic acid. Of the remaining activity, 41% was in stearic acid and about 38% in longer-chain acids. Hence, the elongation of the primer fatty acid by one C2 unit appeared to be the predominant process in this synthesis. In the elongation of myristoyl-C0A by the inner membrane enzyme system, palmitic acid which constituted nearly 78% of the fatty acids synthesized, was the primary product.

Interaction of Fc gamma receptor type IIIB with complement receptor type 3 in fibroblast transfectants: evidence from lateral diffusion and resonance energy transfer studies.

To explore potential inter-receptor interactions between Fc gamma RIIIB, a GPI-linked protein, and the leukocyte integrin CR3, we have prepared transfected 3T3 fibroblast cell lines expressing Fc gamma RIIIB, CR3, or both Fc gamma RIIIB and CR3. We test the hypothesis that Fc gamma RIIIB and CR3 are physically associated in membranes using fluorescence recovery after photobleaching (FRAP) and resonance energy transfer (r.e.t.) microscopy. Cells expressing Fc gamma RIIIB alone displayed a diffusion coefficient (D) of 3.4 x 10(-9) (+/- 2.9 x 10(-9) cm2/second and a mobile fraction (m.f.) of 0.73 (+/- 0.10). In contrast, Fc gamma RIIIB exhibited D = 2.5 x 10(-9) (+/- 1.4 x 10(-9) cm2/second (n.s.) and a m.f. of 0.48 (+/- 0.08) (p < 0.01) on cells expressing both Fc gamma RIIB and CR3, thus indicating that co-expression of CR3 constrains the lateral diffusion of Fc gamma RIIIB. To further test for a direct physical interaction between these gene products, (r.e.t.) microscopy was performed. Donor-labeled anti-CR3 and acceptor-labeled anti-Fc gamma RIIIB on cells expressing both receptors yielded a r.e.t. photon count rate of 8.9(+/- 6.4) kilocounts/second (kC/s), whereas CR3-to-CR3 measurements gave 1.6(+/- 0.6) kC/s (p < 0.01). Moreover, the addition of exogenous agents such as N-acetyl-D-glucosamine, but not indomethacin, diminished the magnitude of these interactions in transfectant membranes. These data support the notion that a subpopulation of Fc gamma RIIIB is physically associated with CR3 and that this association can be affected by exogeneous compounds.