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The underlying basis for hypogammaglobulinaemia in patients with chronic lymphatic leukaemia (CLL) was investigated by measurement of immunoglobulin produced in vitro in cultures of pokeweed mitogen-stimulated B and T lymphocytes. B and T cells were separated by sheep red blood cell rosette techniques and, by culture of these cells from CLL patients in various combinations with B or T cells from normal subjects, it was possible to measure independently the function of B lymphocytes and the helper or suppressor function of T lymphocytes. By these methods it was found that the B lymphocytes of six of eight patients failed to produce immunoglobulins in vitro. B lymphocytes from two patients appeared to produce immunoglobulins in vitro. T lymphocytes from five of the eight patients had low or undetectable helper T cell function and in six patients their T lymphocytes had excessive suppressor activity in comparison to T lymphocyte populations from normal subjects. Whether the primary abnormality in the CLL T cell populations was a deficiency of helper T cells or excess of suppressor T cells was uncertain from these studies. These results suggest that immunoglobulin production by B lymphocytes from most patients with CLL was abnormal but also that T cells from CLL patients may be abnormal in respect to their role in immunoglobulin production at an early stage of the disease. These findings may assist in understanding the pathogenesis of this disease and lead to new approaches in treatment. [ABSTRACT FROM AUTHOR]

Aims: To examine sleep problems in a population-based sample of school-aged children (8-12yo) with Cerebral Palsy (CP) METHOD: Eighty-six children (mean 9 years, 5 months, SD = 1 year, 6 months; male = 60) with CP (Gross Motor Function Classification System; GMFCS I=46; II=21; III=9; IV=6; V=6) participated. Classifications/assessments included: Sleep Disturbance Scale for Children (SDSC), Gross Motor Function Measure (GMFM-66), Manual Ability Classification System (MACS), Communication Function Classification System (CFCS), Strengths and Difficulties Questionnaire (SDQ) and the Cerebral Palsy- Quality of Life (CP-QOL) Pain Impact subscale. Analysis included linear and logistic regression., Results: 38 (44 %) children were within the clinical range for sleep problems. Sleep problems were significantly associated with epilepsy, (95 % CI) = 14.48 (7.95 to 21.01), gross motor function, -0.13 (-0.26 to -0.01), manual ability, 7.26 (0.82 to 13.69), communication, 10.01 (2.21 to 17.80), child behaviour, 1.134 (0.74 to 1.53), and pain related QOL, 0.33 (0.12 to 0.53). For the multivariable model, sleep problems remained significantly associated with epilepsy, b (95 % CI) = 11.72 (4.88 to 18.57), child behaviour, 1.03 (0.65 to 1.41) and pain-related QOL, 0.21 (0.29 to 0.38)., Conclusions: Sleep problems are common and associated with epilepsy, child behaviour and pain related QOL., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Aim: To describe the development of social function in children with cerebral palsy (CP) classified in all levels of the Communication Function Classification System (CFCS)., Method: This prospective, longitudinal population-based cohort study recruited children with CP born in Queensland, Australia. Social functioning was measured using the Pediatric Evaluation of Disability Inventory (PEDI) social function domain at 2 years, 2 years 6 months, 3 years, 4 years, and 5 years, and the PEDI Computer Adaptive Test (PEDI-CAT) social/cognitive domain at 8 to 12 years., Results: Seventy-four children provided 356 observations. PEDI-CAT social/cognitive scaled scores at 8 to 12 years were (mean [SD] n) CFCS level I, 68.6 (2.7) 45; CFCS level II, 64.0 (3.4) 10; CFCS level III, 63.5 (3.7) 4; CFCS level IV, 56.8 (5.0) 9; CFCS level V, 47.2 (5.8) 6. Scores within expected range for age (not less than 2 SD below mean) at 8 to 12 years were achieved by 35 (78%) children in CFCS level I and four (14%) in CFCS levels II to V. Forty-nine per cent of children scored at least two standard deviations below the population mean on a proxy measure of fluid intelligence. Intellectual impairment was associated with lower PEDI-CAT social/cognitive scaled scores in univariable analysis (β = -8.3, 95% confidence interval - 10.91 to -5.63; p < 0.001) but had a smaller effect when modelled together with CFCS., Interpretation: Social function attained by 8 to 12 years of age was strongly related to level of communication function (CFCS). The small number of children classified in CFCS levels II to V necessitates caution when viewing these individual CFCS level trajectories., What This Paper Adds: There is a strong relation between social functioning and Communication Function Classification System (CFCS) levels. At 8 to 12 years, 35 out of 45 children in CFCS level I met social functioning age expectations. Twenty-five out of 29 in CFCS levels II to V had social functioning below that expected for age. CFCS and age were more strongly associated with development of social functioning than Gross Motor Function Classification System or Manual Ability Classification System and age., (© 2022 The Authors. Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Purpose: To investigate, in spastic motor-type cerebral palsy, the association between 1) the location and extent of brain lesions and numerous psychological outcomes; 2) the laterality of brain lesions and performance of verbal-related cognitive functions., Methods: The semi-quantitative scale for MRI (sqMRI) was scored for 101 children with cerebral palsy. Non-verbal and verbal proxy intelligence quotients (IQ), word reading, spelling, numerical operations skills, executive functioning, and psychological adjustment were assessed. Relationships between global and regional sqMRI scores and clinical scores were examined. The best multivariable linear regression model for each outcome was identified using the Bayesian Information Criteria. Regional sqMRI scores, gross motor functioning, manual ability, and epilepsy status were considered for inclusion as covariables. Where sqMRI scores made statistically significant contributions to models of verbal-related functioning, data were reanalysed including these sqMRI scores' laterality index. Verbal-related outcomes were compared between participants with left-sided versus bilateral brain lesions., Results: Medial dorsal thalamus and parietal lobe lesions significantly accounted for poorer verbal proxy-IQ. Left-hemisphere lateralization of temporal lobe lesions was associated with poorer verbal proxy-IQ. Participants with bilateral lesions performed significantly better than those with unilateral left-sided lesions in verbal cognitive functions. Controlling for epilepsy diagnosis, participants with ventral posterior lateral thalamus lesions presented with better Behaviour Rating Inventory of Executive Function scores, although within the normal range. sqMRI scores were not significantly associated with some psychological outcomes or these only bordered on significance after accounting for relevant control variables., Conclusion: The laterality of early-life lesions influences the development of verbal-related cognitive functions., (© 2022 Published by Elsevier Ltd on behalf of European Paediatric Neurology Society.)

Aim: To examine the relationship between self-care and bimanual performance in children aged 8 to 12 years with cerebral palsy (CP)., Method: This was a cross-sectional study of 74 children with CP (unilateral n=30, bilateral n=44; 48 males, 26 females; median age 9y 8mo [25th, 75th centiles 9y 1mo, 10y 8mo], Manual Abilities Classification System level I=30, II=28, III=16). Self-care was measured using the Pediatric Evaluation of Disability Inventory-Computer Adaptive Test (PEDI-CAT), and bimanual performance using the Assisting Hand Assessment (AHA) and Both Hands Assessment (BoHA). Measures of cognition, behavioural regulation, inattention, and gross motor function were included. Analyses used a directed acyclic graph to select variables for linear regression modelling., Results: Higher AHA and BoHA scores were associated with higher PEDI-CAT scores. An increase of 1 AHA unit was associated with an increase of 0.12 PEDI-CAT scores, and a 1 BoHA unit increase was associated with an increase of 0.17 PEDI-CAT scores. The BoHA accounted for 57% of variance in PEDI-CAT scores for children with bilateral CP, while BoHA and cognition accounted for 68% of variance. The AHA accounted for 40% of variance in PEDI-CAT scores for unilateral CP with no effect of cognition on self-care., Interpretation: Self-care was strongly and positively associated with bimanual performance. Associations between self-care and bimanual performance differed for those with unilateral and bilateral CP., What This Paper Adds: There is a strong positive relationship between self-care and bimanual performance for unilateral and bilateral cerebral palsy (CP). Both Hands Assessment (BoHA) scores have a stronger association with self-care than Assisting Hand Assessment scores. BoHA scores also account for more variation in self-care. There is a strong positive relationship between self-care and cognition overall. The effect of cognition on self-care performance differed for bilateral and unilateral CP., (© 2020 Mac Keith Press.)

Background: Supportive and targeted interventions for families are required to optimize parental adjustment and the parent-infant relationship in line with earlier diagnosis of neurodevelopmental risk for infants., Aims: The purpose of this systematic review was to determine the efficacy of interventions in improving psychological adjustment and well-being for parents who have an infant diagnosed with or at risk of neurodevelopmental disability., Methods: The Cochrane Review Group search strategy was followed with search of The Cochrane Central Register of Controlled Trials, PubMed, CINAHL, PsycINFO, and Embase between July and December 2017. Methodological quality of included articles was assessed using the Physiotherapy Evidence Database (PEDro) Scale by two independent reviewers., Results: Twelve studies met the inclusion criteria. A small number of high-quality trials demonstrated moderate to large effectiveness of reducing adverse parent psychological symptoms of trauma and stress. Significant improvements in depression and anxiety symptoms emerged at longer-term (6 months to 8 years) follow-up postinterventions., Conclusions: There is promising support for the effectiveness of some interventions to reduce maladaptive psychological symptoms in parents with infants diagnosed at risk of neurodevelopmental disability. Further quality RCTs of psychological interventions addressing broader neurodevelopmental risk conditions for infants are required., (© 2020 Michigan Association for Infant Mental Health.)

Introduction: Cerebral palsy (CP) is the most common cause of physical disability in children, with an estimated 600-700 infants born with CP in Australia each year. CP is typically associated with motor impairments, but nearly half of all children with CP also experience cognitive impairment, potentially impacting educational and vocational achievement. This paper reports the protocol for a randomised controlled trial of a computerised cognitive training intervention based on behavioural principles: Strengthening Mental Abilities through Relational Training (SMART). The study aims to investigate SMART's effect on fluid reasoning, executive function and academic achievement in children with CP., Methods and Analysis: Sixty children with mild to moderate CP (Gross Motor Function Classification Scale I-IV) aged between 8 years and 12 years will be recruited. Participants will be randomly allocated to two groups: SMART cognitive training and waitlist control. Families will access the programme at home over a 4-month period. Assessments will be administered at baseline, 20 weeks and at 40 week follow-up for retention. The primary outcome will be fluid intelligence, while academic achievement, executive function and social and emotional well-being will be secondary outcomes., Ethics and Dissemination: This study has approval from the Children's Health Queensland Hospital and Health Service Research Ethics Committee (HREC/14/QRCH/377) and The University of Queensland (2017001806). If the computerised cognitive training programme is found to be effective, dissemination of these findings would assist children with CP by providing an accessible, cost-effective intervention that can be completed at home at the individual's own pace., Registration Details: The study was registered prospectively on 10 November 2017 to present. Recruitment is now under way, and we aim to complete recruitment by June 2019, with data collection finalised by March 2020., Trial Registration Number: ACTRN12617001550392; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

We examined the accuracy of Smart Socks - a device that measures foot pressure during gait for detecting step-count across various walking speeds. Thirty-six participants (17 men; 19 women) wore Smart Socks (Sock), a pedometer (Pedometer), and a smartphone with a commercially available Phone Application (Phone) pedometer to measure step-count during 3-min of treadmill or over-ground walking at 1.3, 2.2, 3.0, 3.8, and 4.7 km/h. Steps were compared to a gold-standard tally-counter (Count), collected by independent assessors. All devices (Sock, Pedometer, and Phone) underestimated step-count when compared to Count at 1.3 km/h (p<0.05); however, Sock (27±18%) demonstrated a lower percent error compared to Phone (40±28%) and Pedometer (98±5%) (both p<0.01). At 2.2 km/h, Sock was not different compared to Count (Sock: 213±39; Count: 229±24 steps, p=0.25); however, both Phone (271±55 steps) and Pedometer (169±166 steps) were different compared to Count (p<0.05). At 3.0 km/h, both Sock (258±30 steps) and Pedometer (254±45 steps) were similar to Count (267±22 steps) (p>0.05); however, Phone (291±28 steps) overestimated step-count (p<0.01). All devices (Sock, Pedometer, and Phone) were similar to Count at 3.8, and 4.7 km/h (p>0.05). These findings demonstrate that Smart Socks are more accurate than pedometers used in the present study for detecting step-count during treadmill or over-ground ambulation at slower walking speeds., Competing Interests: The authors declare no conflict of interest., (© Georg Thieme Verlag KG Stuttgart · New York.)

Commercial reagent kits for the evaluation of leukocyte subsets involve the staining of a panel of up to six tubes using combinations of pre-mixed fluorescein isothiocyanate (FITC) and R-phycoerythrin (PE) conjugated monoclonal antibodies. We describe a rapid method whereby total CD3+ T-cells, CD4+ T-cells (CD3+ CD4+), CD8+ T-cells (CD3+ CD8+), putative gamma delta-receptor-T-cells (CD3+ CD4- CD8-), and T-cells that are CD3+ CD4+ CD8+ as well as B-lymphocytes and NK-cells can be enumerated after staining in a single tube. Whole blood specimens are labelled with a mixture of antibodies: FITC-conjugated antibodies to CD4 and CD19, PE-conjugated antibodies to CD8 and CD16, and either peridinin chlorophyll protein (PerCP) or allophycocyanin (APC) labelling for antibodies to CD3. After recording 20,000 events the data were analysed on the Consort 32 computer system and LYSYS-II (Becton Dickinson, San Jose, CA) and all of the lymphocyte subset values were determined by Boolean algebra using a technique we refer to as Boolean gate analysis (BGA). Our study has shown that BGA is statistically equivalent to SimulSET lymphocyte subset analysis. Furthermore, the procedure reduces the number of tubes required to two with consequential saving in reagents, consumables, and time.

Whole-body irradiation has been extensively used to ablate immune responsiveness in rodent recipients in adoptive allograft assays. This study was undertaken to determine the relative radioresistance and the tempo of regeneration, following whole-body irradiation, of cells involved in the allograft response. Six distinct cell populations have been identified in the lymphoid tissues of rats subjected to sublethal whole-body irradiation. The relative representation of these subpopulations was significantly different from that in nonirradiated controls. NK cells, macrophages, and plasma cells, which are present in very low numbers in cell suspensions prepared from normal lymphoid tissues, made up a significant proportion of the residual/regenerating population in the tissues of rats recovering from whole-body irradiation. More significantly perhaps, the mature T cell populations showed a significant increase in the T cytotoxic/suppressor to T helper cell ratio. These observations support the suggestion that a number of the cell types within the mixed cell population observed in the rejecting indicator grafts of irradiated recipients in adoptive allograft assays are host derived. The finding that the T cytotoxic/suppressor population is apparently more radioresistant than the T helper population supports a conclusion that graft rejection in irradiated recipients, restored with pure populations of T helper cells, may not be directly mediated by the injected cells but may be the result of collaboration between these and host-derived cytotoxic cell populations.

Studies using neonatal hearts grafted into the foot pads of adult rats have shown significant differences in the tempo of rejection in various RT1-incompatible combinations of donor and recipient rats. The model allows simultaneous study of events in the graft and in the regional node draining the graft. Removal of the regional node in the inductive stages of the immune response resulted in highly significant prolongation of graft survival. This effect was not due to lymphatic interruption per se or to clonal deletion. The effect was independent of the presence of the primary graft. Second grafts implanted in animals from which both the original graft and its regional node had been removed showed prolonged survival. Once survival of the original graft, from which the node was removed, was established, survival of second grafts bearing the same antigens was also prolonged, although third-party grafts were rejected in first set time. The data suggest that the microenvironment and anatomical connections of the lymph node that first receives antigen, or the cells that have contacted antigen in the graft, or both, play a vital role in an orderly sequence of cellular interaction and migration that culminates in graft rejection. Interruption of this sequence by node removal appears to divert the alloimmune response toward specific enhancement of the graft.

A method of two-colour immunofluorescence staining has been developed to allow the simultaneous analysis of both surface and cytoplasmic antigens. This involves the use of direct fluorochrome antibody conjugates for cell-surface antigen staining, followed by cell permeabilization and the staining of cytoplasmic antigens with biotinylated antibodies and streptavidin-fluorochrome conjugates. Fluorochrome-antibody conjugates bound to cell-surface epitopes were found not to be affected by the subsequent permeabilisation and cytoplasmic staining. This method was used to examine the surface phenotype of T cells expressing a cytoplasmic antigen, STA. STA is a unique determinant detected in activated human T cells by the monoclonal antibody K-1-21, which also recognizes a cross-reactive conformation-dependent epitope on human free kappa light chains. Cytometric analysis showed that STA is found in both Leu 2a+ cytotoxic/suppressor T cells and Leu 3a+ helper/inducer T cells but is not induced in the Leu 15+ population which contains suppressor T cells. STA was also shown to be an activation antigen in murine T cells.

Unfractionated peripheral blood leucocytes from allogeneic hagfish proliferated vigorously in one-way mixed leucocyte reaction (MLR) at 20-22 degrees. Maximum responsiveness was observed after 5 days of co-culture of responder and irradiated stimulator cells. Separation of leucocytes on the basis of laser scatter parameters yielded a small leucocyte population which responded but did not stimulate in MLR and a large leucocyte population capable of stimulating but not responding. Adherent cell depletion of the total leucocyte population did not affect the ability to respond in MLR but did ablate the stimulatory capacity of hagfish leucocytes. Together with previous phenotypic studies, these results confirm the presence of lymphocyte and macrophage/accessory cell populations in hagfish peripheral leucocytes.

Immunological tolerance has been demonstrated in double-transgenic mice expressing the genes for a neo-self antigen, hen egg lysozyme, and a high affinity anti-lysozyme antibody. The majority of anti-lysozyme B-cells did not undergo clonal deletion, but were no longer able to secrete anti-lysozyme antibody and displayed markedly reduced levels of surface IgM while continuing to express high levels of surface IgD. These findings indicate that self tolerance may result from mechanisms other than clonal deletion, and are consistent with the hypothesis that IgD may have a unique role in B-cell tolerance.

Characterization of the effect of immunization of F1 hybrid hosts with low doses of parental cells has shown that the F1 hybrid response to the receptor for the unshared MHC antigen on the immunizing cell induces specific resistance to a GVH challenge from cells of the same parental strain. We have shown that cells from parental rats tolerant to the unshared MHC antigens are capable of inducing GVH resistance in F1 hybrids. Unlike cells from normal parental rats that induce GVH resistance only when given in low immunizing doses of 10(6) cells, 10(6)-10(8) cells from tolerant donors effectively immunize F1 hybrids. This effect does not appear to be the result of passive transfer of suppressor cells from the tolerant donor. An alternative explanation is that tolerant populations contain cells that express the receptor for the tolerated alloantigen. The finding that normal parental populations that have been deleted of receptor-bearing cells by passage through semiallogeneic intermediate hosts do not induce GVH resistance, whereas tolerant cell populations do, confirms that clonal deletion does not adequately account for the functional characteristics of the tolerant cells. Attempts to delete putative receptor-bearing cells from the tolerant population however produced equivocal results.

Flow cytometric analysis of forward angle versus 90 degree scatter patterns of hagfish peripheral blood revealed two distinct leucocyte populations with size characteristics analogous to mammalian monocytes/granulocytes (hagfish large leucocytes) and small lymphocytes (hagfish small leucocytes). A cell population enhanced for the small leucocytes was obtained by density gradient centrifugation. Over 70% of the small leucocyte population consistently stained with a rabbit antiserum directed against polypeptide determinants on hagfish immunoglobulin, while staining of the large cell population was greatly reduced (less than 10%). A panel of monoclonal antibodies raised against a crude hagfish leucocyte preparation distinguished the two cell populations and revealed the existence of subpopulations of both small and large leucocytes.

Tumour-cell heterogeneity has been studied in a continuous cell line, UCRU-BL-17CL, established from a xenografted human primary bladder carcinoma. The cell line, grown in vitro for more than 30 generations, reflects the pathology of both the xenograft from which it was derived and the original human tumour. It comprises mainly adenocarcinoma cells which secrete mucin in vitro, as well as squamous and transitional carcinoma cells. Features of both adenocarcinomatous and squamous differentiation have been observed within the same cell. The line expresses ABH blood group isoantigens, binds to peanut lectin and reacts with monoclonal antibodies (MAbs) raised against keratin and against normal and malignant epithelial cells. It also reacts with MAbs against ras p21 proteins and the epidermal growth factor receptor (EGFR). It shows high levels of lactic acid dehydrogenase isozyme 5, consistent with a high-grade tumour, forms colonies in methylcellulose and is tumorigenic in nude mice. The karyotype (human) shows many marker chromosomes, consistent with expression of EGF receptors and ras p21 proteins, and an 11:13 translocation. DNA content, as studied by flow cytometry, reveals a shift from tetraploid to near triploid. This line may provide a useful model for studies of the histogenesis of bladder cancer and the relationship between transitional-cell carcinoma and the other histological subtypes of this disease.

The quantitative and qualitative capacities of flow cytometric analysis that have made it such a powerful tool in studies of cellular antigens have not previously been exploited when dealing with non-cellular antigens. A new immunofluorescence assay technique was developed, using an indirect staining procedure with monoclonal anti-kappa antibodies, to detect human free kappa light chains covalently bound to microspheres of a size suitable for flow cytometry. The strength of the fluorescent signal produced on the microspheres was related to the amount of antigen bound and the size of the beads. At the time of this work large microspheres (i.e., greater than 3 micron in diameter) suitable for this application were only available as suspensions of polysized beads. The fluorescent signal detected on labelled beads was optimized by selecting for analysis, on the basis of the forward angle laser scatter, only those beads of largest diameter. There are many potential applications for this technique - microspheres can be used for the presentation of virtually any antigen or antibody. The analytical benefits inherent in flow cytometry would be a significant advantage in the development of quantitative assays using this method.