Differences in activities of daily living (ADL) abilities of children across world regions: a validity study of the assessment of motor and process skills.

BACKGROUND: One important goal of paediatric occupational therapy services is to improve activities of daily living (ADL) abilities of children. In order to plan and evaluate the effectiveness of targeted interventions, valid assessments are critically needed. The Assessment of Motor and Process Skills (AMPS) is an internationally standardized assessment of ADL performance that has not been validated for use with children in Middle Europe. AIM: To evaluate for (i) significant differences in mean ADL motor and mean ADL process ability measures among children from Middle Europe compared with children from North America, UK/Republic of Ireland, Nordic countries, Western Europe, Australia/New Zealand and Asia; and (ii) meaningful differences between the international age-normative means of the AMPS and those for children from Middle Europe. METHOD: We analysed data of children across world regions extracted from the international AMPS database using many-facet Rasch and two-way anova analyses and by estimating contrasts to evaluate for significant group differences. RESULTS: anova analyses of data for 11 189 children ages 2-15 revealed significant effects for mean ADL motor and ADL process ability by region [F ≥ 15.32, d.f. = (6, 11 091), MSE ≥ 0.20, P < 0.001, ή(2) ≥ 0.008], and age [F ≥ 253.47, d.f. = (13, 11 091), MSE ≥ 0.20, P < 0.001, ή(2) ≥ 0.229], and a significant interaction effect for mean ADL process ability [F = 1.48, d.f. = (78, 11 091), P = 0.004, ή(2) = 0.010]. Out of 168 estimated contrasts between Middle Europe and the other world regions for mean ADL motor and ADL process ability, seven were statistically significant (4.17%), but none exceeded ±1SE from the international means. CONCLUSION: The AMPS remains free of relevant differences in mean ADL ability measures between Middle Europe and other world regions, indicating that the international age-normative mean values are likely to be applicable to children from Middle Europe. The AMPS can be used internationally to evaluate ADL performance in children and to determine if the child is eligible for occupational therapy services.

Differences between questionnaire- and interview-based measures of activities of daily living (ADL) ability and their association with observed ADL ability in women with rheumatoid arthritis, knee osteoarthritis, and fibromyalgia.

OBJECTIVES: Although self-report based on questionnaire is the common method to obtain information about activities of daily living (ADL) ability in rheumatic diseases, little is known about the relationship between measures of ADL ability based on questionnaire, interview, and observation. The present study examined whether measures of self-reported ADL ability based on questionnaire and interview yielded different results, determined whether the magnitude of the difference varied among women with rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and investigated the relationships between self-reported and observed ADL ability. METHOD: The 47 ADL tasks of the ADL taxonomy were used to evaluate self-reported ADL ability based on questionnaire (ADL-Q) and interview (ADL-I), and the Assessment of Motor and Process Skills (AMPS) was used to obtain measures of observed ADL ability. RESULTS: Participants across diagnostic groups reported significantly more ADL ability based on the ADL-Q than on the ADL-I. Moderate correlations were found between the ADL-Q and ADL-I ability measures. Although low to moderate correlations were seen between measures based on the AMPS ADL motor scale and the ADL-Q and ADL-I, respectively, correlations between measures based on AMPS ADL process scale and ADL-Q and ADL-I were generally low. Overall, there was no difference in how the measures based on the two modes of self-report related to the observed ADL ability measures. CONCLUSION: Measures of self-reported ADL ability based on either questionnaire or interview have limited relationship to each other or to observed performance of ADL tasks.

Expression of alpha- and beta-globin genes occurs within different nuclear domains in haemopoietic cells.

The alpha- and beta-globin gene clusters have been extensively studied. Regulation of these genes ensures that proteins derived from both loci are produced in balanced amounts, and that expression is tissue-restricted and specific to developmental stages. Here we compare the subnuclear location of the endogenous alpha- and beta-globin loci in primary human cells in which the genes are either actively expressed or silent. In erythroblasts, the alpha- and beta-globin genes are localized in areas of the nucleus that are discrete from alpha-satellite-rich constitutive heterochromatin. However, in cycling lymphocytes, which do not express globin genes, the distribution of alpha- and beta-globin genes was markedly different. beta-globin loci, in common with several inactive genes studied here (human c-fms and SOX-1) and previously (mouse lambda5, CD4, CD8alpha, RAGs, TdT and Sox-1), were associated with pericentric heterochromatin in a high proportion of cycling lymphocytes. In contrast, alpha-globin genes were not associated with centromeric heterochromatin in the nucleus of normal human lymphocytes, in lymphocytes from patients with alpha-thalassaemia lacking the regulatory HS-40 element or entire upstream region of the alpha-globin locus, or in mouse erythroblasts and lymphocytes derived from human alpha-globin transgenic mice. These data show that the normal regulated expression of alpha- and beta-globin gene clusters occurs in different nuclear environments in primary haemopoietic cells.

Sensory adaptation in naive peripheral CD4 T cells.

T cell receptor interactions with peptide/major histocompatibility complex (pMHC) ligands control the selection of T cells in the thymus as well as their homeostasis in peripheral lymphoid organs. Here we show that pMHC contact modulates the expression of CD5 by naive CD4 T cells in a process that requires the continued expression of p56(lck). Reduced CD5 levels in T cells deprived of pMHC contact are predictive of elevated Ca(2)+ responses to subsequent TCR engagement by anti-CD3 or nominal antigen. Adaptation to peripheral pMHC contact may be important for regulating naive CD4 T cell responsiveness.

How many thymocytes audition for selection?

T cell maturation requires the rearrangement of clonotypic T cell receptors (TCR) capable of interacting with major histocompatibility complex (MHC) ligands to initiate positive and negative selection. Only 3-5% of thymocytes mature to join the peripheral T cell pool. To investigate the basis for this low success rate, we have measured the frequency of preselection thymocytes capable of responding to MHC. As many as one in five MHC-naive thymocytes show upregulation of activation markers on exposure to MHC-expressing thymic stroma in short-term reaggregate culture. The majority of these cells display physiological changes consistent with entry into the selection process within 24 h. By exposing TCR transgenic thymocytes to a range of MHC-peptide complexes, we show that CD69 induction is indicative of thymocyte selection, positive or negative. Our data provide evidence that the fraction of thymocytes that qualify to enter the thymic selection process far exceeds the fraction that successfully complete it, and suggest that most MHC-reactive thymocytes are actively eliminated in the course of selection.

The sor gene of HIV-1 is required for efficient virus transmission in vitro.

The genome of the human immunodeficiency virus HIV-1 contains at least eight genes, of which three (sor, R, and 3' orf) have no known function. In this study, the role of the sor gene was examined by constructing a series of proviral genomes of HIV-1 that either lacked the coding sequences for sor or contained point mutations in sor. Analysis of four such mutants revealed that although each clone could generate morphologically normal virus particles upon transfection, the mutant viruses were limited in their capacity to establish stable infection. Virus derived from transfection of Cos-1 cells (OKT4-) with sor mutant proviral DNA's was resistant to transmission to OKT4+ "susceptible" cells under cell-free conditions, and was transmitted poorly by coculture. In contrast, virus derived from clones with an intact sor frame was readily propagated by either approach. Normal amounts of gag-, env-, and pol-derived proteins were produced by all four mutants and assays in both lymphoid and nonlymphoid cells indicated that their trans-activating capacity was intact and comparable with wild type. Thus the sor gene, although not absolutely required in HIV virion formation, influences virus transmission in vitro and is crucial in the efficient generation of infectious virus. The data also suggest that sor influences virus replication at a novel, post-translational stage and that its action is independent of the regulatory genes tat and trs.

Type-restricted neutralization of molecular clones of human immunodeficiency virus.

In a study of the immunologic significance of the genetic diversity present within single isolates of human immunodeficiency virus type 1 (HIV-1), the neutralization of viruses derived from molecular clones of the HIV-1 strain HTLV-IIIB by an extensive panel of sera was compared. Sera from HIV-1-infected patients and from goats immunized with polyacrylamide gel-purified HIV-1 envelope glycoprotein (gp120), native gp120, or gp120-derived recombinant peptides, showed marked heterogeneity in neutralizing activity against these closely related viruses. The change of a single amino acid residue in gp120 may account for such "clonal restriction" of neutralizing activity.

Infectious mutants of HTLV-III with changes in the 3' region and markedly reduced cytopathic effects.

A variant of human T-lymphotropic virus type III (HTLV-III) is described that replicates but does not kill normal human T cells in vitro. This variant, designated X10-1, was derived from the genome of a cytopathic HTLV-III clone (pHXB2D) by excision of a 200-base pair segment in the 3' region of the virus, spanning the env and 3'-orf genes. Comparable variants with 55 to 109 base pairs deleted exclusively in 3'-orf produced, in contrast, virus that was extremely cytopathic. On the basis of these findings it is concluded that the 3'-orf gene is not required for cytopathogenicity or replication of HTLV-III. In addition, the results suggest that virus replication and cytotoxicity are not intrinsically coupled. Furthermore, since clone X10-1 retains the ability to trans-activate genes linked to the viral long terminal repeats, trans-activation per se is not responsible for T-cell killing by HTLV-III. These results also raise the possibility that the carboxyl terminus of the envelope gene of HTLV-III has a direct role in T-cell killing by this virus.

Type 1 human T-cell leukemia virus small envelope protein expressed in mouse cells by using a bovine papilloma virus-derived shuttle vector.

In an attempt to express the small (transmembrane) envelope protein p21e of type 1 human T-cell leukemia (lymphotrophic) virus (HTLV-1) exclusive of other viral gene products, we have constructed a recombinant plasmid clone (pMBE-1) in a bovine papillomavirus-derived mammalian expression vector. Mouse C127 cells transfected with the pMBE-1 plasmid expressed the introduced HTLV-1 viral gene(s) as demonstrated by Northern blot and indirect immunofluorescence with natural human antisera. The transfected mouse cells were injected into BALB/c mice, and a monoclonal antibody was recovered which specifically recognizes a 21-kilodalton protein present in HTLV-1 virions, indicating that the pMBE-1 plasmid encodes the small envelope protein.

Aerobic exercise in water versus walking on land: effects on indices of fat reduction and weight loss of obese women.

AIM: It has been suggested, that water exercise is less effective than weight-bearing exercise on land for body fat reduction. METHODS: To test this hypothesis 38 middle-aged obese women (25-47% body fat) participated in a 13 week exercise-diet program to compare the effects of aerobic exercise in water versus walking on land on indices of fat reduction and weight loss changes. Subjects were randomly assigned to 1 of 3 exercise groups: 1) walking on land (WL), 2) swimming (SW) at 27 degrees C water temperature and 3) walking in 29 degrees C water (WW) at the shallow end of a declining pool with the water at navel height. Subjects in the SW group alternated breast-, side-, and backstroke swimming without face immersion. Exercise parameters were kept constant for all three groups. Subjects participated in supervised exercise sessions for 40 min, 4 times a week at 70% of age-predicted maximum heart rate. Subjects were tested before and after the 13-week experimental period. RESULTS: Significant reductions in body weight, (5.9 kg), percent body fat, (3.7%), and skinfold and girth measurements, occurred in all groups. There where no significant differences between groups. CONCLUSIONS: The results of this study indicate that there are no differences in the effect of aerobic activities in the water versus weight-bearing aerobic exercise on land on body composition components as long as similar intensity, duration and frequency are used.

T cell development: new approaches.

The differentiation of T lymphocyte precursors into functionally mature progeny proceeds in distinct stages. Since these are identified by characteristic constellations of phenotypic markers, the effects of experimental manipulations on T cell development can be readily monitored. In order to complete their developmental program, thymocytes must interact with stromal elements, which positively and negatively select the functional T cell receptor (TCR) repertoire. This process normally assures self tolerance and immunocompetence. Disturbances are of practical importance for clinical disorders including immunodeficiencies and autoimmune phenomena, raising a particular interest in human T cell development and repertoire formation. Here, we discuss results and possible applications of a culture system for human thymocytes. Further, we describe an in vitro approach addressing the requirements for a crucial step in T cell development; the transition from the immature CD4 CD8 double positive (DP) to the mature CD4 single positive (SP) stage.

Lymphoproliferative disorders in an IL-7 transgenic mouse line.

A high incidence of severe lymphoproliferative disease was observed in a newly generated strain of mice carrying murine IL-7 as a transgene under the control of the E alpha (MHC class II) promoter. An analysis of the cells from lesions in these mice shows the selective expansion of cells at an early stage of B cell development and, more interestingly, expansion of cells phenotypically identical to the recently reported bipotent (B/macrophage) stem cell populations described in midgestation embryonic liver. Such cells can be propagated (and remain dependent upon) bone marrow feeder cell lines obtained from IL-7 transgenic mice. A molecular analysis of fresh and cultured cells reveals that the lesions are oligoclonal, or in rare cases monoclonal, and include clones of cells with unrearranged Ig heavy chain loci. These data suggest that IL-7 acts at multiple stages of B cell development. Furthermore cell lines derived from IL-7 transgenic mice may provide a novel source of rare factor-dependent bipotent stem cells.

Isolation and characterisation of dimethylsulphoxide resistant variants from the human promyeloid cell line HL60.

The HL60 line can be induced to differentiate into neutrophils by 1.25% dimethylsulphoxide (DMSO) or monocytes by 12-O-tetradecanoylphorbol-13-acetate (TPA). Seven variants of this line have been isolated which do not respond to 1.25% DMSO. Five of these lines can be induced to mature into neutrophils using DMSO concentrations of 1.75% (HL60 m2, m4, Sp1 and Ast3) and 2.0% (HL60 Ast25). Two lines, HL60 Ast1 and 4, showed minimal differentiation even at a concentration of 2.0% DMSO, and 2.25% DMSO was toxic to these cells. Of the seven variant lines, HL60 Ast3, Ast4 and Sp1 failed to differentiate into monocytes in response to TPA. Sublines from HL60 that either require higher concentrations of DMSO to induce maturation or fail to differentiate into neutrophils, such as those described above, can be used to investigate how genetically determined properties within HL60 cells affect the ability to mature into neutrophils.

A monoclonal antibody identifies a 215 000-dalton nuclear envelope protein restricted to certain cell types.

The monoclonal antibody, AGF2.3, was isolated from mice immunised with the human promyeloid cell line HL60. By immunofluorescence and immunoelectron microscopy the antibody was shown to bind to the nuclear envelope in uninduced HL60 cells. Immunofluorescent staining was reduced to very low levels in HL60 cells induced to mature to monocytes or neutrophils by addition of 12-0-tetradecanoylphorbol-13-acetate or dimethyl sulfoxide respectively. Blood neutrophils did not express the antigen. Weak immunofluorescent staining of cell nuclei was observed in peripheral blood lymphocytes and in sections of normal human kidney, tonsil and skin epithelium. The AGF2.3 antigen was strongly expressed on the nuclei of 21/21 haemopoietic cell lines and 21/25 permanent non-haemopoietic cell lines representing various cell types. In contrast, the antigen was not expressed by any of six primary (untransformed) cell cultures. These included fibroblasts, endothelial cells and keratinocytes. The antigen was expressed in the Q10 SV-40 transformed cell line derived from a non-expressing primary fibroblast culture. AGF2.3 antibody precipitated a protein with an apparent subunit molecular weight of approximately 215 kDa from Triton X-100 extracts of HL60 and HeLa cells labelled with 35S-methionine. This protein was not detectable in extracts of primary skin fibroblasts prepared in parallel. We conclude that AGF2.3 antibody recognises a previously undescribed protein associated with the nuclear envelope which is expressed at high levels in most transformed cell lines but which is weakly expressed or absent in normal tissues and primary cell cultures.

Calorie-restricted low-fat diet and exercise in obese women.

The effects of caloric restriction and exercise on body composition, resting metabolic rate (RMR), and maximal oxygen uptake (VO2 max) were studied for 16 wk in 26 premenopausal obese women. Exercise (X) vs nonexercise (NX) was crossed with a low-fat, ad libitum-carbohydrate (AL) diet vs a restricted (R) (800 kcal) low-fat, high-carbohydrate diet in a 2 x 2 factorial design. Subjects were randomly assigned to one of the four treatment groups. Body-weight and percent-fat losses were significant (p less than 0.05) in all groups but greater in subjects assigned to the R diet (p less than 0.05) and/or X (p less than 0.10) groups. Exercise increased (p less than 0.01) VO2 max but neither exercise nor diet influenced fat-free mass or RMR (kcal.m-2.h-1), both of which remained unchanged over time. A program similar to that followed by the ALX group is recommended for long-term weight control and overall health.

In vitro construction of graded thymus chimeras.

A simple in vitro approach is described for constructing chimeric thymi in which the degree of chimeric contribution can be tightly controlled. This is achieved by protease-assisted dissociation of fresh fetal thymic tissue, mixing the resulting cell suspensions at the desired ratios, and subsequent reaggregation. Analysis of these graded chimeras shows that stromal elements become evenly interspersed and form a microenvironment able to support the maturation of endogenous T cell precursors. Chimeras between normal and MHC-deficient thymi have been used to demonstrate the rescue of mutant, allotype-marked thymocytes by wild-type stromal cells. Other potential applications of the method include quantitative studies on positive and negative thymic selection, the functional role of defined stromal cell types in these processes, and the analysis of mutants (either natural or engineered) by complementation.

Noninvasive evaluation of world class athletes engaged in different modes of training.

This study evaluated by noninvasive methods the cardiac structure and functional characteristics of world class athletes participating in different types of training programs. Fourteen subjects, including 4 strength-trained (discus and shot put), 4 endurance-trained (long distance runners), 4 decathlon-trained (strength and endurance), 2 wheelchair athletes and 31 college-age control subjects were evaluated using electrocardiography, M-mode echocardiography and maximal oxygen consumption. M-mode echocardiography measurements of left ventricular structure and function were compared before and after normalization for lean body weight. As expected, endurance athletes had greater maximal O2 consumption than the other groups (p less than 0.05). Before normalization for lean body weight, there were no significant differences in end-diastolic dimensions. After normalization, the endurance, wheelchair and control subjects had end-diastolic dimensions larger than those of strength athletes. Strength athletes appeared to have a much larger posterior wall and septal thickness than all groups except the decathlon athletes. However, when normalized, there was no difference among any of the groups. Previous investigators have attempted to determine "normalcy" of cardiac hypertrophy by looking at the ratio of left ventricular wall thickness to left ventricular radius. In the present study, the thickness to radius ratio in strength athletes was 33% greater than that in endurance athletes. It appears that the left ventricular wall thickness in the strength athletes occurred without a concomitant increase in left ventricular radius and that the left ventricular hypertrophy of world class athletes is related to the total increase in lean body weight. However, ventricular dimensions may be related more to the type of overload experienced.

A recombinant clone of HIV-1 preferentially transmitted in normal peripheral blood mononuclear cells.

To study biologic properties associated with specific regions of HIV-1, a chimera, pHX-JY1, was constructed by exchanging the vif-env region of a Zairian molecular clone (JY1) with that of pHXB2gpt, a full-length biologically active proviral clone of North American origin. Virus was produced by transfection of permissive cells with parental and recombinant clones, and the biologic and molecular properties of these viruses were compared. Virus derived from pHXB2gpt infected phytohemagglutinin (PHA)-activated normal peripheral blood mononuclear cells (PBMC) and CD4+ leukemic T cell lines equally well. In contrast, virus derived from pHX-JY1 was transmitted slowly to both PBMC and cell lines, and the infectivity of pHX-JY1 virus was two orders of magnitude greater for PBMC than for T cell lines. All essential viral genes in the exchanged JY1 vif-env region were intact and functioned comparably to those of the parent clone in transfected COS-1 cells. The findings suggest differences in these regions of the HIV-1 genome may play an important role in differential cell tropism.

Role of the carboxy-terminal portion of the HIV-1 transmembrane protein in viral transmission and cytopathogenicity.

The transmembrane glycoprotein (gp41) of human immunodeficiency virus type-1 (HIV-1) has a long cytoplasmic domain of unknown functional significance. To investigate the role of the carboxy-terminal (C-terminal) portion of the HIV-1 envelope protein in viral replication, infectivity, and cytopathogenicity, we examined the properties of a panel of mutants with variable deletions in the 3'-env region. Deletion of the C-terminal 76 amino acids did not abolish production of reverse transcriptase upon transfection of COS-1 cells. Deletion of the C-terminal 6-14 amino acids appeared sufficient to alter the replication pattern, infectivity, and cytopathogenicity of some clones. The data suggest that conformational determinants or specific sequences are responsible for the observed changes, rather than simply the length of the gp41 cytoplasmic tail.

Heritability estimates of pulmonary function.

To test the hypothesis that there is genetic control of pulmonary function parameters independent of that influencing height, we evaluated 74 pairs of asymptomatic, nonsmoking twins. FVC, FEV1, FEF25-75%, TLCsb, RVsb, Dsb, and D/VA were measured. Pulmonary function indices were adjusted for height using simple linear regression. Mean intrapair differences (unadjusted and adjusted for height) were compared using t tests of independent samples. Within pair, Holzinger's, and Falconer's heritability estimates were calculated using height-adjusted residual values. When total variances of a function parameter were statistically different between monozygotes and dizygotes, the among component heritability estimate was calculated and used as the best indicator of heritability. Following adjustment for height, no measure of pulmonary function which satisfied the requirements of the analysis was found to be significantly heritable.