A Systematic Review of the Effects of Exercise Interventions on Body Composition in HIV+ Adults.

Over the years, physical activity and exercise have been used to positively impact the health and quality of life of persons infected with HIV and, more recently, has been associated with a spectrum of body composition changes. The aim of this review was to examine the effects of various exercise interventions on body composition in HIV positive adults, using a search strategy of randomized, controlled trials (RCTs). A systematic review was performed by five independent reviewers using a predetermined protocol adapted from previous research for assessing the articles for inclusion, the extracted data, and methodological quality. Eight RCTs involving 430 (26% female) HIV positive adults performing exercise a minimum of thrice weekly for at least six weeks were finally selected: Four were progressive resistance training (PRT) studies, three were aerobic training (AT) studies, and one involved yoga. In the PRT studies, there were significant increases in three anthropometric measures, namely, body mass, sum of skinfolds and sum of limb girths. In the AT studies, significant decreases were found in seven anthropometric measures, namely, body mass index, waist-hip ratio, body mass, triceps skinfold, waist circumference and sum of skinfolds. With yoga, the changes were non-significant. Exercise contributes to improved body composition and, when applied safely, appears to be beneficial for adults living with HIV/AIDS. However, these findings should be interpreted cautiously due to the relatively few RCTs published to date. Future studies would benefit from increased attention to sample size, female participants, participant follow-up, complete statistical analysis and intention-to-treat analysis.

Effects of modified tall oil and creatine monohydrate on growth performance, carcass characteristics, and meat quality of growing-finishing pigs.

The effects of feeding modified tall oil (MTO) and creatine monohydrate (CMH) on growing-finishing pig growth performance, carcass characteristics, and meat quality were determined. Eighty cross-bred barrows (initially 45.4 kg) were allotted randomly to one of four dietary treatments by weight and ancestry. The experiment was arranged as a 2 x 2 factorial with two levels of MTO (0 or 0.50%), which were fed throughout the growing-finishing period, and two levels of CMH (0 or 25 g/d), which were fed for the final 10 d before slaughter. The corn-soybean meal diets were fed in two phases (45.4 to 78.9 kg and 78.9 to 117.5 kg BW). When CMH was added to the diet in place of corn, average BW was 107.5 kg. Feeding MTO increased (P < 0.05) ADG and gain:feed ratio (G/F) during the 45.4- to 78.9-kg growth interval and tended to improve (P = 0.10) G/F during the 45.4- to 107.5-kg growth interval. Dietary treatment did not affect (P > 0.15) growth performance during the 78.9- to 107.5-kg growth interval. Modified tall oil increased (P = 0.02) G/F during the 10-d CMH supplementation period, and CMH numerically (P = 0.11) increased ADG and G/F. Supplementation of CMH did not affect (P > 0.20) any measured carcass characteristic or measures of meat quality at 24 h or 14 d postmortem. Feeding MTO reduced average back-fat (P = 0.05) and 10th rib backfat (P = 0.01) but did not affect (P > 0.10) other measured carcass characteristics or measures of meat quality at 24 h postmortem. Modified tall oil increased (P = 0.02) L* values (lightness) and tended to increase (P < 0.10) thawing and cooking losses of longissimus muscle chops at 14 d postmortem. These data demonstrate that MTO improves growth performance and reduces backfat in growing-finishing pigs, but supplementation of CMH, under the conditions of this experiment, was not beneficial for growing-finishing pigs.

Clinical and biological characteristics of Ureaplasma urealyticum induced polyarthritis in a patient with common variable hypogammaglobulinaemia.

Persistent infectious polyarthritis caused by Ureaplasma urealyticum in a patient with common variable hypogammaglobulinaemia is described. The patient developed a symmetrical, destructive polyarthritis and tenosynovitis associated with a markedly depressed synovial fluid glucose concentration and characteristic soft tissue abscesses. The ureaplasma organism developed resistance to multiple antibiotics and persisted for five years. The organism was identified repeatedly in many joints by culture, confirmed by DNA hybridisation, and mycoplasma-like structures were shown in synovial tissues by electron microscopy.

Conservation of tissue factor primary sequence among three mammalian species.

Tissue factor (TF) is a transmembrane glycoprotein that serves as the cofactor for the initiation of the coagulation protease cascades. To identify conserved sequences of this molecule, a 1753-nucleotide cDNA encoding rabbit TF (rbTF) was isolated and sequenced. An open reading frame encoded a predicted precursor protein of 292 amino acids (aa), and a functionally active protein was synthesized when this cDNA was expressed in a eukaryotic cell system. The aa sequence of mature rbTF was 71% identical to human TF (huTF) and 58% to murine TF (muTF), consistent with the relative functional activity of each in human plasma. The structural organization of the protein was comparable in all three species, with a high degree of conservation of the extracellular domain, including the relative positions of cysteine residues and, to a lesser extent, the tripeptide motifs tryptophan-lysine-serine of huTF. In view of the uniform occurrence of TF functional activity throughout vertebrates, the sampling of these three distant mammalian species suggests that there is limited variance in primary sequence, consistent with the conserved function of TF.

Is the WKS motif the tissue-factor binding site for coagulation factor VII?

Human tissue factor (TF), the membrane-bound glycoprotein receptor for the blood-clotting factor VII/VIIa, contains in its extracellular domain three repeats of the rare motif, tryptophan-lysine-serine (WKS). Murine tissue factor, which binds human factor VII/VIIa poorly, contains only one WKS motif suggesting that the WKS motif may be involved in the binding of human factor VII/VIIa to human TF. Sequence analysis has revealed a WKS motif in 23 human proteins, seven of which are involved in the coagulation process. Another five WKS-containing proteins share some functional properties with the coagulation proteins. Analysis of the properties of these proteins provides some insight into the possible functional role of the WKS motif.

Effects of human 17 kDa interleukin 1, 25-31 kDa thymocyte stimulating activity and the 6-9 kDa interleukin 1 inhibitor on calcium release in the newborn murine calvarial assay.

The effects of human monokines on calcium release from cultured newborn murine calvarium were studied. Highly purified interleukin 1 (IL-1) (17 kDa) and recombinant IL-1 beta in the concentration range 0.2-20 U/ml released significant amounts of calcium. Mean resorption indices (RI) at 0.2 U/ml were 1.28 and 1.49, and at 20 U/ml, were 1.82 and 1.72, respectively. Calcium release was abrogated by the cyclooxygenase inhibitor piroxicam. Thymocyte stimulating activity (TSA) 25-31 kDa alone at 0.14 U/ml released calcium in a prostaglandin dependent manner with a mean RI of 2.13, a significantly greater calcium release than that obtained by 17 kDa IL-1 at 20 U/ml. The 6-9 kDa inhibitor of IL-1 induced thymocyte proliferation alone also released calcium in a prostaglandin dependent manner with a mean RI of 2.29 at 200 inhibitory U/ml. Addition of 6-9 kDa IL-1 inhibitor to the 25-31 kDa material did not significantly change the calcium release, whereas addition of the inhibitor to 17 kDa IL-1 produced a significant increase in calcium release.

The metabolism and immunology of bone.

Many cells and their cytokines produce a significant effect on bone metabolism. Bone matrix synthesis is a function of the osteoblast (Fig 1), influenced directly by numerous local and systemic factors (Tables 1 and 2). Locally synthesized factors such as SGF, BMP, and BDGF may be particularly important in stimulating new bone formation at sites of bone resorption or following bony injury. Of the systemic factors, GH; somatomedin C (IGF-1); high concentrations of insulin, testosterone, PDGF and TGF beta; and low concentrations of PGE2 and IL-1 appear to stimulate bone formation in vitro. These latter factors may be more important in maintaining skeletal growth and bone mass. Bone resorption by osteoclasts (Figs 2 and 3) is also controlled by the osteoblast, as this cell produces a leukotriene-dependent polypeptide that stimulates osteoclastic bone resorption. Osteoblasts cover the periosteal and endosteal bone-surfaces and limit exposure of the underlying bone to osteoclasts. PTH, vitamin D, PGE2, and other systemic factors interact directly with the osteoblast, not the osteoclast. Surface receptor binding of PTH increases intracellular cAMP and calcium and results in release of the factor that stimulates osteoclastic bone resorption. PGE2 induces osteoblasts to activate osteoclasts and is a major controlling factor in bone metabolism; the osteoblast produces PGE2, which can then modify osteoblastic function by positive feedback. Although low concentrations of PGE2 stimulate bone formation, higher concentrations promote osteoblast-mediated bone resorption. Furthermore, many of the systemic factors stimulate bone resorption via a PGE2-associated mechanism. Immune cytokines also appear to exert a profound influence on bone metabolism. INF-gamma inhibits osteoclastic resorption, whereas IL-1, TNF, and LT strongly stimulate bone resorption. However, low concentrations of IL-1 paradoxically result in stimulation of bone formation. These cytokines, particularly in various combinations, may prove extremely important in understanding and treating the bone loss associated with malignancies, osteoporosis, and rheumatoid arthritis.

The effects of scleroderma serum on human microvascular endothelial cells. Induction of antibody-dependent cellular cytotoxicity.

To investigate the vascular immunopathology of systemic sclerosis, we developed a model consisting of human microvascular endothelial cells, leukocytes, and serum. Sera from 19% of the patients studied mediated antibody-dependent cellular cytotoxicity against endothelial cells. Some sera also mediated cytotoxicity against aortic endothelium and fibroblasts. K lymphocytes, the cells that mediate antibody-dependent cellular cytotoxicity, were identified in the skin of some patients. The sera alone were not cytotoxic or growth inhibitory, and did not affect endothelial prostacyclin production.

Kinetochore appearance during meiosis, fertilization and mitosis in mouse oocytes and zygotes.

The events of mammalian fertilization overlap with the completion of meiosis and first mitosis; the pro-nuclei never fuse, instead the parental genomes first intermix at the mitotic spindle equator at metaphase. Since kinetochores are essential for the attachment of chromosomes to spindle microtubules, this study explores their appearance and behavior in mouse oocytes, zygotes and embryos undergoing the completion of meiosis, fertilization and mitoses. Kinetochores are traced with immunofluorescence microscopy using autoimmune sera from patients with CREST (CREST = calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia) scleroderma. These sera cross-react with the 17 kDa centromere protein (CENP-A) and the 80 kDa centromere protein (CENP-B) found at the kinetochores in human cell cultures. The unfertilized oocyte is ovulated arrested at second meiotic metaphase and kinetochores are detectable as paired structures aligned at the spindle equator. At meiotic anaphase, the kinetochores separate and remain aligned at the distal sides of the chromosomes until telophase, when their alignment perpendicular to the spindle axis is lost. The female pronucleus and the second polar body nucleus each receive a detectable complement of kinetochores. Mature sperm have neither detectable centrosomes nor detectable kinetochores, and shortly after sperm incorporation kinetochores become detectable in the decondensing male pronucleus. In pronuclei, the kinetochores are initially distributed randomly and later found in apposition with nucleoli. At mitosis, the kinetochores behave in a pattern similar to that observed at meiosis or mitosis in somatic cells: irregular distribution at prophase, alignment at metaphase, separation at anaphase and redistribution at telophase. They are also detectable in later stage embryos. Colcemid treatment disrupts the meiotic spindle and results in the dispersion of the meiotic chromosomes along the oocyte cortex; the chromosomes remain condensed with detectable kinetochores. Fertilization of Colcemid-treated oocytes results in the incorporation of a sperm which is unable to decondense into a male pronucleus. Remarkably kinetochores become detectable at 5 h post-insemination, suggesting that the emergence of the paternal kinetochores is not strictly dependent on male pronuclear decondensation.

Changes in circulating monocytes in patients with progressive systemic sclerosis.

Circulating monocytes in 30 patients with progressive systemic sclerosis (PSS, scleroderma) and 28 age and sex matched normal controls were studied. Binding of the lectin peanut agglutinin (PA) was significantly reduced in PSS monocytes (p less than 0.001) together with a reduction in the density of nonspecific esterase staining (p less than 0.001) suggesting advanced maturation. Using monoclonal antibodies to identify cell surface markers, we demonstrated a significant reduction in PSS monocytes bearing the Leu M2 antigen (Mac 120, antigen presenting cells) over controls (p less than 0.05), but were unable to show any differences in the monocyte subpopulations using antisera against Leu M3 and HLA-DR surface antigens. The ectoenzymes 5'-nucleotidase (5'N) and alkaline phosphodiesterase 1 (APD1) were lower and leucine aminopeptidase (LAP) levels were higher in patients with PSS, compatible with immune activation. Interferon-gamma levels in serum did not appear to account for these changes, whereas the levels of Clq binding complexes correlated inversely with the levels of LAP (p less than 0.05). There was a strong correlation between the number of Leu M3 positive cells and the level of the ectoenzyme LAP (p less than 0.001). With increasing disease duration, higher levels of Clq binding complexes were detected (p less than 0.05). These results indicate that monocytes in PSS differ from those in normals and appear to have undergone advanced differentiation and activation changes.

A 17-kD centromere protein (CENP-A) copurifies with nucleosome core particles and with histones.

We have detected and begun to characterize a 17-kD centromere-specific protein, CENP-A (Earnshaw, W. C., and N. Rothfield, 1985, Chromosoma., 91:313-321). Sera from several humans with CREST scleroderma autoimmune disease (CREST: calcinosis, Raynaud's phenomenon, esophageal dsymotility, sclerodactyly, and telangiectasia) bind this protein in immunoblot assays of HeLa whole cell or nuclear extracts. We have affinity purified the anti-17-kD centromere protein (anti-CENP-A) specific antibodies from immunoblots of HeLa nuclear protein. The antibodies react with epitopes present on CENP-A derived from humans but apparently do not recognize specific epitopes in either rat or chicken nuclei. Only human nuclear protein is CENP-A positive by immunoblot. Furthermore, human cells show localization of anti-CENP-A antibody to centromeres by immunofluorescence microscopy, whereas rat cells do not. On extraction from the nucleus, CENP-A copurifies with core histones and with nucleosome core particles. We conclude that this centromere-specific protein is a histone-like component of chromatin. The data suggest that CENP-A functions as a centromere-specific core histone.

Interleukin 1 inhibitor masks high interleukin 1 production in acquired immunodeficiency syndrome (AIDS).

Monocyte functions, including interleukin 1 (IL-1) production, have been shown previously to be impaired in acquired immunodeficiency syndrome (AIDS). We have fractionated culture supernatants from unstimulated peripheral blood mononuclear cells (PBMCs) to determine whether the low IL-1 activity in AIDS was due to the presence of IL-1 inhibitors. The results demonstrate that PBMCs from patients with AIDS produce increased amounts of IL-1 activity compared with those of controls together with marked increases (10- to 20-fold) in the amounts of 50,000-100,000 and 6000-9000 molecular weight (MW) factors which inhibit IL-1 activity. These inhibitors mask IL-1 activity measured in the standard thymocyte proliferation assay for IL-1. The 6000-9000 MW IL-1 inhibitor shows the greatest increase in all AIDS patients (n = 5) compared with that of controls (n = 7). This inhibitor may block the IL-1 dependent maturation of T lymphocytes in AIDS and thereby contribute to the immunodeficiency.

Increased production of an interleukin 1 (IL-1) inhibitor with fibroblast stimulating activity by mononuclear cells from patients with scleroderma.

We have previously demonstrated low IL-1 activity produced by peripheral blood mononuclear cells (PBMC) from patients with scleroderma (Sandborg et al., 1985) and the production of a 6-9 K IL-1 inhibitor by normal monocytes (Berman et al., 1986). To determine whether this inhibitor accounted for the low IL-1 activity present in scleroderma, the production of IL-1 and IL-1 inhibitor by PBMC from eight scleroderma patients was studied. Concentrated supernatants from 24 h cultures of unstimulated PBMC were fractionated on Sephacryl S-200 and tested for IL-1 and IL-1 inhibitor activity in the standard IL-1 thymocyte proliferation assay. In seven of eight patients, IL-1 inhibitor production was increased (average 3.3 X) compared to matched controls. IL-1 production was less than controls in six of eight patients. Partially purified preparations of the 6-9 K mol. wt IL-1 inhibitor were inhibitory to IL-1 induced thymocyte proliferation but stimulatory to fibroblast proliferation when purified by gel chromatography and chromatofocusing (pI 4.5-5.6). These data suggest that an IL-1 inhibitor with fibroblast stimulating activity is produced in higher amounts by PBMC from patients with scleroderma, and may contribute to the fibroblast proliferation and excessive collagen synthesis which is typical of this disease.

Immune complexes in synovial fluid and serum from patients with disseminated gonococcal infection: evidence for local immune complex formation within the joint.

Twenty one patients with acute arthritis associated with disseminated gonococcal infection (DGI) were studied. Synovial fluid (SF) from 14 and serum from 15 (matched in eight) were assayed for the presence of immune complexes (IC) by the Raji cell immunofluorescent assay (Raji IFA) and the 125I-Clq polyethylene glycol (PEG) binding assay. Higher levels and frequency of IC were detected in the SF by both IC assays and these were associated with a significant increase in complexes containing IgM over serum (p less than 0.02). Complexes containing IgG were found predominantly in serum and were infrequent in SF (p less than 0.003). These data suggest that the arthritis of DGI may result from primary immune complex formation within the synovial cavity after local antibody synthesis within the synovium in response to gonococcal seeding.

Immunopathology of cutaneous human lupus erythematosus defined by murine monoclonal antibodies.

Skin biopsy specimens obtained from involved skin from sixteen patients with systemic and discoid lupus erythematosus were studied. Murine monoclonal antibodies with a biotin-avidin-horseradish peroxidase staining system were used. The findings consisted of a marked reduction in the number of epidermal Langerhans cells defined by surface antigens, reduced HLA-DR (Ia-like) antigens on the surface of dermal capillary endothelium, and mononuclear cell infiltrates characterized by a predominance of helper T lymphocytes and an increase in the number of mononuclear phagocytic cells. B lymphocytes were rarely identified. The number of T lymphocytes within the dermis correlated inversely with both the number of HLA-DR-positive epidermal Langerhans cells (p less than 0.01) and the HLA-DR staining of dermal capillary endothelium (p less than 0.01). These findings suggest that a T lymphocyte-mediated immune response associated with a reduction in Langerhans cells and capillary endothelium HLA-DR antigens is involved in the inflammatory process of lupus erythematosus skin.

Studies of an interleukin 1 inhibitor: characterization and clinical significance.

Supernatants from 24 h cultures of human peripheral blood mononuclear cells (PBMNC) were fractionated and tested for interleukin (IL-1) activity in the mouse thymocyte assay with phytohaemagglutinin (PHA). By the addition of individual supernatant fractions together with partially purified IL-1 to the thymocyte assay, we demonstrate the presence of strong inhibitory activity with a mol. wt of 5,000-9,000 and an isoelectric point of 4.5-5.6. The activity is both heat (56 degrees C) and acid (pH 1.5) resistant. This inhibitor has no detectable suppressive effect on optimal and suboptimal concanavalin A (Con A), pokeweed mitogen (PWM), and PHA responses of PBMNC. The action of the inhibitor appears to be specifically directed against IL-1 action on thymocytes and has no inhibitory effect on interleukin 2 (IL-2) activity. The findings show that adherent PBMNC produce both IL-1 and a factor which opposes IL-1 action on thymocytes but not on peripheral (mature) T cells. This factor may regulate T cell maturation, activation, and proliferation.

Loss of epidermal Langerhans' cells and endothelial cell HLA-DR antigens in the skin in progressive systemic sclerosis.

Skin biopsies from the volar aspect of the forearm were studied in 26 patients with progressive systemic sclerosis (PSS) (16 diffuse, 10 CREST) and 4 controls using monoclonal antibodies against Langerhans' cells, T lymphocytes, macrophages, B lymphocytes, NK/K cells and HLA-DR antigen(s). Langerhans' cells were reduced or absent (anti-T6, anti-HLA-DR) in 19 of 20 clinically involved and in all 6 uninvolved PSS skin biopsies. Electron microscopic studies of 3 PSS patients indicated a reduction in the number of Langerhans' cells, with normal morphology of the remaining. HLA-DR antigen(s) on dermal endothelial cells were absent or reduced in 8 of 20 involved and 5 of 6 uninvolved PSS skin biopsies, but were present on the surface of dermal mononuclear cells presumably representing activated T lymphocytes. Increased numbers of dermal macrophages were found in 19% of PSS biopsies compared with controls. Absence of Langerhans' cells appears to represent the most widespread immunopathological feature of PSS. It is also associated with absent endothelial HLA DR surface antigens and activated T lymphocytes within the dermis.

Palmar fasciitis and arthritis with ovarian and non-ovarian carcinomas. New syndrome.

Paraneoplastic syndromes affect a variety of organ systems and often suggest occult malignancy. Recently, a distinct syndrome of palmar fasciitis and arthritis has been associated with ovarian carcinomas. The two cases presented illustrate the fasciitis-arthritis association with other non-ovarian malignancies and suggest an immunologic cause for this disorder.

The Raji cell radioimmunoassay in patients with systemic lupus erythematosus: clinical significance and relationship to other serologic variables assessed by discriminant analysis.

Our aim was to determine the clinical usefulness of the Raji cell radioimmunoassay (RIA) in 30 patients with systemic lupus erythematosus (SLE) studied over a 30-month period. Raji RIA correlated positively (p less than 0.001) with antibodies to dsDNA, anti-Sm, erythrocyte sedimentation rate and central nervous system involvement and inversely with the white blood count, hematocrit and CH50. There was a lack of correlation (p greater than 0.05) between the Raji RIA and cryoglobulins, Clq binding assay, lymphocyte count, rheumatoid factor and anti-RNP. Raji RIA values paralleled disease activity in 50% and were predictive of flares in 17%. By discriminant analysis, the Raji RIA could not predict nephritis as well as a variety of routine laboratory tests in SLE. The Raji RIA, while helpful in SLE, does not appear to offer any advantage over standard assays in monitoring SLE disease activity.