Cellular immunity in Guamanians with amyotrophic lateral sclerosis and Parkinsonism-dementia.

To test the hypothesis that host resistance factors may be abnormal in Guamanians in whom amyotrophic lateral sclerosis and Parkinsonism-dementia develop, cellular immunity was evaluated in both diseases and compared to that of Guamanians with other nervous-system diseases, normal adult Guamanians and non-Guamanians with amyotrophic lateral sclerosis and Parkinsonism. Diminished responses to skin-test antigens, lymphopenia, diminished per cent and total T cells and, less frequently, decreased mitogen responses were seen in Guamanian patients with amytorophic lateral sclerosis and Parkinsonism-dementia but not in the other patient or normal groups. Guamanian patients with amyotrophic lateral sclerosis and diminished cellular immunity had an increased frequency of HLA-Bw35 (P less than 0.005) and shorter mean duration of disease (P less than 0.05) than those with normal cellular immunity. In Parkinsonism dementia diminished cellular immunity was less strongly associated with HLA-BW35 (P less than 0.05) and was not associated with differences in duration of disease. Normal Guamanians and those with other nervous-system diseases showed no association of diminished cellular immunity with HLA-Bw35. The association appeared disease-related, with onset concomitant with the neurologic expression of Guamanian amyotrophic lateral sclerosis and Parkinsonism-dementia.     

Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy

A deficiency of the protein dystrophin has recently been shown to be the probable cause of Duchenne's muscular dystrophy. We sought to determine the relation between the clinical phenotype and the status of dystrophin in muscle-biopsy specimens from 103 patients with various neuromuscular disorders. We found very low levels (less than 3 percent of normal levels) or no dystrophin in the severe Duchenne phenotype (35 of 38 patients), low concentrations of dystrophin in the intermediate (outlier) phenotype (4 of 7), and dystrophin of abnormal molecular weight in the mild Becker phenotype (12 of 18). Normal levels of dystrophin of normal molecular weight were found in nearly all the patients (38 of 40) with 20 other neuromuscular disorders we studied. These data show the clinical consequences of both quantitative alterations (in Duchenne's and intermediate dystrophy) in a single protein. The biochemical assay for dystrophin should prove helpful in delineating myopathies that overlap clinically with Duchenne's and Becker's dystrophies, and it shows promise as an accurate diagnostic tool.     

Elevated fibroblast growth factor-23 in hypophosphatemic linear nevus sebaceous syndrome

We report on an adolescent who experienced the onset of linear nevus sebaceous syndrome (LNSS) prior to 1 year of age. At 7 years of age he was diagnosed to have hypophosphatemic rickets. He was suboptimally controlled with phosphate and calcitriol treatment and sustained numerous insufficiency fractures ipsilateral to the linear sebaceous nevus. Fibroblast growth factor-23 (FGF-23), the phosphaturic peptide, was elevated in the plasma. Treamtent with the somatostatin agonist, octreotide, and excision of the nevus were followed by normalization of FGF-23 and clinical improvement. The patient also had hyperimmunoglobulinemia E, which responded to octreotide and surgery. We speculate that in some patients with LNSS there may be more than one mediator of hypophosphatemia and that FGF-23 is the mediator of hyperphosphaturia in this and other hypophosphatemic syndromes.     

Family interaction and the development of borderline personality disorder: a transactional model

Although no prospective epidemiological studies have evaluated the relationship between family interactions and the development of borderline personality disorder (BPD), there is considerable evidence for the central role of family interactions in the development of BPD. This paper describes the role of family interactions or processes, especially those that might be regarded as invalidating or conflictual, negative or critical, and the absence of more validating, positive, supportive, empathic interactions, in the development of BPD. Perhaps more importantly, the proposed model considers how these parental and family behaviors transact with the child's own behaviors and emotional vulnerabilities, resulting in a developmental model of BPD that is neither blaming of the family member with BPD nor of her or his parents and caregivers, and has important and specific implications for both prevention and intervention.     

Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity and relation with rheumatoid factor

Anti-citrullinated protein/peptide antibodies (ACPA) are highly specific and sensitive markers for rheumatoid arthritis (RA). For instance, for the anti-CCP2 assay, sensitivities ranging from 55% to 80% and specificities ranging from 90% to 98% have been reported. Despite their high specificity, recent reports have suggested that ACPA may be found in some patients with other rheumatic autoimmune diseases, including psoriatic arthritis, systemic lupus erythematosus and Sj?gren's syndrome. Also, the differences between the classical rheumatoid factor (RF) and ACPA, as well as the complementarity between both tests have recently been demonstrated more clearly. Indeed, both antibody systems have a different association with specific RA features like extra-articular manifestations, a different association with the HLA shared epitope and, behave differently following anti-TNF therapy.     

Murine splenic hematopoietic subpopulations: the enlarged undifferentiated subset in New Zealand black mice is multipotent stem cells.

We recently reported that a significant population of the murine splenic non-T, non-B "null" cell compartment consists of non-lineage-specific, undifferentiated cells which are in the G0 and G1 phases of the cell cycle and that their numbers are particularly high in the spleens of New Zealand Black mice. A highly enriched population of these non-lineage-specific cells obtained by successive elimination of differentiated cells was further purified to homogeneity by fluorescence-activated cell sorting. The morphologic, phenotypic, and histochemical characteristics of this purified population suggest that these cells may be primitive hematopoietic stem cells. The germ line configuration of the genomic DNA establishes that these are uncommitted stem cells. In vivo, these cells form day 12 colonies in the spleen and liver of lethally irradiated recipients and confer radioprotection. These cells also differentiate into T- and B-cell lineages and reconstitute the immunodeficiency in mice with severe combined immunodeficiency. In response to a combination of a very few early-acting lymphokines and/or stromal cell-conditioned medium in vitro, these cells differentiate into both myeloid and lymphoid cell types. More of these cells are obtained from the enlarged spleens of New Zealand Black mice than from those of BALB/c mice. The presence of a comparatively higher number of stem cells in the spleen than in the marrow or fetal liver provides an alternative, and possibly superior, source of uncommitted stem cells for a variety of experimental investigations or therapeutic manipulations.     

Comparison of immunofluorescence, enzyme immunoassay, and Western blot (immunoblot) methods for detection of antibody to human T-cell leukemia virus type I.

A total of 3,349 serum samples were screened by the immunofluorescence (IF) method for antibody to human T-cell leukemia virus type I (HTLV-I). Only 9 of 2,409 specimens from selected individuals, blood bank donors, patients with encephalitis-meningitis, and human immunodeficiency virus antibody-positive homosexual or bisexual men were reactive by IF. In addition, 940 serum samples from intravenous drug abusers were tested by IF and also by an HTLV-I enzyme immunoassay (EIA) method. Of these, 222 (24%) were positive for both HTLV-I and HTLV-II antigens by IF, and 191 of these 222 were also reactive in the HTLV-I EIA. Of the 31 IF-positive, EIA-negative serum samples, 20 exhibited optical density readings greater than or equal to 70% of the positive cutoff in the EIA, and 29 samples reacted with 1 or more bands in the Western blot (immunoblot) test. An additional 10 specimens that were EIA negative reacted only with HTLV-I by IF. Differences in staining morphology and in reactions on HTLV-I and HTLV-II antigens before and after absorption of the serum specimens with HTLV-I and HTLV-II-infected cell pellets revealed six distinct serological patterns by IF. These results indicate that infections by HTLV-I or by another closely related retrovirus(es) occur in California. Further studies utilizing statistically valid sampling methods are needed to estimate true prevalence rates among various groups. IF and Western blot tests should supplement the EIA method to maximize sensitivity and specificity of test procedures.     

Identification and characterization of a Candida albicans-binding proteoglycan secreted from rat submandibular salivary glands.

A previously identified Candida albicans-binding glycoprotein secreted from rat submandibular glands (RSMG) has been further purified from an aqueous RSMG extract by ion-exchange chromatography and gel filtration. Biochemical analysis of the glycoprotein revealed high levels of uronic acid and sulfate, suggesting that it was a proteoglycan. Its amino acid and carbohydrate compositions were similar to those observed for other proteoglycans and differed significantly from those of RSMG mucin, the major secretory glycoprotein of RSMG. In addition, the apparent molecular weight of the glycoprotein was reduced following treatment with either chondroitinase ABC or heparitinase, demonstrating the presence of chondroitin sulfate and heparan sulfate. On the basis of its structure and anatomical source, the glycoprotein is referred to as submandibular gland secreted proteoglycan 1 (SGSP1). SGSP1 also binds monoclonal antibody 1F9, which recognizes the human blood group A carbohydrate epitope found on RSMG mucin. Hence, SGSP1 appears to be a hybrid molecule with carbohydrate structures found in both proteoglycans and RSMG mucin. Enzymatic digestion of SGSP1, followed by its interaction with a radiolabelled C. albicans strain in a filter-binding assay, demonstrated that binding to this strain appears to be mediated primarily via the heparan sulfate side chains of SGSP1 and not via the blood group A oligosaccharide.     

The effect of an intercollegiate soccer game on maximal power performance.

The effect of a competitive soccer match on maximal power performance was assessed on 19 members of an NCAA Division III female soccer team. Performance testing occurred within 24 hours prior to the game (Pre), immediately postgame (IP), and 24 hours postgame (24P). Each subject performed a squat jump (SJ) and countermovement jump (CMJ). Comparisons between starters (n = 10) and nonstarters (n = 9) revealed no between-group differences in power performance at IP, but starters were found to have significantly lower power and force measures at 24P than nonstarters. There were significant correlations between playing time and peak force during the SJ at 24P (r = -0.47), and between playing time and peak power during the SJ at IP (r = -0.57) and 24P (r = -0.51), and during the CMJ at IP (r = -0.49). Comparisons between different positions revealed no differential fatigue patterns. Results of this study show that power performance appears to be maintained for the duration of a soccer match but declines significantly within 24 hours after the match. Position played does not appear to affect performance decrements seen at 24 hours postmatch.