The putative R1 protein of Streptococcus agalactiae as serotype marker and target of protective antibodies

The streptococcal R1 protein was studied by means of anti-R1 antibodies prepared by appropriate cross-absorption of rabbit antiserum raised against the group B streptococcal (GBS) strain ATCC 12403 (D136C), serotype III/R1. The protein was a ladder-forming antigen according to banding patterns in immunoblotting, similar to several other GBS proteins, and was susceptible to digestion by both pepsin and trypsin. Antibody-based testing revealed that 10% of Norwegian GBS isolates expressed the R1 protein, most frequently capsular antigen type V strains (72%) and less frequently type III strains (3%). None of 132 GBS strains from Zimbabwe, including 39 type V strains, expressed the R1 protein. R1-specific rabbit antibodies showed protective activity in mice challenged with a GBS type V/R1 strain. The results show that the R1 protein is an important GBS serotype marker in strains from certain geographical areas, notably for the subtyping of capsular type V strains, and that this protein is a target of protective antibodies.     

Gastrointestinal disturbances in marathon runners.

To determine the prevalence of various gastrointestinal disturbances related to long-distance running and its effect on weight, diet and everyday digestive problems, we gave a questionnaire to 279 leisure-time marathon runners, comprising 10% of the participants in a local marathon race. Their answers disclosed a prevalence of dietary changes, weight reduction and altered bowel habits (mainly looser stools and/or more frequent defaecation) of 37, 38 and 48% respectively. A quarter reported earlier long lasting gastrointestinal problems, which improved in 41% of the runners after they started regular training. Thirty-four percent experienced gastrointestinal disturbances during or after running, 20% to such an extent that it seriously affected their performance.     

Changes in plasma potassium concentration during carbon dioxide pneumoperitoneum

Hyperkalaemia with ECG changes had been noted during prolonged carbon dioxide pneumoperitoneum in pigs. We have compared plasma potassium concentrations during surgery in 11 patients allocated randomly to undergo either laparoscopic or open appendectomy and in another 17 patients allocated randomly to either carbon dioxide pneumoperitoneum or abdominal wall lifting for laparoscopic colectomy. Despite an increasing metabolic acidosis, prolonged carbon dioxide pneumoperitoneum resulted in only a slight increase in plasma potassium concentrations, which was both statistically and clinically insignificant. Thus hyperkalaemia is unlikely to develop in patients with normal renal function undergoing carbon dioxide pneumoperitoneum for laparoscopic surgery.      

Positioning of temperature measurement points using multiplanar computed tomography

A method is described for the use of computed tomography and multiplanar reconstruction to depict in single images the full course of obliquely running thermometry catheters. In 14 patients given thermoradiotherapy for locally advanced breast carcinoma, reformatted images of the full catheter course were obtained for all 98 catheters so far tested. The main clinical advantage of this time-consuming procedure was the ability to determine the localization within the catheters of individual temperature measurement points of multipoint thermistor probes. It was also possible to study the localization of the measurement points in relation to the tumour margins.     

Cytotoxic T-cell response to ectromelia virus-infected cells. Different H-2 requirements for triggering precursor T-cell induction or lysis by effector T cells defined by the BALB/c-H-2(db) mutation

The T(c)-cell response to ectromelia virus infection was studied in BALB/c-H-2(db) mice which carry a loss mutation in the H-2D region that results in the absence from cell surfaces of a molecule (D’) bearing certain public H-2 specificities. When infected, these mice showed a poor response of T(c) cells that recognize H-2D(d) plus virus-specific determinants on infected macrophage targets, but gave a normal response to H-2K d plus virus-specific antigens. However, their own infected macrophages do display wild-type antigenic patterns involving virus and H-2D(d) since they were killed as efficiently as wild-type (BALB/c,H- 2(d))-infected cells by T(c) cells specific only for H-2D(d) plus viral antigens. When tested in vitro, infected BALB/c-H-2(db) cells stimulated a poor T(c)-cell response to H-2D plus virus-specific antigens, but stimulated a normal response (in comparison with infected BALB/c macrophages) to H-2K(d) plus viral antigens. Uninfected BALB/c-H-2(db) cells stimulated a normal T(c)-cell response to minor H antigens or trinitrophenyl in association with H-2D(d), thus suggesting that the defective response to infection may reside in a failure of the relevant H-2D(d) antigens of mutant cells to physically associate with viral antigens. Close association of viral and H-2D-coded molecules was also suggested by ability of specific anti-H-2K or -H-2D to partially block T(c)-cell-mediated lysis of infected targets. These results were interpreted to mean that H-2Dd-dependent, virus- immune T(c) cells recognized an antigenic pattern consisting of virus- specific and H-2D(d) determinants with the latter borne on an H-2D molecule carrying serologically-defined H-2D(d) private specificities. A second H-2D(d)-coded molecule (D’) was not required for recognition and lysis by activated T(c) cells, but was apparently necessary for efficient stimulation of precursor T(c) cells, perhaps by promoting appropriate physical association of viral and H-2D(d) molecules.     

Genomic survey of early responses to viruses in Atlantic salmon, Salmo salar L

Viral diseases are one of the main problems and risk factors in aquaculture. At present diseases are diagnosed by detection of pathogens and clinical symptoms. Identification of genes involved in early responses to viruses is important for better knowledge of antiviral defence and development of diagnostic tools. The aim of this study was to search for gene markers common for viral infections in Atlantic salmon based on microarray analyses of a wide range of samples. Gene expression profiles from fish and cell cultures infected with different viruses and treated with the synthetic double-stranded RNA poly(I:C) were compared in order to identify virus responsive genes (VRG). The list of VRG defined in this study contained 117 genes with known or unidentified functions. Several genes, including the most highly ranked one (receptor transporting protein), had not been previously reported to be involved in antiviral defence. VRG were characterized by a rapid induction and low tissue specificity, and their expression levels were related to the viral load. Immunofluorescence analyses of proteins encoded by VRG in cardiac tissue of salmon with the viral disease cardiomyopathy syndrome (CMS) revealed a common expression pattern. In head kidney leukocytes VRG showed comparable or equal responses to CpG and poly(I:C), which mimic respectively bacterial DNA and viral RNA. Most VRG showed highly correlated expression with interferon-a (IFNa). Sequence comparison of salmon VRG with those from other species gave an understanding of the evolution of these genes, which showed a remarkably rapid sequence divergence in comparison with the entire proteome. VRG emerged both before and after separation of teleosts and tetrapods, and among genes found exclusively in fish species there were members of several multigene families: tripartite motif proteins, gig1- and gig2-like proteins. Several VRG, including genes with unknown functions and orthologs to mammalian RNA helicase RIG-I and chemokine C-X-C type 10, were present in cyprinid and salmonid fish but not in the phylogenetically advanced orders, suggesting that they have been lost in the evolution of Teleostei. Apparently, a number of genes involved in antiviral responses in salmon have acquired different functional roles in higher vertebrates.     

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.     

A prospective, randomized comparison of the use versus non-use of topical corticosteroids after laser in situ keratomileusis.

OBJECTIVE: To evaluate the benefit and safety of topical corticosteroids after laser in situ keratomileusis (LASIK). DESIGN: Prospective, randomized, double-masked clinical trial. PARTICIPANTS: A consecutive series of 1747 eyes in 897 patients desiring surgical correction of myopia from plano to -16 diopters (D) with up to 6 D of astigmatism. INTERVENTION: Patients were randomly assigned to topical corticosteroids or artificial tears. MAIN OUTCOME MEASURES: The primary outcome measure was stability of refraction. Secondary outcome measures were differences in best-corrected visual acuity, decrease in spherical refractive myopia, improvement in uncorrected visual acuity, predictability of achieved corrections versus planned corrections, evaluation of postoperative haze, preservation of best-corrected visual acuity, intraocular pressure, and incidence of complications and adverse events. RESULTS: No difference was found between the groups for refractive accuracy, best-corrected or uncorrected visual acuity, or safety. Topical corticosteroids were associated with a prolonged period of refractive regression in moderate to high myopes (-7.25 to -16.00 D) (P = 0.01). Increased haze was noted at the 1 week examination for eyes not receiving topical steroids (P = 0.008); however, in most cases this was clinically insignificant. Thirty-six eyes (2.1%) required supplemental topical corticosteroids unrelated to reoperation. Two eyes received these on the first postoperative day and 15 at the 1-week examination. CONCLUSIONS: Topical corticosteroids did not seem to play any beneficial role in routine postoperative treatment after LASIK, and they were associated with decreased stability of refraction in more highly myopic eyes. Eyes that require additional topical corticosteroids are easily identified at either the initial postoperative examinations or during the course of routine postoperative care.