Differential presentation of group A streptococcal superantigens by HLA class II DQ and DR alleles.

Superantigens have been implicated as pivotal mediators of severe invasive group A streptococcal (GAS) infections, by virtue of their potent immunostimulatory activity. HLA polymorphism has been suggested to influence the susceptibility to severe invasive GAS infection. Here we studied the influence of allelic and isotypic variation of HLA class II molecules on GAS superantigen-induced immune responses using cells derived from patients with bare lymphocyte syndrome, untransfected or transfected with various HLA class II alleles.

Shoulder fusion and free-functioning gracilis transplantation in patients with elbow and shoulder paralysis caused by poliomyelitis.

Six children between 7-16 years of age presented with flail shoulder and elbow caused by poliomyelitis. Shoulder fusion was followed by free-functioning gracilis transplantation to replace the atrophied biceps muscle. The transplanted muscle was reinnervated by either the spinal accessory or phrenic nerve.

Microsurgical reconstruction of lower limb bone defects following tumor resection using vascularized fibula osteoseptocutaneous flap.

This study included 25 patients with lower limb tumors who had wide local resection and reconstruction by vascularized fibula osteoseptocutaneous flap, and who had their surgery performed at least 24 months before the end of the study. The average age at operation was 23.5 years.

Resection replantation of the upper limb for aggressive malignant tumors.

Stage IIB malignant tumors of the upper limb have been traditionally treated by amputation or disarticulation. There have been isolated reports on the technique of segmental resection of the tumor-bearing segment complete with the skin, and replanting the distal arm or forearm with or without neurovascular repair. The present paper describes four cases in which a wide resection margin was achieved in all by resecting the affected cylinder of the limb.

Improved in vivo pancreatic islet function after prolonged in vitro islet culture.

Background: Difficulties with recovering and preserving pancreatic islets have hampered progress in islet transplantation. In previous in vitro studies, our laboratory successfully demonstrated that using serum-free medium for prolonged pancreatic islet culture allows postculture recovery ratios greater than those obtained with standard media with sustained in vitro islet function. The goal of this study was to determine whether culturing of islets in a modified serum-free medium (M-SFM) would sustain function in vivo.

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease.

Devascularization procedure and DSRS: a controlled randomized trial on selected haemodynamic portal flow pattern in schistosomal portal hypertension with variceal bleeding.

Objectives: The use of duplex studies for the portal tree has revolutionized the concepts of haemodynamic pathophysiology in the case of portal hypertensive bleeders. The identification of possible haemodynamic patterns in schistosomal bleeders, and the effects of devascularization procedure and distal lienorenal shunts on a selected haemodynamic pattern, are the aim of this work.

Patients And Methods: Patients (219) with schistosomal hepatic fibrosis and history of bleeding oesophageal varices were studied.

Evidence for superantigen involvement in severe group a streptococcal tissue infections.

Host-pathogen interactions were studied in tissue biopsy samples from patients with severe invasive group A streptococcus (GAS) infections. Skin, subcutaneous tissue, and fascia biopsy samples were divided into clinical grade 1 (no evidence of inflammation [n=7]) or clinical grade 2 (inflamed tissue--erythema and edema including cellulitis, fasciitis, and necrotizing fasciitis [n=24]). In situ imaging demonstrated significantly higher bacterial load in biopsy samples of higher clinical grade (P<.

Evaluation of the triangular cord sign in the diagnosis of biliary atresia.

Background: Infantile cholestasis continues to represent a diagnostic challenge. It is very important to diagnose surgically correctable disorders, such as biliary atresia, in a timely manner to prevent progressive damage to the liver. It has been recently suggested that the triangular cord (TC) sign is a simple and useful tool in the diagnosis of biliary atresia.

Distinct patterns of protein binding to the MAT2A promoter in normal and leukemic T cells.

The metabolism of S-adenosylmethionine (AdoMet), a key molecule in regulating T cell differentiation and proliferation, is different in normal and leukemic T cells. To delineate the basis for these differences we studied the transcriptional regulation of human methionine adenosyltransferase II (MAT II), which catalyzes AdoMet synthesis in these cells. Recently, we identified an Sp1 site in the proximal promoter of the MAT2A gene, which encodes the alpha2 catalytic subunit of MAT II, that is essential for the in vitro and in vivo promoter activity in Jurkat leukemic T cells, and that involves binding of the nuclear factors Sp2 and Sp3, but not Sp1.

Reciprocal, temporal expression of SpeA and SpeB by invasive M1T1 group a streptococcal isolates in vivo.

The streptococcal pyrogenic exotoxins (Spes) play a central role in the pathogenesis of invasive group A streptococcal (GAS) infections. The majority of recent invasive GAS infections have been caused by an M1T1 strain that harbors the genes for several streptococcal superantigens, including speA, speB, speF, speG, and smeZ. However, considerable variation in the expression of Spe proteins among clonal M1 isolates has been found, and many of the speA-positive M1 strains do not produce detectable amounts of SpeA in vitro.

Regulation of the human MAT2B gene encoding the regulatory beta subunit of methionine adenosyltransferase, MAT II.

Methionine adenosyltransferase (MAT) catalyzes the biosynthesis of S-adenosylmethionine (AdoMet), a key molecule in transmethylation reactions and polyamine biosynthesis. The MAT II isozyme consists of a catalytic alpha2 and a regulatory beta subunit. Down-regulation of the MAT II beta subunit expression causes a 6-10-fold increase in intracellular AdoMet levels.

Invasive Group C Streptococcus infection associated with rhabdomyolysis and disseminated intravascular coagulation in a previously healthy adult.

Infections with Group C Streptococci can lead to severe disease, particularly in individuals with underlying illnesses such as cardiovascular disease, malignancy or immunosuppression. We report the first case of rhabdomyolysis and disseminated intravascular coagulation secondary to Group C Streptococcus in a previous healthy male. A toxic shock-like syndrome associated with Group C and Group G Streptococci has been reported.

Three-phase double-arc plasma for spectrochemical analysis of environmental samples.

A new instrument, which uses a three-phase current to support a double-arc argon plasma torch for evaporation, atomization and excitation of solid or powder samples, is described. The sampling arc is ignited between the first and second electrode while the excitation arc is ignited between the second and third electrode. Aerosol generated from the sample (first electrode) is swept by argon gas, through a hole in the second electrode (carbon tubing electrode), into the excitation plasma.

Blocking pulmonary ICAM-1 expression ameliorates lung injury in established diet-induced pancreatitis.

Objective: To determine whether blocking the cell surface expression of intracellular adhesion molecules (ICAM-1) in established severe acute pancreatitis (AP) would ameliorate pulmonary injury.

Summary Background Data: Lung injury in AP is in part mediated by infiltrating leukocytes, which are directed to lung tissue by ICAM-l. The authors' laboratory has previously demonstrated that AP results in overproduction of inflammatory cytokines, upregulation of pulmonary ICAM-1 expression, and a concomitant infiltration of neutrophils, which results in lung injury.

Regulation of the human MAT2A gene encoding the catalytic alpha 2 subunit of methionine adenosyltransferase, MAT II: gene organization, promoter characterization, and identification of a site in the proximal promoter that is essential for its activity.

Mammalian methionine adenosyltransferase II (MAT II) consists of a catalytic alpha2/alpha2' and a regulatory beta subunit. Up-regulation of alpha2 subunit expression is associated with increased intracellular levels of S-adenosylmethionine, the major methyl group donor and a key compound in cell metabolism and polyamine synthesis. Previous studies have shown that expression of the alpha2 subunit is differentially regulated in normal and malignant cells.

Host variation in cytokine responses to superantigens determine the severity of invasive group A streptococcal infection.

Cytokines elicited by superantigens have been suggested to play a central role in severe systemic clinical manifestations of gram-positive sepsis. Here we provide evidence for a potent inflammatory cytokine response in acute invasive group A streptococcal infections, and show a direct correlation between the magnitude of this response and the severity of systemic manifestations of the disease. Severe invasive cases suffering from toxic shock and/or necrotizing fasciitis had significantly higher frequencies of IL-2-, IL-6-, and TNF-alpha-producing cells in their circulation as compared to non-severe invasive cases (p=0.

Relative neutralizing activity in polyspecific IgM, IgA, and IgG preparations against group A streptococcal superantigens.

In this study we compared the ability of different immunoglobulin (Ig) preparations containing IgG, IgM, and/or IgA to neutralize the activity of streptococcal pyrogenic exotoxin A (SpeA) or culture supernatant from a clinical group A streptococcal isolate. All Ig preparations markedly inhibited the mitogenic and cytokine-inducing activity of SpeA and culture supernatant at concentrations of 0.05-0.

Inverse relation between disease severity and expression of the streptococcal cysteine protease, SpeB, among clonal M1T1 isolates recovered from invasive group A streptococcal infection cases.

The streptococcal cysteine protease (SpeB) is one of the major virulence factors produced by group A streptococci (GAS). In this study we investigated if differences exist in SpeB production by clonally related M1T1 clinical isolates derived from patients with invasive infections. Twenty-nine of these isolates were from nonsevere cases and 48 were from severe cases, including streptococcal toxic shock syndrome (STSS) and necrotizing fasciitis (NF) cases.

Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivo.

Acute pancreatitis (AP) is characterized by release of proteolytic enzymes from the pancreas and a powerful inflammatory cytokine cascade that mediates the systemic manifestations and contributes to the mortality of the disease. The purpose of this study was to examine a potential link between pancreatic proteolytic enzymes, which are increased in AP, and cytokine production. To evaluate this, we incubated rat peritoneal macrophages (PMO) with increasing concentrations of trypsin and measured cytokine production.

Intravenous immunoglobulin therapy for streptococcal toxic shock syndrome--a comparative observational study. The Canadian Streptococcal Study Group.

Twenty-one consecutive patients with streptococcal toxic shock syndrome (TSS) between December 1994 and April 1995 were treated with a median dose of 2 g of intravenous immunoglobulin (IVIG)/kg (cases) and were compared with 32 patients with streptococcal TSS between 1992 and 1995 who did not receive IVIG therapy (controls). The outcome measure was 30-day survival. Patient plasma was tested for its ability to inhibit T cell activation induced by the infecting strain.

Genetic relatedness and superantigen expression in group A streptococcus serotype M1 isolates from patients with severe and nonsevere invasive diseases.

The relatedness of group A streptococcal (GAS) strains isolated from 35 Canadian patients with invasive disease of different severity was investigated by a variety of molecular methods. All patients were infected with M1T1 strains and, based on clinical criteria, were classified as severe (n = 21) and nonsevere (n = 14) invasive GAS infection cases. All the M1 strains studied had the emm1.

Temporal correlation of tumor necrosis factor-alpha release, upregulation of pulmonary ICAM-1 and VCAM-1, neutrophil sequestration, and lung injury in diet-induced pancreatitis.

Lung injury is a major cause of patient morbidity in acute pancreatitis. The purpose of this study was to examine the mechanism of pulmonary infiltration and lung injury in acute pancreatitis. Mice were fed a choline-deficient/ethionine-supplemented (CDE) diet for 144 hours to induce severe acute pancreatitis.

Preferential stimulation of human lymphocytes by oligodeoxynucleotides that copy DNA CpG motifs present in virulent genes of group A streptococci.

Immunostimulatory oligodeoxynucleotides (ODN) containing CpG dinucleotides have been shown to stimulate murine and human lymphocytes. We investigated the presence of stimulatory DNA motifs in specific group A streptococcal (GAS) genes to elucidate the potential role of DNA in the immunopathogenesis of GAS infections. Despite low GC content in GAS DNA, the emm1 gene encoding the streptococcal M1 protein contained a relatively high frequency of TTCG(T/C), TCGTCG and (G/A)TCGT motifs that preferentially stimulated human lymphocytes.

Quantitative measurement of P- and E-selectin adhesion molecules in acute pancreatitis: correlation with distant organ injury.

Objective: To determine whether expression of P- and E-selectin molecules is associated with the development of systemic organ manifestations in acute pancreatitis (AP).

Summary Background Data: Overproduction of inflammatory cytokines in AP induces expression of adhesion molecules, which may lead to increased leukocytic infiltration and tissue damage. Understanding the temporal expression of these molecules could afford better measures for therapeutic intervention.