Bilateral rupture of diaphragm with delayed strangulation

A 64-year-old woman presented in shock. The computed tomography (CT) scan confirmed rupture of the left diaphragm with strangulation. Three days after surgery, the patient developed herniation of abdominal contents on the right side with cardiorespiratory collapse. Marlex mesh was used to repair on the right side. Postoperatively, she needed partial gastrectomy for massive duodenal ulcer bleeding. A dual chamber pacemaker was used to correct the complete heart block.     

Cardiac beta-adrenergic responsiveness is well preserved in moderate protein calorie malnutrition from semistarvation

Twenty-one dogs underwent instrumentation of the left ventricle with ultrasonic dimension to study the effects of acute protein-calorie malnutrition on the adrenergic responsiveness of the heart. This study allowed a chronic and dynamic measurement of the major cardiac axes and the ventricular wall thickness, which in turn can be used to derive sophisticated measurements of global and intrinsic left ventricular function. Of the 21 dogs, 11 received a protein- and calorie-deficient diet designed to achieve a mean weight loss from a baseline of 20-25% over a 4-week period. The other 10 dogs received a normal diet. Dogs were also randomized to receive either acute propranolol beta-receptor blockade (n = 9) or acute isoproterenol beta-receptor stimulation (n = 12) during their baseline studies. Of the nine dogs given propranolol, five were subsequently malnourished and four served as controls. Of the 12 given isoproterenol, six were rendered malnourished and six were controls. All dogs were studied at both baseline and 4 weeks and received drugs in an identical fashion during both studies. The significant changes with malnutrition consisted of decreases in heart rate, cardiac mass, and left ventricular wall thickness. The degree of change in stroke volume, ejection fraction, cardiac output, dp/dt, and Emax (index of left ventricular contractility), with the administration of propranolol or isoproterenol was unaltered by malnutrition. These data support the contention that moderate protein-calorie malnutrition is well tolerated in instrumented, unstessed dogs and that the left ventricle's capacity to respond to beta-stimulation and to tolerate beta-blockade is largely unimpaired.     

Immunogenicity and protective efficacy of the alpha C protein of group B streptococci are inversely related to the number of repeats.

Infection by group B streptococci (GBS) is an important cause of bacterial disease in neonates. Alpha C protein is a protective cell surface-associated protein of GBS. This protein contains a repeat region flanked by N and C termini. Variable expression of tandem repeating units of alpha C proteins had been found among clinical isolates of GBS. We examined the effect of the number of repeats on the immunogenicity of the alpha C protein and its ability to elicit protection from GBS infection in a neonatal mouse model. Mice were immunized with purified alpha C proteins of constructs containing various numbers of repeats (n = 1, 2, 9, and 16) and the N- and C-terminal regions. Both the N-terminal and the repeat regions contain protective and opsonic epitopes. Antibody responses to the alpha C protein constructs with various numbers of repeats were tested with enzyme-linked immunosorbent assay plates coated with either native, nine-repeat alpha C protein or "repeatless" N-terminal antigen. An inverse relationship was found between the number of repeats and the immunogenicity of the alpha C protein; this effect was most pronounced on titers of antibody to the N-terminal region. An inverse relationship was also observed between the number of repeats and protective efficacy, i.e., mouse dams immunized with 5 microg of one- or nine-repeat alpha C protein transferred protective immunity to 65 or 11% of their pups, respectively (P < 0.0001). Thus, the presence of multiple repeats appears to lessen the antibody response to the complete alpha C protein, and especially the antibody response to its N-terminal region, and suggests a mechanism whereby repeat elements contribute to the evasion of host immunity.     

A monoclonal antibody identifies a protective C-protein alpha-antigen epitope in group B streptococci.

Group B streptococci (GBS) are the leading causes of neonatal sepsis and meningitis in the United States, with a high rate of fatality and serious morbidity despite appropriate therapy. The C-protein antigens of GBS appear to be important in immunity to experimental infection, yet these antigens remain incompletely characterized with respect to their number, structure, and function. None of these proteins has yet been purified to homogeneity. We have developed a novel method for extraction of surface proteins from the A909 (Ia/c) strain of GBS by using mutanolysin. Antibodies raised in rabbits against these partially purified proteins conferred passive protection to lethal GBS infection in mice challenged with a GBS strain expressing C proteins with a heterologous capsule type. In addition, mouse monoclonal antibodies were produced and identified by reactivity with the mutanolysin-extracted proteins. One of these monoclonal antibodies (4G8) identifies an epitope on the alpha-antigen of the GBS C proteins (identified by protease susceptibility and mouse protection). On sodium dodecyl sulfate-polyacrylamide gels, this epitope appears as a series of regularly spaced bands ranging in apparent molecular mass from 160,000 to 30,000 Da. The monoclonal antibody 4G8 induces opsonic killing of GBS and protects mice from lethal challenge with GBS. Thus, the 4G8 monoclonal antibody identifies a fully protective epitope on the C-protein alpha-antigen of GBS.     

Cloned alpha and beta C-protein antigens of group B streptococci elicit protective immunity.

Streptococcus agalactiae (group B streptococci [GBS]) is the leading cause of neonatal sepsis and meningitis in the United States. The surface-associated C proteins of GBS play a role in immunity, but their number, size, structure, function, and virulence properties have not been well characterized. A recombinant library of DNA fragments from GBS strain A909 (type Ia/C) was prepared in the plasmid pUX12, a specially constructed Escherichia coli expression vector. The library was screened with a rabbit antiserum shown to be protective for passive immunity to GBS infection in a mouse lethality model. Clones were divided into two distinct groups on the basis of DNA-DNA cross-hybridization, restriction enzyme analysis, and the expression of antigenic proteins in E. coli. A characteristic clone from each group was chosen for further study. Clone pJMS23 expresses gene products that biochemically and immunologically correspond to the trypsin-resistant, C-protein alpha antigen. Clone pJMS1 expresses a gene product that binds to immunoglobulin A and is similar to the trypsin-sensitive, C-protein beta antigen. Antisera raised in rabbits against E. coli containing each of the plasmid clones were able to elicit protective immunity in mice challenged by GBS strains carrying the C proteins but not by non-C-protein-bearing strains. Southern blot analysis shows no DNA homology between the clones, and there is no immunological cross-reactivity between the antigens they express. Therefore, pJMS23 and pJMS1 encode two different C proteins that define unique protective epitopes.     

doublecortin is the major gene causing X-linked subcortical laminar heterotopia (SCLH)

Subcortical laminar heterotopia (SCLH), or 'double cortex', is a cortical dysgenesis disorder associated with a defect in neuronal migration. Clinical manifestations are epilepsy and mental retardation. This disorder, which mainly affects females, can be inherited in a single pedigree with lissencephaly, a more severe disease which affects the male individuals. This clinical entity has been described as X- SCLH/LIS syndrome. Recently we have demonstrated that the doublecortin gene, which is localized on the X chromosome, is implicated in this disorder. We have now performed a systematic mutation analysis of doublecortin in 11 unrelated females with SCLH (one familial and 10 sporadic cases) and have identified mutations in 10/11 cases. The sequence differences include nonsense, splice site and missense mutations and these were found throughout the gene. These results provide strong evidence that loss of function of doublecortin is the major cause of SCLH. The absence of phenotype-genotype correlations suggests that X-inactivation patterns of neuronal precursor cells are likely to contribute to the variable clinical severity of this disorder in females.