Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1.

BACKGROUND: The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to provide nonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least at the phenotypic level. The underlying genetic mechanisms are as yet poorly understood. RESULTS: We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes combined with activation of Ebox transcription factors appears to enhance susceptibility to B. thuringiensis. CONCLUSIONS: Our findings highlight the role of a single gene, npr-1, in fine-tuning nematode immune defense, showing the ability of the invertebrate immune system to produce highly specialized and potentially opposing immune responses via single regulatory genes.

Anti-Aspergillus immunoglobulin-G testing in serum of hematopoietic stem cell transplant recipients.

BACKGROUND: Pulmonary invasive aspergillosis (IA) is a major clinical problem in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Acquisition of IA during allo-HSCT by inhalation of spores is the rationale for the widespread use of air filtration systems. Recent data suggest that activation of fungal growth in already colonized patients is a relevant factor, and a recent study found a positive correlation of serum immunoglobulin responses against purified recombinant Aspergillus fumigatus proteins before allo-HSCT with the incidence of IA after allo-HSCT. METHODS: To investigate the clinical utility of this approach, we performed a prospective study. We used a commercially available and standardized assay for detection of anti-Aspergillus immunoglobulin-G (aA-IgG) in serum (Platelia(™) Aspergillus IgG) that has previously demonstrated high sensitivity and specificity. RESULTS: In a cohort of 104 allo-HSCT recipients, we measured aA-IgG and Aspergillus antigen serum levels before allo-HSCT, and weekly during hospital stay. Overall prevalence of possible, probable, and proven IA during hospital stay was 10%, 6%, and 0%. We found no correlation between aA-IgG levels before allo-HSCT, or after allo-HSCT, and the prevalence of IA during hospital stay. Furthermore, median aA-IgG levels did not differ between patients with history of probable or proven IA, as compared to patients without history of IA. CONCLUSIONS: Taken together, our data argue against the clinical utility of measuring aA-IgG levels for diagnosis or prediction of IA in patients undergoing allo-HSCT.

A Super-Capacitive Pressure Sensor for a Urethral Catheter.

Urinary incontinence can be due to neuromuscular or structural problems in either the bladder or the urethra. Urodynamics is often used to analyze the patientspecific cause of urinary incontinence. In urodynamics, a challenging part of the studies involves measurement of the urethral (contact) pressure profile. Here we present an instrumented urethral catheter that is equipped with a novel super-capacitive pressure transducer that is highly sensitive to the applied pressure. A solid ionic electrolyte is used to create a high capacitance device. Through an innovative design the solid electrolyte is made and bounded to a 3d printed soft balloon and then assembled on a 6 Fr urethral catheter. In this paper the design, fabrication and evaluation of the highly-sensitive instrumented catheter's performance are discussed.

Genitourinary prosthetics of the present and future.

Development of implantable prosthetic devices to restore genitourinary function has evolved from applying electrical stimulation techniques for bladder evaluation to adapting fluid energy transfer system for occlusion of the urethra to increase outlet resistance. These hydraulic prostheses have been implanted in several hundred patients in medical centers around the world. The principles behind the operation of this closed-loop system, an some alternative designs that simplify the implant procedure, are described here.

Cystometry. VI. Interpretation.

Cystometry should be performed under direct supervision of a physician, and interpretation must be supplemented by additional test procedures.

An implantable mechanical urinary sphincter: a new nonhydraulic design concept.

OBJECTIVES: We present data concerning an artificial implantable mechanical urinary sphincter that was designed to eliminate the inherent problems of the current hydraulic artificial urinary sphincter (American Medical System [AMS] 800). Our goal was to design a sphincter that creates urethral compression similar to the AMS 800 but creates the force without the use of fluid, thereby eliminating as much as 50% of the reoperations seen with the AMS 800, which occur because of fluid-related malfunctions. METHODS: An implantable artificial mechanical sphincter consisting of a compressive coil encompassed in a polytetrafluoroethylene sheath was devised and tested in 6 live mongrel dogs to establish compressive force versus bladder pressure data, so as to provide data to create a mechanical sphincter for use in humans. RESULTS: A direct relationship between bladder leakage pressure and cable tension force was demonstrated in all 6 experimental animals, thereby creating a mathematical equation that can be used by mechanical engineers to design a mechanical sphincter for use in humans. CONCLUSIONS: This study demonstrated that a mechanical urinary sphincter can be created that will provide continence and eliminate the problems associated with the hydraulic aspect of the AMS 800. In doing so, nearly 50% of the reoperations seen with the current AMS 800 can be eliminated, thereby improving the quality of life of patients for whom an artificial urinary sphincter is indicated.

Cystometry. (2). Central nervous system organization of detrusor reflex.

Micturition is a brain stem reflex dependent on the integrity of reticulospinal and sensory pathways in a manner similar to respiration and blood pressure regulation. The detrusor reflex which is evoked by bladder distention and may appear in the normal cystometrogram is a result of the integrity of the circuit. Interruption of the spinal cord pathways of this loop by trauma or by spinal cord tumors results in abolition of detrusor reflex. Partial interruption results in an uninhibited detrusor reflex.

Cystometry: III. Cystometers.

Cystometers may employ either fluid (water) or gas (air or carbon dioxide) as the distending medium. The operation of air and carbon dioxide cystometers is described, and a comparison is given of the various systems currently in use.

Cystometry. V. Bladder sensation.

Bladder sensation is an important variable in cystometry. Sensory complaints are a valuable portion of the history which may be further defined and documented by the cystometric examination.

New method for continuous measurement of nocturnal penile tumescence and rigidity.

A new technique for continuous recording of penile rigidity and tumescence has been developed. This methodology has been utilized in initial studies to define erectile function in both normal and impotent males. Accurate recording of tumescence and rigidity have been utilized to document the decline in erectile function associated with organic impotence.

Electrophysiological technique for evaluating lesions of the conus medullaris and cauda equina.

The authors describe the use of evoked electromyographic responses recorded in the anal sphincter induced by stimulation of the bladder wall and urethra in evaluating lesions of the conus medullaris and cauda equina in 110 patients. This reflex response took effect by way of the pelvic nerves and cauda equina to the sacral cord where the pudendal nerve nucleus was activated, resulting in a contraction of the external anal sphincter. Various lesions along this pathway have been shown to produce either increased latencies and depressed responses or complete loss of response depending on the extent of the lesion. The correlation of results of this technique with clinical, myelographic, and operative findings indicate it to be a useful clinical tool.

[Development of an implantable artificial urinary sphincter (author's transl)]. / Entwicklung eines implantierbaren künstlichen Blasenverschlussmechanismus

Fifteen years experience with investigations of the neurologic aspects of lower urinary tract function has produced a therapeutic rationale that includes utilization of prosthetic devices in selected patients. Development of an implantable artificial sphincter evolved as a necessity for restoring urinary continence became apparent. The experimental design of animal models and the technologic methods in device development are herein described.