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Microreview: capsule-associated genes of Cryptococcus neoformans.

Cryptococcosis, caused by Cryptococcus neoformans is a common systemic mycosis in man and animals, particularly immunocompromised patients. This pathogenic fungus produces a thick extracellular polysaccharide capsule. Four capsule-associated genes (CAP10, CAP59, CAP60, CAP64) were cloned and sequenced, and proved to be essential for capsule synthesis. However biochemical functions of CAP gene products have not been clarified yet. Recently, the relatedness of the polysaccharide capsule and four capsule-associated genes has partly been elucidated. Nucleotide sequence of four CAP gene fragments was analyzed for phylogenetic relationships, and they were in agreement with the conventional classification of varieties and serotypes within C. neoformans. Expression of four CAP genes and capsule size were examined using two media containing different amount of glucose, and the results indicated that CAP genes might play important roles in elaboration of extracellular polysaccharide capsule. Furthermore, analyses of CAP genes in various clinical samples would give the useful information to diagnose cryptococcosis in human and animals.

Animals↗

Endocytosis and transcytosis by the capsule cell of vertebrate muscle spindles.

The vertebrate muscle spindle has been observed to be ionically and biochemically isolated from the surrounding muscle fibers by the spindle capsule. We have explored the possibility that the capsular cells are endocytically active and can transport both small molecules and macromolecules into the capsular space. Transcytosis (the endocytic transport of extracellular substances across a cell) through the capsule cell layer was examined with muscle spindles of snake, rat, and cat using fluorescent markers for fluorescence microscopy and horseradish peroxidase (HRP) and ferritin for electron microscopic examination. The fluorescent markers were actively taken up by capsule cells, making it easy to locate the spindle capsular region of spindles among extrafusal fibers by their strong fluorescence. Ferritin and HRP were used to identify the pathway of transcytosis by electron microscopy. These markers were found in endocytic vesicles of capsule cells, in the narrow space between capsule layers and in the capsular space, indicating that the marker was transferred to the capsular space by the pinocytic activity of capsule cells. Scattered cells in the capsule of cat muscle spindles appeared to take up fluorescein isothiocyanate (FITC)-coupled beta-glucuronidase by a receptor-mediated process. The uptake was sensitive to temperature and [Ca2+], and specifically inhibited by yeast mannan. By electron microscopy with dilute HRP (10 micrograms/ml) this specific uptake was by isolated cells in the interlamellar space. The functional significance of the above findings is discussed.

Animals↗

Hearing loss in Paget's disease of bone: the relationship between pure-tone thresholds and mineral density of the cochlear capsule.

We have developed a unique method of quantitative computed tomography (QCT) that enables measurement of the density of the cochlear capsule in vivo. We performed pure-tone audiometry and QCT on 67 ears from 35 subjects with radiographically confirmed Paget's disease of the skull and on 40 ears from twenty volunteer subjects. The Pearson product-moment correlation coefficients (age- and sex-adjusted) in the group affected by Paget's disease were -0.63 for left ears and -0.73 for right ears for high-frequency air conduction pure-tone thresholds (mean of 1, 2, and 4 kHz) versus cochlear capsule density. Correlation coefficients (age- and sex-adjusted) between cochlear capsule density and air-bone gap (mean at 0.5 and 1 kHz) for the affected group were -0.67 for left ears and -0.63 for right ears. All correlations between hearing thresholds and cochlear capsule density in pagetic subjects were significant at p < 0.001. The regressions were consistent throughout the ranges of hearing level. There were no significant correlations between cochlear capsule mean density and hearing level in the volunteer subjects. These findings demonstrate the feasibility of precise and accurate density measurements in the temporal bone in vivo and support the use of the mean cochlear capsule density as a marker of disease effect. Alteration of cochlear capsule bone density may be related to the mechanisms of hearing loss in Paget's disease of bone.

Adult↗

Deletion of the tissue response against alginate-pll capsules by temporary release of co-encapsulated steroids.

Transplantation of encapsulated living cells is a promising approach for the treatment of a wide variety of diseases. Large-scale application of the technique, however, is hampered by inflammatory responses against the capsules. In the present study, we investigate whether tissue responses against alginate-PLL-alginate capsules can be modulated by co-encapsulation and temporary release of immunomodulating factors such as dexamethasone. Such an approach may be mandatory in order to increase the function and survival of encapsulated tissue since it has been shown that the tissue response can be caused by many, insurmountable factors. In an in vitro assay, we demonstrated an antiproliferative effect of dexamethasone-containing capsules on L929-mouse-fibroblasts. Subsequently, capsules prepared of purified alginate with or without solved dexamethasone were implanted in the peritoneal cavity of rats and retrieved one month later for histological evaluation. Most of the capsules without dexamethasone proved to be overgrown and adherent to the abdominal organs whereas with co-encapsulated dexamethasone the majority of the capsules were found freely floating in the peritoneal cavity without overgrowth. We conclude that co-encapsulation of dexamethasone has a profound effect on fibroblasts and macrophages adherence to immunoisolating capsules.

Alginates↗

The volume and hydration of the Cryptococcus neoformans polysaccharide capsule.

We present a new method to measure capsule size in the human fungal pathogen Cryptococcus neoformans that avoids the limitations and biases inherent in India ink measurements. The method is based on the use of gamma-radiation, which efficiently releases the capsule from the cell. By comparing the volume of irradiated and non-irradiated cells, one can accurately estimate the relative size of the capsule per cell. This method was also used to obtain an estimate of the capsule weight and water content. The C. neoformans capsule is a highly hydrated structure in all the conditions measured. However, after capsule enlargement, the amount of capsular polysaccharide significantly increases, suggesting a that capsule growth has a high energy cost for the cell.

Cryptococcus neoformans↗

Effect of shear stress on adhering polyelectrolyte capsules.

A parallel plate flow chamber was implemented to study the deformation and adhesion of individual spherical hollow polyelectrolyte multilayered shells adhering to a coated surface. The device provides a well-defined laminar flow allowing the determination of the shear stress to which the capsules are being exposed up to 15 N/m(2). The results of the investigations indicate a strong dependence of the adhesion and mechanical resistance on the capsule size and wall thickness. Thin walled capsules, constituted of 8 polyelectrolyte layers (thickness congruent with 12 nm), are immediately deformed when exposed to flow while thick capsules, constituted of 16 layers (thickness congruent with 24 nm), of equal dimensions are detached from the surface for drag forces below 50 nN. It was observed that adhering capsules exposed to flow undergo an increase in their adhesion area in the direction of flow, resulting in rolling of the capsules. It was also found that the resistance of the capsules decreases after acetone treatment, indicating a weakening of the polyelectrolyte multilayer structure in the presence of this solvent.

Journal Article↗

Comparison of intravitreal versus posterior sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema.

PURPOSE: To compare the safety and efficacy of intravitreal versus posterior Sub-Tenon's capsule injection of triamcinolone acetonide for diffuse diabetic macular edema. DESIGN: Prospective, double-masked, randomized controlled trial. PARTICIPANTS: Twelve patients (24 eyes) with bilateral diffuse diabetic macular edema. INTERVENTION: One eye of each patient was randomly assigned to receive a single 4-mg triamcinolone acetonide intravitreal injection and the fellow eye to receive a 40-mg triamcinolone acetonide posterior Sub-Tenon's capsule injection. MAIN OUTCOME MEASURES: Changes in visual acuity and central macular thickness obtained using optical coherence tomography were measured during a 6-month follow-up. Potential treatment complications were monitored, including increases in intraocular pressure (IOP) and cataract progression. RESULTS: Both intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide resulted in significant but transient improvements in central macular thickness. The mean (+/-standard deviation [SD]) central macular thickness in eyes with intravitreal injection was significantly thinner than in the Sub-Tenon's capsule-injected eyes at 1 month (226.8+/-41.7 microm and 431.5+/-165.8 microm, respectively; P = 0.002) and 3 months (242.3 +/- 93.9 microm and 364.7+/-78.2 microm, respectively; P = 0.005) after triamcinolone acetonide injection. The mean visual acuity (logarithm of the minimum angle of resolution) in the intravitreally injected eyes was significantly better than in the Sub-Tenon's capsule-injected eyes at 3 months post injection (0.832+/-0.293 and 1.107+/-0.339, respectively; P = 0.004). Intraocular pressure did not show any significant difference between the 2 forms of triamcinolone acetonide delivery at any follow-up visit, and no eyes had IOPs >25 mmHg. CONCLUSIONS: The findings from our study neither advocate nor support the use of corticosteroids for the treatment of diabetic macular edema, but do imply that both intravitreal and Sub-Tenon's capsule injections of triamcinolone acetonide may be equally tolerated, with short-term performance clearly favoring the intravitreal (4 mg) more than the SBT capsule (40 mg) route for the anatomic and functional aspects of improvement tested in this investigation.

Adult↗

[Retention of a videoendoscopy capsule leading to small bowel obstruction in a patient with recurrence of rectum carcinoma].

Wireless capsule endoscopy has become the most sensitive and most specific diagnostic modality for evaluation of the mucosa of the small bowel and is increasingly used by gastroenterologists. The most important complication is retention of the video capsule in patients with pre-existing strictures of the small bowel. We report on a case of a 73-year-old man who underwent capsule endoscopy because of obscure gastrointestinal bleeding. The capsule was retained in the ileum leading to small bowel obstruction during the following days. Surgery demonstrated that the capsule had been retained in a segment of the ileum which was infiltrated by a recurrence of rectum carcinoma. Radiologists should know this complication of capsule endoscopy as well as the relative importance of the radiographic techniques for evaluating the small bowel, which possibly could predict a free passage of the video capsule.

Aged↗

Human lumbar facet joint capsule strains: II. Alteration of strains subsequent to anterior interbody fixation.

BACKGROUND CONTEXT: In cases of low back pain associated with biomechanical lumbar instability, anterior interbody fixation can be used as a surgical treatment, but its affect on facet joint capsule strains is unknown. PURPOSE: To determine the effect of a single-level anterolateral interbody fixation, the changes in lumbar facet joint capsule strains at the level of and adjacent to the fixation were evaluated. STUDY DESIGN/SETTING: Human cadaveric lumbar spine specimens were tested under displacement control before and after the addition of a single anterior thoracolumbar plate (ATLP) on the L4-L5 motion body. METHODS: Ligamentous lumbar spine specimens (n=7) were potted and actuated before and after fixation of the L4-L5 motion segment with an ATLP in motions of extension, flexion, left and right bending. Joint moments were calculated from the applied load and respective moment arms. Intervertebral angulation was measured using biaxial inclinometers mounted onto adjacent vertebrae. Plane strains of the capsules were measured by optically tracking the displacements of small, infrared reflective markers glued to capsule surfaces. Statistical differences (p<.05) in moment, intervertebral angle and capsular strain were assessed using analysis of variance and comparison of linear regression lines. RESULTS: Fixation resulted in an increase in moment at the three vertebral levels for all motions. There was also an increase in intervertebral angle at L3-L4 and L5-S1, and a decrease in intervertebral angle at L4-L5 for all motions. Plane strains in the L3-L4 and L5-S1 facet capsules increased as a result of the fixation. L4-L5 facet capsules experienced decreased and increased strains ipsilateral and contralateral, respectively, to the instrumentation. CONCLUSION: Restriction of a vertebral motion segment using a single ATLP increased adjacent capsular strains, which if suprathreshold for capsule nociceptors, could play a role in low back pain.

Adult↗

Endoscopic capsule endoscope delivery for patients with dysphagia, anatomical abnormalities, or gastroparesis.

BACKGROUND: Capsule endoscopy relies on an intact swallowing mechanism and unimpeded passage of the capsule through the pylorus. A technique is described for endoscopic delivery of the capsule in patients with dysphagia, anatomical abnormality, or gastroparesis. METHODS: EGD is performed with concomitant placement of an overtube. A foreign body net retrieval device is passed through the endoscope and used to grasp the activated capsule in the net. The endoscope then is advanced through the overtube, and the capsule is released in the duodenum. OBSERVATIONS: Five patients underwent endoscopic placement of the capsule. Relative contraindications to peroral ingestion were the following: oropharyngeal dysphagia, pyloric stenosis (2), prior gastric surgery, and gastroparesis. Endoscopic delivery was successful in all cases and yielded positive findings in 4. There was no complication. CONCLUSIONS: Endoscopic delivery of the capsule endoscope for patients with dysphagia, anatomical abnormality, or gastroparesis is safe and effective.

Adult↗

Capsule endoscopy is safe and effective after small-bowel resection.

BACKGROUND: Because capsule endoscopy is a relatively new technique, the indications, the contraindications, and the complications of the procedure have not been fully delineated. The present study was undertaken to determine the utility and the safety of capsule endoscopy in patients who have undergone small-bowel resection. METHODS: Ten patients (mean age 48.5 [8.4] years) were included in the study. Eight had undergone surgical resection for Crohn's disease and two for malignancy. Indications for capsule endoscopy included suspected relapse of Crohn's disease or of malignancy, with a negative conventional evaluation that included barium contrast radiography, upper endoscopy, colonoscopy, US, CT, and push enteroscopy. Capsule endoscopy was performed in the standard fashion. OBSERVATIONS: No side effects were observed in any patient. Natural excretion of the capsule was reported at a mean of 72 hours. In 7 patients (70%), capsule endoscopy revealed recurrence of disease in the small bowel: one recurrent malignancy, 6 recurrent Crohn's disease. The information gained was helpful with respect to further treatment for all of these patients. CONCLUSIONS: Capsule endoscopy is safe and effective in the evaluation of patients who have undergone surgical resection of the small bowel for benign or malignant disease.

Crohn Disease↗

Immunohistochemical and ultrastructural study of rhabdosphincter component of the prostatic capsule.

PURPOSE: There has been no complete agreement on functional anatomy of muscular components of the urethral sphincteric mechanism, particularly in the male patient. The prostatic capsule was studied to define its histological structure and to determine whether its rhabdosphincter component (prostatocapsular rhabdosphincter) consists only of slow twitch or slow and fast twitch striated myofibers. MATERIALS AND METHODS: We studied 11 whole prostates, including 1 obtained at autopsy and 10 by radical prostatectomy. Samples of prostatic capsule from 4 operative specimens were studied by electron microscopy. Whole mount paraffin sections from transverse slices of the remaining 7 prostates were double labeled with avidin biotin conjugate immunostaining using the primary monoclonal antibodies anti-alpha smooth muscle actin plus anti-alpha sarcomeric actin (all striated myofibers) or antiskeletal myosin fast (fast myofibers only). Tissue components of the prostatic capsule, including smooth muscle and slow versus fast twitch striated myofibers, were quantified by computerized image analysis. RESULTS: The prostatic capsule consisted of collagen, smooth muscle and striated myofibers. It varied in thickness and proportion of the 3 components among specimens, and in each in relation to transverse circumferential aspect and craniocaudal (horizontal) level of the prostate. Collagen and smooth muscle were equally important components. Striated muscle elements within the capsule consisted of fast twitch and dominant slow twitch myofibers, and were much more abundant in the caudal (distal, lower) than the cranial (proximal, upper) half of the capsule, where they were deficient ventrally (anteriorly) and dorsally (posteriorly). The prostatocapsular rhabdosphincter thus had a butterfly-like appearance, with a thick posteriorly open ring at the apex and 2 thinner, divergent leaflets tapering toward the base at the bladder neck. The fast myofiber population decreased progressively from apex to base of prostate. CONCLUSIONS: Proof is provided for mixed slow and fast twitch myofiber structure of the prostatocapsular component of human male rhabdosphincter. Sustained (tonic) contraction of slow myofibers probably reinforces the role of urethral smooth muscle in maintaining continence during bladder filling. Swift contraction of fast myofibers that abound caudally in the capsule probably supplements urethral closure by the bulkier membranous urethral part of the rhabdosphincter in preventing leakage of urine under stress when voiding is imminent or willfully withheld.

Aged↗

Posterior capsule opacification: a specular microscopic study.

Posterior capsule opacification following extracapsular cataract extraction is a manifestation of migration of lens epithelial cells onto the posterior capsule. Collagen production by these epithelial cells results in white "fibrotic" opacities. These cells have myoblastic features and their contraction produces wrinkling of the posterior capsule resulting in visual distortion. A high magnification, in vivo specular microscopic study of human posterior capsules following extracapsular cataract extraction is described. In vivo findings correlate with histopathologic observations made on opacified posterior capsules. Lens epithelial cells migrate onto the posterior capsule and produce basement membrane and collagen. Collagen production is associated with a spindle-shaped appearance of the hyperplastic cells. This technique is useful for clinical research on posterior capsule opacification, including the evaluation of interventions designed to treat or prevent this complication.

Adult↗

Capsule enteroscopy in small bowel transplantation.

BACKGROUND: Enteroscopy plays a key role in the post-operative monitoring of patients with small bowel transplantation for the early detection of post-transplant complications and for the assessment of the graft's integrity. Routine surveillance enteroscopies (trans-stomal terminal ileoscopy or jejunoscopy) are invasive, may be unsafe in frail patients, and only allow incomplete exploration of the transplanted graft, which may be unsatisfactory. since the distribution of the lesions is often patchy or segmental. AIMS. To evaluate the potential of capsule enteroscopy, a new, minimally invasive technique which allows complete exploration of the small bowel. in small bowel transplant recipients. METHODS: Five small bowel transplanted patients underwent capsule enteroscopy with the GIVEN endoscopy system. The results of capsule enteroscopy were compared with those of trans-stomal ileoscopy. RESULTS: Capsule enteroscopy was better tolerated than ileoscopy and good quality images of the small bowel were obtained in four patients. The terminal ileum was normal both on ileoscopy and capsule enteroscopy. Mucosal changes in segments not reached by ileoscopy were detected by capsule enteroscopy in three of four patients. CONCLUSIONS: Capsule enteroscopy is better tolerated than ileoscopy, allows complete exploration of the transplanted graft and can detect mucosal changes in segments not reached by ileoscopy.

Adult↗

Isolation and characterization of capsule structure mutant strains of Cryptococcus neoformans.

The capsule of Cryptococcus neoformans is the most obvious virulence factor of this pathogenic yeast. The main capsule constituents are glucuronoxylomannans (GXM). Although several studies have focused on GXM composition and structure, very little is known about their genetics. To elucidate the relationship between the capsule structure and the pathophysiology of the cryptococcosis, genetic screening for mutant strains producing a structurally modified capsule was set up. Using monoclonal antibodies specific for different capsule sugar epitopes, we isolated strains with different mutated capsule structures (Cas mutants). According to their reactivities with various monoclonal antibodies, the mutants were classified into six groups (Cas1 to Cas6). One Cas2 mutant was used to clone the corresponding gene by complementation. This gene (USX1) encodes the previously identified UDP-xylose synthase. We demonstrated that it is necessary for both capsule xylosylation and C. neoformans virulence.

Animals↗

An anatomical investigation of the human cervical facet capsule, quantifying muscle insertion area.

Facet capsule injury has been hypothesised as a mechanism for neck pain. While qualitative studies have demonstrated the proximity of neck muscles to the cervical facet capsule, the magnitude of their forces remains unknown owing to a lack of quantitative muscle geometry. In this study, histological techniques were employed to quantify muscle insertions on the human cervical facet capsule. Computerised image analysis of slides stained with Masson's trichrome was performed to characterise the geometry of the cervical facet capsule and determine the total insertion area of muscle fibres into the facet capsule for the C4-C5 and C5-C6 joints. Muscle insertions were found to cover 22.4+/-9.6% of the capsule area for these cervical levels, corresponding to a mean muscle insertion area of 47.6+/-21.8 mm2. The magnitude of loading to the cervical facet capsule due to eccentric muscle contraction is estimated to be as high as 51 N. When taken in conjunction with the forces acting on the capsular ligament due to vertebral motions, these forces can be as high as 66 N. In that regard, these anatomical data provide quantitative evidence of substantial muscle insertions into the cervical facet capsular ligament and provide a possible mechanism for injury to this ligament and the facet joint as a whole.

Aged↗

A prospective trial comparing small bowel radiographs and video capsule endoscopy for suspected small bowel disease.

BACKGROUND & AIMS: This study was undertaken to prospectively compare the clinical outcomes of small bowel radiographs with the wireless capsule endoscopy. METHODS: Twenty-two patients were selected consecutively because of suspected small bowel disease. Two patients were excluded owing to ileal stenosis. Thus, the results of barium follow-through and the Given M2A wireless video capsule (Given Imaging Ltd., Yoqneam, Israel) endoscopy were compared in 20 patients (13 men; mean age, 52.5 yr; range, 29-78 yr). RESULTS: Barium follow-through was normal in 17 patients and showed ileal nodularity in 3 patients. Capsule endoscopy was normal in 3 patients and showed positive findings in the remaining 17 patients. The barium study was considered diagnostic in 4 (20%) patients. The capsule endoscopy was considered diagnostic in 9 (45%) patients, suspicious in 8 (40%) patients, and failed in 3 (15%) patients. For obscure gastrointestinal (GI) bleeding, the diagnostic potential of barium follow-through was much worse as compared with the capsule endoscopy (5% vs. 31%, P < 0.05). Capsule endoscopy was well tolerated and better accepted by patients when compared with the most recently performed endoscopic procedure. CONCLUSIONS: The video capsule endoscope was found to be superior to small bowel radiograph for evaluation of small bowel diseases. However, this novel wireless endoscope system needs further assessment because of limitations such as difficulties in interpretation of potentially nonspecific findings.

Adenomatous Polyposis Coli↗

Endoscopically assisted video capsule endoscopy of the small bowel in patients with functional gastric outlet obstruction.

Since the introduction in 2001 of M2A video capsule imaging of the small bowel in humans, this technique has been used increasingly in patients with disorders of the small bowel. In particular the assessment of small obscure gastrointestinal bleeding sources and the detection of shallow inflammatory lesions in the small bowel, have been greatly facilitated by this novel imaging procedure. We report two cases of patients with obscure gastrointestinal bleeding, in whom normal passage of the capsule through the antroduodenal junction was inhibited. This was because of delayed gastric emptying in both patients, which was presumably caused by functional impairment of pyloric motility. To facilitate capsule transport into the small bowel, after swallowing the capsule each patient underwent unsedated upper gastrointestinal endoscopy during which the capsule was grasped with a polypectomy snare, directly transported through the pylorus, and finally released upon arrival in the second portion of the duodenum. Capsule recordings revealed the source of bleeding in both patients and their medical or surgical treatment was subsequently escalated. Capsule imaging of the small bowel facilitated by esophagogastroduodenoscopy (EGD) is safe, and can be applied when patients have functional disorders of pyloric motility.

Endoscopy, Gastrointestinal↗