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A biomechanical model of the posterior knee capsule of the cat.

A biomechanical model is presented which represents the upper edge of the posterior knee capsule in the cat as a two-segment, vertically loaded catenary suspension cable from which the capsule sheet is suspended. Data are presented which show that the upper edge of the capsule is organized as a cable, which spans the notch between the femoral condyles. When a point load is applied to the cable, measurement of the cable shape allows for calculation of the cable tension and the downward distributed loads acting on the cable. This method was used to measure the in-vivo cable tension and the distributed downward loading acting on the capsule cable. The results show that the lateral side of the posterior joint capsule sustains a higher loading than the medial side.

Animals↗

Capsule-transmitted gut symbiotic bacterium of the Japanese common plataspid stinkbug, Megacopta punctatissima.

The Japanese common plataspid stinkbug, Megacopta punctatissima, deposits small brown particles, or symbiont capsules, on the underside of the egg mass for the purpose of transmission of symbiotic bacteria to the offspring. We investigated the microbiological aspects of the bacteria contained in the capsule, such as microbial diversity, phylogenetic placement, localization in vivo, and fitness effects on the host insect. Restriction fragment length polymorphism analysis of 16S ribosomal DNA clones revealed that a single bacterial species dominates the microbiota in the capsule. The bacterium was not detected in the eggs but in the capsules, which unequivocally demonstrated that the bacterium is transmitted to the offspring of the insect orally rather than transovarially, through probing of the capsule content. Molecular phylogenetic analysis showed that the bacterium belongs to the gamma-subdivision of the Proteobacteria. In adult insects the bacterium was localized in the posterior section of the midgut. Deprivation of the bacterium from the nymphs resulted in retarded development, arrested growth, abnormal body coloration, and other symptoms, suggesting that the bacterium is essential for normal development and growth of the host insect.

Animals↗

Capsule size of Cryptococcus neoformans: control and relationship to virulence.

Capsule size of five isolates of Cryptococcus neoformans was controlled by cultivation in media containing varying amounts of sugar. High concentrations of sugar (e.g., 16%) suppressed encapsulation whereas low concentrations (e.g., 1%) allowed maximal encapsulation. Suppression of capsule size was attributed at least in part to the increased osmolarity of the medium because a medium with low sugar concentration but having high osmolarity (by virtue of added sodium chloride) also produced cells having small capsules. The extent of control was more marked with certain of the isolates than with others. Mice were intravenously inoculated with cells of a single isolate cultivated so as to have either small or large capsules, and virulence was measured by comparing death rates. Results indicate that virulence after such an inoculation is a constant characteristic of an isolate and is not affected by size of the capsule of the cells in the inoculum.

Cryptococcus↗

Hyaluronate capsule prevents attachment of group A streptococci to mouse peritoneal macrophages.

The antiphagocytic properties of the streptococcal hyaluronic acid capsule were explored in a system in which binding of the organism to the phagocyte, but not ingestion, could occur. The capsule was found to be highly effective in preventing attachment of two strains of group A streptococci to mouse peritoneal macrophages. Variation in attachment with phase of growth in broth culture (low in early log phase, high in late-log phase and thereafter) could be accounted for by production and subsequent loss of capsule. Hyaluronidase treatment removed the capsule and increased adherence; treatment with proteolytic enzymes removed M protein and decreased resistance to phagocytosis in whole human blood but did not remove the capsule or increase adherence to the mouse peritoneal macrophages.

Animals↗

Genetics of spontaneous, high-frequency loss of b capsule expression in Haemophilus influenzae.

We determined that the frequency of spontaneous capsule loss in Haemophilus influenzae type b is 0.1 to 0.3%. All of 10 independent capsule-deficient variants (derived from four different type b strains) were found to be missing an identical 9-kilobase EcoRI restriction fragment when probed with a cloned piece of DNA containing sequences known to be necessary for type b capsule expression. These results suggest the existence of a specific mechanism for shutting off type b capsule synthesis at a high frequency. Intranasal infection of infant rats showed that capsule loss occurred in vivo at frequencies comparable to those observed in vitro.

Antigens, Bacterial↗

The second capsule gene of cryptococcus neoformans, CAP64, is essential for virulence.

The extracellular polysaccharide capsule produced by Cryptococcus neoformans is essential for its pathogenicity. We have isolated and characterized a gene, (AP64, which is required for capsule formation. An encapsulated strain created by complementation of the cap64 mutation produced fatal infection of mice within 25 days, while the cap64 acapsular strain was avirulent. Gene deletion of CAP64 from a wild-type strain resulted in the loss of capsule as well as virulence. Contour-clamped homogeneous electric field gel analysis indicates that CAP64 is located on chromosome III which is different from the localization of another capsule-related gene, CAP59. The nonlinkage between CAP64 and CAP59 was also supported by classical recombinational analysis. Database searches did not reveal any sequence with high similarity to CAP64. We also found that the CAP64 locus is contiguous to a convergently transcribed gene which has significant similarity to the gene encoding the yeast proteasome subunit, PRE1. The distance between the cDNA ends of these two genes is only 22 bp. This study confirms the previous molecular genetic evidence that capsule is an essential factor for the virulence of C. neoformans in the murine model.

Amino Acid Sequence↗

Isolation of the third capsule-associated gene, CAP60, required for virulence in Cryptococcus neoformans.

A polysaccharide capsule is one of the most important virulence factors for the pathogenic fungus Cryptococcus neoformans. We previously characterized two capsule-associated genes, CAP59 and CAP64. To further dissect the molecular mechanism of capsule synthesis, 16 acapsular mutants induced by 4-nitroquinoline-1-oxide were obtained. The acapsular phenotype of one of these mutants was complemented. The cloned gene was designated CAP60, and deletion of this newly described capsule-associated gene resulted in an acapsular phenotype. The proposed 67-kDa Cap60p contains 592 amino acids and appears to have a putative transmembrane domain close to the N terminus. DNA sequence analysis revealed that CAP60 has similarity to CAP59 at the center portion of its coding regions. Contour-clamped homogeneous electric field blot analysis suggested that these two genes are on the same chromosome. CAP60 and CAP59, however, could not be functionally substituted for each other by direct complementation or by domain swap experiments. In addition, CAP60 is closely linked to a gene which is similar to a cellulose growth-specific gene of Agaricus bisporus, CEL1. Immunogold electron microscopy studies of the epitope-tagged CAP60 gene revealed that Cap60p was primarily localized to the nuclear membrane. Animal model studies indicated that CAP60 is essential for virulence. Thus, CAP60 is required for both capsule formation and virulence.

Amino Acid Sequence↗

Ultrastructural characterization of capsulated Haemophilus influenzae type b and two spontaneous nontypable mutants.

Capsulated Haemophilus influenzae type b and two spontaneous mutants (classes I and II variants) were characterized by transmission and scanning electron microscopy. When cells were treated with type b-specific antiserum prior to manipulations for electron microscopy, sectioned capsulated cells had electron-dense, fibrous capsular antigen-antibody complexes around them. In negatively stained preparations, the complexes appeared as electron-transparent zones surrounding cells. In contrast, only residual electron-dense, extracellular material was seen in sectioned, untreated, capsulated cells, and electron-dense "bridges" connected adjacent cells in negatively stained preparations. No extracellular capsular material was seen around the class I and II variants. Characteristic electron-translucent regions were always observed within the cytosol of the class I cells, both in thin sections and by negative staining. These areas were located adjacent to the cell envelope separating the plasma membrane from the dense cytoplasmic matrix. At times, electron-dense, thread-like material extended from the dense cytoplasmic matrix to the plasma membrane. No such regions were seen in the capsulated and class II cells. Class I cells fixed with methanol or suspended in NaCl or phosphate-buffered saline prior to treatment with fluorescein-tagged type b-specific antiserum (FTA reagent) exhibited, by immunofluorescence, patches of capsular antigen along their sides. However, when fixed with glutaraldehyde or OsO4 or suspended in tris-(hydroxymethyl)aminomethane plus Ca2+ buffer prior to treatment with FTA reagent, no patches of capsular antigen were seen. Subsequent exposure of the latter cells to methanol followed by treatment with FTA reagent resulted in the reappearance of the patches of capsular antigen. Thus, in the class I variant the capsular antigen is unlikely to be surface located. Scanning electron microscopy revealed that class I and II variant cells within undisturbed colonies were regularly aligned side-by-side, whereas cells within colonies of the capsulated strain were randomly distributed.

Antigen-Antibody Complex↗

Interstitial fluid pressure of ileum measured from chronically implanted polyethylene capsules.

Steady-state fluid pressure measurements were obtained from polyethylene capsules chronically implanted in the walls of cat ileum. Measurements were performed while ileal venous outflow pressure was maintained at 0, 10, 20, or 30 mmHg. The resulting mean steady-state capsule pressure ranged from -0.56 to 7.3 mmHg over the range of imposed venous outflow pressures. The data provide evidence that at an ileal venous outflow pressure in the range of 10 mmHg, comparable to a normal portal pressure, interstitial fluid pressure is positive, increasing as tissue hydration increases, and is a significant contributing force opposing increases in the transcapillary filtration force. Additionally, the qualitative response of implanted capsules to close intra-arterial infusion of normal saline (transcapillary filtration), Dextran 40 (transcapillary absorption), and histamine (transcapillary filtration-permeability changes), and during and after an arterial occlusion of 60-s duration (transcapillary absorption-filtration) were obtained. The results demonstrate that the implanted capsules appropriately track changes in interstitial fluid pressure when the state of tissue hydration is altered by an induced net transcapillary fluid filtration or absorption. Finally, total protein concentration of capsule fluid was not significantly different from lymph fluid derived from a lymphatic vessel draining the ileal segment.

Animals↗

Collagen fiber arrangement of the human shoulder joint capsule--an anatomical study.

The polariscopic examination of isolated shoulder joint capsules shows that the entire capsule does not have a homogeneous collagen structure. Most of the capsule is characterized by regular collagen fibers which cross at an obtuse angle in the area of the musculus supraspinatus and at an acute angle in the area of the m. infraspinatus. The density of the collagen network increases from the medial to the lateral part. Deviating from this basic pattern of the joint capsule, there is a different collagen texture in the area between the m. supraspinatus and the m. subscapularis. This texture has dissociated, rarefied and irregular collagen fibers. This means that the area--in comparison with the remainder of the capsule--is characterized not only by missing reinforcing ligaments but also by a deviating pattern of the collagen fibers. This different collagen structure is already existent in the fetus.

Adult↗

Intrinsic innervation of the rat knee joint articular capsule and ligaments.

In spite of the practical importance of having a detailed knowledge of knee joint innervation to understand the pathophysiologic aspects, little information is now available concerning the density and pattern of the nerve fibres which are distributed to it. The present study has been designed to investigate the density and distribution of nerve fibres and receptor corpuscles in the knee joint articular capsule, cruciate and collateral ligaments in the rat, using the acetylcholinesterase (AChE) histochemical in toto staining technique. The investigation was performed on male Wistar rats of 3 months of age, some of which had been treated with capsaicin to deplete their afferent 'C' fibres of their content of neuropeptides. AChE-positive nerve fibres and different types of receptor corpuscle endings were found within articular capsule and ligaments. The highest density of AChE-positive nerve fibres was noticeable in the fibular collateral ligament followed by the tibial collateral ligament, the posterior cruciate ligament, the anterior cruciate ligament and the articular capsule. In the articular capsule the number of type I endings was higher than in the ligaments. The opposite is true for the other type of receptor corpuscles found as well as for nerve endings. Capsaicin treatment significantly reduced the density of AChE-positive nerve fibres in knee joint ligaments but did not affect nerve fibres in the articular capsule. Moreover, it caused the disappearance of some kind of receptor corpuscles within the collateral and cruciate ligaments. The above data collectively suggest that the AChE in toto staining technique may represent a good method for investigating joint innervation and that a significant percentage of nerve fibres supplying knee joint ligaments is represented by C fibre afferents.

Acetylcholinesterase↗

Otago glaucoma surgery outcome study: cytology and immunohistochemical staining of bleb capsules around Molteno implants.

PURPOSE: To describe the cytology and immunohistochemistry of Molteno implant capsules from cases of primary and secondary glaucoma. METHODS: Histologic features of capsules including cell cytology, the distribution of activated (proliferating) cells, apoptosing cells, and membrane bound vesicles (presumed death messengers) were assessed by light microscopy and correlated with clinicopathological features in 10 noninflamed eyes with good intraocular pressure control (nine autopsy and one enucleation) obtained from 2 months to 16.8 years after insertion of Molteno implants. RESULTS: All bleb capsules demonstrated two distinct layers. The thin external layer was cellular with fairly numerous small blood vessels coursing through normally staining, regularly arranged collagen fibers. The thicker, deeper layer was avascular, relatively acellular, and characterized by regularly arranged swollen and fragmented collagen fibers. Most cells in the external layer appeared normal; however, between 5% (in recently formed blebs) and approximately 50% (in well established blebs) showed cytological and/or immunohistochemical changes characteristic of metabolic activation and/or apoptosis. All cells in the deeper layer, regardless of time after surgery, also demonstrated cytological and/or immunohistochemical staining characteristic of metabolic activation and/or apoptosis. In addition, the deeper layer evidenced large numbers of minute membrane-bound vesicles (presumed death messengers). CONCLUSIONS: The balance between activation and apoptosis regulates the thickness and permeability of bleb capsules, and the normal lifecycle of bleb capsules includes continual inner surface degeneration and external surface renewal.

Adult↗

Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide.

Cryptococcus neoformans is variably encapsulated in vitro, whereas in tissues it develops a large capsule. We observed that cells of a strain with thin capsules, when growing in a standard fungal culture medium, became heavily encapsulated when incubated in serum-free cell culture medium (Dulbecco's modified Eagle's medium [DME]). Capsule size was quantitated physically by measuring cell volume, and chemically by determining the content of a capsular monosaccharide, glucuronate. The CO2/HCO-3 couple stimulated capsule development, resulting in visible enlargement by 3 h after exposure to high CO2/HCO-3. The amount of capsule per cell was directly proportional to the total millimolar CO2/HCO-3 concentration between 24 and 2.4 mM at pH 7.35, but at constant PCO2 (40 torr) and varying [HCO-3], the cells were heavily encapsulated down to pH 6.8. Concentration of CO2/HCO-3 in the physiologic range increased elaboration of polysaccharide into the medium and slowed the cell generation time from 2 to 6 h. Four other first-passage clinical isolates were all heavily encapsulated in DME with CO2/HCO-3, but variably encapsulated in DME without CO2/HCO-3. Exposure of yeast to increased CO2/HCO-3 caused a marked reduction in complement-mediated phagocytosis by mouse macrophages. A stable clone was isolated which contained capsular polysaccharide, but lacked the CO2-inducible phenotype. This clone was avirulent for steroid-treated rabbits. Thus, the prevailing CO2 concentration in mammalian tissues may be one stimulus for capsular polysaccharide synthesis. This could serve as an adaptive mechanism favoring parasite survival in the host.

Animals↗

Internal capsule size in good-outcome and poor-outcome schizophrenia.

Converging lines of research suggest that white matter abnormalities may be central to the pathophysiology of schizophrenia. The purpose of this study was to examine regional white matter in the anterior limb of the internal capsules in patients with schizophrenia. The authors obtained high-resolution magnetic resonance imaging in 106 patients with schizophrenia and 42 age and sex-matched healthy comparison subjects. The area of the anterior limb of the internal capsule was measured at five proportionately spaced dorsal-to-ventral levels. Schizophrenia patients were divided into good-outcome and poor-outcome groups, based on longitudinal analysis of self-care deficits. Patients with poor-outcome had significantly smaller dorsal areas than healthy comparison subjects, but good-outcome patients did not differ from healthy comparison subjects. Larger relative volumes of the caudate, putamen, and thalamus tended to be associated with relatively larger volumes of the internal capsule in healthy comparison subjects and good-outcome patients, consistent with the known frontal-striatal-thalamic pathways. Larger ventricles were associated with smaller internal capsules, particularly in healthy comparison subjects. The findings suggest disruption of internal capsule fibers in poor-outcome patients with schizophrenia. These abnormalities may be independent of other structural changes in schizophrenia.

Adult↗

An ultra-low-power image compressor for capsule endoscope.

BACKGROUND: Gastrointestinal (GI) endoscopy has been popularly applied for the diagnosis of diseases of the alimentary canal including Crohn's Disease, Celiac disease and other malabsorption disorders, benign and malignant tumors of the small intestine, vascular disorders and medication related small bowel injury. The wireless capsule endoscope has been successfully utilized to diagnose diseases of the small intestine and alleviate the discomfort and pain of patients. However, the resolution of demosaicked image is still low, and some interesting spots may be unintentionally omitted. Especially, the images will be severely distorted when physicians zoom images in for detailed diagnosis. Increasing resolution may cause significant power consumption in RF transmitter; hence, image compression is necessary for saving the power dissipation of RF transmitter. To overcome this drawback, we have been developing a new capsule endoscope, called GICam. METHODS: We developed an ultra-low-power image compression processor for capsule endoscope or swallowable imaging capsules. In applications of capsule endoscopy, it is imperative to consider battery life/performance trade-offs. Applying state-of-the-art video compression techniques may significantly reduce the image bit rate by their high compression ratio, but they all require intensive computation and consume much battery power. There are many fast compression algorithms for reducing computation load; however, they may result in distortion of the original image, which is not good for use in the medical care. Thus, this paper will first simplify traditional video compression algorithms and propose a scalable compression architecture. CONCLUSION: As the result, the developed video compressor only costs 31 K gates at 2 frames per second, consumes 14.92 mW, and reduces the video size by 75% at least.

Algorithms↗

The adrenal capsule alters the response of zona glomerulosa cells to atrial natriuretic peptide.

Atrial natriuretic peptide (ANP) is a potent inhibitor of potassium-stimulated aldosterone secretion. In the present study, we observed rat alpha ANP to inhibit aldosterone secretion stimulated by 10 mM potassium with an IC50 of 0.15 +/- 0.02 nM (mean +/- SE) in dispersed rat adrenal glomerulosa cells. However, when rat adrenal capsules, which contain the zona glomerulosa, were superfused in vitro, ANP had no effect on aldosterone secretion. Superfusion with 10 mM potassium increased aldosterone secretion 3- to 4-fold above baseline. Addition of 10 nM ANP to the superfusate did not lower potassium-stimulated aldosterone secretion. When this same ANP-containing superfusate was incubated with dispersed adrenal glomerulosa cells, potassium-stimulated aldosterone secretion was inhibited by 90%, proving sustained biological potency of the superfused ANP. Incubation of [125I]iodo-ANP with adrenal capsules for 60 min resulted in 83% degradation of [125I]iodo-ANP, whereas no detectable degradation was observed with dispersed adrenal glomerulosa cells. Removal of blood from the adrenal capsules or culturing the capsules for 48 h did not render them responsive to superfused ANP. In contrast, superfusion of 0.1 mM cycloheximide inhibited potassium-stimulated aldosterone secretion by 90%. These results suggest that the adrenal capsule contains an ANP-degrading enzyme(s). This enzyme may be produced by adrenal glomerulosa cells. The local existence of a degrading enzyme for ANP may allow the zone glomerulosa to regulate its response to ANP.

Adrenal Cortex↗

Absorption of vitamin K2 by dogs after oral administration of a soft gelatin capsule formulation containing a new emulsion-type vehicle.

This study has evaluated the performance of a newly developed vehicle for administration of a drug in a soft gelatin capsule. The absorption of vitamin K2 in dogs after oral administration of the vitamin in a soft gelatin capsule containing the newly developed vehicle was compared with absorption after administration of a control formulation prepared by encapsulating the contents of a commercially available vitamin K2 capsule (Glakay capsules 15 mg) in the same type of soft gelatin. Under non-fasted conditions the profile of the plasma concentration of vitamin K2 against time for the test formulation was comparable with that for the control formulation in non-fasted dogs. Under fasted conditions, however, both the maximum concentration (Cmax) and the area under the plot of concentration against time (AUC) were significantly smaller for the test formulation than for the control formulation. The Cmax and AUC for the test formulation were about 10 times larger for non-fasted dogs than for fasted dogs whereas values for the control formulation were about twice as large. These results suggest that both formulations might require the presence of food or digestive fluid components, or both, for better absorption of vitamin K2. It seems that although the performances of the test and control formulations were comparable in the presence of these components, the control formulation works better in their absence. It should be also noted that, in contrast with the results from the absorption tests, the dispersibility of the test vehicle in water was much better than that of the control vehicle. This suggests that dispersibility does not significantly affect vitamin K2 absorption. In conclusion, although the new vehicle did not perform better than the control vehicle in terms of vitamin K2 absorption, the performance of the control formulation was comparable for non-fasted dogs. Because the new vehicle contains considerably less surfactant than the vehicles currently used in soft gelatin capsules, it could be a safer alternative for use under non-fasted conditions.

Administration, Oral↗

Foxd1-dependent signals control cellularity in the renal capsule, a structure required for normal renal development.

Development of the metanephric kidney involves the establishment of discrete zones of induction and differentiation that are crucial to the future radial patterning of the organ. Genetic deletion of the forkhead transcription factor, Foxd1, results in striking renal abnormalities, including the loss of these discrete zones and pelvic fused kidneys. We have investigated the molecular and cellular basis of the kidney phenotypes displayed by Foxd1-null embryos and report here that they are likely to be caused by a failure in the correct formation of the renal capsule. Unlike the single layer of Foxd1-positive stroma that comprises the normal renal capsule, the mutant capsule contains heterogeneous layers of cells, including Bmp4-expressing cells, which induce ectopic phospho-Smad1 signaling in nephron progenitors. This missignaling disrupts their early patterning, which, in turn, causes mispatterning of the ureteric tree, while delaying and disorganizing nephrogenesis. In addition, the defects in capsule formation prevent the kidneys from detaching from the body wall, thus explaining their fusion and pelvic location. For the first time, functions have been ascribed to the renal capsule that include delineation of the organ and acting as a barrier to inappropriate exogenous signals, while providing a source of endogenous signals that are crucial to the establishment of the correct zones of induction and differentiation.

Animals↗