RP-HPLC binding domains of proteins

Procedures have been developed to identify the chromatographic binding domains of horse heart cytochrome c (Cyt c) and bovine growth hormone (bGH) during their interaction with reversed-phase sorbent materials. The procedure involves adsorption of the protein solute to the chromatographic sorbent, followed by proteolytic cleavage. Comparison of the proteolytic map obtained for Cyt c and bGH in free solution with the corresponding map obtained when these proteins are adsorbed to the chromatographic sorbent revealed significant differences in the digestion pattern. Following characterization of the peptides generated in both maps, the results indicated that specific regions on the surface of both Cyt c and bGH are inaccessible to tryptic cleavage when adsorbed to the hydrophobic surface of both a C-4 and a C-18 sorbent. Based on the assumption that the region of the protein surface that is in contact with the sorbent remains intact and bound to the sorbent during the digestion step, while the protein surface that is exposed to the solvent is accessible to proteolysis, the regions that were inaccessible to tryptic digestion were found to correspond to hydrophobic domains on the protein surface. These results also suggest that the three-dimensional structures of these proteins remain largely intact upon adsorption to the hydrophobic surface.     

Mesh plug repair and groin hernia surgery

Since the mid-1980s, dramatic progress has been made in the evolution of hernia surgery, highlighted by the increasing use of prosthetic mesh. Among the mesh-based "tension-free" hernioplasties, the use of mesh plugs has garnered a large number of spirited enthusiasts, and plug herniorrhaphy has become the fastest growing hernia repair currently employed by the American surgeon. To demonstrate the simplicity and effectiveness of mesh plugs, a 9-year experience with almost 3300 patients is reported. Technical details are discussed and presentation of a literature search serves to further emphasize the utilitarian nature of this elegantly unsophisticated surgical operation.     

A clinical evaluation in children of the Pharmacia ImmunoCAP system for inhalant allergens

BACKGROUND: The Pharmacia ImmunoCAP system (CAP) for assaying serum IgE specific antibodies was evaluated in a clinical setting against skin-prick test (SPT) performed using Dome/Hollister-Steir allergen extracts. The five common inhalant allergens D. pteronyssinus, D. farinae, mould mix, grass mix and cat epithelium were tested concurrently by both methods in 167 children aged 7.5-12 years. The specific SPT for D. pteronyssinus and D. farinae were also tested against the CAP house dust mite (HDM) mix. OBJECTIVE: The purpose of the study was to determine the sensitivity and specificity of the Pharmacia ImmunoCAP system for detecting serum IgE specific antibodies to inhalant allergens in a clinical setting, using SPT result as the "gold standard'. METHODS: The SPTs were performed using Dome/Hollister-Steir allergen extracts. The serum IgE specific antibodies were quantitated using the radioimmunoassay version of the Pharmacia ImmunoCAP system. A history of allergic disease was assessed using a validated questionnaire. RESULTS: SPT gave more positive reactions than CAP with the exception of cat epithelium. The concordance between SPT and CAP results was 91% over all the tests. The concordance with SPT was slightly higher for the specific CAP for D. pteronyssinus and D. farinae (93% and 95% respectively) than for the CAP HDM mix (86% and 90% respectively). There was a higher proportion of positive results for both SPT and CAP in the 115 children defined as having a history of allergic disease. Using SPT defined allergy as the gold standard, the sensitivity of the CAP system was 87% for the two specific house dust mites but was lower for cat epithelium (67%), mould mix (59%) and grass mix (46%). The sensitivity of the CAP system improved for D. pteronyssinus (96%) and the HDM mix (91%) when tested in subjects defined as having a history of allergy associated disease. The specificity of the CAP system showed less variation between allergens and ranged from 90-99%. CONCLUSION: The results of this study of children aged 7.5-12 years demonstrate that, for the inhalant allergens tested, the Pharmacia ImmunoCAP system performs well in the setting of known allergic disease.     

Costimulatory molecule-deficient dendritic cell progenitors (MHC class II+, CD80dim, CD86-) prolong cardiac allograft survival in nonimmunosuppressed recipients

We have shown previously that granulocyte-macrophage colony-stimulating factor-stimulated mouse bone marrow-derived MHC class II+ dendritic cell (DC) progenitors that are deficient in cell surface expression of the costimulatory molecules B7-1 (CD80) and B7-2 (CD86) can induce alloantigen-specific T-cell anergy in vitro. To test the in vivo relevance of these findings, 2 x 10(6) B10 (H2b) mouse bone marrow-derived DC progenitors (NLDC 145+, MHC class II+, B7-1dim, B7-2-/dim) that induced T-cell hyporesponsiveness in vitro were injected systemically into normal C3H (H2k) recipients. Seven days later, the mice received heterotopic heart transplants from B10 donors. No immunosuppressive treatment was given. Median graft survival time was prolonged significantly from 9.5 to 22 days. Median graft survival time was also increased, although to a lesser extent (16.5 days), in mice that received third-party (BALB/c; H2d) DC progenitors. Ex vivo analysis of host T-cell responses to donor and third-party alloantigens 7 days after the injection of DC progenitors (the time of heart transplant) revealed minimal anti-donor mixed leukocyte reaction and cytotoxic T lymphocyte reactivity. These responses were reduced substantially compared with those of spleen cells from animals pretreated with "mature" granulocyte-macrophage colony-stimulating factor + interleukin-4-stimulated DC (MHC class IIbright, B7-1+, B7-2bright), many of which rejected their heart grafts in an accelerated fashion. Among the injected donor MHC class II+ DC progenitors that migrated to recipient secondary lymphoid tissue were cells that appeared to have up-regulated cell surface B7-1 and B7-2 molecule expression. This observation may explain, at least in part, the temporary or unstable nature of the hyporesponsiveness induced by the DC progenitors in nonimmunosuppressed recipients.     

Ambulatory urodynamics: extramural testing of the lower and upper urinary tract by Holter monitoring of cystometrogram, uroflowmetry, and renal pelvic pressures

This article elucidates the clinical applicability and state of the art of ambulatory urodynamics. Ambulatory urodynamics have evolved into practical investigations like EAC, HFM, and EAC combined with renal pelvimetry. EAC has been shown to be the method of preference if detrusor overactivity is involved. Conventional filling cystometry has proved to be an unreliable way to exclude detrusor instability. De novo instability after suspension surgery often indicates that an existing detrusor overactivity was not identified preoperatively. EAC including flowmetry has shown considerable variance in obstructive and contractility parameters in males with LUTS indicative for BPH. This raises doubt whether the clinical flow analysis is the suitable "gold standard" as advocated by the ICS. For a real break through of EAC, less complex automatic analysis is necessary. HFM is a newer method within the range of ambulatory urodynamic tests. It has not yet been completely evaluated. But, because the technique is analogous to the office flowmetry, noninvasive and very well accepted by the patients, it is expected to be widely used. This expectation is strengthened by the fact that HFM seems to show individual therapeutic efficacy of drugs, such as alpha-blockers. As a research tool to evaluate efficacy, it is far more powerful than conventional methods because of the reduction of within-patient standard deviation to about 10%. Finally, EAC combined with pelvimetry offers a promising method for the clinical evaluation of a combined dysfunction of upper and lower urinary tract.     

Ethics of the distribution of health care

While the concept of a "right to health care" has been evolving in the United States, this should be distinguished from "the right to health," guaranteed in the constitutions of many socialist countries. In an effort to promote "quality of life" for their citizens, governments can, and do provide health care, but this does not always lead to health. In so doing, governments open access to care for those previously underserved--or unserved. For the United States at this time the goal becomes one of assuring equity, which will likely be achieved by locally based private and/or governmental entities, federated for greater efficiency and regulated by federal and state governments. Such programs will be staffed by a new breed of physician, the medical student of today.     

Microstructure evolution and strain localization in Cu and Cu-8Al single crystals subjected to channel-die compression

Single crystals of pure Cu and Cu‐8%Al with two initial orientations, {112}〈111〉 and {112}〈110〉, were subjected to monotonic compression in channel‐die at room temperature (293 K). The dislocation microstructure and local crystallography were investigated by transmission electron microscopy after different amounts of deformation. Various factors, such as initial single crystal orientation, chemical composition and amount of plastic deformation, were analysed in order to determine their influence on the microstructure evolution, local orientation variations and strain localization phenomena.     

Determining dynamic output feedback of the least order for SIMO systems to locate poles in a specified region†

This paper presents a new theory for determining dynamic output feedback of the least order for a linear, time-invariant, controllable and observable SIMO system, such that poles of the closed-loop system lie in a given region Γ in the complex plane. When some poles have prespecified stationary locations in the complex plane, dynamic output feedback is obtained in the sense that the remaining poles lie in Γ This theory applies to continuous-time as well as discrete-time systems. Here a design algorithm for complete system realization and an illustrative example are given.