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PubMed1984

Structure-activity studies of homologues of short chain neurotoxins from Elapid snake venoms.

Three neurotoxin homologues (CM10 and CM12 from Naja haje annulifera and S5C10 from Dendroaspis jamesoni kaimosae) and two short neurotoxins (CM14 from Naja haje annulifera and erabutoxin b from Laticauda semifasciata) were examined by circular dichroism (c.d.) and tested for neuromuscular activity on chick biventer cervicis nerve-muscle preparations. All three homologues had acetylcholine receptor blocking activity, as they abolished responses to indirect stimulation, acetylcholine and carbachol but had no effect on responses to direct muscle stimulation. CM10 was only about 5 times less potent than the short neurotoxin CM14; S5C10 and CM12 were respectively 30 and 300 times less active. The block induced by the three homologues, but not by the neurotoxins, was readily reversed by washing. CM10 and CM12 had virtually identical c.d. spectra which were closely similar to those of the neurotoxins. The spectrum of S5C10 indicated changes in the environment of tyrosine-25 and in the position of tryptophan-29. These alterations could distort the 3-dimensional arrangement of the residues postulated to form the receptor binding site. The results with CM10 and CM12 highlight a role for the first loop (residues 6-16) in the binding of neurotoxins to acetylcholine receptors, in addition to the previously postulated reactive site.

Animals↗
PubMed1980

Level effects in psychophysical two-tone suppression.

Measurements of psychophysical two-tone suppression in a number of subjects are described. Levels of the stimulus components (suppressee, L1, and suppressor, L2) were the primary experimental variables. In all experiments the pulsation threshold was used with the probe frequency fr fixed at the suppressee frequency f1. In an initial experiment f1 was fixed at 1 kHz. The suppressor frequency f2 ranged from 0.2 to 1.4 kHz. At appropriate levels all subjects showed significant suppression. Suppression was found to decrease to zero as f2 approached f1. The amount of suppression depended on both L1 and L2 in a way not accounted for by any of the current theories of two-tone suppression. At higher overall levels suppression became increasingly prominent. The amount of two-tone suppression in a given stimulus condition depended strongly on the subject. The maximum amount of suppression measured was about 35 dB. In a second experiment it was verified that suppression follows the same pattern at other frequencies f1 (0.5, 2, and 4 kHz). Data for equal f2/f1 ratios were quite similar. The two-tone suppression effect decreased in a noisy environment. Within a 20-dB range of signal-to-noise ratios the effect of noise changed from negligible to the virtually complete elimination of two-tone suppression.

Acoustic Stimulation↗
PubMed1998

Microbiological investigations to validate the preparation of corneal transplants.

The globe and cornea are colonized by microorganisms and cannot be removed as sterile products. Antiseptic measures and storage of the cornea in medium containing antibiotics lead to an obvious reduction of the microbial flora. Unfortunately there is the possibility of secondary microbial contamination during the preparation. Large amounts of bacteria or resistant bacteria can ruin attempts to reduce the microbial flora. To validate the whole process of preparation we investigated the contamination of removed globes, environment, materials, instruments and media for each sequence of operation and eliminated sources of contamination. Recommendations are given to ensure a virtually sterile product at the end of preparation.

Bacteria↗
PubMed2003

The fruitful flaws of strategy metaphors.

The business world is rife with metaphors these days, as managers look to other disciplines for insights into their own challenges. And metaphors can--despite their somewhat flaky image--be powerful catalysts for generating new business strategies. But metaphors are often improperly used, their potential left unrealized. We tend to look for reassuring parallels in business metaphors instead of troubling differences, the author contends. In fact, using metaphors to come up with new strategic perspectives begins to work only when the metaphors themselves don't work, or at least don't seem to. Take the following case in point. An insurance company's corporate headquarters put together a team of experts to discuss ways the firm might respond to the challenges of conducting business via the Internet. Once the team drafted a master plan, the idea was that it would be promulgated to the individual agents and offices of this widely dispersed organization. In a meeting with the company's top managers, the author talked about Charles Darwin's conceptual breakthrough in formulating the principles of evolution. As his overview of Darwin's theories about variation and natural selection gave way to questions, a heretical notion took shape: Those far-flung agents' offices, instead of being strategic liabilities in a suddenly virtual age, might instead be the mechanism for achieving an incremental but powerful corporate transformation in response to the changing business environment. But it was only when the evolutionary metaphor began to break down--when the elements of Darwin's theory clearly were at odds with the besieged insurance company's situation--that real strategic insight occurred. This anecdote offers, in a compressed form, an example of how the process of using metaphors can play out and what managers can learn from it.

Commerce↗
PubMed2006

Characterisation of dendritic cell subsets in lung cancer micro-environments.

The aim of the current study was to seek evidence for a correlation between mediators present in lung cancer micro-environments and subsets of dendritic cells (DCs) infiltrating these tumours. Immunohistochemistry and recently available antibodies were used to define the phenotype of DCs present in surgical biopsies from 12 patients with lung carcinomas, and the local expression of chemokines potentially involved in the recruitment of these cells was evaluated, both at mRNA and protein levels. Real-time PCR was used to analyse the expression of mRNA coding for cytokines known to influence the maturation of DCs in vitro. Different subsets of myeloid DCs were present in lung cancers, but no plasmocytoid DCs were identified. Both Langerhans cells and CD1a+/Langerin cells were interspersed among tumour cells, in numbers that were correlated to the amounts of CC chemokine ligand 20 produced in these tumours. In most specimens, DC-specific intercellular adhesion molecule-grabbing nonintegrin-positive DCs were also present at the periphery of the tumour beds. No DC-lysosomal associated membrane protein-positive DCs were identified and CD83+ DCs were rarely present in the tumour stroma. All tumours expressed interleukin (IL)-10, transforming growth factor-beta and vascular endothelial growth factor, whereas IL-12 was virtually absent. Thus, various types of dendritic cells infiltrate lung carcinomas and display an immature phenotype, presumably because of the inhibitory cytokine micro-environment.

Adenocarcinoma↗
PubMed2004

Memory for targets in a multi-level simulated-environment: a comparison between able-bodied and physically disabled children.

Two groups of children, one able-bodied and the other with physical disabilities, explored a symmetrical three-tiered virtual building that contained six distinctive target objects, two on each story. In a subsequent test, the target objects were removed and participants were asked to make judgments of the directions to the former target locations from each floor in turn. At each test site, judgments were required for targets that were formerly on the same floor and for those on higher and lower floors. Relative tilt error scores suggested a bias for both groups, in that targets that were higher than the test location were judged as consistently lower than their actual position, whereas targets that were lower than the test location were judged as higher than their actual position. Absolute tilt errors revealed an asymmetry in both groups, with more accurate tilt errors for judgments directed to lower than higher floors. The relevance of these results for the source of the asymmetry is discussed.

Child↗
PubMed1984

Transplantation of extensor carpi radialis longus muscle in normal and dystrophic chicks.

The etiology of avian muscular dystrophy was examined by a cross-transplantation technique. Care was taken for the transplants to regenerate and develop under neural influence, by using the small extensor carpi radialis longus (ECRL) muscle. The ECRL muscles were exchanged between normal and dystrophic chicks 2 to 3 days ex ovo, and the muscle weight, number of muscle fibers, muscle fiber size, and contractile properties of the transplanted muscles were observed 60 to 65 days after operation when the tissue reconstitution was virtually complete. The results obtained for the physiologic, anatomic, and histologic parameters strongly suggested that there exists some failure in the host environment of the dystrophic chicken. The analyses of the histologic parameters suggested that a genetic disorder may also reside in the muscle tissue itself. The myotonic nature of the muscle membrane, however, probably does not contribute significantly to the abnormal behavior of dystrophic chickens. The importance of some neurogenic abnormalities in avian muscular dystrophy is discussed in relation to the results reported by other investigators.

Action Potentials↗
PubMed2000

Audiovisual sexual stimulation by virtual glasses is effective in inducing complete cavernosal smooth muscle relaxation: a pharmacocavernosometric study.

Audiovisual sexual stimulation (AVSS) is frequently employed to promote cavernosal smooth muscle relaxation (SMR) in hemodynamic diagnostic settings for erectile dysfunction. Our aim has been to adapt conventional AVSS to the particular test conditions of pharmacocavernosometry and pharmacocavernosography (DICC), by the use of virtual glasses. Thirty-seven consecutive patients undergoing DICC were randomized in two groups: no-AVSS and AVSS through commercially available virtual glasses (VG-AVSS) with tri-dimensional capabilities and stereophonic headphones. Such device partially excludes the patient from the surrounding environment. In both groups a standard dose of vasoactive agents was intracavernosally administered, and possibly repeated (re-dosing), until complete SMR was obtained (3 doses/patient maximum). Psychometric tests (State Trait Anxiety Inventory and ad hoc visual analogue scales for embarrassment, stress and pain) were administered before and after DICC. The no-AVSS group consisted of 18 patients, the AVSS group of 19. Number of needed vasoactive agent doses: in the no-AVSS group 6 patients needed 1 dose, 3 patients 2, 9 patients 3 (mean dose number: 2.17); in the AVSS group 15 patients needed 1 dose, 1 patient 2, 3 patients 3 (mean dose number: 1.37). The difference in the number of doses used in the two groups was statistically significant (Student's t-test P = 0.007). Complete SMR, regardless of the number of used doses: in the no-AVSS group 9 patients (50%) achieved complete SMR, in the AVSS group 16 patients (84.2%). The difference in the two groups was statistically significant (chi-square P = 0.026). From evaluated psychometric measures no statistically significant difference between the two groups was detected. VG-AVSS significantly promotes complete SMR without increasing test related stress or anxiety. Its induced arousal suggests the possibility of performing dynamic evaluations of the erectile function with the oral agent sildenafil in place of intracavernosally administered vasoactive agents. VG-AVSS furthermore constitutes a promising tool for the investigation of normal physiology and pathophysiology of female sexual function.

Adult↗
PubMed1995

Carbonic anhydrase III. Oxidative modification in vivo and loss of phosphatase activity during aging.

Oxidative modification of DNA, lipids, and proteins occurs as a consequence of reaction with free radicals and activated oxygen. Oxidative modification of total cellular proteins has been described under many pathologic and experimental conditions, but no specific proteins have been identified as in vivo targets for oxidative modification. Utilizing an immunochemical method for detection of oxidatively modified proteins, we identified a protein in rat liver that was highly oxidized. It was purified to homogeneity and identified as carbonic anhydrase, isozyme III. Its characteristics match those previously described for a protein that was lost during aging of the rat, senescence marker protein-1. Carbonic anhydrase III was purified from rats aged 2, 10, and 18 months, and the proteins were characterized. All three preparations were highly oxidatively modified as assessed by their carbonyl content. The enzyme has three known catalytic activities, and the specific activities for carbon dioxide hydration and for ester hydrolysis decreased during aging by approximately 30%. However, the third activity, that of a phosphatase, was virtually lost during aging. While the physiologic role of carbonic anhydrase III is unknown, we suggest that it functions in an oxidizing environment, which leads to its own oxidative modification.

Aging↗
PubMed2003

Behavioural accident avoidance science: understanding response in collision incipient conditions.

Road traffic accidents are the single greatest cause of fatality in the workplace and the primary cause of all accidental death in the US to the age of 78. However, behavioural analysis of response in the final seconds and milliseconds before collision has been a most difficult proposition since the quantitative recording of such events has largely been beyond cost feasibility for road transportation. Here, a new and innovative research strategy is reported that permits just such a form of investigation to be conducted in a safe and effective manner. Specifically, a linked simulation environment has been constructed in which drivers are physically located in two adjacent, full-vehicle simulators acting within a shared single virtual driving world. As reported here for the first time, this innovative technology creates situations that provide avoidance responses paralleling those observed in real-world conditions. Within this shared virtual world 46 participants (25 female, 21 male) were tested who met in two ambiguous traffic situations: an intersection and a hill scenario. At the intersection the two drivers approached each other at an angle of 135 degrees and buildings placed at the intersection blocked the view of both drivers from early detection of the opposing vehicle. The second condition represented a 'wrong' way conflict. Each driver proceeded along a three-lane highway from opposite directions. A hill impeded the oncoming view of each driver who only saw the conflicting vehicle briefly as it crested the brow of the hill. Driver avoidance responses of steering wheel, brake, and accelerator activation were recorded to the nearest millisecond. Qualitative results were obtained through a post-experience questionnaire in which participants were asked about their driving habits, simulator experience and their particular response to the experimental events which they had encountered. The results indicated that: (1) situations have been created which provided avoidance responses as they have been recorded in real-world circumstances, (2) the recorded avoidance responses depended directly upon viewing times, and (3) the very short viewing times in this experiment resulted in a single avoidance action, largely represented by a random choice of swerve to either right or left. The present results lead us to posit that in order to be able to design accident avoidance mechanism that respond appropriately in the diverse situations encountered, there is a need to pay particular attention to mutual viewing times for drivers. The general implications for a behavioural science of collision-avoidance are evaluated in light of the present findings.

Accidents, Traffic↗
PubMed2005

Jesuit scientific activity in the overseas missions, 1540-1773.

Within the context of national traditions in colonial science, the scientific activities of Jesuit missionaries present us with a unique combination of challenges. The multinational membership of the Society of Jesus gave its missionaries access to virtually every Portuguese, Spanish, and French colony. The Society was thus compelled to engage an astonishingly diverse array of cultural and natural environments, and that diversity of contexts is reflected in the range and the complexity of Jesuit scientific practices. Underlying that complexity, however, was what I see as a unique combination of institutional structures; namely, European colleges, overseas mission stations, and the regular circulation of personnel and information. With this institutional framework as a backdrop, I briefly trace what I see as the most salient themes emerging from recent studies of Jesuit overseas science: (1) the Societys ability to use scientific expertise to its advantage amid the complex web of dependencies upon which it missionary activities rested; (2) the ability of its missionaries to become intimate with a wide range of cultures and to appropriate natural knowledge held by indigenous peoples, especially in the fields of material medica and geography; and (3) the different ways Jesuits used published accounts of "remote nature" (i.e., natural histories of overseas colonies) to advance their corporate and religious causes.

Catholicism↗
PubMed1993

A high-resolution solid-state 13C-NMR study on [1-13C]Ala and [3-13C]Ala and [1-13C]Leu and Val-labelled bacteriorhodopsin. Conformation and dynamics of transmembrane helices, loops and termini, and hydration-induced conformational change.

We have recorded 100.7-MHz high-resolution solid-state 13C-NMR spectra of [3-13C]Ala, [1-13C]Ala-labelled, Leu-labelled and Val-labelled bacteriorhodopsin (bR), to analyze the conformation and dynamics of transmembrane alpha helices and hydration-induced conformational changes. We assigned the 13C-NMR signals of these 13C-labelled amino acid residues to portions of the transmembrane alpha helices, loops and N-terminus and C-terminus, based on the conformation-dependent 13C chemical shift. The assignment of peaks to the transmembrane alpha helices is straightforward in view of the characteristic 13C chemical shifts of the C beta and carbonyl carbons, referred to the data of the model system. The signals of the transmembrane alpha helices were further divided into three or four peaks which are ascribed to either a dispersion of torsion angles of the alpha helices or variation of environments around the helices. In addition, we found that conformation of the N-terminus and C-terminus of bR is virtually the random-coil form which undergoes rapid reorientational motion in the hydrated system. Further, we show that the higher-order (secondary and/or tertiary) structure of bR is influenced by the hydration/dehydration process of the purple membrane, as viewed from the peak profile of the Ala C beta 13C signals. This change of structure occurs between relative humidities of 2% and 4%, consistent with the shift of the absorption maxima of retinal, which arise from the protonation/deprotonation processes of the Schiff base. In contrast, no such change of the carbonyl signals occurs for the Leu, Val and Ala residues. For the latter two residues, some spectral changes were noted at the stage of full hydration.

Alanine↗
PubMed2005

Selective rather than inductive mechanisms favour specific replacement of Purkinje cells by embryonic cerebellar cells transplanted to the cerebellum of adult Purkinje cell degeneration (pcd) mutant mice.

Cell replacement after neuronal degeneration in the adult CNS depends on the availability of specific cues to direct specification, differentiation and integration of newly born neurons into mature circuits. Following recent reports indicating that neurogenic signals may be reactivated in the adult injured CNS, here we asked whether such signals are expressed in the cerebellum after Purkinje cell degeneration. Thus, we compared the fate of embryonic cerebellar cells transplanted to the cerebella of adult wild-type and Purkinje cell degeneration (pcd) mutant mice. Donor cells were dissected from beta-actin-enhanced green fluorescent protein (EGFP) transgenic mice and transplanted as a single cell suspension. In both hosts, grafted cells generated all major cerebellar phenotypes, with a precise localization in the recipient cortex or white matter. Nevertheless, the phenotypic distributions showed striking quantitative differences. Most notably, in the pcd cerebellum there was a higher amount of Purkinje cells, while other phenotypes were less frequent. Analysis of cell proliferation by 5-bromo-2'-deoxyuridine (BrDU) incorporation revealed that in both hosts mitotic activity was strongly reduced shortly after transplantation, and virtually all donor Purkinje cells were actually generated before grafting. Together, these results indicate that some compensatory mechanisms operate in the pcd environment. However, the very low mitotic rate of transplanted cells suggests that the adult cerebellum, either wild-type or mutant, does not provide instructive neurogenic cues to direct the specification of uncommitted progenitors. Rather, specific replacement in mutant hosts is achieved through selective mechanisms that favour the survival and integration of donor Purkinje cells at the expense of other phenotypes.

Animals↗
PubMed2001

Impact of ambulance diversion policies in urban, suburban, and rural areas of Central Maryland.

UNLABELLED: As a method to control patient flow to overburdened hospitals, effective emergency medical services (EMS) systems provide policies for ambulance diversion. The Maryland state EMS system supports two types of alert for general hospital use: red alert, aimed at limiting the delivery of patients who may require intensive care unit (ICU) admission, and yellow alert, aimed at preventing further overload of already overtaxed emergency departments (EDs). OBJECTIVE: To examine the effect of those alert policies in different geographical environments, urban, suburban, and rural. METHODS: Alert data for 23 hospitals in Central Maryland and ambulance arrival data for approximately 138,000 ambulance calls during calendar year 1996 were combined and analyzed. The impacts of diversion practices in the geographic areas were compared. RESULTS: Red alert reduced volume in all patient acuity levels in all geographic areas by a statistically significant 0.4 patient/hr. Yellow alert diverted low-acuity patients at the rate of 0.13 patient/hr (p<0.001) in urban areas and at the rate of 0.16 patient/hr (p<0.001) in suburban areas, but had minimal impact in the flow of patients in the rural environment. CONCLUSIONS: The ED diversion policy has some limited effect in preventing further patient volume in urban and suburban areas, but has virtually no impact in rural areas. However, an ICU diversion policy diverts patients of all acuities uniformly and inordinately diverts patients not likely to require ICU admissions while having only minimal impact on patients who do require ICU resources. The impact of red alert is uniform in all geographic areas. The impact and efficacy of ambulance diversion policies should be evaluated to ensure they are having the intended effect. While perhaps initially effective, the impact of alert policies may change over time.

Ambulances↗
PubMed1985

Entamoeba histolytica trophozoites in the lumen and mucus blanket of rat colons studied in vivo.

Trophozoites of Entamoeba histolytica HM-1 were cultivated axenically in TYI-S medium. The amoebae were then transferred into this medium lacking serum (TYI) and inoculated into in vivo colon loops of adult Sprague-Dawley rats. The trophozoites were rapidly absorbed by the mucus, and few were found free in the luminal fluid by 1 h. By 4 h, the amoebae began to reappear in the lumen, aggregated in sloughed mucus blanket fragments. The colon was examined histologically and by scanning electron microscopy. There was no evidence of invasion or even brush-border attachment by the trophozoites within 4 h. In TYI, trophozoite motility was low. Exposure to the colonic lumen environment for 5 min in this medium significantly increased motility. However, as the trophozoites became absorbed to mucus fragments, their observed motility virtually ceased despite some morphological evidence of pseudopod extension. Erythrophagocytosis was not significantly affected by either exposing trophozoites to TYI washings of the colonic lumen, or by the more complete medium, TYI-S, in which the amoebae were significantly more motile. Two major mucus glycoprotein oligosaccharide end-group sugars, L-fucose and N-acetyl-neuraminic acid, were tested for their effects on trophozoite motility in both TYI and TYI-S. L-Fucose reduced motility; the sialic acid increased motility. It is concluded that the intestinal lumen contains several compartments, including the luminal fluid and the mucus blanket, and that Entamoeba trophozoites exist in a highly motile state in the former and a low motility state in the latter. The mucus blanket provided a significant barrier to trophozoite access to intestinal epithelium target tissue.

Amebiasis↗
PubMed1990

Use of NEXIS in a medical research library.

The NEXIS online system is used a great deal in business and law libraries, but has been virtually overlooked by medical librarians due to their perception of the system as expensive and difficult to search. The changing health care environment has placed new demands on medical searchers for just the type of legal, business, governmental, and news information found in the full-text files in NEXIS. Through the recent introduction of News Plus software, NEXIS can be searched as never before by those unaccustomed to full-text search techniques. Besides simplifying the search process, the new software has cost-saving features since search building and file selection are accomplished offline, and several activities may be done simultaneously. NEXIS via News Plus should be seriously considered as an addition to the repertoire of online systems accessed by medical librarians.

Cancer Care Facilities↗
PubMed1977

[Studies on mortality in diabetics in a circumscribed region: age and death, length of diabetes and causes of death].

Studies were carried out in regard to the age at death, duration of diabetes mellitus at the time of death and cause of death in an unselected evaluation of the findings in all 1694 diabetics who died in Erfurt and environs over an 11-year period. The The mean age of the patients at the time of death was 70.6 years, with virtually no difference between the sexes. Only six patients died prior to the age of 40. In accordance with the age structure of diabetics in a circumscribed area, the average survival time was 6.5 years. The interval between the first manifestation of the disease and death was 0 to 4 years in 45% of the patients; only every fifth patient survided for 10 or more years. These results are interpreted as being a reflexion of the frequent incidence of preceding or simultaneously-occuring atherosclerosis in these diabetics. Cardiovascular incidents affecting, above all, the coronary and cerebral vessels, account for about 60% of the deaths. Differences between these results and other statistical analyses can be explained on the basis of the unselective nature of the case material in the present study which was, moreover, collected in a defined region over a definite period of time.

Adult↗
PubMed2000

Functional morphology of the gas-gland cells of the air-bladder of Oreochromis alcalicus grahami (teleostei: cichlidae): an ultrastructural study on a fish adapted to a severe, highly alkaline environment.

Oreochromis alcalicus grahami is a small cichlid fish that lives in shallow peripheral lagoons of Lake Magadi, Kenya. The internal surface of the air-bladder is highly vascularized, illustrating possible utilization as an accessory respiratory organ. The wall of the bladder consists of five distinct tissue layers. From the outer to the inner surfaces are: a squamous, undifferentiated epithelial cell; a collagen-elastic tissue space; a smooth muscle tissue band; an inner connective tissue space; and columnar gas-gland cells projecting into the lumen. The cell membrane over the perikarya of the gas-gland cells was sporadically broken. The disruptions were ascribed to possible physical damage by discharging gas-bubbles. Juxtaluminally, the gas-gland cells attached across tight junctions. The cells have highly euchromatic nuclei and conspicuously large intracytoplasmic secretory bodies. On the blood capillary facing (basal) aspect, the cell membrane of the gas-gland cells is highly amplified. The cells insert onto a smooth muscle tissue band. The morphological features and the topographical arrangement of the gas-gland cells in O. a. grahami are indicative of an operative exchange of materials between them and the underlying tissue components especially the blood capillaries. For a fish that subsists in hot, highly saline and alkaline water heavily invested by avian predators and where the partial pressure of oxygen diurnally shifts from virtual anoxia to hyperoxia, development of a versatile air-bladder for efficient buoyancy control conforms to the functional demands placed on it by a unique environment. Illustratively, instead of the gas-gland morphology in O. a. grahami resembling that in the freshwater fishes, the group from which the fish has evolved, it compares more closely to that of the marine fish. This similarity suggests amazing parallel evolutionary adaptation to biophysically corresponding aquatic milieus.

Africa↗