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PubMed1996

Bilateral interactions in saccade programming. A saccade-latency study.

Subjects were required to make a saccade to a target appearing randomly 4 degree to the left or right of the current fixation position (1280 trials per experiment). Location cues were used to direct visual attention and start saccade preparation to one of the two locations before target onset. When the cue indicated the target location (valid trials), the generation of express saccades (visually guided saccades with latencies around 100 ms) was strongly facilitated. When the opposite location was cued (invalid trials), express saccades were abolished and replaced by a population of mainly fast-regular saccades (latencies around 150 ms). This was found with a peripheral cue independently of whether the fixation point was removed before target onset (gap condition; experiment 1) or remained on throughout the trial (overlap condition; experiment 2). The same pattern also was observed with a central cue that did not involve any visual stimulation at a peripheral location (experiment 3). In the case where the primary saccade was executed in response to the cue and the target appeared at the opposite location, continuous amplitude transition functions were observed: starting at about 60-70 ms from target onset onward, the amplitude of the cue-elicited saccades continuously decreased from 4 degree to values below 1 degree. The results are explained by a fixation-gating model, according to which the antagonism between fixation and saccade activity gives rise to multimodal distributions of saccade latencies. It is argued that allocation of visual attention and saccade preparation to one location entails a successive disengagement of the fixation system controlling saccade preparation within the hemifield to which the saccade is prepared and a partial engagement of the opposite fixation system.

Adult↗
PubMed1981

Measles virus: evolution of a persistent infection in BGM cells.

An African green monkey kidney cell line (BGM) persistently infected with measles virus (BGM/Hallé cells) has been studied during 3 years in culture. The early cell passages were characterized by slow growing cultures producing high yields of infections virus (10(6)--10(7) PFU/ml). These cells were gradually replaced by a population of cells multiplying at a similar rate as non-infected cells. During this evolution, the virus released from the cells changed from a large plaque variant, to a small plaque and eventually unlysed foci. Despite greater than or equal to 95 per cent of the cells being infected, the virus yield fell to the limits of detection. [35S]-methionine labelling of BGM/Hallé cultures at the 20th and 140th passage showed that in both cases all the measles virus structural proteins were synthesized. There were no changes in the apparent molecular sizes of the viral proteins during passage. Cell surface [125I]-labelling of BGM/Hallé cells indicates that viral envelope antigens are inserted into the membrane despite the diminution in virus yield. Several cell proteins not labelled in non-infected BGM cells are also labelled. These proteins could also be [125I]-labelled in clones of BGM/Hallé cells with had been "cured" of virus. Chase experiments of [125I]-pre-labelled BGM/Hallé cultures showed the radiolabelled antigen to be incorporated into virus particles. Non-infections virus particles released from the cells contained the same polypeptides as those released from a lytic infection.

Animals↗
PubMed2000

Restoring control: the Acticon Neosphincter artificial bowel sphincter in the treatment of anal incontinence.

PURPOSE: Anal incontinence is a socially disabling problem affecting 1 to 2 percent of the population. Anal sphincter replacement is a treatment option if the problem is severe and not amenable to direct repair. The artificial bowel sphincter is an innovative approach. We report the technique for placement and the outcomes which have occurred in an initial series of 13 patients. METHODS: The Acticon Neosphincter artificial bowel sphincter consists of an inflatable cuff of silicone elastomer placed around the anal canal and connected to a pressure-regulating balloon in the iliac fossa via a control pump placed in the labium or scrotum. Thirteen patients with severe anal incontinence not amenable to other methods were treated. Causes of incontinence included obstetric damage in eight patients, surgical damage in two patients, imperforate anus in two patients, and spina bifida in one patient. RESULTS: Surgical placement of the device was straightforward, mean operating time was 65 minutes, and median length of stay was 3.6 days. One infection of the perineal wound occurred in the early postoperative period necessitating removal of the device. In two further patients the artificial bowel sphincter was removed because of late infection in one at seven months and because of erosion through the skin in another at three months. The artificial bowel sphincter has been activated in ten patients resulting in full continence to solids and liquids except in one patient with postvagotomy diarrhea who had some leakage of liquids during episodes of diarrhea. The mean (+/- standard deviation) continence score (Cleveland Clinic system; maximal incontinence = 20) changed from 18.7 +/- 1.6 preoperatively to 2.1 +/- 2.6 after activation (P < 0.0001). Quality of life measured using a continence-specific series of up to 39 questions changed from 77 +/- 16 percent of maximal reduction of quality preoperatively to 12 +/- 19 percent postoperatively (P < 0.001). CONCLUSIONS: The artificial bowel sphincter can be placed without technical difficulty and with low morbidity. Preliminary experience shows full restoration of continence in most patients and ease of use. Longer follow-up is needed to determine the extent of problems with infection, erosion, and mechanical failure.

Adult↗
PubMed1985

Phenotypic variations among enterotoxinogenic Escherichia coli from Swedish piglets with diarrhoea.

Escherichia coli strains causing diarrhoea in Swedish piglets were isolated; this investigation was made over a 20-year period, from 1964 to 1984. Many of the isolates belonged to O-groups 8, 141 and 149. These strains were separated into different phenotypes with the aid of a new method, "biochemical fingerprinting". This method has been especially designed to sort E. coli-isolates into various phenotypes based on a pattern of quantitatively measured biochemical reactions. It was found that most pathogenic isolates carrying O-antigen 8 belonged to the same phenotype. This phenotype was common in the 1960's, but later it disappeared from the population and was replaced by a wide variety of different phenotypes, most of them non-enterotoxinogenic, but still belonging to O-group 8. In O-group 141 one phenotype dominated in the 1960's, but in the 1970's a new phenotype appeared, which further increased in number in the 1980's. By contrast, in the O-group 149 practically all strains isolated during the 20-year period were found to carry the relevant virulence factors and belong to the same phenotype.

Animals↗
PubMedDate not supplied

Undifferentiated embryonal sarcoma with unusual features arising within mesenchymal hamartoma of the liver: report of a case and review of the literature.

Undifferentiated embryonal sarcoma (UES) is a rare and highly malignant hepatic neoplasm, affecting almost exclusively the pediatric population. It has replaced malignant mesenchymoma, under which diagnostic term the first three cases were described. A link between embryonal sarcoma and mesenchymal hamartoma of the liver (MHL) has long been proposed, because of clinicopathologic overlaps of these entities; however, until recently, this association remained tenuous. Cases of UES arising in a background of mesenchymal hamartoma of the liver have previously been reported in two teenage girls. Discovery of a similar genetic abnormality in MHL and UES has clinched the supposed link between them. There have also been two reports of UES with prominent cystification, one associated with peripheral eosinophilia, and thereby masquerading as hydatid cyst of the liver. We report a case of UES arising in a young boy with MHL, with unusual histologic features, including large mesothelial-lined cysts and ectopic adrenal cortical tissue under Glisson's capsule.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

A role for L3T4+ T cells and their lymphokines in the generation of suppressor effector (TS3) cells.

The cellular requirements for the in vitro induction of antigen-specific suppressor T cells were examined. Previous reports indicated that Ia-bearing macrophages and anti-idiotypic B cells are required as accessory cells to facilitate the generation of suppressor effector (TS3) cells which regulate the response to the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten. The present study describes two distinct T cell populations which interact to generate antigen-specific TS3. Fractionation of the T cell populations with monoclonal antibody to the L3T4 determinant led to the identification of an NP-specific L3T4- TS3 progenitor population and an L3T4+ helper/inducer subset. In the presence of NP-coupled antigen, the L3T4+ subset could induce progenitor TS3 to differentiate into mature TS3 cells. The activity of the L3T4+ inducer population could be replaced with specifically activated cloned helper cells which were not NP-reactive since an I-Ab-restricted, insulin-reactive, L3T4+ clone was capable of supporting the generation of NP-specific TS3. Inducer activity appeared to be confined to the Th1 but not the Th2 subset. In addition, 18-hr supernatants from antigen-activated clones were capable of substituting for L3T4+ cells or T cell clones in TS3 induction cultures. The TS maturation/differentiation factor(s) active in these supernatants does not appear to be IL-1, IL-2, IL-3, or interferon-gamma alone since purified sources of these lymphokines failed to induce TS3 activity.

Animals↗
PubMed1994

Regeneration of the endothelium in the canine and feline thoracic duct.

Recent improvements in microsurgical techniques on lymphatic vessels facilitated the treatment of lymphoedema. But it is becoming clear that a successful treatment of lymphatic disease has to be based on knowledge of ongoing processes. Particularly, one of the important and unclear issue is cellular mechanisms of lymphatic regeneration. The regeneration of endothelial and the smooth muscle cells of the thoracic duct has been experimentally tested in vivo. The canine and feline thoracic duct was cryo-injured using 3 mm-based copper rod. Damaged endothelial cells remained attached to the substrate and lost unthrombogenecy within 48 hr. Adjacent EC restored the defect within 3 days by migration and proliferation. We observed that on the first day, the endothelial monolayer included some elongated multinuclear cells with blind silver lines whereas, on the third day, they were replaced by a population of smaller ECs with numerous mitoses. Organization of the monolayer was restituted within 7 days. The newly formed endothelium was similar to regenerating endothelium of arteries. In general, the clot that appeared at the zone of injury on the second day was dissolved by the third day. Occasionally, the dense polymorphic clot adhered to the wall and caused a delay in reendothelisation. Complete restitution of the tunica media which involved migration and proliferation mechanisms accompanied the endothelium regeneration.

Animals↗
PubMed1982

Changes in the density of circulating erythrocytes of the bullfrog tadpole, Rana catesbeiana, in relation to the transition of hemoglobin during metamorphosis.

1. The circulating erythrocytes of Rana catesbeiana tadpoles at varying metamorphic stages were studied by the phthalate-microcapillary technique of Danon & Marikovsky (1964 J. Lab. Clin. Med. 64, 668-674) and by the method of Murphy (1973 J. Lab. Clin. Med. 82, 334-341), which are used for the separation of erythrocytes according to the density. 2. The erythrocytes of tadpoles were different in the mean density from those of adult frogs. 3. At the metamorphic climax, aged erythrocytes having the tadpole hemoglobin coexisted with young erythrocytes having the frog hemoglobin in the circulating blood. 4. The frog hemoglobin was preferentially synthesized during metamorphosis. 5. All the results suggested that the transition of hemoglobin during metamorphosis was associated with the replacement of erythrocyte population.

Animals↗
PubMed1995

There is nothing permanent except change. The emergence of new virus diseases.

The sudden appearance of apparently new viruses with pathogenic potential is of fundamental importance in medical microbiology and a constant threat to humans and animals. The emergence of a "new" pathogen is not an isolated event, as for instance the frequent appearance of new influenza virus strains demonstrates. Often the new virus strains co-circulate with the older strains in a susceptible population, but a replacement of the older strains has been also observed. In rare instances the new viruses can cause dramatic epidemics or pandemics, such as those observed with the human immunodeficiency virus, canine parvovirus, or most recently, with the agent of bovine spongiform encephalopathy in the United Kingdom. The mechanisms of the emergence are not always clearly understood, but an altered host range appears to be a common event. Whether a true change in host range occurs, or whether the virus adapted to the host and replicated more efficiently, is often unknown. This review tries to summarize the facts that are known about a wide variety of "new" viruses of mammals, such as the simian, human and feline lentiviruses, the feline coronaviruses, the feline parvoviruses, the carnivore morbilliviruses, the influenza A viruses, and the transmissible spongiform encephalopathies. A particular emphasis will be put on the genetic mechanisms that might have taken place and that might have been responsible for their sudden appearance.

Animals↗
PubMed1997

The archaeological attributes of behaviour: difference or variability?

Did the Neanderthals evolve into anatomically modern humans, or were they replaced by incoming populations of Homo sapiens sapiens? This is perhaps the most well-known question debated by palaeoanthropologists and archaeologists interested in the period from roughly 250,000 to 30,000 years ago in Eurasia. But while this debate may have attracted most of the media attention, there are other research questions that are at least as worthy of public interest as biological origins.

Animals↗
PubMed1999

Automation of functional assays by flow injection fluorescence microscopy.

Bead-injection spectroscopy is a novel technique that uses immobilized eukaryotic cells on microbeads as a renewable biosensor for fluorescence microscopy. The use of a flow injection instrument allows fast functional assays that generate full kinetic characterization of a drug. Because the cell population is automatically replaced for each assay, variability is minimized, thus allowing greater accuracy.

Biotechnology↗
PubMed1997

Atherosclerotic ischemic renal disease.

Over the past decade, ischemic nephropathy has gained recognition as a distinct and treatable clinical entity. Atherosclerotic renal artery stenosis is the leading cause of ischemic renal disease. Among the aging population entering renal replacement programs, both renal artery and systemic atherosclerosis are common. Over recent years, patients with ischemic renal disease are presenting later and have diffuse atherosclerosis and other comorbid conditions. Improved screening techniques, patient selection, and interventional approaches have resulted in better outcomes in most centers. Percutaneous transluminal renal angioplasty has emerged as the treatment of choice in some centers for nonostial renal artery stenosis. Both percutaneous transluminal renal angioplasty and surgical repair have proven beneficial for renal function salvage. Many studies have elegantly demonstrated the pathophysiologic consequences of acute ischemia to the kidney. The concepts derived from acute studies have served as a springboard for considering the adaptive and maladaptive renal responses to chronic ischemia.

Arteriosclerosis↗
PubMed1995

Epidemic spread and antigenic variability of Neisseria meningitidis.

Genetic variation of cell-surface antigens of serogroup A meningococci arises from horizontal genetic exchange. Most clonal variants are lost by clonal reduction during epidemic and pandemic spread, but in exceptional cases, genetic variants are rapidly fixed in the bacterial population by clonal replacement.

Africa, Western↗
PubMed1994

Causes of hemodialysis access failure.

Complications of hemodialysis access remain significant problems in the population receiving renal replacement therapy. The causes of access loss must be recognized before appropriate interventions can be designed. The native primary arteriovenous fistula is the access of choice because of its good survival characteristics and low rate of complications. Unfortunately, a substantial number of patients have vasculature insufficient to create and maintain this access. Once a primary fistula is established, thrombosis is the leading cause of failure: its causes can be divided into early (less than 6 weeks) and late complications. In patients unable to have fistulas, arteriovenous conduits of expanded polytetrafluoroethylene (ePTFE) are now the prostheses of choice. Again thrombosis is the leading cause of this access loss but there is also a substantial rate of failure from infection, pseudoaneurysms, perigraft hematomas, and simple attrition of the prosthesis. Thrombosis of ePTFE grafts is usually associated with anatomic stenosis at the venous anastomosis, within the graft itself, or in the central venous system. Graft thromboses cannot always be attributed to anatomic lesions: in these circumstances, thrombosis has been attributed to low-flow states. It is possible that the normal balance between endothelial procoagulant and anticoagulant forces are disrupted within the arteriovenous conduit. Recurrent venipuncture, hemodialysis therapy itself, or pathophysiological forces inherent in the access may all favor hemostasis. Infection also causes significant hemodialysis access morbidity. The causative organism is usually Staphylococcus aureus but several other pathogens have been reported. Ideally, all prostheses should be removed when infected, but this approach must be tempered by the reality of limited hemodialysis access sites. There is no consensus as to the best therapeutic approach to access infection.

Arteriovenous Shunt, Surgical↗
PubMed2004

Statistical issues in a modeling approach to assessing bioequivalence or PK similarity with presence of sparsely sampled subjects.

Drug development at different stages may require assessment of similarity of pharmacokinetics (PK). The common approach for such assessment when the difference is drug formulation is bioequivalence (BE), which employs a hypothesis test based on the evaluation of a 90% confidence interval for the ratio of average pharmacokinetic (PK) parameters. The role of formulation effect in BE assessment is replaced by subject population in PK similarity assessment. The traditional approach for BE requires that the PK parameters, primarily AUC and Cmax, be obtained from every individual. Unfortunately in many clinical circumstances, some or even all of the individuals may be sparsely sampled, making the individual evaluation difficult. In such cases, using models, particularly population models, becomes appealing. However, conducting an appropriate statistical test based on population modeling in a form consistent, at least in principle, with traditional 90% confidence interval approach is not so straightforward as it may appear. This manuscript proposes one such approach that can be applied to sparse sampling situations. The approach aims to maintain, as much as possible, the appropriateness of the hypothesis test. It is applied to data from clinical studies to address a need in drug development for assessment of PK similarity in different populations.

Area Under Curve↗
PubMed1997

Immunological requirements for a subunit vaccine against tuberculosis.

Tuberculosis remains one of the most important threats to world health. Current vaccination and prevention strategies are inadequate and there is an urgent need for a new vaccine. The current vaccine bacille Calmette-Guérin (BCG), is unable to protect against re-activation of disease in later life and its efficacy varies tremendously in different human populations. An ideal replacement would be a non-living subunit vaccine that could impart protective efficacy greater than BCG but without its drawbacks. Before such a goal is achieved, however, there are many parameters that need to be examined in experimental systems. Such studies have revealed that apart from the selection of immunologically relevant antigens, dosage of antigen and type of adjuvant need to be chosen carefully. These parameters need to be examined in the context of the complex biology of the disease and, despite recent progress in defining host/pathogen interactions, experimental vaccines tested so far have fallen short of the protective efficacy of BCG. A coordinated approach, stimulating the various facets of cell-mediated immunity will probably be essential for development of protective immunity through subunit vaccination.

Animals↗
PubMed1996

Isolation and characterization of human epidermal stem cells.

1. The keratinocytes in human epidermis are constantly turned over and replaced by a population of stem cells located in the basal epidermal layer. Until recently there were no markers allowing the isolation of viable epidermal stem cells. However, it has now been shown that epidermal stem cells can be isolated both in vitro and direct from the epidermis as they express high levels of functional beta 1 integrin family receptors for extracellular matrix proteins. 2. The evidence for integrins as stem cell markers and the insights that have been gained into stem cell behaviour are reviewed.

Animals↗
PubMed2004

The incidence and risk of acute renal failure after cardiac surgery.

OBJECTIVE: To evaluate outcome and risk factors of acute renal failure in a surgical population with or without preoperative renal dysfunction. DESIGN: Observational study. SETTING: Intensive care unit at a University Hospital. PARTICIPANTS: Five thousand sixty-eight consecutive adult patients who underwent cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: Perioperative variables measured were age, sex, basic pathology, preoperative renal impairment defined as creatinine >1.4 mg/dL, ventricular dysfunction, preoperative neurologic event, chronic obstructive pulmonary disease, diabetes, type of surgery, use of intra-aortic balloon pump (IABP), cardiopulmonary bypass (CPB) duration, redo or emergency surgery, hemorrhage, blood transfusion, surgical revisions, and postoperative complications. MEASUREMENTS AND MAIN RESULTS: Acute renal failure (100% creatinine increase) developed in 171 (3.4%) patients, whereas 94 patients (1.9% of the population) had renal replacement therapy. Hospital mortality was 40.9% in patients with acute renal failure and increased to 63.8% when renal replacement therapy was requested. Sex, age, emergency surgery, low ejection fraction, IABP device, redo, diabetes, mitral valve surgery, CPB duration, and preoperative renal disease were independently associated with acute renal failure at a multivariate analysis. CONCLUSION: This study confirms that acute renal failure is one of the major complications of cardiac surgery, identifies the risk factors, and suggests that optimizing cardiac output and reducing CPB time could improve the outcome of patients at high risk of acute renal failure.

Acute Kidney Injury↗