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Overlapping and differential expression of BIG-2, BIG-1, TAG-1, and F3: four members of an axon-associated cell adhesion molecule subgroup of the immunoglobulin superfamily.

Axon-associated cell adhesion molecules (AxCAMs) play crucial roles in the formation, maintenance, and plasticity of functional neuronal networks. We report here a molecular cloning of a novel AxCAM, BIG-2. BIG-2 is a member of TAG-1/F3 subgroup of the immunoglobulin (Ig) superfamily, with six Ig-like domains, four fibronectin type III-like repeats, and a glycosyl phosphatidylinositol-anchoring domain. Recombinant BIG-2 protein had a neurite outgrowth-promoting activity when used as a substrate for neurons in vitro. To survey the spatial expression pattern of BIG-2 in comparison with other TAG-1/F3 subgroup members, an in situ hybridization analysis was performed in adult and developing rat brain sections with riboprobes specific for BIG-2, BIG-1, TAG-1, and F3. The four AxCAM transcripts displayed cell type-specific expression patterns with overlapping and distinct profiles. In adult hippocampus, for example, we observed BIG-1 mRNA specifically in granule cells of the dentate gyrus, BIG-2 mRNA highly in the CA1 pyramidal cells, TAG-1 mRNA predominantly in the CA3 pyramidal cells, and F3 mRNA in neurons in all of these fields. These results suggest that BIG-2, BIG-1, TAG-1, and F3 may play important roles in the formation and maintenance of specific neuronal networks in the brain.

Amino Acid Sequence↗

Gene transfer mediated by polyarginine requires a formation of big carrier-complex of DNA aggregate.

Cationic peptide, poly-arginine, promotes transfection efficiency under a proper concentration. Using fluorescence microscopy, we observed the structure of the DNA carrier-complex in solution directly. Under low concentration of poly-arginine, small complexes were observed with fluorescence images like a blight light spot. This small complex (sizes are c.a. 1 approximately 2 microns order) had no transfection ability. As the concentration of poly-arginine became high, the complex grew into a big one whose size reached to a degree of 10 microns. Transfection was succeeded under that condition. The relationship between transfection efficiency and higher-order structure of the DNA carrier-complex was discussed.

Amino Acid Sequence↗

BIG-1: a new TAG-1/F3-related member of the immunoglobulin superfamily with neurite outgrowth-promoting activity.

We have cloned a rat cDNA for a novel brain-derived immunoglobulin (Ig) superfamily molecule, BIG-1, by using PCR based on the amino acid sequences of the two closely related and well-known Ig superfamily members, rat TAG-1 and mouse F3. BIG-1 is a glycosylphosphatidylinositol-anchored membrane protein with six Ig-like domains and four fibronectin type III repeats, belonging to the TAG-1/F3 subgroup. The expression of BIG-1 mRNA is developmentally regulated with the highest level in the adult brain. It is restricted to subsets of neurons such as Purkinje cells of the cerebellum, granule cells of the dentate gyrus, and neurons in the superficial layers of the cerebral cortex. Recombinant BIG-1 protein has a neurite outgrowth-promoting activity when used as a substrate for neurons in vitro. These results suggest that BIG-1 may be involved in the formation and maintenance of neuron type-specific networks in the brain.

Amino Acid Sequence↗

Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia.

In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62+/-1.8, range; 9-86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 microU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4+/-0.6 kg/m2) and serum total protein levels (6.6+/-0.1g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.

Adolescent↗

Metatarsalgia in hallux valgus deformity: a pedographic analysis.

The purpose of this study was to analyze the plantar loading patterns in patients with hallux valgus (HV) with and without symptoms of metatarsalgia in order to find predictive pressure variabilities which are likely to result in metatarsalgia. Two groups of subjects (100 feet) volunteered for this study. Both groups provided the diagnosis of HV deformity. Group A (50 feet) exhibited a metatarsalgia symptomatology, whereas group B was asymptomatic. Plantar loading patterns were assessed using the two-step method and data were collected by the use of a capacitive pressure measurement platform. For each patient, 10 acceptable trials were collected. For the analysis, the foot was divided into six plantar regions: heel, midfoot, medial forefoot, lateral forefoot, medial toe, and lateral toe. Maximal peak pressure (PP, N/cm2), pressure-time integral (P/T integral, N/cm2*s), and force-time integral (%) were calculated. In group A, loading patterns (PP, P/T integral) of the lateral forefoot were significantly higher than in group B. The mediolateral pressure transfer from the big toe to the lateral metatarsal region was significantly greater in group A compared to group B. Regarding the lateral forefoot, a pressure time integral < 10 N/cm2*s was indicative of asymptomatic HV feet, whereas in symptomatic HV feet, a pressure time integral >28 N/cm2*s was observed. These results were statistically significant at the p < .01 level.

Biomechanical Phenomena↗

Ozone exposures and implications for vegetation in rural areas of the central Appalachian Mountains, U.S.A.

The United States is making the transition from the 1979 1 hr maximum ozone standard to the newly adopted 8 hr ozone standard (3 yr average of the 4th highest maximum 8 hr ozone concentration). Consequently, we analyzed and compared ozone concentrations under both standards from a variety of monitoring sites throughout the central Appalachian region of Kentucky (KY), West Virginia (WV), and Virginia (VA). Data from 1988-1999 were used to determine how ozone exposure between the two metrics compared for remote sites. Most sites exceeded the 1 hr standard in 1988-1990 due to the 3 yr averaging and multiple high ozone concentrations that occurred over the region in 1988. All sites were in compliance with the 1 hr standard every year after 1991. It was much more common for the ozone exposure to exceed the 8 hr standard, particularly from 1997-1999. Many sites showed exceedences beginning in 1995; Big Meadows (VA) exceeded the 8 hr standard all years except 1994 and 1996. Response of vegetation to ozone in these areas was determined using the combination of W126 values (sigmoidally weighted exposure index), the number of hours that average concentrations > or = 0.10 ppm (N100), and the presence of moderate or more extreme droughts. In general, W126 and N100 values suggested that negative vegetation growth responses over most of the 12 yr would have been minimal for most sites, even for those exceeding ozone standards. Drought-induced stomatal closures would have overridden more extreme negative growth responses at all but the Big Meadows site in 1988.

Air Pollutants↗

Gene flow between insular, coastal and interior populations of brown bears in Alaska.

The brown bears of coastal Alaska have been recently regarded as comprising from one to three distinct genetic groups. We sampled brown bears from each of the regions for which hypotheses of genetic uniqueness have been made, including the bears of the Kodiak Archipelago and the bears of Admiralty, Baranof and Chichagof (ABC) Islands in southeast Alaska. These samples were analysed with a suite of nuclear microsatellite markers. The 'big brown bears' of coastal Alaska were found to be part of the continuous continental distribution of brown bears, and not genetically isolated from the physically smaller 'grizzly bears' of the interior. By contrast, Kodiak brown bears appear to have experienced little or no genetic exchange with continental populations in recent generations. The bears of the ABC Islands, which have previously been shown to undergo little or no female-mediated gene flow with mainland populations, were found not to be genetically isolated from mainland bears. The data from the four insular populations indicate that female and male dispersal can be reduced or eliminated by water barriers of 2-4 km and 7 km in width, respectively.

Alaska↗

Parental attitudes towards the uptake of smoking by children.

ISSUE ADDRESSED: Factors related to parental smoking and parenting practice have a big effect on adolescent smoking. More in-depth information about these relationships can be used to inform interventions. This study investigated Maori, Pacific Islander, New Zealand European and Asian parent attitudes and practices in relation to smoking uptake in children. METHODS: Parents of children aged 8-15 years, recruited through the researchers' community networks and the media, participated in focus groups or interviews run by ethnically matched facilitators. Areas addressed included parents' beliefs about children smoking, their actions, and their suggestions for tobacco control activities. The data were analysed thematically. RESULTS: Parents believed that parental smoking, peer pressure and smoking role models in the media influenced smoking uptake in children. They said they would be disappointed if their children started smoking, but their confidence in influencing them varied. Many talked to their children about the health consequences of smoking, including their own negative perceptions of smoking and smokers. Most had smoke-free homes. The parents who smoked tried to avoid smoking around children. There was a good deal of commonality across the different ethnic groups. Important differences related to the provision of interventions. CONCLUSIONS: Parents believed in the value of a smoke-free lifestyle and wanted to protect their children from smoking. Important strategies to prevent smoking in children may include supporting parents to quit, informing them that discouraging children of any age from smoking can be effective, and providing culturally appropriate education and resources to facilitate parent/child communication about smoking.

Adolescent↗

A novel big defensin identified in horseshoe crab hemocytes: isolation, amino acid sequence, and antibacterial activity.

Hemocytes of the horseshoe crab (limulus) contain a family of arthropodous peptide antibiotics, termed the tachyplesin family, and antibacterial protein, called anti-LPS factor, of which the former is located in the small (S) granules and the latter in the large (L) granules of the hemocytes. In our ongoing studies on granular components, we have identified here a novel defensin-like substance present in both L- and S-granules. This substance strongly inhibits the growth of Gram-negative and -positive bacteria, and fungi, such as Candida albicans. The isolated substance, tentatively termed "big defensin," consists of 79 amino acid residues, of which the COOH-terminal 37 residues have a sequence similar to those of mammalian neutrophil-derived defensins, especially rat defensin. Characterization of the disulfide motif in big defensin indicated that the disulfide array is identical to that of beta-defensins from bovine neutrophils. One clear structural difference is that the limulus hemocyte-derived big defensin has an extension of the NH2-terminal hydrophobic sequence with 35 amino acid residues followed by the COOH-terminal cationic defensin portion. This amphipathic nature of big defensin seems likely to be associated with its potent antibacterial activity. Furthermore, antibacterial activities of the NH2-terminal hydrophobic region and the COOH-terminal defensin portion separated by tryptic digestion are significantly different: the former displays a more potent activity against Gram-positive bacteria, whereas the latter is more potent against Gram-negative bacteria. Big defensin, therefore, may prove to represent a new class of defensin family possessing two functional domains with different antimicrobial activities.

Amino Acid Sequence↗

Drosophila homologs of the proto-oncogene product PEBP2/CBF beta regulate the DNA-binding properties of Runt.

The Drosophila runt gene is the founding member of the Runt domain family of transcriptional regulators. Mammalian Runt domain genes encode the alpha subunit of the heterometric DNA-binding factor PEBP2/CBF. The unrelated PEBP2/CBF beta protein interacts with the Runt domain to increase its affinity for DNA. The conserved ability of the Drosophila Runt protein to respond to the stimulating effect of mammalian PEBP2/CBF beta indicated that flies were likely to have a homologous beta protein. Using the yeast two-hybrid system to isolate cDNAs for Runt-interacting proteins, we identified two Drosophila genes, referred to as Brother and Big-brother, that have substantial sequence homology with PEBP2/CBF beta. Yeast two-hybrid experiments as well as in vitro DNA-binding studies confirmed the functional homology of the Brother, Big-brother, and PEBP2/CBF beta proteins and demonstrated that the conserved regions of the Runt and Brother proteins are required for their heterodimeric interaction. The DNA-bending properties of Runt domain proteins in the presence and absence of their partners were also examined. Our results show that Runt domain proteins bend DNA and that this bending is influenced by Brother protein family members, supporting the idea that heterodimerization is associated with a conformational change in the Runt domain. Analysis of expression patterns in Drosophila embryos revealed that Brother and Big-brother are likely to interact with runt in vivo and further suggested that the activity of these proteins is not restricted to their interaction with Runt.

Amino Acid Sequence↗

Rural tourism as risk factor for the transmission of schistosomiasis in Minas Gerais, Brazil.

Recently, the booming rural tourism in endemic areas of the state of Minas Gerais was identified as a contributing factor in the dissemination of the infection with Schistosoma mansoni. This article presents data from six holiday resorts in a rural district approximately 100 km distant from Belo Horizonte, MG, Brazil, where a possibly new and until now unperceived way of transmission was observed. The infection takes place in swimming pools and little ponds, which are offered to tourists and the local population for fishing and leisure activities. The health authorities of the district reported cases of schistosomiasis among the local population after visiting these sites. As individuals of the non-immune middle class parts of the society of big urban centers also frequent these resorts, infection of these persons cannot be excluded. A malacological survey revealed the presence of molluscs of the species Biomphalaria glabrata and Biomphalaria straminea at the resorts. The snails (B. glabrata) of one resort tested positive for S. mansoni. In order to resolve this complex problem a multidisciplinary approach including health education, sanitation measures, assistance to the local health services, and evolvement of the local political authorities, the local community, the tourism association, and the owners of the leisure resorts is necessary. This evidence emphasizes the urgent need for a participative strategic plan to develop the local tourism in an organized and well-administered way. Only so this important source of income for the region can be ensured on the long term without disseminating the disease and putting the health of the visitors at risk.

Animals↗

Why PACS is no longer a four-letter word.

The real value of PACS is not realized until widespread adoption exists among physicians other than interpreting radiologists. Referring physicians at the office level, in the operating room and in other departments must be willing to embrace the reading of images on monitors. That takes time. The payoff for a PACS system is therefore not realized until sometime in the future. Given the huge up-front capital expenditure required of PACS solutions, it is no wonder that the decision has historically been a difficult one to make. Enter the application service provider (ASP). The marriage of the ASP model to PACS seems to be one of the true "killer apps" currently available in the healthcare technology space. An ASP can host and maintain the software inherent in PACS solutions. Images are centrally archived over the short-, medium-, and long-term timeframe, utilizing state-of-art data management facilities. Some ASPs also provide the necessary bandwidth to office sites and the small amount of hardware that is required onsite, such as viewing stations or monitors. Costs for Internet-based image management under the ASP model rely on a pay-as-you-go formula, which may include all software, support, required hardware and bandwidth as part of the service. There may be a minor up-front fee for installation. The ASP pricing model eliminates the huge gamble an organization takes on "big iron" PACS purchases. Those benefits rely on the first rule of finance: a dollar today is worth more than a dollar tomorrow. PACS and ASPs were made for one another. Because the financial benefits of PACS are realized over time, the timing of cash flows is extremely important. Other benefits inherent in the ASP model such as scalability, diminished need for IT personnel, software version integrity and better pricing because of economies of scale are attractive also.

Capital Expenditures↗

Biochemical and functional characterization of endothelin peptides with special reference to vascular effects.

1. Detection of ET-LI in porcine and human tissues in the present study revealed the presence of high levels in blood vessels, heart, airways, kidney, placenta, amnion and umbilical vessels. ET-1 was the predominant form in both porcine and human tissues, while evidence for additional occurrence of ET-3 was obtained in the porcine kidney and spinal cord. No evidence for presence of VIC or ET-2 was obtained in the studied porcine or human tissues. Immunohistochemical techniques revealed the presence of ET-LI in the amniotic membrane cells as well as in vascular endothelial cells. 2. Transient release of ET-LI from the porcine spleen was observed during endotoxin infusion and after a 2 min period of asphyxia. During endotoxin administration plasma ET-LI increased progressively and the presence of both ET-1 and big ET-1 in the plasma was shown. Short term sympatho-adrenal activation did not evoke ET-release, however. In man, high levels of ET-LI, indicating release, were observed in the amniotic fluid and umbilical plasma at birth. 3. Specific, high affinity ET receptors were demonstrated in human and porcine tissues. One main characteristic for ET binding was the extremely slow dissociation rate. The ET-1 selective ETA receptor was predominant in the porcine spleen and renal artery as well as in the human heart and umbilical arteries, whereas the ETB receptor predominated in the porcine renal medulla and the spinal cord and the human placenta. In the porcine and human lung a mixed population of ETA and ETB receptors seemed to be present. ET-1 but not ET-3 increased IP turnover in the spleen, while both ET-1 and ET-3 was effective in the lung, suggesting the same second messenger system for both receptor subtypes. Neither ET-1 nor ET-3 was observed to have any effect on the adenylate cyclase system. 4. ET-1 was extremely potent as a vasoconstrictor in the porcine kidney and spleen in vivo, while the effect in the femoral vascular bed was less pronounced. ET-3 was considerably less potent than ET-1 as vasoconstrictor in the kidney and the spleen. However, ET-1 and ET-3 acted equipotently as vasodilators in the bronchial circulation, suggesting opposite vascular effects in the different vascular beds. Big ET-1 caused only minor vasoconstriction. ET-1 was a potent constrictor agent of human coronary, pulmonary and umbilical vessels as well as of human bronchi in vitro.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

[Muscular and subcutaneous hydatidosis].

Among unusual echinococcus cysts, muscular hydatidosis merits particular attention. Careful analysis of the statistics provided by the literature shows that the condition is not all that rare: its incidence varies from 0.5 to 4.7%, making it less common than hepatic or pulmonary cysts but more frequent than cysts of the kidneys, bone, pancreas, spleen or mesenterium. There are disagreements about the percentage distribution in the various muscular districts but it seems that the incidence gradually decreases as we go from the muscles of the torso and the root of the limbs to the distal extremities. The Palermo University case series includes 6 cases of which 5 muscular and one in the connective tissue. Of the 4 muscular cases, only one is to be considered secondary. For the purposes of correct preoperative diagnosis we should not neglect either anamnestic data or laboratory tests. Though the latter are not specific they are helpful for differential diagnosis from other muscular neoformation. Exploratory centesis that must be performed very cautiously in order to prevent dissemination appears to be more specific. Radiography and ultrasound examinations permit the direct study of cystic formations and a general assessment of the possibility of multiple hydatid locations. The only possible treatment is surgical. Though total removal of the cyst is the operation of choice, this is not always possible if the cyst is very big and adhering to other structures. In this case the procedure to be adopted is sterilisation and aspiration of the content, removal of the membrane and treatment of the pericystium.(ABSTRACT TRUNCATED AT 250 WORDS)

Echinococcosis↗

Measuring pain in the (knockout) mouse: big challenges in a small mammal.

The increasing popularity of the mouse as a subject in basic science studies of pain can largely be attributed to the development of transgenic "knockout" technology in this species only. To take advantage of this biological technique, many investigators are rushing to adapt to the mouse experimental protocols that were designed for the rat. However, the myriad physiological and behavioral differences between these two rodent species render such adaptations non-trivial and in many cases seriously problematic. In this article we review the basic nociceptive assays used in behavioral pain research (thermal, mechanical, electrical and chemical), and highlight how species differences affect their proper application. In addition, some of the issues specifically pertaining to the interpretation of such data in knockout studies are addressed.

Animals↗

Reliable assessment of the effects of treatment on mortality and major morbidity, I: clinical trials.

This two-part review is intended principally for practising clinicians who want to know why some types of evidence about the effects of treatment on survival, and on other major aspects of chronic disease outcome, are much more reliable than others. Although there are a few striking examples of treatments for serious disease which really do work extremely well, most claims for big improvements turn out to be evanescent. Unrealistic expectations about the chances of discovering large treatment effects could misleadingly suggest that evidence from small randomised trials or from non-randomised studies will suffice. By contrast, the reliable assessment of any more moderate effects of treatment on major outcomes--which are usually all that can realistically be expected from most treatments for most common serious conditions--requires studies that guarantee both strict control of bias (which, in general, requires proper randomisation and appropriate analysis, with no unduly data-dependent emphasis on specific parts of the overall evidence) and strict control of random error (which, in general, requires large numbers of deaths or of some other relevant outcome). Past failures to produce such evidence, and to interpret it appropriately, have already led to many premature deaths and much unnecessary suffering.

Clinical Trials as Topic↗

The surveillant assemblage.

George Orwell's 'Big Brother' and Michel Foucault's 'panopticon' have dominated discussion of contemporary developments in surveillance. While such metaphors draw our attention to important attributes of surveillance, they also miss some recent dynamics in its operation. The work of Gilles Deleuze and Felix Guattari is used to analyse the convergence of once discrete surveillance systems. The resultant 'surveillant assemblage' operates by abstracting human bodies from their territorial settings, and separating them into a series of discrete flows. These flows are then reassembled in different locations as discrete and virtual 'data doubles'. The surveillant assemblage transforms the purposes of surveillance and the hierarchies of surveillance, as well as the institution of privacy.

Confidentiality↗

Falling through the cracks of the big cities: who is meeting the needs of HIV-positive youth?

BACKGROUND: Globally, half of all new HIV infections occur among youth under 25. As of June 30, 2002, more than 13,000 youth and young adults had tested positive for HIV in Canada. Despite this prevalence, there is a lack of resources for Canadian HIV-positive youth. OBJECTIVE: To investigate what can be done to better support the needs of HIV-positive youth in Canada. METHODS: A community-based participatory research approach was adopted. Thirty-four qualitative in-depth semi-structured interviews were conducted with youth (ages 12-24) living with HIV in Ontario. A stakeholder group of youth living with HIV, professionals and researchers collaboratively analyzed the data for emerging themes. RESULTS: When asked about areas in their lives where youth needed support, three major themes emerged: 1) Personal feelings about HIV: Youth identified a wide range of emotional response to their HIV status; however feelings of isolation, loneliness and hopelessness were dominant. 2) Barriers to full participation in society: Youth described a number of social and structural barriers to their full participation in society. 3) Specific support needs: Youth had difficulty accessing appropriate support services; they had very mixed feelings about both youth- and AIDS-serving organizations. INTERPRETATION: The youth we interviewed are interested in targeted programs, have difficulty accessing appropriate resources and would benefit greatly from increased social support. Specialized health and support services that are developmentally appropriate may be necessary. Where specialized services do exist, more research may be necessary to understand why they are underutilized and/or perceived as inappropriate. While this was a small exploratory study, our data suggest that better supporting the needs of HIV-positive youth might directly benefit this vulnerable population.

Adolescent↗