Patterning activities of vertebrate hedgehog proteins in the developing eye and brain

BACKGROUND: The hedgehog (hh) family of secreted signaling proteins is responsible for developmental patterning in a variety of systems, including the neural tube, limbs and somites. Within the neural tube, at the level of the spinal cord, products of the vertebrate gene sonic hedgehog (shh) are proposed to function as a ventral patterning influence, with the capability of inducing floor plate and motor neurons. RESULTS: We report the isolation of tiggy-winkle hedgehog (twhh), a novel member of the zebrafish hh gene family. Both twhh and shh are expressed in the ventral midline of the embryonic zebrafish neural tube and brain, but twhh expression becomes limited to the neural tube, whereas shh is also expressed in the notochord. Both genes are expressed in the developing brain, in domains that include a discrete region in the floor of the diencephalon, located between the sites of the future optic stalks. Using pax-2 and pax-6 as markers of proximo-distal fate within the developing eye, we found that ectopic expression of either hh gene promoted proximal fates and suppressed distal fates. In contrast, proximal fates were lost in cyclops mutant embryos, which lack twhh- and shh-expressing forebrain cells. Both twhh and shh proteins undergo autoproteolytic processing in vivo; a fragment corresponding to the amino-terminal cleavage product was sufficient to carry out all signaling activities associated with twhh in eye and brain development. CONCLUSIONS: These findings suggest that secreted signals encoded by members of the hedgehog gene family, emanating from the ventral midline of the neural tube, not only play important roles in dorso-ventral patterning of the brain but also appear to constitute an early patterning activity along the proximo-distal axis of the developing eyes.     

Effects of feeding on protein turnover in healthy children and in children with cystic fibrosis

In 24 patients presenting with 55 renal lesions (mean size, 20.8 mm), single-breath-hold (SBH) fast spin-echo (FSE) techniques allowing T1 and T2 images to be produced within 20 and 23 sec, respectively, were compared with routine non-breath-hold (NBH) spin-echo (SE) T1 and NBH-FSE T2 sequences. Contrast-to-noise ratios (CNRs) measured from SBH-FSE T1 images were an average of 97% higher than their NBH counterparts (P = .0001) and allowed an improved lesion conspicuity in 80% of the cases (P = 0.0001). For T2 imaging, SBH-FSE and NBH-FSE sequences were not statistically different with respect to lesion conspicuity (P = .55) and CNR values (P = .19). This was observed despite a 35% average decrease in CNR of SBH-FSE compared to NBH-FSE images. By reducing respiratory motion artifacts while preserving SE-like image contrast, SBH-FSE techniques have the potential to replace routine NBH sequences for an optimal diagnosis of renal masses.     

A characterization of first-generation flowable composites

A plethora of new low-viscosity composite resin materials, or flowable composites, have been marketed during the last two years, but little has been published about them. The authors describe research in which they compared the properties--filler, depth or cure, flow, wear, compressive strength, diametral tensile strength, indented biaxial flexure strength and toughness--of flowable and hybrid composites. Mechanical property tests (ISO 4049, ISO/DIS 6872) of eight flowable composites and two hybrid composites were conducted. The flowable composite with the least flow was similar to traditional composites. Mechanical properties were generally about 60 to 90 percent of those of conventional composites. The authors conclude that flowable materials should be used with caution in high-stress applications for restorative dentistry.     

Olfactory dysfunction in Guamanian ALS, parkinsonism, and dementia

OBJECTIVES: To assess whether olfactory deficits are present in the general Guamanian Chamorro population and to evaluate olfaction in each of the four neurodegenerative disease syndromes of Guam: ALS, pure parkinsonism, pure dementia, and the combined parkinsonism-dementia complex (PDC). BACKGROUND: Olfactory dysfunction was previously reported in patients with PDC of Guam. METHODS: We developed a culturally adjusted olfactory test battery, derived from the original University of Pennsylvania Smell Identification Test (UPSIT), and administered this to Chamorro residents with ALS (n=9), pure parkinsonism (n=9), pure dementia (n=11), PDC (n=31), and 53 neurologically normal Chamorro and 25 North American control subjects. RESULTS: Similar, marked olfactory dysfunction was found in all four syndromes of Guamanian neurodegenerative disease. This correlated poorly with measures of parkinsonism and cognition. In the neurologically normal Chamorro control group, six subjects (11%) had very low olfactory scores; these were less than the lowest North American score, raising a question of subclinical neurodegenerative disease. CONCLUSIONS: Marked olfactory deficits are common to all four Guamanian neurodegenerative syndromes, and suggest the possibility of similar central neuropathologic substrates. The deficit in the Guamanian ALS group contrasts with idiopathic ALS, in which olfactory function has been reported to be only slightly compromised.     

Mechanism of biochemical action of substituted 4-methylbenzopyran-2-ones. Part II: Mechanism-based inhibition of rat liver microsome-mediated aflatoxin B1-DNA binding by the candidate antimutagen 7,8-diacetoxy-4-methylcoumarin

7,8-Diacetoxy-4-methylcoumarin (DAMC), with no prerequisite for oxidative biotransformation has been reported to produce suicide inactivation of microsomal cytochrome P-450-catalysed formation of aflatoxin B1-8,9-oxide that binds to DNA. Parenteral administration of DAMC to rats caused significant inhibition of AFB1 binding to hepatic DNA in vivo as well as AFB1-induced micronuclei formation in bone marrow cells. These results highlight the antimutagenic potential of DAMC.     

Magnetic resonance spectroscopy or imaging for a diagnosis of poliomyelitis or neurovirulence assay of poliovirusese

An integrated database and search system has been developed for protein family identification and information retrieval, as an approach to undertake the highly complex, genomic-scale problem of molecular sequence database search and organization. AVAILABILITY: http://diana.uthct.edu CONTACT: wu@uthct.edu     

Localized mucosal involvement and severe pulmonary involvement in a young patient with paraneoplastic pemphigus associated with Castleman''s tumour

OBJECTIVES: This study examined the impact of state legislation on mammography quality and access in Michigan. METHODS: The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. RESULTS: The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. CONCLUSIONS: Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery.     

Alternative locations for internal defibrillator electrodes

Successful defibrillation is described in two patients in whom the defibrillating electrode was positioned in the coronary sinus and right ventricular outflow tract as alternative sites. Internal cardiac defibrillation has been successful with single or multiple endocardial electrodes, epicardial patch electrodes, and subcutaneous surface electrodes (patch, array) in varying combinations and recently with an active can electrode. While the traditional location of the endocardial electrode has been the right ventricular apex, we describe two patients in whom defibrillation was successful in alternate locations, the coronary sinus and the right ventricular outflow tract.     

Analysis of donor versus nondonor demographics

A retrospective analysis of the demographic features of all potential organ donors over a 3-year period (1994-1996) at one organ procurement organization was conducted. The potential donor pool of 495 people was 42% female and 58% male, with a slight difference in consent by gender. The mean income difference between donors and nondonors was less than $3000 per year (obtained from zip code census data). Educational achievement affected donation at the lowest educational levels. Cause of death influenced donation, with motor vehicle crash victims donating more often. The strongest factor in consent for donation was ethnicity; whites were more likely to donate than were other ethnic groups. The combination of gender, ethnicity, and cause of death improved the probability of determining a positive outcome to 63%. Demographic information on donors and nondonors can increase public and professional understanding as well as influence decision making to improve donation.     

Coordinated actions of RuvABC in Holliday junction processing

The objective of this article is to describe the creation and operation of a multidisciplinary group to examine the Oklahoma City (OKC) bombing. The OKC bombing presented an opportunity to study a major disaster within 2 days of the incident. The Disaster Health Studies Group (DHSG) was created to facilitate this effort. The creation, organization, and operation of the DHSG is outlined. In addition the mission statement, participants, communications, political empowerment, data preservation and collection, data ownership, patient rights, threats to the DHSG, media interactions, funding, the institutional review board process, and results reporting will be detailed. The 22 projects of the DHSG are listed. In conclusion, four main findings are examined: 1) A multidisciplinary disaster study group is feasible and can be rapidly organized; 2) certain organizations and institutions form a core group for facilitation of the research effort; 3) specific issues must be addressed in order for the group to succeed; and 4) the group leader should have disaster expertise and be committed to the multidisciplinary process.