Fine mapping of the Darier's disease locus on chromosome 12q

Darier's disease (DD) is an autosomal dominant genodermatosis characterized by epidermal acantholysis and dyskeratosis. We have performed genetic linkage studies in 10 families with DD (34 affected) by analyzing 14 polymorphic microsatellite markers. Our results confirm recent reports mapping the DD gene to chromosome 12q23-q24.1. Haplotype analysis of recombinant chromosomes in our families, along with previously reported data, narrow the location of the DD gene to a 5 cM interval flanked by the loci D12S354 and D12S84/D12S105. This localization allowed exclusion of two known genes, PLA2A and PAH, as candidate loci for DD. Three other gene loci (PPP1C, PMCH, PMCA1), mapping in 12q21-q24, remain potential candidates.     

Center-specific graft and patient survival rates: 1997 United Network for Organ Sharing (UNOS) report

CONTEXT: Multiple comprehensive, risk-adjusted studies evaluating short-term surgical mortality have been reported previously. This report analyzes short-term and long-term outcomes, both nationally and at each individual transplant program, for all solid organ transplantations performed in the United States. OBJECTIVES: To report graft and patient survival rates for all solid organ transplantations, both nationally and at each specific transplant program in the United States, and to compare the expected survival rate with the actual survival rate of each individual program. DESIGN AND SETTING: Multivariate regression analysis of donor and recipient factors affecting graft and patient survival of all kidney, liver, pancreas, heart, lung, and heart-lung transplants reported to the United Network for Organ Sharing from 742 separate transplant programs. PATIENTS: A cohort of 97587 solid organ transplantations performed on 92966 recipients in the United States from January 1988 through April 1994. MAIN OUTCOME MEASURES: Short-term and conditional 3-year national and individual transplant program graft and patient survival rates overall and from 2 separate eras (era 1, January 1988-April 1992; era 2, May 1992-April 1994); comparison of actual center-specific performance with risk-adjusted expected performance and identification of centers with better-than-expected or worse-than-expected survival rates. RESULTS: One-year graft follow-up exceeded 98% and conditional 3-year follow-up exceeded 91% for all organs. Graft and patient survival improved significantly in era 2 compared with era 1 for all cadaver organs except heart, which remained the same. One-year cadaveric graft survival ranged from 81.5% for heart to 61.9% for heart-lung and 3-year conditional graft survival ranged from 91.3% for pancreas to 74.7% for lung. The percentage of programs whose actual 1-year graft survival was not different from or was better than their risk-adjusted expected survival ranged from 98.3% for heart-lung to 75.7% for liver. Most kidney, liver, and heart programs whose actual survival was significantly less than expected performed small numbers (less than the national average) of transplantations per year. CONCLUSIONS: Graft and patient survival for solid organ transplantations showed improvement over time. Conditional 3-year graft and patient survival rates were approximately 90% for all organs except for lung and heart-lung. The conditional 3-year survival rates were better than 1-year survival rates, indicating the major risk after transplantation occurs in the first year. The majority of transplant programs achieved actual survival rates not significantly different from their expected survival rates. Center effects were most significant within the first year after transplantation and had much less influence on long-term survival outcomes.     

Diaspirin cross-linked hemoglobin resuscitation improves cerebral perfusion after head injury and shock

BACKGROUND: Shock associated with traumatic brain injury (TBI) doubles the mortality of TBI alone by inducing a secondary ischemic injury. Rapid correction of cerebral perfusion pressure (CPP) is thought to be essential to improving outcome. Diaspirin cross-linked hemoglobin (DCLHb) has been shown to improve cerebral blood flow, increase mean arterial pressure (MAP), and reduce lesion size in models of occlusive cerebral ischemia but has not been evaluated in a model of TBI combined with hemorrhagic shock. METHODS: We studied the effects of DCLHb resuscitation in a porcine model of cryogenic TBI and hemorrhagic shock (MAP = 50 mmHg). After combined insults, animals were randomized to receive a bolus of 4 mliters/kg of either lactated Ringer's solution (n = 5) or DCLHb (n = 6). Lactated Ringer's solution was then infused in both groups to maintain MAP at baseline. Shed blood was returned 1 hour after the initiation of resuscitation (R1). Animals were studied for 24 hours. RESULTS: DCLHb infusion resulted in a significantly greater MAP at R1 and R24 (95 +/- 4 vs. 82 +/- 2 and 99 +/- 3 vs. 85 +/- 3 mm Hg, respectively) and a significantly greater CPP at R1 and R24 (83 +/- 10 vs. 68 +/- 5 and 89 +/- 6 vs. 71 +/- 11 mm Hg, respectively). Intracranial pressure was lower in the DCLHb group, but this difference was not significant. There was no significant difference between the groups in cerebral oxygen delivery. DCLHb animals required less fluid to maintain MAP (12,094 +/- 552 vs. 15,542 +/- 1094 mliters, p < 0.05). CONCLUSION: These data suggest that DCLHb is beneficial in the early resuscitation of head injury and shock and that further investigation is warranted. Key Words: Diaspirin cross-linked hemoglobin, Head injury, Shock, Cerebral perfusion pressure.     

Poly(lactide-co-glycolide) microencapsulation of vaccine antigens

Fimbriae from Bordetella pertussis have been encapsulated in poly(lactide-co-glycolide) (PLG) microspheres of a size appropriate for oral administration. The binding of antibodies which react with conformational or linear fimbrial epitopes, to fimbriae released from microspheres, suggested that the process of was not detrimental to the native integrity of the protein. Mice were immunised by oral gavage with a single dose of microencapsulated fimbriae, or with fimbriae adsorbed onto alhydrogel and administered by intraperitoneal injection. The resulting immune responses in serum were comparable but only oral administration of microencapsulated fimbriae elicited specific immune responses in external secretions. Six weeks after immunisation, both groups of immunised animals were protected against challenge with live B. pertussis.     

cis-acting RNA elements required for replication of bovine viral diarrhea virus-hepatitis C virus 5'' nontranslated region chimeras

Pestiviruses, such as bovine viral diarrhea virus (BVDV), share many similarities with hepatitis C virus (HCV) yet are more amenable to virologic and genetic analysis. For both BVDV and HCV, translation is initiated via an internal ribosome entry site (IRES). Besides IRES function, the viral 5' nontranslated regions (NTRs) may also contain cis-acting RNA elements important for viral replication. A series of chimeric RNAs were used to examine the function of the BVDV 5' NTR. Our results show that: (1) the HCV and the encephalomyocarditis virus (EMCV) IRES element can functionally replace that of BVDV; (2) two 5' terminal hairpins in BVDV genomic RNA are important for efficient replication; (3) replacement of the entire BVDV 5' NTR with those of HCV or EMCV leads to severely impaired replication; (4) such replacement chimeras are unstable and efficiently replicating pseudorevertants arise; (5) pseudorevertant mutations involve deletion of 5' sequences and/or acquisition of novel 5' sequences such that the 5' terminal 3-4 bases of BVDV genome RNA are restored. Besides providing new insight into functional elements in the BVDV 5' NTR, these chimeras may prove useful as pestivirus vaccines and for screening and evaluation of anti-HCV IRES antivirals.     

Design synthesis in VLSI and software engineering

In this paper we present the results of the Working Group on Design Synthesis and Measurement. This group explored the issues that separate and bind software engineering and VLSI design. The issues on which we comment are design views and tradeoff, levels of abstraction and their importance, and design methodologies and their effect on decisions. We also examine the support environments needed to facilitate design in VLSI and software engineering, state-of-the-art of silicon compilation today, and the types of problems that are best suited to silicon compilation.     

On Optimum Sampled-Data FM Demodulation

Since the introduction of large-scale integration (LSI) techniques, there has been a continuing effort to develop digitalization techniques for communication equipment amenable to LSI implementation. Hopefully, this will permit expanded capability in the equipment while taking advantage of the cost reliability attributed of LSI. In this paper, a digitalized or sampled-data FM demodulator recursive algorithm is synthesized and its signal-to-noise ratio performance compared with the optimum analog demodulator and the conventional limiter discriminator demodulator. The demodulator is shown to exhibit threshold extension capability and automatic time-varying gain (bandwidth) adjustments from acquisition through tracking of the incoming modulated signal.     

Self-infusion of GABAA antagonists directly into the ventral tegmental area and adjacent regions.

This study used an intracerebral self-administration paradigm in rats to determine if blockade of GABAA receptors in the ventral tegmental area (VTA) has a reinforcing effect. Rats quickly learned to self-infuse a picrotoxin solution into the anterior VTA; rats discriminated the lever that produced picrotoxin infusions from the lever without consequences; and when the response requirement was increased, rats increased response levels for picrotoxin infusion. The reinforcing effect of picrotoxin was site-specific: Anterior VTA regions supported vigorous self-infusions, but not the posterior VTA, substantia nigra, or lateral hypothalamus. Muscimol, a GABAA agonist, disrupted picrotoxin self-infusion, but bicuculline, a GABAA antagonist, was self-infused into the VTA. The results suggest that blockade of GABAA receptors in the anterior VTA is reinforcing and that functional organization of the GABA systems within the VTA is heterogeneous. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Social experience with siblings fosters species specific responsiveness to maternal visual cues in bobwhite quail chicks (Colinus virginianus).

Examined the role of visual and social experience with siblings in the development of bobwhite quail chicks' preference for species-specific maternal visual cues. Chicks were reared in 1 of 4 conditions: group, isolation, partial isolation, and heterospecific group. They were tested in simultaneous choice tests with species-typical and species-atypical audiovisual stimuli. Results revealed that only Ss that were reared in a group with same-aged conspecifics preferred the visual features of a bobwhite hen model. Ss in the other 3 conditions did not exhibit species-specific visual preference. Findings suggest that visual experience and direct social interaction with siblings facilitate the development of bobwhite chicks' species-specific responsiveness to static maternal visual cues and illustrate the important influence of experience with conspecifics in the development of early perceptual preferences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)