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Biomedical subjects

Mark Johnson

Publications and source records attributed to Mark Johnson.

At least 19 recordsLinked to original sources
PubMed2004

Transcatheter occlusion of baffle leaks following atrial switch procedures for transposition of the great vessels (d-TGV).

Baffle-related complications following atrial switch procedures for transposition are relatively common. Transcatheter treatment of baffle stenosis has an established role as a therapeutic modality. However, transcatheter device closure of atrial baffles leaks has rarely been reported. We report four patients who underwent device closure of baffle leaks using the Amplatzer septal occluder following atrial switch procedures in order to demonstrate the safety and utility of this method of treatment and to establish its role as a suitable alternative to surgical closure.

Adolescent↗
PubMed2003

A principled method for determining the functionality of brain responses.

A challenging issue in relating brain function to perception and cognition concerns the functional interpretation of brain responses. For example, while there is agreement that the N170 component of event-related potentials is sensitive to face processing, there is considerable debate about whether its response reflects a structural encoder for faces, a feature (e.g. eye) detector, or something else. We introduce a principled approach to determine the stimulus features driving brain responses. Our analyses on two observers resolving different face categorization tasks (gender and expressive or not) reveal that the N170 responds to the eyes within a face irrespective of task demands. This suggests a new methodology to attribute function to different components of the neural system for perceiving complex stimuli.

Brain↗
PubMed2003

Two studies examining environmental predictors of heavy drinking by college students.

Two sequential studies are presented that examine the validity of a set of environmental variables to predict heavy drinking at college students' most recent drinking occasions. Random telephone interviews (n=1609, n=400) of graduate and undergraduate students attending two large public universities in the southwestern United States were conducted during three separate surveys in 2000 and 2001. An original interview schedule was used and it included measures that examined environmental characteristics of students' most recent drinking events, motivations for drinking, demographics, and alcohol consumption. Using nonparametric exploratory and confirmatory discriminant analyses to distinguish between heavy episodic and non-heavy episodic drinking events, a discriminant function was identified that included the following environmental variables: (1) having many people intoxicated at an event, (2) having illicit drugs available at an event, (3) BYOB events and, (4) the playing of drinking games at the event. The validity of these environmental variables to predict heavy drinking among students was supported in a subsequent study examining a separate sample from the same student population. Environmental factors can be useful to predict heavy drinking events experienced by students. Prevention programs would benefit from targeting such factors in combination with more traditional individual-level approaches.

Adolescent↗
PubMed2003

BioSPICE: access to the most current computational tools for biologists.

The goal of the BioSPICE program is to create a framework that provides biologists access to the most current computational tools. At the program midpoint, the BioSPICE member community has produced a software system that comprises contributions from approximately 20 participating laboratories integrated under the BioSPICE Dashboard and a methodology for continued software integration. These contributed software modules are the BioSPICE Dashboard, a graphical environment that combines Open Agent Architecture and NetBeans software technologies in a coherent, biologist-friendly user interface. The current Dashboard permits data sources, models, simulation engines, and output displays provided by different investigators and running on different machines to work together across a distributed, heterogeneous network. Among several other features, the Dashboard enables users to create graphical workflows by configuring and connecting available BioSPICE components. Anticipated future enhancements to BioSPICE include a notebook capability that will permit researchers to browse and compile data to support model building, a biological model repository, and tools to support the development, control, and data reduction of wet-lab experiments. In addition to the BioSPICE software products, a project website supports information exchange and community building.

Computational Biology↗
PubMed2003

The effect of intrauterine myelomeningocele repair on the incidence of shunt-dependent hydrocephalus.

BACKGROUND: Intrauterine myelomeningocele repair (IUMR) was first successfully performed in 1997. Preliminary reports suggest that this procedure reduces the incidence of shunt-dependent hydrocephalus when compared to conventional postnatal therapy. However, the existing cohort of IUMR patients has not yet been systematically compared to a comparable group of conventionally treated controls. METHODS: Patients 1 year old or greater who had undergone IUMR at either Vanderbilt University or the Children's Hospital of Philadelphia (CHOP) were compared to a group of conventionally treated historical controls treated and followed at CHOP. In order to measure any differences between the groups, patients were stratified according to the level of the myelomeningocele lesion and the gestational age at the time of IUMR. RESULTS: One hundred and four IUMR patients were compared to 189 conventionally treated controls. IUMR resulted in statistically significant reductions in the incidence of shunt-dependent hydrocephalus at both lumbar and sacral lesion levels. When lumbar lesion levels were further stratified, from L1 to L5, it appeared that the benefit of IUMR was statistically significant only at levels below L2. Other factors with a significant impact on hydrocephalus were estimated gestational age and ventricular size at the time of surgery. In particular, statistically significant differences compared to controls were seen in the younger (< or =25 weeks) group but not in the older (>25 weeks) group. CONCLUSIONS: IUMR appears to substantially reduce the incidence of shunt-dependent hydrocephalus when compared to conventional treatment even when lesion level is taken into account. Patients with lesions above L3 may not share in this benefit. IUMR cannot be justified in fetuses older than 25 weeks of gestation. Additional improvements might be obtained by further reducing the average age at which fetuses are operated upon. It remains to be determined whether this benefit outweighs the potential risks of intrauterine surgery.

Cerebrospinal Fluid Shunts↗
PubMed2003

Quick-freeze/deep-etch visualization of age-related lipid accumulation in Bruch's membrane.

PURPOSE: To examine age-related changes in the ultrastructure of Bruch's membrane with quick-freeze/deep-etch (QFDE) and conventional thin-section transmission electron microscopy (TEM). METHODS: Four eyes from human donors aged 27, 41, 76, and 78 years were preserved within 4 hours of death. Full-thickness tissue blocks from the macula were prepared for TEM or for QFDE. RESULTS: Ultrastructure seen by conventional TEM was revealed in greater detail by QFDE. Cholesterol-containing particles (mean diameter, 80 nm) formed a thin densely packed layer external to the basal lamina of the retinal pigment epithelium (RPE) only in older eyes. The mesh size of the RPE basal lamina was smaller than the particles, and it appeared larger in older eyes. QFDE also revealed less decorated collagen fibrils in older eyes. CONCLUSIONS: The data suggest that the predilection of a extremely thin sublayer of inner Bruch's membrane for accumulating lipid particles may eventually lead to a confluent lipid wall capable of isolating the retina from its blood supply. If these lipids originate in the retinal pigment epithelium, then they are unlikely to have passed through the basal lamina in this form. The age-related increase in lipid particles corresponds with an age-related increase in hydraulic resistance determined in excised Bruch's membrane/choroid by others. QFDE will be useful for future modeling studies of Bruch's membrane transport and to identify those moieties responsible for deleterious age-related transport changes in Bruch's membrane.

Adult↗
PubMed2002

FANCE: the link between Fanconi anaemia complex assembly and activity.

The Fanconi anaemia (FA) nuclear complex (composed of the FA proteins A, C, G and F) is essential for protection against chromosome breakage. It activates the downstream protein FANCD2 by monoubiquitylation; this then forges an association with the BRCA1 protein at sites of DNA damage. Here we show that the recently identified FANCE protein is part of this nuclear complex, binding both FANCC and FANCD2. Indeed, FANCE is required for the nuclear accumulation of FANCC and provides a critical bridge between the FA complex and FANCD2. Disease-associated FANCC mutants do not bind to FANCE, cannot accumulate in the nucleus and are unable to prevent chromosome breakage.

Active Transport, Cell Nucleus↗
PubMed2002

Established human papillomavirus type 16-expressing tumors are effectively eradicated following vaccination with long peptides.

Peptide-based vaccines aimed at the induction of effective T cell responses against established cancers have so far only met with limited clinical success and clearly need to be improved. In a preclinical model of human papillomavirus (HPV)16-induced cervical cancer we show that prime-boost vaccinations with the HPV16-derived 35 amino-acid long peptide E7(43-77), containing both a CTL epitope and a Th epitope, resulted in the induction of far more robust E7-specific CD8(+) T cell responses than vaccinations with the minimal CTL epitope only. We demonstrate that two distinct mechanisms are responsible for this effect. First, vaccinations with the long peptide lead to the generation of E7-specific CD4(+) Th cells. The level of the induced E7-specific CD8(+) T cell response proved to be dependent on the interactions of these Th cells with professional APC. Second, we demonstrate that vaccination with the long peptide and dendritic cell-activating agents resulted in a superior induction of E7-specific CD8(+) T cells, even when T cell help was excluded. This suggests that, due to its size, the long peptide was preferably endocytosed, processed, and presented by professional APCs. Moreover, the efficacy of this superior HPV-specific T cell induction was demonstrated in therapeutic prime-boost vaccinations in which the long peptide admixed with the dendritic cell-activating adjuvant oligodeoxynucleotide-CpG resulted in the eradication of large, established HPV16-expressing tumors. Because the vaccine types used in this study are easy to prepare under good manufacturing practice conditions and are safe to administer to humans, these data provide important information for future clinical trials.

Adjuvants, Immunologic↗
PubMed2002

Spintronics: spin accumulation in mesoscopic systems.

In spintronics, in which use is made of the spin degree of freedom of the electron, issues concerning electrical spin injection and detection of electron spin diffusion are fundamentally important. Jedema et al. describe a magneto-resistance study in which they claim to have observed spin accumulation in a mesoscopic copper wire, but their one-dimensional model ignores two-dimensional spin-diffusion effects, which casts doubt on their analysis. A two-dimensional vector formalism of spin transport is called for to model spin-injection experiments, and the identification of spurious background resistance effects is crucial.

Journal Article↗
PubMed2002

Detection of spin-polarized electrons injected into a two-dimensional electron gas.

The spin-dependent mean-free path of electrons in a high-mobility InAs two-dimensional electron gas (2DEG) is measured. Ferromagnetic metal/insulator/2DEG junctions are fabricated on a common channel in a nonlocal geometry and used as spin injectors and detectors. For electrons in spin-orbit eigenstates at 4.5 K, lower bounds for the spin mean-free path and relaxation time are Lambda(S) > or = 4.6 microm and tau(s) > or = 3.8 ps, respectively. The temperature dependence is weak over the range 4.5<T<150 K.

Journal Article↗
PubMed2002

Liver transplantation in Ellis-van Creveld syndrome: a case report.

This case represents a rare association of Ellis-van Creveld (EvC) syndrome, a chondroectodermal disorder, with congenital paucity of bile ducts. Sequential liver biopsies during the patient's childhood demonstrated progressive fibrosis that can occur in other chondrodysplastic malformations. However, this EvC case is the first report to demonstrate paucity of intra-hepatic bile ducts progressing to cirrhosis and subsequently requiring transplant.

Ellis-Van Creveld Syndrome↗
PubMed2002

Ethnicity in pressure ulcer risk assessment, with specific relation to the Pakistani ethnic minority in Burton, England.

BACKGROUND: There has been little work on ethnicity related to pressure ulcers in general and little or nothing specific to South Asians, and the Pakistani ethnic group in particular. AIM: To explore the relevance of ethnicity in pressure ulcers. METHODS: All admissions over a 5-year period to a District General Hospital in Burton, United Kingdom (UK) were considered where data were present on Waterlow Score, ethnicity and pressure sore status. Logistic regression analysis was conducted using ethnicity and other variables to predict ulcer formation. RESULTS; Age is predictive, but ethnicity was not found to be a significant predictor. CONCLUSION: There is no evidence that members of the Pakistani ethnic minority are at higher risk than the majority White population in Burton, with respect to pressure ulcers.

Age Factors↗
PubMed2002

Cystic adenomatoid malformation volume ratio predicts outcome in prenatally diagnosed cystic adenomatoid malformation of the lung.

BACKGROUND/PURPOSE: Cystic adenomatoid malformation of the lung (CAM) diagnosed in utero has a variable natural history that may result in hydrops in up to 40% or regress in up to 15%. No criteria have been available to determine which lesions would grow and develop hydrops versus those whose growth would stabilize or regress. To better understand the natural history of CAM the authors developed a measure of tumor volume normalized for gestation age, the CAM volume ratio, or CVR. The results of an initial retrospective review of CVR at presentation suggested its usefulness as a predictor of outcome in CAM. The authors now report the results of prospective use of the CVR both to track tumor growth and regression during gestation and confirm its predictive value in fetuses with CAM. METHODS: In the retrospective review performed between November 1998 and August 1999, 32 fetuses with CAM were reviewed and divided into those with hydrops and those in whom hydrops never developed. The CVR was determined by measuring 3 dimensions of the CAM using the formula for the volume of an ellipse and dividing by the head circumference to correct for differences in gestational age. Of the 32 fetuses in the retrospective study, the 8 that had hydrops had a significantly higher CVR (3.1 plus minus 1.1) compared with hydropic fetuses (0.74 plus minus 0.48; P <.001). The mean of the nonhydropic fetus's CVR plus 2 standard deviations (0.74 + 0.96 = 1.7) was used as a cutoff in the subsequent prospective study. From September 1, 1999 through March 1, 2001, the authors evaluated prospectively 58 patients with CAM by CVR measurement. These patients were followed up with serial ultrasound scans, and CVR at presentation correlated with the development of hydrops, survival, need for fetal intervention, and the need for ventilatory support or extracorporeal membrane oxygenation (ECMO), and length of hospital stay postnatally. The indication for fetal intervention was the development of hydops. RESULTS: The fetuses with CVR less-than-or-equal1.6 (n = 42) were considered to be at low risk for the development of hydrops, and those with CVR greater than 1.6 (n = 16) were considered at increased risk for developing hydrops. Of the 42 fetuses in the low-risk group, 7 (16.7%) developed hydrops, and all but 1 had a dominant cyst. If CAMs with a dominant cyst are excluded, only 1 of 36 (2.8%) of CAMs with CVR less-than-or-equal 1.6 developed hydrops (P <.001). In fetuses with CVR at presentation more than 1.6, 12 of 16 (75%; P <.005) developed hydrops. Seventeen fetuses underwent fetal treatment (8 CVR less-than-or-equal 1.6; 9 CVR > 1.6): 7 patients required open fetal surgery (survival rate, 2 of 7), 6 patients thoracoamniotic shunting (survival rate, 6 of 6); and 4 patients cyst aspiration (survival rate, 4 of 4). All survivors of fetal intervention required at a least brief period of ventilatory support; none required ECMO. CONCLUSIONS: A CVR of greater than 1.6 at presentation accurately predicts increased risk of hydrops developing in CAM. A CVR of less-than-or-equal1.6 at presentation suggests that the risk of hydrops developing in the absence of a dominant cyst is less than 3%. The CVR is a useful sonographic indicator of fetuses at risk for hydrops who require close ultrasound observation and possible fetal intervention.

Cystic Adenomatoid Malformation of Lung, Congenita↗
PubMed2002

Expression of Bcl-2 family proteins in advanced laryngeal squamous cell carcinoma: correlation with response to chemotherapy and organ preservation.

OBJECTIVES/HYPOTHESIS: Induction chemotherapy and definitive radiation therapy in advanced laryngeal cancer has been shown to achieve survival rates that are similar to total laryngectomy and postoperative radiation therapy. In patients with advanced laryngeal cancer, quality of life can be significantly enhanced by treatment regimens that preserve the larynx. However, which patients will respond best to organ preservation protocols remains unknown. The Bcl-2 family proteins are involved in control of apoptosis and, potentially, tumor response to chemotherapy. STUDY DESIGN: Retrospective analysis of immunohistochemical tumor characteristics and clinical outcome. METHODS: To determine whether Bcl-2 family proteins were predictive of successful organ preservation, immunohistochemical analysis of tissue specimens from 47 patients with advanced laryngeal cancer from the U.S. Department of Veterans Affairs Cooperative Study Program (VA CSP-268) were evaluated for the expression of Bcl-2, Bcl-X(L), and Bax protein expression. Tumor response was classified as either complete or partial/nonresponse after induction chemotherapy. Protein expression was correlated with tumor response, organ preservation, and overall patient survival. RESULTS: The Bcl-2 protein was expressed at high levels in only 15% of specimens, but five of seven tumors with high Bcl-2 showed complete response (P = .10). The majority of tumors expressed high levels of Bcl-X(L) (74%). Reduced expression of Bcl-X(L) was associated with a complete response (P = .143) and with larynx preservation (P = .06). Most patients (81%) had increased levels of Bax expression. Reduced expression of Bax was associated with a complete response rate (P = .074), but there was no correlation between Bax expression and larynx preservation. CONCLUSIONS: The findings indicate that laryngeal cancer cells typically produce high levels of only one of the apoptosis protective proteins, Bcl-2 or Bcl-X(L). Prospective studies of larger numbers of patients are under way to determine whether Bcl-X(L) expression will be a useful marker predicting larynx preservation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Permission to cross the border: effective policy reduces high-risk drinking by Marines.

OBJECTIVE: At a Marine Corps base near the Mexican border, off-base alcohol- related incidents increased when serving alcohol to personnel under age 21 on the base was no longer permitted. The bars across the Mexican border, where the legal drinking age is 18, are an important source of alcohol for the Marine enlisted men. To reduce cross-border drinking, the base command instituted a "chit" system requiring enlisted men to receive written permission to cross the border. This study evaluates the effectiveness of that policy. METHOD: Breath test surveys of American youths returning from Tijuana to San Diego County provided counts and blood alcohol concentration (BAC) of marines returning from a night of drinking in Mexico before and after the "chit" policy. Comparison counts and breath tests for Navy personnel from a San Diego base not affected by the "chit" policy were available for the same time periods. RESULTS: The number of underage marines returning from Mexican bars was reduced by 78%, and of those the number with illegal (> or = .08%) BACs was reduced by 84%. There was no significant change for the comparison group of sailors. CONCLUSIONS: It appears that the "chit" policy was highly effective at least for the 6-month post-period covered by this study. This apparent success influenced the implementation of the "chit" policy on all naval facilities in the San Diego area.

Adolescent↗