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PubMed2001

Confirmation of a gene locus for medullary cystic kidney disease (MCKD2) on chromosome 16p12.

BACKGROUND: Autosomal-dominant medullary cystic kidney disease (MCKD) is an interstitial nephropathy characterized by structural renal tubular defects that result in salt wasting and a reduction in urinary concentration. The condition has clinical and morphological similarities to autosomal-recessive juvenile nephronophthisis. Two genes predisposing to MCKD have been localized. MCKD1 on chromosome 1q21 was localized in two Cypriot families, and MCKD2 on chromosome 16p12 was localized in a single Italian family. We have evaluated a large Welsh MCKD family for linkage at these two loci. METHODS: Clinical data and DNA samples were collected from affected family members. Polymorphic microsatellite markers spanning the critical regions on chromosome 1 and chromosome 16 that encompass MCKD1 and MCKD2 were analyzed. Two-point and multipoint LOD scores were calculated. RESULTS: The family fulfilled previously published criteria for the diagnosis of MCKD, but hyperuricemia and gout were not prominent features. Twenty-one affected individuals were identified. Mean age at death or end-stage renal disease was 47 years (37 to 60). Linkage and haplotype analysis generated strongly negative results at MCKD1 on chromosome 1q21 (two-point LOD score = -5.32). Strong evidence of linkage to MCKD2 was generated with a maximum multi-point LOD score of 3.75. CONCLUSION: These results provide the first independent confirmation of a gene predisposing to MCKD on chromosome 16p12 and indicate that mutation of this gene is not restricted to a single family or population. The absence of hyperuricemia and gout in our family indicates that these are not obligatory features of MCKD2 mutations.

Adult↗

PubMed2000

Development of an extrachromosomal cloning vector system for use in Borrelia burgdorferi.

Molecular genetic analysis of Borrelia burgdorferi, the cause of Lyme disease, has been hampered by the absence of any means of efficient generation, identification, and complementation of chromosomal and plasmid null gene mutants. The similarity of borrelial G + C content to that of Gram-positive organisms suggested that a wide-host-range plasmid active in Gram-positive bacteria might also be recognized by borrelial DNA replication machinery. One such plasmid, pGK12, is able to propagate in both Gram-positive and Gram-negative bacteria and carries erythromycin and chloramphenicol resistance markers. pGK12 propagated extrachromosomally in B. burgdorferi B31 after electroporation but conferred only erythromycin resistance. pGK12 was used to express enhanced green fluorescent protein in B31 under the control of the flaB promoter. Escherichia coli transformed with pGK12 DNA extracted from B31 expressing only erythromycin resistance developed both erythromycin and chloramphenicol resistance, and plasmid DNA isolated from these transformed E. coli had a restriction pattern similar to the original pGK12. Our data indicate that the replicons of pGK12 can provide the basis to continue developing efficient genetic systems for B. burgdorferi together with the erythromycin resistance and reporter egfp genes.

Borrelia burgdorferi Group↗

PubMed2002

Therapeutic cloning: from consequences to contradiction.

The British Parliament legalized therapeutic cloning in December 2000 despite opposition from the European Union. The watershed event in Parliament's move was the active and unprecedented government support for the generation and destruction of human embryonic life merely as a means of medical advancement. This article contends that the utilitarian analysis of this procedure is necessary to identify the real world risks of therapeutic cloning but insufficient to identify the breach of defensible ethical limits that this procedure represents. A value-oriented approach to Kantian ethics demonstrates that the utilitarian endorsement of therapeutic cloning entails a contradiction of the necessity of human vulnerability and a faulty valuation of the human embryo. The concern is that a narrow utilitarian focus ultimately commodifies human embryonic life and preferences outcomes as the sole determinant of moral value.

Biotechnology↗

PubMed2005

A regional comparison of mold spore concentrations outdoors and inside "clean" and "mold contaminated" Southern California buildings.

A total of 625 buildings and outdoor locations in the San Diego, California, area were monitored using the Allergenco Sampl-Air MK-3 impaction sampler or the Zefon Air-O-Cell slit bioaerosol cassette. Locations were classified by rigid criteria as clean commercial, commercial with mold growth, clean residential, residential with water staining, and residential with mold growth. In addition, coastal and inland outdoor locations were measured. Seven categories (total spores, Ascospores/Basidiospores, Cladosporium, Smut/Myxomycetes-like, Aspergillus/Penicillium (AS/PE), Alternaria, and Unidentified/Other) were detected frequently enough that maximum likelihood estimate techniques could be used to determine distribution parameters and, thus, treat these as continuous variables. For total counts (no nondetectables) an analysis of variance was used to examine differences in location means. For the other categories Land's confidence limits were generated and visually compared for differences among locations. For 12 other categories (Curvularia, Dreschlera, Epicoccum, Fusarium, Mildew-like, Pithomyces, Rusts, Stachybotrys, Stemphyllium, Torula, Ulocladium, and Zygomycetes-like), detection generally occurred in less than 10% of samples. These genera were treated as dichotomous (detect/nondetect) data, and Chi-square analyses differentiated between locations. For total counts, values were significantly different on the order of clean < outdoor < moldy. There was a large difference between the moldy and other location classes. For AS/PE, moldy location means were clearly higher than those for clean buildings and outdoors, although the clean and outdoor means could not be differentiated. For all other genera the results tend to indicate little or no ability to discriminate location. For example, there were no differences in the probabilities of detecting Stachybotrys among the various locations. In our study only total counts, usually driven by AS/PE concentrations, had value in determining whether a building is mold contaminated employing our set of rigorous location classification criteria.

Air Pollution, Indoor↗

PubMed2003

MatArray: a Matlab toolbox for microarray data.

The microarray technology allows the high-throughput quantification of the mRNA level of thousands of genes under dozens of conditions, generating a wealth of data which must be analyzed using some form of computational means. A popular framework for such analysis is Matlab, a powerful computing language for which many functions have been written. However, although complex topics like neural networks or principal component analysis are freely available in Matlab, functions to perform more basic tasks like data normalization or hierarchical clustering in an efficient manner are not. The MatArray toolbox aims at filling this gap by offering efficient implementations of the most needed functions for microarray analysis. The functions in the toolbox are command-line only, since it is geared toward seasoned Matlab users.

Algorithms↗

PubMed1999

Intrinsic localized modes and chaos in damped driven rotator lattices.

It is shown that intrinsic localized rotational modes (ILRMs) in parametrically driven damped lattices of coupled classical dipole rotators can become chaotic without losing their localized character. Insight into this behavior is obtained by means of a nonlinear stability analysis. Moreover, we discuss a robust scheme for exploiting a spatially extended chaotic state to generate stationary randomly spaced arrays of driven ILRMs, and show that the associated absorption exhibits unusual signatures.

Journal Article↗

PubMed2002

Diamond patterns in the cellular front of an overdriven detonation.

A nonlinear integral-differential equation describing the cellular front of an overdriven detonation is obtained by an analysis carried out in the neighborhood of the instability threshold. The analysis reveals both an unusual mean streaming motion, resulting from the rotational part of the oscillatory flow, and pressure bursts generated by the crossover of cusps representative of Mach stems propagating on the detonation front. A numerical study of the nonlinear equation exhibits the "diamond" patterns observed in experiments. An overall physical understanding is provided.

Journal Article↗

PubMed1996

Influence of obesity on left ventricular midwall mechanics in arterial hypertension.

The evaluation of the effect of obesity on left ventricular systolic performance may differ in relation to the method used to measure left ventricular function and to the type of study population. Whether obesity worsens left ventricular midwall mechanics in arterial hypertension has never been investigated. Accordingly, we assessed echocardiographic left ventricular midwall shortening-circumferential end-systolic stress relations in 156 normotensive and normal-weight (reference) adults, 94 normotensive and overweight (1985 National Institutes of Health partition values) to obese (body mass index > 30 kg/m2) adults, 263 hypertensive and normal-weight adults, and 224 hypertensive and overweight-to-obese adults. There was an inverse relation of midwall shortening to circumferential end-systolic stress in all groups (all P < .005). Left ventricular performance as a ratio of observed to predicted midwall shortening fell below the fifth percentile in 4 of 94 (4%) of overweight-to-obese normotensive individuals. Eighty-eight of 487 hypertensive subjects (18.1%) exhibited depressed midwall shortening as a percentage of the value predicted from wall stress, with no difference between normal-weight (50 of 263 [19%]) and overweight (38 of 224 [17%]) subjects. Sixty-one normotensive and 131 hypertensive subjects were frankly obese. After adjustment for sex and age, midwall shortening, as either absolute values or a percentage of predicted, was not statistically different among obese, overweight, and normal-weight subjects in both normotensive and hypertensive groups. For each quartile of observed-to-predicted midwall shortening ratio, obese subjects had greater left ventricular end-diastolic volume than normal-weight subjects among both normotensive and, more evidently, hypertensive subjects. A predicted midwall shortening was generated from both wall stress and left ventricular volume with the use of multiple regression analysis. High body mass index, mean blood pressure, aging, and male sex independently predicted low afterload and left ventricular volume-independent midwall left ventricular performance (multiple R = .31, P < .0001). Thus, (1) midwall left ventricular systolic performance in asymptomatic overweight or frankly obese individuals is comparable to that in normal-weight individuals in both the presence and absence of arterial hypertension; (2) however, maintenance of normal life ventricular performance in obese individuals is associated with the use of Starling reserve; and (3) this compensatory mechanism is especially evident when arterial hypertension and obesity coexist.

Adult↗

PubMed2003

Variation of fetal humeral length in second-trimester fetuses according to race and ethnicity.

OBJECTIVE: To determine the influence of race and ethnicity on the expected humeral length based on biparietal diameter measured in second-trimester fetuses. METHODS: We searched our ultrasound, obstetric, and cytogenetic databases from 1995 through 2001 for all fetuses who underwent an anatomic survey between 15 and 22 weeks' gestation. Fetuses with Down syndrome were identified and removed for separate analysis. Linear regression curves were generated for humeral length by biparietal diameter according to race and ethnicity. Analysis of variance was used to compare the mean variation of observed from expected humeral length by biparietal diameter according to race and ethnicity. RESULTS: There were 11,278 humeral length-by-biparietal diameter pairs that were available for analysis in our population, including 4202 African American, 2269 Hispanic, 639 Asian, and 4168 white fetuses. Humeral length was highly correlated with biparietal diameter for each race (R2 = 0.8). There were no differences in mean variances according to race or ethnicity (P = .75). CONCLUSIONS: Race and ethnicity do not affect the mean regression line of expected humeral length by biparietal diameter among fetuses in the second trimester. Genetic sonographic norms, therefore, do not require race- or ethnic-specific formulas for humeral length.

Analysis of Variance↗

PubMed2005

Effect of tank mixed adjuvants on the drift potential of phenmedipham formulations.

The aim of this paper is to analyse the effect of adjuvants and formulations on drift. The spray liquids consisted of four adjuvants (Actirob 0.4 %, Tensiofix 0.2%, Breakthru 0.2%, Silwet L-77 0.1%) with water and with two formulations of Phenmediphame (C16H16N2O4, 4.45%): an emulsion-forming (EC) and a suspension concentrate (SC). A standard flat fan nozzle at a pressure of 3 bar was used. The droplet size spectrum of each combination was determined using a Malvern granulometer. The droplet size was characterized by the volume median diameter (VMD) and the percentage of spray volume contained in droplets <100 microm (%<100). The relative drift potential was measured for each combination of formulation and adjuvant in a wind-tunnel. This latter has a working section 2.0 m wide by 2.0 m high by 6.0 m long. The air-stream is drawn by a 1.2 m diameter axial flow fan, powered by a 22 kW electric motor. Wind speed was 5 m/s. Its uniformity was controlled by a three-dimensional sonic anemometer able to move on a linear translation beam placed in the tunnel cross section. The wind-tunnel was operated under ambient conditions and three repetitions were performed randomized in order to eliminate variations in temperature and humidity for each combination. The ground spray deposits were measured on glass fibber collectors using a fluorescent tracer dye (sodium fluorescein), at a concentration of 2.5 mg/l. The statistical analysis of the droplet spectrum showed that the Phenmediphame SC formulation generated droplets of higher size than the EC. The mean VMD values were respectively equal to 228+/-11 microm and 185+/-11 microm for these formulations. For SC formulation, Break-thru decreased the VMD while Tensiofix increased the %<100. This confirmed that the degree to which an adjuvant influences spray characteristics is very variable. The drift profiles produced by the different combinations were similar, but the relative drift potential was significantly different comparing SC and EC formulations: it respectively reached 0.8+/-0,08% and 1.2+/-0,08%, whatever the adjuvant used in the liquid. Clearly, when using a flat fan nozzle to spray Phenmediphame, the droplet size and the drift potential are mainly governed by the kind of formulation, even if an interaction between the formulation and the adjuvant exists.

Agriculture↗

PubMed1978

[Intracellular regeneration and structuro-functional analysis of biological processes in normal cases and in pathology].

The author elucidates some problems in the history and the modern state in the doctrine on intracellular regenerative processes. Electron microscopic radioautography is considered as the most adequate method for studying intracellular regeneration. Certain examples are given to illustrate principally new possibilities of the structural-functional analysis of intracellular processes, normal and pathologic, studied by means of this method in view of the conception of intracellular generation. At the same time, new perspectives for further elaborating the problem of structural and functional integrity are stressed.

Animals↗

PubMed1996

Learning to care: gender issues for male nursing students.

The following article is a description of one aspect of a phenomenological research study designed to investigate the lived experience of male nursing students as they learned to care as nurses. Data-collection strategies included paradigm case narratives and interviews. Data analysis was characterized by four major strategies: analysis, synthesis, criticism, and understanding. These strategies were used to identify meanings of the text of transcribed interviews and to generate interpretive commentary. Learning to care was described by the participants as a complex entity that incorporates the gender of the student, the patient, the teacher, and the nurse. As students progressed through the program, their experience of gender issues in learning to care was shaped by personal experiences, the expectations of a predominantly female faculty and nursing staff, and their evolving understanding of the ways of caring that are gender based.

Adolescent↗

PubMed2000

Comparative analysis of the isoform expression pattern of Ca(2+)-regulatory membrane proteins in fast-twitch, slow-twitch, cardiac, neonatal and chronic low-frequency stimulated muscle fibers.

Although all muscle cells generate contractile forces by means of organized filament systems, isoform expression patterns of contractile and regulatory proteins in heart are not identical compared to developing, conditioned or mature skeletal muscles. In order to determine biochemical parameters that may reflect functional variations in the Ca(2+)-regulatory membrane systems of different muscle types, we performed a comparative immunoblot analysis of key membrane proteins involved in ion homeostasis. Cardiac isoforms of the alpha(1)-dihydropyridine receptor, Ca(2+)-ATPase and calsequestrin are also present in skeletal muscle and are up-regulated in chronic low-frequency stimulated fast muscle. In contrast, the cardiac RyR2 isoform of the Ca(2+)-release channel was not found in slow muscle but was detectable in neonatal skeletal muscle. Up-regulation of RyR2 in conditioned muscle was probably due to degeneration-regeneration processes. Fiber type-specific differences were also detected in the abundance of auxiliary subunits of the dihydropyridine receptor, the ryanodine receptor and the Ca(2+)-ATPase, as well as triad markers and various Ca(2+)-binding and ion-regulatory proteins. Hence, the variation in innervation of different types of muscle appears to have a profound influence on the levels and pattern of isoform expression of Ca(2+)-regulatory membrane proteins reflecting differences in the regulation of Ca(2+)-homeostasis. However, independent of the muscle cell type, key Ca(2+)-regulatory proteins exist as oligomeric complexes under native conditions.

Animals↗

PubMed1992

Antibiotic prophylaxis for cardiothoracic operations. Meta-analysis of thirty years of clinical trials.

Antistaphylococcal penicillins and first-generation cephalosporins have traditionally been the prophylactic antibiotics of choice for patients undergoing cardiothoracic operations. Recently published studies have claimed improved outcomes with respect to postoperative wound infection when second-generation cephalosporins were used for prophylaxis. The purpose of this study was to critically review the infectious outcomes of prospective, randomized, and controlled studies of cardiothoracic surgery prophylaxis by means of meta-analytic techniques. For each of 28 studies meeting the meta-analysis entry criteria, odds ratios with 95% confidence intervals were calculated to compare the prophylactic efficacy of the antibiotic regimens. Odds ratios were then pooled, and a summary odds ratio was calculated for each pairing of antibiotic treatments. Placebo-controlled trials of cardiothoracic prophylaxis demonstrated a consistent benefit to the administration of antibiotic prophylaxis, with an approximate fivefold reduction in wound infection rate. The second-generation cephalosporins, cefamandole and cefuroxime, performed better than cefazolin, with an approximate one and one-half-fold reduction in wound infection rate. Administration of prophylaxis beyond 48 hours was not associated with improved infectious outcomes.

Anti-Bacterial Agents↗

PubMed1997

Analysis of data about epileptic patients using the GUHA method.

In this paper we search for hypotheses on association between the memory quotient and 13 clinical variables examined in a sample of 214 epilepsy patients. We introduce the General Unary Hypotheses Automaton (GUHA) method that automatically generates hypotheses from empirical data by means of computer procedures. Procedure ASSOC of the program GUHA generates and evaluates the hypotheses on symmetrical association or asymmetrical association using quantifiers. The most used symmetrical and asymmetrical quantifiers of the ASSOC procedure are introduced. Data analysis on epileptic patients using the GUHA method is done and the results are presented. We propose a new interpretation of the results including a graphical presentation.

Age of Onset↗

PubMed1999

A new multiparameter flow cytometer: optical and electrical cell analysis in combination with video microscopy in flow.

BACKGROUND: Flow cytometers, which are commercially available, do not necessarily meet all demands of actual biomedical research. This is the case for the investigation of mechanisms involved in cell volume regulation, which requires electrical volume measurement and ratiometric multichannel fluorescence analysis for the simultaneous assessment of different physiologic parameters (intracellular pH and the intracellular concentration of calcium ions, etc). METHODS AND RESULTS: We describe the construction of a new nonsorting flow cytometer designed for the simultaneous acquisition of seven parameters including fluorescence signals, forward and perpendicular light scatter, cell volume according to the electrical Coulter principle, and flow cytometric imaging. The instrument is equipped with three different light sources. A tunable argon-ion laser generates efficient excitation of the most standard fluorescent probes in the visible spectral range, and an arc lamp provides the means for ultraviolet excitation at low cost. Because of the spatial filtering by the excitation and detection optics, two independent sets of dual fluorescence measurements can be performed, a prerequisite for flexible ratiometric fluorescence analysis. A flow video microscope integrated into the optical system optionally generates either brightfield or phase images of selected flowing particles. Only particles whose individual datasets meet predefined gating conditions are imaged in real time. To avoid smear effects, the motion of the object to be imaged (speed approximately 8 m/s) is frozen on the target of a CCD camera by flash illumination. For this purpose, a high radiance gas discharge lamp with 25-mJ electric pulse energy provides an illumination time of 18 ns (full width half maximum). Test results obtained from latex spheres and cells are shown. CONCLUSIONS: Test results indicate that our instrument can perform Coulter measurements in combination with flexible optical analysis. Moreover, integration of an adapted video microscope into a flow cytometer is an approach to overcome the gap between flow and image cytometry.

Animals↗

PubMed1985

An electromyographic analysis of electrically-evoked prey-catching behavior by means of stimuli applied to the optic tectum in the Japanese toad.

As a step toward elucidating the tectal-controlling functions for generating the prey-catching motor pattern, electrically-evoked "snapping" (the final consummatory phase of the prey-catching sequence) by means of stimuli applied to the optic tectum was analyzed using electromyographic methods in freely-moving Japanese toads. Electromyographic activities were recorded from the following 7 muscles in the head region (the presumed "snapping"-related muscles): M. depressor mandibulae, M. temporalis, M. sternohyoideus, M. geniohyoideus, M. genioglossus, M. hyoglossus, and M. submentalis. It was found that the characteristic activities evoked in these muscles were associated with jaw/tongue movements during the electrically-evoked "snapping". All of these muscles, except for sternohyoideus and geniohyoideus muscles, were activated in an all-or-nothing manner which corresponded to the elicitation of the electrically-evoked "snapping". It was suggested that such an all-or-nothing character may reflect an all-or-nothing property of the neuronal circuits for generating the prey-catching motor-pattern.

Animals↗

PubMed2005

Magnetoencephalographic analysis in children with Panayiotopoulos syndrome.

The aims of this study were to identify the generator of the paroxysmal partial discharges in Panayiotopoulos syndrome by means of magnetoencephalography and to determine the significance of these formations in the epileptogenesis of the developing nervous system. We report magnetoencephalographic data for two cases of Panayiotopoulos syndrome showing the rapid generalization of the source of interictal spikes that explains extraoccipital manifestations such as ictal vomiting and consciousness disturbance.

Cerebral Cortex↗