Biomedical subjects

John P Miller

Publications and source records attributed to John P Miller.

13 recordsLinked to original sources

PubMed2006

Volume progression in polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive enlargement of cyst-filled kidneys. METHODS: In a three-year study, we measured the rates of change in total kidney volume, total cyst volume, and iothalamate clearance in patients with ADPKD. Of a total of 241 patients, in 232 patients without azotemia who were 15 to 46 years old at baseline we used magnetic-resonance imaging to correlate the total kidney volume and total cyst volume with iothalamate clearance. Statistical methods included analysis of variance, Pearson correlation, and multivariate regression analysis. RESULTS: Total kidney volume and total cyst volume increased exponentially, a result consistent with an expansion process dependent on growth. The mean (+/-SD) total kidney volume was 1060+/-642 ml at baseline and increased by a mean of 204+/-246 ml (5.27+/-3.92 percent per year, P<0.001) over a three-year period among 214 patients. Total cyst volume increased by 218+/-263 ml (P<0.001) during the same period among 210 patients. The baseline total kidney volume predicted the subsequent rate of increase in volume, independently of age. A baseline total kidney volume above 1500 ml in 51 patients was associated with a declining glomerular filtration rate (by 4.33+/-8.07 ml per minute per year, P<0.001). Total kidney volume increased more in 135 patients with PKD1 mutations (by 245+/-268 ml) than in 28 patients with PKD2 mutations (by 136+/-100 ml, P=0.03). CONCLUSIONS: Kidney enlargement resulting from the expansion of cysts in patients with ADPKD is continuous and quantifiable and is associated with the decline of renal function. Higher rates of kidney enlargement are associated with a more rapid decrease in renal function.

Adult↗

PubMed2006

Comparative analysis of Saccharomyces cerevisiae WW domains and their interacting proteins.

BACKGROUND: The WW domain is found in a large number of eukaryotic proteins implicated in a variety of cellular processes. WW domains bind proline-rich protein and peptide ligands, but the protein interaction partners of many WW domain-containing proteins in Saccharomyces cerevisiae are largely unknown. RESULTS: We used protein microarray technology to generate a protein interaction map for 12 of the 13 WW domains present in proteins of the yeast S. cerevisiae. We observed 587 interactions between these 12 domains and 207 proteins, most of which have not previously been described. We analyzed the representation of functional annotations within the network, identifying enrichments for proteins with peroxisomal localization, as well as for proteins involved in protein turnover and cofactor biosynthesis. We compared orthologs of the interacting proteins to identify conserved motifs known to mediate WW domain interactions, and found substantial evidence for the structural conservation of such binding motifs throughout the yeast lineages. The comparative approach also revealed that several of the WW domain-containing proteins themselves have evolutionarily conserved WW domain binding sites, suggesting a functional role for inter- or intramolecular association between proteins that harbor WW domains. On the basis of these results, we propose a model for the tuning of interactions between WW domains and their protein interaction partners. CONCLUSION: Protein microarrays provide an appealing alternative to existing techniques for the construction of protein interaction networks. Here we built a network composed of WW domain-protein interactions that illuminates novel features of WW domain-containing proteins and their protein interaction partners.

Amino Acid Motifs↗

PubMed2006

Visualization of ensemble activity patterns of mechanosensory afferents in the cricket cercal sensory system with calcium imaging.

The cercal sensory system of the cricket mediates the detection and analysis of low velocity air currents in the animal's immediate environment, and is implemented around an internal representation of air current direction that demonstrates the essential features of a continuous neural map. Previous neurophysiological and anatomical studies have yielded predictions of the global spatio-temporal patterns of activity that should be evoked in the sensory afferent map by air current stimuli of different directions. We tested those predictions by direct visualization of ensemble afferent activity patterns using Ca2+ -sensitive indicators. The AM ester of the fluorescent Ca2+ indicator (Oregon Green 488 BAPTA-1 AM) was injected under the sheath of a cercal sensory nerve containing all of the mechanosensory afferent axons from one cercus. Optical signals were recorded with a digital intensified CCD camera. Control experiments using direct electrical stimulation of stained and unstained nerves demonstrated that the observed Ca2+ signals within the terminal abdominal ganglion (TAG) were due to activation of the dye-loaded sensory afferent neurons. To visualize the spatial patterns of air-current-evoked ensemble activity, unidirectional air currents were applied repeatedly from eight different directions, and the optically recorded responses from each direction were averaged. The dispersion of the optical signals by the ganglion limited the spatial resolution with which these ensemble afferent activity patterns could be observed. However, resolution was adequate to demonstrate that different directional stimuli induced different spatial patterns of Ca2+ elevation in the terminal arbors of afferents within the TAG. These coarsely- resolved, optically-recorded patterns were consistent with the anatomy-based predictions.

Air Movements↗

PubMed2006

Outcomes of 122 diverse adult and pediatric cord blood transplant recipients from a large cord blood bank.

BACKGROUND: Umbilical cord blood is a useful stem cell source for some patients. The American Red Cross Cord Blood Program was established as a national network of cord blood banks. Nine thousand cord blood units were cryopreserved for transplant use. STUDY DESIGN AND METHODS: This report summarizes the experience with the first 125 cord blood units that have been distributed for transplant for 122 patients at 36 different transplant centers worldwide. Patients were treated with a variety of conditioning regimens. RESULTS: Most patients had acute myelogeneous leukemia (21%), genetic disorders (22%), or acute lymphoblastic leukemia (18%). The median age of the patients was 11 years with a range of 2 months to 63 years. The patients ranged in size from 3 to 120 kg (median, 39 kg). The median number of days to neutrophil engraftment was 22, and the median number of days to platelet engraftment was 63. Thirty percent of patients experienced Grades III to IV acute graft-versus-host disease (GVHD). Survival at 1 year after transplant was 35 percent, with recurrent disease the major cause of death. In multivariate analysis, only age less than 18 years was a significant predictor for improved survival. Forty-two percent of patients were non-Caucasian. Engraftment, GVHD, survival, and disease-free survival were similar among Caucasian and non-Caucasian patients. CONCLUSION: Umbilical cord blood serves as a satisfactory stem cell source for a diverse group of pediatric and adult patients.

Adolescent↗

PubMed2005

A rose by any other code.

In this issue of Neuron, Mazor and Laurent demonstrate that the internal representation of an odor in the antennal lobe of locusts is broadly distributed across the population of projection neurons and is formatted in a manner that requires deciphering of response transients rather than steady-state activity patterns.

Animals↗

PubMed2005

Large-scale identification of yeast integral membrane protein interactions.

We carried out a large-scale screen to identify interactions between integral membrane proteins of Saccharomyces cerevisiae by using a modified split-ubiquitin technique. Among 705 proteins annotated as integral membrane, we identified 1,985 putative interactions involving 536 proteins. To ascribe confidence levels to the interactions, we used a support vector machine algorithm to classify interactions based on the assay results and protein data derived from the literature. Previously identified and computationally supported interactions were used to train the support vector machine, which identified 131 interactions of highest confidence, 209 of the next highest confidence, 468 of the next highest, and the remaining 1,085 of low confidence. This study provides numerous putative interactions among a class of proteins that have been difficult to analyze on a high-throughput basis by other approaches. The results identify potential previously undescribed components of established biological processes and roles for integral membrane proteins of ascribed functions.

Algorithms↗

PubMed2005

Dejittered spike-conditioned stimulus waveforms yield improved estimates of neuronal feature selectivity and spike-timing precision of sensory interneurons.

What is the meaning associated with a single action potential in a neural spike train? The answer depends on the way the question is formulated. One general approach toward formulating this question involves estimating the average stimulus waveform preceding spikes in a spike train. Many different algorithms have been used to obtain such estimates, ranging from spike-triggered averaging of stimuli to correlation-based extraction of "stimulus-reconstruction" kernels or spatiotemporal receptive fields. We demonstrate that all of these approaches miscalculate the stimulus feature selectivity of a neuron. Their errors arise from the manner in which the stimulus waveforms are aligned to one another during the calculations. Specifically, the waveform segments are locked to the precise time of spike occurrence, ignoring the intrinsic "jitter" in the stimulus-to-spike latency. We present an algorithm that takes this jitter into account. "Dejittered" estimates of the feature selectivity of a neuron are more accurate (i.e., provide a better estimate of the mean waveform eliciting a spike) and more precise (i.e., have smaller variance around that waveform) than estimates obtained using standard techniques. Moreover, this approach yields an explicit measure of spike-timing precision. We applied this technique to study feature selectivity and spike-timing precision in two types of sensory interneurons in the cricket cercal system. The dejittered estimates of the mean stimulus waveforms preceding spikes were up to three times larger than estimates based on the standard techniques used in previous studies and had power that extended into higher-frequency ranges. Spike timing precision was approximately 5 ms.

Action Potentials↗

PubMed2004

Phased-array processing for spike discrimination.

We present a novel approach for the detection, discrimination, and identification of superimposed neuronal action potentials from multineuronal, multichannel extracellular nerve recordings with low signal-to-noise ratios. The approach uses phased-array processing techniques to identify the spikes from different neurons on the basis of their unique propagation velocities. We evaluated this new approach using simulated electrophysiological data, under conditions that are known to limit the effectiveness of existing spike discrimination techniques. This approach enabled discrimination of simulated spikes from multiple simultaneously active neurons with a high degree of reliability and robustness within the expected range of experimental recording conditions, even in situations where there was a high degree of spike waveform superposition on the recording channels. Moreover, the technique enables the reliable detection and discrimination of spikes recorded with signal-to-noise ratios less than 1.

Action Potentials↗

PubMed2004

Racial diversity with high nucleated cell counts and CD34 counts achieved in a national network of cord blood banks.

Banked, unrelated, partially HLA-matched, umbilical cord blood is an alternative stem cell source for patients in need of transplantation therapy who lack traditionally matched donors. A presumed advantage of cord blood is the ability to increase recruitment of donors of minority ethnic backgrounds. The American Red Cross Cord Blood Program was established in 1999 with 6 banks and 10 collection sites throughout the country. Cord blood donors self-report racial designations on questionnaires, and donor race was collected from each site. Postprocessing nucleated cell counts and CD34(+) counts were obtained on the cord blood units, and results from each racial group (white, black, Asian, Hispanic, and Native American) were compared in the natural logarithmic scale by using analysis of variance. A total of 18878 donors consented: 64% white, 16% black, 12% Hispanic, 4% Asian, 1% Native American, and 3% other. The Detroit area consented the highest percentage of black donors (87%), San Diego consented the highest percentage of Hispanic donors (59%), and Oakland consented the highest percentage of Asian donors (15%). Seven thousand eight hundred sixty-six cord blood units have been banked for transplantation. The mean preprocessing nucleated cell count was 1220 x 10(6) (range, 327-7300 x 10(6)). There was no difference among racial groups when controlled for site (P =.395). The mean CD34(+) count was 3.28 x 10(6). Blacks had a significantly lower CD34(+) count than the other racial/ethnic groups in the Midwest, Northwest, and North Carolina collection sites. A racially diverse cord blood bank can be achieved. Nucleated cell counts were similar among the different racial/ethnic groups. CD34(+) counts were lower for blacks in some collection sites.

Antigens, CD34↗

PubMed2004

Evidence that Hy- RBCs express weak Joa antigen.

BACKGROUND: RBCs of the Hy- phenotype have, in the past, been typed as Gy(a+w), Hy-, Jo(a-), and RBCs with the Jo(a-) phenotype type Gy(a+), Hy+w, and Jo(a-). Anti-Hy and anti-Joa are difficult to identify mainly because appropriate reagent RBCs are poorly characterized. Historically, anti-Joa has not reacted with RBCs with either phenotype. This report describes a case of an anti-Joa that shows Hy- RBCs express some Joa antigen, albeit weakly. CASE REPORT: Anti-Joa was identified in a serum sample of a 71-year-old woman. The antibody reacted 1+ to 2+ by the IAT with all untreated and ficin-treated panel RBCs and did not react with Gy(a-) RBCs and Jo(a-) RBCs. Unexpectedly, the serum sample reacted weakly with six of eight RBC samples with the Hy- phenotype. The anti-Joa was adsorbed onto and eluted from Hy- RBCs, indicating the presence of weak Joa antigen. The patient's RBCs typed Gy(a+), Hy+, Jo(a-). DNA studies using PCR-RFLP analysis showed the patient to be homozygous for the JO allele, which is consistent with the serologically determined Jo(a-) status. CONCLUSION: The DNA and serologic evidence of this case show that Hy- RBCs may express low levels of Joa antigen, which contradicts previously published data concerning the Joa type of Hy- RBCs.

Aged↗

PubMed2003

Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red Cross adult blood donors.

Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper and packaging treatments, and surface protectants (e.g., for carpet, upholstery, textile). Depending on the specific functional derivatization or degree of polymerization, such products may degrade or metabolize, to an undetermined degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product that has the potential to bioaccumulate. In this investigation, a total of 645 adult donor serum samples from six American Red Cross blood collection centers were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray tandem mass spectrometry. PFOS concentrations ranged from the lower limit of quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95% confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3). No substantial difference was observed with age. The estimate of the 95% tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The measures of central tendency for the other fluorochemicals (N-ethyl perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide, perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of magnitude lower than PFOS. Because serum PFOS concentrations correlate with cumulative human exposure, this information can be useful for risk characterization.

Adult↗

PubMed2003

Analysis of neural coding through quantization with an information-based distortion measure.

We discuss an analytical approach through which the neural symbols and corresponding stimulus space of a neuron or neural ensemble can be discovered simultaneously and quantitatively, making few assumptions about the nature of the code or relevant features. The basis for this approach is to conceptualize a neural coding scheme as a collection of stimulus-response classes akin to a dictionary or 'codebook', with each class corresponding to a spike pattern 'codeword' and its corresponding stimulus feature in the codebook. The neural codebook is derived by quantizing the neural responses into a small reproduction set, and optimizing the quantization to minimize an information-based distortion function. We apply this approach to the analysis of coding in sensory interneurons of a simple invertebrate sensory system. For a simple sensory characteristic (tuning curve), we demonstrate a case for which the classical definition of tuning does not describe adequately the performance of the cell studied. Considering a more involved sensory operation (sensory discrimination), we also show that, for some cells in this system, a significant amount of information is encoded in patterns of spikes that would not be discovered through analyses based on linear stimulus-response measures.

Air↗

PubMed2002

In utero or ex utero cord blood collection: which is better?

BACKGROUND: The relative nucleated cell count of umbilical cord blood (CB) correlates with improved engraftment and survival. This study compares two collection methods to assess CB content, including cell numbers. STUDY DESIGN AND METHODS: The Massachusetts CB bank used trained obstetricians and midwives to collect CB in utero before the delivery of the placenta. The banks in California, Ohio, Oregon, and Minnesota used trained American Red Cross (ARC) personnel who collected CB ex utero after the delivery of the placenta. All banks processed CB by RBC sedimentation and volume reduction. RESULTS: The volume and total nucleated cell count of collected CB before processing, as well as after processing CFU-GM and CD34+ cells, showed no advantage of either method. In utero collections resulted in more rejections of collected units (due to labeling problems, bacterial contamination, clotting, and delay between collection and processing) than ex utero collections. There were fewer medical exclusions after in utero collection. CONCLUSION: CB can be collected successfully using either the in utero or ex utero methods; both methods produce comparable nucleated cell, MNC, CD34+, and CFU-GM numbers. Bacterial contamination, low volume, clotting, and delay until processing are generally higher with in utero collection.

Adult↗