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Biomedical subjects

J M Harris

Publications and source records attributed to J M Harris.

At least 109 records · Page 6Linked to original sources
PubMed1997

Fine-scale processing in human binocular stereopsis.

Many studies have demonstrated that the human visual system is sensitive to very small differences in relative binocular disparity. It is not known over what monocular regions information is spatially integrated to mediate performance in such tasks. In this study we present psychophysical observations that define the smallest spatial scale involved in disparity processing, and we indicate the nature of the computations performed by the units mediating that disparity discrimination. We show that human observers can identify the sign of disparity of a single target dot when it is embedded in a row of identical dots, with these noise dots presented either in the fixation plane or with a proportion binocularly uncorrelated. In conjunction with the psychophysical data, we explore how a class of simple correlator models of stereopsis must be constrained in order to account for human performance for the same fine-scale tasks. Such models can perform the task only when the correlation is carried out over a very small region of the image, for a very small range of disparities. Our results demonstrate that there is a fine-scale input to the stereo system, mediated by foveal mechanisms that spatially integrate visual signals over a region as small as 4-6 arcmin in diameter.

Depth Perception↗
PubMed1997

Differences in costs of treatment for foot problems between podiatrists and orthopedic surgeons.

We examined charge data for health insurance claims paid in 1992 for persons under age 65 covered by a large California managed care plan. Charge and utilization comparisons between podiatrists and orthopedic surgeons were made for all foot care and for two specific foot problems, acquired toe deformities and bunions. Podiatrists provided over 59% of foot care services for this commercial population of 576,000 people. Podiatrists charged 12% less per individual service than orthopedists. However, podiatrists performed substantially more procedures per episode of care and treated patients for longer time periods, resulting in 43% higher total charges per episode. Hospitalization was infrequent for all providers, although podiatrists had the lowest rates. In a managed care setting in which all providers must adhere to a preestablished fee schedule, regardless of specialty, the higher utilization by podiatrists should lead to higher overall costs. In some cases, strong utilization controls could offset this effect. We do not know if the utilization difference is due to actual treatment or billing differences. Further, we were unable to determine from the claims data if one specialty had better outcomes than the other.

Blue Cross Blue Shield Insurance Plans↗
PubMed1997

A consensus sequence for a functional human endogenous retrovirus K (HERV-K) dUTPase.

Amino acid sequence comparisons have revealed that a potential dUTPase gene is encoded by the retrovirus HERV-K, a defective multicopy virus that is transmitted vertically in humans. This gene is distinct from the human cellular dUTPase gene and thus two potential sources of the enzyme exist in human cells. dUTPases characterized from various sources each contain five conserved amino acid sequence motifs that form the active site of the enzyme. The protein sequence of the putative HERV-K dUTPase deduced from previous DNA sequence data from one proviral clone (HERV-K10) shows marked deviations at highly conserved residues in four of five of these motifs. Therefore, the reported DNA sequence may represent a mutated form of the viral dUTPase gene. To address this possibility, we cloned and sequenced 22 copies of the HERV-K dUTPase gene from human DNA. The results of this analysis indicate that variations evident in the HERV-K10 dUTPase amino acid sequence represent mutations of the wild-type viral DNA sequence. A version of the HERV-K dUTPase gene that corresponds to the ancestral, wild-type DNA sequence was constructed and adapted for expression in Escherichia coli. The resulting enzyme was found to exhibit properties similar to those of dUTPases isolated from other systems. A possible role of the HERV-K dUTPase in human disease is discussed.

Amino Acid Sequence↗
PubMed1997

The utility of ultrasonography in the evaluation of groin masses: a case report.

Surgeons are often faced with the evaluation and management of groin masses. In most cases, an accurate history and physical examination will establish a diagnosis. Ultrasonography is being increasingly used in the evaluation of surgical problems. A case is presented in which bedside ultrasound was utilized in the evaluation of a large, symptomatic left inguinal mass found to be a synovial cyst on exploration. The differential diagnosis of cystic groin lesions and the impact of ultrasonography on diagnosis is reviewed with emphasis on synovial cysts. Surgeon-directed ultrasonography is an asset in the diagnosis of some patients with groin masses and may assist in the identification of those lesions requiring prompt operative intervention.

Aged↗
PubMed1996

Human dUTP pyrophosphatase: uracil recognition by a beta hairpin and active sites formed by three separate subunits.

BACKGROUND: The essential enzyme dUTP pyrophosphatase (dUTPase) is exquisitely specific for dUTP and is critical for the fidelity of DNA replication and repair. dUTPase hydrolyzes dUTP to dUMP and pyrophosphate, simultaneously reducing dUTP levels and providing the dUMP for dTTP biosynthesis. A high cellular dTTP: dUTP ratio is essential to avoid uracil incorporation into DNA, which would lead to strand breaks and cell death. We report the first detailed atomic-resolution structure of a eukaryotic dUTPase, human dUTPase, and complexes with the uracil-containing deoxyribonucleotides, dUMP, dUDP and dUTP. RESULTS: The crystal structure reveals that each subunit of the dUTPase trimer folds into an eight-stranded jelly-roll beta barrel, with the C-terminal beta strands interchanged among the subunits. The structure is similar to that of the E. coli enzyme, despite low sequence homology between the two enzymes. The nucleotide complexes reveal a simple and elegant way for a beta hairpin to recognize specific nucleic acids: uracil is inserted into a distorted antiparallel beta hairpin and hydrogen bonds entirely to main-chain atoms. This interaction mimics DNA base pairing, selecting uracil over cytosine and sterically precluding thymine and ribose binding. Residues from the second subunit interact with the phosphate groups and a glycine-rich C-terminal tail of the third subunit caps the substrate-bound active site, causing total complementary enclosure of substrate. To our knowledge, this is the first documented instance of all three subunits of a trimeric enzyme supplying residues that are critical to enzyme function and catalysis. CONCLUSIONS: The dUTPase nucleotide-binding sites incorporate some features of other nucleotide-binding proteins and protein kinases, but seem distinct in sequence and architecture. The novel nucleic acid base recognition motif appears ancient; higher order structures, such as the ribosome, may have evolved from a motif of this kind. These uracil-beta-hairpin interactions are an obvious way for peptides to become early coenzymes in an RNA world, providing a plausible link to the protein-DNA world. Within the beta hairpin, there is a tyrosine corner motif that normally specifies beta-arch connections; this tyrosine motif was apparently recruited to discriminate against ribonucleotides, more recently than the evolution of the beta hairpin itself.

Amino Acid Sequence↗
PubMed1996

Disease management: new wine in new bottles?

Cost pressures are driving the reorganization of the health care delivery system in the United States, causing health care delivery organizations to become larger and more diversified. These new health care delivery entities are arriving at the same time as a new approach to clinical care: commercial population-based medicine. This approach is sharing an increasing amount of space with the traditional physician-patient-based approach and offers strategies for managing a population's risk, demand, diseases, and outcomes. Although commercial population-based medicine strategies such as disease management may use many of the same tools as traditional public health approaches, they focus on the relatively short-term health needs of defined populations because of the underlying economic incentives facing payers. Population-based-medicine promises better use of resources and a systems approach to health care delivery, but it also presents the pitfalls of subversion by the needs of commercial companies, unanticipated adverse effects, and wide application without adequate preparation.

Case Management↗
PubMed1996

Poor speed discrimination suggests that there is no specialized speed mechanism for cyclopean motion.

Luminance-defined and stereo-defined (cyclopean) motion share some common properties, suggesting that the two forms of motion may be detected by similar mechanisms. For luminance-defined motion there are at least two levels of processing: direction is detected and then speed is thought to be extracted by a specialized processing mechanism at a higher level. Here, we tested whether there is also a specialized speed processing mechanism for stereo-defined motion. Speed discrimination thresholds were compared for stimuli containing only stereo-defined motion, and stimuli that contained both stereo-defined and luminance-defined motion. When the stimulus contained luminance-defined motion, increment thresholds were around 0.05-0.1. For stereo-defined motion, increment thresholds were never better than 0.3. By careful analysis, it was possible to test what cues were being used to solve the speed discrimination task. Results were consistent with observers responding to distance cues rather than to speed for stereo-defined motion, suggesting that there is no specialized mechanism for processing the speed of stereo-defined motion.

Cues↗
PubMed1996

Incubation periods of experimental rhinovirus infection and illness.

Eleven young adults with experimental rhinovirus infection (cases) and six noninfected saline-challenged young adults (controls) underwent nasal washings and symptom evaluations at 2-hour intervals for 24 hours after intranasal challenge. The mean and median periods to the first recovery of virus were 11.3 hours and 10 hours, respectively. Geometric mean rhinovirus titers in cases reached 10(0.2) log10 TCID50 (50% tissue culture infective dose)/0.1 mL at 10 hours and rose to 10(1.0) log10 TCID50/0.1 mL at 18 hours. Nine (82%) of 11 cases and one (16.7%) of six controls had colds. Mean total symptom scores for cases became significantly higher than those for controls at 16 hours. Sore or scratchy throat appeared between 10 and 12 hours in cases, but nasal obstruction and rhinorrhea first appeared at 2 hours, thus suggesting some nasal irritation from the viral inoculum pool. The incubation period of experimental rhinovirus infection is similar to that in cell culture. Nasal and pharyngeal symptoms began early in infection.

Adult↗
PubMed1996

Use of radiolabelled thymidine and leucine to estimate bacterial production in soils from continental antarctica.

Tritiated thymidine incorporation (TTI) into DNA was used to examine bacterial production in two soil types from the Robertskollen group of nunataks in northwestern Dronning Maud Land, providing the first estimates of bacterial production in soil habitats on the Antarctic continent. Although estimates of bacterial productivity in soils near to bird nests (344 (plusmn) 422 ng of C g [dry weight](sup-1) h(sup-1)) were higher than those for soils from beneath mosses (175 (plusmn) 90 ng of C g [dry weight](sup-1) h(sup-1); measured by TTI at 10(deg)C), these differences were not significant because of patchiness of bacterial activity (P > 0.05). TTI- and [(sup14)C]leucine ([(sup14)C]Leu)-derived estimates of bacterial production were similar when incubations of 3 h were used, although incubations as short as 1 h were sufficient for measurable uptake of radiolabel. Dual-label incorporation of [(sup3)H]thymidine ([(sup3)H]TdR) into DNA and [(sup14)C]Leu into protein indicated that TTI did not reflect bacterial production of in situ assemblages when incubations were longer than 3 h. Isotope dilution analysis indicated that dilution of the specific activity of exogenously supplied [(sup3)H]TdR by de novo synthesis of TdR precursor could be limited by additions of [(sup3)H]TdR at a concentration of 1 nmol per ca. 115 mg of soil. TTI exhibited a psychrotrophic response to variation in temperature, with a temperature optimum of ca. 15(deg)C and a Q(inf10) value for 0 to 10(deg)C of 2.41.

Journal Article↗
PubMed1996

Does disease management work?

Is disease management the "solution of the month" or a valid approach to organizing patient care? In the era of rapid change in health care, disease management is emerging as one technique suited to improving measurable health care outcomes at greater cost effectiveness. By taking a leading role in the process, those physician executives who commit to this approach can greatly enhance the potential of these programs to accomplish the desired results.

Cost Control↗
PubMed1996

Cystoscopic holmium lithotripsy of large bladder calculi.

Patients with large bladder stones are often difficult to treat endoscopically with the current modalities available to the practicing urologist. We present the results of cystolithotripsy of bladder stones larger than 4 cm with the holmium: Yag (Ho:Yag) laser. In our three patients, all patients were rendered stone free without complication using the Ho:Yag laser, with an average anesthesia time of 50 min. Minimal tissue trauma or stone movement were observed. All stones were easily fragmented, even one stone that had previously been refractory to electrohydraulic lithotripsy. Our conclusion is that the Ho:Yag laser is a safe and effective treatment for patients with large bladder stones. Its use may make it possible to eradicate stones endoscopically that otherwise would require open surgery.

Cystoscopy↗
PubMed1995

Control of protein-ligand recognition using a stimuli-responsive polymer.

Stimuli-responsive polymers exhibit reversible phase changes in response to changes in environmental factors such as pH or temperature. Conjugating such polymers to antibodies and proteins provides molecular systems for applications such as affinity separations, immunoassays and enzyme recovery and recycling. Here we show that conjugating a temperature-sensitive polymer to a genetically engineered site on a protein allows the protein's ligand binding affinity to be controlled. We synthesized a mutant of the protein streptavidin to enable site-specific conjugation of the responsive polymer near the protein's binding site. Normal binding of biotin to the modified protein occurs below 32 degrees C, whereas above this temperature the polymer collapses and blocks binding. The collapse of the polymer and thus the enabling and disabling of binding, is reversible. Such environmentally triggered control of binding may find many applications in biotechnology and biomedicine, such as the control of enzyme reaction rates and of biosensor activity, and the controlled release of drugs.

Acrylic Resins↗
PubMed1995

Independent neural mechanisms for bright and dark information in binocular stereopsis.

Early visual processing is organized into a number of independent channels. In the retina, increments and decrements of brightness are processed independently by different groups of neurons. For psychophysical measurements of human vision, independence can be tested statistically. Using this criterion in a depth judgement task, we show here that, for binocular stereo vision, increments and decrements are treated independently, at least as far as the level at which information from the left and right eyes is first combined. At later stages of stereo processing, the information from the two channels is no longer independent. Because the signals for stereo vision are first combined at the visual cortex, these results suggest that the neural 'on' and 'off' channels remain independent right up to early cortical stages. Theoretical studies of stereo vision have proposed that visual features in the views of the two eyes are matched on the basis of 'similarity'. Our results show that stereo matching treats features as statistically independent (and therefore dissimilar) if they appear perceptually bright and dark relative to the background. If features differ perceptually but only in the degree of brightness or darkness, human stereo vision treats them as similar.

Darkness↗
PubMed1995

Lateral diffusion of molecules partitioned into C-18 ligands on silica surfaces.

Lateral diffusion rates of a fluorescent probe molecule partitioned into chromatographic C-18 ligands on a planar silica substrate were measured as a function of overlaying solvent composition. Diffusion coefficients of the probe were measured with a fluorescence recovery after patterned photobleaching experiment. A total internal reflection fluorescence flow cell held the derivatized planar substrate in contact with various aqueous solutions and allowed the fluorescence signal from two interfering, total internally reflected laser beams to be imaged onto a detector. Diffusion coefficients for the partitioned probe were approximately 3 orders of magnitude smaller than diffusion in solution and were found to increase with increasing methanol concentration in the overlaying aqueous solvent mixture. Inability of a solution phase ionic quencher to quench the fluorescence of sorbed rubrene confirmed that the probe is fully partitioned into the C-18 chains.

Chromatography↗