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Biomedical subjects

D A Benson

Publications and source records attributed to D A Benson.

At least 19 recordsLinked to original sources

Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.

We have shown recently (B. A. Yoshida et al., Cancer Res., 59: 5483-5487) that mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate cancer metastases in vivo. Evaluation of the expression of components of the MKK4 signaling cascade showed a loss or down-regulation of expression of MKK4 or c-Jun, a downstream mediator of MKK4, in six of eight human prostate cancer cell lines. Given these findings, we next assessed whether MKK4 dysregulation occurs during the development of clinical prostate cancer. Immunohistochemical studies showed high levels of MKK4 expression in the epithelial but not the stromal compartment of normal prostatic tissues. In neoplastic tissues, a statistically significant, direct, inverse relationship between Gleason pattern and MKK4 was established. These results demonstrate that MKK4 protein is consistently down-regulated during prostate cancer progression and support a role for dysregulation of its signaling cascade in clinical disease. To test the possibility that down-regulation of MKK4 protein is the result of allelic loss, metastatic prostate cancer lesions were examined for loss of heterozygosity (LOH) within the MKK4 locus (D17S969). These studies showed a 31% (5 of 16) LOH of MKK4 that is not associated with coding region mutations, which suggests that the nucleotide sequence of the gene in the remaining allele is infrequently mutated.

Enzyme Activation↗

Operator Lévy motion and multiscaling anomalous diffusion.

The long-term limit motions of individual heavy-tailed (power-law) particle jumps that characterize anomalous diffusion may have different scaling rates in different directions. Operator stable motions [Y(t):t> or =0] are limits of d-dimensional random jumps that are scale-invariant according to c(H)Y(t)=Y(ct), where H is a dxd matrix. The eigenvalues of the matrix have real parts 1/alpha(j), with each positive alpha(j)< or =2. In each of the j principle directions, the random motion has a different Fickian or super-Fickian diffusion (dispersion) rate proportional to t(1/alpha(j)). These motions have a governing equation with a spatial dispersion operator that is a mixture of fractional derivatives of different order in different directions. Subsets of the generalized fractional operator include (i) a fractional Laplacian with a single order alpha and a general directional mixing measure m(straight theta); and (ii) a fractional Laplacian with uniform mixing measure (the Riesz potential). The motivation for the generalized dispersion is the observation that tracers in natural aquifers scale at different (super-Fickian) rates in the directions parallel and perpendicular to mean flow.

Journal Article↗

Eulerian derivation of the fractional advection-dispersion equation.

A fractional advection-dispersion equation (ADE) is a generalization of the classical ADE in which the second-order derivative is replaced with a fractional-order derivative. In contrast to the classical ADE, the fractional ADE has solutions that resemble the highly skewed and heavy-tailed breakthrough curves observed in field and laboratory studies. These solutions, known as alpha-stable distributions, are the result of a generalized central limit theorem which describes the behavior of sums of finite or infinite-variance random variables. We use this limit theorem in a model which sums the length of particle jumps during their random walk through a heterogeneous porous medium. If the length of solute particle jumps is not constrained to a representative elementary volume (REV), dispersive flux is proportional to a fractional derivative. The nature of fractional derivatives is readily visualized and their parameters are based on physical properties that are measurable. When a fractional Fick's law replaces the classical Fick's law in an Eulerian evaluation of solute transport in a porous medium, the result is a fractional ADE. Fractional ADEs are ergodic equations since they occur when a generalized central limit theorem is employed.

Computer Simulation↗

Results of treatment with tamsulosin in men with acute urinary retention.

PURPOSE: The aim of this study was to prospectively assess the outcome in men treated with temporary catheter drainage and tamsulosin after an episode of acute urinary retention (AUR). MATERIALS AND METHODS: Thirty-three consecutive men with AUR were treated with tamsulosin 0.4 mg daily for at least 4 days before a trial of voiding. Those men who were able to void adequately continued taking tamsulosin and were evaluated at 2-week and 3-month follow-up. After 3 months, additional follow-up was obtained at regular intervals as determined by the treating physician. RESULTS: Median follow-up was 6.5 months. Mean urine volume at the time of initial bladder drainage was 790 mL. Eighty-eight percent (29/33) of men were able to void initially. Transurethral prostatectomy or intermittent catheterization were necessary in 9 (27%) of 33 patients during the follow-up period. A poor quality-of-life score on the initial International Prostate Symptom Score (p = .038) and a high postvoid residual volume 2 weeks after catheter removal (p = .013) correlated with failure of medical therapy. Patients with AUR after nonurologic surgery had a significantly better outcome than those with AUR that did not occur postoperatively. Mean symptom score, quality-of-life score, and postvoid residual urine volume were 12.9, 2.7, and 111 mL, respectively, at 2-week follow-up and were 11.9, 2.8, and 61.7 mL, respectively, at 3-month follow-up. Mean peak urinary flow rate at 3 months was 7.7 mL/s. CONCLUSIONS: Tamsulosin appears to be helpful in the management of men with AUR. The majority of men were able to avoid surgery after temporary catheter drainage.

Acute Disease↗

High HIV seroprevalence associated with gonorrhea: New York City Department of Health, sexually transmitted disease clinics, 1990-1997.

OBJECTIVE: To measure trends in HIV seroprevalence associated with gonorrhea in patients presenting to New York City Department of Health sexually transmitted disease (STD) clinics, 1990-1997 (n = 94 577). METHOD: Unlinked HIV-1 serosurvey using remnant serum originally drawn for routine serologic tests for syphilis (STS). Demographic, risk factor, clinical and laboratory data were abstracted from clinic charts. No other data sources were used. Patients were not interviewed. RESULTS: During 1990-1997 HIV seroprevalence declined from 9 to 6% (P for trend < 0.01) in the STD clinic sample. Gonorrhea incidence city-wide declined from 481 per 100 000 to 194 per 100 000. HIV seroprevalence in patients with a diagnosis of gonorrhea (n = 11 914) remained stable at 10-11% during the period, whereas HIV seroprevalence associated with all other STDs combined declined from 8 to 5% (P for trend < 0.01). Seroprevalence in women with gonorrhea (n = 2243) declined from 8 to 4% (P for trend < 0.001), whereas seroprevalence in men with gonorrhea was stable at 11-12%. Seroprevalence in men aged less than 25 years and diagnosed with gonorrhea declined from 5 to 3% (P for trend = 0.02). In contrast, in men aged 25 years and older and diagnosed with gonorrhea, seroprevalence remained at 14-16% throughout the period 1990-1997. Among men with gonorrhea, seroprevalence was associated with same gender or bisexual contact [odds ratio (OR), 9.2; 95% confidence interval (CI), 8.1-10.4], age > 25 years (OR, 5.1; 95% CI, 4.6-5.7), and white race/ethnicity (OR, 1.3; 95% CI, 1.2-1.4). CONCLUSIONS: In this 9-year serosurvey the association between HIV and gonorrhea remained strong during a period when HIV seroprevalence and gonorrhea incidence declined. The data suggest that a gonorrhea diagnosis is an important risk marker in this era of 'safe sex' and that behavior patterns of patients with gonorrhea warrant further study.

Adolescent↗

GenBank.

The GenBank((R))sequence database incorporates publicly available DNA sequences of >55 000 different organisms, primarily through direct submission of sequence data from individual laboratories and large-scale sequencing projects. Most submissions are made using the BankIt (Web) or Sequin programs and accession numbers are assigned by GenBank staff upon receipt. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome, mapping and protein structure information, plus the biomedical literature via PubMed. Sequence similarity searching is provided by the BLAST family of programs. Complete bimonthly releases and daily updates of the GenBank database are available by FTP. NCBI also offers a wide range of WWW retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the NCBI home page at http://www.ncbi.nlm.nih.gov

Animals↗

GenBank.

The GenBank (Registered Trademark symbol) sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from individual laboratories and from large-scale sequencing projects. Most submitters use the BankIt (Web) or Sequin programs to format and send sequence data. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez, which integrates data from the major DNA and protein sequence databases along with taxonomy, genome and protein structure information. MEDLINE (Registered Trademark symbol) s from published articles describing the sequences are included as an additional source of biological annotation through the PubMed search system. Sequence similarity searching is offered through the BLAST series of database search programs. In addition to FTP, Email, and server/client versions of Entrez and BLAST, NCBI offers a wide range of World Wide Web retrieval and analysis services based on GenBank data. The GenBank database and related resources are freely accessible via the URL: http://www.ncbi.nlm.nih.gov

Amino Acid Sequence↗

Multidimensional advection and fractional dispersion.

Extension of the fractional diffusion equation to two or three dimensions is not as simple as extension of the second-order equation. This is revealed by the solutions of the equations: unlike the Gaussian, the most general stable vector cannot be generated with an atomistic measure on the coordinate axes. A random combination of maximally skewed stable variables on the unit sphere generates a stable vector that is a general model of a diffusing particle. Subsets are symmetric stable vectors that have previously appeared in the literature and the well-known multidimensional Brownian motion. A multidimensional fractional differential operator is defined in the process.

Journal Article↗

GenBank.

The GenBank(R) sequence database (http://www.ncbi.nlm.nih.gov/) incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from individual laboratories and from large-scale sequencing projects. Most submitters use the BankIt (WWW) or Sequin programs to send their sequence data. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive worldwide coverage. GenBank data is accessible through NCBI's integrated retrieval system, Entrez , which integrates data from the major DNA and protein sequence databases along with taxonomy, genome and protein structure information. MEDLINE(R) abstracts from published articles describing the sequences are also included as an additional source of biological annotation. Sequence similarity searching is offered through the BLAST series of database search programs. In addition to FTP, e-mail and server/client versions of Entrez and BLAST, NCBI offers a wide range of World Wide Web retrieval and analysis services of interest to biologists.

Animals↗

GenBank.

The GenBank sequence database incorporates DNA sequences from all available public sources, primarily through the direct submission of sequence data from authors and from large-scale sequencing projects. Data exchange with the EMBL Data Library and the DNA Data Bank of Japan helps ensure comprehensive coverage. GenBank continues to focus on quality control and annotation while expanding data coverage and retrieval services. An integrated retrieval system, known asEntrez, incorporates data from the major DNA and protein sequence databases, along with genome maps and protein structure information. MEDLINE abstracts from published articles describing the sequences are also included as an additional source of biological annotation. Sequence similarity searching is offered through the BLAST family of programs. All of NCBI's services are offered through the World Wide Web. In addition, there are specialized server/client versions as well as FTP and e-mail server access.

Amino Acid Sequence↗

GenBank.

The GenBank sequence database continues to expand its data coverage, quality control, annotation content and retrieval services. GenBank is comprised of DNA sequences submitted directly by authors as well as sequences from the other major public databases. An integrated retrieval system, known as Entrez, contains data from GenBank and from the major protein sequence and structural databases, as well as related MEDLINE abstracts. Users may access GenBank over the Internet through the World Wide Web and through special client-server programs for text and sequence similarity searching. FTP, CD-ROM and e-mail servers are alternate means of access.

Base Sequence↗

Trends in HIV seroprevalence in men who have sex with men: New York City Department of Health sexually transmitted disease clinics, 1988-1993.

OBJECTIVE: To measure HIV seroprevalence trends in a primarily non-white sample (n = 1618) of men who have sex with men (MSM). The MSM were sampled at New York City Department of Health (NYC-DOH) sexually transmitted disease (STD) clinics during 1988-1993. DESIGN: Unlinked HIV-1 serosurvey using remnant serum originally drawn for routine syphilis screening. METHOD: Demographic, clinical and risk exposure data were abstracted from clinic charts. No other sources of data were used, and patients were not interviewed. RESULTS: HIV seroprevalence in the overall sample declined from 53 to 34% between 1988 and 1993. The most dramatic decline was observed in white MSM (from 47 to 17%; n = 457). Seroprevalence in black MSM also fell (from 60 to 45%; n = 691). Seroprevalence in Hispanic men (n = 332) showed no decline, starting and ending the 5-year period at 39%. Bisexual MSM, who comprised one-quarter of the sample, experienced a shallower decline than other MSM (from 41 to 33%). The magnitude of the decline decreased with increasing age--for example, seroprevalence in MSM aged 20-24 years dropped by 62% (from 39 to 15%), whereas seroprevalence in MSM aged 40-44 years dropped by 10% (from 48 to 43%)--up through age 45 years, at which point another dramatic decline (from 53 to 21%) was observed. There was no decline in the high seroprevalence associated with a discharge diagnosis of gonorrhea (58%) or any genital ulcer disease (GUD; e.g., primary or secondary syphilis, chancroid or genital herpes, 52%). The proportion of STD diagnoses attributed to GUD rose from 8 to 14%. CONCLUSION: A small number of MSM continued to present to NYC-DOH STD clinics and to leave with a diagnosed STD at a time when safe sex was aggressively promoted. The biological and behavioral associations between GUD and gonorrhea and HIV seroprevalence warrant continued investigation. Prevention programs targeted to young, minority and bisexual MSM are needed.

Adult↗

Increasing HIV-1 seroprevalence associated with genital ulcer disease, New York City, 1990-1992.

OBJECTIVE: To measure HIV seroprevalence trends associated with sexually transmitted diseases (STD) causing ulcerative lesions [genital ulcer disease (GUD)], such as syphilis, chancroid and genital herpes, in New York City between 1990 and 1992. DESIGN: Unlinked HIV-1 serosurvey using remnant serum drawn originally for routine syphilis screening. SETTING AND PATIENTS: Consecutive sample of patients presenting to New York City Department of Health STD clinics for STD examination (n = 41,678). MAIN OUTCOME MEASURE: Serologic evidence of antibody to HIV-1. RESULTS: Although overall HIV seroprevalence and GUD incidence declined between 1990 and 1992, seroprevalence in patients with GUD increased from 10 to 16%. In contrast, seroprevalence in patients with non-ulcerative STD decreased. The most dramatic changes in seroprevalence associated with GUD occurred in patients using crack cocaine and injecting drugs. CONCLUSIONS: Despite declining HIV seroprevalence and GUD incidence, the association between GUD and HIV infection has strengthened over time in New York City STD clinics. Longitudinal incidence studies are needed to elucidate the biological, behavioral and temporal associations between GUD and HIV. Timely diagnosis and treatment of acute STD and more intensive risk reduction strategies at the clinics and associated testing sites, with a particular focus on GUD patients, are indicated.

Female↗

GenBank.

The GenBank sequence database continues to expand its data coverage, quality control, annotation content and retrieval services for the scientific community. Besides handling direct submissions of sequence data from authors, GenBank also incorporates DNA sequences from all available public sources; an integrated retrieval system, known as Entrez, also makes available data from the major protein sequence and structural databases, and from U.S. and European patents. MIDLINE abstracts from published articles describing the sequences are also included as an additional source of biological annotation for sequence entries. GenBank supports distribution of the data via FTP, CD-ROM, and E-mail servers. Network server-client programs provide access to an integrated database for literature retrieval and sequence similarity searching.

Amino Acid Sequence↗

Information resources at the National Center for Biotechnology Information.

The National Center for Biotechnology Information (NCBI), part of the National Library of Medicine, was established in 1988 to perform basic research in the field of computational molecular biology as well as build and distribute molecular biology databases. The basic research has led to new algorithms and analysis tools for interpreting genomic data and has been instrumental in the discovery of human disease genes for neurofibromatosis and Kallmann syndrome. The principal database responsibility is the National Institutes of Health (NIH) genetic sequence database, GenBank. NCBI, in collaboration with international partners, builds, distributes, and provides online and CD-ROM access to over 112,000 DNA sequences. Another major program is the integration of multiple sequences databases and related bibliographic information and the development of network-based retrieval systems for Internet access.

Animals↗

Alignment of Escherichia coli K12 DNA sequences to a genomic restriction map.

We use the extensive published information describing the genome of Escherichia coli and new restriction map alignment software to align DNA sequence, genetic, and physical maps. Restriction map alignment software is used which considers restriction maps as strings analogous to DNA or protein sequences except that two values, enzyme name and DNA base address, are associated with each position on the string. The resulting alignments reveal a nearly linear relationship between the physical and genetic maps of the E. coli chromosome. Physical map comparisons with the 1976, 1980, and 1983 genetic maps demonstrate a better fit with the more recent maps. The results of these alignments are genomic kilobase coordinates, orientation and rank of the alignment that best fits the genetic data. A statistical measure based on extreme value distribution is applied to the alignments. Additional computer analyses allow us to estimate the accuracy of the published E. coli genomic restriction map, simulate rearrangements of the bacterial chromosome, and search for repetitive DNA. The procedures we used are general enough to be applicable to other genome mapping projects.

Amino Acid Sequence↗

The medical information needs of internists and pediatricians at an academic medical center.

Medical information needs were examined in a survey of sixty-seven physicians selected from the faculty and housestaff at Johns Hopkins Hospital. A standardized questionnaire was administered personally by a medical informatics physician to collect data on information needs, attitudes, and previous experience with computers. The types of information most frequently required by both faculty and housestaff were treatment recommendations and differential diagnosis. The sources of reference information most commonly used were textbooks and colleagues. The information needs of housestaff differed significantly in several categories from those of faculty physicians. Housestaff more frequently needed information for patient care (P less than 0.05), and preferred the use of textbooks (P less than 0.01) and handbooks (P less than 0.001) as information sources. Faculty more frequently needed information for activities unrelated to patient care (P less than 0.01) and placed greater importance on basic science information (P less than 0.01). When asked to suggest references for online access, the respondents named 143 journals and textbooks, with journals overwhelmingly preferred over textbooks. Only one reference, the New England Journal of Medicine, was requested by a majority of the respondents. The importance of a broad understanding of physician information needs through improved data-collection techniques is discussed as a means of increasing the use of medical information systems.

Academic Medical Centers↗

Unit study of monkey frontal cortex: active localization of auditory and of visual stimuli.

The influence of sound localization behavior on unit activity in the frontal cortex of awake rhesus monkeys was examined by comparing responses under three behavioral conditions: auditory localization, during which a response was required to the location of a sound (broad-band noise) source; auditory detect, during which a response was required to indicate the occurrence of the sound regardless of location; visual localization, during which no sounds were presented and a response was required to the location of a visual stimulus; and nonperform, presentation of auditory stimuli as in the first two conditions, but with the animal sitting passively. Extracellular microelectrode recordings were made in the periarcuate region and dorsal and ventral prefrontal areas near the principal sulcus. Four monkeys were used with a total of 498 cells studied. Of the total population, only five cells were found to have characteristics similar to those of auditory units in the primary auditory cortex and the surrounding belt area. More typically, units were found that had strong short-latency responses specific to the auditory and/or visual localization tasks. These units had no or weak responses when the same sound stimuli were presented in the auditory detect task or when a monkey received the sound stimuli in a nonperforming condition. Two regions were identified, one medial and/or posterior to the arcuate sulcus, in Brodmann's area 6; the second included parts of areas 8 and 9 within the genu of the arcuate sulcus. Units from these regions are referred to, respectively, as the postarcuate and the prearcuate populations. Both populations responded predominantly during active localization behavior. Sixty-two percent of the postarcuate population responded during auditory localization, 32% responded during auditory detect, and only 18% responded to acoustic stimuli presented in the nonperforming condition. In the prearcuate population percentages in these three conditions were 35, 25, and 12%, respectively. For visual localization, 54% in the postarcuate population responded, whereas 42% in the prearcuate responded. Spatial tuning of units during auditory localization was similar to that seen in units of the primary auditory cortex, with the greatest percentages of units responding to stimuli contralateral to the recording site. Similar tuning was observed for the visual localization task as well. Similarities in spatial tuning between the auditory and visual localization conditions were examined to assess the "bimodal" nature of the units.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗