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PubMed1979

Trends and developments in physical anthropology, 1978-1979.

Members of the American Association of Physical Anthropologists were asked to supply information about their current programs and their own graduate training in order to compile a training directory and to analyze certain aspects of the discipline. The data indicate that the majority consider their graduate training to have been deficient, mainly in statistics, genetics, chemistry, physiology, and mathematics. The areas though most important for future research in physical anthropology include fields such a genetics, anatomy, ecology, physiology, and paleontology, although a great many individuals are engaged in teaching and research in other areas. A brief analysis of relative growth in the field over the last few decades indicates a serious imbalance between the number of new Ph.D.'s and available employment opportunities.

Anthropology, Physical↗

PubMed2001

Trends in cardiac catheterization laboratories in the United States.

The Society for Cardiac Angiography and Interventions has periodically published a Directory of Cardiac Catheterization Laboratories in the United States. All known catheterization laboratories are surveyed and certain operational characteristics are queried. These surveys, in 1983, 1987, 1993, 1995 and 1998, have demonstrated a 2.5 fold increase in cardiac catheterization laboratories since 1983, corresponding increases in numbers of physicians that perform procedures, and in the numbers of procedures performed, reflecting advances in cardiovascular medicine and technology. These surveys have also documented the evolution of interventional techniques, and a shift away from film based imaging, to digitally based methods. These data provide a substrate for consideration of national cardiovascular objectives and planning of future resource allocation by cardiovascular physicians and their colleagues.

Cardiac Catheterization↗

PubMed2003

Has the investment in public cancer education delivered observable changes in knowledge over the past 10 years?

BACKGROUND: During the 1990s, Western countries, such as Australia, directed substantial funds toward public cancer education. An important indicator of whether this investment has been worthwhile is a shift over time in the proportion of the population who have accurate knowledge regarding cancer. METHODS: In the year 2000, a cross-sectional telephone survey was administered to 685 residents selected from the New South Wales (Australia) Electronic White Pages telephone directory. This study replicated in part a survey conducted in 1989. RESULTS: In the 2000 survey, smoking (96.0%) and sun exposure (80.4%) were well-known as risk factors for lung cancer and melanoma, respectively. However, community knowledge of risk factors for colorectal, breast, cervical, and prostate cancer was poor. Most respondents were able to nominate mammograms (82.2%) and Pap tests (86.8%) as screening tests for breast and cervical cancer, respectively. Approximately two-thirds of the sample were able to nominate foods that reduce the risk of developing cancer. Compared with the 1989 data, there appeared to have been improvements in community knowledge of mammograms as a screening test for breast cancer. For the other cancers, knowledge gains appeared smaller or marginal. With regard to the lifetime risk of developing these cancers, community understanding remains poor. Predictors of greater knowledge include a higher level of education. CONCLUSIONS: Where ongoing investments have been made, like in the case of breast cancer education, there have been improvements in community knowledge. However, major challenges remain. Potential targets for future public education campaigns are discussed.

Australia↗

PubMed1993

Cloning and sequencing of human immunoglobulin V lambda gene segments.

To provide the building blocks for making synthetic antibody fragments we have used the polymerase chain reaction (PCR) to clone human variable (V) gene segments of lambda light chains. The PCR primers were based on the sequences of known human V lambda segments, and were used to isolate 14 new V lambda segments (including 4 pseudogenes) from a single individual. We have compiled a sequence directory from this data and other sources to include all known human V lambda segments with open reading frames and we have identified a new V lambda family (V lambda IX). Almost all of the segments (22/24) have different sequences in the complementarity-determining regions, setting a lower limit to the structural diversity of the antigen binding sites encoded by human V lambda genes in the human population.

Base Sequence↗

PubMed2002

Making epidemiologic studies responsive to the needs of participants and communities: the Carolina Breast Cancer Study experience.

In this report, we present the results of surveys administered to participants and nonparticipants in the Carolina Breast Cancer Study (CBCS). Surveys and structured interviews were administered to determine women's concerns regarding participation in research studies, access to health care, and beliefs regarding causes of breast cancer. Survey results showed the highest concern for the growing number of women diagnosed with breast cancer in North Carolina and potential environmental agents that may cause breast cancer. Negative responses were noted for time constraints related to participation and lack of familiarity with epidemiologic research; another concern noted was the lack of centralized information regarding breast cancer treatment. These issues were addressed by (1) developing a web site that provided background information about the CBCS, summaries of published study results, and information about the etiology of breast cancer; and (2) creating a statewide, comprehensive breast cancer resource directory for women who need information about breast cancer diagnosis, treatment, and support. These two projects were carried out in collaboration with breast cancer advocates, and demonstrate the important role that advocates can play in making epidemiologic research more responsive to the needs of communities.

Adult↗

PubMed2001

Go!Poly: A gene-oriented polymorphism database.

Human genome polymorphisms play a key role in defining the molecular basis of phenotypic differences between individuals in aspects such as disease susceptibility and drug responses. The database requirements for supporting the study of human genetic variation have been well recognized. In order to meet these needs, several generalized databases have been built. However, it is still hard for users to find gene-related variation data from these huge and sophisticated databases. In its role as a gene-oriented directory of polymorphism data, Go!Poly (Gene Oriented Polymorphism Database; http://61.139.84.5/gopoly/) utilizes two new highly curated and non-redundant resources, LocusLink (http://www.ncbi.nlm.nih.gov/LocusLink/) and RefSeq (http://www.ncbi.nlm.nih.gov/LocusLink/refseq.html), as the standard for identifying and positioning nucleotide variations. As a generalized polymorphism database, Go!Poly extracts human gene-linked sequence variations of all common types (SNP, insertion-deletion, simple tandem repeat, and complex nucleotides variations) from various public resources including scientific journals and internet resources, such as HGBASE (http://hgbase.cgr.ki.se) and dbSNP (http://www.ncbi.nlm.nih.gov/SNP/). The polymorphism data are then categorized into different gene loci, and the reference sequences given by LocusLink are used as positioning references. Through close integration with LocusLink, Go!Poly also provides facilitated connections among sequence data, gene name, and related biological information. This feature also makes Go!Poly easy to search and navigate. Future automated annotations and internal consistency checking may also benefit from this. Extensive efforts are being taken to make the polymorphism information generated by the Chinese scientific community available from this resource.

China↗

PubMed1993

Summary of results of 1991 ASFA apheresis survey. American Society for Apheresis.

As part of gathering data for its Networking Directory, the Registry/Directory Committee of the American Society for Apheresis solicited data on the types of apheresis procedures performed, equipment used, and diseases treated in the year 1991. In this voluntary solicitation of the 266 centers responding, 94% were from the United States. For those centers reporting exact numbers of procedures performed out of all institutions doing the procedures 48,221 therapeutic and 330,702 donor procedures were reported. The dominant type of equipment being used is the centrifugal type. For therapeutic procedures plasma exchange is the most prevalent procedure and for donor procedures it is plateletpheresis. For therapeutics, Guillain-Barre syndrome was the most prevalent disease treated by plasmapheresis and leukemias by cytapheresis. The survey methodology proved to be valuable in gathering the data on a voluntary basis. With subsequent surveys and refinement of its methodology the apheresis practices in the United States could be assessed quantitatively to provide information on the number and types of procedures being carried out. Such information is required to assess the impact of apheresis technology on health care, to project trends, and to review the cost impact of this technology.

Blood Component Removal↗

PubMed2002

Role of nerve growth factor in the olfactory system.

Olfactory neurons are unique in the mammalian nervous system because of their capacity to regenerate in adult animals. It has been shown that olfactory receptor cells located in the olfactory epithelium are replaced on a continuous basis and in response to injury throughout the life span of most species. NGF, which is one of the neurotrophic factors, is present in many areas of the central and peripheral nervous system. It has been shown that NGF in the olfactory bulb plays a role in the survival of cholinergic neurons in the horizontal limb of the diagonal band (HDB). Recent studies of NGF in the olfactory bulb suggest that it is involved in the development, maintenance, and regeneration of olfactory receptor cells. In this study, we review reports examining the relationship between NGF in the olfactory bulb and neuronal regeneration and development in the mammalian olfactory systems. Low- and high-affinity NGF receptor immunoreactivity is markedly expressed during regeneration and at different stages of development in the mouse olfactory system. This level of immunoreactivity is no longer present after completion of regeneration and at maturation. Other findings indicate that NGF injected into the olfactory bulb is transported retrogradely to the olfactory epithelium. It has also been shown that continuous anti-NGF antibody injection into the olfactory bulb causes degeneration and olfactory dysfunction. Administration of NGF directory into nasal cavity results in an increase in the expression of olfactory marker protein within the olfactory epithelium in axotomized rats. These findings suggested that the presence of NGF in the olfactory bulb plays an essential role in regeneration, maintenance, and development in the olfactory system of mammals.

Animals↗

PubMedDate not supplied

Structure-based discovery of a new affinity ligand to pancreatic alpha-amylase.

A ligand useful for affinity capture of porcine pancreatic alpha-amylase was found by virtual screening of the commercially available compound data base MDL Available Chemicals Directory. Hits from the virtual screening were investigated for binding by nuclear magnetic resonance (NMR) and surface plasmon resonance. Selected compounds were tested for inhibition of the enzyme using a NMR-based assay. One of the binders found was covalently coupled to a chromatographic resin and a column, packed with this resin, could retain alpha-amylase, which subsequently was eluted by introduction of the known inhibitor acarbose to the elution buffer.

Animals↗

PubMedDate not supplied

A new strategy for improved secondary screening and lead optimization using high-resolution SPR characterization of compound-target interactions.

Biophysical label-free assays such as those based on SPR are essential tools in generating high-quality data on affinity, kinetic, mechanistic and thermodynamic aspects of interactions between target proteins and potential drug candidates. Here we show examples of the integration of SPR with bioinformatic approaches and mutation studies in the early drug discovery process. We call this combination 'structure-based biophysical analysis'. Binding sites are identified on target proteins using information that is either extracted from three-dimensional structural analysis (X-ray crystallography or NMR), or derived from a pharmacore model based on known binders. The binding site information is used for in silico screening of a large substance library (e.g. available chemical directory), providing virtual hits. The three-dimensional structure is also used for the design of mutants where the binding site has been impaired. The wild-type target and the impaired mutant are then immobilized on different spots of the sensor chip and the interactions of compounds with the wild-type and mutant are compared in order to identify selective binders for the binding site of the target protein. This method can be used as a cost-effective alternative to high-throughput screening methods in cases when detailed binding site information is available. Here, we present three examples of how this technique can be applied to provide invaluable data during different phases of the drug discovery process.

Adenosine Deaminase↗

PubMed1991

Use of exercise in the management of cystic fibrosis: short communication about a survey of cystic fibrosis referral centers.

A survey of 47 cystic fibrosis referral centers was conducted to study the use of exercise in the management of patients with cystic fibrosis (CF). A questionnaire with 5 brief questions concerning the prescription and application of exercise therapy was sent to the first 47 centers (38.5%) listed in the 1988 CF Foundation Directory, and 46 (97.9%) were returned. While all but one of the respondents recommend exercise at least to selected patients, and while 80.4% of the centers refer patients to summer camp programs, only 43.5% offer exercise stress testing and only 21.7% offer an exercise program for their patients. Most of the respondents who recommend exercise prescribe aerobic exercise, swimming being the most frequently chosen type. Although there is a large discrepancy between those centers that acknowledge the benefits of exercise and those that have arranged for regularly available exercise services, inroads have been made in utilizing this therapeutic tool for patients with CF.

Community Health Centers↗

PubMed2004

Virtual screening for inhibitors of human aldose reductase.

The inhibition of aldose reductase (AR) provides an interesting strategy to prevent the complications of chronic diabetes. Although a large number of different AR inhibitors are known, very few of these compounds exhibit sufficient efficacy in clinical trials. We performed a virtual screening based on the ultrahigh resolution crystal structure of the inhibitor IDD594 in complex with human AR. AR operates on a large scale of structurally different substrates. To achieve this pronounced promiscuity, the enzyme can adapt rather flexibly to its substrates. Likewise, it has a similar adaptability for the binding of inhibitors. We applied a protocol of consecutive hierarchical filters to search the Available Chemicals Directory. In the first selection step, putative ligands were chosen that exhibit functional groups to anchor the anion-binding pocket of AR. Subsequently, a pharmacophore model based on the binding geometry of IDD594 and the mapping of the binding pocket in terms of putative "hot spots" of binding was applied as a second consecutive filter. In a third and final filtering step, the remaining candidate molecules were flexibly docked into the binding pocket of IDD594 with FlexX and ranked according to their estimated DrugScore values. Out of 206 compounds selected by this search and complemented by a cluster analysis and visual inspection, 9 compounds were selected and subjected to biological testing. Of these, 6 compounds showed IC50 values in the micromolar range. According to the proposed binding mode, the two inhibitors BTB02809 (IC50 = 2.4 +/- 0.5 microM) and JFD00882 (IC50 = 4.1 +/- 1.0 microM) both place a nitro group into the hydrophobic specificity pocket of human AR in an orientation coinciding with the position of the bromine atom of IDD594. The interaction of this Br with Thr113 has been identified as a key feature that is responsible for selectivity enhancement.

Acetates↗

PubMed1999

SHC1, a high pH inducible gene required for growth at alkaline pH in Saccharomyces cerevisiae.

In this study, we carried out a large-scale transposon tagging screening to identify genes whose expression is regulated by ambient pH. Of 35,000 transformants, two strains carrying the genes whose expression is strictly dependent on pH of growth medium were identified. One of the genes with 20-fold induction by alkali pH was identified as SHC1 gene in the Yeast Genome Directory and its expression was the highest at alkaline pH and moderately induced by osmotic stress. However, the gene was expressed neither at acidic pH nor by other stress conditions. The haploid mutant with truncated shc1 gene showed growth retardation and an abnormal morphology at alkaline pH. On the other hand, the mutant strain carrying the wild-type SHC1 gene reverted to the mutant phenotype. To confirm that Shc1p is an alkali-inducible protein, a monoclonal antibody to Shc1p was produced. While a 55-kDa protein band appeared on the Western blot of cells grown at alkaline pH, Shc1p was barely detectable on the blots of cells grown in YPD. Our results indicate that yeast cells have an efficient system adapting to large variations in ambient pH and SHC1 is one of the genes required for the growth at alkaline pH.

Amino Acid Sequence↗

PubMed1997

Leishmania major: molecular modeling of cysteine proteases and prediction of new nonpeptide inhibitors.

The crystal structures of papain, cruzain, and human liver cathepsin B were used to build homology-based enzyme models of a cathepsin L-like cysteine protease (cpL) and a cathepsin B-like cysteine protease (cpB) from the protozoan parasite Leishmania major. Although structurally a member of the cathepsin B subfamily, the L. major cpB is not able to cleave synthetic substrates having an arginine in position P2. This biochemical property correlates with the prediction of a glycine instead of a glutamic acid at position 205 (papain numbering). The modeled active sites of the L. major cpB and cpL were used to screen the Available Chemicals Directory (a database of about 150,000 commercially available compounds) for potential cysteine protease inhibitors, using DOCK3.5. Based on both steric and force field considerations, 69 compounds were selected. Of these, 18 showed IC50's between 50 and 100 microM and 3 had IC50's below 50 microM. A secondary library of compounds, originally derived from a structural screen against the homologous protease of Plasmodium falciparum (falcipain), and subsequently expanded by combinatorial chemistry, was also screened. Three inhibitors were identified which were not only effective against the L. major protease but also inhibited parasite growth at 5-50 microM.

Animals↗

PubMed1995

A survey of blood transfusion practices of gynecologic oncologists.

OBJECTIVE: To survey the attitudes of gynecologic oncologists about indications for blood transfusion, and compare them to current recommendations about transfusion practice. METHODS: With the permission of the Society of Gynecologic Oncologists (SGO), a study questionnaire was mailed to 548 members and candidates in their directory. The questions asked about transfusion threshold before chemotherapy, following ovarian debulking, and after endometriosis surgery. Indications for transfusion were assessed using a qualitative/quantitative scale. Responses were analyzed with respect to years of SGO membership and practice setting using the chi 2 test and analysis of variance. Results were compared to the 1992 guidelines for transfusion of the American College of Physicians (ACP). RESULTS: Two hundred eighty-five forms were returned (52% of total). Fifty-one percent of respondents were in full-time academic positions; 36% were in private practice. Sixty-one percent were full SGO members, and 35% were candidates. The average prechemotherapy transfusion threshold (TT) was a hemoglobin concentration (hgb) of 7.9 +/- 0.7 g/dl (g). At that level the mean transfusion was 1.9 +/- 0.5 units of packed red blood cells (U). For the ovarian debulking scenario, the mean postoperative TT was 8.1 +/- 0.8 g with a mean transfusion of 1.9 +/- 0.4 U. For the endometriosis case, the mean TT was 7.0 +/- 0.8 g, with a mean transfusion of 1.9 +/- 0.5 U. Analysis showed no difference in practice based on years of SGO membership or practice setting. CONCLUSION: A majority of the gynecologic oncologists surveyed offers transfusion at levels of anemia similar to ACP recommendations, but frequently transfuse more units than recommended. A substantial minority does not follow the guidelines at all.

Blood Transfusion↗

PubMed1999

The use of adjuvant radiation therapy by members of the Society of Gynecologic Oncologists.

UNLABELLED: OBJECTIVES. The aim of this study was to determine the attitudes of the members of the Society of Gynecologic Oncologists with respect to the use of adjuvant radiation therapy in women with endometrial cancer. METHODS: An anonymous survey concerning the use of adjuvant radiation therapy in endometrial cancer was mailed to all members of the Society of Gynecologic Oncologists listed in the 1998 directory. RESULTS: Of the 767 listed members, 325 (42%) returned completed surveys. Less than 20% of respondents recommended adjuvant radiation therapy in stage IA grade 1 or 2 and stage IB grade 1 endometrial cancer. Adjuvant radiation is recommended by 40 to 50% of respondents in women with stage IA grade 3 and IB grade 2 tumors. Most recommend adjuvant radiation for all women with >50% myometrial invasion or grade 3 tumors with any myometrial invasion. Lymph node sampling is attempted in all cases by 48% of respondents. For those familiar with Gynecologic Oncology Group (GOG) Study No. 99, 20% stated that they were more likely to recommend adjuvant radiation and 27% stated that they were less likely to recommend adjuvant radiation based on the preliminary results. Except in stage IA grade 1 tumors, the chance of recommending further therapy in women with all stages and grades was significantly less if a complete staging procedure including lymph node dissection had been performed. CONCLUSIONS: Complete staging appears to decrease the chance that postoperative therapy will be recommended. The use of adjuvant radiation therapy seem to have declined slightly as a result of GOG Study No. 99. Future studies in women with endometrial cancer that do not require lymph node sampling should evaluate the frequency of adjuvant therapy in the absence of complete staging.

Adenocarcinoma↗

PubMed1999

Surgical experiences and training of residents: perspective of experienced gynecologic oncologists.

OBJECTIVE: The aim of this study was to report the opinions of experienced gynecologic oncologists concerning the surgical education and experiences of residents. METHODS: The 1997 membership directory of the Society of Gynecologic Oncologists was used to identify individuals who were members for at least 5 years and on the faculty of residency training programs. One hundred seventy members were identified and a nine-question survey was mailed to them. RESULTS: One hundred nineteen (70%) surveys were returned. One hundred seventeen individuals were on the faculty of residency training programs and involved in the surgical training of residents. Ninety-six percent reported that gynecologic oncologists were a major resource for surgical education at their institution. Eight-nine (76%) reported a change in the volume of major abdominal and vaginal surgical procedures performed for noninvasive disease over the past 5 years. Of these 89, 16 (18%) reported that surgical volume at their institution decreased by 10%, 38 (43%) reported that surgical volume decreased by 10-25%, and 17 (19%) reported that surgical volume decreased by more than 25%. Sixty-three percent of all respondents reported that residents were not as well versed in pre- and postoperative care when compared to those of 5 years ago. Sixty-five percent of all respondents reported that graduating residents were less prepared in surgical techniques when compared to those of 5 years ago. Seventy-five percent of respondents reported that the primary care requirements of the RRC have decreased the amount of surgical experience, ICU rotations, and anesthesia rotations. Sixty percent of all respondents operated with other attending surgeons on more difficult cases, and 29% had changed to this practice within the past 5 years. Eighty-two percent believed that more time during residency training needs to be devoted gynecologic surgical experience. CONCLUSIONS: Experienced gynecologic oncologists on the faculty of residency training programs report a decrease in surgical skills and surgical experiences when compared to residents trained 5 years ago.

General Surgery↗

PubMed2000

Contemporary surgical management of borderline ovarian tumors: a survey of the Society of Gynecologic Oncologists.

OBJECTIVE: The objective of this study was to review the current practice patterns regarding the surgical management of borderline ovarian tumors. METHODS: A one-page survey was mailed to the members of the Society of Gynecologic Oncologists (SGO), using the directory of the Society. The survey addressed the demographics of the respondent and the recommended staging procedure for presumed early-stage disease. RESULTS: Of the 660 surveys mailed, 274 (42%) were returned. Ninety-seven percent (267/274) of respondents advocate surgical staging. Of this group, 96% (257/267) perform peritoneal washings, 97% (259/267) sample the omentum, and 92% (245/267) submit random peritoneal biopsies. Eighty-eight percent (235/267) perform lymph node sampling: paraaortic biopsies by 89% (210/235) and pelvic biopsies by 97% (228/235). Of this latter group, 91% sample the external iliac chain, 82% submit hypogastric nodal tissue, and 70% remove obturator lymph nodes. CONCLUSION: Diversity exists in the surgical management of borderline ovarian tumors among members of the SGO who responded to this survey. Efforts to ensure a consistent approach to the management of borderline ovarian tumors are warranted.

Biopsy↗