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Biomedical subjects

E Rice

Publications and source records attributed to E Rice.

At least 19 recordsLinked to original sources
PubMed2005

Families living with HIV.

Given the historical emergence of the AIDS epidemic first among gay men in the developed world, HIV interventions have primarily focused on individuals rather than families. Typically not part of traditional family structures, HIV-positive gay men in Europe and the US lived primarily in societies providing essential infrastructure for survival needs that highly value individual justice and freedom. Interventions were thus designed to focus on at-risk individuals with programmes that were age and gender segregated. As the epidemic has unfolded, the early focus on individuals has become inadequate: families live with HIV, not just individuals. Families' structure, economy, migration patterns, and developmental life cycles are affected by HIV, and these changes radiate throughout the community creating parallel stresses. Family-based, intergenerational models of detection, prevention and treatment services offer enhanced opportunities for effective interventions and suggest very different intervention settings and strategies. However, these models also require addressing the family's basic needs for survival and security in order to be successfully implemented and sustained over time. As HIV was an opportunity for marginalized persons in the developed world to 'turn their life around', the strengths of families in the developing world may be mobilized to contribute to the community's long-term health, survival and security needs.

Community Health Services↗
PubMed2001

Molecular fingerprinting on the SIMD parallel processor Kestrel.

In combinatorial library design and use, the conformation space of molecules can be represented using three-dimensional (3-D) pharmacophores. For large libraries of flexible molecules, the calculation of these 3-D pharmacophoric fingerprints can require examination of trillions of pharmacophores, presenting a significant practical challenge. Here we describe the mapping of this problem to the UCSC Kestrel parallel processor, a single-instruction multiple-data (SIMD) processor. Data parallelism is achieved by simultaneous processing of multiple conformations and by careful representation of the fingerprint structure in the array. The resulting application achieved a 35+ speedup over an SGI 2000 processor on the prototype Kestrel board.

Combinatorial Chemistry Techniques↗
PubMed1998

The Human Genome Project and gene therapy: a genetic counselor's perspective.

The Human Genome Project (HGP) and clinical trials of gene therapy create an expanded role for genetic counselors, nurses, and other health care practitioners. Translating fundamental advances in genetics into a benefit of clinical practice can be challenging. In addition to patients, the public and other professionals, including judges and lawyers, need to be educated about genetics and genetic testing and the potential for genetic intervention. The article provides an overview of the HGP, explains the concept of gene transfer, provides examples of clinical trials for specific diseases, and addresses practical issues related to the role of the coordinator in clinical trials of gene transfer.

Ethics, Nursing↗
PubMed1998

Comparison of methods for retroviral mediated transfer of glucocerebrosidase gene to CD34+ hematopoietic progenitor cells.

Gaucher disease is an excellent candidate for gene therapy by transduction of hematopoitic stem cells. In this study, we compared methods which allow an increase in transfer of the glucocerebrosidase gene to human hematopoietic progenitor cells. Several techniques were employed, including the use of cytokines, bone marrow stroma, fibronectin, centrifugal enhancement and in vitro long-term culture. The effect of prestimulation with cytokines interleukin-3 (IL-3), interleukin-6 (IL-6) and stem cell factor (SCF) on transduction of cord blood CD34+ cells was examined. The results suggest that 16-h prestimulation was sufficient for efficient transduction. We examined the effect of bone marrow stroma and fibronectin, both of which increased transduction efficiency up to 36% and 44%, respectively, as measured by PCR for the integrated GC-cDNA in clonogenic cells (9% without any support). Transduction efficiency of 83% was obtained using 2-h centrifugation. Combining centrifugation and in vitro culture in long-term bone marrow culture media containing cytokines (IL-3/IL-6/SCF), CD34+ cells from cord blood and peripheral blood of 3 Gaucher patients were transduced weekly for 21 d. The results of 6 separate experiments consistently demonstrated transduction efficiency of 100% after 7-d in vitro culture. This transduction protocol combining centrifugation and in vitro long-term culture is an attractive method and can be applied to clinical trials.

Antigens, CD34↗
PubMed1997

A novel complementary deoxyribonucleic acid is abundantly and specifically expressed in the uterus during pregnancy.

OBJECTIVE: Our purpose was to identify novel genes expressed by the uterus during late pregnancy. STUDY DESIGN: A complementary deoxyribonucleic acid library constructed from late pregnancy mouse uterus was screened by differential hybridization with complementary deoxyribonucleic acid probes constructed from late pregnancy mouse uterus and nonpregnant mouse uterus. Radiolabeled complementary deoxyribonucleic acid probes derived from one of the complementary deoxyribonucleic acids isolated were used in northern hybridizations against ribonucleic acid collected from pregnant and nonpregnant uterus and a variety of other mouse tissues. RESULTS: A total of 40 positive clones were isolated; half were identified as cytotoxic T-lymphocyte antigen-2 alpha (a putative inhibitor of the protease cathepsin L) and the other half represented a novel complementary deoxyribonucleic acid. Conceptual translation of the complementary deoxyribonucleic acid predicted a novel protein of 154 amino acids that is proline rich and acidic (pregnancy-specific uterine protein). Northern hybridizations demonstrated that message is abundant in the uterus during late pregnancy. After birth expression rapidly decreased and message was no longer found in the uterus by the third day. A minimal amount of message is present in placental ribonucleic acid, but expression is otherwise not detected in a variety of adult and fetal tissues surveyed, suggesting that expression of this gene is limited to the pregnant uterus. CONCLUSIONS: The abundance of message and expression apparently limited to the pregnant uterus suggests that the protein represented by this complementary deoxyribonucleic acid may play an important role in pregnancy.

Animals↗
PubMed1995

Cytokine mobilization of peripheral blood stem cells in patients with Gaucher disease with a view to gene therapy.

As clinical trials for gene therapy in Gaucher disease (GD) begin, questions regarding the biology of the hematopoietic stem cell in this disease remain unanswered. This study demonstrates the ability to mobilize and collect CD34+ cells in three patients with the disorder. Our RAC/FDA-approved clinical trial utilizes mobilized peripheral blood stem cells (PBSC) as the target cells for gene transfer. In this approach, a white blood cell fraction is collected by apheresis, enriched for CD34+ cells, and transduced with a retroviral vector carrying the glucocerebrosidase (GC) gene. Transduced cells from the patient with activity corrected to at least normal levels will be returned to the patient without myelosuppressive therapy. We report here the effect of cytokines in mobilizing PBSC in three patients with GD. Two (patients 1 and 2) were given granulocyte colony-stimulating factor (G-CSF) at a dose of 5 micrograms/kg/d and one (patient 3) was given 10 micrograms/kg/d for 10 days. Leukaphereses were done daily for 5 days and the products enriched for CD34+ cells using the clinical Ceprate (CellPro) column. The CD34+ cells in all fractions were monitored daily during mobilization and leukaphereses. Subset analysis for the expression of Thy-1, CD38, HLA-DR, and CD33 on the CD34+ cells was performed. An increase in CD34+ cells in the peripheral blood was noted from day 5 onward (up to a six-fold increase). Up to a 625-fold enrichment in CD34+ cells in the apheresis product was noted using the clinical Ceprate column. Totals of 1.2, 3.5, and 2.1 x 10(6) CD34+ cells/kg were collected in the three patients. A diminution in the percent of CD34+/Thy-1+ cells was noted with enrichment. In vitro retroviral transduction of the CD34-enriched cells using centrifugation promoted transduction protocol previously described (Bahnson AB et al., Centrifugal enhancement of retroviral-mediated gene transfer. Journal of Virology Methods 54:131, 1995) and modified for clinical use, demonstrated a mean transduction efficiency of 37% (range 8.3-87.1%) in clonogenic cells and up to 50% in long-term culture-initiating cells (LTC-IC) at week 6. Significantly, we have been able to achieve up to a 50-fold increase in the level of GC above deficient levels in the patients' CD34+ enriched cells when maintained in vitro in culture. The study demonstrates that up to a six-fold increase in CD34+ cells in the PB can be achieved with cytokines in patients with GD. CD34+ cells can be collected in numbers sufficient for conventional transplantation and transduced efficiently in vitro. In gene therapy trials for genetic disorders to date, myelosuppressive therapy is not advocated. The clinical trial will demonstrate whether this number of transduced CD34+ cells will be adequate for competitive engraftment of genetically corrected PBSC.

Adult↗
PubMed1995

Molecular diagnosis of cystic fibrosis.

The clinical and pathologic features of patients with cystic fibrosis are summarized, and generalized genotype or phenotype correlations are discussed in this article. Incorporation of modern molecular biologic techniques into a rapid, cost-efficient, and specific diagnostic laboratory test is outlined. The protocol for the multiplex polymerase chain reaction detection of five common cystic fibrosis transmembrane conductance regulator (CFTR) mutations by ASO hybridization is detailed. Neonatal screening and issues involved in the genetic counseling of families at risk for cystic fibrosis are presented. Recommendations for molecular diagnostic testing in cystic fibrosis are made.

Base Sequence↗
PubMed1995

Enzymatic and molecular diagnosis of Gaucher disease.

Advances in the knowledge of the molecular genetics of Gaucher disease has made diagnosis more certain. Carrier detection in kindreds in which the responsible mutation has been defined is completely reliable now. Coupled with enzymatic assays, the diagnostic capabilities are greater than before. Use of these methods provides important information to individuals at risk and allows them to make critical decisions. The new, simplified methods reviewed in this article permit the molecular diagnosis of the disease and carrier stage of large numbers of samples within 1 week.

Base Sequence↗
PubMed1984

Cancer incidence at a hydrometallurgical nickel refinery.

Sherritt Gordon Mines Limited established hydrometallurgical nickel refining operations at Fort Saskatchewan, Alberta, in 1954. Records of workers with a minimum of one year's employment with Sherritt Gordon Mines were obtained and identification information as well as details of work history were collected and placed on computer. Cancer cases were identified by matching the study records with the computer listings of the Alberta Cancer Registry. Cancer deaths were verified utilizing record-linkage with death registrations of the Alberta Vital Statistics Division. The files of the Alberta Health Care Insurance Commission were used to ascertain the vital status of past employees of Sherritt Gordon Mines Limited. Among the 993 employees in the nickel refining and maintenance groups at Sherritt Gordon Mines, 30 cases of cancer were identified occurring at 13 diagnostic sites. No neoplasms of the nasal cavities or paranasal sinuses were found in the study population. Two cases of lung cancer were detected among maintenance workers. A single case of renal-cell cancer was diagnosed in the nickel-exposure category as well as in the maintenance group. None of the observed-to-expected cancer incidence ratios at the various diagnostic sites were statistically significant at the p less than 0.05 level.

Adult↗
PubMed1979

Computerized tomography in hereditary nonprogressive chorea.

A 56-year-old woman had a 50-year history of childhood-onset chorea without progressive neurologic deficit. The patient's father had a lifelong extrapyramidal disorder characterized by a head-nodding tremor and involuntary movements especially evident with anxiety. The computerized tomographic scan was normal, without evidence of cortical or caudate atrophy. The computerized tomographic scan supports the notion of a functional rather than a structural lesion, and may aid in the discrimination of hereditary nonprogressive chorea from more devastating forms of hereditary chorea.

Adolescent↗