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Biomedical subjects

S Russell

Publications and source records attributed to S Russell.

At least 73 records · Page 4Linked to original sources
PubMed1996

Blood island formation in attached cultures of murine embryonic stem cells.

Differentiation of murine embryonic stem cells in suspension culture results in the formation of cystic embryoid bodies that develop blood islands. In this study pre-cystic embryoid bodies were attached to a substratum, and the program of differentiation was monitored. The attached ES cell cultures formed blood islands on a cell layer that migrated out from the center of attachment and beneath a mesothelial-like cell layer. Morphological and in situ marker analysis showed benzidine-positive hematopoietic cells surrounded by vascular endothelial cells that expressed PECAM and took up DiI-Ac-LDL. Waves of morphological differentiation were evident, suggesting a graded response to differentiation signals. Electron microscopy of the blood islands showed that they were similar to blood islands of cystic embryoid bodies and mouse yolk sacs, and cell-cell junctions were evident among the blood island cells. RNA expression analysis was consistent with the presence of hematopoietic precursor cells of several lineages and a primitive vascular endothelium in the cultures. Thus a program of vascular and hematopoietic development can be elaborated in attached ES cell cultures, and these blood islands are accessible to experimental manipulation.

Animals↗
PubMed1996

Ability to pay for health care: concepts and evidence.

In many developing countries people are expected to contribute to the cost of health care from their own pockets. As a result, people's ability to pay (ATP) for health care, or the affordability of health care, has become a critical policy issue in developing countries, and a particularly urgent issue where households face combined user fee burdens from various essential service sectors such as health, education and water. Research and policy debates have focused on willingness to pay (WTP) for essential services, and have tended to assume that WTP is synonymous with ATP. This paper questions this assumption, and suggests that WTP may not reflect ATP. Households may persist in paying for care, but to mobilize resources they may sacrifice other basic needs such as food and education, with serious consequences for the household or individuals within it. The opportunity costs of payment make the payment 'unaffordable' because other basic needs are sacrificed. An approach to ATP founded on basic needs and the opportunity costs of payment strategies (including non-utilization) is therefore proposed. From the few studies available, common household responses to payment difficulties are identified, ranging from borrowing to more serious 'distress sales' of productive assets (e.g. land), delays to treatment and, ultimately, abandonment of treatment. Although these strategies may have a devastating impact on livelihoods and health, few studies have investigated them in any detail. In-depth longitudinal household studies are proposed to develop understanding of ATP and to inform policy initiative which might contribute to more affordable health care.

Africa↗
PubMed1996

Targeted infection of human cells via major histocompatibility complex class I molecules by Moloney murine leukemia virus-derived viruses displaying single-chain antibody fragment-envelope fusion proteins.

As an approach to cell targeting by retroviruses, the lack of which constitutes one major limitation of retroviral vector technology, we engineered the Moloney murine leukemia virus ecotropic envelope glycoprotein. When inserted between amino acids 6 and 7 of the latter, a single-chain antibody fragment (ScFv) specific for human major histocompatibility complex class I molecules was shown to be able to redefine the tropism of ecotropic Moloney murine leukemia virus-derived retroviral particles by allowing infection of major histocompatibility complex class I-positive human cells. At variance with other recently described experimental systems, the type of modification adopted here allowed targeted infection in the absence of coexpressed wild-type env-encoded protein molecules. Interestingly, the chimeric ScFv-env protein also retained the ability to recognize the ecotropic receptor and allowed infection of murine cells, albeit at a reduced efficiency.

3T3 Cells↗
PubMed1996

A novel packaging system for the generation of helper-free oncolytic MVM vector stocks.

MVM-based autonomous parvoviral vectors have been shown to target the expression of heterologous genes in neoplastic cells and are therefore of interest for cancer gene therapy. The traditional method for production of parvoviral vectors requires the cotransfection of vector and helper plasmids into MVM-permissive cell lines, but recombination between the cotransfected plasmids invariably gives rise to vector stocks that are heavily contaminated with wild-type MVM. Therefore, to minimise recombination between the vector and helper genomes we have utilised a cell line in which the MVM helper functions are expressed inducibly from a modified MVM genome that is stably integrated into the host cell chromosome. Using this MVM packaging cell line, we could reproducibly generate MVM vector stocks that contained no detectable helper virus.

Animals↗
PubMed1996

Controlling elements of platelet glycoprotein Ib alpha expression.

Our objectives are to define and characterize molecular events of megakaryocytopoiesis and platelet production by analyzing the in vivo expression of platelet glycoprotein (GP) receptors. Our studies target the platelet GP Ib-IX-V complex since the congenital absence of the receptor results in the Bernard-Soulier syndrome, a condition linking the expression of the complex to normal platelet morphogenesis. We have previously described the generation of a transgenic mouse colony expressing the alpha-subunit (GP Ib alpha) of the human platelet GP Ib-IX-V complex. These studies established methodologies to manipulate GP Ib-IX-V on the platelet surface and examine unique aspects of hemostasis, megakaryocytopoiesis, platelet structure and platelet release. Our recent studies have defined the genetic elements supporting the megakaryocytic-expression of GP Ib alpha. These results are defining essential cis-acting elements responsible for the expression of GP Ib alpha and are providing insights into molecular events coinciding with the release of normal platelets into the bloodstream.

Animals↗
PubMed1995

Management of mitochondrial disease on an intensive care unit.

Patients with mitochondrial disease may present to the Intensive Care Unit (ICU) with a variety of neurological and general medical disorders. Eleven patients were admitted to a neurological ICU between 1970 and 1992 because of respiratory insufficiency, status epilepticus and/or metabolic encephalopathy associated with mitochondrial disease. Respiratory impairment occurred in eight patients and was associated with nocturnal hypoventilation due to respiratory muscle weakness, aspiration due to bulbar weakness and abnormalities of central control leading to a reduced CO2 drive, irregular respiratory patterns and sleep apnoea. Seven patients received continuous respiratory support during the acute illness; three were subsequently weaned to domiciliary ventilation, and four died. Five patients had stroke-like episodes, which in two were recurrent. Four patients developed tonic-clonic grand mal epilepsy associated with myoclonic fits (2 patients), absences (2), focal fits (1) and status epilepticus (2). Encephalopathy was associated with recurrent lactic acidosis (2 patients), cardiac failure (2), hyponatraemia (2), renal abnormalities (3) and complete heart block (1). Although rare, mitochondrial disease should be considered in any patient with unexplained respiratory failure, intractable epilepsy, lactic acidosis or recurrent stroke.

Acidosis, Lactic↗
PubMed1994

Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection.

Live proliferation-competent and irradiated proliferation-incompetent L5178 murine lymphoma cells (Eb cell line) were compared for their potency to induce systemic anti-tumor immunity in syngeneic DBA/2 mice. The tumorigenic potential in vivo of live Eb cells was suppressed through local secretion of interleukin 4 (IL4) or alternatively by injection of parental cells at a site refractory to tumor growth. Inoculation of nontumorigenic doses of live Eb or Eb-IL4 cells led to long-lasting specific and systemic T-cell-mediated antitumor response requiring both CD4+ and CD8+ T lymphocytes. Irradiated cells offered only limited short-term protection, which could be marginally improved by IL4. The more effective protection offered by vaccination with live tumor cells correlated with rapid migration and persistence of tumor cells in the bone marrow of host animals after tumor cell inoculation. In contrast, irradiated Eb-lacZ cells had a short persistence. Tumor cells recovered from the bone marrow of host animals injected with live Eb-IL4 cells still expressed IL4. These observations indicate that in the course of vaccination with live Eb or Eb-IL4 cells, a fraction of these cells escaped destruction by host mechanisms and persisted in a dormant state in the bone marrow for long periods of time. Persistence of dormant tumor in the bone marrow correlated with the duration of anti-tumor immunity.

Animals↗
PubMed1994

Full-time attending physician coverage in a pediatric emergency department. Effect on risk management.

OBJECTIVE: To determine the effect on risk management of full-time attending physician coverage in a pediatric emergency department. DESIGN: Retrospective, with data collected through a review of malpractice cases from August 1, 1984 through July 31, 1990. SETTING: Large urban teaching hospital's pediatric emergency department. RESULTS: Malpractice cases from August 1, 1984 to July 31, 1987, when there was part-time attending physician coverage, were compared with those of 1987 through 1990, when full-time attending physician coverage was instituted. Medical records from the pediatric emergency department, subsequent hospital records, and abstracts of claims were reviewed. Disbursements and the types of lawsuits were also analyzed. There was a 41.7% decrease in the number of claims filed and a 44.3% reduction in payments with full-time coverage. CONCLUSIONS: Full-time attending physician coverage in a pediatric emergency department was associated with a decrease in the number of malpractice claims and the amounts of disbursements. Further research in this area on a larger study sample is advisable.

Adolescent↗
PubMed1994

Abdominal adhesions in laparoscopic hernia repair. An experimental study.

Laparoscopic herniorrhaphy is becoming an increasingly common procedure. The possible creation of intraperitoneal adhesions during laparoscopic herniorrhaphy has not been examined. For the transperitoneal hernia repair to be an acceptable option, the hypothesis that this approach will incite significant adhesions must be rejected. To test this hypothesis, 21 pigs underwent laparoscopic herniorrhaphy using a standard procedure with the implantation of a polypropylene mesh graft on one side while a sham procedure was performed on the other. These animals were later examined laparoscopically for adhesion formation and the condition of the graft. None of the 21 animals developed adhesions to the trocar sites, 12 animals developed adhesions to the area of the polypropylene mesh, and 3 developed adhesions to the side of the sham procedure. There were no adhesions involving the small intestine. It is therefore concluded that the hypothesis should be rejected and that laparoscopic herniorrhaphy does not incite significant adhesions.

Abdomen↗
PubMed1994

Efficacy of 2'-deoxy-2'-fluororibosides against influenza A and B viruses in ferrets.

Single-dose treatments (5 to 40 mg/kg of body weight given intraperitoneally) of ferrets with 2'-deoxy-2'-fluoroguanosine or its prodrug, 2,6-diamino-purine-2'-fluororiboside, 1 h after infection with influenza A virus significantly inhibited replication of virus in the upper respiratory tract, resulting in amelioration of fever and nasal inflammation. Replication of virus in the lower respiratory tract was also reduced > 100-fold, but three doses were required to prevent replication in the lungs. In ferrets infected with influenza B virus, single-dose treatment (40 mg/kg given intraperitoneally) produced a similar but reduced response in comparison with that in ferrets infected with influenza A virus, indicating that dosing was not optimal for this virus.

Adenosine↗
PubMed1994

Discrimination between alternatively spliced STP-A and -B isoforms of CD46.

CD46 (membrane cofactor protein; MCP) is ubiquitously expressed on nucleated human cells; it has a protective function, binding C3b and C4b, which are then cleaved by serum factor I. CD46 molecules (55,000-65,000 MW) have four short consensus repeats (SCR): the function of SCR-1 and -2 is unknown; SCR-3 and -4 bind C3b and C4b. These are succeeded by the STP region, which can contain three separate regions (STP-A, -B, -C) rich in serine, threonine and proline and which are heavily glycosylated, succeeded by transmembrane and cytoplasmic tail regions (of which there are several). Multiple isoforms exist due to the different splicing of exons: STP-A and -B can thus be present or absent. So far these products can only be detected separately by polymerase chain reaction (PCR) and RNA studies; we now describe their detection by anti-peptide antibodies. Peptides whose sequences corresponded with those of STP-A and STP-B were synthesized and used for the immunization of mice; although they differ in only seven of 21 amino acids, monoclonal antibodies (mAb) that reacted specifically with STP-A but not with STP-B, and mAb that reacted specifically with STP-B but not with STP-A, were produced; these reacted specifically with native CD46 on human tissues and cell lines. STP-A mAb reacted with tissues in which STP-A RNA had been found, some leukaemias and cell lines; in normal tissue expression was mainly found in the intestine (large and small) and salivary gland. Anti-STP-B reacted with most tissues and cell lines. The antibodies should be of use in defining the expression and function of CD46 in different tissues.

Acetylgalactosamine↗