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Biomedical subjects

J Alexander

Publications and source records attributed to J Alexander.

At least 19 recordsLinked to original sources
PubMed1992

[Cancer in Pasvik. II. Pollution from Nikel--no relationship after all?].

Previous medical investigations have indicated a connection between heavy metal pollution from the metallurgical industry in the Russian town of Nikel on the Kola peninsula and an observed increase of incidence of cancer among the Norwegian population living near the Russian border. This report contains the latest measurements of heavy metals in the local environment and discusses exposure levels in relation to possible health effects. It is concluded that exposure to heavy metals via food, water and air is considered so low as to be unlikely to cause any increase in incidence of cancer. Thus, the previously held hypothesis of a connection between heavy metal pollution from Nikel and cancer in Pasvik is not confirmed.

Adult↗
PubMed1992

Role of endogenous peptides in murine allogenic cytotoxic T cell responses assessed using transfectants of the antigen-processing mutant 174xCEM.T2.

One model to explain the high frequency of alloreactive T cells proposes that allogeneic MHC molecules are recognized together with host cell-derived peptides. A model system was developed to investigate the relevance of this mechanism by expression of H-2Dd or H-2Ld in 174xCEM.T2 (T2) cells. This human cell line contains a mutation in its Ag-processing pathway that should restrict the association of endogenous peptides with cell surface class I molecules. CTL generated by stimulating C57BL/6 (H-2b) responder cells with H-2Dd or H-2Ld transfectants of the human B cell line C1R or the murine T cell lymphoma EL4 were assayed for their ability to recognize alloantigenic determinants on these transfectants. The major fraction of the H-2Dd-specific allogeneic CTL response, generated in a MLC or under clonal limiting dilution conditions, was composed of T cells that recognized H-2Dd expressed on C1R or EL4 cells, but failed to recognize this molecule on T2 cells. Clonal analysis indicated that approximately one-third of these CTL recognized determinants that were unique to H-2Dd expressed on C1R stimulator cells whereas the remainder recognized determinants that were also found on EL4 transfectants. Less than 10% of H-2Dd-reactive CTL recognized the T2 transfectant, and these clones also killed C1R-Dd and EL4-Dd. This result suggests that the great majority of H-2Dd-specific alloreactive CTL recognize determinants that are formed by a complex of H-2Dd with endogenous peptides that are absent or significantly reduced in T2 cells. Based on recognition of human or murine transfectants, these CTL exhibit some level of specificity for the structure or composition of the bound peptides. Examination of allogeneic CTL specific for H-2Ld revealed populations similar to those described for H-2Dd. In addition, a major new population was present that recognized determinants shared between C1R-Ld and T2-Ld but not present on EL4-Ld. These results are consistent with the idea that the alloreactive response to H-2Ld is also largely dependent on the presence of bound peptide. However, they also may indicate that the H-2Ld molecule expressed on T2 cells is occupied by one or more peptides that are shared with other human, but not murine, cells. The significance of these results to current models of alloreactivity is discussed.

Animals↗
PubMed1992

Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor.

A novel mechanism for inhibition of T cell responses is described. Using the recognition of the influenza hemagglutinin (HA) 307-319 peptide in the context of DR1 class II major histocompatibility complex molecules, we have found that nonstimulatory analogs of the HA peptide preferentially inhibit HA-specific T cells in inhibition of antigen presentation assays. This antigen-specific effect could be generalized to another DR1-restricted peptide, Tetanus toxoid 830-843. Direct binding and cellular experiments indicated that the mechanism responsible was distinct from competition for binding to DR1 molecules. Likewise, negative signaling and induction of T cell tolerance could also be excluded as effector mechanisms. Thus, the most likely mechanism for this effect is engagement of antigen-specific T cell receptors by DR1-peptide analog complexes, which results in antigen-specific competitive blocking of T cell responses by virtue of their capacity to compete with DR1-antigen complexes for binding to the T cell receptor.

Adjuvants, Immunologic↗
PubMed1992

Clinicopathologic correlation of occult choroidal neovascularization in age-related macular degeneration.

We report the clinicopathologic features of an eye with occult choroidal neovascularization associated with age-related macular degeneration. Ophthalmoscopic findings at presentation included subretinal fluid and lipid. We noted angiographic staining of irregularly elevated areas of retinal pigment epithelium. In the late phase of the angiogram, fluorescein leakage at the level of the outer retina was observed that did not correspond to well-demarcated areas of hyperfluorescence in earlier phases. The patient was randomized to treatment in a pilot trial comparing the effects of grid laser treatment with the effects of no treatment for occult choroidal neovascularization. Three weeks after treatment, some of the subretinal fluid had cleared and vision improved. The patient died 6 weeks after laser treatment. Histopathologic study disclosed a subretinal pigment epithelial fibrovascular membrane. Neovascularization originated from the choroid.

Aged↗
PubMed1992

Pancreaticoduodenectomy without homologous blood transfusion in an anemic Jehovah's Witness.

Whipple pancreaticoduodenectomy is an accepted procedure for management of periampullary and pancreatic carcinomas and has modern mortality rates of less than 10%. The procedure is associated with significant operative blood loss. Therefore, blood transfusion is an important supportive measure. We report the case of a bleeding ampullary carcinoma in a Jehovah's Witness who refused transfusion of all homologous blood products. Despite a preoperative hemoglobin level of 51 g/L, curative pancreaticoduodenectomy was successfully performed. The success of the procedure can be primarily attributed to careful surgical technique, intraoperative autotransfusion, avoidance of postoperative complications, minimization of perioperative phlebotomies, use of human recombinant erythropoietin, and, possibly, the use of the perfluorocarbon emulsion Fluosol DA-20%. The case illustrates several important principles for the surgical treatment of patients with severe anemia who refuse transfusion of homologous blood products.

Adult↗
PubMed1992

Kinetics of cytokine mRNA production in the brains of mice with progressive toxoplasmic encephalitis.

C57BL/10 ScSn (B10) mice infected orally with Toxoplasma gondii were killed on days 5, 10, 15, 20 and 30 post infection and their brains excised. These were either used to count total tissue cyst numbers or divided for RNA purification and histopathological studies. The first signs of inflammation were on day 10 post infection, before the appearance of cysts in the brain, and correlating with the appearance of activated astrocytes. These mice had a mild meningitis with areas of encephalitis. Small numbers of cyst stages were first observed in the brain on day 15 and by day 20 the cyst numbers had increased dramatically but were not always associated with inflammation. After this time point, total cyst numbers did not increase significantly though there developed a marked variation in tissue cyst size with larger cysts becoming more numerous. The use of the polymerase chain reaction to assist in the amplification of brain RNA allowed the characterization of the kinetics of cytokine production within the brains of these animals. Only IL-1 alpha was found to be expressed constitutively in control mice. Transcripts for other cytokines associated with activated monocytes, microglial cells and astrocytes [tumor necrosis factor (TNF)-alpha and interleukin (IL)-6] were present on day 10, (IL-6) and day 15 (TNF-alpha) post infection. Thereafter, these cytokines were present in all infected animals. Of the T cell-associated cytokines, IL-4, a characteristic product of the T helper (Th)2 cell subset, was detected on days 10 and 15, while granulocyte macrophage colony stimulating factor (GM-CSF) which can be produced not only by this cell type but also by Th1 cells and CD8+ T cells, was also present on day 15 but not thereafter. Transcripts for interferon (IFN)-gamma, present from day 15 post infection, were probably produced by CD8+ T cells, as IL-2 which would indicate Th1 cell involvement was only detected 30 days after infection. The continual presence of IFN-gamma and TNF-alpha, cytokines with reported anti-toxoplasmic activity, in the CNS of B10 mice throughout the latter half of the experimental period did not diminish the severity of infection. These results indicate that the CD4+ Th2 subset may allow a rapid rise in cyst numbers and so be important in determining susceptibility to toxoplasmic encephalitis.

Animals↗
PubMed1992

Typing and screening of blood from intraosseous access.

STUDY OBJECTIVE: To determine if intramedullary aspirate from intraosseous needle placement can be used as a source for evaluating blood compatibility. DESIGN: A prospective, nonrandomized, crossover study. SETTING/PARTICIPANTS: Patients admitted to the hematology/oncology service undergoing bone marrow aspiration for medical purposes. INTERVENTIONS: Patients had simultaneous samples of bone marrow aspiration from the posterior iliac crest and peripheral venous blood drawn and sent for typing and screening. MEASUREMENTS AND MAIN RESULTS: The paired samples were evaluated for ABO and Rh typing as well as the presence of human leukocyte activity by evaluating the reaction strength between the marrow and venous samples. RESULTS: No differences were seen in the reaction strength between the paired samples in any subjects for ABO and Rh typing (P = .90, yielding beta = .0523). In addition, human leukocyte activity was detected in both the marrow and venous samples in one patient. CONCLUSION: Bone marrow aspirates following intraosseous infusion can be used for accurate and reliable typing and screening of blood.

ABO Blood-Group System↗
PubMed1992

Studies on a murine model of congenital toxoplasmosis: vertical disease transmission only occurs in BALB/c mice infected for the first time during pregnancy.

The incidence of congenital toxoplasmosis was determined by an ELISA in the litters of BALB/c mice which had been infected 8 weeks before mating, on day 12 of pregnancy, or on both these occasions. Of those mice given the infection for the first time on day 12 of pregnancy, 5 out of 6 gave birth to infected litters with approximately 50% of the individuals in each litter being infected. BALB/c mice which had been infected 8 weeks before mating did not give birth to infected litters, even if they were reinfected on day 12 of pregnancy. Following infection BALB/c mice were found to harbour significantly fewer tissue cysts than the congenic H-2 derivative BALB/K strain. However, chronically infected BALB/K mice also failed to produce infected litters, indicating that tissue cyst burden in the dam did not influence congenital infection at least on the BALB background. This study demonstrates that BALB/c dams chronically infected with Toxoplasma gondii, have immunity capable of protecting their embryos from congenital infection, even if the dams are reinfected during pregnancy. Our results demonstrate that the BALB/c mouse can be used as a model of human or ovine congenital T. gondii infection suitable for testing putative vaccines.

Animals↗
PubMed1992

Serological responses and immunity produced in salmonids by vaccination with Australian strains of Vibrio anguillarum.

The Australian populations of rainbow trout (Onchorhynchus mykiss) and Atlantic salmon (Salmo salar) were found to have similar immunological responses to local strains of Vibrio anguillarum as those reported for the more genetically diverse populations of these fish and strains of V. anguillarum found in the Northern Hemisphere. In addition, our studies more precisely defined the respective responses of rainbow trout and Atlantic salmon to immersion vaccination by the bath and dip methods.

Animals↗
PubMed1992

Hospital board effectiveness: relationships between board training and hospital financial viability.

This study examined whether hospital governing boards that invest in board education and training are more informed and effective decision-making bodies. Measures of hospital financial viability (i.e., selected financial ratios and outcomes) are used as indicators of hospital board effectiveness. Board participation in educational programs was significantly associated with improved profitability, liquidity, and occupancy levels, suggesting that investment in the education of directors is likely to enhance hospital viability and thus increase board effectiveness.

Bed Occupancy↗
PubMed1992

Continuous pulse oximetry and the diagnosis of pulmonary embolism in critically ill trauma patients.

The diagnosis of pulmonary embolism (PE) may be difficult to establish in trauma patients, particularly those who are unresponsive or mechanically ventilated. Based on a prior retrospective study, we hypothesized that patients monitored by continuous pulse oximetry who experienced a 10% or greater sudden sustained drop in arterial oxygen saturation (SaO2) without a change in static lung compliance (Cst) were most likely to have had a PE. We followed SaO2 in 972 patients admitted to our trauma ICU during the 18-month period ending in December 1990. Forty-eight patients (5%) with SaO2 changes, but no Cst changes, were evaluated for suspected PE using pulmonary arteriography (PA). Of these, 21 (44%) had a positive PA study. All patients with a positive PA had either clear chest roentgenograms or no change in underlying pulmonary pathologic processes. Of the remainder, 26 had evidence of a new pathologic entity on chest roentgenograms and only one patient had a SaO2 decrease, no change in Cst, and a negative PA. All mechanically ventilated trauma patients should have SaO2 monitored continuously. Patients with a > 10% drop in Sao2 with no change in Cst and no new roentgenographic chest findings should undergo PA. Based on our experience, this approach would yield a sensitivity, specificity, and predictive value of 100%, 99.9%, and 95%, respectively, for the diagnosis of clinically significant PE.

Adolescent↗
PubMed1992

Cytokine control of Leishmania infection in the BALB/c mouse: enhancement and inhibition of parasite growth by local administration of IL-2 or IL-4 is species and time dependent.

The therapeutic potential of locally injected interleukin-2 (IL-2) or interleukin-4 (IL-4) was studied in the footpads of Leishmania mexicana or Leishmania major infected BALB/c mice. The disease state was measured both pathologically, by measuring lesion size, and parasitologically, by counting total parasite numbers from infected footpads. IL-2 (0.5 microgram/dose) or IL-4 (0.1 microgram/dose) was administered either early, 1 day and/or 15 days after infection, or late, after palpable lesions had developed. Results differed markedly depending on which Leishmania species was used and at what time during the course of disease that therapy commenced. Both L. major and L. mexicana infections, as measured by footpad thickness and parasite number, were exacerbated if IL-4 was injected into the infected footpads early, during the first two weeks of infection. Paradoxically, late intralesional injection (i.e. after measurable lesions had developed) of IL-4 markedly inhibited both lesion size and parasite growth in L. major, though not L. mexicana, infected mice. IL-2 had no measurable effect on the course of L. major infections no matter when or how often, the infected footpads of mice were treated. However, early administration of IL-2 did exacerbate L. mexicana lesion and parasite growth while late treatment had no effect. Generally, but not always, increases in footpad size correlated with increases in parasite number.

Animals↗
PubMed1992

Detection of cytokine mRNA in the brains of mice with toxoplasmic encephalitis.

C57Bl/10 ScSn mice infected with Toxoplasma gondii developed a meningoencephalitis, characterized by areas of tissue destruction and cellular infiltration including foci of neutrophils. Large numbers of cyst stages were found throughout the brain but were not always associated with inflammation. The use of immunocytochemistry to detect glial fibrillary acidic protein, an astrocyte specific marker, showed a widespread astrocyte activation. This was particularly prominent in areas of intense inflammation but cysts were negative for glial fibrillary acidic protein, indicating that astrocytes were not host cells for the bradyzoites. The use of the polymerase chain reaction to assist in the amplification of total brain RNA allowed the characterization of the cytokines being produced locally within the brains of infected animals. beta-actin transcripts were detected in all of the uninfected and infected mice. In only one of the seven uninfected control mice were other transcripts found. Transcripts for tumour necrosis factor-alpha, interleukin-1 alpha and beta, interleukin-6, macrophage inflammatory protein-1 and interferon-gamma as well as the CD4 marker were detected in all of the infected mice. However, transcripts for IL-2 and IL-4 were not present. Several of the cytokines present are capable of initiating meningeal inflammation and may play a role in the immunopathogenesis of toxoplasmic encephalitis.

Animals↗