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Jesse L Goodman

Publications and source records attributed to Jesse L Goodman.

8 recordsLinked to original sources
PubMed2006

Anaplasma phagocytophilum causes global induction of antiapoptosis in human neutrophils.

Anaplasma phagocytophilum (Ap), the agent of the tick-borne disease human granulocytic anaplasmosis, is an obligate intracellular pathogen unique in its ability to target and replicate within neutrophils. It profoundly inhibits neutrophil apoptosis, prolonging neutrophil survival from hours to days. To determine the basis of antiapoptosis, we compared gene expression in Ap-infected vs mock-infected human neutrophils. Antiapoptosis genes were consistently and significantly up-regulated (2- to 15-fold) within 1-3 h. These genes synergistically inhibit apoptosis through several interconnected pathways, including p38MAPK (MAP2K3), ERK (IER3), PI3K (PRKCD), and NF-kappaB (BCL2A1, NFKB1, NFKBIA, GADD45B). Both extrinsic death receptor (TNFAIP3, CFLAR, SOD2) and intrinsic mitochondrial (BCL2A1, PIM2, BIRC3) pathways were affected as confirmed by reductions in both caspase 3 and caspase 8 activities. Several important antiapoptotic genes noted to be up-regulated in Ap-infected neutrophils were not up-regulated during Ap infection of HL-60 cells (which is not antiapoptotic). In conclusion, just as apoptosis may be triggered through multiple molecular pathways, effective antiapoptosis of neutrophils is achieved rapidly and redundantly by this intracellular pathogen dependent on cell survival.

Anaplasma phagocytophilum↗
PubMed2006

Quality prediction of cell substrate using gene expression profiling.

Changes in cell culture conditions influence the metabolism of cells, which consequently affects the quality of the products that they produce, such as viral vectors, recombinant proteins, or vaccines. Currently there is no effective technique available to monitor global quality of cells in cell culture. Here we describe a new method using gene expression profiling by microarray to predict the quality of cell substrates. Human embryonic kidney 293 cells are a commonly used cell substrate in the production of biological products. We demonstrate that the yield of adenoviral vectors was lower in over-confluent 293 cells, compared to 40 or 90% confluent cells. Total RNA derived from these cells of different confluence states was reverse transcribed, labeled, and used to hybridize 10K cDNA arrays to determine biomarkers for confluence states. Phenotype scatter-plot analysis and cluster analysis were used for class discovery. Based on this approach, we identified genes that were either up-regulated or down-modulated in response to different cell confluence states. By multivariate predictive models we identified a set of 37 genes that were either down-regulated or up-regulated compared to 90% confluent cells as a predictor of cell confluence and quality of 293 cell cultures. The predictive accuracy of these models was assessed by the leave-one-out cross-validation method. The expression of selected gene predictors was validated by quantitative PCR analysis. Our results demonstrate that gene expression profiling can assess the quality of cell substrates prior to large-scale production of a biological product.

Adenoviridae↗
PubMed2004

Infection of endothelial cells with Anaplasma marginale and A. phagocytophilum.

Anaplasma marginale and A. phagocytophilum are obligate intracellular, tick-borne pathogens that target erythrocytes and neutrophil granulocytes, respectively. Because ticks do not directly tap blood vessels, an intermediate tissue may mediate infection of blood cells. We considered that vascular endothelium interacts with circulating blood cells in vivo, and could be involved in pathogenesis and dissemination of the organisms. We used light and electron microscopy and immune labeling to show that A. phagocytophilum invaded rhesus (RF/6A), human (HMEC-1, MVEC), as well as bovine (BCE C/D-1b) endothelial cell lines, whereas A. marginale infected rhesus and bovine endothelial cells. A. marginale formed large intracellular inclusions that appeared smooth and solid at first, and subsequently coalesced into discrete granules. A. phagocytophilum formed numerous smaller inclusions in each cell. Within 1-3 weeks, the monolayers were destroyed, and lysed cultures were diluted onto fresh monolayers. Electron microscopy demonstrated uneven distribution of A. marginale inside large inclusions, with reticulated forms grouped more tightly than denser cells, whereas in A. phagocytophilum individual organisms appeared more evenly spaced. Specific polyclonal and monoclonal antibodies both labeled A. marginale and A. phagocytophilum in endothelial cells, and oligonucleotide primers complimentary to either A. marginale or A. phagocytophilum amplified their expected target from these cultures. In conclusion, we demonstrate that relevant microvascular endothelium is susceptible to anaplasmas in vitro and may present a link that could explain development of the immune response and persistent infection.

Anaplasma marginale↗
PubMed2003

Transmission of West Nile virus through blood transfusion in the United States in 2002.

BACKGROUND: During the 2002 West Nile virus epidemic in the United States, patients were identified whose West Nile virus illness was temporally associated with the receipt of transfused blood and blood components. METHODS: Patients with laboratory evidence of recent West Nile virus infection within four weeks after receipt of a blood component from a donor with viremia were considered to have a confirmed transfusion-related infection. We interviewed the donors of these components, asking them whether they had had symptoms compatible with the presence of a viral illness before or after their donation; blood specimens retained from the time of donation and collected at follow-up were tested for West Nile virus. RESULTS: Twenty-three patients were confirmed to have acquired West Nile virus through transfused leukoreduced and nonleukoreduced red cells, platelets, or fresh-frozen plasma. Of the 23 recipients, 10 (43 percent) were immunocompromised owing to transplantation or cancer and 8 (35 percent) were at least 70 years of age. Immunocompromised recipients tended to have longer incubation periods than nonimmunocompromised recipients and infected persons in mosquito-borne community outbreaks. Sixteen donors with evidence of viremia at donation were linked to the 23 infected recipients; of these donors, 9 reported viral symptoms before or after donation, 5 were asymptomatic, and 2 were lost to follow-up. Fever, new rash, and painful eyes were independently associated with being an implicated donor with viremia rather than a donor without viremia. All 16 donors were negative for West Nile virus-specific IgM antibody at donation. CONCLUSIONS: Transfused red cells, platelets, and fresh-frozen plasma can transmit West Nile virus. Screening of potential donors with the use of nucleic acid-based assays for West Nile virus may reduce this risk.

Adolescent↗
PubMed2003

Transmission of West Nile virus from an organ donor to four transplant recipients.

BACKGROUND: In August 2002, fever and mental-status changes developed in recipients of organs from a common donor. Transmission of West Nile virus through organ transplantation was suspected. METHODS: We reviewed medical records, conducted interviews, and collected blood and tissue samples for testing with a variety of assays. Persons who donated blood to the organ donor and associated blood components were identified and tested for West Nile virus. RESULTS: We identified West Nile virus infection in the organ donor and in all four organ recipients. Encephalitis developed in three of the organ recipients, and febrile illness developed in one. Three recipients became seropositive for West Nile virus IgM antibody; the fourth recipient had brain tissue that was positive for West Nile virus by isolation and nucleic acid and antigen assays. Serum specimens obtained from the organ donor before and immediately after blood transfusions showed no evidence of West Nile virus; however, serum and plasma samples obtained at the time of organ recovery were positive on viral nucleic acid testing and viral culture. The organ donor had received blood transfusions from 63 donors. A review of blood donors and follow-up testing identified one donor who had viremia at the time of donation and who became seropositive for West Nile virus IgM antibodies during the next two months. CONCLUSIONS: Our investigation of this cluster documents the transmission of West Nile virus by organ transplantation. Organ recipients receiving immunosuppressive drugs may be at high risk for severe disease after West Nile virus infection. Blood transfusion was the probable source of the West Nile virus viremia in the organ donor.

Adult↗
PubMed2003

Bacterial contamination of blood components: risks, strategies, and regulation: joint ASH and AABB educational session in transfusion medicine.

Bacterial contamination of transfusion products, especially platelets, is a longstanding problem that has been partially controlled through modern phlebotomy practices, refrigeration of red cells, freezing of plasma and improved materials for transfusion product collection and storage. Bacterial contamination of platelet products has been acknowledged as the most frequent infectious risk from transfusion occurring in approximately 1 of 2000-3000 whole-blood derived, random donor platelets, and apheresis-derived, single donor platelets. In the US, bacterial contamination is considered the second most common cause of death overall from transfusion (after clerical errors) with mortality rates ranging from 1:20000 to 1:85000 donor exposures. Estimates of severe morbidity and mortality range from 100 to 150 transfused individuals each year. Concern over the magnitude and clinical relevance of this issue culminated in an open letter calling for the "blood collection community to immediately initiate a program for detecting the presence of bacteria in units of platelets." Thereafter, the American Association of Blood Banks (AABB) proposed new standards to help mitigate transfusion of units that were contaminated with bacteria. Adopted with a final implementation date of March 1, 2004, the AABB Standard reads "The blood bank or transfusion service shall have methods to limit and detect bacterial contamination in all platelet components." This Joint ASH and AABB Educational Session reviews the risks, testing strategies, and regulatory approaches regarding bacterial contamination of blood components to aid in preparing practitioners of hematology and transfusion medicine in understanding the background and clinical relevance of this clinically important issue and in considering the approaches currently available for its mitigation, as well as their implementation. In this chapter, Drs. Hillyer and Josephson review the background and significance of bacterial contamination, as well as address the definitions, conceptions and limitations of the terms risk, safe and safety. They then describe current transfusion risks including non-infectious serious hazards of transfusion, and current and emerging viral risks. In the body of the text, Dr. Blajchman reviews the prevalence of bacterial contamination in cellular blood components in detail with current references to a variety of important studies. He then describes the signs and symptoms of transfusion-associated sepsis and the sources of the bacterial contamination for cellular blood products including donor bacteremia, and contamination during whole blood collection and of the collection pack. This is followed by strategies to decrease the transfusion-associated morbidity/mortality risk of contaminated cellular blood products including improving donor skin disinfection, removal of first aliquot of donor blood, pre-transfusion detection of bacteria, reducing recipient exposure, and pathogen reduction/inactivation. In the final sections, Drs. Vostal, Epstein and Goodman describe the regulations and regulatory approaches critical to the appropriate implementation of a bacterial contamination screening and limitation program including their and/or the FDA's input on prevention of bacterial contamination, bacterial proliferation, and detection of bacteria in transfusion products. This is followed by a discussion of sampling strategy for detection of bacteria in a transfusion product, as well as the current approval process for bacterial detection devices, trials recommended under "actual clinical use" conditions, pathogen reduction technologies, and bacterial detection and the extension of platelet storage.

Bacterial Infections↗
PubMed2002

Fluconazole to prevent yeast infections in bone marrow transplantation patients: a randomized trial of high versus reduced dose, and determination of the value of maintenance therapy.

PURPOSE: To determine the optimal dose and duration of fluconazole antifungal prophylaxis therapy in bone marrow transplantation patients. SUBJECTS AND METHODS: Two hundred and fifty-three pediatric and adult bone marrow transplantation patients were randomly assigned to receive fluconazole 400 mg daily (high dose) or 200 mg daily (low dose) while they were neutropenic. After neutrophil recovery, patients were randomly assigned to receive maintenance therapy with either fluconazole (100 mg daily) or clotrimazole troches (10 mg 4 times daily) until 100 days after transplantation. Patients were monitored until 2 weeks after completion of early prophylaxis and to 100 days after transplantation. RESULTS: During the early prophylaxis phase, rates of yeast colonization and infections were similar in both treatment groups. By day 50, the incidence of Candida infections in the high-dose group was 4% (95% confidence interval [CI]: 1% to 7%; n = 5), compared with 1% in the low-dose fluconazole group (95% CI: 0% to 3%; n = 1; P = 0.08). During the same period, the incidence of Aspergillus infections was 4% (95% CI: 1% to 7%; n = 5) in the high-dose group and 2% (95% CI: 0% to 4%; n = 2; P = 0.33) in the low-dose group. During the maintenance prophylaxis phase, rates of yeast colonization and superficial infections were similar in the fluconazole and clotrimazole groups. Four patients developed systemic fungal infection in the maintenance phase (1 who received clotrimazole and 3 who received fluconazole). CONCLUSION: High-dose (400 mg daily) and low-dose (200 mg daily) fluconazole have similar efficacy in reducing the incidence of yeast colonization, superficial infection, and systemic infection in neutropenic pediatric and adult patients undergoing bone marrow transplantation. Rates of yeast colonization after neutrophil recovery were similar in patients treated with fluconazole or clotrimazole.

Adolescent↗