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Biomedical subjects

W E Jackson

Publications and source records attributed to W E Jackson.

At least 19 recordsLinked to original sources
PubMed2005

Clindamycin and quinolone therapy for Bacillus anthracis Sterne infection in 60Co-gamma-photon-irradiated and sham-irradiated mice.

OBJECTIVES: Sublethal ionizing doses of radiation increase the susceptibility of mice to Bacillus anthracis Sterne infection. In this study, we investigated the efficacy of clindamycin in 60Co-gamma-photon-irradiated and sham-irradiated mice after intratracheal challenge with B. anthracis Sterne spores. Clindamycin has in vitro activity against B. anthracis and inhibits the production of toxin from other species, although no direct evidence exists that production of B. anthracis toxin is inhibited. METHODS: Ten-week-old B6D2F1/J female mice were either sham-irradiated or given a sublethal 7 Gy dose of 60Co-gamma-photon radiation 4 days prior to an intratracheal challenge with toxigenic B. anthracis Sterne spores. Mice were treated twice daily with 200 mg/kg clindamycin (subcutaneous or oral), 100 mg/kg moxifloxacin (oral), 50 mg/kg ciprofloxacin (subcutaneous) or a combination therapy (clindamycin + ciprofloxacin). Bacteria were isolated and identified from lung, liver and heart blood at five timed intervals after irradiation. Survival was recorded twice daily following intratracheal challenge. RESULTS: The use of clindamycin increased survival in gamma-irradiated and sham-irradiated animals challenged with B. anthracis Sterne in comparison with control mice (P < 0.001). Ciprofloxacin-treated animals had higher survival compared with clindamycin-treated animals in two experiments, and less survival in a third experiment, although differences were not statistically significant. Moxifloxacin was just as effective as clindamycin. Combination therapy did not improve survival of sham-irradiated animals and significantly decreased survival among gamma-irradiated animals (P = 0.01) in comparison with clindamycin-treated animals. B. anthracis Sterne was isolated from lung, liver and heart blood, irrespective of the antimicrobial treatment. CONCLUSIONS: Treatment with clindamycin, ciprofloxacin or moxifloxacin increased survival in sham-irradiated and gamma-irradiated animals challenged intratracheally with B. anthracis Sterne spores. However, the combination of clindamycin and ciprofloxacin increased mortality associated with B. anthracis Sterne infection, particularly in gamma-irradiated animals.

Administration, Oral↗
PubMed2002

Hematopoietic responses under protracted exposures to low daily dose gamma irradiation.

In attempting to evaluate the possible health consequences of chronic ionizing radiation exposure during extended space travel (e.g., Mars Mission), ground-based experimental studies of the clinical and pathological responses of canines under low daily doses of 60Co gamma irradiation (0.3-26.3 cGy d-1) have been examined. Specific reference was given to responses of the blood forming system. Results suggest that the daily dose rate of 7.5 cGy d-1 represents a threshold below which the hematopoietic system can retain either partial or full trilineal cell-producing capacity (erythropoiesis, myelopoiesis, and megakaryopoiesis) for extended periods of exposure (>1 yr). Trilineal capacity was fully retained for several years of exposure at the lowest dose-rate tested (0.3 cGy d-1) but was completely lost within several hundred days at the highest dose-rate (26.3 cGy d-1). Retention of hematopoietic capacity under chronic exposure has been demonstrated to be mediated by hematopoietic progenitors with acquired radioresistance and repair functions, altered cytogenetics, and cell-cycle characteristics. Radiological, biological, and temporal parameters responsible for these vital acquisitions by hematopoietic progenitors have been partially characterized. These parameters, along with threshold responses, are described and discussed in relation to potential health risks of the space traveler under chronic stress of low-dose irradiation.

Animals↗
PubMed2001

In vivo radioprotection by 5-androstenediol: stimulation of the innate immune system.

We showed previously that 5-androstenediol stimulates myelopoiesis, increases the numbers of circulating neutrophils and platelets, and enhances resistance to infection in gamma-irradiated mice. We have extended those studies to include monocytes, natural killer (NK) cells, eosinophils and basophils, and we have measured the activation marker CD11b using flow cytometry. Androstenediol (160 mg/kg) was administered subcutaneously to female B6D2F1 mice 24 h before whole-body gamma irradiation. Androstenediol treatments increased the blood levels of neutrophils, monocytes and NK cells in unirradiated animals; decreased the numbers of circulating eosinophils; and ameliorated radiation-induced decreases in neutrophils, monocytes, NK cells, erythrocytes and platelets. The androstenediol treatments had no significant effect on the numbers of circulating B cells or T cells. CD11b labeling intensity on monocytes was decreased slightly after androstenediol treatment. In contrast, radiation or androstenediol alone caused increases in CD11b labeling intensity on NK cells. Androstenediol and radiation combined caused a marked increase in NK cell CD11b. The results indicate that androstenediol increases the numbers of the three major cell types of the innate immune system (neutrophils, monocytes and NK cells), that androstenediol-induced changes in blood elements in irradiated animals persist for at least several weeks, and that there is a significant positive interaction between radiation and administration of androstenediol in the activation of NK cells.

Androstenediol↗
PubMed2001

Biodosimety Assessment Tool: a post-exposure software application for management of radiation accidents.

The Biodosimetry Assessment Tool software application under development will equip health care providers with diagnostic information (clinical signs and symptoms, physical dosimetry, etc.) germane to the management of human radiation casualties. Designed primarily for prompt use after a radiation incident, the user-friendly program facilitates collection, integration, and archiving of data obtained from exposed persons. Data collected in templates are compared with established radiation dose responses obtained from the literature to provide multiparameter dose assessments. The program archives clinical information (e.g., extent of contamination, wounds, infection, etc.) useful for casualty management, displays relevant diagnostic information in a concise format, and can be used to manage both military and civilian radiation accidents. In addition, monitoring of diagnostic information of individuals using this program could potentially minimize the severity of psychological casualties by making a marked impact on the way that both radiation casualties and the worried well view their exposure, dose, and future risk for the development of disease.

Humans↗
PubMed2001

Combined effects of Venezuelan equine encephalitis IIIA virus and gamma irradiation in mice.

The combined effects of injury from exposure to ionizing radiation and the potential biological warfare agent Venezuelan equine encephalitis (VEE) virus remain largely unknown. To study these effects, 4- to 5-week-old B6D2F1/J female mice were given a sublethal whole-body 7 Gy dose of 60Co gamma-photon radiation followed 48 hours later by aerosol or intraperitoneal challenge with enzootic VEE IIIA virus. Survival was observed for 30 days. A single sublethal 7 Gy dose of gamma radiation reduced the LD50/30 of VEE IIIA virus, in intraperitoneal challenged mice by a factor of 10(4) from 1.1 x 10(6) plaque-forming units (pfu) to 1 x 10(2) pfu, and in aerosol challenged mice, by a factor of 5 from 70 pfu to 14 pfu. These findings further confirm there is a combined effect of exposure to ionizing radiation and biological warfare agents, which could be devastating to unprotected populations and thus should be investigated further.

Animals↗
PubMed2000

WR-151327 increases resistance to Klebsiella pneumoniae infection in mixed-field- and gamma-photon-irradiated mice.

PURPOSE: To determine the efficacy of WR-151327 (WR) [S-3-(3-methylaminopropylamino) propylphosphorothioic acid; (CH3-HN-(CH2)3-NH-(CH2)3-S-PO3H2)] in increasing resistance to bacterial infection after a sublethal dose of gamma-photons or mixed-field neutrons plus gamma-photons. MATERIALS AND METHODS: B6D2F1/J female mice received 200 mg/kg WR i.p. or saline vehicle 20-30 min before or after sham (0 Gy) or 7.0 Gy 60Co gamma-photon irradiation. WR or saline vehicle was given only before 3.5 Gy TRIGA-reactor-produced mixed-field [n/(n+y) = 0.67] irradiation. Four days after drug treatment or drug treatment and irradiation, graded doses of Klebsiella pneumoniae were injected s.c. into mice, and 30-day survival was recorded. To assess haemopoietic changes other unirradiated and irradiated mice not injected with bacteria were given WR or saline. Peripheral blood (PB) and femoral bone marrow (BM) cells were measured 1, 3 or 4, 7, 10 and 14 or 15 days later. RESULTS: WR pretreatment increased resistance to infection in irradiated but not in unirradiated mice. Bacterial CFU-LD50/30 values for 0 Gy saline-treated mice were 1.20x10(6); for 0 Gy WR-treated mice 1.16x10(6); for gamma-photon-irradiated saline-treated mice 3.02x10(1); for gamma-photon-irradiated WR-treated mice 1.24x10(4); for mixed-field-irradiated saline-treated mice 1.94x10(2); and for mixed-field-irradiated WR-treated mice 6.13x10(3). WR-induced resistance to infection paralleled increased numbers of PB white cells, neutrophils, platelets, femoral BM cells and granulocyte macrophage colony-forming cells (GM-CFC) in irradiated mice not given bacteria. CONCLUSIONS: These studies quantify the resistance to bacterial infection in mice treated with WR before sublethal irradiation. The findings suggest that WR treatment increases resistance to infection in immunocompromised hosts.

Animals↗
PubMed2000

Ionizing radiation and bacterial challenge alter splenic cytokine gene expression.

Irradiation increases susceptibility to bacterial infection. Exogenous proinflammatory cytokines can alter the response of mice to gamma radiation, but the role of endogenous inflammatory cytokines after bacterial infection in irradiated animals is not known. Gene expression of hematopoietic (GM-CSF) and proinflammatory (IL-1 beta, IL-6 and TNF-alpha) cytokines were examined in spleens of B6D2F1/J female mice after irradiation alone (1.0- and 7.0-Gy), and after irradiation followed by Klebsiella pneumoniae s.c. challenge 4 days postirradiation by using the reverse transcription-polymerase chain reaction (RT-PCR) and Southern blot hybridization. At 4, 8, and 24 h after bacterial challenge in 7.0-Gy-irradiated mice, GM-CSF mRNA increased (p < 0.05). TNF-alpha mRNA in irradiated mice were slightly decreased, whereas after bacterial challenge, TNF-alpha mRNA elevated at 30 h in 7.0-Gy-irradiated mice; at 4, and 8 h in 1.0-Gy-irradiated mice, and at 1 h in sham-irradiated mice (p < 0.05). IL-6 mRNA displayed a biphasic response in 7.0-Gy-irradiated mice, and, after bacterial challenge, in both irradiated mice (1.0- and 7.0-Gy) and sham-irradiated mice. IL-1 beta mRNA remained at or below normal for 8 h and increased at 24 h after bacterial challenge on day 4 in 7.0-Gy-irradiated mice. These results indicate that sublethal gamma radiation alters the patterns of the hematopoietic and proinflammatory cytokine responses to bacterial challenge in vivo. Consequently, treatment protocols may need to take into account changes in cytokine gene responses to resolve infection after irradiation.

Animals↗
PubMed1998

Urinary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets.

During the 1991 Persian Gulf War several US military personnel were wounded by shrapnel fragments consisting of depleted uranium. These fragments were treated as conventional shrapnel and were not surgically removed to spare excessive tissue damage. Uranium bioassays conducted over a year after the initial uranium injury indicated a significant increase in urine uranium levels above natural background levels. The potential mutagenic effects of depleted uranium are unknown. To assess the potential mutagenic effects of long-term exposure to internalized depleted uranium, Sprague-Dawley rats were implanted with depleted uranium and their urine and serum were evaluated for mutagenic potential at various times after pellet implantation using the Ames Salmonella reversion assay. Tantalum, an inert metal widely used in prosthetic devices was used for comparison. Enhancement of mutagenic activity in Salmonella typhimurium strain TA98 and the Ames II mixed strains (TA7001-7006) was observed in urine samples from animals implanted with depleted uranium pellets. In contrast, urine samples from animals implanted with tantalum did not show a significant enhancement of mutagenic activity in these strains. In depleted uranium-implanted animals, urine mutagenicity increased in a dose- and time-dependent manner demonstrating a strong positive correlation with urine uranium levels (r = 0.995, P < 0.001). There was no mutagenic enhancement of any bacterial strain detected in the sera of animals implanted with either depleted uranium or tantalum pellets. The results suggest that uranium content in the urine is correlated with urine mutagenicity and that urinary mutagenicity might be used as a biomarker to detect exposure to internalized uranium.

Animals↗
PubMed1995

Comparison of interleukin-1 alpha gene expression and protein levels in the murine spleen after lethal and sublethal total-body irradiation.

To understand the effects of ionizing radiation on the production of IL-1 alpha in vivo within a hematopoietic organ, we evaluated acute changes in splenic IL-1 alpha mRNA and IL-1 alpha protein after exposing B6D2F1 mice to lethal and sublethal 60Co radiation. Results suggest that in vivo, ionizing radiation induces a time- and dose-dependent accumulation of IL-1 alpha mRNA in the mouse spleen after exposure to gamma radiation. Time-dependent increases in the level of IL-1 alpha protein were also observed, although the magnitude of increased protein expression did not complement the magnitude of the accumulation of the message. Selective concentration of cells producing IL-1 alpha does not appear to account completely for the increase in splenic IL-1 alpha mRNA observed in this in vivo system.

Animals↗
PubMed1994

Gene expression of hematoregulatory cytokines is elevated endogenously after sublethal gamma irradiation and is differentially enhanced by therapeutic administration of biologic response modifiers.

Prompt, cytokine-mediated restoration of hematopoiesis is a prerequisite for survival after irradiation. Therapy with biologic response modifiers (BRMs), such as LPS, 3D monophosphoryl lipid A (MPL), and synthetic trehalose dicorynomycolate (S-TDCM) presumably accelerates hematopoietic recovery after irradiation by enhancing expression of cytokines. However, the kinetics of the cytokine gene response to BRMs and/or irradiation are poorly defined. One hour after sublethal (7.0 Gy) 60Cobalt gamma irradiation, B6D2F1/J female mice received a single i.p. injection of LPS, MPL, S-TDCM, an extract from Serratia marcescens (Sm-BRM), or Tween 80 in saline (TS). Five hours later, a quantitative reverse transcription-PCR assay demonstrated marked splenic gene expression for IL-1 beta, IL-3, IL-6, and granulocyte-CSF (G-CSF). Enhanced gene expression for TNF-alpha, macrophage-CSF (M-CSF), and stem cell factor (SCF) was not detected. Injection of any BRM further enhanced cytokine gene expression and plasma levels of CSF activity within 24 h after irradiation and hastened bone marrow recovery. Mice injected with S-TDCM or Sm-BRM sustained expression of the IL-6 gene for at least 24 h after irradiation. Sm-BRM-treated mice exhibited greater gene expression for IL-1 beta, IL-3, TNF-alpha, and G-CSF at day 1 than any other BRM. When challenged with 2 LD50/30 of Klebsiella pneumoniae 4 days after irradiation, 100% of Sm-BRM-treated mice and 70% of S-TDCM-treated mice survived, whereas < or = 30% of mice treated with LPS, MPL, or TS survived. Thus, sublethal irradiation induces transient, splenic cytokine gene expression that can be differentially amplified and prolonged by BRMs. BRMs that sustained and/or enhanced irradiation-induced expression of specific cytokine genes improved survival after experimental infection.

Animals↗
PubMed1994

Oral contraceptives and renal and retinal complications in young women with insulin-dependent diabetes mellitus.

OBJECTIVE: To evaluate the effects of oral contraceptives (OCs) as a possible risk factor for early diabetic renal and/or retinal complications. DESIGN: A retrospective case-control study. SETTING: A university hospital diabetes clinic. PARTICIPANTS: Forty-three diabetic women who used OCs for 1 year or longer (mean, 3.4 years; range, 1.0 to 7.0 years) were compared with a computer-matched control group of 43 diabetic women who never used OCs. MAIN OUTCOME MEASURES: Hemoglobin A1c levels, albumin excretion rates, and mean retinopathy scores. RESULTS: The mean +/- SEM age and duration of diabetes were 22.7 +/- 0.5 years (range, 17.1 to 30.5 years) and 13.8 +/- 0.8 years, respectively, for the study group. The mean longitudinal hemoglobin A1c values were similar for study subjects and control subjects. The final mean albumin excretion rates, reflecting diabetic renal damage, and the mean eye grades were not significantly different between the groups. CONCLUSIONS: The use of OCs among young women with insulin-dependent diabetes mellitus does not pose an additional risk for the development of early diabetic retinopathy and/or nephropathy.

Adolescent↗
PubMed1994

Effects of radiation on survival and recovery of T lymphocyte subsets in C3H/HeN mice.

The aims of this study were to determine the radiosensitivities of murine thymic and splenic CD4+ and CD8+ lymphocytes and to evaluate the regeneration of these cells in a model of radiation-induced hematopoietic and immune suppression. CD4+ and CD8+ cells were quantitated using two-color flow-cytometric analysis. Cells obtained from C3H/HeN mice 24 hours after exposure to 0.25-8.0 Gy (0.4 Gy/min) 60Co were used to determine D0 values. Thymic CD4+ cells contained a radiosensitive subpopulation with a D0 of 0.97 +/- 0.05 Gy and a radioresistant subpopulation that survived exposures up to 8.0 Gy. CD8+ cells also contained a radiosensitive subpopulation with a D0 of 1.24 +/- 0.05 Gy and a radioresistant subpopulation with a D0 of 3.93 +/- 2.01 Gy. Double-positive thymic CD4+/CD8+ cells were uniformly radiosensitive, with a D0 of 1.03 +/- 0.28 Gy. Multiple T lymphocyte subpopulations based on radiosensitivity and CD4/CD8 antigen expression were also observed in the spleen. When mice were exposed to a sublethal 6.5-Gy radiation dose and recovery of T lymphocyte subsets was monitored, the relative radioresistance of CD4+ cells resulted in a selective enrichment of these cells among the surviving thymocytes and splenic lymphocytes. This relative enrichment of CD4+ cells became even more prominent 7 days after irradiation, when atrophy of the organs was greatest. Similar, although less dramatic, effects were observed for CD8+ cells. These studies demonstrate that (1) multiple T lymphocyte subpopulations can be identified based on radiosensitivity and CD4/CD8 antigen expression; (2) both CD4+ and CD8+ cells contain radioresistant subpopulations, with the CD4+ subpopulation being more resistant than the CD8+ subpopulation; and (3) although the number of radioresistant CD4+ cells is quite small, they persist in increased proportions during the periods preceding and corresponding to postirradiation hematopoietic recovery.

Animals↗
PubMed1993

Factors influencing the onset and progression of diabetic retinopathy in subjects with insulin-dependent diabetes mellitus.

BACKGROUND: The etiology of diabetic retinopathy is poorly understood. In the current study, factor associated with the onset and the progression or regression of retinopathy are evaluated. METHODS: Two hundred seventy-seven subjects with insulin-dependent (type I) diabetes mellitus (IDDM) were evaluated longitudinally for retinal changes over a mean of 2.7 years. The multistate Markov model was used to analyze the influences of the duration of diabetes, a family history of hypertension, age, sex, cigarette smoking, systolic blood pressure, diastolic blood pressure, cholesterol levels, and longitudinal glycohemoglobin (GHb) values on the development and the progression or regression of retinopathy. RESULTS: Univariate analysis confirmed that four factors were significantly associated with the etiology and the progression or regression of diabetic retinopathy: age, duration of diabetes, mean longitudinal GHb levels (all at P < 0.01), and diastolic blood pressure (P < 0.04). However, age was no longer significant when controlled by duration of diabetes. Cigarette smoking was only associated significantly with background retinopathy (stages 2 and 3). Systolic blood pressure, sex, a family history of hypertension, and cholesterol levels were not significantly associated with retinopathy. CONCLUSIONS: The onset of diabetic retinopathy is associated with the duration of diabetes, mean longitudinal GHb levels, smoking, and diastolic blood pressure. A longer duration of diabetes, higher GHb values, and higher diastolic blood pressure levels are associated with an increased risk of progression and a decreased chance of regression of diabetic retinopathy.

Adolescent↗
PubMed1993

Adverse effects of pefloxacin in irradiated C3H/HeN mice: correction with glucan therapy.

Opportunistic bacterial infections are the predominant cause of death following myelosuppressive radiation exposure. When used alone, a variety of immunomodulators and antibiotics have been reported to reduce radiation-induced death. In these studies, the combined therapeutic effects of the immunomodulator glucan and the quinolone antibiotic pefloxacin were evaluated for survival-enhancing effects in myelosuppressed C3H/HeN mice. Mice were exposed to 7.9 Gy of whole-body 60Co radiation and treated with saline, glucan (250 mg/kg of body weight intravenously, 1 h after irradiation), pefloxacin (64 mg/kg/day orally, days 3 to 24 after irradiation), or glucan plus pefloxacin. Survival 30 days after irradiation in mice receiving these respective treatments was 25, 48, 7, and 85%. Evaluation of granulocyte-macrophage progenitor cell (GM-CFC) recovery in mice receiving these treatments revealed that, compared with recovery in saline-treated mice, glucan stimulated GM-CFC recovery, pefloxacin suppressed GM-CFC recovery, and glucan administered in combination with pefloxacin could override pefloxacin's hemopoietic suppressive effect.

Animals↗
PubMed1993

Angiotensin-converting enzyme inhibitor treatment for young normotensive diabetic subjects: a two-year trial.

Microangiopathy characterizes both diabetic retinopathy and nephropathy. It is currently unclear which diabetic subjects should be treated with angiotensin-converting enzyme (ACE) inhibitors. A double-blind, placebo-controlled protocol was implemented using captopril to treat subjects with Type I diabetes, early diabetic nephropathy (albumin excretion rates, 20-200 micrograms/min), and normal blood pressures. After two years, the final eye grades were improved in two treated subjects but not in any of the controls. Three control and one treated subject showed worsening of their eye grade after two years (P < .001, by chi-square test). Significant differences in renal albumin excretion were not seen between the two groups. The distribution of changes in retinal grades in the treatment group compared with the placebo group was improved after two years. Studies of larger numbers of patients will be necessary to determine if ACE inhibitors should be used routinely in subjects with diabetic retinopathy and to determine which subjects are most likely to respond.

Adolescent↗
PubMed1992

Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications.

Three hundred and fifty seven subjects (178 males and 179 females) with insulin dependent diabetes mellitus were evaluated for the presence of limited joint mobility of the interphalangeal joints. Sixty six subjects (19%) had stage 1 and 26 subjects (7%) had stage 2 involvement of their interphalangeal joints. The presence of contractures was significantly related to mean longitudinal glycated haemoglobin (HbA1) concentrations, duration of diabetes, age of onset, mean longitudinal cholesterol concentrations and blood pressure. Limited joint mobility was also significantly associated with early diabetic retinopathy and raised albumin excretion rates. Limited joint mobility remained a significant factor in the logistic regression model for albuminuria and grade of retinopathy when controlled for smoking, cholesterol concentrations, duration of diabetes, age, gender, and blood pressure. However, limited joint mobility was only significantly associated with diabetic retinopathy when the effect of HbA1 concentrations was included in the multivariate model.

Adolescent↗
PubMed1992

Changes in the microbial flora of airline headset devices after their use.

The bacterial flora of 20 headset devices were evaluated before and after they were worn for 1 hour. Bacteria were recovered from all headsets, and their number increased from a mean (+/- standard deviation) of 60 +/- 5 organisms per device to 650 +/- 51 organisms per device (P less than .001). The predominant organisms recovered were Staphylococcus spp, Streptococcus spp, Propionibacterium spp, and Peptostreptococcus spp. This study demonstrates the presence of potential pathogens in headset devices, as well as the increase in the number of these pathogens after the headsets have been worn for 1 hour.

Adolescent↗