Browse Health
Internist, Critical Care Specialist, Pulmonologist (lungs), Hospice & Palliative Specialist
24 years of experience
Accepting new patients


Education ?

Medical School Score
Texas Tech University (1988)

Awards & Distinctions ?

American Board of Internal Medicine

Affiliations ?

Dr. Jumper is affiliated with 5 hospitals.

Hospital Affiliations



  • Covenant Medical Center
    Pulmonary Disease
    3615 19th St, Lubbock, TX 79410
    Top 50%
  • University Medical Center - Lubbock
    Pulmonary Disease
    602 Indiana Ave, Lubbock, TX 79415
  • TX Tech Physicians Associates
  • University Medical Center
  • Lincoln County Medical Center
  • Publications & Research

    Dr. Jumper has contributed to 25 publications.
    Title Vaccines and Immunotherapeutics for the Treatment of Malignant Disease.
    Date February 2011
    Journal Clinical & Developmental Immunology

    The employment of the immune system to treat malignant disease represents an active area of biomedical research. The specificity of the immune response and potential for establishing long-term tumor immunity compels researchers to continue investigations into immunotherapeutic approaches for cancer. A number of immunotherapeutic strategies have arisen for the treatment of malignant disease, including various vaccination schemes, cytokine therapy, adoptive cellular therapy, and monoclonal antibody therapy. This paper describes each of these strategies and discusses some of the associated successes and limitations. Emphasis is placed on the integration of techniques to promote optimal scenarios for eliminating cancer.

    Title Role of the Innate Immune Response and Tumor Immunity Associated with Simian Virus 40 Large Tumor Antigen.
    Date September 2010
    Journal Journal of Virology

    We examined properties of the innate immune response against the tumor-specific antigen simian virus 40 (SV40) large tumor antigen (Tag) following experimental pulmonary metastasis in naive mice. Approximately 14 days after mKSA tumor cell challenge, expression of inflammatory mediators such as tumor necrosis factor alpha (TNF-alpha), interleukin-2 (IL-2), and RANTES was upregulated in splenocytes harvested from mice, as assessed by flow cytometry and antibody array assays. This response was hypothesized to activate and induce tumor-directed NK cell lysis since IL-2-stimulated NK cells mediated tumor cell destruction in vitro. The necessary function of NK cells was further validated in vivo through selected antibody depletion of NK cells, which resulted in an overwhelming lung tumor burden relative to that in animals receiving a control rabbit IgG depletion regimen. Interestingly, mice achieved increased protection from experimental pulmonary metastasis when NK cells were further activated indirectly through in vivo administration of poly(I:C), a Toll-like receptor 3 (TLR3) agonist. In a separate study, mice receiving treatments of poly(I:C) and recombinant SV40 Tag protein immunization mounted effective tumor immunity in an established experimental pulmonary metastasis setting. Initiating broad-based immunity with poly(I:C) was observed to induce a Th1 bias in the SV40 Tag antibody response that led to successful antitumor responses not observed in animals treated only with poly(I:C) or SV40 Tag. These data have direct implications for immunotherapeutic strategies incorporating methods to elicit inflammatory reactions, particularly NK cell-driven lysis, against malignant cell types that express a tumor-specific antigen such as SV40 Tag.

    Title Growth and Mycotoxin Production by Chaetomium Globosum is Favored in a Neutral Ph.
    Date June 2010
    Journal International Journal of Molecular Sciences

    Chaetomium globosum is frequently isolated in water-damaged buildings and produces two mycotoxins called chaetoglobosins A and C when cultured on building material. In this study, the influence of ambient pH on the growth of C. globosum was examined on an artificial medium. This fungus was capable of growth on potato dextrose agar ranging in pH from 4.3 to 9.4 with optimal growth and chaetoglobosin C production occurring at a neutral pH. In addition, our results show that sporulation is favored in an acidic environment.

    Title Detection of Macrocyclic Trichothecene Mycotoxin in a Caprine (goat) Tracheal Instillation Model.
    Date February 2010
    Journal Toxicology and Industrial Health

    This study demonstrates the detection and dynamics of macrocyclic trichothecene mycotoxin (MTM) tissue loading using a commercially available assay in a goat model. The detection of MTMs has been difficult and complex due to the uncertainty of what tissues to examine and when to sample. Twelve goats (two groups of each) were instilled with Stachybotrys chartarum conidial suspension via the trachea. The first group was challenged repeatedly with fungal conidia containing 1 mg/kg of MTM per instillation whereas the second group was exposed once, to spores with a calculated concentration of 5 microg/kg of mycotoxin. These toxin estimates were generated by the QuantiTox(TM) Kit assay; a conidium of S. chartarum possessed 8.5 pg of MTM. After repeated exposure of 3 days, MTM was detected in one of six animals. This animal and two others from the same group had mycotoxin detected in their serum 24 hours after challenge at a comparable level (1.69 ng/mL) to the six animals challenged with a single dose (2.02 ng/mL) at the same time post-instillation. Results showed that MTMs are detectable in experimental animals soon after challenge and contribute to the understanding of the role of these mycotoxins in the disease process following mold exposure.

    Title Tumor Immunity Against a Simian Virus 40 Oncoprotein Requires Cd8+ T Lymphocytes in the Effector Immune Phase.
    Date January 2010
    Journal Journal of Virology

    The required activities of CD4(+) T cells and antibody against the virally encoded oncoprotein simian virus 40 (SV40) Tag have previously been demonstrated by our laboratory to be mediators in achieving antitumor responses and tumor protection through antibody-dependent cell-mediated cytotoxicity (ADCC). In this study, we further characterize the necessary immune cell components that lead to systemic tumor immunity within an experimental pulmonary metastatic model as the result of SV40 Tag immunization and antibody production. Immunized animals depleted of CD8(+) T cells at the onset of experimental tumor cell challenge developed lung tumor foci and had an overall decreased survival due to lung tumor burden, suggesting a role for CD8(+) T cells in the effector phase of the immune response. Lymphocytes and splenocytes harvested from SV40 Tag-immunized mice experimentally inoculated with tumor cells synthesized increased in vitro levels of the Th1 cytokine gamma interferon (IFN-gamma), as assessed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry assays. CD8(+) T-cell activity was also heightened in SV40 Tag-immunized and tumor cell-challenged mice, based upon intracellular production of perforin, confirming the cytolytic properties of CD8(+) T cells against tumor cell challenge. Altogether, these data point to the role of recombinant SV40 Tag protein immunization in initiating a cytotoxic T-lymphocyte (CTL) response during tumor cell dissemination and growth. The downstream activity of CD8(+) T cells within this model is likely initiated from SV40 Tag-specific antibody mediating ADCC tumor cell destruction.

    Title Evidence of Simian Virus 40 Exposure in a Colony of Captive Baboons.
    Date July 2008
    Journal Virology

    Simian virus 40 (SV40) is a polyomavirus for which non-human primates are the permissive host. The baboon (Papio spp.) is an old world monkey that is used in a variety of research investigations; however, natural infection of SV40 among baboons has not been thoroughly examined or reported. Initially, we were interested in determining the prevalence of SV40 infection among a captive colony of baboons based on the presence of antibodies to SV40 large T-antigen (Tag). An overall seroprevalence rate of >50% was found after screening sera from 142 baboons in the colony based on ELISA. Endpoint titer values for serum antibody binding to SV40 Tag reached as high as 1280 for 5 out of 142 baboons. Peptide binding assays revealed that a range of SV40 Tag epitopes are immunogenic in the baboon, and that individual animals differ in their humoral immune responses to SV40 Tag based on epitope recognition. Specificity to SV40 Tag and not some other primate polyomavirus encoded large Tag was further examined by serologic reactivity to peptide epitopes unique to SV40 Tag. Additional serology was performed to assess SV40 Tag reactivity by Western blot and whether antibodies were capable of neutralizing SV40 infectivity in vitro. Although antibodies with high levels of SV40 neutralization were observed in a number of the baboons, there was a lack of correlation between viral neutralization and antibodies to SV40 Tag. Further examination using molecular-based diagnosis and SV40 Tag specific real-time quantitative PCR determined that some of the baboons appeared to be exposed to SV40. DNA sequence analysis of the PCR products confirmed that SV40 Tag specific sequences were detected in baboons.

    Title Heat Stability of Chaetoglobosins A and C.
    Date July 2008
    Journal Canadian Journal of Microbiology

    Chaetomium globosum is commonly found in water-damaged buildings and produces the mycotoxins chaetoglobosin A and chaetoglobosin C (Ch-A and Ch-C, respectively). While attempting to purify Ch-A and Ch-C, we observed that these mycotoxins were broken down after heating. The objective of this study was to determine the temperature and the amount of time necessary to break down Ch-A and Ch-C. We demonstrated that the amounts of Ch-A were significantly reduced when exposed to 75 degrees C for 24 h and 100 degrees C for 90, 120, or 150 min. Under the same conditions, the levels of Ch-C were also lower (although not significantly). At 175 degrees C, no Ch-A was detected after 15 min and Ch-C was significantly reduced after 30 min. Our findings will aid other researchers who work with these mycotoxins in the future.

    Title Towards Progress on Dna Vaccines for Cancer.
    Date November 2007
    Journal Cellular and Molecular Life Sciences : Cmls

    Cancer immunotherapy faces many obstacles that include eliciting immune reactions to self antigens as well as overcoming tumor-derived immunosuppressive networks and evasion tactics. Within the vaccine arsenal for inhibiting cancer proliferation, plasmid DNA represents a novel immunization strategy that is capable of eliciting both humoral and cellular arms of the immune response in addition to being safely administered and easily engineered and manufactured. Unfortunately, while DNA vaccines have performed well in preventing and treating malignancies in animal models, their overall application in human clinical trials has not impacted cancer regression to date. Since the establishment of these early trials, progress has been made in terms of increasing DNA vaccine immunogenicity and subverting the suppressive properties of tumor cells. Therefore, the success of future plasmid DNA use in cancer patients will depend on combinatorial strategies that enhance and direct the DNA vaccine immune response while also targeting tumor evasion mechanisms.

    Title Growth and Mycotoxin Production by Chaetomium Globosum.
    Date August 2007
    Journal Mycopathologia

    Chaetomium globosum, the most common species within this genus, produces chaetoglobosins A and C when cultured on building material. Relatively low levels of these compounds have been shown to be lethal to various tissue culture cell lines. This study had two major objectives: (1) to determine the frequency at which Chaetomium species are isolated in water-damaged buildings and (2) to examine the production of chaetoglobosins A and C in isolates of C. globosum obtained from different buildings. Out of 794 water-damaged buildings, Chaetomium species were isolated in 49% of these structures. C. globosum ATCC 16021 was grown on four different media: oatmeal agar (OA), potato dextrose agar (PDA), corn meal agar (CMA), and malt extract agar (MEA). After 4 weeks, fungal growth was evaluated based on colony diameter and the quantity of spores produced on agar plates. In addition, production of chaetoglobosin A and C was monitored using high performance liquid chromatography. Colony diameter, spore production, and mycotoxin production by C. globosum were the highest on OA. Out of 30 C. globosum isolates cultured on OA for 4 weeks, 16 produced detectable amounts of chaetoglobosin A and every isolate produced chaetoglobosin C.

    Title Mold Contamination and Air Handling Units.
    Date August 2007
    Journal Journal of Occupational and Environmental Hygiene

    An investigation was conducted on selected locations in air handling units (AHUs) to (a) identify common mold species found on these locations, (b) determine whether some locations (and subsets) featured mold growth sites more frequently than others, (c) ascertain whether the operating condition of AHUs is related to mold contamination, and (d) provide a basis for a microbial sampling protocol for AHUs. A total of 566 tape lifts and 570 swab samples were collected from the blower wheel fan blades, insulation, cooling coil fins, and ductwork from 25 AHUs. All AHU conditions were numerically rated using a heating, ventilation and air-conditioning (HVAC) survey. Results showed that Cladosporium sp. fungi were commonly recovered in terms of growth sites and deposited spores, and they were found mainly in the blower wheel fan blades, the ductwork, and the cooling coil fins. Subsections of the fan blades, insulation, and cooling coil fins showed no preferred area for mold growth sites. Other organisms such as Penicillium sp., Aspergillus sp., and Paecilomyces sp. were recovered from the cooling coil fins and insulation. Because of the widespread prevalence of Cladosporium sp., there was no relationship between mold growth and operating condition. However, the presence of different species of molds in locations other than the blower wheel blades may indicate that the AHU condition is not optimal. A suggested microbial sampling protocol including interpretations of sample results is presented.

    Title Fc Gamma Receptors Play a Dominant Role in Protective Tumor Immunity Against a Virus-encoded Tumor-specific Antigen in a Murine Model of Experimental Pulmonary Metastases.
    Date July 2007
    Journal Journal of Virology

    Simian virus 40 (SV40) large tumor antigen (Tag) represents a virus-encoded tumor-specific antigen expressed in many types of human cancers and a potential immunologic target for antitumor responses. Fc receptors are important mediators in the regulation and execution of host effector mechanisms against conditions including infectious diseases, autoimmunity, and cancer. By examining tumor protection in SV40 Tag-immunized wild-type BALB/c mice using an experimental pulmonary metastasis model, we attempted to address whether engagement of the immunoglobulin G Fc receptors (FcgammaRs) on effector cells is necessary to mediate antitumor responses. All immunized BALB/c FcgammaR-/- knockout mice developed anti-SV40 Tag antibody responses prior to experimental challenge with a tumorigenic cell line expressing SV40 Tag. However, all mice deficient in the activating FcgammaRI (CD64) and FcgammaRIII (CD16) were unable to mount protective immunologic responses against tumor challenge and developed tumor lung foci. In contrast, mice lacking the inhibitory receptor FcgammaRII (CD32) demonstrated resistance to tumorigenesis. These results underscore the importance of effector cell populations expressing FcgammaRI/III within this murine tumor model system, and along with the production of a specific humoral immune response, antibody-dependent cell-mediated cytotoxicity (ADCC) may be a functioning mechanism of tumor clearance. Additionally, these data demonstrate the potential utility of ADCC as a viable approach for targeting vaccination strategies that promote FcgammaRI/III scavenging pathways against cancer.

    Title Sv40 Association with Human Malignancies and Mechanisms of Tumor Immunity by Large Tumor Antigen.
    Date May 2007
    Journal Cellular and Molecular Life Sciences : Cmls

    SV40 was discovered as a contaminate of poliovirus vaccine lots distributed to millions of individuals in the United States between 1955 and 1963 while contaminated vaccine batches were later circulated worldwide. After SV40 was observed to cause in vitro animal and human cell transformations and in vivo tumor formations in animals, the search for a connection between the virus and human malignancies has continued to the present day. Different molecular methods have been used to detect SV40 gene products in a variety of human cancers, though SV40 causality in these tumor types has yet to be established. These data, however, are not without controversial issues related to inconclusive SV40 serological and epidemiological evidence alongside tools and methodologies that may contribute to false-positive results in human specimens. This review will also explore how vaccination against SV40 protein products may be used to help prevent and treat individuals with SV40-expressing cancers.

    Title Immunological Treatment of Liver Tumors.
    Date March 2006
    Journal World Journal of Gastroenterology : Wjg

    Although multiple options for the treatment of liver tumors have often been described in the past, including liver resection, radiofrequency ablation with or without hepatic pump insertion, laparoscopic liver resection and the use of chemotherapy, the potential of immunotherapy and gene manipulation is still largely unexplored. Immunological therapy by gene manipulation is based on the interaction between virus-based gene delivery systems and dendritic cells. Using viruses as vectors, it is possible to transduce dendritic cells with genes encoding tumor-associated antigens, thus inducing strong humoral and cellular immunity against the antigens themselves. Both chemotherapy and radiation therapy have the disadvantage of destroying healthy cells, thus causing severe side-effects. We need more precisely targeted therapies capable of killing cancer cells while sparing healthy cells. Our goal is to establish a new treatment for solid liver tumors based on the concept of cytoreduction, and propose an innovative algorithm.

    Title A Randomized Trial Assessing the Utility of a Test-dose Program with Taxanes.
    Date February 2006
    Journal Current Medical Research and Opinion

    OBJECTIVE: Taxanes are commonly used anticancer agents with a potential of producing an allergic or hypersensitivity reaction (HSR). We performed a randomized study to evaluate the value of a test dose given prior to the full dose of either paclitaxel or docetaxel.Research design and methods: Patients were randomly assigned to either the administration of the full dose or to the prior administration of a 1 mg intravenous test dose of either paclitaxel or docetaxel. The primary endpoints were severity of the HSR and the cost of drug wastage due to a HSR.RESULTS: Two hundred and eighteen patients were randomized from three different treatment sites. The overall incidence of HSR was 6.5% and there was no significant difference in the incidence of HSR in either group. The mean HSR severity grade was 2.8 for patients without a test dose and 2.3 for those receiving a test dose. There was, however, a reduction in the wastage of taxane in the test dose arm. Wastage avoided in the test dose arm was $1573 per patient who had a HSR and $104 per patient treated with a taxane.CONCLUSION: Although a test dose may not reduce the severity of a HSR with the administration of a taxane, it does reduce the cost associated with drug wastage.

    Title Effect of Chlorine Dioxide Gas on Fungi and Mycotoxins Associated with Sick Building Syndrome.
    Date October 2005
    Journal Applied and Environmental Microbiology

    The growth of indoor molds and their resulting products (e.g., spores and mycotoxins) can present health hazards for human beings. The efficacy of chlorine dioxide gas as a fumigation treatment for inactivating sick building syndrome-related fungi and their mycotoxins was evaluated. Filter papers (15 per organism) featuring growth of Stachybotrys chartarum, Chaetomium globosum, Penicillium chrysogenum, and Cladosporium cladosporioides were placed in gas chambers containing chlorine dioxide gas at either 500 or 1,000 ppm for 24 h. C. globosum was exposed to the gas both as colonies and as ascospores without asci and perithecia. After treatment, all organisms were tested for colony growth using an agar plating technique. Colonies of S. chartarum were also tested for toxicity using a yeast toxicity assay with a high specificity for trichothecene mycotoxins. Results showed that chlorine dioxide gas at both concentrations completely inactivated all organisms except for C. globosum colonies which were inactivated an average of 89%. More than 99% of ascospores of C. globosum were nonculturable. For all ascospore counts, mean test readings were lower than the controls (P < 0.001), indicating that some ascospores may also have been destroyed. Colonies of S. chartarum were still toxic after treatment. These data show that chlorine dioxide gas can be effective to a degree as a fumigant for the inactivation of certain fungal colonies, that the perithecia of C. globosum can play a slightly protective role for the ascospores and that S. chartarum, while affected by the fumigation treatment, still remains toxic.

    Title In Vitro Simian Virus 40 Large Tumor Antigen Expression Correlates with Differential Immune Responses Following Dna Immunization.
    Date May 2005
    Journal Virology

    Simian virus 40 (SV40) contains an essential protein, large tumor antigen (Tag), which assists in viral replication and causes cell transformation and immortalization. Our laboratory has examined plasmid DNA, expressing SV40 Tag under two different promoters, for use in potential cancer vaccination strategies. One plasmid, pSV3-neo, failed to induce SV40 Tag antibody, produced a weak cell-mediated response, and only partial protection in murine experimental tumor challenge systems. The second plasmid, pCMV-Tag, induced antibodies to SV40 Tag, produced a robust cell-mediated response, and invoked complete tumor immunity in vivo. The induction of CD4+ and CD8+ T cell responses following plasmid DNA immunization and tumor cell challenge reflected a type 1 cytokine secretion profile. Our hypothesis for this differential immune response is that pCMV-Tag exhibits a higher level of transgene expression due to a more efficient promoter. We determined that pCMV-Tag levels of SV40 Tag mRNA and protein expression were higher when compared to pSV3-neo. A threshold amount of SV40 Tag may be required to stimulate antibody production and provide complete systemic tumor immunity.

    Title Acneiform Eruption Induced by Iressa (gefitinib) Tablets Used to Treat Non-small Cell Lung Cancer.
    Date January 2005
    Journal Journal of Drugs in Dermatology : Jdd

    Many medications have been reported to induce acneiform eruptions. A relatively new chemotherapy drug, gefitinib (Iressa), approved by the Food and Drug Administration in 2003 for the treatment of advanced-stage non-small cell lung cancer (NSCLC), has been reported to cause acne or an acne-like eruption. We report an Asian female who presented with hundreds of erythematous papules and pustules on her face, chest, and back, all of which appeared after starting gefitinib to treat non-small cell lung cancer.

    Title Fungi and the Indoor Environment: Their Impact on Human Health.
    Date December 2004
    Journal Advances in Applied Microbiology
    Title Anti-idiotype Responses Abrogate Anti-cd4-induced Tolerance to a Tumor-specific Antigen and Promote Systemic Tumor Immunity.
    Date November 2004
    Journal Cancer Immunology, Immunotherapy : Cii

    PURPOSE: Immunologic-based cancer treatment modalities represent an active area of investigation. Included in these strategies are passive administration of monoclonal antibodies which recognize tumor-associated antigens and active vaccination with identified tumor antigens. However, several problems associated with these types of treatment strategies have been identified. METHODS: In this report, we address certain issues by employing a murine model for experimental pulmonary metastasis and a tumor antigen vaccination strategy that induces complete tumor immunity in this system. Utilizing this model, we attempt to address issues related to unresponsiveness to tumor antigen immunization induced by passive administration of a rat monoclonal anti-CD4 and the induction of anti-idiotype responses to a passively administered monoclonal antibody and the effects on the induction of tumor immunity. RESULTS: The results presented indicate that passive administration of rat monoclonal anti-CD4 exhibits immunosuppressive effects that inhibit the production of antibodies to the tumor antigen immunization and abolishes tumor immunity. Repeated administration of the rat monoclonal anti-CD4 results in an anti-idiotype response that can abrogate unresponsiveness to tumor antigen immunization and promote systemic tumor immunity. CONCLUSIONS: The data examine a number of potential problems associated with immunologic-based treatments for cancer. These problems include the potential for tolerance to the tumor antigen and establishing an immunocompromised state where immunization with a tumor antigen failed to generate tumor immunity. Approaches to eliminate tolerant T cells by targeting anti-CD4 via anti-idiotype responses that could be generated in vivo without CD4+ T cells allowed for recovery of nontolerant T cells, and an antibody response to the tumor antigen that results in tumor immunity.

    Title Studies on the Role of Fungi in Sick Building Syndrome.
    Date July 2004
    Journal Archives of Environmental Health

    Sick Building Syndrome is a term used to describe symptoms in humans which result from problems with indoor air quality. Common complaints include dyspnea, flu-like symptoms, watering eyes, and allergic rhinitis. Although there is likely no single cause for Sick Building Syndrome, fungal contamination in buildings has increasingly been associated with this spectrum of symptoms. The authors describe 2 case studies, and other experimentation, that have investigated the role of fungi in the occurrence of Sick Building Syndrome.

    Title Characterization of Exposure to Low Levels of Viable Penicillium Chrysogenum Conidia and Allergic Sensitization Induced by a Protease Allergen Extract from Viable P. Chrysogenum Conidia in Mice.
    Date April 2003
    Journal International Archives of Allergy and Immunology

    BACKGROUND: Previous evidence by our laboratory has shown that mice inoculated with viable Penicillium Chrysogenum conidia or spores at levels comparable to those found in contaminated buildings induced spore antigen-specific allergic responses. We proposed that mice exposed to low levels of viable P. Chrysogenum conidia would not develop allergic symptoms. We also hypothesized that the symptoms induced by high numbers of conidia were the result of sensitization to allergens released by the conidia. METHODS: C57BL/6 and BALB/c mice were exposed to 1 x 10(2) viable P. Chrysogenum conidia by intranasal instillation weekly for a period of 11 weeks. C57BL/6 mice were also sensitized to a viable P. Chrysogenum conidia protease extract by intraperitoneal injections for a period of 6 weeks followed by intranasal challenge with protease extract, viable, or nonviable P. Chrysogenum conidia for 2 weeks. RESULTS: C57BL/6 mice inoculated with low numbers of conidia developed no significant lung inflammation or increased serum immunoglobulins. Mice sensitized to the protease extract and challenged with both protease extract and viable conidia produced significant increases in serum IgE and IgG1. Mice sensitized to and challenged with the protease extract developed significant eosinophilia and mucus hyperproduction as determined by bronchoalveolar lavage and histopathological examination of lung tissue. CONCLUSIONS: Mice did not develop allergic symptoms in response to challenge with low levels of P. Chrysogenum conidia. Protease allergens from viable conidia induced specific allergic responses in mice, indicating the importance of P. Chrysogenum conidia in allergic sensitization to the organism.

    Title An Animal Model for Allergic Penicilliosis Induced by the Intranasal Instillation of Viable Penicillium Chrysogenum Conidia.
    Date July 2000
    Journal Thorax

    BACKGROUND: A study was undertaken to determine the consequences of long term intranasal instillation of Penicillium chrysogenum propagules in a mouse model. METHODS: C57 Black/6 mice were inoculated intranasally each week for six weeks with 10(4) viable and non-viable P chrysogenum conidia. Cytokine levels and cellular responses in these animals were then measured. RESULTS: Compared with controls, mice inoculated intranasally each week for six weeks with 10(4) P chrysogenum conidia (average viability 25%) produced significantly more total serum IgE (mean difference 1823.11, lower and upper 95% confidence intervals (CI) 539.09 to 3107.13), peripheral eosinophils (mean difference 5.11, 95% CI 2.24 to 7.99), and airway eosinophilia (rank difference 11.33, 95% CI 9.0 to 20.0). With the exception of airway neutrophilia (mean difference 20.89, 95% CI 3.72 to 38.06), mice inoculated intranasally with 10(4) non-viable conidia did not show significant changes in total serum IgE, peripheral or airway eosinophils. However, when compared with controls, this group (10(4) non-viable) had a significant increase in total serum IgG(2a) (mean difference 1990.56, 95% CI 790.48 to 3190.63) and bronchoalveolar lavage (BAL) fluid levels of interferon (IFN)-gamma (mean difference 274.72, 95% CI 245.26 to 304.19). In addition, lung lavages from mice inoculated intranasally with 10(4) viable P chrysogenum conidia had significantly increased levels of interleukin (IL)-4 (mean difference 285.28, 95% CI 108.73 to 461.82) and IL-5 (mean difference 16.61, 95% CI 11.23 to 21.99). The IgG(2a)/IgE ratio and the IFN-gamma/IL-4 ratio was lower in the group of mice inoculated intranasally with 10(4) viable conidia than in the 10(4) non-viable conidia group and the controls. When proteins were extracted from P chrysogenum conidia, attached to microtitre plates and incubated with serum from the 10(4) viable group, significant increases in conidia-specific IgE and IgG(1) were observed compared with controls, while serum from the 10(4) non-viable group was similar to controls. CONCLUSIONS: These data suggest that long term inhalation of viable P chrysogenum propagules induces type 2 T helper cell mediated (Th2) inflammatory responses such as increases in total and conidia-specific serum IgE and IgG(1), together with BAL fluid levels of IL-4 and IL-5 and peripheral and airway eosinophilia, which are mediators of allergic reactions.

    Title Correlation Between the Prevalence of Certain Fungi and Sick Building Syndrome.
    Date December 1998
    Journal Occupational and Environmental Medicine

    OBJECTIVE: To examine the role of fungi in the production of sick building syndrome. METHODS: A 22 month study in the United States of 48 schools (in which there had been concerns about health and indoor air quality (IAQ). Building indoor air and surface samples, as well as outdoor air samples were taken at all sites to look for the presence of fungi or their viable propagules. RESULTS: Five fungal genera were consistently found in the outdoor air and comprised over 95% of the outdoor fungi. These genera were Cladosporium (81.5%), Penicillium (5.2%), Chrysosporium (4.9%), Alternaria (2.8%), and Aspergillus (1.1%). At 20 schools, there were significantly more colony forming units per cubic metre (CFU/m3) (p < 0.0001) of propagules of Penicillium species in the air samples from complaint areas when compared with the outdoor air samples and the indoor air samples from noncomplaint areas. At five schools, there were more, although not significant (p = 0.10), Penicillium propagules in the air samples from complaint areas when compared with the outdoor air samples and the indoor air samples from noncomplaint areas. In 11 schools, the indoor air (complaint areas) fungal ratios were similar to that in the outdoor air. In these 11 schools Stachybotrys atra was isolated from swab samples of visible growth under wetted carpets, on wetted walls, or behind vinyl wall coverings. In the remaining 11 schools, the fungal ratios and CFU/m3 of air were not significantly different in different areas. Many of the schools took remedial action that resulted in an indoor air fungal profile that was similar to that outdoors. CONCLUSIONS: Propagules of Penicillium and Stachybotrys species may be associated with sick building syndrome.

    Title 4-hydroxynonenal Mimics Ozone-induced Modulation of Macrophage Function Ex Vivo.
    Date September 1996
    Journal American Journal of Respiratory Cell and Molecular Biology

    Ozone is a ubiquitous pollutant that can cause acute pulmonary inflammation, cellular injury and may contribute to the development or exacerbation of chronic lung diseases. Despite much research, the effects of ozone on humans and potential cellular mechanisms of injury are still uncertain. However, ozone has been reported to increase the formation of aldehydes that could react with cellular proteins. Therefore, the purpose of these studies was to determine whether 4-hydroxynonenal (HNE), a previously unidentified aldehyde product of ozone exposure, is formed in human subjects exposed to ozone, and whether the response of human alveolar macrophages (AM) following a 1-h exposure to 0.25 ppm ozone with moderate exercise could be mimicked by in vitro incubation of AM with HNE. Western analysis demonstrated increased HNE protein adducts in airway fluid and alveolar macrophages after ozone exposure. AM were examined for endotoxin (lipopolysaccharide [LPS])-stimulated interleukin-1 beta (IL-1 beta) release and expression of heat shock protein 72 (HSP72). Immediately after ozone exposure there was no change in HSP72, but a 5-fold increase occurred 4 h after exposure. By 18 h after exposure, HSP72 levels decreased to below comparable air-exposed levels. Immediately after ozone exposure there was no effect on IL-1 beta release stimulated by LPS. However, IL-1 beta release stimulated by LPS was significantly inhibited 4 h after ozone exposure. By 18 h after ozone exposure, IL-1 beta release stimulated by LPS returned to normal. Incubation of human AM in vitro with HNE induced HSP72 and blocked LPS-stimulated IL-1 beta release possibly by inhibiting interleukin converting enzyme. Consequently, the in vitro results and demonstration of HNE protein adducts following ozone exposure are consistent with HNE being involved in this process in vivo and suggest that the cellular toxic effects of ozone could be a result of thiol reactive aldehydes produced by ozone.

    Title Low-dose Oral Interferon {alpha} Possibly Retards the Progression of Idiopathic Pulmonary Fibrosis and Alleviates Associated Cough in Some Patients.
    Journal Thorax

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