Biomedical subjects

R E Lewis

Publications and source records attributed to R E Lewis.

At least 19 recordsLinked to original sources

PubMed2002

Cellular and molecular alterations in spinal cord injury patients with pressure ulcers: a preliminary report.

The study was designed to investigate the changes, both numerically and functionally, of the molecules critical to wound healing in spinal cord injury (SCI) patients. Spinal cord injury patients who demonstrated delayed healing of their pressure ulcers were used as study subjects. Age-matched healthy individuals served as controls. Adhesion molecule expression of the peripheral blood leukocytes, including lymphocytes and granulocytes, was measured by flow cytometric analysis. Binding capacity of the lymphocytes was evaluated using human umbilical cord vein endothelial cells (HUVECs) as the binding matrix. Samples from pressure ulcers of the patients were immunostained to define fibronectin, kalinin, beta4 integrin, alpha2beta1, alpha3beta1, alpha5beta1, and CD138 expression. Compared to healthy controls, there was decreased expression of CD11a, CD11b, CD18, CD49b, CD49c, CD49d, CD54, and CD8 in patients' lymphocyte populations and CD11a, CD18, CD49c, CD49d, and CD8 in patients' granulocyte populations. The binding capacity, expressed as percentage binding of the lymphocytes to the HUVEC matrix, was greatly diminished in the patients. There was markedly diminished immunohistochemical staining of fibronectin in pressure ulcers. These findings showed that delayed healing of pressure ulcers in SCI patients can be attributed to reduced adhesion molecule expression, impaired cell-cell interaction, and lack of extracellular matrix structural and functional protein.

Adult↗

PubMed2002

Aspergillus nidulans is frequently resistant to amphotericin B.

The high failure rate of amphotericin B-based therapy in patients with Aspergillus nidulans infections may not be entirely a result of host factors as suggested previously. Innate resistance of A. nidulans to polyenes may contribute to the poor response in patients.

Amphotericin B↗

PubMed2002

Comparison of Etest, chequerboard dilution and time-kill studies for the detection of synergy or antagonism between antifungal agents tested against Candida species.

Currently, there is considerable debate regarding the best in vitro method for testing antifungal combinations against Candida spp. In this study, we compared the results obtained by chequerboard dilution, time-kill studies and Etest for several antifungal combinations against Candida spp. Three Candida albicans isolates (fluconazole MICs of 1.0, 32 and >256 mg/L) and three non-albicans Candida isolates (C. glabrata, C. tropicalis and C. krusei) were tested in RPMI 1640 medium. By chequerboard testing, the majority of antifungal combinations were found to be indifferent. Notably, antagonism was identified by time-kill studies and by Etest for combinations of amphotericin B-fluconazole, but it was not detected by the chequerboard method. Pre-exposure of isolates to fluconazole did not affect results of the Etest or chequerboard method, but it did increase the frequency of antagonism noted by time-kill methods. This study indicates that chequerboard dilution testing in RPMI medium may not reliably detect the attenuation of amphotericin B activity. Of the three methods, Etest was the simplest to use and yielded reproducible results for testing antifungal combinations.

Amphotericin B↗

PubMed2001

Pulmonary candidiasis in patients with cancer: an autopsy study.

For patients who had cancer and autopsy-proven pneumonia, we evaluated whether cultures of respiratory secretions (sputum and/or bronchoalveolar lavage) performed < or =4 weeks before autopsy were a reliable basis for the diagnosis of pulmonary candidiasis. Pulmonary candidiasis was identified at autopsy in 36 patients, but common clinical predictors were insensitive for this diagnosis. For sputum culture, the sensitivity, specificity, and the positive and negative predictive values were 85%, 60%, 42%, and 93%, respectively; for bronchoalveolar lavage culture, these values were 71%, 57%, 29%, and 89%, respectively.

Autopsy↗

PubMed2001

PARP co-activates B-MYB through enhanced phosphorylation at cyclin/cdk2 sites.

PARP is a multifunctional protein that can affect genome stability, transcription control, telomere length and cell death. Recently we have reported that PARP binds to and enhances B-MYB transactivating potential. B-MYB is a potentially oncogenic transcription factor involved in mammalian cell proliferation, survival and differentiation. B-MYB gene expression is growth regulated and B-MYB protein is phosphorylated during S phase by cyclin A or E/cdk2 kinase, resulting in augmented transactivating potential. Here we show that PARP induces phosphorylation of B-MYB protein at cdk2 phosphorylation sites, since a B-MYB protein with mutated cdk2 phosphorylation sites is refractory to PARP-induced phosphorylation and co-activation in mammalian cells. We propose that PARP functions as a B-MYB co-factor by promoting cyclin/cdk2-dependent B-MYB phosphorylation. These results highlight a novel role for PARP as a factor that integrates cyclin-dependent kinases signaling with gene transcription.

CDC2-CDC28 Kinases↗

PubMed2001

Progressive disseminated aspergillosis in a bone marrow transplant recipient: response with a high-dose lipid formulation of amphotericin B.

We present a case of progressive disseminated aspergillosis that involved multiple sites in a bone marrow transplant recipient with severe, chronic graft-versus-host disease. The patient failed to respond to treatment with a conventional dosage of a lipid formulation of amphotericin B (lifoAmB; 5 mg/kg/day) given alone or in combination with itraconazole, and he responded only to an aggressive strategy that included a very high dosage of lifoAmB (15 mg/kg/day) given in combination with itraconazole as well as a rapid reduction in immunosuppression. Despite the patient's abnormal baseline kidney function, the very high doses of lifoAmB were well tolerated and did not result in additional renal toxicity.

Adult↗

PubMed2001

High panel reactive antibody against cross-reactive group antigens as a contraindication to renal allotransplantation.

Preformed circulating cytotoxic IgG anti-HLA alloantibodies induced by previous failed grafts, blood transfusion, or pregnancy are a contraindication to allotransplantation and result in hyperacute rejection. These persistent, highly cytotoxic panel reactive antibodies (PRAs) may be specific for epitopes that are shared among HLA antigens known as cross-reactive groups (CREGs). The present investigation includes 24 subjects awaiting renal transplants with flow cytometric PRAs >30%. Eighty-seven percent of the patients developed alloantibodies specific for the mismatched antigens of previous failed grafts. The complement-dependent cytotoxicity test revealed that A1 and A2 antigens were highly immunogenic, whereas A23, B35, and B7 were less so. All patients who formed anti-A1 and anti-A2 also had developed alloantibodies specific for other antigens of the 1C and 2C CREGs, respectively. The presence of anti-class II HLA alloantibodies led to poor graft survival, i.e., a maximum of 2 years.

Adult↗

PubMed2001

Evaluation of amphotericin B and flucytosine in combination against Candida albicans and Cryptococcus neoformans using time-kill methodology.

In this study, time-kill methods were used to evaluate the antifungal activity of amphotericin B and flucytosine, alone and in combination, against six isolates of Candida albicans and Cryptococcus neoformans. Five regimens were tested against each isolate: (1) flucytosine, (2) low-dose amphotericin B, (3) high-dose amphotericin B, (4) low-dose amphotericin B plus flucytosine, and (5) high-dose amphotericin B plus flucytosine. Low-dose amphotericin B and flucytosine, administered alone and simultaneously, demonstrated fungistatic activity against all sample isolates except C. albicans 90028, in which fungicidal activity was detected with the combination. High-dose amphotericin B, alone and in combination, resulted in a rapid fungicidal effect in all isolates. In both the low and high-dose combinations, indifferent activity was demonstrated against all tested isolates. By virtue of the absence of an antagonistic interaction between these two agents, complementary pharmacokinetic profiles, and non-overlapping toxicities, continued clinical use of these agents in combination may be considered.

Amphotericin B↗

PubMed2001

Histamine utilizes JAK-STAT pathway in regulating cytokine production.

Histamine shifts TH1/TH2 cytokine balance from TH1 to TH2 cytokines. The phosphorylation of STAT factors and their translocation to nucleus are important steps in the regulation of TH1/TH2 cytokine balance. This study was designed to investigate the effects of histamine on Janus kinases-signal transducers and activators of transcription (JAK-STAT) pathway. The splenocytes were treated with histamine in the presence or absence of JAK-STAT inhibitor, tyrphostin, activated with IFNgamma for 30 min, and phosphorylated STAT1 was detected by immunoblotting. We found that histamine up-regulated the phosphorylation of STATI and tyrphostin prevented this phosphorylation. We then studied the effects of tyrphostin on histamine-mediated inhibition of IFNgamma production and histamine-mediated stimulation of IL-5 and IL-10 production. Tyrphostin dose-dependently reversed the effects of histamine on IFNgamma, IL-5 and IL-10 production, as evident by ELISA. These observations suggest that histamine regulated JAK-STAT signal transduction, which is involved in cytokine secretion.

Animals↗

PubMed2001

Candida lusitaniae catheter-related sepsis.

OBJECTIVE: To present a case describing Candida lusitaniae candidemia in an immunocompetent patient successfully treated with fluconazole antifungal therapy. Time-kill studies of the C. lusitaniae isolate using amphotericin B, and an extensive review of the literature are also presented. CASE SUMMARY: A 52-year-old immunocompetent Latin-American woman was admitted to the special care unit with severe sepsis. Her recent medical history included an exploratory laparotomy for gallstone pancreatitis, requiring cholecystectomy, segmental sigmoid colectomy, drainage of peritoneal abscesses, and a colostomy. In addition, the patient required a central venous catheter (CVC) placement for prolonged broad-spectrum antibiotic therapy and total parenteral nutrition therapy. Yeast was isolated from the abdominal abscess and blood cultures obtained on day 1, and from the catheter tip on day 5. The woman received initial empiric antifungal therapy with fluconazole, which was later changed to amphotericin B. After the yeast was identified as C. lusitaniae on day 8, this was changed to fluconazole for the duration of therapy. C. lusitaniae was not present in blood cultures taken two weeks after the CVC was removed, and the cultures remained negative thereafter. After a prolonged hospitalization, the patient was discharged home. DISCUSSION: Disseminated infections with C. lusitaniae usually occur in immunocompromised patients, although isolated reports of C. lusitaniae infections in immunocompetent patients have been described. Therapeutic challenges of C. lusitaniae treatment include its primary resistance to amphotericin B and species misidentification. Isolates recovered from our patient were submitted for fungus time--kill studies that suggested unique susceptibility patterns to amphotericin B, indicating a trend toward resistance. CONCLUSIONS: Based on variable susceptibility patterns of C. lusitaniae to amphotercin B and flucytosine, fluconazole is an appropriate choice as first-line therapy for C. lusitaniae candidemia.

Amphotericin B↗

PubMed2001

Rationale for combination antifungal therapy.

The relentless increase of invasive fungal infections and poor outcomes associated with available antifungal agents prompted the search for better therapeutic strategies. Combining antifungal drugs was recommended as a means to enhance efficacy in a variety of invasive infections including cryptococcosis, candidiasis, and aspergillosis. With the exception of cryptococcal meningitis, data from controlled clinical trials supporting such combinations are sparse. Moreover, little consensus exists regarding which combinations are synergistic or antagonistic in vitro and in vivo. Based on available data, several principles underlie these combinations.

Antifungal Agents↗

PubMed2001

A review of the North American Catallagia Rothschild, 1915, with the description of a new species (Siphonaptera: Ctenophthalmidae: Neopsyllinae: Phalacropsyllini).

Catallagia duffneri Lewis and Haas is described from the Pinaleno Mountains of southeastern Arizona. The 15 known North American members of the genus are illustrated, a key to them is included and the individual species are discussed with respect to their taxonomic characters, host preferences and geographic distribution.

Animals↗

PubMed2001

A taxonomic review of the Ceratophyllus Curtis, 1832 of North America (Siphonaptera: Ceratophyllidae: Ceratophyllinae).

The 22 North American taxa assigned to the flea genus Ceratophyllus Curtis, 1832, are reviewed. All are parasites of birds and include 17 species in the nominate subgenus, 3 in Emmareus and 2 in Celeophilus. Keys to the subgenera are provided, distinguishing characters of the individual species are discussed and illustrated and the various aspects of distribution and host preferences are cited.

Animals↗

PubMed2000

Association of HLA-DQ and -DR alleles with protection from or infection with HIV-1.

Infection with human immunodeficiency virus type 1 (HIV-1) and progression to acquired immune deficiency syndrome (AIDS) are controlled by both host genetic factors and viral factors. The HLA (human leukocyte antigen) region in humans controls immune response functions and tissue rejection and influences susceptibility to neoplasia, autoimmune diseases, and infectious diseases including HIV. Twenty-eight African American and 12 Caucasian patients participated in the study. HLA-DQB1 and HLA-DRB1 genotyping was performed using PCR and sequence-specific oligonucleotide probe reverse hybridization and analyzed with the LiPA Key Typing System and LiPA software. DQB1*0603 was found to be positively associated with HIV-1 infection and with HIV-1 infection in Caucasians but not African Americans. DQB1*03032 frequencies indicate a positive association with protection from HIV-1 infection. It was further found to be protective against HIV-1 infection in Caucasians but not in African Amens. DQB1*0201 was observed more frequently in HIV(+) African Americans than HIV(-) African Americans, suggesting a positive association with HIV-1 infection in this ethnic group. HLA-DRB1*04 exhibited a positive association with HIV-1 infection in Caucasians. These data show that there are HLA class II alleles associated with susceptibility to and protection from HIV-1 infection and that these differ between ethnic groups.

Adolescent↗

PubMed2000

Facilitation of immune function, healing of pressure ulcers, and nutritional status in spinal cord injury patients.

Multiple communicative pathways among nervous, endocrine, and immune systems facilitate physiological immunoregulation. Spinal cord injury (SCI) patients had strikingly decreased natural and adaptive immune responses by 2 weeks post injury. While NK-cell function was decreased, plasma ACTH and urine-free cortisol levels were increased. T cell function and activation were both diminished. With rehabilitation therapy, NK and T function increased; without rehabilitation, NK levels remained depressed. When rehabilitation ceased, NK function decreased. Cervical SCI patients had less NK and T function than thoracic injury patients. SCI patients also had reduced levels of cellular adhesion molecules (CAMs) that participate in immune function and wound healing. SCI patients with pressure ulcers were compared to those without pressure ulcers. LFA-1, VLA-4, and other surface markers were decreased on the lymphocytes of all SCI patients. SCI patients with pressure ulcers had lower CAM levels than did patients without pressure ulcers. Nutritional status was determined by zinc, albumin, and prealbumin levels. SCI patients had decreased albumin levels. Those with pressure ulcers had decreased prealbumin levels and zinc levels.

Adrenocorticotropic Hormone↗

PubMed2000

Fate of immune complexes, glomerulonephritis, and cell-mediated vasculitis in lupus-prone MRL/Mp lpr/lpr mice.

Immune complex formation was induced by the injection of (125)I-BSA into female MRL/Mp lpr/lpr mice, which develop spontaneous systemic lupus erythematosus (SLE)-like disease, and MRL/Mp +/+ mice, which do not. At designated intervals following the injection of 10 mg of (125)I-bovine serum albumin (BSA), the nonlupus mice developed sparse, small electron-dense deposits in mesangial areas and subepithelial immune deposits that underwent partial resolution. By contrast, glomeruli of the SLE-prone mouse kidneys revealed proliferation of mesangial cells and some increase in mesangial matrix material. Numerous subepithelial and mesangial electron-dense deposits were present. Some subendothelial and intramembranous deposits were also demonstrated. Capillary lumens contained massive electron-dense deposits. The resolving subepithelial deposits observed were fewer than half the number found in kidneys of the non-SLE mice. Whole body counts were also recorded daily following the injection of (125)I-BSA. Whereas, both lupus-prone and non-SLE control mice eliminated (125)I-BSA at equivalent rates through day 12 postinoculation, those with SLE-like disease showed a decreased (125)I-BSA elimination rate between days 6 and 12. Results suggest an impairment in the ability of SLE-prone mice to resolve immune complexes, whether they are nuclear-antinuclear or from an exogenous source, i.e., BSA-anti-BSA, compared to controls in this experimental model of the superimposition of exogenous immune complex formation on systemic lupus erythematosus-like disease.

Animals↗

PubMed2000

Comparison of oral immediate-release (IR) and extended-release (ER) metronidazole bactericidal activity against Bacteroides spp. using an in vitro model of infection.

We used an anaerobic infection model capable of simulating human serum pharmacokinetic parameters (C(max), C(min), half-life, and AUC) to compare the activity of oral immediate-release (IR) and extended-release (ER) MTZ formulations. Four oral regimens of MTZ plus a control regimen were simulated in the model: [i] (IR) 500 mg q8h, [ii] ER 750 mg q12h, [iii] ER 750 mg q24h, and [iv] ER 1500 mg q24h. Two clinical Bacteroides fragilis isolates (MICs 0.5, 4.0 microg/mL) and two non-fragilis Bacteroides isolates (MICs 0.5, 3 microg/mL) were studied. All four oral MTZ regimens exhibited rapid, bactericidal activity (> or =3-log(10) decrease from the starting inoculum) within 12 h against both fragilis and non-fragilis Bacteroides isolates. Overall, no appreciable difference in the rate of bacteria killing was noted among the four MTZ formulations against either B. fragilis isolates (P = 0.907, 0.737) or non-fragilis isolates (P = 0.809, 0.768). We conclude that ER MTZ dosed at 12 or 24-h intervals possesses equivalent bactericidal activity to standard IR MTZ dosed every eight hours against susceptible Bacteroides spp.

Administration, Oral↗

PubMed2000

In vitro pharmacodynamic characteristics of flucytosine determined by time-kill methods.

Two Candida albicans isolates, three non-albicans Candida isolates (Candida glabrata, Candida krusei, and Candida tropicalis), and one Cryptococcus neoformans isolate were evaluated by time-kill methods to characterize the relationship of flucytosine concentrations to antifungal activity and the duration of the post-antifungal effect (PAE). Against Candida and Cryptococcusisolates, flucytosine at concentrations > 1 x MIC exhibited fungistatic (</=99% reduction in CFU) activity over a 24-h time-period. The rate and extent of fungistatic activity of flucytosine against all isolates was generally not increased when 5-FC concentrations exceeded 4 x MIC. A notable PAE was detected for flucytosine against both Candida and Cryptococcus species that persisted 2 to 4 h. These in vitro data suggest that flucytosine is predominately a concentration-independent fungistatic agent at clinically achieved serum concentrations. This pharmacodynamic characteristic coupled with the persistent PAE and the relatively long half-life of flucytosine in humans (> 5 h), suggests lower daily dosing may possible without loss of antifungal efficacy.

Antifungal Agents↗