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J Chawla

Publications and source records attributed to J Chawla.

15 recordsLinked to original sources
PubMed2001

Ex vivo cytokine activation of peripheral blood stem cells: a potential role for adoptive cellular immunotherapy.

Ex vivo activation of peripheral blood stem cells (PBSC) using interleukin-2 (IL-2) results in cytotoxic effector cells that may possess beneficial in vivo effects. We proposed to evaluate ex vivo stimulation of PBSC using various cytokines alone or in combination to optimize their function. Cytokine-activated PBSC were analyzed for tumor-directed cytotoxicity and their ability to remove tumor cells from long-term clonogenic assays. Mononuclear cells were obtained from the apheresis products of normal donors and cultured with IL-2 (1000 U/ml), interferon-alpha (IFN-alpha) (1000 U/ml), or IL-12 (50 U/ml) either alone or in combinations at 37 degrees C and 5% CO(2) for 24 h. Colony-forming unit-tumor (CFUT) assays were initiated using cytokine-activated PBSC with varying concentrations of MCF-7 or SKBR-3 human breast cancer cells. Standard 4-h (51)Cr-release assays were performed with cytokine-activated PBSC using MCF-7 or SKBR-3 cells as targets. Activation of PBSC with IL-2, IFN-alpha, or IL-12 resulted in enhanced cytotoxicity against the two breast cancer cell lines when compared to controls. PBSC activated with IL-2 and IFN-alpha or IL-2 and IL-12 were more cytotoxic than PBSC activated with single cytokines (p = 0.0004 for MCF-7 cells and p < 0.001 for SKBR-3 cells). Using clonogenic assays, IL-2-activated PBSC reduced the number of CFU-T to a greater extent than did IL-12 or IFN-alpha-activated PBSC (p = 0.0006). However, PBSC activated with a combination of IL-2 and IFN-alpha or IL-2 and IL-12 demonstrated 95% and 90% reductions, respectively, compared to 79% reduction using IL-2-activated PBSC (p < 0.0001). The greatest reduction in cytotoxicity occurred in the cell populations depleted of CD56(+) cells (p = 0.016) and CD8(+) CD56(+) cells (p = 0.002), suggesting that the effector cell population includes a combination of cytotoxic CD8(+) T cells and CD56(+) natural killer cells. These results demonstrate that the ex vivo activation of PBSC with cytokines, either alone or in combination, enhances cytotoxicity against, and removal of two human breast cancer cells. The combinations of IL-2 with IFN-alpha or IL-12 are most beneficial in cytotoxicity and purging assays. These results could play an important role in designing adoptive cellular immunotherapy clinical trials in the autologous hematopoietic stem cell transplant setting.

Blood Component Removal↗
PubMed1999

Paclitaxel vs cyclophosphamide in peripheral blood stem cell mobilization: comparative studies in a murine model.

Paclitaxel is a promising drug for the treatment of breast and ovarian cancer. It also may play a role in mobilization of peripheral blood stem cells (PBSC), as an alternative to cyclophosphamide (Cy). We investigated the PBSC-mobilizing potential of paclitaxel compared to Cy in a murine model. C57B1/6 mice were primed with intraperitoneal injections of Cy (200 mg/kg) or paclitaxel (60 mg/kg) and were sacrificed 4, 6, 8, or 10 days later. Spleens were harvested and processed to obtain low-density mononuclear cells that were used as PBSC. The number of hematopoietic progenitors (CFU-C) on day 4 was significantly higher in the paclitaxel group when compared to mice receiving Cy (72.0 +/- 1.8 vs 9.8 +/- 2.8, p < 0.001). By day 6, CFU-C became significantly higher in the Cy-treated group compared to the paclitaxel-treated group (195.6 +/- 31.9 vs 95.8 +/- 20.7, p < 0.05) and this trend was maintained. However, the total number of CFU-C recovered per spleen was greater in the paclitaxel-treated group (1.27 x 10(5) +/- 0.53 x 10(5) vs 1.06 x 10(5) +/- 0.36 x 10(5), NS). In contrast to paclitaxel, mobilization with Cy was associated with marked perturbation in the proportion of lymphoid cell subsets in the PBSC population along with functional impairment of lymphocytes. After 24 hours of in vitro IL-2 activation, the cytotoxic effector cell function of the Cy-mobilized PBSC population was lower than that of paclitaxel-mobilized cells when tested against three tumor cell lines (B16, melanoma; C1498, AML; and Yak-1, lymphoma). These results indicate that paclitaxel is an efficient mobilizer of PBSC, leading to early (day 4 to 6) mobilization of PBSC when compared to Cy (day 6 to 8). In addition, paclitaxel was associated with less perturbation of phenotypic and functional characteristics of cells contained within the mobilized PBSC population.

Animals↗
PubMed1998

Induction of DNA damage, inhibition of DNA synthesis and suppression of c-myc expression by the anthracycline analog, idarubicin (4-demethoxy-daunorubicin) in the MCF-7 breast tumor cell line.

PURPOSE: Studies were designed to elucidate the basis for the antiproliferative activity of the anthracycline antibiotic, idarubicin (4-demethoxy-daunorubicin) in MCF-7 breast tumor cells. METHODS: Growth inhibition was evaluated using the MTT tetrazolium dye assay, induction of DNA strand breaks was determined by alkaline elution, inhibition of DNA synthesis was assessed by measuring the incorporation of labelled thymidine into DNA, modulation of the expression of the c-myc oncogene was determined by Northern blotting and the induction of apoptosis was evaluated by alkaline unwinding, static field gel electrophoresis, terminal end labelling and assessment of cell morphology. RESULTS: MCF-7 cells were relatively sensitive to idarubicin, with an IC50 value for growth inhibition of approximately 0.01 microM. While DNA strand breakage was not evident below a concentration of 0.1 microM idarubicin, where growth inhibition exceeded 70%, both the inhibition of DNA synthesis and suppression of c-myc expression closely paralleled the profile of antiproliferative activity for idarubicin. Finally, while exposure to idarubicin resulted in a substantial loss of viable cells within 48-72 h, there was no morphological evidence of apoptotic body formation. The absence of apoptosis in cells exposed to idarubicin was supported by studies demonstrating the absence of DNA fragmentation using gel electrophoresis, alkaline elution and in situ DNA end-labelling assays. CONCLUSIONS: The results of these studies extend previous results from this laboratory indicating an association between suppression of c-myc expression, inhibition of DNA synthesis and growth arrest by topoisomerase II inhibitors, as well as the lack of induction of apoptotic cell death by topoisomerase II inhibitors in MCF-7 breast tumor cells.

Antibiotics, Antineoplastic↗
PubMed1992

Scanning electron microscopy of bacterial biofilms on indwelling bladder catheters.

Fifty Foley bladder catheters that had been indwelling for periods ranging from 3 to 83 days (mean 35 days) were examined for the presence of bacterial biofilm. Scanning electron microscopy on freeze-dried cross-sections and fixed, critical point-dried longitudinal sections revealed biofilm formation on the luminal surfaces of 44 of the catheters. Culture of urine samples and sonicates from catheters revealed that the prevalence of bacteriuria was less than that of catheter colonization. A wide range of nosocomial species were found colonizing the catheters, Escherichia coli being most often isolated. The bacterial composition of the biofilms ranged from single species to mixed communities containing up to four species. There was no relationship between the length of time that the catheter had been in situ and the extent of biofilm formation. The biofilms varied in thickness from 3 to 490 microns and were visible as layers of bacterial cells up to about 400 cells deep, embedded in a matrix.

Bacterial Adhesion↗
PubMed1992

Virulence factors in Escherichia coli from urinary tract infections in patients with spinal injuries.

A collection of 70 strains of Escherichia coli from urinary tract infections in spine-injured patients undergoing long-term bladder catheterization were tested for characteristics that have been associated with the ability to produce pyelonephritis. The incidence of the virulence factors were: mannose-resistant haemagglutinins (30%), P-fimbriae (17%), haemolysin (27%), K-antigens (28%) and aerobactin (by bioassay 33%, by gene probe 39%). Only 54% of the strains belonged to the O-serotypes usually associated with urinary tract infections. E. coli carrying the full complement of virulence factors were rare in the urinary tract of the spinal patients and were not associated with episodes of symptomatic pyelonephritis. It is clear that the neuropathic bladder and the presence of the catheter permits a wide variety of bacterial types to colonize the urinary tract and cause infection of the kidney. The identification of host markers rather than bacterial factors is suggested as a more fruitful approach to the early detection of cases likely to progress to pyelonephritis in this group of patients.

Cross Infection↗
PubMed1992

The effect of intravesical Marcain instillation on hyperreflexic detrusor contractions.

Thirty-six patients with suprasacral spinal injury were treated with intravesical local anaesthetic instillation. Eighteen of 32 patients (56%) were converted from an 'ice water positive' hyperreflexic state to an 'ice water negative' state by bupivacaine hydrochloride. Four patients treated with lignocaine hydrochloride showed no benefit. Intravesical local anaesthetic instillation is suggested as a possible treatment for selected cases of detrusor hyperreflexia in patients on intermittent catheterisation.

Administration, Intravesical↗
PubMed1992

International infant mortality rankings: a look behind the numbers.

The very unfavorable infant mortality ranking of the United States in international comparisons is often used to question the quality of health care there. Infant mortality rates, however, implicitly capture a complicated story, measuring much more than differences in health care across countries. This article examines reasons behind international infant mortality rate rankings, including variations in the measurement of vital events, and differences in risk factors across countries. Its goal is to offer a broader context for more informed debate on the meaning of international infant mortality statistics. These statistics offer opportunities to identify strategies for improving the U.S. health care system and learn from other countries that have been more successful.

Adolescent↗
PubMed1991

Activity of some antiseptics against urinary tract pathogens growing as biofilms on silicone surfaces.

The activity of chlorhexidine, mandelic acid and a mandelic/lactic mixture were tested against biofilms of four species of gram-negative nosocomial organisms that commonly infect the catheterized urinary tract. Cells growing on silicone discs were exposed to concentrations of agents used in bladder instillation. Citrobacter diversus biofilms proved to be sensitive to all three agents. Pseudomonas aeruginosa, Proteus mirabilis and Klebsiella pneumoniae all survived well in chlorhexidine but their viability was significantly reduced by the mandelic acid formulations. These results suggest that bladder instillations of mandelic acid or mandelic/lactic acids would be more effective than chlorhexidine in eliminating biofilms from catheter surfaces.

Anti-Infective Agents, Urinary↗
PubMed1990

Significance of false-positive serologic tests for histoplasmosis and blastomycosis in an endemic area.

False-positive serologic tests for histoplasmosis (H) and blastomycosis (B) are common in populations from endemic areas. In order to determine the significance of false-positive test results, we reviewed the final diagnoses of all patients whose sera were submitted to our laboratory for radioimmunoassay (RIA) and immunodiffusion (ID) during a 3-yr period. Of the 263 patients whose sera were examined, 29 (11%) had H or B; 41 (17.5%) of the remaining 234 patients had false-positive test results. Of these 41 patients, 31 were positive for H alone, and 10 had antibodies to both H and B. All three patients with false-positive ID tests for histoplasmosis also had positive titers (greater than or equal to 1:16) on RIA. No patient had a false-positive ID result for blastomycosis. The percentage of patients in each of five major diagnostic categories with and without false-positive serologic tests was similar (p greater than 0.05). The majority of patients had pulmonary infections, almost half of which were granulomatous infections other than H or B; this reflects the clinical indications for requesting fungal serologic tests. A positive fungal serology is not useful in suggesting the presence of a pulmonary disease other than H or B in patients from an endemic area suspected of having a pulmonary mycosis.

Blastomycosis↗
PubMed1989

Activity of antiseptics against Escherichia coli growing as biofilms on silicone surfaces.

The activity of chlorhexidine, acetic, lactic and mandelic acids were examined against biofilms of Escherichia coli established on silicone discs and against the test strain growing in suspension in urine. The results showed that the concentrations of chlorhexidine and acetic acid normally used for bladder instillations to control infections in patients with indwelling catheters failed to eliminate cells from the biofilm in exposure periods of up to 2 h. Lactic acid (1% v/v) had a bactericidal effect on planktonic cells but poor activity against cells in the biofilm. Mandelic acid (1% v/v), and mandelic (1% v/v) and lactic acid (1% v/v) mixtures eliminated organisms from both suspensions and biofilms. It is suggested that these solutions be considered as alternatives to acetic acid and chlorhexidine for the washing of catheterized bladders.

Acetates↗
PubMed1982

Dynamic urethral function in the assessment of spinal injury patients.

Forty-two spinal injury patients underwent single or sequential urodynamic studies to assess the value of dynamic urethral pressure using transducer tipped catheters. Three groups of patients were identified: those with poor detrusor function, those with unsustained dyssynergia and those with sustained dyssynergia. All patients demonstrated some dyssynergia. Urethral needle EMG mirrored urethral pressure changes accurately. The addition of dynamic profilometry to fluoroscopy, detrusor pressure and urethral EMG has clarified our understanding of lower urinary tract behaviour after cord lesions.

Adolescent↗
PubMed1977

Identification of semen in 500 patients seen because of rape.

Of 500 patients seen because of rape, semen was identified in vaginal secretions by the identification of spermatozoa in 61%, by an acid phosphatase value of 50 units or more in 40%, and by the identification of a foreign blood group substance or a high titer of own blood group substance in 16%. The addition of the determination of the acid phosphatase to the search for spermatozoa identified semen in only 1.4% more patients, or a total of 62.4%. Identification and titers of blood group substance were confirmatory only, but further characterized the source of the semen in 25% of those patients with spermatozoa. Spermatozoa were identified for as long as 48 hours, and elevated acid phosphatase was not found after 18 hours. Acid phosphatase was elevated in only 62% of patients with spermatozoa.

ABO Blood-Group System↗
PubMed1975

EEG in brain abscess: its value in localization compared to other diagnostic tests.

The EEG records of 13 cases of brain abscess were reviewed for their value in localization. Of the 11 cases of supratentorial abscesses localization was achieved in 10, and correct lateralization in the remaining 1 case. Two other cases were cerebellar abscesses; 1 of them showed a false cerebral localization; the other showed no focal abnormalities. The most consistent EEG localizing sign was focal arrhythmic delta waves. These were as slow as 0.5 c/sec in 6 of the 13 cases. Epileptiform discharges in the pre-operative EEG were seen in 4 of the 13 cases. Asymmetry of beta activity correctly lateralized the abscess in 7 of the 11 supratentorial abscesses. Generalized abnormalities when present correlated with depression of consciousness rather than with the duration of illness or the presence of raised intracranial pressure. Indium brain scans were done in 6 supratentorial abscesses and provided correct or approximate localization in 5. Carotid angiograms were also done in 7 cases and localized the abscess in 6. Our findings show that the EEG is comparable to brain scans and contrast radiological studies in localizing supratentorial abscesses. We feel that the combination of EEGs and brain scanslization in suspected brain abscess.

Adolescent↗