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Biomedical subjects

J Glass

Publications and source records attributed to J Glass.

At least 19 recordsLinked to original sources
PubMed2005

Transvaginal contraception--avoid the bladder.

We report two cases of female contraceptive methods, resulting in urological presentation, with bladder foreign bodies. History, mode of diagnosis and surgical extraction technique differed in both patients. The first, where a thermometer was lost intravesically whilst measuring an internal temperature, presented immediately. A plain abdominal X-ray confirmed the position of the foreign body. Extraction was performed cystoscopically with the thermometer intact. A second patient, with recurrent urinary tract infections, was found to have an intrauterine contraceptive device (IUCD) in her bladder on ultrasound. Attempts to remove it endoscopically failed, and an, open procedure was required to free the IUCD from the bladder sidewall.

Adult↗
PubMed2004

Methylation of tumor suppressor gene p16 and prognosis of epithelial ovarian cancer.

OBJECTIVE: Methylation of p16 promoter was evaluated in ovarian cancer to determine the role of p16 methylation in ovarian cancer prognosis. METHODS: Two hundred and forty-nine patients with primary epithelial ovarian cancer were selected for the study; these patients were followed for a median of 31 months. Genomic DNA extracted from fresh frozen tumor tissues were treated with sodium bisulfite and were analyzed for p16 methylation using methylation-specific PCR (MSP). Cox regression survival analysis was performed to examine the associations of p16 methylation with progression-free and overall survivals. RESULTS: Of the 249 patients, 100 (40%) were tested positive for p16 promoter methylation. The status of p16 methylation did not change significantly with patient age, disease stage, histological grade, residual tumor size, and debulking results, although p16 methylation seemed to occur more often in patients with advanced diseases or aggressive tumors. Compared to those without p16 methylation, patients with p16 methylation had significantly higher risk for disease progression (P = 0.01). The relative risk for progression was 1.69 (95% CI: 1.12-2.54), and the association remained statistically significant (RR = 1.54, 95% CI: 1.01-2.34) after adjusting for clinical and pathological variables. The risk for death was also higher in methylation positive patients than in methylation negative patients (RR = 1.33, 95% CI: 0.88-2.00), but the difference was not statistically significant. CONCLUSION: The study suggests that promoter methylation in the p16 gene is associated with ovarian cancer progression, and evaluation of p16 methylation may have values in predicting ovarian cancer prognosis.

Adult↗
PubMed2004

Contribution of PET imaging to the initial staging and prognosis of patients with Hodgkin's disease.

BACKGROUND: Positron emission tomographic (PET) scanning utilizing [18F]fluorodeoxyglucose (FDG) is a new method of tumor imaging based on the increased glucose metabolic activity of malignant tumors. In Hodgkin's disease (HD), PET has proven value for the evaluation of residual masses following treatment and for the early diagnosis of relapse. In the initial staging of HD, PET frequently shows a higher stage than conventional methods (upstaging by PET). In the present study, we evaluated the frequency of stage changes by PET in a multicenter setting and determined its prognostic relevance. PATIENTS AND METHODS: A total of 73 patients with newly diagnosed HD were staged with both conventional methods and whole-body PET scanning. All histological types and stages were represented. The median time of follow-up after the initial diagnosis was 25 months (range 1 month to 5 years). The response to treatment was determined by standard clinical and diagnostic criteria. For the purpose of this analysis, data from a PET center associated with a university medical center and a PET center associated with a group oncology practice were combined. RESULTS: A total of 21 patients (28.8%) were upstaged by PET compared with conventional methods. In two cases (2.7%), a lower stage was suggested by PET scanning. With one possible exception, the upstaging had no obvious clinical or biological correlate. Among 12 patients in stage I (A + B) by conventional methods, seven were upstaged by PET (58.3%), four to stage II, one to stage III and two to stage IV. Among 42 patients in stage II, eight were upstaged by PET (19.0%), six to stage III and two to stage IV. Among 12 patients in stage III, six (50%) were upstaged to stage IV by PET. If only early-stage patients and major changes are considered (stages IA-IIB to III or IV), among 49, 10 were upstaged to III or IV, whereas in 39 staging was unchanged following PET. In the former group, three relapsed or were refractory compared with none in the latter group (P<0.006). In advanced stage patients (IIIA or IIIB) a trend toward treatment failure was apparent in patients who were upstaged by PET. CONCLUSIONS: PET scanning is an interesting new modality for the accurate staging of patients with HD and frequently shows a higher stage than conventional methods. PET should be performed at initial diagnosis and should be included in prospective studies of patients with HD. Upstaging by PET may represent a risk factor for a more advanced stage or a biologically more aggressive tumor. Patients with early-stage disease as identified by conventional methods have a significant risk of treatment failure if a more advanced stage is indicated by PET. At present, major stage changes suggested by PET imaging should be confirmed by an independent diagnostic method.

Adult↗
PubMed2004

Pseudoaneurysm formation after flexible ureterorenoscopy and electrohydraulic lithotripsy.

Although electrohydraulic lithotripsy (EHL) is regularly used to fragment urinary calculi, it has the potential to cause significant renal tract damage. We report a complication of EHL use during flexible ureterorenoscopy, where recovery was complicated by delayed, prolonged haematuria secondary to the formation of a pseudoaneurysm in an interlobar renal artery. Embolisation was achieved by the insertion of a coil.

Adult↗
PubMed2004

Percutaneous nephrolithotomy in early pregnancy.

Most cases of urolithiasis in pregnancy are managed conservatively either with ureteric stents or percutaneous nephrostomy tubes, which need to be changed at regular intervals. Definitive management of the stone is usually delayed till after delivery. We describe a patient who presented with pyonephrosis in the fifth week of gestation, due to a stone obstructing the right ureteropelvic junction. This was managed by insertion of a nephrostomy tube. She declined nephrostomy tube/stent changes during the rest of her pregnancy and requested termination as an alternative. She successfully underwent percutaneous nephrolithotomy in the 14th week of pregnancy, with radiation exposure strictly localised to the kidney for 6 s. A healthy male baby was delivered at term.

Adult↗
PubMed2003

Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans.

BACKGROUND: Animal studies have documented significantly better preserved postoperative cell-mediated immune function, as measured by serial delayed-type hypersensitivity (DTH) challenges, after laparoscopic-assisted than after open bowel resection. Similarly, in humans, the DTH responses after open cholecystectomy have been shown to be significantly smaller than preoperative responses; whereas after laparoscopic cholecystectomy, no significant change in DTH response has been noted. The purpose of this study was to assess cell-mediated immune function via serial DTH skin testing in patients undergoing laparoscopic or open colectomy. METHODS: A total of 35 subjects underwent either laparoscopic (n = 18) or open colectomy (n = 17) in this prospective but not randomized study. Only patients who were judged to be immunoresponsive by virtue of having responded successfully to a preoperative DTH challenge were eligible for entry in the study. DTH challenges were carried out at three time points in all patients: preoperatively, immediately following surgery, and on the third postoperative day (POD 3). Responses were measured 48 h after each challenge and the area of induration calculated. There were no significant differences between the laparoscopic (LC) and open (OC) colorectal resection groups in regard to demographics, indications for surgery, or type of resection carried out. The percentage of patients transfused was similar in both groups (17%, LC; 12% OC; p = NS). In the LC group, all cases were completed without conversion using minimally invasive methods. There were no perioperative deaths, and the rate of postoperative complications was similar in both groups. The preoperative and postoperative DTH results were analyzed and compared within each surgical group using several methods. RESULTS: In regards to the OC group results, the median sum-total DTH responses for the day of surgery challenges (0.44 +/- 69 cm2) and the POD 3 challenges (0.72 +/- 3.37 cm2) were significantly smaller than the preoperative results (3.61 +/- 3.83 cm2, p <0.0005 vs op day and p <0.0003 vs POD 3 results). When the LC group results were similarly analyzed, no significant difference in DTH response was noted between the pre- and the postoperative challenge results. Additionally, when the median percent change from baseline was calculated and considered for the OC group's DTH results, both postoperative challenge time points demonstrated significantly decreased responses when compared to their preoperative results (vs day of surgery, p <0.007; vs POD 3, p <0.006). Similar analysis of the LC group's results yielded nonsignificant differences between the pre- and postoperative responses. Lastly, when the LC and the OC groups median percent change from baseline results were directly compared for each of the postoperative challenges, a significant difference was noted for the POD 0 challenge (LC, -21%; OC 88%; p <0.004) but not for the POD 3 challenge. CONCLUSIONS: The postoperative DTH responses of the open surgery patients were significantly smaller than their preoperative responses. This was not the case for the laparoscopic group (a combination of fully laparoscopic and laparoscopic-assisted resections). When the open and laparoscopic groups results are directly compared, regarding the results of the day of surgery DTH challenges, the LC groups median percent change from baseline was significantly less than that observed in the OC group. These results imply that open colorectal resection is associated with a significant suppression of cell-mediated immune response postoperatively, whereas in this study laparoscopic colorectal resection was not. Further human studies are needed to verify these findings and to determine the clinical significance, if any, of this temporary difference in immune function following colon resection.

Antigens, Fungal↗
PubMed2001

COX-2 expression in dysplasia of the head and neck: correlation with elF4E.

BACKGROUND: COX-2 inhibitors have shown promise in chemoprevention of epithelial tumors. eIF4E is a biomarker that has identified individuals at high risk for relapse after definitive treatment for head and neck squamous cell cancer (HNSCC). Hence, the authors wanted to determine if COX-2 is expressed in dysplasia of the head and neck and to study the correlation of expression of COX-2 with eIF4E as a potential surrogate endpoint for determining response to COX-2 inhibitors. METHODS: The authors studied the expression of COX-2 and eIF4E in normal epithelium (n = 8), dysplasia (n = 51), mucosa adjacent to tumors (n = 11), and cancer of the head and neck (n = 19) using immunohistochemistry. In addition, Western blot analysis was performed on a subset of the above patient samples and HNSCC cell lines. RESULTS: Immunohistochemical analysis showed expression of COX-2 and eIF4E in all cancers and no expression in normal tissues. In dysplastic epithelium, there was a significant correlation between the expression of eIF4E and COX-2 for all groups of dysplasia combined (chi-square = 40.3, P < 0.001). A Cochran-Armitage trend test showed a significant increase in the proportion of cases that expressed both molecular markers with increasing grades of dysplasia (P = 0.001). Western blot analysis showed increased expression of COX-2 and eIF4E in tumors compared with adjacent mucosa. All three HNSCC cell lines analyzed had increased expression of eIF4E, although only two had increased COX-2 expression. CONCLUSIONS: Expression of COX-2 in dysplasia suggested that COX-2 inhibitors may play a role in chemoprevention of head and neck cancers and that the correlation of Cox-2 with eIF4E indicates that eIF4E can be a potential surrogate marker in chemoprevention trials.

Anticarcinogenic Agents↗
PubMed2001

Levels of insulin-like growth factor after stem cell transplantation.

Some cytokines, i.e. tumor necrosis factor-, interleukin-6 and soluble interleukin-2 receptors are associated with complications of stem cell transplantation. Insulin-like growth factors (IGFs) are a family of peptides essential for the proliferation of normal and malignant cells. Recently increased levels of IGFs have been associated with the development of malignant tumors. In this communication we report on 96 measurements of insulin-like growth factor-I (IGF-1), insulin-like growth factor-II (IGF-2), and insulin-like growth factor-binding protein-3 (IGFBP-3) performed in 19 patients following stem cell transplants. Seventeen patients had allogeneic and 2 patients autologous transplants. Most IGF determinations were made at days 0, 7, 14, 21 and 28, some at other time points. The baseline values (day 0) of IGF-1 and IGFBP-3 were not different from controls. IGF-2 values were slightly lower than controls. Following transplantation, a consistent increase of IGF-1 was observed in 9/16 patients at days 7 and 14. Later the values decreased again. IGF-2 and IGFBP-3 did not change significantly after transplantation. No direct correlation could be established with the severity of graft-versus-host disease, levels of interleukin-6 and the time to hematopoietic recovery. A potential relevance of IGFs following stem cell transplantation may be the early diagnosis of liver damage and the development of second malignancies. More studies are necessary to investigate the pathophysiology and the clinical relevance of the increase of IGF-1 following stem cell transplantation.

Adolescent↗
PubMed2001

Increased frequency of the tumor necrosis factor-alpha-308 A allele in adults with human immunodeficiency virus dementia.

Genetic polymorphisms in the regulatory regions of various cytokine genes influence the amount of cytokine produced in response to inflammatory stimuli. To determine whether such polymorphisms might play a role in human immunodeficiency virus (HIV) dementia, a disease process in which tumor necrosis factor (TNF)-alpha is believed to play a role, we analyzed HIV-infected adults with and without dementia and control populations for a polymorphic site located in the promoter region of the gene coding for TNF-alpha. The presence of the A allele at the TNF-alpha-308 site was overrepresented among adults with HIV dementia compared to those without dementia (0.28 vs 0.07; OR 5.5; 95% CI 1.8-17.0) and a healthy control population (0.28 vs 0.11). The increased frequency of the A allele in HlV-infected adults with dementia suggests that this locus may play a role in the pathophysiology of dementia and suggests a genetic predisposition for the development of HIV dementia.

AIDS Dementia Complex↗
PubMed2001

Breast cancer: a socioeconomic and racial comparison in northwest Louisiana.

A tumor registry data review on breast cancer populations seen at two hospitals in North Louisiana was completed in order to determine if race is independent of socioeconomic status (SES) factors related to breast cancer stage at diagnosis. The North Louisiana tumor registry identified 1183 patients diagnosed with breast cancer between 1987 and 1991, 304 patients from Louisiana State University Health Science Center (LSUHSC), a state supported hospital providing predominantly indigent care, and 879 patients from a private hospital (PH) serving predominantly insured patients. Hospital site was used as a proxy for SES (LSUHSC low, PH high). The patient populations differed significantly by age, racial makeup, and stage at presentation. Both white and African-American patients seen at PH had more stage 0 disease compared with LSUHSC (9.2% and 2.7%). White patients seen at PH had more stage I cancer as compared to white patients at LSUHSC (31.3% and 19.2%) or African-American patients at either PH or LSUHSC (19.4% and 19.9%). The frequency of stage III/IV cancer was higher in African-American patients at both LSUHSC (30.1%) and PH (29.0%) and white patients at LSUHSC (24.0%) as compared to white patients at PH (14.7%). Two hundred and nine patients were available for individual interview and specific definition of SES. LSUHSC patients were predominantly indigent (83% indigent and without insurance), while only 10% of PH patients lacked insurance. This study provides further support that the SES of white patients influences breast cancer stage at presentation. African-American patients, however, presented with more advanced breast cancer stages regardless of SES. Factors influencing African-American patient's disease stage are not limited to defined SES factors. Further studies are needed to define barriers and develop intervention strategies.

Breast Neoplasms↗
PubMed2000

Zinc transport and metallothionein secretion in the intestinal human cell line Caco-2.

Caco-2, a human cell line, displays several biochemical and morphological characteristics of differentiated enterocytes. Among these is the ability to transport zinc from the apical to the basal compartment. This process was enhanced following exposure by the apical compartment to increasing concentrations of the metal. High pressure liquid chromatography fractionation of the media obtained from cells labeled with radioactive zinc showed that metallothioneins (MTs), small metal-binding, cysteine-rich proteins), were present in the apical and basal media of controls as well as in cells grown in the presence of high concentrations of zinc. Following exposure to the metal, the levels of Zn-MTs in the apical medium increased, while in the basal compartment the greatest part of zinc appeared in a free form with minor changes in the levels of basal MTs. Metabolic labeling experiments with radioactive cysteine confirmed the apical secretion of MTs. A stable transfectant clone of Caco-2 cells (CL11) was selected for its ability to express constitutively high levels of the mouse metallothionein I protein. This cell line showed an enhanced transport of the metal following exposure to high concentrations of zinc and a constitutive secretion of the mouse metallothionein I protein in the apical compartment. Together, these findings strongly support the hypothesis of a functional role between the biosynthesis and secretion of MTs and the transport of zinc in intestinal cells.

Animals↗
PubMed2000

Correlation of p53 and the proto-oncogene eIF4E in larynx cancers: prognostic implications.

p53 abnormalities constitute the most frequent genetic alterations identified in larynx cancers. p53 overexpression in histologically "tumor-free" surgical margins correlates with a high recurrence rate. However, only 50-60% of tumors overexpress p53. The tumor marker eIF4E is overexpressed in 100% of larynx cancers, and overexpression of eIF4E in histologically "tumor-free" margins predicts a significantly higher recurrence. We undertook this study to correlate the expression of p53 and eIF4E in the tumors and surgical margins of squamous cell cancers of the larynx and to determine their prognostic value. A retrospective analysis was performed on 54 patients who underwent surgery for squamous cell cancers of the larynx. Patient and tumor characteristics were reviewed, and the time to recurrence was noted. Paraffin-embedded sections from the tumors and surgical margins were immunostained with antibodies to eIF4E and p53, and a qualitative analysis was performed. All 54 patients (100%) overexpressed eIF4E in the primary tumor, whereas 25 of 53 patients (47%) were p53 positive. Thirty-two of the 54 patients (59%) had eIF4E-positive margins. All 6 of 53 patients (11%) with p53-positive margins also overexpressed eIF4E in the margins. There was a significant correlation between p53 and eIF4E being positive in the margins (Spearman's correlation coefficient, P = 0.03). Twenty-one of the 25 patients (84%) that recurred, including the 6 patients with p53-positive margins, had eIF4E-positive margins. Hence, although the univariate analysis showed that nodal status and both eIF4E and p53 expression in the margins were significant predictors of recurrence (P < 0.05), in the multivariate analyses only nodal status (P < 0.001) and eIF4E in the margins (P < 0.001) were significant predictors of recurrence. Kaplan-Meier analysis demonstrated that the disease-free intervals for eIF4E-positive margins were significantly shorter than eIF4E-negative margins (P = 0.0007). There was no additional effect to the combination of positive p53 and eIF4E margins (P = 0.21). The overexpression of eIF4E in the margins appears to be a more sensitive indicator of recurrence and may be an earlier event in the process of tumorigenesis than p53.

Analysis of Variance↗
PubMed2000

Apo-transferrin is internalized and routed differently from Fe-transferrin by caco-2 cells: a confocal microscopy study of vesicular transport in intestinal cells.

Caco-2 cells grown as monolayers on porous membranes in bicameral chambers have been used to study the transport of Fe from the apical (lumenal) chamber to the basal (serosal) chamber. The transport of Fe is stimulated by the presence of either apo-transferrin (apo-Tf) or ferri-transferrin (Fe-Tf) in the basal chamber with the stimulation occurring at much lower concentrations of apo-Tf than Fe-Tf. To further explore the involvement of Tf in Fe transport across the basal surface, laser scanning confocal microscopy with 3-dimensional reconstruction of the confocal images was used to visualize the internalization of Texas Red-labeled apo-Tf and Bodipy-labeled Fe-Tf from the basal chamber. These studies show that apo-Tf was readily internalized and routed preferentially to a perinuclear region of the Caco-2 cells while internalized Fe-Tf stayed preferentially below the nuclei. These findings suggest that intestinal cells have a specialized mechanism to recognize and sort apo-Tf. (Blood. 2000;95:721-723)

Apoproteins↗
PubMed2000

Workshop III: late motor complications of Parkinson's disease.

The aim in the current treatment of Parkinson's disease is to delay L-Dopa administration and to keep the L-Dopa dosage as low as possible. Such a treatment strategy can delay the onset of late motor complications and reduce their severity. L-Dopa remains the most potent anti-parkinsonian medication, but its use for the initial therapy of Parkinson's disease is limited to elderly patients. In all other cases, dopamine agonists, budipine, amantadine and selegiline are primarily used. With the occurrence of late motor complications continuous dopamine receptor stimulation becomes essential. In this situation, combination therapy has to be individualized, with dopamine agonists playing a key role. In addition, COMT inhibitors, budipine, amantadine and selegiline may be used. Anticholinergic drugs are of very limited importance in the current treatment of Parkinson's disease.

Antiparkinson Agents↗
PubMed2000

Rapid activation of NF-kappaB and AP-1 and target gene expression in postischemic rat intestine.

BACKGROUND & AIMS: The molecular mechanisms underlying intestinal mucosal damage-repair processes induced by ischemia-reperfusion (IR) remain unknown. We determined nuclear factor-kappaB (NF-kappaB) and activator protein 1 (AP-1) activities and the expression of potential target genes relevant to damage-repair events. METHODS: Rat jejunal segment was subjected to ischemia for 30 minutes followed by reperfusion for defined times. NF-kappaB and AP-1 activities; mucosal p105, p50, and inhibitor kappaB-alpha (IkappaB-alpha) levels; and c-fos, neurotensin, and ferritin H expression were determined by electrophoretic mobility shift assay and Western and Northern analyses, respectively. RESULTS: NF-kappaB and AP-1 activities were significantly elevated from 1 to 12 hours after reperfusion. The activated NF-kappaB in the nuclear extract consisted of solely p50 homodimers. Activation of p50 was associated with a decrease of p105, generation of p50, and increased phosphorylation and degradation of IkappaB-alpha. The activated AP-1 contained c-fos but not c-jun, fosB, and Fra-1. Reperfusion induced a transient elevation of c-fos, prolonged increase of neurotensin, and early reduction followed by recovery of ferritin H messenger RNA. CONCLUSIONS: The intestine shows organ-specific responses to IR, characterized by prolonged NF-kappaB and AP-1 activation involving NF-kappaB p50 dimers and excluding AP-1 c-jun protein. Degradation of the IkappaB-gamma component of p105 and partial reduction IkappaB-alpha selectively activate p50/p50 dimers. Temporal patterns of target gene expression reflect functional relevance to mucosal damage-repair processes after IR.

Animals↗
PubMed2000

Phase II study of combination taxol and estramustine phosphate in the treatment of recurrent glioblastoma multiforme.

Taxol has activity in the treatment of high grade gliomas but estramustine phosphate (EMP) has not been used in this setting. In vitro data demonstrates that EMP is cytotoxic to glioma cell lines and estramustine binding proteins are expressed by glioma cells. The combination of Taxol and EMP is reported to be active in the treatment of hormone-refractory prostate cancer and in taxane-resistant breast and ovarian cancer. We therefore performed a phase II study to assess the activity and toxicity of this combination in high grade gliomas. Taxol was given at a dose of 225 mg/m2 intravenously over three hours on day 1 and EMP was given at a dose of 900 mg/m2 orally on days 1 through 3. Cycles were repeated every three weeks. Twenty patients with recurrent glioblastoma multiforme (GBM) were enrolled: 11 male, median age 45 years. All patients received anti-epileptic medications and 17 (80%) had received prior chemotherapy. Of 18 evaluable patients, two had partial responses (11) and six had stable disease (33%) for a minimum of eight weeks. Treatment was well tolerated with grade 3 neutropenia occurring in only three patients. There were no other grade 3 or 4 toxicities. The median time to progression for the cohort was only six weeks (range 3-60+ weeks). The median overall survival was 12 weeks (range 3-60+ weeks). In conclusion, the combination of Taxol and EMP is well tolerated and has modest activity in the treatment of recurrent GBM.

Adult↗
PubMed2000

Evidence for the induction of apoptosis by endosulfan in a human T-cell leukemic line.

Several organochlorinated pesticides including DDT, PCBs and dieldrin have been reported to cause immune suppression and increase susceptibility to infection in animals. Often this manifestation is accompanied by atrophy of major lymphoid organs. It has been suggested that increased apoptotic cell death leading to altered T-B cell ratios, and loss of regulatory cells in critical numbers leads to perturbations in immune function. The major objective of our study was to define the mechanism by which endosulfan, an organochlorinated pesticide, induces human T-cell death using Jurkat, a human T-cell leukemic cell line, as an in vitro model. We exposed Jurkat cells to varying concentrations of endosulfan for 0-48 h and analyzed biochemical and molecular features characteristic of T-cell apoptosis. Endosulfan lowered cell viability and inhibited cell growth in a dose- and time-dependent manner. DAPI staining was used to enumerate apoptotic cells and we observed that endosulfan at 10-200 microM induced a significant percentage of cells to undergo apoptotic cell death. At 48 h, more than 90% cells were apoptotic with 50 microM of endosulfan. We confirmed these observations using both DNA fragmentation and annexin-V binding assays. It is now widely being accepted that mitochondria undergo major changes early during the apoptotic process. We examined mitochondrial transmembrane potential (deltapsim) in endosulfan treated cells to understand the role of the mitochondria in T-cell apoptosis. Within 30 min of chemical exposure, a significant percentage of cells exhibited a decreased incorporation of DiOC6(3), a cationic lipophilic dye into mitochondria indicating the disruption of deltapsim. This drop in deltapsim was both dose- and time-dependent and correlated well with other parameters of apoptosis. We also examined whether this occurred by the down regulation of bcl-2 protein expression that is likely to increase the susceptibility of Jurkat cells to endosulfan toxicity. Paradoxically, the intracellular expression of bcl-2 protein was elevated in a dose dependent manner suggesting endosulfan-induced apoptosis occurred by a non-bcl-2 pathway. Based on these data, as well as those reported elsewhere, we propose the following sequence of events to account for T-cell apoptosis induced by endosulfan: uncoupling of oxidative phosphorylation --> excess ROS production --> GSH depletion --> oxidative stress --> disruption of deltapsim --> release of cytochrome C and other apoptosis related proteins to cytosol --> apoptosis. This study reports for the first time that endosulfan can induce apoptosis in a human T-cell leukemic cell line which may have direct relevance to loss of T cells and thymocytes in vivo. Furthermore, our data strongly support a role of mitochondrial dysfunction and oxidative stress in endosulfan toxicity.

Annexin A5↗