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Biomedical subjects

G Arya

Publications and source records attributed to G Arya.

15 recordsLinked to original sources
PubMed1998

Minimally invasive surgery does not improve the outcome in a model of retroperitoneal murine neuroblastoma.

Minimally invasive surgery (MIS) for cancer patients has become widely accepted in general surgery, however, it has not completely replaced the standard open operative procedures in pediatric oncology. The aim of this study was to evaluate the host relationship following MIS in a murine model of retroperitoneal neuroblastoma (NB) Immature, 5- to 7-week-old male A/J mice weighing 18-23 g were inoculated with either C1300 or TBJ NB in the left retroperitoneal space. At 4 days (early stage) or 11 days (late stage) following tumor inoculation, the animals underwent a laparotomy or pneumoperitoneum with carbon dioxide under general inhalational anesthesia. Animal survival, tumor growth, and postoperative changes in body weight were observed. In the model of subcutaneous TBJ NB, distant metastases following the laparotomy or MIS technique were also evaluated. Each surgical group had a sample size > or = 12, and data were statistically analyzed by ANOVA and the chi-square test where appropriate. P < 0.05 was considered to be significant. There were no significant differences in animal survival, tumor growth, or distant metastases among surgical groups in any combination of type and stage of tumor. The only salutary influence of MIS was seen in a model of early-stage NB, where the decrease in body weight on postoperative day 7 was preserved when compared to post-laparotomy weight loss. We conclude that when compared to conventional laparotomy, the MIS access technique does not influence the outcome in a model of retroperitoneal murine NB.

Animals↗
PubMed1998

Mechanism and prevention of port-site tumor recurrence after laparoscopy in a murine model.

BACKGROUND/PURPOSE: Although minimally invasive surgery (MIS) has been broadly applied in patients with cancer of the gastrointestinal tract, the etiology of port-site tumor recurrence (PSR) after laparoscopic cancer surgery remains unclear. The authors report here an analysis of PSR in a model of murine neuroblastoma after laparoscopic tumor biopsy and propose a mechanism for this complication as well as a potential treatment. METHODS: Immature 5- to 7-week old male A/J mice (18-23 g) were subcutaneously inoculated with the minimally immunogenic TBJ-neuroblastoma (TBJ-NB) in the left flank and divided into three treatment groups. The following operations were performed 14 days after tumor inoculation: group 1, additional intraperitoneal or intravenous injection of TBJ-NB during CO2 pneumoperitoneum; group 2, simulated transperitoneal tumor biopsy using MIS techniques during either CO2 pneumoperitoneum or gasless suspension; Group 3, intraperitoneal (IP) or intravenous (IV) administration of cyclophosphamide on postoperative days 0 and 3 to prevent PSR after simulated tumor biopsy during CO2 pneumoperitoneum. RESULTS: In group 1, the incidence of PSR was 0% in the intravenously injected mice versus 63% in mice injected intraperitoneally with TBJ-NB. In group 2, no significant difference in the incidence of PSR was seen between simulated tumor biopsy (89%) animals with CO2 pneumoperitoneum versus animals with gasless suspension (81%). In group 3, mice that did not receive any chemotherapy had an 89% incidence of PSR. Administration of cyclophosphamide via either the IP or IV route effectively prevented PSR, although there was no difference in the incidence of PSR between the two routes (IP 12% versus IV 13%). CONCLUSIONS: The data suggest that PSR in tumor-bearing hosts may be caused by direct seeding of exfoliated tumor cell, and not by hematogenous metastases. Contrary to the other reports, CO2 pneumoperitoneum was not found to be essential for the development of PSR. Furthermore, the authors conclude that postoperative chemotherapy may be useful in preventing PSR after MIS in patients bearing chemotherapy-sensitive tumors such as neuroblastoma.

Animals↗
PubMed1997

A comparative review of the immunobiology of murine neuroblastoma and human neuroblastoma.

BACKGROUND: The prognosis for children with neuroblastoma (NB) remains dismal, in part because of extent of disease at diagnosis as well as resistance of tumors to conventional therapies. However, human NB exhibits many favorable traits, including the capability to mature into a more benign form or to regress spontaneously. A murine model of disease that could permit eventual genetic manipulation, so that such beneficial traits could be identified or even augmented, would be most useful. METHODS: This report details an analysis of the contemporary study of the tumor growth, metastases, immunogenicity, and immunotherapy of murine NB and compares it with known patterns of clinical NB. RESULTS: Striking similarities exist in the local tumor growth and metastatic behaviors of murine and human NB, behaviors that in part may be related to a host-tumor immunologic response. The naturally low expression of class I antigen in NB, the ability to augment that expression with cytokines, and the phenotype of the cellular and humoral immune response to NB are strikingly similar in human and murine hosts. Comparable immunotherapeutic potential exists. There have been rare and sporadic observations of spontaneous regression of an existing murine NB, unlike the more predictable regression of Evans Stage IV-S clinical NB. CONCLUSIONS: The many similar biologic, physiologic, and immunologic characteristics of human and murine NB make the murine model a valuable adjunctive aid in furthering our understanding of human disease.

Animals↗
PubMed1997

Evaluation of operative stress and peritoneal macrophage function in minimally invasive operations.

BACKGROUND: Laparoscopic operative procedures have decreased postoperative pain and the length of hospitalization. In addition, evidence supports a physiologic benefit from laparoscopic surgery. By analyzing several parameters of peritoneal macrophage function, we report a comparison of the magnitude of postoperative stress between two types of minimally invasive access techniques contrasted with an open laparotomy, in a murine model. STUDY DESIGN: Immature male A/J mice were exposed to pneumoperitoneum using carbon dioxide, gasless suspension, or laparotomy. Peritoneal macrophages were then harvested, and the number and viability of the macrophages from each group of mice were compared. Last, as a marker of postoperative stress, the in vitro production of nitric oxide and tumor necrosis factor alpha by these macrophages was determined. RESULTS: The number of peritoneal macrophages and the viability of the macrophages in the laparotomy group were significantly decreased 4 hours after operation compared with the minimally invasive and control groups. In addition, macrophage production of tumor necrosis factor alpha and nitric oxide, two markers of macrophage stress, 24 hours after operation was significantly increased in the laparotomy group compared with animals serving as controls. Gasless suspension and pneumoperitoneum decreased the number of macrophages to a lesser degree than did open laparotomy and did not affect macrophage viability. Moreover, gasless suspension and pneumoperitoneum did not lead to an increase in tumor necrosis factor alpha or nitric oxide production by peritoneal macrophages. CONCLUSIONS: Postoperative stress, assessed by a decrease in macrophage viability and an increase in cytotoxic cytokine production, is maximized after laparotomy compared with stress in murine hosts that underwent minimally invasive treatment. These data provide basic scientific evidence for the possible physiologic benefit of minimally invasive techniques.

Animals↗
PubMed1996

The interval between a septic stimulus and hypoxia/reoxygenation affects cytokine elaboration by murine peritoneal macrophages.

The critically ill patient is commonly exposed to various physiological insults. The authors have previously shown that in vivo hypoxia/reoxygenation (H/R) alters the pattern of cytokines elaborated by murine peritoneal macrophages given a septic stimulus. In this study they sought to determine whether the interval between a septic stimulus and H/R affected the release of inflammatory mediators by macrophages. Adult CBA-strain mice were injected intraperitoneally with 10 micrograms of lipopolysaccharide (LPS). On day 0, 1, 2, 3, 4, or 5 after LPS injection, animals were exposed to 16 hours of hypoxia followed by 2 hours of reoxygenation. Harvested peritoneal macrophages were restimulated in vitro with 2.5 micrograms/mL LPS or left unstimulated. Culture supernatants collected at 2, 4, 6, 8, 10, and 12 hours after LPS injection were assayed for tumor necrosis factor (TNF), prostaglandin E2 (PGE2), and nitric oxide (NO) production. Macrophage-derived mediator production peaked when H/R occurred 3 days following LPS injection (P < .05). These data suggest that the interval between sepsis and subsequent H/R influences the pattern of cytokines elaborated by peritoneal macrophages given a septic stimulus.

Analysis of Variance↗
PubMed1995

Hypoxia/reoxygenation affects endotoxin tolerance.

Pretreatment of animals with sublethal doses of endotoxin renders them tolerant to subsequent endotoxin challenge. Tissue hypoxia following infection may potentiate the immune response to injury. To evaluate the effect of hypoxia/reoxygenation (H/R) on endotoxin tolerance by macrophages, adult CBA mice were pretreated with 10 micrograms/animal of LPS injected intraperitonealy. Five days later, animals were subjected to 16 hr of hypoxia followed by 2 hr of reoxygenation. Harvested peritoneal macrophages were cultured and either stimulated in vitro with LPS or left unstimulated. Culture supernatants collected at 2, 4, and 6 hr were assayed for tumor necrosis factor (TNF), prostaglandin E2 (PGE2), and nitric oxide (NO). Control animals underwent the same procedures, but were maintained in normoxia. H/R resulted in significantly greater TNF production but significantly lower PGE2 and NO production, P < 0.05 by ANOVA. These data suggest that LPS-induced tolerance of macrophages to the same stimulus is abated by H/R.

Animals↗
PubMed1995

Weanling and adult rats differ in fatty acid and carnitine metabolism during sepsis.

Increased oxidation of fat is an important host response to sepsis, and carnitine is essential for long-chain fatty acid oxidation. Because neonates have low levels of carnitine, their ability to respond to a septic insult may be impaired. The purpose of this study was to compare fatty acid and carnitine metabolism in septic weanling (60 to 85 g) and septic adult (285 to 310 g) rats. Sepsis was induced in weanling and adult male Sprague-Dawley rats by cecal ligation and puncture (CLP). The rats were killed 16 hours after CLP or sham operation, and serum glucose, lactate, beta-hydroxybutyrate, fatty acid, carnitine, liver fatty acid, and tissue carnitine levels were measured. The data suggest that during sepsis weanling rats may be more dependent on fatty acid oxidation than adult rats are, as evidenced by their elevated serum fatty acid and acylcarnitine levels, and relative hypoglycemia and hyperketonemia. In addition, although total serum carnitine levels were increased in both adult and weanling septic rats, tissue carnitine levels of weanling rats became significantly depleted during sepsis, unlike in adult rats. This study supports further investigation regarding the role of exogenous carnitine in newborn sepsis.

3-Hydroxybutyric Acid↗
PubMed1994

Dietary fish oil enhances macrophage production of nitric oxide.

Nitric oxide (NO) is recognized as an important mediator of hemodynamic regulation and multisystem organ failure (MOF). Although polyunsaturated fatty acids (PUFA) are known to modify the elaboration of some humoral mediators in MOF, their effect upon NO production has not been evaluated. This study was designed to examine the effect of omega-3 (omega 3) and omega-6 (omega 6) PUFA on macrophage production of NO, TNF, PGE2, and PGI2. Rats were fed diets of 18% by calorie safflower oil (omega 6) or fish oil (omega 3) for 12 days. Bronchoalveolar macrophages (BAM) were divided into group A (medium only), group B (0.5 microgram/ml PGE2 or PGI2 + medium) or group C (10 microM indomethacin+medium). Cells were stimulated with 100 U/ml interferon-gamma and 10 micrograms/ml Escherichia coli-LPS. In group A, BAM from animals fed omega 3 produced significantly more NO (3.64 vs 1.92 microM, P < 0.05) and TNF (8.52 vs 1.75 micrograms/ml, P < 0.05) than BAM from omega 6-fed animals. The addition of exogenous PGE2 or PGI2 (group B) ablated the difference in NO and TNF observed in group A. Indomethacin also (group C) ablated the difference in NO and TNF production seen in omega 3- and omega 6-fed animals noted in group A. These data demonstrate that PUFA influence BAM production of NO and TNF. Changes in the omega 6-derived prostanoids may account for the differences in TNF production, but these data suggest that PGE2 and PGI2 are not responsible for the observed differences in NO production.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Epidermal growth factor enhances intestinal adaptation after massive small bowel resection.

Epidermal growth factor (EGF) has documented trophic effects on several tissues, including small bowel (SB) mucosa. The purpose of this study was to determine the effect of EGF on intestinal adaptation after massive resection. Young Sprague-Dawley rats (weight, 154 +/- 8.6 g) underwent a 75% proximal SB resection, with primary reanastomosis, and were continuously infused with equivalent volumes of either saline or human recombinant EGF (6.25 micrograms/kg/h) via a subcutaneous osmotic pump. In other animals, the SB was transected and reanastomosed without resection and either saline or EGF was infused. The animals were allowed standard rat chow and water ad libitum and were killed after 28 days. SB was harvested and subjected to histological examination. Intestinal mucosa was analyzed for total DNA and protein contents. After massive SB resection, subcutaneous administration of EGF resulted in significantly increased animal weight (294.5 +/- 16 v 242.8 +/- 14g; P < .05), SB weight (52.8 +/- 7.0 v 37.2 +/- 6.0 cm; P < .05), SB length (14.0 +/- 1.3 v 7.4 +/- 1.6 g; P < .05), and mucosal thickness (1.04 +/- 0.2 v 0.68 +/- 0.2 mm; P < .05). DNA and protein analyses suggest that EGF may augment the mucosal hyperplasia response to massive SB resection. Administration of EGF after massive SB loss may be of nutritional benefit to the host through its enhancement of the normal postresection intestinal response.

Adaptation, Physiological↗
PubMed1994

Prostaglandin and tumor necrosis factor levels in early wound inflammatory fluid: effects of parenteral omega-3 and omega-6 fatty acid administration.

Monokines are important mediators of wound healing. Specifically, the proportions of proinflammatory (tumor necrosis factor and PGE2) and antiinflammatory (PGF2 alpha) monokines may modulate its early phases. Using a polyvinyl alcohol sponge model of rat wounding, the authors determined the temporal changes in the levels of monokines in wound inflammatory fluid, and examined whether dietary manipulation for 6 days with the precursors (omega 6 fatty acids) and inhibitors (fish oil omega 3 fatty acids) of the prostaglandin-2 series influenced monokine composition of wound fluid. For 3 days before the wounding, adult rats received isocaloric, isovolemic, and isonitrogenous total parenteral nutrition (TPN), in which lipids supplied either 35% (Intralipid [IL] or fish oil emulsion [FO]) or 8% (minimal essential fatty acid; EFA) of the total calories. Control rats received isocaloric enteral chow. The controls were studied at 24, 48, 72, and 96 hours, and the experimentals at 72 hours after wounding. Cell counts were performed, and cell-free fluid was analyzed for PGE2, PGF2 alpha, and TNF. In control rats, the total WBC count was highest at 24 to 48 hours, and decreased significantly by 96 hours. The percentage of mononuclear cells progressively increased throughout the 96 hours, and the total mononuclear cell count peaked at 72 hours. The TNF and prostaglandin levels were highest at 24 hours; these decreased rapidly by 72 hours. At all time-points, the levels of PGE2 remained higher than those of PGF2 alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Immune-mediated regression of 'metastatic' neuroblastoma in the liver.

It is understood that neuroblastoma (NB) in the liver of patients with clinical stage IV-S disease may disappear, but the mechanism of such regression is unclear. A genetic hypothesis has previously been suggested, although heretofore an immunologic explanation had not been reported. Using C1300 NB in AJ mice, we developed a model of liver metastatic disease by directly injecting tumor cells into a subcutaneously translocated spleen. Intrasplenic inoculation of 2 x 10(6) C1300 NB cells produced liver subcapsular foci of NB in 100% of animals, whose mean survival period was 18 days. Three days after tumor inoculation, interleukin-2 (IL-2) (2,400 U/d) was continuously infused for 14 days via a miniosmotic pump, and daily survival was followed. Animals were sampled serially by histological and immunohistochemical staining. Animal survival was significantly prolonged (P < .05) in the IL-2 group when compared with that of saline controls, but importantly, 50% of the mice were cured. Histological examination showed early infiltration of mononuclear cells, predominantly lymphocytes, around liver metastatic foci; and phenotypic analysis of these cells showed them to be Thy-1.2-positive and asialo GM1-positive, suggesting they are of natural killer (NK) and lymphokine-activated killer (LAK) origin. Most importantly, in cured animals the histological analysis of the liver demonstrated reversion to a scar-free anatomy, akin to that seen in stage IV-S NB survival. These data suggest that immune-mediated regression of NB in the liver is possible; whether the result of therapy or spontaneous, the liver histology reverts to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Serial culture and characterization of the chinchilla middle ear epithelium.

We have successfully cultured a fibroblast-free chinchilla middle ear epithelium up to the 10th passage by using conditioned medium or using irradiated 3T3 cells as feeder cells. The cultured epithelial cells assumed a polygonal shape with a cobblestone appearance, indicating tight junction formation. A small number of the cells began to show abnormal morphology, such as indistinct cell boundaries, fibroid appearance, or giant cell formation, as the passage increased, particularly after the 5th passage. These morphologically transformed cells showed positive labeling with an anticytokeratin antibody, which indicated the epithelial origin of these cells. Neither ciliated nor secretory cells were observed in the serially cultured cells. The rate of cell growth slowed after the 7th passage, and after the 11th passage the cells no longer proliferated. Even with the above limitations, these cultured cells can be used for a number of in vitro experiments.

Animals↗
PubMed1990

Enzyme linked immunosorbent assay for the diagnosis of human neurocysticercosis: a preliminary report.

The diagnostic efficacy of an indirect enzyme linked immunosorbent assay (ELISA) was evaluated in cases of neurocystecercosis. Subjects studied included 22 cases and 30 controls (comprising 12 cases of surgically confirmed hydatid disease, 5 cases each of tuberculoma and P.U.O. and 8 cases of pyogenic meningitis). A standard ELISA was performed using porcine cysticerci as antigen. Sensitivity and specificity of the test were calculated for serum and cerebrospinal fluid separately. The test was found to give a sensitivity of 68 and 33 per cent for serum and C.S.F. respectively. The specificity for confirmed case was found to be cent per cent for both with the criteria of reporting used. The sensitivity of the test may be increased by using purified specific antigen and/or sandwich ELISA instead of indirect ELISA technique.

Brain Diseases↗
PubMedDate not supplied

Long-chain predominant lipid emulsions inhibit in vitro macrophage tumor necrosis factor production.

Intravenous lipid emulsions are an important component of parenteral nutrition. Despite their benefits, lipid emulsions have been associated with higher rates of bacteremia in neonates. Therefore we investigated the effect of lipid emulsions on the inflammatory response by examining their effect on in vitro macrophage tumor necrosis factor (TNF) production of two distinct macrophage populations. Through the use of endotoxin-free phosphate buffered saline, peritoneal (PER) and alveolar (ALV) macrophages were isolated from male Sprague-Dawley rats (weighing 125 to 150 g) with endotoxin-free phosphate buffered saline. Cell counts were adjusted to 2 x 10(6) cells/mL in RPMI with 2% fetal calf serum. Three hundred microliters of the cells were incubated in a 24-well culture dish with media or media with intralipid (100 micrograms/dL) for 16 hours. After washing each well three times, the cells were stimulated for 2 or 16 hours with Escherichia coli lipopolysaccharide (150 microL of 1 microgram/mL). The supernatants were assayed for TNF using the WEHI 164:13 bioassay and TNF levels were expressed as picograms per milliliter. Student's unpaired t test was used for data analysis. Lipid-exposed PER and ALV macrophages in vitro TNF levels were significantly lower-after 2 hours (12,591 pg/mL +/- 3837 vs 20,591 pg/mL +/- 6344 for PER, 3894 pg/mL +/- 1258 vs 13,177 pg/mL +/- 3266 for ALV) and 16 hours (6427 pg/mL +/- 3050 vs 12,353 pg/mL +/- 4877 for PER; 131,6000 pg/mL +/- 7317 vs 354,680 pg/mL +/- 31,605 for ALV) of endotoxin stimulation. TNF production seems to be impaired in macrophages exposed to a .1% lipid emulsion for 16 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗