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Biomedical subjects

A Ayala

Publications and source records attributed to A Ayala.

At least 55 records · Page 3Linked to original sources
PubMed2000

L-arginine attenuates trauma-hemorrhage-induced liver injury.

OBJECTIVES: Liver injury is common after trauma-hemorrhage for which the underlying mechanism is not clear. Although administration of the essential amino acid L-arginine has been reported to restore the depressed cardiovascular functions and cell-mediated immune responses after trauma-hemorrhage, it remains unknown whether L-arginine protects against liver injury under those conditions. DESIGN: A prospective, controlled animal study. SETTING: A university research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: Rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, four times the maximum shed blood volume over 1 hr. During resuscitation, animals received either 300 mg/kg of L-arginine or saline (vehicle) intravenously. At 3 and 5 hrs after resuscitation, rats were killed, blood was obtained, and the liver was fixed for histology (hematoxylin & eosin staining). Plasma glutathione S-transferase (a marker of liver damage), L-arginine, citrulline, and ornithine concentrations were assessed. MEASUREMENTS AND MAIN RESULTS: The increased concentrations of plasma glutathione S-transferase observed in vehicle-treated hemorrhage animals were normalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the histology indicated that L-arginine prevented liver edema and neutrophil infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline were increased in L-arginine-treated rats. CONCLUSIONS: Because citrulline is a by-product of nitric oxide generation by nitric oxide synthase from L-arginine, this amino acid may be a useful adjunct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.

Animals↗
PubMed2000

Septic mucosal intraepithelial lymphoid immune suppression: role for nitric oxide not interleukin-10 or transforming growth factor-beta.

OBJECTIVE: Recent studies indicate that sepsis induces a marked depression in the splenocyte immune response (as illustrated by decreased interleukin [IL]-2 production, interferon [IFN]-gamma production, or both) in response to T-cell mitogen. However, it is not known whether a similar depression is evident in the phenotypically distinct, small intestine intraepithelial lymphocytes (IELs) or what regulates this process during sepsis. Because the maintenance of a competent mucosal immune response is thought to be central to the animal's ability to survive sepsis, we attempted to determine whether IEL's IL-2/IFN-gamma production is suppressed and what mediates this depression. RESULTS: Our studies indicated that C3H/HeN mice subjected to cecal ligation and puncture (CLP) exhibited a marked decline in the ability of IELs to release IL-2/IFN-gamma at 24 hours and that this decline is associated with increased secretion of IL-10 and nitric oxide (NO). To the extent that IL-10 accounted for this loss of IL-2/IFN-gamma release, we observed that IL-10 gene deficiency neither restored the IL-2/IFN-gamma release nor suppressed the increase in NO when compared with background control, C57BL/6J mouse cells. To further study whether NO was involved in this immune suppression, iNOS knockout (iNOS -/-) were also subjected to the same procedure; however, the depression in IL-2/IFN-gamma was not seen in iNOS -/- mice when compared with background controls. CONCLUSION: Our data indicate that IL-10, which affects splenic lymphoid response, may not be a key mediator of IEL immune suppression and that the induction of NO may play a more significant role in gastrointestinal immune dysfunction seen in late sepsis.

Animals↗
PubMed2000

CXC chemokine suppression of polymorphonuclear leukocytes apoptosis and preservation of function is oxidative stress independent.

Interleukin 8 (IL-8) and growth-related oncogene alpha (Gro-alpha) delay neutrophil apoptosis, which is thought to be important for the resolution of inflammation. We hypothesized that (IL-8) and Gro-alpha interfere with extracellular death receptor signaling or intracellular caspase activation to suppress neutrophil apoptosis. In addition, we sought to determine if prolonged neutrophil half-life was associated with preservation of function. Polymorphonuclear leukocytes (PMN) were cultured with IL-8 or Gro-alpha (0-100 ng/mL) in normoxia or hypoxia, and the extent of apoptosis was assessed by histology and TdT-mediated dUTP nick end labeling (TUNEL). Subsequently, to determine the role of apoptotic-associated receptors, PMN were cultured with IL-8 and neutralizing monoclonal antibody to Fas (CD95), TNFR55, and TNFR75. To establish the effect of IL-8 or Gro-alpha on pro-apoptotic caspase activity, the cleavage of specific colorimetric substrates was assessed. Functional changes in PMN included the capacity to produce superoxide anion and phagocytosis of Escherichia coli. At the 100 ng/mL dose, the addition of IL-8 and Gro-alpha maximally suppressed PMN apoptosis from 54% (untreated) to 5% and 6%, respectively. The addition of neutralizing antibodies to Fas, TNFR55, or R75 caused no change in IL-8 suppression of apoptosis. Caspase 3 activity was markedly suppressed at 24 h by the inclusion of either IL-8 and Gro-alpha. IL-8 and Gro-alpha-stimulated PMN released more superoxide anion and had an increased phagocytic index vs. control PMN. IL-8 and Gro-alpha suppress neutrophil apoptosis to a similar level that is not influenced by oxygen tension at high doses. The effect of IL-8 and Gro-alpha does not depend on activation of the Fas, TNFR55, or R75 receptor pathways but involves suppression of caspase 3 activity. IL-8 or Gro-alpha extends the functional half-life of neutrophils and may explain their role in disease states such as acute respiratory distress syndrome.

Antibodies↗
PubMed2000

Effect of gender and sex hormones on immune responses following shock.

Several clinical and experimental studies show a gender dimorphism of the immune and organ responsiveness in the susceptibility to and morbidity from shock, trauma, and sepsis. In this respect, cell-mediated immune responses are depressed in males after trauma-hemorrhage, whereas they are unchanged or enhanced in females. Sex hormones contribute to this gender-specific immune response after adverse circulatory conditions. Specifically, studies indicate that androgens are responsible for the immunodepression after trauma-hemorrhage in males. In contrast, female sex steroids seem to exhibit immunoprotective properties after trauma and severe blood loss, because administration of estrogen prevents the androgen-induced immunodepression in castrated male mice. Nonetheless, the precise underlying mechanisms for these immunomodulatory effects of sex steroids after shock remain unknown. Although testosterone depletion, testosterone receptor antagonism, or estrogen treatment has been shown to prevent the depression of immune functions after trauma-hemorrhage, it remains to be established whether differences in the testosterone-estradiol ratio are responsible for the immune dysfunction. Furthermore, sex hormone receptors have been identified on various immune cells, suggesting direct effects. Thus, the immunomodulatory properties of sex hormones after trauma-hemorrhage might represent novel therapeutic strategies for the treatment of immunodepression in trauma patients.

Androgen Antagonists↗
PubMed2000

TNFalpha-induced suppression of PMN apoptosis is mediated through interleukin-8 production.

Dysregulated neutrophil (polymorphonuclear PMN) apoptosis is thought to contribute to the onset of adult respiratory distress syndrome (ARDS) in critically ill patients. Tumor necrosis factor-alpha (TNFalpha), which is present in elevated levels in the bronchoalveolar lavage fluid in patients with ARDS, is thought to play a central role in regulating PMN function in the lungs. Studies have shown that short-term culture with TNFalpha increases apoptosis yet extended culture with TNFalpha suppresses apoptosis. However, it is unclear whether this latter effect of TNFalpha is directly or indirectly mediated through production of anti-apoptotic cytokines such as interleukin (IL)-8. To investigate the role of IL-8 in TNFalpha-induced apoptosis PMN were exposed to TNFalpha (100 ng/mL) in the presence or absence of antibodies to IL-8, and the extent of apoptosis was assessed. An enzyme-linked immunoassay was used to measure levels of the anti-apoptotic cytokine IL-8, induced by TNFalpha-stimulation. Because TNFalpha may mediate its effect through various cell-signaling pathways, we next assessed the effect of kinase inhibition on the ability of TNFalpha to effect apoptosis and IL-8 production. Treatment with TNFalpha had a biphasic effect: at 4-8 h, apoptosis was increased but was markedly suppressed at 24 h (P < 0.05). PMN cultured for 24 h with TNFalpha also showed markedly increased levels of IL-8. Neutralization of IL-8 inhibited the ability of TNFalpha to suppress apoptosis (P < 0.05). Incubation of TNFalpha + p38-mitogen-activated protein kinase (MAPK) inhibitor SB202190 increased apoptosis (P < 0.01) and decreased IL-8 production to PMN control. To a lesser extent, incubation of TNFalpha with inhibitors to NF-kappaB (SN50) and PI3K (LY294002) also increased apoptosis and decreased IL-8 production (P < 0.05). These data illustrate a novel mechanism by which TNFalpha can indirectly elicit an anti-apoptotic effect via p38-MAPK induced release of the anti-apoptotic chemokine IL-8. The exploitation of such a pathway represents a potential target for regulation of PMN-mediated acute lung injury.

Antibodies↗
PubMed2000

Reversal of sexual dimorphism in splenic T lymphocyte responses after trauma-hemorrhage with aging.

Previous studies have demonstrated that hemorrhagic shock produces immunodepression in young male mice, whereas the immunoresponsiveness in young proestrus female mice is enhanced under such conditions. This sexually dimorphic immune response to hemorrhage appears to be related to high estrogen and testosterone levels in females and males, respectively. Nonetheless, it is unknown what impact the age-related decline in the sex steroid levels has on the immune response after hemorrhage. To study this, young (2-3 mo) and aged (18-19 mo) male and female CBA/J NIA mice were subjected to laparotomy (i.e., soft tissue trauma) and hemorrhage (35 +/- 5 mmHg for 90 min and fluid resuscitation) or sham operation. Twenty-four hours later, splenocyte responses were assessed in vitro. Splenic T lymphocyte responses [i.e., proliferation, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) release] were depressed in young males and enhanced in young females after trauma-hemorrhage. In contrast, in the aged male and female groups these parameters of splenocyte function were reversed after trauma-hemorrhage (i.e., increased proliferation and IL-2 release in aged males compared with suppressed proliferation and IFN-gamma release in aged females). Furthermore, the release of the immunosuppressive cytokine IL-10 inversely correlated with the age- and gender-related changes in splenocyte responses after trauma-hemorrhage. Thus the sexually dimorphic immune response in young males and females to trauma-hemorrhage appears to reverse as sex hormone levels decline with age.

Aging↗
PubMed2000

Insight into the mechanism by which metoclopramide improves immune functions after trauma-hemorrhage.

Although studies have shown that prolactin (Prl) and metoclopramide (Mcp) administration restores the depressed cell-mediated immune functions after hemorrhage, the underlying mechanism responsible for the immunostimulatory effects of Mcp remains unknown. We hypothesized that Mcp improves immune responses by upregulating the secretion of Prl. To test this hypothesis, male C3H/HeN mice were subjected to sham operation or laparotomy (i.e., soft tissue trauma) and hemorrhagic shock (Hem; 35 +/- 5 mmHg for 90 min) and then resuscitated. Plasma Prl levels were determined 30 min after Mcp (1 microgram/g body wt sc at end of Hem) or vehicle (Veh) treatment in sham and Hem mice. The results indicate that plasma Prl levels increased significantly in Mcp-treated mice (sham-Veh 249.9 +/- 5.3, Hem-Veh 229.9 +/- 7.6, Hem-Mcp 596.9 +/- 73.1 ng/ml, one-way ANOVA, P < 0.05 vs. Veh). To determine whether Mcp produces its salutary effects directly or indirectly via increased Prl secretion, splenocyte proliferation and splenocyte interleukin (IL)-2 and IL-3 release from untreated sham or Hem mice were determined in the presence of increasing concentrations of mouse Prl or Mcp. The addition of Mcp had no effect on splenocyte immune functions in vitro. However, the addition of Prl restored the hemorrhage-induced depressed splenocyte proliferation as well as splenocyte IL-2 and IL-3 release in vitro in a dose-dependent manner. Thus the beneficial effects of Mcp on immune functions after Hem appear to be mediated by Prl. Because Mcp increases plasma levels of the immunoenhancing hormone Prl, this agent should be considered a useful adjunct for the treatment of immunodepression in trauma victims.

Animals↗
PubMed2000

Insights into the role of gammadelta T lymphocytes in the immunopathogenic response to thermal injury.

Studies have shown that cell-mediated immunity is markedly suppressed after thermal injury. T lymphocyte dysfunction and macrophage hyperactivity have been implicated as causative factors. Previous studies have primarily examined the effects of thermal injury on alphabeta T lymphocytes; however, the role of gammadelta T lymphocytes in the immune response after thermal injury is unclear. Therefore, wild-type mice and mice lacking the TCR delta gene (TCR delta-/-) were subjected to a third-degree scald burn and cell-mediated immune responses assessed at 7 days post-injury. TCR delta-/- mice had 75% mortality after burn injury compared with 25% mortality in the wild-type group. Plasma interleukin-6 (IL-6) levels were significantly elevated at 2, 4, and 18 h post-injury, whereas no difference was observed in tumor necrosis factor alpha (TNF-alpha) and prostaglandin E2 (PGE2) plasma levels. Plasma levels of these inflammatory mediators were similar in wild-type and TCR delta-/- mice post-injury. Splenic macrophage PGE2, IL-6, TNF-alpha, and IL-10 production was significantly increased in wild-type mice at 7 days post-injury, whereas macrophages from injured TCR delta-/- mice had a significantly attenuated capacity to produce IL-6 and TNF-alpha. In contrast, the increased release of PGE2 and IL-10 by macrophages post-injury was not reduced in TCR delta-/- mice. These results implicate a dual role for gammadelta T lymphocytes in the immunopathogenic response to burn injury: (1) they contribute to survival from the insult; and (2) they mediate the induction of a pro-inflammatory macrophage phenotype at 7 days post-injury. Thus, gammadelta T lymphocytes, in part through the modulation of macrophage activity, appear to contribute to the immune dysfunction after thermal injury.

Animals↗
PubMed2000

The loss of Mcl-1 expression in human polymorphonuclear leukocytes promotes apoptosis.

The regulation of polymorphonuclear leukocyte (PMN) apoptosis can influence the duration of the inflammatory response. We have previously shown that PMN apoptosis is delayed by matrix adhesion and hypoxia; however, the mechanisms responsible for this delay are not well understood. Mcl-1, an antiapoptotic Bcl-2 family member, is present in neutrophils; therefore, we sought to characterize its localization and function as it relates to PMN apoptosis. We found that Mcl-1 localized to the nucleus and cytoplasm and that expression levels decreased as PMN were aged in culture. Reducing available Mcl-1 through the use of antisense oligonucleotides demonstrated that Mcl-1 is necessary to delay apoptosis during normal PMN aging and hypoxia but is not required for suppression of apoptosis by laminin adhesion. Our results demonstrate a distinct expression pattern of Mcl-1 and that Mcl-1 is crucial for the delay of apoptosis initiated by certain antiapoptotic factors.

Adult↗
PubMed1999

Role of protein kinase C in cyclic AMP-mediated suppression of T-lymphocyte activation following burn injury.

Major burn injury induces T-lymphocyte dysfunction. Previous studies suggest that prostaglandin (PG) E2, which is elevated post-burn, is the causative factor via a cyclic AMP-dependent process. The present study was conducted to elucidate the mechanism by which cAMP induces T-lymphocyte dysfunction following burn injury. Splenocytes were isolated from mice 7 days after receiving a scald burn covering 25% of their total body surface or sham procedure. ConA-induced proliferation by splenocytes from burned mice was significantly suppressed. Macrophage depletion of the splenocyte cultures abrogated the suppression. Concanavalin A-stimulated proliferation by macrophage-depleted splenocytes was suppressed by PGE2 and dibutyryl cAMP in both groups. The IC50 of these cAMP-elevating agents, however, was approximately 100-fold lower for cells from burned mice, indicating an increased sensitivity to cAMP. PGE2 did not suppress PMA/Ca2+ ionophore-induced T-lymphocyte activation. Addition of PMA to ConA-stimulated cultures prevented the suppression of proliferative responses by PGE2, whereas Ca2+ ionophore had no effect. Thus, the suppression of T-lymphocyte activation following burn injury is macrophage-dependent, related to an increased sensitivity to cAMP and due to an uncoupling of cell surface receptors from protein kinase C activation.

Animals↗
PubMed1999

Splenic immune suppression in sepsis: A role for IL-10-induced changes in P38 MAPK signaling.

BACKGROUND: Studies have indicated that following the induction of sepsis, there is a late (24 h) generalized suppression of the immune response which is associated with increased anti-inflammatory mediator release (e.g., IL-10). However, the mechanisms by which this occurs are unknown. In this regard, recent studies indicate that p38 mitogen-activated protein kinase (p38 MAPK) may play a central role in transducing the signals from immunosuppressive agents which in turn may alter lymphoid cytokine release. The aim of this study, therefore, was to determine whether the anti-inflammatory mediator IL-10 alters splenocyte IL-2 and IFN-gamma release, as well as the expression and activation of p38 MAPK in septic animals. MATERIALS AND METHODS: Splenocytes (SPL) (or for some experiments purified T cells) were harvested from mice subjected 24 h earlier to either sepsis by cecal ligation and puncture (CLP) or Sham-CLP and stimulated with 2.5 microg concanavalin A (ConA)/ml in the presence or absence of either monoclonal antibody (Mab) to IL-10 (4 microg/ml) or IgG control. In subsequent studies, sepsis was induced in C57BL/6J and C57BL/6 IL-10 knockout mice, and SPL harvested and stimulated with ConA. SPL cytokine release was measured by ELISA, and the expression and phosphorylation of p38 MAPK were measured by Western analysis. RESULTS: The results indicate that Th1 cytokine (IL-2, IFN-gamma) release was depressed by sepsis, while p38 MAPK expression and activity were increased in SPL as well as in T-cells. Neutralization of IL-10 by in vitro use of anti-IL-10 Mab and in the IL-10 knockout animal restored the Th1 response and caused a downregulation of p38 MAPK expression and activity after CLP. Thus, IL-10 appears to contribute to the increase in p38 MAPK activity and expression and the corresponding suppression of Th1 response seen in late sepsis.

Animals↗
PubMed1999

Dehydroepiandrosterone restores immune function following trauma-haemorrhage by a direct effect on T lymphocytes.

Although a profound depression in immune function occurs following injury, the mechanism responsible for this is not fully understood. Furthermore, steroid hormones are known to be important mediators in the regulation of immune function. Although dehydroepiandrosterone (DHEA), the most plentiful steroid hormone, has been shown to stimulate immune function in normal animals, it is unknown whether DHEA has any salutary or detrimental effects on immune responses after trauma and haemorrhage. To study this, male mice were subjected to trauma, haemorrhage and resuscitation, following which they received either DHEA or vehicle subcutaneously. DHEA administration restored the normally depressed splenocyte proliferation as well as interleukin 2, interleukin 3, and interferon gamma elaboration following trauma and haemorrhage. In an attempt to determine the mechanisms mediating this effect, T cells were stimulated in vitro in the presence of DHEA and a variety of hormone antagonists. The stimulatory effect of DHEA on splenocyte proliferation was unaltered by the testosterone receptor antagonist flutamide, while the oestrogen antagonist tamoxifen completely abrogated its effect. In addition, DHEA administration normalized the elevated serum corticosterone level typically seen following injury. These results indicate, therefore, that DHEA improves splenocyte function after trauma and haemorrhage by directly stimulating T cells and also by preventing a rise in serum corticosterone.

Adjuvants, Immunologic↗
PubMed1999

Effects of aging on the various steps of protein synthesis: fragmentation of elongation factor 2.

The possible mechanism responsible for the in vivo protein synthesis decline during aging was studied. In order to determine the effect of aging on the various steps of protein synthesis, we determined the ribosomal state of aggregation and the time of assembly and release of polypeptide chains in the process of protein synthesis in rat liver. The results suggest that elongation is the most sensitive step to aging. A molecular study of the Elongation Factor 2 (EF-2), the main protein involved in the elongation step, shows that this protein has a higher content of carbonyl groups and is less active in old rats. In addition, the molecular mass analysis of EF-2 shows that this protein becomes fragmented in old rats. A similar pattern of fragmentation is found in 3-month-old rats suffering oxidative stress, in that the decline in protein synthesis is similar to that found in old rats. These data suggest that: i) oxidative stress seems to be involved in the modifications of EF-2 observed during aging, and ii) the observed modifications (oxidation and fragmentation) of EF-2 could account for the decline in protein synthesis in old animals.

Aging↗
PubMed1999

Induced mono-(ADP)-ribosylation of rat liver cytosolic proteins by lipid peroxidant agents.

We have studied the effect of free radical generating agents on the mono-(ADP)-ribosylation of rat liver cytosolic proteins. Our results show that this post-translational modification, whose physiological significance is still unclear, is activated by lipid peroxidant agents via activation of cytoplasmatic mono-(ADP)-ribosyltransferases. The implication of free radicals in this process is demonstrated by the fact that mono-(ADP)-ribosylation can be prevented by melatonin, N-tert-butyl-alpha-phenylnitrone and dithiothreitol. On the basis of our results, we discuss the modification of proteins caused by free radicals as a possible mechanism by which they damage the cell.

ADP Ribose Transferases↗
PubMed1999

Increased inducible apoptosis in CD4+ T lymphocytes during polymicrobial sepsis is mediated by Fas ligand and not endotoxin.

Recent studies suggest that increased lymphocyte apoptosis (Ao) detected in peripheral blood T cells from burn patients appears to contribute to decreased lymphocyte immunoresponsiveness. However, while it is known that sepsis induces a marked depression in the splenocyte immune response (i.e. decreased interleukin-2, interferon-gamma production and proliferation) in response to the T-cell mitogen concanavalin A (Con A), it is unknown whether this depression is associated with an increase in inducible Ao and if so, which mediators control this process. To assess this, splenocytes were harvested from mice at 24 hr (a period associated with decreased Con A response) after the onset of polymicrobial sepsis [caecal ligation and puncture (CLP)] or sham-CLP (Sham) and then stimulated with 2.5 microg Con A/ml (24 hr). Septic mouse splenocytes stimulated with Con A, while not showing a change in their phenotypic make-up, did exhibit a marked increase in the percentage of splenocyte that were Ao+ which was associated with altered cytokine release. This appears to be due to an increase in the percentage of Ao+ cells in the CD4+ CD8- population and was associated with enhanced Fas antigen expression as well as an increase in mRNA for the Fas-FasL gene family. To determine if the changes in Ao are due to either endotoxin (a product of Gram-negative bacteria seen in CLP mice) or the expression of Fas ligand (FasL; a mediator of activation-induced lymphocyte Ao), a second set of studies examining Con A-inducible Ao was performed with splenocytes harvested from septic endotoxin-tolerant C3H/HeJ and the FasL-deficient C3H/HeJ-Fasl gld mice. The results show that increased splenocyte Ao detected following CLP is due to a FasL-mediated process and not to endotoxin. Thus the inadvertent up-regulation of FasL-mediated splenocyte Ao may contribute to the depression of splenocyte immune responses seen during polymicrobial sepsis.

Animals↗
PubMed1999

Clear cell sarcoma of kidney in an adolescent and in young adults: a report of four cases with ultrastructural, immunohistochemical, and DNA flow cytometric analysis.

Clear cell sarcoma of the kidney is a distinct, highly malignant pediatric neoplasm. Its occurrence in adults is extremely rare and the subject of isolated case reports. We present a series of four cases (three males and one female) identified in an adolescent and in young adults (16, 18, 20, and 25 years) with flank mass (three cases), hematuria (two cases), flank pain (two cases), and hypertension (one case). Three patients had stage III disease and one had stage I disease (National Wilms' Tumor Study staging system). All tumors had predominantly or exclusively the classic histology of a monotonous proliferation of uniform small round cells with evenly distributed fine chromatin, although focal microcyst formation (two cases) and spindled architecture (one case) (variant patterns) were also noted. Therapy in all cases consisted of surgery and chemotherapy with or without radiation. Follow-up data (29-202 months) showed distant metastases in all four cases, including the lung (four cases), bone (two cases), and the liver (two cases). Three patients died of disease at 29, 59, and 63 months (mean, 50.3 months), and one patient is alive with no evidence of disease at 202 months. Ultrastructural features included scattered primitive junctions, short and irregular cytoplasmic extensions, and scant to a moderate amount of mitochondria. Immunohistochemical study (three cases) showed immunoreactivity with vimentin (two cases) and no reaction with cytokeratin, epithelial membrane antigen, S-100 protein, or desmin. Flow cytometric analysis showed diploid DNA content in three primary tumors and tetraploidy in one metastatic tumor. The proliferative activity (S-phase fraction) was low to intermediate (mean, 9.8%). Our data suggest that clear cell sarcoma of the kidney in the young adult age group resembles its pediatric counterpart in ultrastructural and immunohistochemical characteristics, proclivity for skeletal and visceral metastasis, DNA diploid status with relatively low S-phase, and aggressive clinical course. Clear cell sarcoma of the kidney in adult patients, although rare, must be differentiated from sarcomatoid carcinoma, sarcomas, and round cell tumors because of its unique characteristics in comparison to other renal neoplasms.

Adolescent↗