Dermatopathic lymphadenopathy. An immunophenotypic comparison of cases associated and unassociated with mycosis fungoides

Documenting focal mycosis fungoides in lymph node biopsies that exhibit dermatopathic lymphadenopathy is morphologically difficult. Since mycosis fungoides is a lymphoma with the phenotype of mature T cells, usually of the T-helper class, the authors investigated whether there are alterations in the ratio of Leu 3a (T-helper):Leu 2a (T-suppressor) cells in dermatopathic lymphadenopathy in order to determine the significance of immunologic markers as a possible solution to the problem. Ten lymph node biopsy specimens with diagnostic evidence of dermatopathic lymphadenopathy, but not of mycosis fungoides, were studied with the use of fresh-frozen section immunohistochemistry (FS), cell suspensions (CS), or both; five of the specimens came from patients with known cutaneous mycosis fungoides, and the other five came from patients without mycosis fungoides. The mean Leu 3a/Leu 2a ratio was 7.0 +/- 1.06 (SE) in all 10 cases of dermatopathic lymphadenopathy studied by FS and 6.9 +/- 1.14 in the 6 cases studied by CS. These ratios were significantly higher (P less than 0.001) than the mean Leu 3a/Leu 2a ratios of 2.9 +/- 0.29 (FS) and 2.4 +/- 0.22 (CS) in control lymph nodes exhibiting nonspecific reactive follicular hyperplasia, but were comparable to the mean Leu 3a/Leu 2a ratio of 5.9 obtained in two lymph node biopsies with unequivocal involvement by mycosis fungoides. Despite the increase in Leu 3a staining cells in dermatopathic lymphadenopathy, however, there were no essential differences in the Leu 3a/Leu 2a ratios between patients with and those without known mycosis fungoides. The use of other antibodies reactive with T cells, such as anti-Leu 8, anti-Leu 9, and anti-Tac also did not aid in this discrimination. The results indicate that determination of the Leu 3a/Leu 2a ratio and use of other conventional T-cell monoclonal antibodies do not provide conclusive evidence in support of a presumptive or early diagnosis of mycosis fungoides in a lymph node which fails to show histologic evidence of the disease.     

Thrombospondin-1-deficient mice exhibit increased vascular density during retinal vascular development and are less sensitive to hyperoxia-mediated vessel obliteration.

Thrombospondin-1 (TSP1) is a natural inhibitor of angiogenesis. Its expression is most prominent during the late stages of vascular development and in the adult vasculature. Our previous studies have shown that TSP1 expression promotes a quiescent, differentiated phenotype of vascular endothelial cells. However, the physiological role TSP1 plays during vascular development and neovascularization requires further delineation. Here, we investigated the role of TSP1 during development of retinal vasculature and retinal neovascularization during oxygen-induced ischemic retinopathy. The retinal vascular density was increased in TSP1-deficient (TSP1-/-) mice compared with wild-type mice. This finding was mainly attributed to increased number of retinal endothelial cells in TSP1-/- mice. During oxygen-induced ischemic retinopathy, the developing retinal vasculature of TSP1-/- mice was less sensitive to vessel obliteration induced by hyperoxia but exhibited a similar level of neovascularization induced by normoxia compared with wild-type mice. This finding is consistent with the similar pattern of VEGF expression detected in wild-type and TSP1-/- mice. Furthermore, the increased expression of TSP1 during development of retinal vasculature was not affected by oxygen-induced ischemic retinopathy. In addition, the regression of ocular embryonic (hyaloid) vessels, as well as the newly formed retinal vessels during oxygen-induced ischemic retinopathy, was delayed in TSP1-/- mice. Therefore, TSP1 is a modulator of vascular homeostasis and its expression is essential for appropriate remodeling and maturation of retinal vasculature.     

L&H variants of Reed-Sternberg cells express sialylated Leu M1 antigen.

Anti-Leu M1 generally does not stain the lymphocytic and histiocytic (L&H) variants of Reed-Sternberg cells in the lymphocyte predominant type of Hodgkin's disease. However, the authors found that after neuraminidase treatment for removal of sialic acid, the L&H cells in more than half of the cases studied could be stained by anti-Leu M1. This result strongly suggests that L&H cells differ from the Reed-Sternberg cells in other types of Hodgkin's disease in their unique capacity to sialylate the 150-kd Leu M1 antigen.     

Erythropoietin attenuates motor impairments induced by bilateral renal ischemia/reperfusion in rats

Neurologic sequelae remain a common and destructive problem in patients with acute kidney injury. The objective of this study was to evaluate the possible neuroprotective effect of erythropoietin (EPO) on motor impairments following bilateral renal ischemia (BRI) in two time points after reperfusion: short term (24 h) and long term (1 week). Male Wistar rats underwent BRI or sham surgery. EPO or saline administration was performed 30 min before surgery (1000 U/kg, i.p.). Explorative behaviors and motor function of the rats were evaluated by open field, rotarod, and wire grip tests. Plasma concentrations of blood urea nitrogen (BUN) and creatinine (Cr) were significantly enhanced in BRI rats 24 h after reperfusion. BRI group had only an increased level of BUN but not Cr 1 week after reperfusion. Impairment of balance function by BRI was not reversed by EPO 24 h after reperfusion, but counteracted 7 days after renal ischemia. Muscle strength had no significant differences between the groups. BRI group had a decrease in locomotor activity, and EPO could not reverse this reduction in both time points of the experiment. Although EPO could not be offered as a potential neuroprotective agent in the treatment of motor dysfunctions induced by BRI, it could be effective against balance dysfunction 1 week after renal ischemia.     

Spermidine reduced neuropathic pain in chronic constriction injury-induced peripheral neuropathy in rats

Neuropathic pain is one of the most critical types of chronic pain despite the increasing advances in medical science. Spermidine (SPD) is a natural polyamine that has wide roles in several cellular processes inducing autophagy and reducing oxidative stress. This study aimed to investigate the effects of SPD on oxidative stress markers and pain threshold in the neuropathic rat model of chronic constriction injury (CCI) model. Eighteen adult male rats were divided into three groups: sham, CCI and CCI+SPD. After induction of neuropathy via CCI model in the CCI and CCI+SPD groups, SPD (1 mg/kg/day, orally) was administered to the CCI+SPD group for 3 weeks. The behavioral tests (von Frey, hot plate) were done four times during the experiment. At the end of the study, electrophysiological tests, the H & E staining, and oxidative stress assay of the prefrontal cortex (PFC), spinal cord, and sciatic nerve were performed. The threshold of pain in hot plate and von Frey tests was significantly lower in the CCI group than in the sham group, which was reversed by SPD treatment in the CCI+ SPD group. In addition, nerve conduction was considerably lower in the CCI group than in the sham and CCI+SPD groups (P < 0.01, P < 0.05, respectively). The CCI group showed neuronal degeneration and fibrosis in the different tissues in the H & E assay; elevated tissues level of nitrite, decreased levels of superoxide dismutase (SOD), glutathione (GPx), and catalase were also observed. However, SPD treatment modulated the pathological changes and oxidative stress biomarkers. In conclusion, SPD showed beneficial effects in decreasing neuropathic pains. SPD treatment reduced oxidative stress and improved histopathological changes and behavioral tests in the CCI-induced neuropathic pain in in vivo model.     

Tumor DNA content in the prognosis of colorectal carcinoma

Tumor DNA content has been described as having prognostic significance in patients with colorectal carcinoma. It has been unclear, however, whether tumor ploidy as a prognostic factor is independent of various standard prognostic variables such as depth of invasion and lymph node involvement by the tumor. We retrospectively examined 77 patients who were diagnosed between 1974 and 1980 as having had resectable Dukes' stage A, B, or C colorectal carcinomas. The DNA content of each tumor was analyzed by flow cytometry on paraffin-embedded specimens. Both for aneuploid stage B tumors and for the entire group of aneuploid tumors, the disease-free and overall survival times of the patients were significantly shorter than those of patients with diploid colorectal carcinomas. Logistic regression analysis demonstrated that aneuploidy was an independent prognostic variable in predicting recurrent disease as well as death from the colorectal cancer. Tumor ploidy was, in fact, the single most important prognostic factor among all of the clinical and pathologic variables studied. Thus, the DNA content of colorectal carcinoma appears to play an important role in indicating the biologic aggressiveness of the disease.     

Olive (Olea europaea L.) leaf extract elicits antinociceptive activity, potentiates morphine analgesia and suppresses morphine hyperalgesia in rats

Aim of the study

Olive (Olea europaea) leaves are used as anti-rheumatic, anti-inflammatory, antinociceptive, antipyretic, vasodilatory, hypotensive, antidiuretic and hypoglycemic agents in traditional medicine. Recently, it has been shown that olive leaf extract (OLE) has calcium channel blocker property; however, its influences on nociceptive threshold and morphine effects have not yet been clarified.

Materials and methods

All experiments were carried out on male Wistar rats. The tail-flick, hot-plate and formalin tests were used to assess the effect of OLE on nociceptive threshold. To determine the effect of OLE on analgesic and hyperalgesic effects of morphine, OLE (6, 12 and 25 mg/kg i.p.) that had no significant nociceptive effect, was injected concomitant with morphine (5 mg/kg and 1 μg/kg i.p., respectively). The tail-flick test was used to assess the effect of OLE on anti- and pro-nociceptive effects of morphine.

Results

The data showed that OLE (50-200 mg/kg i.p.) could produce dose-dependent analgesic effect on tail-flick and hot-plate tests. Administration of 200 mg/kg OLE (i.p.) caused significant decrease in pain responses in the first and the second phases of formalin test. In addition, OLE could potentiate the antinociceptive effect of 5 mg/kg morphine and block low-dose morphine-induced hyperalgesia.

Conclusion

Our results indicate that olive leaf extract has analgesic property in several models of pain and useful influence on morphine analgesia in rats. Therefore, it can be used for the treatment and/or management of painful conditions.     

Hairy cells and monocytoid B lymphocytes: are they related?

The normal tissue counterpart of hairy cell leukemia is unknown. Because of the morphologic similarities of hairy cells to reactive and lymphomatous monocytoid cells, we compared the phenotypic characteristics of seven spleens involved by hairy cell leukemia with four reactive lymph nodes containing benign monocytoid B cells and three lymph nodes diagnosed as monocytoid B cell lymphoma. The hairy cells had a phenotype of surface Ig+, B1/Leu-14+, Leu-M5+, PCA-1+, Tac+, B2-, BA-1-, BA-2-, J5-, T10-, T11-, Leu-1-, Leu-2a-, Leu-3a-. The immunophenotype of both the reactive and neoplastic monocytoid B lymphocytes was virtually identical to the hairy cells. The major difference was that monocytoid B cells failed to react with anti-Tac and that PCA-1 expression was inconsistent. Despite these variances, the immunophenotypic similarities are remarkable, particularly the common expression of B1/Leu-14 and Leu-M5 (S-HCL3), and suggest a possible lineage relationship between hairy and monocytoid B cells.     

Coincidence of B-cell chronic lymphocytic leukemia and cutaneous T-cell lymphoma (mycosis fungoides): immunologic characterization by monoclonal antibodies

Although rare cases of chronic lymphocytic leukemia (CLL) of the T-cell type have been reported, CLL is more commonly found to be a neoplastic lymphoproliferative disease of B-cell origin. In this article, we describe a patient with long-standing CLL that was immunologically shown to be of the B-cell type, who, during the course of his disease, developed cutaneous T-cell lymphoma (CTCL), which was shown to be of the helper/inducer subtype. The neoplastic lymphoid cells in the skin infiltrate differed morphologically and immunologically from those in the peripheral blood. The occurrence of CTCL during this patient's clinical course represents a second neoplasm arising from a different cell line, rather than a tissue manifestation of the patient's CLL. To our knowledge, this is the first report in which the occurrence of CTCL is documented in a patient with immunologically known B-cell CLL. In addition to establishing the presence of B-cell CLL and CTCL of the helper/inducer T-cell type in the same patient, this case report demonstrates the usefulness and necessity of evaluating lymphoproliferative disorders by means of a multidisciplinary approach.     

Characterization of the CA1 pyramidal neurons in rat model of hepatic cirrhosis: insights into their electrophysiological properties

Although the key contributors of altering neurological function in hepatic encephalopathy are relatively well known, the electrophysiological mechanism of CA1 damage, a key vulnerable area during hyperammonemia, have not yet been defined. Therefore, here we focus on the electrophysiological mechanisms of cognitive impairments following bile duct ligation (BDL). We performed patch-clamp recordings from the CA1 pyramidal neurons in hippocampus of male Wistar rats, which underwent sham or BDL surgery. A striking electrophysiological change of hippocampal neurons in experimental model of BDL was observed in the present study. Spontaneous firing frequency and rate of action potential (AP) rebound was decreased and afterhyperpolarization amplitude (AHP) was increased significantly in hippocampal cells of BDL animals compared to sham group. Together, the results suggest that altered intrinsic properties of the hippocampal neurons may contribute to the cognitive abnormalities during hepatic encephalopathy (HE), highlighting the electrophysiological mechanisms for providing new treatments against HE.