Clinical significance of anti-Epstein-Barr virus antibodies in systemic chronic active Epstein-Barr virus disease.

Systemic chronic active Epstein-Barr virus disease (sCAEBV) is a rare and fatal neoplasm, involving clonally proliferating Epstein-Barr virus (EBV)-infected T cells or natural killer cells. Patients with sCAEBV have abnormal titers of anti-EBV antibodies in their peripheral blood, but their significance is unknown. We retrospectively investigated titers and their relationship with the clinical features of sCAEBV using the data collected by the Japanese nationwide survey. Eighty-four patients with sCAEBV were analyzed. The anti-EBV nuclear antigen (EBNA) antibody, targeting EBNA-expressing EBV-positive cells, was found in 87.5% of children (<15 years old), 73.7% of adolescents and young adults (15-39 years old), and 100% of adults (≥40 years old). Anti-EBNA antibody titers were significantly lower and anti-VCA-IgG antibody titers significantly higher in patients with sCAEBV than those in healthy controls (p < 0.0001). Patients with high anti-VCA-IgG and anti-early antigen-IgG antibody (antibodies against the viral particles) levels had significantly better 3-year overall survival rates than those with low titers, suggesting that patients with sCAEBV have a reduced immune response to EBV-infected cells.

Interferon-γ Produced by EBV-Positive Neoplastic NK-Cells Induces Differentiation into Macrophages and Procoagulant Activity of Monocytes, Which Leads to HLH.

Epstein-Barr virus (EBV)-positive T- or NK-cell neoplasms show progressive systemic inflammation and abnormal blood coagulation causing hemophagocytic lymphohistiocytosis (HLH). It was reported that inflammatory cytokines were produced and secreted by EBV-positive neoplastic T- or NK-cells. These cytokines can induce the differentiation of monocytes into macrophages leading to HLH. To clarify which products of EBV-positive neoplastic T- or NK-cells have effects on monocytes, we performed a co-culture assay of monocytes with the supernatants of EBV-positive T- or NK-cell lines. The expression of differentiation markers, the phagocytosis ability, and the mRNA expression of the inflammatory cytokines of THP-1, a monocytic cell line, clearly increased after culturing with the supernatants from EBV-NK-cell lines. Co-culturing with the supernatants promoted the expression of CD80 and CD206 as well as M1 and M2 macrophage markers in human monocytes. Co-culturing with the supernatants of EBV-NK-cell lines significantly enhanced the procoagulant activity and the tissue factor expression of monocytes. Interferon (IFN)-γ was elevated extremely not only in the supernatant of EBV-NK-cell lines but also in the plasma of EBV-positive NK-cell neoplasms patients accompanying HLH. Finally, we confirmed that IFN-γ directly enhanced the differentiation into M1-like macrophages and the procoagulant activity of monocytes. Our findings suggest that IFN-γ may potentially serve as a therapeutic target to regulate HLH in EBV-positive NK-cell neoplasms.

Cold weather is a predisposing factor for testicular torsion in a tropical country. A retrospective study / Clima frio é um fator predisponente para torção testicular num país tropical. Um estudo retrospectivo

CONTEXT AND OBJECTIVE: Testicular torsion is a medical and urological emergency because it can lead to loss of the organ. The theory of seasonal testicular torsion occurrence is based on studies from institutions located in cold and temperate regions. The objective here was to determine whether cold weather is associated with higher incidence of testicular torsion in a tropical country, such as Brazil. DESIGN AND SETTING: Retrospective study, conducted in a tertiary and teaching hospital. METHODS: Patients with acute testicular torsion confirmed by surgery between April 2006 and March 2011 were studied. Information on weather conditions at the time of symptom onset was collected. RESULTS: A total of 64 testicular torsion cases were identified. The months with the highest incidences of testicular torsion were June (16%), July (19%) and August (11%), which had the lowest mean temperatures, of 17.6 °C, 16.4 °C and 18.2 °C, respectively. Eleven percent of cases occurred during spring (October to December), 16% occurred in summer (January to March), 34% occurred in fall (April to June) and 39% occurred in winter (July to September). There was a significant association between the incidence of testicular torsion and the season (fall and winter), P < 0.001. CONCLUSIONS: Testicular torsion follows a seasonal association even in a tropical country, and is more frequent in the colder months of the year, namely fall and winter, when almost three-quarters of the cases occurred. These observations add further evidence that cold weather has an etiologic role in testicular torsion occurrence. .

CONTEXTO E OBJETIVO: A torção testicular é uma emergência médica e urológica, pois pode levar à perda do órgão. A teoria da ocorrência sazonal da torção testicular é baseada em estudos de instituições localizadas em regiões frias e temperadas. O objetivo foi determinar se o clima frio está associado a uma maior incidência de torção testicular em um país tropical, como o Brasil. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo, realizado em um hospital terciário e de ensino. MÉTODOS: Foram estudados pacientes com torção testicular aguda confirmada na cirurgia, durante o período de abril de 2006 a março de 2011. Informações sobre as condições climáticas no início dos sinto-mas foram coletadas. RESULTADOS: Um total de 64 casos de torção testicular foi identificado. Os meses com maiores incidên-cias foram junho (16%), julho (19%) e agosto (11%), que assinalaram as menores temperaturas médias, de 17,6 °C, 16,4 °C e 18,2 °C, respectivamente. Onze por cento dos casos ocorreram durante a primavera (outubro a dezembro), 16% no verão (janeiro a março), 34% no outono (abril a junho) e 39% no inverno (julho, agosto, setembro). Houve associação significante entre a incidência de torção testicular e a estação (outono e inverno), P < 0,001. CONCLUSÃO: Torção testicular obedece a uma predileção sazonal mesmo num país tropical, sendo mais fre-quente nos meses mais frios do ano, particularmente no outono e inverno, quando ocorrem quase três quartos dos casos. Estes achados acrescentam evidência a um papel etiológico do clima frio na torção testicular. .

Cold weather is a predisposing factor for testicular torsion in a tropical country. A retrospective study.

CONTEXT AND OBJECTIVE: Testicular torsion is a medical and urological emergency because it can lead to loss of the organ. The theory of seasonal testicular torsion occurrence is based on studies from institutions located in cold and temperate regions. The objective here was to determine whether cold weather is associated with higher incidence of testicular torsion in a tropical country, such as Brazil. DESIGN AND SETTING: Retrospective study, conducted in a tertiary and teaching hospital. METHODS: Patients with acute testicular torsion confirmed by surgery between April 2006 and March 2011 were studied. Information on weather conditions at the time of symptom onset was collected. RESULTS: A total of 64 testicular torsion cases were identified. The months with the highest incidences of testicular torsion were June (16%), July (19%) and August (11%), which had the lowest mean temperatures, of 17.6 °C, 16.4 °C and 18.2 °C, respectively. Eleven percent of cases occurred during spring (October to December), 16% occurred in summer (January to March), 34% occurred in fall (April to June) and 39% occurred in winter (July to September). There was a significant association between the incidence of testicular torsion and the season (fall and winter), P < 0.001. CONCLUSIONS: Testicular torsion follows a seasonal association even in a tropical country, and is more frequent in the colder months of the year, namely fall and winter, when almost three-quarters of the cases occurred. These observations add further evidence that cold weather has an etiologic role in testicular torsion occurrence.

Resección de carcionama gigante de la corteza suprarrenal: un caso clínico / Resection of giant adrenal cortical carcinoma: a case report

OBJETIVO: Presentamos un caso de carcinoma gigante de la corteza suprarrenal no funcional al que se le realizó una extirpación completa en nuestro departamento. MÉTODO: Caso clínico y la evolución de un caso de carcinoma gigante de la corteza suprarrenal al que se le realizó una extirpación completa. RESULTADO: Una mujer de 49 años solicitó atención médica por dolor abdominal en el cuadrante superior derecho. Durante la investigación, se le realizó a la paciente una tomografía computada (Figura 1) en la que se observó un gran tumor que ocupaba la topografía suprarrenal derecha con áreas que parecían indicar necrosis, en contacto directo con el hígado, empujando el riñón derecho hacia abajo y extendiéndose a línea media. Después de una hipótesis de carcinoma maligno, se tomaron muestras de sangre para evaluar la hipersecreción hormonal, las cuales dieron como resultado niveles característicos de una neoplasia adrenal no funcional. El tratamiento que se eligió fue la extirpación del tumor; la porción quirúrgica extirpada presentó 21 cm. en su diámetro mayor y un peso de 2.106 gramos. Microscópicamente era un carcinoma de la corteza suprarrenal. CONCLUSIONES: las opciones para el tratamiento de carcinoma de la corteza suprarrenal no mostraron progresos significativos en las últimas décadas; el tratamiento quirúrgico es aún la mejor opción, lo que fomenta la realización de una cirugía importante aun en pacientes con grandes masas tumorales

OBJETIVE: We report a case of nonfunctioning giant adrenal cortical carcinoma undergoing complete resection. METHODS: We report the case and evolution of a woman who underwent resection of a giant adrenal carcinoma at Santa Marcelina Hospital. RESULTS: A 49-year-old female presented with palpable mass in the right hypochondrium extending 5 cm down from the right costal margin. Abdominal CT Scan found a large mass occupying the right adrenal region with areas suggestive of necrosis, in close contact with the liver, pushing the right kidney inferiorly and extending to the midline. Biochemical tests to evaluate hormonal secretion resulted in levels within the normal range characteristic of a non-functioning adrenal neoplasm. The treatment of choice was resection of the abdominal mass; the surgical specimen greatest diameter was 21 cm and weighed 2106 grams. It was an adrenal cortical carcinoma. CONCLUSIONS: Options for the treatment of adrenal cortical carcinoma showed no significant advances in recent decades and complete surgical resection remains the most effective treatment for adrenal cortical carcinoma, even in patients with bulky tumor masses

Resection of giant adrenal cortical carcinoma: a case report.

OBJECTIVE: We report a case of nonfunctioning giant adrenal cortical carcinoma undergoing complete resection. METHODS: We report the case and evolution of a woman who underwent resection of a giant adrenal carcinoma at Santa Marcelina Hospital. RESULTS: A 49-year-old female presented with palpable mass in the right hypochondrium extending 5 cm down from the right costal margin. Abdominal CT Scan found a large mass occupying the right adrenal region with areas suggestive of necrosis, in close contact with the liver, pushing the right kidney inferiorly and extending to the midline. Biochemical tests to evaluate hormonal secretion resulted in levels within the normal range characteristic of a non-functioning adrenal neoplasm. The treatment of choice was resection of the abdominal mass; the surgical specimen greatest diameter was 21 cm and weighed 2106 grams. It was an adrenal cortical carcinoma. CONCLUSIONS: Options for the treatment of adrenal cortical carcinoma showed no significant advances in recent decades and complete surgical resection remains the most effective treatment for adrenal cortical carcinoma, even in patients with bulky tumor masses.

Goserelin versus leuprolide in the chemical castration of patients with prostate cancer.

PURPOSE: To evaluate the relative efficiency of leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg in relation to the reduction in serum testosterone, regarding the levels of castration. MATERIALS AND METHODS: We evaluated prospectively 60 randomized patients with advanced prostate carcinoma, with indication for hormone blockade. The patients were divided into 3 groups of 20: Group (1) received leuprolide 3.75 mg; Group (2) received leuprolide 7.5 mg; and Group (3) received goserelin 3.6 mg. All groups were treated with monthly application of the respective drugs. The patients' levels of serum testosterone were evaluated in two moments: before the treatment and 3 months after the treatment. RESULTS: The patients' ages were similar within the three groups, with a median of 72, 70, and 70 in groups 1, 2, and 3, respectively. Of the patients that received leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, 26.3, 25, and 35%, respectively, did not reach castration levels, considering a testosterone cutoff ≤ 50 ng/dl. And 68.4, 30, and 45%, respectively, did not reach castration levels, considering a testosterone cutoff ≤ 20 ng/dl. CONCLUSIONS: There were no statistically significant differences in the levels of castration when comparing leuprolide 3.75 mg, leuprolide 7.5 mg, and goserelin 3.6 mg, altogether. When compared in groups of two, there was a statistically significant difference between leuprolide 3.75 mg and leuprolide 7.5 mg, the latter presented better results in reaching castration levels, cutoff ≤ 20 ng/dl. The importance of this difference, however, must be measured with caution, since the comparison of the three groups simultaneously did not reach the established significance level, even though it came close.

Decrease and senescence of endothelial progenitor cells in patients with preeclampsia.

BACKGROUND: In preeclampsia, the precise mechanism of impaired vascular function is still unclear. We hypothesized that cellular function of circulating endothelial progenitor cells (EPCs) might be impaired in patients with preeclampsia. OBJECTIVE: The objective of this study was to investigate the number and status of cellular senescence of EPCs in the circulation of women with preeclampsia. METHODS: Circulating EPCs were cultured from patients with preeclampsia (n = 8) and normotensive pregnant women (n = 7). EPC numbers were assessed by colony-forming unit (CFU) methodology as previously reported. In addition, to assess cellular senescence, we measured endogenous beta-galactosidase activity. Moreover, we assessed whether the serum level of C-reactive protein (CRP), a marker for systemic inflammation, was associated with cellular impairment of EPCs. RESULTS: The number of circulating EPCs was decreased in women with preeclampsia controls (median, 10.0 vs. 34.0 CFU; P < 0.01). The rate of cellular senescence was significantly increased in patients with preeclampsia (33.9%) compared with that in controls (22.9%; P < 0.05). Patients with preeclampsia were divided into two subgroups: the CRP-negative group (CRP, <0.1 mg/dl; n = 4) and the CRP-positive group (CRP, > or =0.1 mg/dl; n = 4). Interestingly, EPC CFU counts were markedly decreased in CRP-positive patients compared with those in CRP-negative patients (5.0 and 25.0 CFU, respectively; P < 0.05). Median values for cellular senescence were greater in the CRP-positive group than in the CRP-negative group, although this did not achieve statistical significance (43.5% and 33.3%, respectively; P = 0.12). CONCLUSION: Depletion and cellular aging of EPCs in patients with preeclampsia might be associated with endothelial dysfunction and could be affected by systemic inflammation.

Impaired Ca2+ store functions in skeletal and cardiac muscle cells from sarcalumenin-deficient mice.

Sarcalumenin (SAR), specifically expressed in striated muscle cells, is a Ca2+-binding protein localized in the sarcoplasmic reticulum (SR) of the intracellular Ca2+ store. By generating SAR-deficient mice, we herein examined its physiological role. The mutant mice were apparently normal in growth, health, and reproduction, indicating that SAR is not essential for fundamental muscle functions. SAR-deficient skeletal muscle carrying irregular SR ultrastructures retained normal force generation but showed slow relaxation phases after contractions. A weakened Ca2+ uptake activity was detected in the SR prepared from mutant muscle, indicating that SAR contributes to Ca2+ buffering in the SR lumen and also to the maintenance of Ca2+ pump proteins. Cardiac myocytes from SAR-deficient mice showed slow contraction and relaxation accompanied by impaired Ca2+ transients, and the mutant mice exhibited a number of impairments in cardiac performance as determined in electrocardiography, ventricular catheterization, and echocardiography. The results obtained demonstrate that SAR plays important roles in improving the Ca2+ handling functions of the SR in striated muscle.

Circulating endothelial progenitor cells during human pregnancy.

The precise molecular and cellular mechanisms that regulate maternal vascular development during gestation are largely unknown. Endothelial progenitor cells (EPCs), which play an important role in vascular homeostasis, have been discovered in the circulation. We examined the level of circulating EPCs throughout uncomplicated pregnancies (n = 20) and assessed the correlation between serum estradiol levels and the number of EPCs. The number of circulating EPCs increased gradually and paralleled the progression of gestational age. In addition, the number of EPCs correlated significantly with the level of serum estradiol. The present study suggests that EPCs may play an important role in the regulation and maintenance of the placental development and vascular integrity during pregnancy.

Vasopressin-induced contraction of uterus is mediated solely by the oxytocin receptor in mice, but not in humans.

In the non-pregnant mouse myometrium, both arginine vasopressin and oxytocin induced contractions (pD(2)=8.55+/-0.13 and 9.23+/-0.09, respectively). The effect of oxytocin was the most potent, while the maximum contractions induced by these two peptides were almost of the same magnitude. Both vasopressin- and oxytocin-induced contractions were strongly inhibited by an oxytocin receptor antagonist, CL-12-42 (d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]OVT), and weakly inhibited by a vasopressin V(1a) receptor antagonist, SR49059 ((2S)1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide). Similar results were obtained in the pregnant mouse myometrium. These results suggest that not only oxytocin- but also vasopressin-induced contraction is mediated by the activation of oxytocin receptors in the mouse myometrium. A reverse transcription polymerase chain reaction study failed to reveal mRNA of the vasopressin V(1a) receptor in the mouse myometrium. In contrast, in the non-pregnant human myometrium, vasopressin-induced contraction was inhibited by SR49059. Oxytocin showed no effect on the myometrium. These results suggest that there are significant differences in the functional receptors and contractile responses to vasopressin and oxytocin in the human and mouse uteri.

Increased locomotor activity, increased food and water intake and decreased PVN neurons in H1 calponin gene-deficient mice.

Calponin (h1 or basic) is an actin-binding protein that is expressed abundantly in smooth muscle. Our previous study using h1 calponin-null mutant mice demonstrated that h1 calponin inhibits the shortening velocity of smooth muscle contraction without significantly affecting the amplitude of force production. Furthermore, early onset of osteogenesis and increased bone formation have been reported in mutated mice. In the present study, we examined the effect of h1 calponin depletion on the metabolism and behavior of mice and found that the mutated mice showed increased locomotor activity, as well as increased intake of food and water, associated with the decreased number of neurons in the paraventricular nucleus of the hypothalamus (PVN).

CD38 gene disruption inhibits the contraction induced by alpha-adrenoceptor stimulation in mouse aorta.

CD38 is an ectoenzyme with ADP-ribosyl cyclase and hydrolase activities, which synthesizes cyclic ADP-ribose from NAD and hydrolyzes cyclic ADP-ribose to ADP-ribose. It has been shown that cyclic ADP-ribose is a potent Ca(2+) mobilizing messenger in many cells. To know the physiological role of cyclic ADP-ribose in vascular smooth muscle, we examined the effects of various agonists in the aorta isolated from CD38 knockout (CD38(-/-)) mouse. Western blot analysis showed that CD38 protein was detected in the aorta isolated from wild-type (CD38(+/+)) mouse, but not from CD38(-/-) mouse. In the aortae isolated from both CD38(+/+) and CD38(-/-) mice, KCl, phenylephrine and norepinephrine induced concentration-dependent contraction. KCl produced similar concentration-dependent responses in the aortae from both CD38(+/+) and CD38(-/-) mice. Maximum force of contraction induced by KCl (65 mM) was same in the size. Phenylephrine- and norepinephrine-induced contractions were, however, significantly smaller in the aortae from CD38(-/-) mice than in those from CD38(+/+) mice. 5-Hydroxytryptamine, endothelin-1, caffeine and thapsigargin-induced contractions were not significantly different in these two aortae. These results suggest that CD38 gene disruption inhibits alpha-adrenoceptor-induced vascular contractions and cyclic ADP-ribose-mediated signal transduction system is committed in these responses.

Theonezolide A, a novel marine macrolide, induces drastic shape change in rabbit platelets by reorganization of microtubules.

Theonezolide A, a marine macrolide, and thrombin caused a shape change followed by an aggregation in the rabbit platelets. Theonezolide A-induced platelet shape change, estimated by a decrease in light transmission, appeared to a greater extent than thrombin-induced one. Morphological studies using an electron microscope showed that theonezolide A changed platelet shape with various numbers of long pseudopods, loosing their discoid shape. Theonezolide A-induced shape change was inhibited by a microtubule-stabilizing agent, taxol, but not by an actin-depolymerizing agent, cytochalasin B. In contrast, thrombin-induced shape change was inhibited by cytochalasin B but not by taxol. Confocal fluorescence microscopy showed that circumferential microtubule bundle disappeared in the platelets treated with theonezolide A. Theonezolide A had no direct effect on polymerization of microtubules isolated from bovine brain, indicating that it indirectly causes microtubule reorganization. These results suggest that theonezolide A induces drastic shape change through reorganization of microtubules in rabbit platelets. Thus, theonezolide A is a useful drug to examine microtubule reorganization in the cells.