Extreme Hyperlactatemia After Heart Transplantation: One Center's Experience.

INTRODUCTION: Hyperlactatemia may occur early after cardiac surgery and is correlated with prognosis. This study was conducted to analyze the perioperative variables and postoperative outcomes among heart transplant recipients with extremely high lactate levels (>15 mmol/L). METHODS: The single-center medical records of heart transplantation from June 2006 to May 2013 were retrospectively reviewed for patient characteristics, perioperative hemodynamic variables, arterial blood gas analysis data, and postoperative mortality. RESULTS: Among 58 consecutive heart transplant recipients, lactate levels over the detectable upper limit (>15 mmol/L) were identified in 12 patients after intensive care unit admission, with peak time at 1.9 ± 2.0 (range 0-6.1) hours. The maximal preoperative lactate level was 3.1 mmol/L, and most (11/12) postoperative lactate levels returned to <4 mmol/L at 27.5 ± 12.8 hours after surgery (range 15-58, median 24), displaying a trend toward delayed extubation time in 10 recipients (P < .01). Blood glucose levels elevated significantly from preoperative 148.9 ± 45.2 to 375.7 ± 96.9 mg/dL at peak lactate level (P < .01). Four patients died in the ICU (range 5-32 days), 4 died after discharge (range 5-57 months), with 6 in total surviving over 1 year. CONCLUSION: Extreme hyperlactatemia commonly occurred early after heart transplantation and mostly recovered within 30 hours; however, with delayed extubation time after operation.

Mutation of a Nopp140 gene dao-5 alters rDNA transcription and increases germ cell apoptosis in C. elegans.

Human diseases of impaired ribosome biogenesis resulting from disruption of rRNA biosynthesis or loss of ribosomal components are collectively described as 'ribosomopathies'. Treacher Collins syndrome (TCS), a representative human ribosomopathy with craniofacial abnormalities, is attributed to mutations in the tcof1 gene that has a homologous gene called nopp140. Previous studies demonstrated that the dao-5 (dauer and aged animal overexpression gene 5) of Caenorhabditis elegans is a member of nopp140 gene family and plays a role in nucleogenesis in the early embryo. Here, we established a C. elegans model for studying Nopp140-associated ribosomopathy. A null dao-5 mutant ok542 with a semi-infertile phenotype showed a delay in gonadogenesis, as well as a higher incidence of germline apoptosis. These phenotypes in dao-5(ok542) are likely resulted from inefficient rDNA transcription that was observed by run-on analyses and chromatin immunoprecipitation (ChIP) assays measuring the RNA Pol I occupancy on the rDNA promoter. ChIP assays further showed that the modifications of acetylated histone 4 (H4Ac) and dimethylation at the lysine 9 of histone 3 (H3K9me2) around the rDNA promoter were altered in dao-5 mutants compared with the N2 wild type. In addition, activated CEP-1 (a C. elegans p53 homolog) activity was also linked to the loss of DAO-5 in terms of the transcriptional upregulation of two CEP-1 downstream effectors, EGL-1 and CED-13. We propose that the dao-5 mutant of C. elegans can be a valuable model for studying human Nopp140-associated ribosomopathy at the cellular and molecular levels.

Cardiac hemangioma located at the apex of the left ventricle: a rare case report.

We report the case of a 67-year-old man who was found to have asymptomatic murmurs during his health check-up. Echocardiography revealed a mobile spherical mass in the left ventricle (LV), whereas magnetic resonance imaging (MRI) study revealed a well-circumscribed heterogeneous mass in the LV with its base attached to the LV apex. To the best of our knowledge, such a case of hemangioma, particularly its rare location at the apex of the LV, and its asymptomatic conduction disturbance has not yet been reported in the medical literature. Because of successful surgical intervention, the patient is in good health without any further tumor recurrence at 24 months after the diagnosis.

Surgical treatment of 26 patients with necrotizing pneumonia.

BACKGROUND: This study aimed to review the outcome of patients treated with surgical resection for necrotizing lung infection with various co-morbidities and complications. METHODS: The records of 26 patients treated with pulmonary resection for necrotizing pneumonia between July 2004 and January 2010 were retrospectively reviewed. Surgical procedures included large wedge resection (n = 1), lobectomy (n = 19) and bilobectomy (n = 6). RESULTS: The study cohort consisted of 21 men and 5 women aged 35-85 years (mean 64.7 ± 15.0 years). Twenty-three (88.5%) patients had underlying risk factors. At surgical consultation, 17 patients presented with progressive respiratory distress; 6 required ventilatory support; 12 had empyema, and in 5 patients the conditions were complicated by bronchopleural fistula. Four patients had septic shock requiring vasopressor support. Three patients developed hemoptysis. Two patients had bilateral diffuse pneumonia. Klebsiella pneumoniaeand Streptococcusviridans were the most common pathogens. The right lower (n = 13) and right middle lobes (n = 10) were the most frequently affected. Four deaths (15.4%) occurred: 3 due to perioperative progressing pulmonary infection/inflammation and 1 due to hepatorenal failure. Postoperative empyema occurred in 3 patients. One patient became ventilator dependent. CONCLUSION: Pulmonaryresection for necrotizing pneumonia is a feasible treatment option in patients with progressive pulmonary sepsis.

α-Catulin knockdown induces senescence in cancer cells.

Cellular senescence functions as a tumor suppressor that protects against cancer progression. α-Catulin, an α-catenin-related protein, is reported to have tumorigenic potential because it regulates the nuclear factor-κB (NF-κB) pathway, but little is known about its clinical relevance and the mechanism through which it regulates cancer progression. Here, we found that α-catulin mRNA levels were significantly upregulated in cancer cell lines and clinical oral squamous cell carcinomas, which positively correlated with tumor size (P=0.001) and American Joint Committee on Cancer (AJCC) stage (P=0.004). α-Catulin knockdown in the OC2 and A549 cancer cell lines dramatically decreased cell proliferation and contributed to cellular senescence, and inhibited OC2 xenograft growth. Mechanistic dissection showed that α-catulin depletion strongly induced the DNA-damage response (DDR) in both cell lines, via a p53/p21-dependent pathway in A549 cells, but a p53/p21-independent pathway in OC2 cells carrying mutant p53. Global gene expression analysis revealed that α-catulin knockdown altered cell-cycle regulation and DDR pathways at the presenescent stage as well as significantly downregulate several crucial genes related to mitotic chromosome condensation, DDR and DNA repair systems, which suggests that its depletion-induced cellular senescence might be caused by chromosome condensation failures, severe DNA damage and impaired DNA repair ability. Our study provides evidence that α-catulin promotes tumor growth by preventing cellular senescence and suggests that downregulating α-catulin may be a promising therapeutic approach for cancer treatment.

Successful treatment for a large renal cell carcinoma with tumour thrombus.

We report the case of a 41-year-old man with symptoms of exertional dyspnoea and easy fatigue. Physical examination revealed a palpable mass with knocking pain over the right flank region and a cardiac murmur with jugular vein engorgement. Transoesophageal echocardiography revealed a right atrial mass that caused tricuspid inflow obstruction. Computed tomography revealed a giant mass (approximately 15 x 15 cm2) in the right kidney; this finding was consistent with renal cell carcinoma. Despite the metastatic status, right nephrectomy was performed and the intra-atrial tumour thrombus (TT) was resected under a cardiopulmonary bypass in order to relieve the tricuspid obstruction. Histological examination confirmed renal cell carcinoma with TT. The patient is healthy with satisfactory systolic function at 1-year follow-up.

Protamine-associated hypotension in patients on hemodialysis: retrospective study and prevalence of antiprotamine antibodies.

AIMS: Protamine, when administered to neutralize heparin in cardiovascular surgery, is associated with occasionally severe antigen-antibody reactions associated with substantial morbidity and mortality. The objective of this study is to investigate whether patients on hemodialysis are more susceptible to the protamine adverse effects. METHOD: First, a retrospective analysis of a protamine-associated hypotension episode (PAHE) in 239 patients undergoing coronary artery bypass grafting surgery was performed for the incidence study in the period of 1999 to 2005. Second, an ELISA determination of serum anti-protamine IgG antibody in 255 serum samples from individuals without previous surgical histories was conducted for prevalence survey. In both studies, patients on HD were matched for age with non HD patients. RESULTS: The highest incidence (57%) of PAHE occurred in patients on hemodialysis using of M-insulin (a mixed type of insulin aspart 30%, insulin aspart protamine 70%) formulation, and this group also exhibited a high anti-protamine IgG antibody titer in serum (odds ratio: 18.31). CONCLUSIONS: A substantial proportion of patients on hemodialysis are at high risk of acquiring protamine adverse effects, but definite conclusion about the association between uremia and PAHE, however, still needs to be made with caution.

Acute painful neuropathy in thallium poisoning.

Dysesthesia, allodynia, distal muscle weakness, and sensory impairment were noted in two patients with acute thallium intoxication. Two months later, nerve conduction studies showed an axonal degeneration. Sural nerve biopsy disclosed a decreased fiber density in the large myelinated fibers. Quantitative sensory testing also revealed an impairment of pinprick, temperature, and touch sensations. Cutaneous nerve biopsy confirmed a loss of epidermal nerves indicating an involvement of the small sensory nerves.

Sequential changes in plasma cytokine and endotoxin levels in cirrhotic patients with bacterial infection.

To delineate the clinical roles of plasma cytokine or endotoxin levels in the natural course of infection in patients with decompensated cirrhosis, 66 cirrhotic patients were studied within a 1.5-year period. Plasma levels of tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), IL-6, IL-8 and endotoxin were determined on days 1, 4 and 7 after admission when hospital infection was suspected and 4 months later. A total of 24 patients (36.4%) were proven to be infected during hospitalization (group A), while 42 others were not infected (group B). Fever occurred in a very high proportion (22/24) of group A patients. Baseline levels of TNF-alpha (37.7+/-15.2 compared with 8.7+/-1.2 pg/ml; P<0.01) and IL-6 (180.5+/-20.5 compared with 24.6+/-7.5 pg/ml; P<0.0001) were higher in group A patients, while IL-1beta, IL-8 and endotoxin levels were not significantly different between the two groups. For patients with hospital infection, IL-6 levels determined during the episode were significantly higher than baseline levels. Using IL-6 >80 pg/ml as a baseline cut-off level to diagnose bacterial infection, the sensitivity, specificity and accuracy were 87.5, 100 and 95.5% respectively. The one-year cumulative probability of mortality (61.1% compared with 23.7%; P<0.001) and of bacterial re-infection (72.2% compared with 18.4%; P<0.0001) was higher in group A than in group B. Plasma TNF-alpha and IL-6 levels determined at 4 months were not different between the two groups. In conclusion, fever or elevated plasma IL-6 levels in patients with decompensated cirrhosis calls for early antibiotic treatment to prevent life-threatening bacterial infection. Bacterial infection is likely to recur in those patients with increased IL-6 levels, while severe episodes of infection occur in patients with increased TNF-alpha levels.

Etk, a Btk family tyrosine kinase, mediates cellular transformation by linking Src to STAT3 activation.

Etk (also called Bmx) is a member of the Btk tyrosine kinase family and is expressed in a variety of hematopoietic, epithelial, and endothelial cells. We have explored biological functions, regulators, and effectors of Etk. Coexpression of v-Src and Etk led to a transphosphorylation on tyrosine 566 of Etk and subsequent autophosphorylation. These events correlated with a substantial increase in the kinase activity of Etk. STAT3, which was previously shown to be activated by Etk, associated with Etk in vivo. To investigate whether Etk could mediate v-Src-induced activation of STAT3 and cell transformation, we overexpressed a dominant-negative mutant of Etk in an immortalized, untransformed rat liver epithelial cell line, WB, which contains endogenous Etk. Dominant-negative inactivation of Etk not only blocked v-Src-induced tyrosine phosphorylation and activation of STAT3 but also caused a great reduction in the transforming activity of v-Src. In NIH3T3 cells, although Etk did not itself induce transformation, it effectively enhanced the transforming ability of a partially active c-Src mutant (c-Src378G). Furthermore, Etk activated STAT3-mediated gene expression in synergy with this Src mutant. Our findings thus indicate that Etk is a critical mediator of Src-induced cell transformation and STAT3 activation. The role of STAT3 in Etk-mediated transformation was also examined. Expression of Etk in a human hepatoma cell line Hep3B resulted in a significant increase in its transforming ability, and this effect was abrogated by dominant-negative inhibition of STAT3. These data strongly suggest that Etk links Src to STAT3 activation. Furthermore, Src-Etk-STAT3 is an important pathway in cellular transformation.

Planning of skull base surgery in the virtual workbench: clinical experiences.

Based on the KRDL Virtual Workbench, we present a neurosurgical planning system called VIVIAN (Virtual Intracranial Visualization And Navigation). This VR environment allows for fast and intuitive interaction with three-dimensional multimodal (MRI, MRA, MRV, CT) patient specific data-sets. The user reaches behind a mirror into a 3D workspace where the 3D data is surrounded by interactive virtual tools-racks. Tumors, blood vessels, cranial nerves and surgically relevant parts of the brain are segmented by interactive control of density transfer-functions or by manual outlining and tracing tools. A neurosurgical procedure is planned by using various visualization and measurement tools and the system allows for the simulation of bone drilling and tissue removal. We have planned 16 cases which required tumor surgery at the cranial base. VIVIAN provided an efficient and comprehensive way to understand pre-operatively the complexity of anatomical and pathological relationships. The ideal craniotomy and the extent of the required skull base exposure could be specified accurately.

Interleukin-6 inhibits transforming growth factor-beta-induced apoptosis through the phosphatidylinositol 3-kinase/Akt and signal transducers and activators of transcription 3 pathways.

The multifunctional cytokine interleukin-6 (IL-6) regulates growth and differentiation of many cell types and induces production of acute-phase proteins in hepatocytes. Here we report that IL-6 protects hepatoma cells from apoptosis induced by transforming growth factor-beta (TGF-beta), a well known apoptotic inducer in liver cells. Addition of IL-6 blocked TGF-beta-induced activation of caspase-3 while showing no effect on the induction of plasminogen activator inhibitor-1 and p15(INK4B) genes, indicating that IL-6 interferes with only a subset of TGF-beta activities. To further elucidate the mechanism of this anti-apoptotic effect of IL-6, we investigated which signaling pathway transduced by IL-6 is responsible for this effect. IL-6 stimulation of hepatoma cells induced a rapid tyrosine phosphorylation of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) and its kinase activity followed by the activation of Akt. Inhibition of PI 3-kinase by wortmannin or LY294002 abolished the protection of IL-6 against TGF-beta-induced apoptosis. A dominant-negative Akt also abrogated this anti-apoptotic effect. Dominant-negative inhibition of STAT3, however, only weakly attenuated the IL-6-induced protection. Finally, inhibition of both STAT3 and PI 3-kinase by treating cells overexpressing the dominant-negative STAT3 with LY294002 completely blocked IL-6-induced survival signal. Thus, concomitant activation of the PI 3-kinase/Akt and the STAT3 pathways mediates the anti-apoptotic effect of IL-6 against TGF-beta, with the former likely playing a major role in this anti-apoptosis.

Effect of long-term octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis.

1. Both octreotide and isosorbide dinitrate have been shown to have portal hypotensive effects in animals with portal hypertension. Moreover, in both animals and humans with portal hypertension, the reduction of portal pressure was enhanced when nitrovasodilators were combined with propranolol or vasopressin. The present study was undertaken to evaluate the effect of long-term administration of octreotide and isosorbide dinitrate on haemodynamics in rats with portal vein stenosis. 2. Portal hypertension was induced by portal vein stenosis. Portal hypertensive rats were allocated into one of four groups (eight rats in each group): vehicle group, octreotide group (100 micrograms/kg via subcutaneous injection every 12 h), isosorbide dinitrate group (5 mg/kg via gastric gavage every 12 h) and combined treatment group. Drug was given for eight consecutive days, starting 1 day before surgery. Haemodynamic values were measured using a radioactive microsphere technique. 3. Long-term octreotide treatment decreased portal pressure and improved the hyperdynamic circulation. In contrast, long-term administration of isosorbide dinitrate reduced portal pressure but did not ameliorate vasodilatation. A combination of octreotide and isosorbide dinitrate improved the hyperdynamic circulation with a reduction of portal pressure. In addition, the mean value of portal pressure after combination treatment was significantly lower than in rats receiving octreotide alone. 4. These results showed that, in rats with portal hypertension, long-term combined administration of octreotide and isosorbide dinitrate improved the hyperdynamic circulation together with a more profound reduction of portal pressure than rats receiving octreotide alone.

Hyperdynamic circulation of cirrhotic rats with ascites: role of endotoxin, tumour necrosis factor-alpha and nitric oxide.

1. Hyperdynamic circulation observed in portal hypertensive states is characterized by generalized vasodilation, increased cardiac index and increased systemic and regional blood flows. Endotoxin, tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) have been reported to be involved in the pathogenesis of hyperdynamic circulation, but the interactions between endotoxin, TNF-alpha and NO in cirrhotic rats with ascites have never been specifically addressed. 2. This study was designed to determine systemic and portal haemodynamics and plasma levels of endotoxin, TNF-alpha and nitrate/nitrite in cirrhotic rats with ascites and investigate the relationships between these substances. 3. Plasma concentrations of endotoxin, TNF-alpha and nitrate/nitrite (an index of NO production) were determined in 25 cirrhotic rats with ascites and 17 control rats using the Limulus assay, ELISA and a colorimetric assay respectively. In addition, haemodynamic studies were performed in another ten cirrhotic rats with ascites and ten control rats. 4. Cirrhotic rats with ascites had hyperdynamic circulation accompanied by increased plasma levels of endotoxin, TNF-alpha and nitrate/nitrite, as compared with control rats. Significant correlation existed between plasma levels of endotoxin and nitrate/ nitrite (r = 0.59, P < 0.0001) and between plasma levels of endotoxin and TNF-alpha (r = 0.63, P < 0.0001). No correlation was detected between plasma levels of TNF-alpha and nitrate/nitrite (r = 0.24, P > 0.05). 5. This study suggests that endotoxaemia developed in cirrhotic rats with ascites may stimulate NO formation directly or indirectly via cytokine cascade, and consequently participate in the development and/or maintenance of hyperdynamic circulation.

Prolonged bleeding time: a new clinical manifestation of hepatocellular carcinoma?

The association between prolonged bleeding time and hepatocellular carcinoma (HCC) has not been well studied. We investigated whether bleeding time is prolonged in cirrhotic patients with HCC and studied the role of clinical characteristics, tumour size, and laboratory data in predicting bleeding time prolongation. After excluding patients that presented with blood dyscrasia and uraemia, 58 cirrhotic patients with HCC, 106 cirrhotic patients without HCC, and 44 age-and sex-matched healthy subjects were included in the study. Bleeding time, imaging studies, clinical characteristics and biochemical data were obtained for every patient. Cirrhotic patients with and without HCC had longer bleeding times (554 +/- 32 s, respectively) compared with healthy controls (357 +/- 13 s, P < 0.05). Hepatocellular carcinoma patients with a large tumour burden (> 5 cm in diameter) had a significantly longer bleeding time than those patients without (663 +/- 105 vs 376 +/- 23 s, respectively, P < 0.05). After excluding patients with a platelet count < or = 80 000/mm3, cirrhotic patients classified as Child-Pugh's grading A and with a large tumour burden had longer bleeding times(580 +/- 87 s) than patients with a small tumour burden (< or = 5cm in diameter) and cirrhotic patients without HCC (371 +/- 22 and 416 +/- 29 s, respectively, P < 0.05). In cirrhotic patients with HCC, higher serum bilirubin levels, a Child-Pugh's grading C, and a tumour size > 5 cm in diameter were found to be significant predictors for prolonged bleeding time on univariate analysis. On multivariate analysis, both tumour size > 5 cm in diameter and a Child-Pugh's grading C (odd's ratio, 95% confidence interval and P value were measured as 38.5, 2.8-534.7, < 0.001, and 10.5, 0.9-117.6, 0.02, respectively) were the significant independent predictors. A significant correlation existed between tumour diameter and bleeding time (r = 0.44, P < 0.01). In conclusion, these results suggest that prolonged bleeding time may be categorized as a new clinical manifestation in patients with HCC. In addition to cirrhosis, HCC itself may also participate in the pathogenesis of bleeding time prolongation.

Plasma interleukin-6 levels in patients with cirrhosis. Relationship to endotoxemia, tumor necrosis factor-alpha, and hyperdynamic circulation.

BACKGROUND: Liver cirrhosis with portal hypertension is associated with hyperdynamic circulation characterized by generalized vasodilatation and increased cardiac output and regional blood flows. Patients with liver cirrhosis present with increased levels of interleukin-6 (IL-6), which may inhibit vascular smooth-muscle contraction. We investigated whether increased plasma IL-6 levels contribute to the pathogenesis of hyperdynamic circulation observed in cirrhotic patients and whether they are correlated with plasma tumor necrosis factor-alpha (TNF-alpha) and endotoxin concentrations. METHODS: In 58 consecutive cirrhotic patients and 34 healthy subjects the plasma concentrations of TNF-alpha and IL-6 were measured with enzyme-linked immunosorbent assay, and endotoxin determinations with a limulus assay. In addition, 52 cirrhotic patients underwent a hemodynamic study using Swan-Ganz catheterization. RESULTS: Plasma TNF-alpha, IL-6, and endotoxin levels were significantly higher in cirrhotic patients than in healthy subjects (7.3 +/- 0.2 versus 5.8 +/- 0.1 pg/ml, 6.4 +/ 0.8 versus 2.0 +/- 0.2 pg/ml, and 7.6 +/- 1.2 versus 2.8 +/- 0.3 pg/ml, respectively; p < 0.01). In cirrhotic patients the plasma levels of TNF-alpha IL-6, and endotoxin progressively increased in relation to the severity of liver dysfunction (graded by Pugh's classification). A significant correlation was observed between plasma TNF-alpha and IL-6 levels (r = 0.48, p < 0.001), whereas no correlation was observed between plasma endotoxin levels and plasma TNF-alpha and IL-6 levels. Plasma IL-6 levels correlated negatively with systemic vascular resistance in patients with cirrhosis (r = 0.5, p < 0.01). CONCLUSIONS: Plasma IL-6 levels are increased in patients with cirrhosis. The severity of liver cirrhosis is an important factor for the occurrence of increased IL-6 levels. IL-6 may play a role in the hyperdynamic circulation observed in patients with cirrhosis.

Effects of long-term administration of octreotide in portal vein-stenosed rats.

The hemodynamic effects of long-term administration of octreotide in portal hypertension has not been established. In addition, whether long-term octreotide treatment prevents the development of portosystemic shunts has not yet been evaluated. Hence, the current study was undertaken to evaluate the effects of long-term administration of octreotide in rats with portal vein stenosis. Immediately after portal vein stenosis or sham operation, rats were given either a long-term octreotide administration of 100 micrograms/kg or a placebo every 12 hours by subcutaneous injection for 14 consecutive days. Systemic hemodynamics and regional blood flows, degree of mesenteric-systemic shunts, and plasma glucagon concentrations were measured after the final dose of octreotide or placebo. A fifth group of portal vein-stenosed rats received hemodynamic and plasma glucagon measurements after 1-day octreotide treatment given at 14 days after surgery. Long-term octreotide treatment modified the hyperdynamic circulation without affecting the degree of mesenteric-systemic shunts, and 1-day octreotide treatment decreased portal tributary blood flow without affecting the portal pressure, systemic hemodynamics, and degree of mesenteric-systemic shunts. Plasma glucagon levels were decreased in portal vein-stenosed rats receiving either long-term or 1-day octreodtide compared with rats receiving placebo. In contrast, chronic octreotide treatment did not affect any of the hemodynamic values or plasma glucagon levels in sham-operated rats. In conclusion, long-term administration of octreotide modified in part the development of portal hypertension and hyperdynamic circulation in portal vein-stenosed rats without affecting the degree of mesenteric-systemic shunts.

Decreased vascular reactivity of portal vein in rats with portal hypertension.

BACKGROUND/AIMS: Vascular hyporesponsiveness in portal hypertension is well documented in the arterial tissue. The present study aimed to investigate the possible changes in the portal vein from portal hypertensive rats. METHODS: Portal hypertension was induced by partial portal vein ligation. Fourteen days after surgery, portal veins were removed for contractile study and measurement of cAMP, cGMP and [Ca2+]i. RESULTS: In vitro tension preparation showed a decreased maximum response to norepinephrine in portal vein of portal vein ligated rats (38.3 +/- 4.1 vs. 23.4 +/- 1.5 mN/mm2). The pA2 values of WB4101 and yohimbine (alpha1- and alpha2-adrenoceptor antagonist, respectively) were not different between the two groups. Tissue cAMP (14.4 +/- 0.9 vs. 12.2 +/- 0.7 pmol/mg protein), but not cGMP, content was increased and intracellular calcium [Ca2+]i levels (247 +/- 9 vs. 281 +/- 13 nM) were decreased in portal vein ligated rats. CONCLUSIONS: These results showed that in portal vein from portal vein ligated rats, vascular hyporesponsiveness and an increase in basal cAMP content and a decrease in basal [Ca2+]i were observed.

Detection of Epstein-Barr virus and cytomegalovirus genome in white blood cells from patients with juvenile rheumatoid arthritis and childhood systemic lupus erythematosus.

The role of infectious agents in the pathogenesis of autoimmune diseases has long been a matter of debate. This study investigated the possible role of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) infections in the pathogenesis of autoimmune diseases by an attempt to demonstrate the presence of the viral genome in the leukocyte of 21 juvenile rheumatoid arthritis (JRA) patients, 20 childhood-onset systemic lupus erythematosus (SLE) patients, and 20 age-matched normals, using polymerase chain reaction (PCR) and DNA probes. The results showed: (1) there was no difference in serum IgG anti-EBV antibody titers among three groups; (2) the EBV PCR-positive rates for JRA and SLE patients and normal controls were 5% (1/21), 10 (2/20), and 0% (0/20), respectively; (3) the HCMV PCR-positive rates for JRA and SLE patients and normal controls were 33% (7/21), 25 (5/20), and 10% (2/20), respectively, and (4) the HCMV-positive rate was 25% for JRA patients with steroid treatment and 33% for those without steroid treatment. It is, therefore, concluded that: (1) the data do not support the participation of EBV and HCMV in the pathogenesis of childhood-onset SLE and JRA; (2) steroid therapy does not increase the frequency of HCMV infection in JRA patients, and (3) immunoincompetence might be one of the major factors contributing to increased susceptibility to HCMV infection in JRA and SLE patients.