Phospholipase C signaling is involved in porcine reproductive and respiratory syndrome virus infection in cell cultures.

The phospholipase C (PLC) is a family of kinases that hydrolyze phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] to generate two second messengers, inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG), which stimulate distinct downstream signaling. Recently, it has been reported that PLC signaling is activated by multiple viruses for efficient replication and the virus-induced inflammatory response. In this study, we demonstrated that PLC-specific inhibitor U73122 strongly suppressed porcine reproductive and respiratory syndrome virus (PRRSV) productive infection in cell cultures. The inhibitor affected both viral post-binding cell entry and post-entry processes. The virus infection led to an early transient activation of PLCγ-1 at 0.5 h post-infection (hpi), and sustained event at a stage from 4 to 16 hpi in MARC-145 cells. In addition, U73122 inhibited the activation of p38 MAPK signaling stimulated by PRRSV infection, suggesting that PLC signaling may be associated with the virus infection-induced inflammatory response. Taken together, these studies suggested that PLC signaling played an important role in PRRSV infection or pathogenesis. Keywords: PRRSV; U73122; phospholipase C; PLCγ-1.

Association of Inducible T Cell Costimulator Polymorphisms with Susceptibility and Outcome of Hepatitis B Virus Infection in a Chinese Han Population.

Inducible T cell costimulator (ICOS) functions to regulate cell-cell signalling, immune responses and cell proliferation. ICOS single nucleotide polymorphism (SNP) may affect protein expression and functions. This study investigated the association of ICOS SNPs with hepatitis B virus (HBV) infection and outcome in a Chinese population. A total of 1290 Chinese Han individuals were enrolled, including 63 asymptomatic HBV carriers, 220 chronic hepatitis B patients (CHB), 249 HBV-related liver cirrhosis patients (LC), 108 patients with HBV-related hepatocellular carcinoma (HCC), 338 patients with natural HBV clearance and 312 healthy subjects (as controls). DNA samples from these subjects were genotyped for four ICOS SNPs (rs11883722, rs10932029, rs1559931 and rs4675379) using TaqMan SNP Genotyping Assay and analysed. The data showed that genotype and allele frequencies of ICOS SNPs in cases and controls followed the Hardy-Weinberg distribution. The CC genotype of rs4675379 was higher in patients with HBV infection (including AC, CHB, LC and HCC) than in patients with HBV clearance (P = 0.006). Furthermore, the genotype 'GA' and the minor allele 'A' of rs1559931 were associated with a decreased HCC susceptibility (P < 0.001). Haplotype analysis data showed that 'GC' haplotype in block 2 (rs1559931 and rs4675379) had a lower frequency in patients than in HBV-cleared subjects (P = 0.034), although its overall frequency was only 1.6%. Our study found that ICOS rs1559931 SNP was associated with decreased HBV-related HCC risk in the studied Chinese Han population, except for patients with natural clearance of HBV.

pUC18-CpG stimulates RAW 264.7 via TBK1-mediated pathway and presents adjuvanticity in mice.

Phosphorothioate CpG oligodeoxynucleotides (ODN) are reported to be recognized by the membrane-bound TLR9 and trigger the MyD88-dependent up-regulation of Type I interferons and pro-inflammatory cytokines. Whether plasmids containing multiple CpG motifs stimulate the same signaling pathway is yet to be determined. The present results show that the CpG motifs enrich plasmid pUC18-CpG stimulates RAW 264.7 in vitro, mainly through the TBK1-mediated signaling pathway, causing the up-regulation of IFN-ß, and pro-inflammatory cytokines TNF-α and IL-6. When pUC18-CpG is co-administered with the recombinant Echinococcus granulosus antigen, the antigen-specific antibody titers are markedly increased compared to the Quil-A adju- vanted group. Antigen specific cytokine quantification shows that cytokine profiles from the pUC18-CpG adjuvanted-group are switched to a Th1-biased immune response.

Isolation and sequence analysis of the complete VP2 gene of canine parvovirus from Chinese domestic pets and determination of the pathogenesis of these circulating strains in beagles.

Canine parvovirus (CPV) causes acute gastroenteritis in domestic dogs, cats, and several wild carnivore species. In this study, the full-length VP2 gene of 36 CPV isolates from dogs and cats infected between 2016 and 2017 in Beijing was sequenced and analyzed. The results showed that, in dogs, the new CPV-2a strain was the predominant variant (n = 18; 50%), followed by the new CPV-2b (n = 6; 16.7%) and CPV-2c (n = 3; 8.3%) strains, whereas, among cats, the predominant strain was still CPV-2 (n = 9; 25%). One new CPV-2a strain, 20170320-BJ-11, and two CPV-2c strains, 20160810-BJ-81 and 20170322-BJ-26, were isolated and used to perform experimental infections. Multiple organs of beagles that died tested PCR positive for CPV, and characteristic histopathological lesions were observed in organs, including the liver, spleen, lungs, kidneys, small intestines, and lymph nodes. Experimental infections showed that the isolates from the epidemic caused high morbidity in beagles, indicating their virulence in animals and suggesting the need to further monitor evolution of CPV in China.

L-butyl phthalein improves neural function of vascular dementia mice by regulating the PI3K/AKT signaling pathway.

OBJECTIVE: L-3-n-butylphthalide (L-NBP) is a type of anti-ischemic cranial nerve protective drug that may act on vascular dementia (VD). Phosphatidylinositol-3 kinase (PI3K)/protein kinase B (AKT/PKB) signaling pathway can up-regulate B-cell lymphoma 2 (Bcl-2) expression, reduce reactive oxygen species (ROS) production, and alleviate cell apoptosis. This study aimed at investigating the role of L-NBP on neurological function and cell apoptosis in VD mouse through regulating PI3K/AKT signaling pathway. MATERIALS AND METHODS: The mice were divided into four groups, including Sham, VD, VD + solvent, and VD + L-NBP. HT22 cells were cultured in vitro and treated by ischemia/reperfusion (I/R). HT22 cells were divided into four groups, including I/R, VD + solvent, VD + L-NBP, and VD + L-NBP + LY294002 groups. Phosphorylated AKT (p-AKT) and Bcl-2 expressions were tested. ROS content in hippocampus tissue was detected by flow cytometry. Cell apoptosis was evaluated by transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. RESULTS: ROS content and cell apoptosis increased, while p-AKT and Bcl-2 expressions reduced in hippocampus tissue from VD group compared with sham group. L-NBP significantly up-regulated p-AKT and Bcl-2 expressions and decreased ROS content and cell apoptosis in hippocampus tissue. I/R treatment markedly induced HT22 cell apoptosis and ROS production, and reduced p-AKT and Bcl-2 expressions. L-NBP treatment markedly up-regulated p-AKT and Bcl-2 levels, restrained cell apoptosis, and reduced ROS content in TH22 cells intervened by I/R. LY294002 apparently attenuated the protective effect of L-NBP on HT22 cells. CONCLUSIONS: L-NBP protects VD by up-regulating PI3K/AKT signaling pathway, elevating Bcl-2 expression, reducing nerve cell apoptosis, and restraining ROS production.

Evaluation of proteinuria in healthy living kidney donor candidates.

BACKGROUND: Evaluation of living kidney donor candidates includes careful assessment for the presence or absence of kidney disease. Kidney donation has been considered to be at least relatively contraindicated if urinary total protein excretion is above the normal range. However, at the present time, there is no uniformly accepted level of urine total protein excretion that would exclude donation. Albumin excretion instead of total protein excretion as a criterion has not previously been evaluated. MATERIALS AND METHODS: This was a prospective observational study over a 3-year period in a single tertiary care center designed to assess current selection criteria for kidney donation with respect to urine total protein and albumin excretion. RESULTS: Twenty four percent (25 of 105) of healthy adult kidney donor candidates had elevated urinary total protein excretion rates (150 to 292 mg/24 h). Of these 105 candidates, 39 had simultaneous measurements of both urinary total protein and albumin. Although one-third (13/39) had elevated 24-hour urine total protein values, none had elevated urine albumin excretion. CONCLUSION: Measurement of albumin, the most common single protein found in urine, appears to be helpful in the evaluation of proteinuria in donor candidates. Many healthy adult kidney donor candidates have mildly elevated total protein excretion but normal albumin excretion. We believe that such patients should not be excluded from donation.

[RET pro-oncogene and medullary thyroid carcinoma].

Medullary thyroid carcinoma (MTC) originats from the parafollicular C cells of the thyroid, which is one of the most aggressive forms of thyroid malignancy with the poor prognosis. Hereditary MTC has multiple endocrine neoplasia types 1, 2A and 2B. The mutation of RET proto-oncogene has been identified as the main cause of MTC, and all mutations locate among the exons 5, 8, 10, 11, 13, 14, 15, and 16. Mutation analysis of the RET may provide a theoretical basis for the prevention, diagnosis and treatment of MTC.

Effect of pregnancy on renal function in patients with moderate-to-severe diabetic renal insufficiency.

OBJECTIVE: Previous studies of patients with diabetic nephropathy and mild renal impairment have suggested no determination in renal function as a result of pregnancy. The objective of this study was to determine whether pregnancy may permanently worsen renal function in women with diabetic nephropathy and moderate-to-severe renal insufficiency. RESEARCH DESIGN AND METHODS: Eleven patients were identified with diabetic nephropathy and moderate-to-severe renal dysfunction (creatinine [Cr] > or = 124 mumol/l [1.4 mg/dl]) at pregnancy onset by retrospective chart review. Alterations in glomerular filtration rate were estimated by using linear regression of the reciprocal of Cr over time. An equal number of nonpregnant premenopausal type 1 diabetic women with similar degrees of renal dysfunction served as a comparison group for nonpregnant rate of decline of renal function and potential contributing factors. RESULTS: Mean serum Cr rose from 159 mumol/l (1.8 mg/dl) prepregnancy to 221 mumol/l (2.5 mg/dl) in the third trimester. Renal function was stable in 27%, showed transient worsening in pregnancy in 27%, and demonstrated a permanent decline in 45%. Proteinuria increased in pregnancy in 79%. Exacerbation of hypertension or preeclampsia occurred in 73%. Seven patients progressed to dialysis 6-57 months postpartum, with 71% (five of seven) of these cases attributed to acceleration of disease during the pregnancy. Student's tests and repeated-measures analysis of variance support a pregnancy-induced acceleration in the rate of decline of renal function. CONCLUSIONS: In this series, patients with diabetic nephropathy and moderate-to-severe renal insufficiency were found to have a > 40% chance of accelerated progression of their disease as a result of pregnancy.

Pregnancy in women with renal disease and moderate renal insufficiency.

Data were gathered on 25 pregnancies in 23 women with moderate renal insufficiency as defined by a serum creatinine level of 1.4 mg/dl or greater prior to or at the onset of pregnancy. Twelve of the women had primary glomerular diseases, five (accounting for seven pregnancies) had interstitial diseases, and six had other renal diseases. In seven women with baseline serum creatinine levels ranging from 1.7 to 2.7 mg/dl, pregnancy was accompanied by a decline in renal function that was believed to be greater than expected from the natural history of the disease. The change ranged from a rise in serum creatinine level of 1.2 mg/dl to a functional decline that required dialysis. In 14 women (16 pregnancies), renal function either remained stable or declined to a degree consistent with the natural history of the disease. In two, the follow-up period was not long enough to judge the effect on the natural history of the disease. In 14 pregnancies, development or worsening of hypertension occurred. In nine, the diastolic blood pressure rose to 110 mm Hg or greater, and delivery was required because of hypertension. Twenty-three of 25 pregnancies ended in live births (92 percent) and 21 babies survived (84 percent). Fourteen of the 23 live births were premature. It is concluded that, in a substantial fraction of women with moderate renal insufficiency, pregnancy is accompanied by a decline in renal function; however, the fetal survival is much better than previously reported.

Hospital-acquired renal insufficiency: a prospective study.

Twenty-two hundred sixty-two consecutive medical and surgical admissions were evaluated prospectively to determine the contribution of iatrogenic factors to the development of renal insufficiency in hospital. Of 2,216 patients at risk, some degree of renal insufficiency developed in 4.9 percent. Decreased renal perfusion, postoperative renal insufficiency, radiographic contrast media, and aminoglycosides accounted for 79 percent of the episodes. Iatrogenic factors, broadly defined, accounted for 55 percent of all episodes. Poor prognostic indicators included oliguria, urine sediment abnormalities and, most importantly, severity of renal insufficiency; with an increase in serum creatinine of 3 mg/dl or greater, the mortality rate was 64 percent. Age, admission serum creatinine levels, and the number of episodes of renal insufficiency did not significantly affect outcome. We conclude that there is a substantial risk of the development of renal failure in hospital and that the mortality rate due to hospital-acquired renal insufficiency remains high.

Two-dimensional echocardiographic detection of pericardiocentesis-induced intrapericardial thrombus.

Heart puncture-induced hemopericardium is a serious complication of the pericardiocentesis. Two-dimensional echocardiographic examination performed in two patients just before and after the development of hemopericardium revealed a unique image in which pericardial bleeding manifested itself by an echodensity thrombus appearance adjacent to the cardiac chambers. With appropriate differentiation to some other intrapericardial echodensity masses, such distinctive images can be highly specific for active bleeding into the pericardial sac.

Downward displacement of aortic anulus leading to aortic and mitral regurgitation.

A rare case of combined aortic and mitral regurgitation resulting from downward displacement of the aortic anulus is reported. The patient was treated successfully with an aortic valve replacement with a Björk-Shiley valve prosthesis, which was anchored at the normal site of the aortic anulus. No procedures were performed on the mitral valve, but mitral regurgitation was not evident postoperatively.

Case report: agenesis of the right lung diagnosed by three-dimensional reconstruction of helical chest CT.

Unilateral pulmonary agenesis is extremely rare and the diagnosis can be made by a number of conventional methods. We report two cases: a 16-day-old girl and a 14-year-old girl presenting with tachypnoea in whom three-dimensional reconstruction of helical chest computed tomography was used to demonstrate the complete absence of the carina, right main bronchus and right lung. To our knowledge, these are the first cases of right lung agenesis diagnosed by this method.

Separation of thoracopagus conjoined twins. A case report.

A pair of thoracopagus conjoined twins with a connection at the atrioventricular groove of both hearts and a huge conjoined liver were surgically separated. An aortopulmonary shunt was created for Twin B, a victim of complex congenital heart disease with hypoplastic right heart syndrome, who died 5 hours later. However, Twin A survived after prolonged endotracheal intubation and parenteral nutrition. He survived for 7 months, and went home, but finally died of sepsis. In reviewing 47 pairs of surgically separated thoracopagus conjoined twins, in 30 pairs of type A (Leachman's classification, completely separate hearts), 42 patients survived (70%); in 5 pairs of type B (atrial connection only), one patient survived (10%); in 9 pairs of type C (both atrial and ventricular interconnections), none survived; in 3 pairs of unknown type, 2 survived. Total survival rate of surgically separated thoracopagus conjoined twins was 47.9%. The survival rate was 38.2% in those operated in the neonatal period (n = 34) and 63.6% in those operated over 1 month of age (n = 44) (p = 0.016). In conclusion, thoracopagus conjoined twins are rare. Although its separation carries a high risk, especially in those with cardiac connection, this report confirmed that separation is still feasible under proper preparation and planning.

Surgery for achalasia: long-term results in operated achalasic patients.

Achalasia is a functional disorder of the alimentary tract due to decreased or absent peristalsis of the esophageal body and obstructive outlet of the esophagus. Surgical treatment, eg. esophagomyotomy of the lower esophageal sphincter (LES), was one choice for resolving the problem and its effect was affirmative from reviews of many internationally authorized articles. However, few reports have ever questioned the long-term effects of it. From January 1968 to May 1996, 159 esophageal achalasic patients, 90 males and 69 females, were admitted due to dysphagia or food regurgitation. One hundred and forty-five patients had received 158 operations related to this benign motor disorder. The majority of patients received either modified Heller esophagomyotomy (M) or M plus modified Belsy Mark IV antireflux procedure (M+W) for primary treatment of their esophageal disorder, while conditional selection with addition of esophageal resection as advanced procedures for failure of primary surgery. We retrospectively studied these patients, collected their preoperative and postoperative clinical results, analyzed the causes of recurrent symptoms, compared the long-term results in different surgical procedures and searched for the pathogenesis of their failure. The results disclosed that the overall success rate for both methods was 73.1% with 85.7% for patients receiving M+W (56) and 64.9% of M (77) only. Through long-term follow-up, we had an improvement rate of 97.4% at an early stage and 53.3% for M at a late stage and 98.4% and 55.6% for M+W, respectively. The postoperative natural course of achalasic patients could be seen and progressive deterioration of the operated patients with time was noted. Several factors might contribute to the causes of unsuccessful surgery. We summarized them as incomplete myotomy, fused or healed myotomy, gastroesophageal reflux (GER), mucosal hernia and co-combined antireflux procedure by hypercalibrated or floppy wrapping. Esophagomyotomy or myotomy plus antireflux procedure for the esophagus could be concluded to rather effective in the long-term but palliative treatments for achalasia chronic deterioration of the results could be found for both of them. Defective myotomy and GER may be the major causes for their failure. The choice of types of surgery between M and M+W was not the cause of the unsuccessful results whereas the operative strategy and procedures would have a certain significance on the long-term effect.

Exfoliative dermatitis secondary to tobramycin sulfate.

We report a case of exfoliative dermatitis clearly linked to intravenous and intraperitoneal administration of tobramycin. Despite the complicated drug regimen with which the patient was treated, tobramycin was implicated by rechallenge with the drug once before its role was understood and again at an outside hospital.

Open heart surgery in geriatric patients.

With the progress of medical science, the scope of open heart surgery has expanded. From 1975 through 1987, we operated on 114 consecutive patients aged 65 years and over with the aid of a cardiopulmonary bypass in the Department of Surgery, National Taiwan University Hospital. The annual number of these elderly patients has increased gradually, reaching 6.4% of the annual open heart cases in 1987. Eighty-six of our 114 patients were males and 28 were females. Their ages ranged from 65 to 88 years with an average of 68.5 years. Overall, 65 patients (57%) were operated on for coronary artery disease and/or its associated lesions; 41 (36%), for valvular heart disease; six, for aortic dissection; two, for cardiac tumor; and one, for congenital pulmonary stenosis. One patient had combined coronary artery disease and aortic dissection. The mortality for isolated coronary artery bypass surgery was 12%; for single valvular surgery it was 11%. The complexity of the surgical procedure increased the operative mortality. The overall mortality was 23.6% (27/114), with subsequent death in 5.7% during an average of 25 months of follow-up. Because of the degeneration of organ-systems in elderly patients, and its frequent association with poor cardiac reserve and other medical problems, these elderly cardiac patients should be checked thoroughly before they are considered for open heart surgery. Our experience suggests that open heart surgery can be done in selected patients aged 65 years or older with acceptable risks. Age alone should not be an absolute contraindication to surgery, and clinical improvement is to be expected after surgery.

Midterm outcome of mitral valve regurgitation after repair of atrioventricular septal defect.

The purpose of this retrospective study was to evaluate the outcome of mitral regurgitation (MR) following repair of atrioventricular septal defects (AVSDs). Echocardiograms of all survivors after AVSD surgery between 1991 and 1996 were reviewed. This study enrolled 16 patients who had had more than two postoperative color Doppler studies. On each echocardiogram, MR severity was graded on a 1+ to 4+ scale, based on the size of the MR jet. Mean age at surgery was 31.1 months (range 2.5 to 83) and mean postoperative follow-up duration was 23.6 months (range 1 to 59). Mild deterioration of mitral valve function was common. MR severity increased by one or more grades in 5 patients (31%) between the initial and final examinations. However, the deterioration in mitral valve function occurred primarily on the immediate postoperative stage. On mid-term follow-up, the MR improved, or at least became stationary, in all patients. Mitral valvuloplasty was not necessary in surviving patients. We conclude that postoperative MR remains fairly stable following AVSD repair. Serious deterioration is rare.