The hematopoietic cell-specific Rho GTPase inhibitor ARHGDIB/D4GDI limits HIV type 1 replication

Rho GTPases are able to influence the replication of human immunodeficiency virus type 1 (HIV-1). However, little is known about the regulation of HIV-1 replication by guanine nucleotide dissociation inhibitors (GDIs), one of the three major regulators of the Rho GTPase activation cycle. From a T cell-based cDNA library screening, ARHGDIB/RhoGDIβ, a hematopoietic lineage-specific GDI family protein, was identified as a negative regulator of HIV-1 replication. Up-regulation of ARHGDIB attenuated the replication of HIV-1 in multiple T cell lines. The results showed that (1) a significant portion of RhoA and Rac1, but not Cdc42, exists in the GTP-bound active form under steady-state conditions, (2) ectopic ARHGDIB expression reduced the F-actin content and the active forms of both RhoA and Rac1, and (3) HIV-1 infection was attenuated by either ectopic expression of ARHGDIB or inhibition of the RhoA signal cascade at the HIV-1 Env-dependent early phase of the viral life cycle. This is in good agreement with the previous finding that RhoA and Rac1 promote HIV-1 entry by increasing the efficiency of receptor clustering and virus-cell membrane fusion. In conclusion, the ARHGDIB is a lymphoid-specific intrinsic negative regulator of HIV-1 replication that acts by simultaneously inhibiting RhoA and Rac1 functions.     

Six-transmembrane epithelial antigen of prostate4 (STEAP4) is a tumor necrosis factor alpha-induced protein that regulates IL-6, IL-8, and cell proliferation in synovium from patients with rheumatoid arthritis

Human six-transmembrane epithelial antigen of prostate4 (STEAP4), an ortholog of mouse tumor necrosis factor-α-induced adipose-related protein (TIARP), plays a role in tumor necrosis factor (TNF)-dependent arthritis models. However, its role in rheumatoid arthritis (RA) is still obscure. This study explored such a role for STEAP4. The expressions of STEAP4, TNFα, and IL-6 were compared in synovia of RA and osteoarthritis patients. STEAP4 induction was examined in TNFα-stimulated fibroblast-like synoviocytes (FLS) in vitro. FLS (with/without TNFα stimulation) were also analyzed for IL-6 expression after STEAP4 knockdown, using siRNA or transfection with STEAP4-plasmid DNA. IL-8, cell proliferation, and apoptosis were also evaluated in STEAP4-overexpressing FLS. The expression of STEAP4 in joints correlated with TNFα expression, specifically in RA synovium. In the cultured FLS, STEAP4 protein expression was augmented by TNFα activation, and localized in endosomal/lysosomal compartments. STEAP4 downregulation by siRNA enhanced the expression of IL-6 mRNA, while STEAP4 overexpression suppressed IL-6 and IL-8 expression, inhibited cell proliferation, and induced apoptosis via caspase-3. The results indicated that human STEAP4 is regulated by TNFα in synovium, where it controls IL-6 secretion and proliferation of FLS, suggesting that STEAP4 might potentially suppress the pathogenesis of TNFα-induced arthritis such as RA.     

Visual acuity after intravitreal ranibizumab with and without laser therapy in the treatment of macular edema due to branch retinal vein occlusion: a 12-month retrospective analysis

AIM: To identify factors contributing to visual improvement after treatment of macular edema (ME) secondary to branch retinal vein occlusion (BRVO), and to assess the interaction between laser therapy and intravitreal ranibizumab (IVR). METHODS: We retrospectively reviewed the medical records of patients who had been treated for BRVO-related ME at our hospital. Records were traceable for at least 12mo, and evaluated factors included age, sex, medical history, smoking history, treatment methods, foveal hemorrhage, and change in visual acuity. Treatments included laser therapy, IVR, sub-Tenon’s capsule injection of triamcinolone (STTA), a combination, or no intervention. Multivariate logistic regression analysis and interaction terms were used to assess the clinical efficacy of the treatments, and odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: Seventy-three patients (34 men, 39 women; 73 eyes) with a mean age of 69.4±12.1y were included. Patients who underwent IVR monotherapy, laser monotherapy, and STTA+laser had significantly higher best corrected visual acuity at 12mo compared to baseline (P<0.001, <0.001, and 0.019, respectively). Logistic regression analysis without interaction terms found that IVR was a significant visual acuity recovery factor (adjusted OR: 3.89, 95%CI: 1.25-12.1, P=0.019). Adjusted OR using an interaction model by logistic regression was 16.6 (95%CI: 2.54-108.47, P=0.003) with IVR treatment, and 8.25 (95%CI: 1.34-50.57, P=0.023) with laser treatment. No interaction was observed (adjusted OR: 0.07, 95%CI: 0.01-0.75, P=0.029). CONCLUSION: IVR contributes to improvements in visual acuity at 12mo in ME secondary to BRVO. No interaction is observed between laser therapy and IVR treatments.     

Surgery for a gastroenteropancreatic neuroendocrine tumor (GEPNET) in multiple endocrine neoplasia type 1

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited endocrine tumor syndrome characterized by tumor development in various endocrine organs such as the parathyroid, endocrine pancreas, anterior pituitary and adrenal cortex. The first extensive database for Asian patients with MEN1 was established by the MEN Consortium of Japan. Although the clinical features of Japanese patients with MEN1 are similar to those from Western countries, there are several characteristic differences between them. In particular, gastroenteropancreatic neuroendocrine tumor (GEPNET) is seen in approximately 60 % of patients with MEN1 in Japan. Although its development is the strongest prognostic factor in patients with MEN1, the characteristics of MEN1-associated GEPNET still remain unclear. This is especially true for the differences in clinical features of GEPNET with and without MEN1. Improved long-term survival is obtained by curative surgery for patients with MEN1-associated GEPNET. The current surgical indications are expanding even in patients with hepatic metastases because of the improved surgical outcome. This article reviews the clinical characteristics in these patients with a particular focus on surgery, diagnosis, surgical indications, surgical method, and surgical outcome.     

Risk factors for postoperative mortality and morbidities in emergency surgeries

Background

Emergency surgery itself induces high risk for postoperative mortality and morbidities; however, it remains unknown which concomitant pathological conditions of emergency surgeries are causative factors of deteriorating outcomes. This study examined the causal factors of postoperative mortality and morbidity in cases of emergency surgery.

Methods

Patients undergoing emergency surgery from January to December 2007 were enrolled in this retrospective cohort study. Causal relationships were analyzed by stepwise multivariate logistic regression analysis between possible independent factors (sex, age, kind of surgical department, timing of surgery, duration of surgery, blood transfusion, deteriorated consciousness level, shock state, abnormal coagulate state, and history of hypertension, diabetes, ischemic heart disease, chronic obstructive pulmonary disease, renal failure, and anemia) and postoperative mortality or morbidities (failure of removal of tracheal tube after operation, tracheotomy, cerebral infarction, massive hemorrhage, severe hypotension, severe hypoxemia, and severe arrhythmia during or after surgery).

Results

Shock, deteriorated consciousness level, chronic obstructive lung disease, and ischemic heart disease were significant risk factors for mortality (OR 14.2, 7.9, 6.4, and 3.8, respectively), and deteriorated consciousness level, blood transfusion, shock, chronic obstructive lung disease, diabetes, cardiovascular surgery, and operation longer than 2 h were significant risk factors for morbidity (OR 19.1, 3.3, 3.0, 2.5, 2.4, 2.4, and 1.8, respectively).

Conclusion

State of shock, deteriorated consciousness level, chronic obstructive lung disease, ischemic heart disease, hemorrhage requiring blood transfusion, age over 80 years, cardiovascular surgery, surgeries at night, and surgeries of duration more than 2 h cause patients to be strongly susceptible to postoperative mortality or morbidity in emergency surgeries.     

Ultrasound as visual feedback in speech habilitation: Exploring consultative use in rural British Columbia,Canada

Ultrasound has shown promise as a visual feedback tool in speech therapy. Rural clients, however, often have minimal access to new technologies. The purpose of the current study was to evaluate consultative treatment using ultrasound in rural communities. Two speech‐language pathologists (SLPs) trained in ultrasound use provided consultation with ultrasound in rural British Columbia to 13 school‐aged children with residual speech impairments. Local SLPs provided treatment without ultrasound before and after the consultation. Speech samples were transcribed phonetically by independent trained listeners. Eleven children showed greater gains in production of the principal target // after the ultrasound consultation. Four of the seven participants who received more consultation time with ultrasound showed greatest improvement. Individual client factors also affected outcomes. The current study was a quasi‐experimental clinic‐based study. Larger, controlled experimental studies are needed to provide ultimate evaluation of the consultative use of ultrasound in speech therapy.     

Postmortem detection of rocuronium and sugammadex by LC/MS in the blood of a patient who died on postoperative day 8

Forensic Toxicology - This case report describes the purposeful forensic detection of both the muscle relaxant rocuronium and the reversal agent sugammadex in the blood of a patient who died 8 days...     

Correction to: Cost-effectiveness of mass screening for dipstick hematuria in Japan

Clinical and Experimental Nephrology -