Downregulation of CD4 is required for maintenance of viral infectivity of HIV-1

AbstractDownregulation of virus receptors on the cell surface is considered to be important in preventing superinfection. HIV-1 encodes multiple gene products, Env, Vpu, and Nef, involved in downregulation of CD4, a major HIV-1 receptor. We found that simultaneous mutations in both vpu and nef severely impaired virus replication. We examined the involvement of CD4 downregulation mediated by Vpu and Nef in the modification of virus infectivity. The mutation in vpu increased CD4 incorporation into virions without affecting the Env content in it, inhibiting the attachment step of virions to the CD4-positive cell surface. Although a single mutation in nef suppresses virus infectivity via a CD4-independent mechanism, it could augment CD4 incorporation in virions in combination with a vpu mutation. These results indicated that CD4 downregulation was necessary for maintenance of Env function in the virion

Outcome after resection arthroplasty or shortening oblique osteotomy of the lesser metatarsals combined with arthrodesis of the first metatarsophalangeal joint for severe rheumatoid forefoot deformities

Purpose We investigated objective and patient-reported outcomes after resection arthroplasty or shortening oblique osteotomy (SOO) of the lesser metatarsals combined with arthrodesis of the first metatarsophalangeal (MTP) joint for severe rheumatoid forefoot deformities. Methods 17 feet from 14 women (mean age, 67.8 years) underwent resection arthroplasty of the lesser metatarsal heads (MTH resection group), while 13 feet from nine women and two men (mean age, 68.7 years) underwent SOO of the lesser metatarsals (MTH preservation group). Arthrodesis of the first MTP joint was performed in all cases. Mean follow-up in the MTH resection and preservation groups was 25.0 and 21.3 months, respectively. Preoperative and postoperative clinical evaluation included Japanese Society for Surgery of the Foot (JSSF) scale and self-administered foot evaluation questionnaire (SAFE-Q) scores. Results Mean total JSSF scale significantly improved from 53.4 to 76.4 in the MTH resection group (p < .001) and from 50.1 to 74.2 in the MTH preservation group (p = .002). Pain and pain-related and shoe-related SAFE-Q subscale scores significantly improved after surgery in both groups. In the MTH resection group, recurrence of painful callosities and claw toe deformity was observed in four and three feet, respectively. In the MTH preservation group, one patient experienced recurrence of painful callosities and one underwent revision surgery for IP joint dislocation. Conclusion Resection arthroplasty or SOO of the lesser metatarsals combined with arthrodesis of the first MTP joint achieved significant improvement with respect to pain relief, deformity correction, and footwear comfort

A Novel Radiographic Measurement Method for the Evaluation of Metatarsophalangeal Joint Dislocation of the Lesser Toe in Patients with Rheumatoid Arthritis

Dorsal dislocation of metatarsophalangeal (MTP) joints of the lesser toe frequently occurs in patients with rheumatoid arthritis (RA), and may cause painful and uncomfortable plantar callosities and ulceration. The current study examined the reliability and clinical relevance of a novel radiographic parameter (the MTP overlap distance [MOD]) in evaluating the severity of MTP joint dislocation. The subjects of the current study were 147 RA patients (276 feet; 1104 toes). MOD, defined as the overlap distance of the metatarsal head and the proximal end of the phalanx, was measured on plain radiographs. The relationship between the MOD and clinical complaints (forefoot pain and/or callosity formation) was analyzed to create a severity grading system. As a result, toes with callosities had a significantly larger MOD. ROC analysis revealed that the MOD had a high AUC for predicting an asymptomatic foot (-0.70) and callosities (0.89). MOD grades were defined as follows: grade 1, 0 = 10 mm. The intra- and inter-observer reliability of the MOD grade had high reproducibility. Furthermore, the MOD and MOD grade improved significantly after joint-preserving surgeries for lesser toe deformities. Our results suggest that MOD and MOD grade might be useful tools for the evaluation of deformities of the lesser toe and the effect of surgical intervention for MTP joints in patients with RA

Yeast functional screen to identify genes conferring salt stress tolerance in Salicornia europaea

Salinity is a critical environmental factor that adversely affects crop productivity. Halophytes have evolved various mechanisms to adapt to saline environments. Salicornia europaea L. is one of the most salt-tolerant plant species. It does not have special salt-secreting structures like a salt gland or salt bladder, and is therefore a good model for studying the common mechanisms underlying plant salt tolerance. To identify candidate genes encoding key proteins in the mediation of salt tolerance in S. europaea, we performed a functional screen of a cDNA library in yeast. The library was screened for genes that allowed the yeast to grow in the presence of 1.3 M NaCl. We obtained three full-length S. europaea genes that confer salt tolerance. The genes are predicted to encode (1) a novel protein highly homologous to thaumatin-like proteins, (2) a novel coiled-coil protein of unknown function, and (3) a novel short peptide of 32 residues. Exogenous application of a synthetic peptide corresponding to the 32 residues improved salt tolerance of Arabidopsis. The approach described in this report provides a rapid assay system for large-scale screening of S. europaea genes involved in salt stress tolerance and supports the identification of genes responsible for such mechanisms. These genes may be useful candidates for improving crop salt tolerance by genetic transformation

In Situ Observation and Measurement of Actin Stress Fiber Deformation in Stretched Osteoblast like Cell

It is believed that mechanical stimuli, such as stretching of the extracellular matrix, are transmitted into cells via focal adhesion complexes and the actin cytoskeleton. Transmission dynamics of strain from the extracellular matrix into intracellular organelles is crucial to clarify the mechanosensing mechanisms of cells. In this study, we observed deformation behavior of actin stress fibers under uniaxial stretch using an originally developed cell-stretching microelectromechanical system (MEMS) device. It was difficult to conduct in situ observation of cells under stretch using conventional cell stretching devices, because motion artifacts such as rigid displacement during stretch application were not negligible. Our novel cell-stretching MEMS device suppressed rigid displacement while stretching, and we succeeded in obtaining time-lapse images of stretched cells. Uniaxial strain with a 10% magnitude and strain rate of 0.5%/sec was applied to cells. Deformation behaviors of the cells and actin stress fibers were recorded using a confocal laser scanning microscope. In time-lapse images of stretched cells, strains along each stress fiber were measured manually. As a result, in cells with a relatively homogeneous stress fiber structure oriented in one direction, distribution of the axial strain on stress fibers generally corresponded to deformation of the stretching sheet on which the cells had adhered. However, in cells with a heterogeneous stress fiber structure oriented in several directions, we found that the strain distribution along stress fibers was not homogeneous. In regions around the cell nucleus, there was a more complicated strain distribution compared with other regions. Our results suggest the cell nucleus with a stiff mechanical resistance yields such a complicated strain distribution in stress fibers

New Surgical Procedure for Pancreas Head

In this study, we demonstrate two new methods for pancreaticoduodenectomy (PD). One method is the mini‐laparotomic PD by Shuriken‐shaped umbilicoplasty with the real‐time moving window‘s method. The other method is the new pancreaticojejunostomy (PJ) by punctured stent slide guiding method (PSSGM). This procedure could be performed by complete mini‐laparotomy under direct vision, and the final major wound is only 2 cm of round navel. PSSGM prevents the difference of caliber between pancreatic anastomosis and the inside out of jejunal mucosa in theory. Ten cases of mini‐lap PD were successfully performed under new PJ anastomosis. The pancreatic leakage (PL) was only one case of ISGPF grade A, and its frequency was 9% (1/11). Our mini‐lap PD by Shuriken‐shaped umbilicoplasty might be a useful way for overcoming the obstacles about safety, complication risk, cosmetic demand, and medical cost compared to laparoscopic PD. Also, our new device of PJ reconstruction by PSSGM might be an easy and useful device for the prevention of PL

Preliminary Experience of Laparoscopic Cholecystectomy with Gallbladder Bed Dissection for Suspected Gallbladder Cancer

Selecting the appropriate operation for gallbladder cancer depends on the depth of cancer invasion, which remains difficult to determine preoperatively, especially with respect to the subserosal layer (pT2). We devised a laparoscopic cholecystectomy with gallbladder bed dissection (LC with GBD) as a new total biopsy method for suspected gallbladder cancer. We retrospectively reviewed the medical records of 19 patients who underwent LC with GBD to assess the usefulness of this procedure and the pathological findings. No severe morbidity or recurrence was encountered. LC with GBD could be performed easily and safely, and the patients’ postoperative course was almost equal to that of patients treated by conventional LC. Histologically, gallbladder cancer was diagnosed in five cases (pT1a, 3; pT2, 2). We believe that LC with GBD could play an important role in the potential treatment strategy for pT2 gallbladder cancer

Shortening Oblique Osteotomy with Screw Fixation for Correction of the Lesser Metatarsophalangeal Joints of Rheumatoid Forefoot

The metatarsophalangeal (MTP) joints are often and predominantly affected in rheumatoid arthritis. The aim of the current study was to describe surgical techniques of shortening oblique osteotomy for lesser metatarsal bone with screw fixation at the osteotomy site, and to investigate the short-term clinical outcomes of our procedure. Twenty-seven feet (78 toes) of 24 RA patients underwent the shortening oblique osteotomy for the correction of deformity at the lesser MTP joints. The average Japanese Society of Surgery of the Foot (JSSF) standard rating system for the RA foot and ankle scale improved significantly from 59.6 points preoperatively to 88.3 points postoperatively (p＜0.001). Twenty-four feet (89 ) were free from metatarsalgia and symptomatic callosities at the lesser MTP joint after surgery. Our present findings showed satisfactory early clinical outcomes of the shortening oblique osteotomy of the metatarsal bone with screw fixation for RA forefoot

Comparison of Surgeon Stress and Workload between Reduced-port and Laparoscopic Cholecystectomy : A Prospective Study

Single-port laparoscopic surgery（SPLS）has attracted attention in the field of minimally invasive surgery; however, the associated technical difficulty has delayed its adoption by all surgeons. Reduced-port laparoscopic surgery might be easier to perform than SPLS, and in this prospective study, we compared surgeon stress and workload between reduced-port laparoscopic cholecystectomy（RPLC）and conventional laparoscopic cholecystectomy（CLC）. Twenty consecutive patients were assigned to undergo either RPLC or CLC between July 2016 and April 2017. Two surgeons performed the operations. The differences in surgeon workload and stress between RPLC and CLC were evaluated. Patient factors and operative outcomes were not significantly different between RPLC and CLC. In the surgeon-reported Surgery Task Load Index, the task demand subscale was significantly higher for RPLC than for CLC（P＝0.005）, although the salivary amylase levels were not significantly different between RPLC and CLC. RPLC was similar to CLC with respect to surgeon stress. Considering workload, the task demand was higher in CLC than in RPLC, which therefore might be an acceptable alternative to CLC for treating benign gallbladder disease