Mechanisms of immunotherapeutic intervention by anti-CD154 (CD40L) antibody in high-risk corneal transplantation.

This study aimed to determine the effects of anti-CD154 on T cell cytokine profiles and ocular chemokine gene expression after high-risk corneal transplantation and to specifically determine if CD154 blockade is associated with a switch from a Th1 to a Th2 alloimmune response. Mice were used as recipients of syngeneic or multiple minor H or MHC antigen-mismatched corneal grafts. Recipient beds were neovascularized (high-risk). Hosts were randomized to receive either anti-CD154 antibody or control immunoglobulin (Ig) perioperatively. Two weeks after corneal transplantation, allospecific delayed-type hypersensitivity (DTH) was evaluated. Frequencies of interferon-gamma (IFN-gamma)-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in the hosts were measured by enzyme-linked immunospot (ELISPOT) assay. Ocular chemokine gene expression in anti-CD154-treated and control hamster Ig-treated groups was determined using a multiprobe ribonuclease protection assay (RPA). Leukocyte infiltration of corneal grafts was evaluated microscopically. Anti-CD154-treated mice did not exhibit allospecific DTH. The frequencies of Th1 cytokine-producing but not Th2 cytokine-producing T cells were significantly reduced in anti-CD154-treated hosts. Postoperative mRNA levels of RANTES and macrophage inflammatory protein-1beta (MIP-1beta) in anti-CD154-treated eyes were substantially suppressed compared with hamster Ig-treated controls. Leukocyte infiltration was profoundly suppressed in grafts of anti-CD154-treated hosts. These data demonstrate that blockade of the CD40-CD154 costimulatory pathway after corneal transplantation inhibits Th1-mediated responses but does not induce a switch to a Th2-specific response. In addition, anti-CD154 therapy suppresses ocular chemokine gene expression and leukocytic infiltration into allografts.     

Molecular characterization and pathogenicity of a carrot (Daucus carota) infecting begomovirus and associated betasatellite from India

The yellow mosaic pattern and shortening of leaf petiole are common disease symptoms associated with begomovirus infection in carrot. DNA from field infected carrot leaves was analyzed by rolling circle amplification and sequencing. The results established the presence of ageratum enation virus (AEV), which is referred to here as ageratum enation virus-carrot (AEV-Car). Symptomatic ageratum (Ageratum conyzoides) plants, growing adjacent to the carrot fields, also showed the presence of AEV (AEV-Age). Ageratum yellow leaf curl betasatellite (AYLCB) was also detected in the AEV infected carrot and ageratum samples. AEV-Car and AEV-Age are 95–97% identical in their DNA sequences, represent groups of isolates from the respective plant hosts (carrot and ageratum). Agroinoculation using infectious clones of AEV-Car plus AYLCB or AEV-Age plus AYLCB in carrot, ageratum, tobacco (Nicotiana tabacum) and tomato (Solanum lycopersicum) produced yellow mosaic and curling symptoms in leaves of inoculated plants. Agroinoculation of the two isolates together, along with the betasatellite (AEV-Car plus AEV-Age plus AYLCB) resulted in the enhancement of symptoms in comparison to the plants inoculated with single isolate. Plants with more severe symptoms showed a higher level of viral DNA accumulation, suggesting synergistic interactions between the two isolates of AEV.     

P-glycoprotein (MDR 1 gene product) in cells of the immune system: Its possible physiologic role and alteration in aging and human immunodeficiency virus-1 (HIV-1) infection

P-glycoprotein, a 170-kd glycoprotein encoded by theMDR 1 gene, is a member of a highly conserved superfamily of ATP-binding cassette (ABC) transport proteins. It shares extensive homology with numerous bacterial and eukaryotic ABC transport proteins. P-glycoprotein acts as an energy-dependent efflux pump that appears to transport structurally diverse agents ranging from ions to peptides. P-glycoprotein (P-gP) has been implicated as playing a role in multidrug (MDR) resistance in cancer, chloroquine-resistantPlasmodium falciparum infection, and possibly human immunodeficiency virus-1 (HIV-1) resistance to nucleoside compounds. A number of normal tissues in humans and rodents have been shown to express high levels of P-gp. The expression and function of P-gp in cells of the immune system have been explored in the past 2 years. This review presents a state of the art regarding the expression, regulation, and function of Pgp in cells of the immune system. In addition, its alteration in aging and HIV-1 infection is reviewed. A possible physiologic role of P-gp in cytokine secretion, antigen processing/presentation, and effector functions is also discussed.     

Alcohol consumption and the risk of stroke among hypertensive and overweight men

High blood pressure and overweight are risk factors for stroke. The aim of the present study was to examine the association between alcohol consumption and the risk of stroke according to the level of blood pressure and body weight. This study is a population-based sample of men with an average follow-up of 14.9 years from eastern Finland. A total of 2,599 men with no history of stroke at baseline participated. During the follow-up period, 224 strokes occurred, of which 181 were ischemic strokes. After adjustment for age, year of examination, socioeconomic status, serum LDL cholesterol, body mass index, smoking and energy expenditure of physical activity (kcal/day), there was a significant trend of an increased risk for any and ischemic stroke among hypertensive men. Hypertensive (blood pressure of over 140/90 mm Hg) men, who did not consume alcohol had a 1.72-fold (95 % CI 1.12–2.66; p = 0.014) relative risk (RR) for any stroke and a 1.90-fold (95 % CI 1.15–3.13; p = 0.012) RR for ischemic stroke. Among hypertensive men who consumed alcohol RR was 1.86-fold (95 % CI 1.20–2.89; p = 0.005) for any stroke and 2.02-fold (95 % CI 1.21–3.35; p = 0.007) for ischemic stroke. Men who did not consume alcohol with elevated BMI (≥26.4 kg/m²) had a 1.63-fold RR (95 % CI 1.11–2.40; p = 0.013) for any stroke and a 1.33-fold RR (95 % CI 0.87–2.04; p = 0.199) for ischemic stroke after adjusting for risk factors. Overweight men (≥26.4 kg/m²) who consumed alcohol had a 1.73-fold RR (95 % CI 1.18–2.54; p = 0.005) for any stroke and a 1.71-fold RR (95 % CI 1.14–2.57; p = 0.010) for ischemic stroke after being adjusted for risk factors. In conclusion, this population-based prospective study shows that hypertensive and overweight men who consumed alcohol had an increased risk for stroke.     

Outcome of Laparoscopic Cholecystectomy in Patients 80 Years and Older

Advanced age is associated with an increase in postoperative complications. This study assesses the indications and outcome for laparoscopic cholecystectomy (LC) in patients aged 80 years or older. Consecutive, unselected patients aged 80 years or over undergoing LC between 1991 and 2000 were included. A retrospective case review enabled analysis of clinical and operative factors together with in-hospital morbidity, 30-day mortality, and duration of hospital stay. A series of 117 patients, 79 women and 38 men with a median age of 83 years (range 80–93 years), underwent LC. Indications for LC were chronic cholecystitis in 62 (53%) patients, acute cholecystitis in 28 (24%), gallstone pancreatitis in 12 (10%), and other conditions in 15 (13%). Six (5%) patients required conversion to an open procedure. Overall, 26 (22%) patients developed a postoperative complication. There were no bile leaks or bile duct injuries. One patient, with gangrenous cholecystitis, died after LC. The median postoperative hospital stay was 3 days (range 1–31 days). LC can be performed safely with low morbidity in patients over age 80 years.This study was presented to the Association of Surgeons of Great Britain and Ireland Annual Meeting, Dublin, Ireland, 2002. It was published in abstract form in the British Journal of Surgery 2002;89(S1):3.     

Effects of mTOR inhibitor–related proteinuria on progression of cardiac allograft vasculopathy and outcomes among heart transplant recipients

We have previously described the use of sirolimus (SRL) as primary immunosuppression following heart transplantation (HT). The advantages of this approach include attenuation of cardiac allograft vasculopathy (CAV), improvement in glomerular filtration rate (GFR), and reduced malignancy. However, in some patients SRL may cause significant proteinuria. We sought to investigate the prognostic value of proteinuria after conversion to SRL. CAV progression and adverse clinical events were studied. CAV progression was assessed by measuring the Δ change in plaque volume (PV) and plaque index (PI) per year using coronary intravascular ultrasound. Proteinuria was defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL. Overall, 137 patients were analyzed (26% with proteinuria). Patients with proteinuria had significantly lower GFR (P = .005) but similar GFR during follow-up. Delta PV (P < .001) and Δ PI (P = .001) were significantly higher among patients with proteinuria after adjustment for baseline characteristics. Multivariate Cox regression analysis showed higher all-cause mortality (hazard ratio 3.8; P = .01) with proteinuria but similar risk of CAV-related events (P = .61). Our results indicate that proteinuria is a marker of baseline renal dysfunction, and that HT recipients who develop proteinuria after conversion to SRL have less attenuation of CAV progression and higher mortality risk.     

Posttraumatic osteonecrosis and nonunion of distal pole of scaphoid

Posttraumatic osteonecrosis of distal pole of scaphoid is an extremely rare with only two reported cases so far. We present a case of a 30-year-old male with a 2-year-old posttraumatic osteonecrosis and nonunion of distal pole of scaphoid left wrist. He presented with complaints of pain and restriction of movements. There was no evidence of radiocarpal arthritis. He was managed with open reduction and internal fixation with k-wires, supplemented by a pronator quadratus based muscle pedicle bone graft. The fracture union was achieved at 6 months. After 2 years, he had almost complete range of wrist motion and had returned to his preinjury level of functional activity. His MRI (magnetic resonance imaging) scans showed evidence of revascularization suggesting successful incorporation of bone graft.     

Does the impact of elective temporary clipping on intraoperative rupture really influence neurological outcome after surgery for ruptured anterior circulation aneurysms?—A prospective multivariate study

Background

Elective temporary clipping (ETC) is increasingly used in surgery for aneurysms. This study was to assess whether the impact of ETC on intraoperative aneurysmal rupture (IAR) translates into neurological outcome.

Methods

Patients who underwent surgery for ruptured anterior circulation aneurysms were prospectively studied for various factors related to ETC, IAR and neurological outcome at 3 months. Univariate and multivariate analyses were performed using SPSS20.

Results

Of the total 273 ruptured aneurysm surgeries studied, IAR was observed in only six out of 132 aneurysms (4.5 %) who had ETC, compared with 78 out of 141 (55.3 %) without ETC (p?<?0.001). Aneurysms complicated by IAR had significantly longer clipping time (8.3 min) compared with those without IAR (1.9 min) (p?<?0.001). IAR had significant association with unfavorable outcome (38 % vs. 24 %) (p?=?0.02). Patients with ETC had significantly shorter clipping time (2.9 min) compared with those without ETC (4.8 min) (p?=?0.02). Unfavorable outcome was noted in 30 out of 132 with ETC (23 %), compared with 48 out of 141 without ETC (34 %) (p?=?0.04). This beneficial effect was nonsignificantly greater in younger and good clinical grade patients. While episodes of ETC within clipping time of 20 min did not show significant difference in outcome, repeated rescue clipping (45 % unfavorable outcome, p?=?0.048) and total clipping time of at least 20 min (75 % unfavorable outcome, p?=?0.008) had significant impact on outcome. In multivariate analysis, the use of ETC (p?=?0.027) and total temporary clipping less than 20 min (p?=?0.049) were noted to result in significantly better outcome, independent of other factors.

Conclusions

The use of ETC decreased the occurrence of IAR and the total clipping time, thereby leading to significantly better outcome, independent of other factors. While repeated elective clipping within total clipping time of 20 min did not influence outcome, repeated rescue clipping and total clipping time of at least 20 min had significant impact on outcome.