Reduced thymic IL-4 impairs negative T cell selection in nonobese diabetic mice.

Type 1 diabetes (T1D) develops spontaneously despite functional antigen presentation machinery in the thymus and a perceptible central tolerance process. We found that intrathymic enrichment with IL-4 fine tunes signaling through the IL-4/IL-13 heteroreceptor (HR) in early thymic progenitors (ETPs), augments negative selection of self-reactive T cells, sustains a diverse T cell repertoire devoid of clones expressing disease-associated T cell receptor (TCR) genes, and protects the nonobese diabetic (NOD) mouse from T1D. Indeed, optimal IL-4 activates STAT transcription factors to program ETP fate decision toward CD11c+CD8α+ dendritic cells (DCs) agile in negative T cell selection and clonal deletion of diabetogenic T cells.

Rigid crosslinking of the CD3 complex leads to superior T cell stimulation.

Functionally bivalent non-covalent Fab dimers (Bi-Fabs) specific for the TCR/CD3 complex promote CD3 signaling on T cells. While comparing functional responses to stimulation with Bi-Fab, F(ab')2 or mAb specific for the same CD3 epitope, we observed fratricide requiring anti-CD3 bridging of adjacent T cells. Surprisingly, anti-CD3 Bi-Fab ranked first in fratricide potency, followed by anti-CD3 F(ab')2 and anti-CD3 mAb.

Regional Differences in American Indian/Alaska Native Chronic Respiratory Disease Disparity: Evidence from National Survey Results.

American Indian/Alaska Native (AI/AN) persons in the US experience a disparity in chronic respiratory diseases compared to white persons. Using Behavioral Risk Factor Surveillance System (BRFSS) data, we previously showed that the AI/AN race/ethnicity variable was not associated with asthma and/or chronic obstructive pulmonary disease (COPD) in a BRFSS-defined subset of 11 states historically recognized as having a relatively high proportion of AI/AN residents. Here, we investigate the contributions of the AI/AN variable and other sociodemographic determinants to disease disparity in the remaining 39 US states and territories.

Lower female survival from an opportunistic infection reveals progesterone-driven sex bias in trained immunity.

Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli.

Early expression of mature αβ TCR in CD4CD8 T cell progenitors enables MHC to drive development of T-ALL bearing NOTCH mutations.

During normal T cell development in mouse and human, a low-frequency population of immature CD4CD8 double-negative (DN) thymocytes expresses early, mature αβ T cell antigen receptor (TCR). We report that these early αβ TCR+ DN (EADN) cells are DN3b-DN4 stage and require CD3δ but not major histocompatibility complex (MHC) for their generation/detection. When MHC - is present, however, EADN cells can respond to it, displaying a degree of coreceptor-independent MHC reactivity not typical of mature, conventional αβ T cells.

Transcriptional Regulation of the Human IL5RA Gene through Alternative Promoter Usage during Eosinophil Development.

Regulation of the IL-5 receptor alpha () gene is complicated, with two known promoters (P1 and P2) driving transcription, and two known isoforms (transmembrane and soluble) dichotomously affecting the signaling potential of the protein products. Here, we sought to determine the patterns of P1 and P2 promoter usage and transcription factor occupancy during primary human eosinophil development from CD34 hematopoietic stem cell progenitors. We found that during eosinophilopoiesis, both promoters were active but subject to distinct temporal regulation, coincident with combinatorial interactions of transcription factors, including GATA-1, PU.

Novel peptide nanoparticle-biased antagonist of CCR3 blocks eosinophil recruitment and airway hyperresponsiveness.

Background: Chemokine signaling through CCR3 is a key regulatory pathway for eosinophil recruitment into tissues associated with allergic inflammation and asthma. To date, none of the CCR3 antagonists have shown efficacy in clinical trials. One reason might be their unbiased mode of inhibition that prevents receptor internalization, leading to drug tolerance.

Degree of obesity is not associated with more than one intubation attempt: a large centre experience.

Background: The role of obesity as a risk factor for difficult intubation remains controversial. We primarily assessed the association between body mass index (BMI) and difficult tracheal intubation.

Methods: We analysed electronic records of more than 67 000 adults having elective non-cardiac surgery requiring tracheal intubation at the Cleveland Clinic between 2011 and 2015.

AIDS-related cholangiopancreatographic changes.

The cholangiographic and pancreatographic appearances of the acquired immunodeficiency syndrome (AIDS) associated cholangitis were evaluated in 26 patients. Twenty-four patients were diagnosed by retrograde cholangiography or endoscopic cholangiopancreatography (ERC or ERCP). One patient was diagnosed by T-tube cholangiography and another patient by transhepatic cholangiography.

Hepatobiliary complications of polyarteritis nodosa.

Although polyarteritis nodosa (PAN) may result in thrombosis or aneurysm formation in any organ in the body, hepatobiliary complications are unusual. We reviewed seven cases that demonstrated the diagnostic difficulties and therapeutic options available in the management of hepatobiliary PAN. No consistent sign that indicated the severity of hepatobiliary PAN could be identified.

Colonic diverticulitis in young patients with chronic renal failure and transplantation.

The association of colonic diverticulitis with chronic renal failure is well known. In those patients with "adult" autosomal dominant polycystic kidney disease, colonic diverticulitis is an especially common complication. We present two young patients (one teenager and one mid-twenties) who developed intra-abdominal abscess several years after renal transplantation.

Obstruction of the Roux limb after portoenterostomy for biliary atresia: a delayed complication.

We report the case of a 5-year-old girl who underwent a Kasai portoenterostomy for extrahepatic biliary atresia. The conduit was exteriorized until 11 months of age. She was doing well, with stable portal hypertension until she suddenly developed jaundice, acholic stools, and bacteremia not responsive to a course of steroids and intravenous antibiotics.

Gianturco-Rosch biliary stents: preliminary experience.

Results of long-term follow-up are reported for nine patients who underwent placement of Gianturco-Rosch expandable metallic stents. Seven patients had malignant disease. The average duration of patency was 7 months.

Percutaneous transjejunal approaches to the biliary system.

The authors report 10 cases in which various retrograde manipulations in the biliary tract were performed via percutaneous access from the jejunum in patients who had previously undergone Roux-Y biliary surgery. The first cases involved attempted retrograde cholangiography through the jejunal limb in children who had undergone Roux-Y portoenterostomies, followed by cases of percutaneous placement of U tubes and an attempt at percutaneous creation of an hepaticojejunostomy. When a limb from the Roux-Y has been brought to the skin and marked with clips, jejunal puncture is easily performed, is well tolerated by patients, and may be repeated frequently.

Total occlusions of the femoropopliteal artery: high technical success rate of conventional balloon angioplasty.

Seventy patients 48-93 years of age underwent standard percutaneous transluminal angioplasty (PTA) for femoropopliteal artery occlusions 1-10 cm long. PTA was accomplished through an antegrade puncture of the common femoral artery. The angiographic criterion for technical success was restoration of the vessel lumen with no significant residual stenosis.

Percutaneous drainage of intra-abdominal abscesses following abdominal trauma.

Between January 1, 1984, and June 30, 1987, we performed percutaneous catheter drainage (PCD) of 28 intra-abdominal abscesses in 21 postoperative trauma patients. During this period only three patients had abdominal re-exploration for drainage of abdominal abscess. The PCD patients were predominantly young men who had sustained penetrating abdominal injuries (81% GSW or SW; 19% MVA).

Maintaining quality of life after palliative diversion for malignant ureteral obstruction.

The records of 71 consecutive patients who underwent percutaneous nephrostomy for malignant ureteral obstruction were reviewed. The average post-nephrostomy survival time was seven months, of which 25% was spent in the hospital. When comparing these figures to older studies of open nephrostomy, the percutaneous procedure is associated with less morbidity and an increased percentage of time spent at home (75% compared to 36%).

Hepatic neurofibromatosis, malignant schwannoma, and angiosarcoma in von Recklinghausen's disease.

Liver involvement by neurofibromatosis is rare. This report describes a young man with von Recklinghausen's disease and hepatic neurofibromas who developed a large right hepatic lobe malignancy and died of massive intratumor hemorrhage. Postmortem examination showed the tumor to be composed of both malignant schwannoma and angiosarcoma and to have arisen from contiguous neurofibromas in portal tracts.

Percutaneous creation of a hepaticojejunostomy.

A procedure is described whereby a direct anastomosis may be created percutaneously between the biliary system and a Roux-en-Y limb; in effect a percutaneous hepaticojejunostomy. Although it will have limited applications, it represents a further extension of percutaneous techniques in the biliary system for complex problems.

Cystic duct occlusion and transcatheter sclerosis of the gallbladder in the rabbit.

We have identified a reliable sclerosant of the gallbladder in rabbits. After ligating the cystic ducts with a silk ligature in 24 rabbits and aspirating the bile from the gallbladder, we instilled a mixture of 95% ethanol and either 2 M% trifluoroacetic acid (TFA) or 5 M% TFA into the gallbladder. The animals were killed after 6 or 8 weeks.

Percutaneous removal of large gallstones.

Two patients are described in whom large gallstones, up to 4 cm in diameter, were removed percutaneously. The technique has some relevance to high risk patients with surgical cholecystotomies in whom elective cholecystectomy may be deferred if all the calculi can be removed. It may also be relevant if "percutaneous cholecystectomy" is ever developed clinically.

Transcatheter sclerosis of the gallbladder in rabbits. A preliminary study.

Catheter sclerosis of 56 rabbit gallbladders was attempted at laparotomy. The proximal cystic duct was occluded with a hemoclip and transcatheter administration of six different sclerosing agents and a saline control was performed. Eight animals were used for each agent, three being sacrificed after two weeks and the remainder after six weeks.