Correction to: Clinical Manifestations,Mutational Analysis,and Immunological Phenotype in Patients with RAG1/2 Mutations: First Cases Series from Mexico and Description of Two Novel Mutations

Journal of Clinical Immunology - A Correction to this paper has been published: https://doi.org/10.1007/s10875-021-01075-7     

The role of tissue inhibitors of metalloproteinases in tumorigenesis and metastasis

Tissue inhibitors of metalloproteinases (TIMPs) are classically known for regulating members of the metzincin protease family and are well recognized for their inhibitory effects in cancer development and progression. Despite their common evolutionary structure, the four TIMP proteins have unique properties and regulation, and produce distinct phenotypes when ablated. A comprehensive assessment of their function during tumorigenesis reveals substantial effects on cell proliferation, apoptosis, angiogenesis, invasion, and metastasis as well as a potential role in genomic instability. The TIMPs universally inhibit angiogenesis, invasion, and metastasis, but their specific effects on cell proliferation and apoptosis are both tissue specific and context dependent. They exert these effects in a metalloproteinase-dependent as well as metalloproteinase-independent manner. Knowledge gained from these biological studies provides a foundation for the full understanding of TIMP function in physiology and various pathologies as well as for the development of the next generation of therapeutic metalloproteinase inhibitors.     

Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor

EAT-2 is an adaptor expressed in innate immune cells, including natural killer (NK) cells. It is closely related to the adaptor SAP, which regulates signaling lymphocyte activation molecule (SLAM)-related receptors by recruiting the kinase FynT to the receptors. Here we have studied the function of EAT-2 in NK cells by creating mice lacking or overexpressing EAT-2. Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells. However, unlike SAP, EAT-2 was an inhibitor of NK cell function. EAT-2 repressed natural cytotoxicity and interferon-gamma secretion by a mechanism involving tyrosine phosphorylation of its C terminus. We have demonstrated a similar function for the adaptor ERT, a newly identified SAP family member expressed in mouse NK cells. These data identify a previously unknown mechanism of NK cell inhibition. Moreover, they indicate that EAT-2 and SAP have distinct and at times opposing functions in natural immunity.     

Use of Bariatric Outcomes Longitudinal Database (BOLD) to Study Variability in Patient Success After Bariatric Surgery

Background

This study was conducted to determine the contributions of various predictors to the large variations in absolute weight loss and percent body mass index (BMI) loss after bariatric surgery.

Methods

The data source was the Bariatric Outcomes Longitudinal Database^SM by the Surgical Review Corporation. Eligibility criteria included a first bariatric surgery for adjustable gastric band (AGB), Roux-en-Y gastric bypass (RYBG), or sleeve gastrectomy (SG) between January 2007 and February 2010; age 21 years or older; presurgery BMI?>?30 kg/m²; and at least one preoperative visit within 6 months and at least one postoperative visit 30 days or more after surgery. Potential predictor variables included procedural details, patient demographics, comorbidities, and prior surgical history. Linear regression models of absolute weight loss and %BMI loss were fitted at 12, 18, and 24 months. The 12-month absolute weight loss endpoint was then chosen for a more in-depth analysis of variability through variable transformations and separate models by procedure.

Results

A total of 31,443 AGB, 40,352 RYGB, and 2,194 SG patients met all inclusion criteria. Regression models explained 37 to 55 % of the variability in %BMI loss and 52 to 65 % of variability in absolute weight loss. The key predictors for absolute weight loss at 12 months were procedure (44.8 %) and baseline weight (18.5 %), with 34.2 % of the variability unexplained. Other significant predictors, each of which accounted for <1 % of variability, included age, race, and diabetes.

Conclusions

Research on additional sources of variability is still needed to help explain the remaining differences in outcomes after bariatric surgery.     

Leptin deficiency-induced obesity affects the density of mast cells in abdominal fat depots and lymph nodes in mice

Background  

Mast cells are implicated in the pathogenesis of obesity and insulin resistance. Here, we explored the effects of leptin deficiency-induced obesity on the density of mast cells in metabolic (abdominal fat depots, skeletal muscle, and liver) and lymphatic (abdominal lymph nodes, spleen, and thymus) organs. Fourteen-week-old male leptin-deficient ob/ob mice and their controls fed a standard chow were studied. Tissue sections were stained with toluidine blue to determine the density of mast cells. CD117/c-kit protein expression analysis was also carried out. Furthermore, mast cells containing immunoreactive tumor necrosis factor-α (TNF-α), a proinflammatory cytokine involved in obesity-linked insulin resistance, were identified by immunostaining.     

Assessing risk factors,presentation, and management of portomesenteric vein thrombosis after sleeve gastrectomy: a multicenter case-control study

Background

Portomesenteric vein thrombosis (PMVT) is a rare complication of laparoscopic sleeve gastrectomy.

Mouse models of advanced spontaneous metastasis for experimental therapeutics

An enduring problem in cancer research is the failure to reproduce highly encouraging preclinical therapeutic findings using transplanted or spontaneous primary tumours in mice in clinical trials of patients with advanced metastatic disease. There are several reasons for this, including the failure to model established, visceral metastatic disease. We therefore developed various models of aggressive multi-organ spontaneous metastasis after surgical resection of orthotopically transplanted human tumour xenografts. In this Opinion article we provide a personal perspective summarizing the prospect of their increased clinical relevance. This includes the reduced efficacy of certain targeted anticancer drugs, the late emergence of spontaneous brain metastases and the clinical trial results evaluating a highly effective therapeutic strategy previously tested using such models.