Linda L. Wong

The CD4 (T4) antigen is a cell-surface glycoprotein that is expressed predominantly on the surface of helper T cells and has been implicated in the regulation of T-cell activation and in the associative recognition of class II antigens of the major histocompatibility complex. In addition, the CD4 antigen appears to serve as a receptor for the human immunodeficiency virus (HIV). An important question has been whether the CD4 receptor is linked to an intracellular mediator that could regulate the activation of the CD4+ subset. In this paper, we provide preliminary evidence that the CD4 receptor is complexed in detergent lysates to a protein-tyrosine kinase (PTK) of 55-60 kDa, which is expressed specifically in T cells. The PTK is the human analogue of the murine pp56LSTRA (pp56lck) and has significant homology with c-src, c-yes, and other members of the src family. The identification of the PTK associated with CD4 receptor was made by use of an antiserum to a synthetic peptide that was deduced from the DNA sequence of PTK. Two-dimensional nonequilibrium pH gradient gel electrophoresis/NaDodSO4/PAGE revealed the kinase to focus as a heterogeneous collection of spots in the pH range of 4.0-5.0. Furthermore, in vitro phosphorylation revealed the phosphorylation of two additional polypeptides at 40 and 80 kDa, in addition to the autophosphorylation of the PTK at 55-60 kDa. The potential importance of the association between the CD4 receptor and the PTK of T cells is discussed in relation to T-cell activation and HIV infectivity.

BACKGROUND: Chronic kidney disease (CKD) is a frequent, under-recognized condition and a risk factor for renal failure and cardiovascular disease. Increasing evidence connects non-alcoholic fatty liver disease (NAFLD) to CKD. We conducted a meta-analysis to determine whether the presence and severity of NAFLD are associated with the presence and severity of CKD. METHODS AND FINDINGS: English and non-English articles from international online databases from 1980 through January 31, 2014 were searched. Observational studies assessing NAFLD by histology, imaging, or biochemistry and defining CKD as either estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 or proteinuria were included. Two reviewers extracted studies independently and in duplicate. Individual participant data (IPD) were solicited from all selected studies. Studies providing IPD were combined with studies providing only aggregate data with the two-stage method. Main outcomes were pooled using random-effects models. Sensitivity and subgroup analyses were used to explore sources of heterogeneity and the effect of potential confounders. The influences of age, whole-body/abdominal obesity, homeostasis model of insulin resistance (HOMA-IR), and duration of follow-up on effect estimates were assessed by meta-regression. Thirty-three studies (63,902 participants, 16 population-based and 17 hospital-based, 20 cross-sectional, and 13 longitudinal) were included. For 20 studies (61% of included studies, 11 cross-sectional and nine longitudinal, 29,282 participants), we obtained IPD. NAFLD was associated with an increased risk of prevalent (odds ratio [OR] 2.12, 95% CI 1.69-2.66) and incident (hazard ratio [HR] 1.79, 95% CI 1.65-1.95) CKD. Non-alcoholic steatohepatitis (NASH) was associated with a higher prevalence (OR 2.53, 95% CI 1.58-4.05) and incidence (HR 2.12, 95% CI 1.42-3.17) of CKD than simple steatosis. Advanced fibrosis was associated with a higher prevalence (OR 5.20, 95% CI 3.14-8.61) and incidence (HR 3.29, 95% CI 2.30-4.71) of CKD than non-advanced fibrosis. In all analyses, the magnitude and direction of effects remained unaffected by diabetes status, after adjustment for other risk factors, and in other subgroup and meta-regression analyses. In cross-sectional and longitudinal studies, the severity of NAFLD was positively associated with CKD stages. Limitations of analysis are the relatively small size of studies utilizing liver histology and the suboptimal sensitivity of ultrasound and biochemistry for NAFLD detection in population-based studies. CONCLUSION: The presence and severity of NAFLD are associated with an increased risk and severity of CKD. Please see later in the article for the Editors' Summary.

BACKGROUND: Few articles address the issue of LC in patients with cirrhosis. Existing articles are retrospective and with small sample sizes, which makes it difficult to draw conclusions about indications and complications with LC in this setting. STUDY DESIGN: An extensive search of the Medline, Embase, and Cochrane databases using the terms "laparoscopic cholecystectomy" and "cirrhosis" or "cirrhotic" was conducted. The data from each study were extracted, combined with those of similar studies, and analyzed. RESULTS: Twenty-five publications (400 patients with cirrhosis undergoing LC) from 1993 to 2001 were identified. Four articles compared LC with open cholecystectomy in patients with cirrhosis, and six compared patients with cirrhosis to patients without cirrhosis. Patients were primarily in Child-Pugh class A or B, with only six patients in Child-Pugh class C. Compared with patients without cirrhosis, patients with cirrhosis had higher conversion rates (7.06% versus 3.64%, p = 0.024), operative times (98.2 minutes versus 70 minutes, p = 0.005), bleeding complications (26.4% versus 3.1%, p < 0.001), and overall morbidity (20.86% versus 7.99%, p < 0.001). Acute cholecystitis was evident in 47% of patients with cirrhosis versus 14.7% of patients without cirrhosis (p < 0.001). When LC was compared with open cholecystectomy in patients with cirrhosis, LC was associated with less operative blood loss (113 mL versus 425.2 mL, p = 0.015), operative time (123.3 minutes versus 150.2 minutes, p < 0.042), and length of hospital stay (6 days versus 12.2 days, p < 0.001). CONCLUSIONS: Patients with cirrhosis undergo cholecystectomies for more emergent reasons and have higher morbidity. The laparoscopic approach offers advantages of less blood loss, shorter operative time, and shorter length of hospitalization in patients with cirrhosis. Prospective studies will establish which factors affect outcomes and determine the appropriateness of LC in Child's-Pugh class C cirrhosis.

Percutaneous needle biopsies are frequently used to evaluate focal lesions of the liver. Needle-tract implantation of hepatocellular cancer has been described in case reports, but the true risk for this problem has not been clearly defined. We retrospectively reviewed 91 cases of hepatocellular cancer during a 4-year period from 1994 to 1997. Data on diagnostic studies, therapy, and outcome were noted. Of 91 patients with hepatocellular cancer, 59 patients underwent percutaneous needle biopsy as part of their diagnostic workup for a liver mass. Three patients (5.1%) were identified with needle-tract implantation of tumor. Two patients required en bloc chest wall resections for implantation of hepatocellular cancer in the soft tissues and rib area. The third patient, who also received percutaneous ethanol injection of his tumor, required a thoracotomy and lung resection for implanted hepatocellular cancer. Percutaneous needle biopsy of suspicious hepatic lesions should not be performed indiscriminately because there is a significant risk for needle-tract implantation. These biopsies should be reserved for those lesions in which no definitive surgical intervention is planned and pathological confirmation is necessary for a nonsurgical therapy.