Genotype at a major locus with large effects on apolipoprotein B levels predicts familial combined hyperlipidemia

A sample enriched for familial combined hyperlipidemia (FCHL) was examined for evidence of an association between genotype at an apolipoprotein B (apoB) elevating locus defined by complex segregation analysis and FCHL. Complex segregation analysis detected a locus with a large effect on plasma apoB levels and was used to compute the most probable genotype of family members. None of the 35 normolipidemic adults carried a copy of the allele associated with elevated apoB levels, yet 58% of the 109 adults with FCHL carried 1 (29%) or 2 (28%) copies. Two of 28 (7%) normal children had 1 copy of this allele and none had 2 copies, while 88 of 182 (48%) children with FCHL had 1 (26%) or 2 (22%) copies. Further, 4l of 48 (85%) individuals classified as having hyperapobetalipoproteinemia did not carry a copy of this “elevated apoB” allele. Therefore, the presence of the allele associated with elevation of apoB level is highly predictive of FCHL and this association cannot be explained solely by the presence of elevated apoB levels in FCHL, suggesting that the locus controlling apoB levels may play an etiologic role in FCHL. © 1993 Wiley-Liss, Inc.     

Alcoholic-like drinking in simian social groups

We have developed two protocols for inducing sustained, high-dose, alcohol-reinforced, oral alcohol drinking among some members of Macaca nemestrina social groups. Both protocols initially co-present alcohol and the entire daily food supply in a 2-h daily drinking session, with a later return to continuous availability of food. One protocol presents unflavored aqueous alcohol to partially food-deprived subjects; the other compares the drinking of flavored alcohol solutions with the drinking of equally palatable isocaloric non-alcohol solutions when monkeys are not deprived of food. Daily high-dose drinking developed in both protocols, with biomedical changes similar to those of early human alcoholism. Daily drinking to blood alcohol concentrations above 100 mg/dl was sustained in some animals after return to baseline food conditions, and this may have been related to social rank within the groups. Alcohol reinforced drinking of the flavored solutions. Although food deprivation initially produced heavier drinking, drinking with the two protocols was equivalent after return to baseline feeding conditions. These procedures open new opportunities for examining combined social and genetic influences on alcoholic-like drinking.     

Routine postoperative chest x-ray following laparoscopic nephrectomy.

PURPOSE: To determine whether a routine postoperative chest x-ray is required following uneventful laparoscopic nephrectomy to rule out pneumothorax. METHODS: From June 1999 to May 2003, 308 laparoscopic nephrectomy cases were performed by 5 different surgeons. This consisted of 121 radical nephrectomies, 106 donor nephrectomies, 29 simple nephrectomies, 29 partial nephrectomies, and 23 nephroureterectomies. Of the 308 procedures, 186 postoperative chest x-ray s were obtained in the recovery room: 183 routinely and 3 for known intraoperative diaphragmatic injuries. Routine chest x-rays were not obtained in 122 cases due to the individual surgeon's preference. Of these 122 patients, 15 underwent chest x-ray performed while hospitalized secondary to pulmonary issues or fever. RESULTS: Of the 308 cases, 4 pneumothoraces were identified on chest x-ray. Three were identified in the patients who had intraoperative identification of diaphragmatic injury. The fourth pneumothorax was identified in a patient who did not have a routine postoperative chest x-ray but did have a chest x-ray obtained due to postoperative shoulder pain. The pneumothorax in this patient resolved spontaneously. No incidental findings existed of pneumothorax in any patient who underwent routine postoperative chest x-ray. CONCLUSION: In our series, a pneumothorax was identified either intraoperatively or based on postoperative clinical findings. None of the 183 routine postoperative chest x-rays changed patient management. Routine postoperative chest x-ray is not necessary in uncomplicated laparoscopic nephrectomy.     

Retention weighted recall improves discrimination of Alzheimer's disease.

Impaired recall for early items (primacy) and late items (recency) on word list recall tests are seen in Alzheimer's disease (AD). We compared conventional scoring on the Telephone Instrument for Cognitive Status (TICS) recall list with scorings based on retention-weighted recall (RWR: each item weighted by its serial position) in older adults participating in a community-based aging study. Subjects with mild AD (N=18) did not differ from those without dementia (N=231) with respect to recency (46% vs. 59%, p = 0.2), but had impaired primacy (2% vs. 39%, p < .001) on word recall on the TICS. RWR scoring improved the effect size (1.52 SD) compared to conventional scoring (1.08 SD). With a fixed sensitivity of 85%, specificity was lower using conventional scoring (56%) than RWR (76%) scoring. Our findings suggest that optimized RWR scoring of word list free recall can improve detection of mild AD compared to conventional scoring.     

Mycobacterium tuberculosis and Mycobacterium avium inhibit IFN- gamma -induced gene expression by TLR2-dependent and independent pathways.

Mycobacteria-infected macrophages are poor responders to interferon-gamma (IFN-gamma), resulting in decreased expression of IFN-gamma-induced genes. In the present study, we examined the inhibition of IFN-gamma-induced gene expression by Mycobacterium tuberculosis and four different Mycobacterium avium strains in mouse RAW264.7 macrophages. Gamma-irradiated M. tuberculosis inhibited mRNA expression of a panel of six different IFN- gamma-induced genes. All four of the M. avium strains completely inhibited IFN-gamma-induced expression of MHC class II Aalpha and Ebeta mRNA. However, the Mac101 strain, which is serovar 1, inhibited IFN-gamma induction of IFN regulatory factor-1 (IRF-1) and guanylate-binding protein-1 (GBP-1) mRNA to a greater extent than the other M. avium strains, which are serovar 2. In this study, we also show that mycobacteria inhibit gene expression by both toll-like receptor 2 (TLR2)-dependent and independent pathways. The inhibition of IFN-gamma-induced gene expression by M. avium was reduced but not completely blocked in macrophages from TLR2(/) mice. IFN-gamma-induced gene expression was also inhibited by mycobacteria in RAW264.7 cells expressing dominantnegative TLR2 or myeloid differentiation factor 88 (MyD88), further indicating the existence of a pathway independent of TLR2 and MyD88. These data suggest that mycobacteria inhibit IFN-gamma-induced gene expression by multiple pathways involving both TLR2 and non-TLR receptors.     

Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006.

BACKGROUND: Recently, epidemiological and clinical data have revealed important changes with regard to clinical adenovirus infection, including alterations in antigenic presentation, geographical distribution, and virulence of the virus. METHODS: In an effort to better understand the epidemiology of clinical adenovirus infection in the United States, we adopted a new molecular adenovirus typing technique to study clinical adenovirus isolates collected from 22 medical facilities over a 25-month period during 2004-2006. A hexon gene sequence typing method was used to characterize 2237 clinical adenovirus-positive specimens, comparing their sequences with those of the 51 currently recognized prototype human adenovirus strains. In a blinded comparison, this method performed well and was much faster than the classic serologic typing method. RESULTS: Among civilians, the most prevalent adenovirus types were types 3 (prevalence, 34.6%), 2 (24.3%), 1 (17.7%), and 5 (5.3%). Among military trainees, the most prevalent types were types 4 (prevalence, 92.8%), 3 (2.6%), and 21 (2.4%). CONCLUSIONS: For both populations, we observed a statistically significant increasing trend of adenovirus type 21 detection over time. Among adenovirus isolates recovered from specimens from civilians, 50% were associated with hospitalization, 19.6% with a chronic disease condition, 11% with a bone marrow or solid organ transplantation, 7.4% with intensive care unit stay, and 4.2% with a cancer diagnosis. Multivariable risk factor modeling for adenovirus disease severity found that age <7 years (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4-7.4), chronic disease (OR, 3.6; 95% CI, 2.6-5.1), recent transplantation (OR, 2.7; 95% CI, 1.3-5.2), and adenovirus type 5 (OR, 2.7; 95% CI, 1.5-4.7) or type 21 infection (OR, 7.6; 95% CI, 2.6-22.3) increased the risk of severe disease.