Transporters in cholelithiasis

Gallstones are a common and costly disease with a projected increase in prevalence due to the increasing ageing population. Numerous endogenous and environmental factors are aetiologically related to this multifactorial disease, and genetic studies continue to unravel the pathobiological mechanisms related to gallstone formation. In particular, variants of genes encoding hepatobiliary transporters have been implicated in gallstone disease and, given their ability to influence biliary lipid composition, have undergone considerable investigation. Here we summarize the role of enterohepatic transporters in cholelithogenesis with a particular focus on pertinent ATP-binding cassette transporters (ABCB4, ABCB11, ABCC7, and ABCG5/G8).     

Pathogenesis of human cholesterol cholelithiasis.

The pathogenesis of cholesterol cholelithiasis in humans has been studied by means of three techniques. The cholesterol-solubilizing capacity of bile may be determined by estimation of the relative composition of the three major lipid constituents of bile. Consistent reduction in the cholesterol-carrying capacity of gallbladder bile of persons with gallstones when compared with normal subjects has not been shown. Normal subjects frequently have supersaturated bile. Secretion rates of biliary lipids have been estimated by two methods; with the method that appears to be more physiologic no change in lipid secretion rates was found in gallstone patients. Bile acid pool size has been measured by isotope dilution techniques; it is reduced in patients with gallstones. It is not clear whether this reduction is important in the pathogenesis of cholesterol cholelithiasis, for the bile acid secretion rate is normal because of an increased rate of cycling of the pool through the enterohepatic circulation. The role of the gallbladder in the genesis of cholesterol cholelithiasis may be more important than has been realized.     

Infrequent transposition of Ac in lettuce,Lactuca sativa

The maize transposable element Activator (Ac) is being used to develop a transposon mutagenesis system in lettuce, Lactuca sativa. Two constructs containing the complete Ac from the waxy-m7 locus of maize were introduced into lettuce and monitored for activity using Southern analysis and PCR amplification of the excision site. No transposition of Ac was detected in over 32 transgenic R₁ plants, although these constructs were known to provide frequent transposition in other species. Also, no transposition was observed in later generations. In subsequent experiments, transposition was detected in lettuce calli using constructs that allowed selection for excision events. In these constructs, the neomycin phosphotransferase II gene was interrupted by either Ac or Ds. Excision was detected as the ability of callus to grow on kanamycin. Synthesis of the transposase from the cDNA of Ac expressed from the T-DNA 2 promoter resulted in more frequent excision of Ds than was observed with the wild-type Ac. No excision was observed with Ds in the absence of the transposase. The excision events were confirmed by amplification of the excision site by PCR followed by DNA sequencing. Excision and reintegration were also confirmed by Southern analysis. Ac/Ds is therefore capable of transposition in at least calli of lettuce.     

ABO bloodgroups in cholelithiasis.

In order to search for a probable association between ABO bloodgroups and cholelithiasis, a study was undertaken on 321 patients and 688 controls. It appears that group A subjects are having somewhat higher risk to be affected with the disease than those of groups B or O.     

Dyschromatosis universalis hereditaria: Infrequent genodermatoses in India

Dyschromatosis universalis hereditaria (DUH) is a rare genodermatosis reported initially and mainly in Japan. However, subsequent cases have been reported from other countries. We report a case of DUH in a south Indian woman with a positive family history with cosmetic disfigurement and severe psychological impairment.     

Infrequent involvement of c-fos in avian leukosis virus-induced nephroblastoma.

To determine whether c-fos is involved in avian leukosis virus-induced nephroblastoma, 28 tumors from chickens were analyzed for novel fos fragments. DNA from 1 of 16 clonal outgrowths (in chicken 6561) contained novel fos-related EcoRI and KpnI fragments which hybridized to both v-fos and viral probes. Oncogenicity tests using filtered 6561 tumor cell homogenates did not reveal a tumor-inducing transduction of c-fos. We conclude that c-fos is only an occasional target for proviral insertions or new transductions in avian leukosis virus-induced nephroblastoma. The results also identify a polymorphism in c-fos in K28 chickens and demonstrate that unintegrated viral DNA is not a general characteristic of avian leukosis virus-induced nephroblastoma.     

Ecosystem Management in the Context of Large, Infrequent Disturbances

Large, infrequent disturbances (LIDs) can have significant impacts yet seldom are included in management plans. Although this neglect may stem from relative unfamiliarity with a kind of event that rarely occurs in the experience or jurisdiction of individual managers, it may also reflect the assumption that LIDs are so large and powerful as to be beyond the ability of managers to affect. However, some LIDs can be affected by management, and for many of those that cannot be affected, the resilience or recovery of the system disrupted by the disturbance can be influenced to meet management goals. Such results can be achieved through advanced planning that allows for LIDs, whether caused by natural events, human activities, or a combination of the two. Management plans for LIDs may adopt a variety of goals, depending on the nature of the system and the nature of the anticipated disturbance regime. Managers can choose to influence (a) the system prior to the disturbance, (b) the disturbance itself, (c) the system after the disturbance, or (d) the recovery process. Prior to the disturbance, the system can be managed in ways that alter its vulnerability or change how it will respond to a disturbance. The disturbance can be managed through no action, preventive measures, or manipulations that can affect the intensity or frequency of the disturbance. Recovery efforts can focus on either managing the state of the system immediately after the disturbance or managing the ongoing process of recovery. This review of the management implications of LIDs suggests that management actions should be tailored to particular disturbance characteristics and management goals. Management actions should foster survival of residuals and spatial heterogeneity that promote the desired recovery pattern and process. Most importantly, however, management plans need to recognize LIDs and include the potential for such disturbances to occur. Received 14 July 1998; accepted 16 September 1998