Genotype-specific transcriptional regulation of PAI-1 gene by insulin, hypertriglyceridemic VLDL, and Lp(a) in transfected, cultured human endothelial cells

Plasminogen activator inhibitor-1 (PAI-1) has been shown to be an independent risk factor for coronary artery disease. Variations in plasma PAI-1 levels have been attributed to variations in the PAI-1 gene, and associations between PAI-1 levels and PAI-1 genotypes suggest that PAI-1 expression may be regulated in a genotype-specific manner by insulin, hypertriglyceridemic (HTG) very low density lipoprotein (VLDL), or lipoprotein(a) [Lp(a)]. Polymerase chain reaction-amplified 1106-bp fragments of the promoter of the 1/1 and 2/2 PAI-1 genotypes were sequenced and showed 5 regions of small nucleotide differences in the 1/1 versus 2/2 PAI-1 promoters that consistently occurred with high frequency. These fragments were ligated into the luciferase reporter gene, and 1/1 and 2/2 PAI-1 genotype human umbilical vein endothelial cell (HUVEC) cultures were transiently transfected with their respective p1PAI110/luc and p2PAI110/luc constructs and vice versa. Insulin induced an approximately 12- to 16-fold increase in luciferase activity in both the 1/1 and 2/2 PAI-1 genotype HUVEC cultures transfected with the p1PAI110/luc construct. HTG-VLDL and Lp(a) induced luciferase activity by approximately 14- to 16- and approximately 8- to 11-fold, respectively, in both the 1/1 and 2/2 PAI-1 genotype HUVEC cultures transfected with the p2PAI110/luc construct. The positive control interleukin-1 showed an approximately 7- to 12-fold response in the 1/1 and 2/2 PAI-1 genotype HUVEC cultures transfected with either of the constructs. These cross-over results demonstrate that regulation of either the 1/1 or 2/2 PAI-1 genotype by its respective inducer is due to the promoter itself and not to some factor(s) expressed differently in the 1/1 or 2/2 PAI-1 genotype HUVEC cultures.     

Protective factors in adolescent health behavior

The role of psychosocial protective factors in adolescent health-enhancing behaviors--healthy diet, regular exercise, adequate sleep, good dental hygiene, and seatbelt use--was investigated among 1,493 Hispanic, White, and Black high school students in a large, urban school district. Both proximal (health-related) and distal (conventionality-related) protective factors have significant positive relations with health-enhancing behavior and with the development of health-enhancing behavior. In addition, in cross-sectional analyses, protection was shown to moderate risk. Key proximal protective factors are value on health, perceived effects of health-compromising behavior, and parents who model health behavior. Key distal protective factors are positive orientation to school, friends who model conventional behavior, involvement in prosocial activities, and church attendance. The findings suggest the importance of individual differences on a dimension of conventionality-unconventionality. Strengthening both proximal and distal protective factors may help to promote healthful behaviors in adolescence.     

Giant bladder diverticulum in Ehlers-Danlos syndrome type I causing outflow obstruction

A series of 33 patients with juvenile dermatomyositis was reviewed in terms of their prognosis in relation to their drug therapy. This retrospective study was intended to help clarify the use of various therapies in this rare, heterogeneous disease from our hospital's experience in the last 24 years. The results confirmed that oral corticosteroids should remain the undisputed first line of treatment. For more refractory, chronic patients, the results suggest that azathioprine should be the favored drug of first choice (in addition to corticosteroids). There may be a role for cyclosporine as a "rescue" treatment, but this needs to be further defined.     

Structural characterization of the L-to-M transition of the bacteriorhodopsin photocycle

Structural intermediates occurring in the photocycle of wild-type bacteriorhodopsin are trapped by illuminating hydrated, glucose-embedded purple membrane at 170 K, 220 K, 230 K, and 240 K. We characterize light-induced changes in protein conformation by electron diffraction difference Fourier maps, and relate these to previous work on photocycle intermediates by infrared (FTIR) spectroscopy. Samples illuminated at 170 K are confirmed by FTIR spectroscopy to be in the L state; a difference Fourier projection map shows no structural change within the 0.35-nm resolution limit of our data. Difference maps obtained with samples illuminated at 220 K, 230 K, and 240 K, respectively, reveal a progressively larger structural response in helix F when the protein is still in the M state, as judged by the FTIR spectra. Consistent with previous structural studies, an adjustment in the position or in the degree of ordering of helix G accompanies this motion. The model of the photocycle emerging from this and previous studies is that bacteriorhodopsin experiences minimal change in protein structure until a proton is transferred from the Schiff base to Asp85. The M intermediate then undergoes a conformational evolution that opens a hydrated "half-channel," allowing the subsequent reprotonation of the Schiff base by Asp96.     

A case of split notochord syndrome: presence of dorsal enteric diverticulum adjacent to the dorsal enteric fistula

Like umblical enteric remnants (eg, umblical sinus and omphalomesenteric fistula), enteric remnants can be seen on the dorsal aspect of the body (dorsal enteric sinus, dorsal enteric fistula IDEF], dorsal enteric diverticulum) in conjunction with complete cleft of the vertebral column. Complete cleft of the vertebral column associated with gastrointestinal tract and central nervous system anomalies is known as "split notochord syndrome" (SNS). The authors present an unreported variant of SNS having dorsal enteric diverticulum adjacent to the DEF. The patient died 17 days after surgical repair.