Attention-deficit hyperactivity symptomatology after traumatic brain injury: a prospective study

OBJECTIVE: To study prospectively the course of attention-deficit hyperactivity (ADH) symptomatology in children and adolescents after traumatic brain injury (TBI). It was hypothesized that ADH symptomatology would be significantly related to severity of injury. METHOD: Subjects were children (n = 50) aged 6 to 14 years at the time they were hospitalized after TBI. The study used a prospective follow-up design. Assessments of preinjury psychiatric, behavioral, socioeconomic, family functioning, and family psychiatric history status were conducted. Severity of injury was assessed by standard clinical scales, and neuroimaging was analyzed. RESULTS: The main finding of this study was that change in ADH symptomatology in the first 2 years after TBI in children and adolescents was significantly related to severity of injury. Overall ADH symptomatology during the study was significantly related to a measure of family dysfunction when family psychiatric history, socioeconomic status, and severity of injury were controlled. CONCLUSION: The presence of a positive "dose-response" relationship between severity of injury and change in ADH symptoms, present from the 3-month assessment, was consistent with an effect directly related to brain damage.     

Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum

A vestigial, nonphotosynthetic plastid has been identified recently in protozoan parasites of the phylum Apicomplexa. The apicomplexan plastid, or "apicoplast," is indispensable, but the complete sequence of both the Plasmodium falciparum and Toxoplasma gondii apicoplast genomes has offered no clue as to what essential metabolic function(s) this organelle might perform in parasites. To investigate possible functions of the apicoplast, we sought to identify nuclear-encoded genes whose products are targeted to the apicoplast in Plasmodium and Toxoplasma. We describe here nuclear genes encoding ribosomal proteins S9 and L28 and the fatty acid biosynthetic enzymes acyl carrier protein (ACP), beta-ketoacyl-ACP synthase III (FabH), and beta-hydroxyacyl-ACP dehydratase (FabZ). These genes show high similarity to plastid homologues, and immunolocalization of S9 and ACP verifies that the proteins accumulate in the plastid. All the putatively apicoplast-targeted proteins bear N-terminal presequences consistent with plastid targeting, and the ACP presequence is shown to be sufficient to target a recombinant green fluorescent protein reporter to the apicoplast in transgenic T. gondii. Localization of ACP, and very probably FabH and FabZ, in the apicoplast implicates fatty acid biosynthesis as a likely function of the apicoplast. Moreover, inhibition of P. falciparum growth by thiolactomycin, an inhibitor of FabH, indicates a vital role for apicoplast fatty acid biosynthesis. Because the fatty acid biosynthesis genes identified here are of a plastid/bacterial type, and distinct from those of the equivalent pathway in animals, fatty acid biosynthesis is potentially an excellent target for therapeutics directed against malaria, toxoplasmosis, and other apicomplexan-mediated diseases.     

IkappaBalpha degradation is not a requirement for the X-ray-induced activation of nuclear factor kappaB in normal rat astrocytes and human brain tumour cells

The combined effect of lane line width and line-pavement contrast upon lanekeeping was studied through simulation. Some 124 subjects, ages 17-79 (x = 56.30), 52% male, each performed 42 trials over road segments representing three levels of width crossed with 14 line-pavement contrast ratios. Lanekeeping performance was recorded in terms of heading error, position error, lane excursions and road excursions. Subjects were stratified into two levels of ability on a combined measure of visual, attentional and psychomotor variables known to decline with age. Contrast and width had a negligible effect upon performance except at very low contrast ratios, ca 1.02 at high pavement luminance levels (e.g. concrete) and 1.04 for very low luminance levels (e.g. asphalt). These ratios are similar to those encountered at night on wet roads. Mean overall performance error at the low contrast ratios increased by a factor of 1.6, 1.8 and 2.2 for 8, 6 and 4" widths, respectively. Lower ability subjects exhibited greater error at almost all contrast ratios, with no consistent relationship between degree of decrement and either width or contrast. The results suggest that lane line width and contrast have a negligible effect upon lanekeeping performance except at extremely low levels of contrast, where both have large effects. Further research in the roadway environment is needed to determine the relationships of line width and contrast ratio to lanekeeping on normal and degraded surface conditions.     

Relationship between schistosomiasis and bladder cancer

Carcinoma of the urinary bladder is the most common malignancy in the Middle East and parts of Africa where schistosomiasis is a widespread problem. Much evidence supports the association between schistosomiasis and bladder cancer: this includes the geographical correlation between the two conditions, the distinctive patterns of gender and age at diagnosis, the clinicopathological identity of schistosome-associated bladder cancer, and extensive evidence in experimentally infected animals. Multiple factors have been suggested as causative agents in schistosome-associated bladder carcinogenesis. Of these, N-nitroso compounds appear to be of particular importance since they were found at high levels in the urine of patients with schistosomiasis-associated bladder cancer. Various strains of bacteria that can mediate nitrosation reactions leading to the formation of N-nitrosamines have been identified in the urine of subjects with schistosomiasis at higher intensities of infection than in normal subjects. In experimental schistosomiasis, the activities of carcinogen-metabolizing enzymes are increased soon after infection but are reduced again during the later chronic stages of the disease. Not only could this prolong the period of exposure to activated N-nitrosamines, but also inflammatory cells, stimulated as a result of the infection, may induce the endogenous synthesis of N-nitrosamines as well as generating oxygen radicals. Higher than normal levels of host cell DNA damage are therefore anticipated, and they have indeed been observed in the case of alkylation damage, together with an inefficiency in the capacity of relevant enzymes to repair this damaged DNA. In experimental schistosomiasis, it was also found that endogenous levels of host cell DNA damage were related to the intensity of infection. All of these factors could contribute to an increased risk of bladder cancer in patients with schistosomiasis, and in particular, the gene changes observed may have potential for use as biomarkers in the early detection of bladder cancer that may assist in alleviating the problem.     

Cytotoxicity and accumulation of ganciclovir triphosphate in bystander cells cocultured with herpes simplex virus type 1 thymidine kinase-expressing human glioblastoma cells

The ability of herpes simplex virus type 1 thymidine kinase (HSV-TK)-expressing cells incubated with ganciclovir (GCV) to induce cytotoxicity in neighboring HSV-TK-negative (bystander) cells has been well documented. Although it has been suggested that this bystander cell killing occurs through the transfer of phosphorylated GCV, there is little direct proof that bystander cells can accumulate GCV nucleotides. We have studied the ability of U251 human glioblastoma cells expressing HSV-TK (U251tk cells) to induce cytotoxicity in neighboring U251 bystander cells that lack the viral kinase (U251beta gal cells) and evaluated whether this bystander cell killing is mediated by GCV nucleotides. The cytotoxicity studies demonstrated that the ratio of HSV-TK-expressing cells:bystander cells was important in determining the sensitivity of both cell types to GCV. U251tk cells cocultured with an equal number of U251beta gal cells (a 50:50 ratio) exhibited a sensitivity to GCV similar to that observed in the absence of bystander cells, with >99.8% cell kill at 1 microm GCV. However, in cultures with 10% U251tk cells and 90% bystander cells (a 10:90 ratio), 1 microM GCV decreased the survival of U251tk cells by only 54%. Strong bystander cell killing was observed at both ratios. In a 50:50 coculture of U251tk and U251beta gal cells, the survival of bystander cells was decreased by >99.5% with 3 microM GCV, whereas 30 microM GCV was required to effect a similar decrease in bystander cell survival when 90% of the culture consisted of U251beta gal cells. To determine whether this bystander cell killing may be mediated by GCV nucleotides, we developed a technique to separate the two cell populations after coculture. A U251 bystander cell line was developed from the parental cell line by transfection with the cDNA coding for green fluorescent protein (U251gfp cells), which permitted the separation of U251gfp cells from nonfluorescing U251tk cells by flow cytometry with cell sorting. With this technique, bystander cells were isolated in a viable state with >97% purity within 1 h after harvest, permitting analysis of the nucleotide pools for the presence of phosphorylated GCV. The results demonstrated that significant levels of the triphosphate of GCV (GCVTP) accumulated in bystander cells within 4 h of coculture, and this accumulation was dependent upon the percentage of HSV-TK-expressing cells as well as the concentration of GCV and the length of incubation. The proportion of GCVTP in bystander cells was consistently 50-80% of that in HSV-TK-expressing cells in the 50:50 or 10:90 cocultures, suggesting a facile transfer of phosphorylated GCV. However, the actual amount of GCVTP was as much as 8-fold lower in both the U251tk and U251beta gal cells cocultured at a ratio of 10:90 compared to those cocultured at a ratio of 50:50, which is consistent with the lesser effect on cell survival. When U251tk and U251gfp cells were cultured with 1-beta-D-arabinofuranosylthymine (araT), the 5'-triphosphate of araT accumulated in the bystander cells, demonstrating that the transfer of phosphorylated compounds between these cell types is not restricted to GCV nucleotides. However, the proportion of araT-5'-triphosphate in bystander cells compared to that in HSV-TK-expressing cells was lower than that for GCVTP, and the amount was not sufficient to decrease survival in the bystander population.     

Effects of locus coeruleus stimulation on the responses of SI neurons of the rat to controlled natural and electrical stimulation of the skin

Recent epidemiologic data demonstrate a dramatic increase in the incidence of end-stage renal disease (ESRD) in patients with non-insulin-dependent diabetes mellitus (NIDDM), thus dispelling the mistaken belief that renal prognosis is benign in NIDDM. Currently, the leading cause of ESRD in the United States, Japan, and in most industrialized Europe is NIDDM, accounting for nearly 90% of all cases of diabetes. In addition to profound economic costs, patients with NIDDM and diabetic nephropathy have a dramatically increased morbidity and premature mortality. NIDDM-related nephropathy varies widely among racial and ethnic groups, genders and lifestyles; and gender may interact with race to affect the disease progression. While the course of insulin-dependent diabetes mellitus (IDDM) progresses through well-defined stages, the natural history of NIDDM is less well characterized. NIDDM patients with coronary heart disease have a higher urinary albumin excretion rate at the time of diagnosis and follow-up. This greater risk may also be associated with hypertension and hyperlipidemia, and genes involved in blood pressure are obvious candidate genes for diabetic nephropathy. Hyperglycemia appears to be an important factor in the development of proteinuria in NIDDM, but its role and the influence of diet are not yet clear. Tobacco smoking can also be deleterious to the diabetic patient, and is also associated with disease progression. Maintaining euglycemia, stopping smoking and controlling blood pressure may prevent or slow the progression of NIDDM-related nephropathy and reduce extrarenal injury. Treatment recommendations include early screening for hyperlipidemia, appropriate exercise and a healthy diet. Cornerstones of management should also include: (1) educating the medical community and more widely disseminating data supporting the value of early treatment of microalbuminuria; (2) developing a comprehensive, multidisciplinary team approach that involves physicians, nurses, diabetes educators and behavioral therapists; and (3) intensifying research in this field.     

Human intestinal M cells display the sialyl Lewis A antigen

The biochemical features that distinguish human M cells from other intestinal epithelial cell types are important for understanding microbial pathogenesis and for targeting vaccines to the mucosal immune system. We applied a large panel of carbohydrate-specific monoclonal antibodies and lectins to Peyer's patch and cecum biopsy specimens from three normal individuals and a patient with inflammatory bowel disease. The results show that human M-cell glycosylation patterns are distinct from those of other species examined and that human M cells preferentially display the sialyl Lewis A antigen. This carbohydrate epitope is also present in a small subpopulation of enterocytes in the follicle-associated epithelium and in goblet cell mucins.     

SH3P7 is a cytoskeleton adapter protein and is coupled to signal transduction from lymphocyte antigen receptors

Lymphocytes respond to antigen receptor engagement with tyrosine phosphorylation of many cellular proteins, some of which have been identified and functionally characterized. Here we describe SH3P7, a novel substrate protein for Src and Syk family kinases. SH3P7 migrates in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a 55-kDa protein that is preferentially expressed in brain, thymus, and spleen. It contains multiple amino acid sequence motifs, including two consensus tyrosine phosphorylation sites of the YXXP type and one SH3 domain. A region of sequence similarity, which we named SCAD, was found in SH3P7 and three actin-binding proteins. The SCAD region may represent a new type of protein-protein interaction domain that mediates binding to actin. Consistent with this possibility, SH3P7 colocalizes with actin filaments of the cytoskeleton. Altogether, our data implicate SH3P7 as an adapter protein which links antigen receptor signaling to components of the cytoskeleton.     

Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial

BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent placement (PTAS) may be more effective. We undertook a randomised prospective study to compare PTA with PTAS in patients with ostial atherosclerotic renal-artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA failed immediately or during 6 months' follow-up. Analysis was by intention to treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one patient in the PTAS group was excluded from the study. Primary success rate (<50% residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients) for PTAS (difference between groups 31% [95% CI 12-50]). Complications were similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and 75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12 patients underwent secondary stenting for primary or late failure of PTA within the follow-up period: success was similar to that of primary PTAS. Evaluation based on intention to treat showed no difference in clinical results at six months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However, the burden of reintervention after PTA outweighs the potential saving in stents, so primary PTAS is a better approach to use.