Pediatric head injuries and deaths from bicycling in the United States

OBJECTIVE: To estimate the potential benefit of increasing bicycle helmet use among children and adolescents in the United States. DESIGN: All bicycle-related deaths (Multiple Cause-of-Death Public Use Data Tapes, 1989 through 1992) and bicycle-related injuries treated in sampled emergency departments (National Electronic Injury Surveillance System, 1989 through 1993) were used to calculate traumatic brain injury-associated death and head injury rates per 1,000,000 US residents. Preventable injuries and deaths were estimated by calculating the population-attributable risk of head injury due to nonuse of bicycle helmets. PATIENTS: US residents aged 0 through 19 years who were injured or who died as a result of a bicycle crash. RESULTS: An average of 247 traumatic brain injury deaths and 140,000 head injuries among children and adolescents younger than 20 years were related to bicycle crashes each year in the United States. As many as 184 deaths and 116,000 head injuries might have been prevented annually if these riders had worn helmets. An additional 19,000 mouth and chin injuries were treated each year. The youngest age groups had the highest proportions of both head and mouth injuries. CONCLUSION: There continues to be a need to advocate for greater use of bicycle helmets, particularly among young children. Helmet design changes should be considered to prevent mouth injuries.     

Purification and characterization of a tumor lipid-mobilizing factor

Cancer patients with weight loss showed urinary excretion of a lipid-mobilizing factor (LMF), determined by the ability to stimulate lipolysis in isolated murine epididymal adipocytes. Such bioactivity was not detectable in the urine of cancer patients without weight loss or in normal subjects. The LMF was purified using a combination of ion exchange, exclusion, and hydrophobic interaction chromatographies to give a single component of apparent Mr 43,000, which showed homology in amino acid sequence with human plasma Zn-alpha2-glycoprotein. Both substances showed the same mobility on denaturing and nondenaturing gels and the same chymotrypsin digestion pattern, both stained heavily for carbohydrate, and they showed similar immunoreactivity. Polyclonal antisera to human plasma Zn-alpha2-glycoprotein was also capable of neutralization of the bioactivity of human LMF in vitro. Using competitive PCR to quantify expression of Zn-alpha2-glycoprotein, we found that only those tumors that were capable of producing a decrease in carcass lipid expressed mRNA for Zn-alpha2-glycoprotein. These results provide strong evidence to suggest that tumor production of Zn-alpha2-glycoprotein is responsible for the lipid catabolism seen in cancer patients.     

Multiple mechanisms may affect birth sex ratio in domestic pigs

No abstract. Copyright 1998 The Association for the Study of Animal Behaviour.     

The tumour-suppressor gene patched encodes a candidate receptor for Sonic hedgehog

The protein Sonic hedgehog (Shh) controls patterning and growth during vertebrate development. Here we demonstrate that it binds Patched (vPtc), which has been identified as a tumour-suppressor protein in basal cell carcinoma, with high affinity. We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened (vSmo), and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly. These findings, combined with available genetic evidence from Drosophila, support the hypothesis that Ptc is a receptor for Shh, and that vSmo could be a signalling component that is linked to Ptc.     

Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors

Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.     

Glutamate receptor-mediated calcium entry in neurons derived from P19 embryonal carcinoma cells

We have examined the control of calcium elevation by glutamate in neurons derived from the mouse P19 embryonal carcinoma cell line. Following transient exposure to retinoic acid, P19 cells differentiate into neurons that express both NMDA and non-NMDA glutamate receptor subtypes. Fluorescence videomicroscopy using the indicator fura-2 revealed concentration-dependent elevation in cytosolic calcium levels with exposure to NMDA or kainate. Replacement of extracellular sodium with N-methylglucamine significantly reduced the action of kainate. Exposure to high K+ medium also elicited an elevation of cytosolic calcium in P19 cells, which was partially inhibited by the calcium channel antagonist nimodipine. These experiments suggest that the elevation in calcium produced by kainate involves the activation of voltage-gated calcium channels as a consequence of membrane depolarization, in contrast to direct calcium entry through NMDA receptor channels. Whole-cell recordings revealed that P19 NMDA receptors were highly permeable to calcium (PCa/PNa = 5.6 +/- 0.2). In most cells, channels gated by kainate displayed low permeability to calcium; the median permeability ratio, PCa/PNa, was 0.053 (range 0.045 to 0.132). Activation of peak currents by NMDA, glycine, and kainate was half-maximal at 24 microM, 240 nM, and 81 microM, respectively. In addition, cadmium-sensitive currents through voltage-gated calcium channels were recorded in P19 cells bathed in barium/TEA chloride. Staining with antibodies directed against AMPA receptor subunits revealed wide-spread immunoreactivity for anti-GluR-B/C and anti-GluR-B/D. About half of the P19 cells were stained with antibodies selective for GluR-D but there was little or no immunoreactivity for the GluR-A subunit.     

Diagnosis of pancreatic carcinoma: role of FDG PET

OBJECTIVE: The purpose of this study was to investigate the role of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) in differentiating benign from malignant disease in patients with possible pancreatic malignancy. SUBJECTS AND METHODS: All patients with a possible diagnosis of pancreatic carcinoma based on CT or ERCP findings were eligible for inclusion in this prospective study. PET imaging of the abdomen was performed in 37 patients and was interpreted as positive if FDG activity in the pancreas exceeded background activity and as negative if activity was less than or equal to background activity. Semiquantitative analysis was performed by calculating a standardized uptake ratio. Studies were reviewed independently by two radiologists, and results were correlated with biopsy results and with CT and ERCP findings. Sensitivity and specificity of FDG PET for revealing pancreatic malignancy was determined. RESULTS: FDG activity in the pancreas was increased in 24 patients, and adenocarcinoma was diagnosed in 22 of these patients (92%). Two patients (8%) with increased activity had benign disease, including one patient with chronic pancreatitis who showed no evidence of tumor at laparotomy and one patient with a mucinous cystic tumor who showed no malignant features at laparotomy. FDG uptake was low or normal in 13 patients, 10 of whom (77%) had benign disease. FDG uptake was also low in three patients with adenocarcinoma, whose tumor size ranged from 2 to 4 cm in diameter. The mean standardized uptake ratio value for malignant disease was 5.1 (range, 1.0-10.1) and for benign disease was 1.9 (range, 0.0-5.8) (p < .001). The sensitivity of FDG PET for revealing malignant disease in the pancreas was 88% and the specificity was 83%. CONCLUSION: FDG PET is a sensitive and specific noninvasive technique for the diagnosis of pancreatic malignancy.     

Comparison of sire breed solutions for growth traits adjusted by mean expected progeny differences to a 1993 base

Records on growth traits were obtained from five Midwestern agricultural experiment stations as part of a beef cattle crossbreeding project (NC-196). Records on birth weight (BWT, n =3,490), weaning weight (WWT, n = 3,237), and yearling weight (YWT, n = 1,372) were analyzed within locations and pooled across locations to obtain estimates of breed of sire differences. Solutions for breed of sire differences were adjusted to the common base year of 1993. Then, factors to use with within-breed expected progeny differences (EPD) to obtain across-breed EPD were calculated. These factors were compared with factors obtained from similar analyses of records from the U. S. Meat Animal Research Center (MARC). Progeny of Brahman sires mated to Bos taurus cows were heaviest at birth and among the lightest at weaning. Simmental and Gelbvieh sires produced the heaviest progeny at weaning. Estimates of heritability pooled across locations were .34, .19, and .07 for BWT, WWT, and YWT, respectively. Regression coefficients of progeny performance on EPD of sire were 1.25+/-.09, .98+/-.13, and .62+/-.18 for BWT, WWT, and YWT, respectively. Rankings of breeds of sire generally did not change when adjusted for sire sampling. Rankings were generally similar to those previously reported for MARC data, except for Limousin and Charolais sires, which ranked lower for BWT and WWT at NC-196 locations than at MARC. Adjustment factors used to obtain across-breed EPD were largest for Brahman for BWT and for Gelbvieh for WWT. The data for YWT allow only comparison of Angus with Simmental and of Gelbvieh with Limousin.     

Functional role of hepatitis C virus chimeric glycoproteins in the infectivity of pseudotyped virus

The putative envelope glycoproteins of hepatitis C virus (HCV) likely play an important role in the initiation of viral infection. Available information suggests that the genomic regions encoding the putative envelope glycoproteins, when expressed as recombinant proteins in mammalian cells, largely accumulate in the endoplasmic reticulum. In this study, genomic regions which include the putative ectodomain of the E1 (amino acids 174 to 359) and E2 (amino acids 371 to 742) glycoproteins were appended to the transmembrane domain and cytoplasmic tail of vesicular stomatitis virus (VSV) G protein. This provided a membrane anchor signal and the VSV incorporation signal at the carboxy termini of the E1 and E2 glycoproteins. The chimeric gene constructs exhibited expression of the recombinant proteins on the cell surface in a transient expression assay. When infected with a temperature-sensitive VSV mutant (ts045) and grown at the nonpermissive temperature (40.5 degrees C), cells transiently expressing the E1 or E2 chimeric glycoprotein generated VSV/HCV pseudotyped virus. The resulting pseudotyped virus generated from E1 or E2 surprisingly exhibited the ability to infect mammalian cells and sera derived from chimpanzees immunized with the homologous HCV envelope glycoproteins neutralized pseudotyped virus infectivity. Results from this study suggested a potential functional role for both the E1 and E2 glycoproteins in the infectivity of VSV/HCV pseudotyped virus in mammalian cells. These observations further suggest the importance of using both viral glycoproteins in a candidate subunit vaccine and the potential for using a VSV/HCV pseudotyped virus to determine HCV neutralizing antibodies.