Showing papers by "Loma Linda University published in 1998"
TL;DR: Results from discriminant function analyses indicate that both push and pull factors were important differentiators when deciding to retire and after retirement, the push (or negative) factors became more salient differentiator.
398 citations
TL;DR: Intramuscular ketamine may be administered safely by emergency physicians to facilitate pediatric procedures in accordance with a defined protocol and with appropriate monitoring, and is highly effective, has a wide margin of safety, does not require intravenous access, and uniquely preserves protective airway reflexes.
392 citations
Journal Article•
TL;DR: It is indicated that classical and cellularCMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS, which is virtually identical histologically to congenital fibrosarcoma.
Abstract: Congenital mesoblastic nephroma (CMN) is an infantile spindle cell tumor of the kidney that is subdivided into "classical" and "cellular" forms based on the degree of cellularity and mitotic activity. The histogenesis of CMN remains obscure, but relationships to other pediatric renal neoplasms have been proposed. However, cellular CMN is virtually identical histologically to congenital fibrosarcoma (CFS), a malignant tumor of fibroblasts in children of the same age group. Moreover, cytogenetic studies have reported common trisomies in CFS and cellular CMN, particularly of chromosome 11. We show here that t(12;15)(p13;q25)-associated ETV6-NTRK3 gene fusions described in CFS are also present in cellular CMN. ETV6-NTRK3 chimeric transcripts were detected in 8 of 9 cellular CMNs and 2 of 2 mixed CMNs. In contrast, all of the four classical CMNs tested were negative, as were cases of Wilms' tumor and clear cell sarcoma of the kidney. Moreover, we found trisomy 11 only in cellular or mixed CMNs with the ETV6-NTRK3 gene fusion. Our studies indicate that classical and cellular CMN have different genetic features and support the concept that cellular CMN is histogenetically related to CFS. They also provide insight into potential mechanisms involved in the transformation of the classical into the cellular form of CMN.
365 citations
TL;DR: Frequent consumption of soy milk was associated with 70 per cent reduction of the risk of prostate cancer and the association was upheld when extensive adjustments were performed.
Abstract: Objectives: Recent experimental studies have suggested that isoflavones (such as genistein and daidzein) found in some soy products may reduce the risk of cancer The purpose of this study was to evaluate the relationship between soy milk, a beverage containing isoflavones, and prostate cancer incidence Methods: A prospective study with 225 incident cases of prostate cancer in 12,395 California Seventh-Day Adventist men who in 1976 stated how often they drank soy milk Results: Frequent consumption (more than once a day) of soy milk was associated with 70 per cent reduction of the risk of prostate cancer (relative risk=03, 95 percent confidence interval 01-10, p-value for linear trend=003) The association was upheld when extensive adjustments were performed Conclusions: Our study suggests that men with high consumption of soy milk are at reduced risk of prostate cancer Possible associations between soy bean products, isoflavones and prostate cancer risk should be further investigated
364 citations
TL;DR: The ability of transgenic food plants to generate protective immunity in mice against a bacterial enterotoxin is demonstrated and demonstrated to be effective against cholera holotoxin.
Abstract: Transgenic potatoes were engineered to synthesize a cholera toxin B subunit (CTB) pentamer with affinity for GM1-ganglioside. Both serum and intestinal CTB-specific antibodies were induced in orally immunized mice. Mucosal antibody titers declined gradually after the last immunization but were restored following an oral booster of transgenic potato. The cytopathic effect of cholera holotoxin (CT) on Vero cells was neutralized by serum from mice immunized with transgenic potato tissues. Following intraileal injection with CT, the plant-immunized mice showed up to a 60% reduction in diarrheal fluid accumulation in the small intestine. Protection against CT was based on inhibition of enterotoxin binding to the cell-surface receptor GM1-ganglioside. These results demonstrate the ability of transgenic food plants to generate protective immunity in mice against a bacterial enterotoxin.
358 citations
TL;DR: A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables.
Abstract: In a 6-year prospective study, the authors examined the relation between diet and incident colon cancer among 32,051 non-Hispanic white cohort members of the Adventist Health Study (California, 1976-1982) who, at baseline, had no documented or reported history of cancer. The risk of colon cancer was determined from proportional hazards regression with adjustment for age and other covariates. The authors found a positive association with total meat intake (risk ratio (RR) for > or =1 time/week vs. no meat intake = 1.85, 95% confidence interval (CI) 1.19-2.87; p for trend = 0.01) and, among subjects who favored specific types of meat, positive associations with red meat intake (RR for > or =1 time/week vs. no red meat intake = 1.90, 95% CI 1.16-3.11; p for trend = 0.02) and white meat intake (RR for > or =1 time/week vs. no white meat intake = 3.29, 95% CI 1.60-6.75; p for trend = 0.006). An inverse association with legume intake (RR for >2 times/week vs. 25.6 kg/m2) vs. tertile I (<22.5 kg/m2) = 2.63, 95% CI 1.12-6.13; p for trend = 0.05). A complex relation was identified whereby subjects exhibiting a high red meat intake, a low legume intake, and a high body mass experienced a more than threefold elevation in risk relative to all other patterns based on these variables. This pattern of putative risk factors would likely contribute to increases in both insulin resistance (high body mass, high red meat intake) and glycemic load (low legume intake), a synergism that, if causal, implicates hyperinsulinemic exposure in colon carcinogenesis. The overall findings from this cohort identify both red meat intake and white meat intake as important dietary risk factors for colon cancer and raise the possibility that the risk due to red meat intake reflects a more complex etiology.
314 citations
TL;DR: Transgenic potato plants that synthesize human insulin, a major insulin-dependent diabetes mellitus autoantigen, are generated and food plants are feasible production and delivery systems for immunotolerance against this T cell–mediated autoimmune disease.
Abstract: Oral administration of disease-specific autoantigens can prevent or delay the onset of autoimmune disease symptoms. We have generated transgenic potato plants that synthesize human insulin, a major insulin-dependent diabetes mellitus autoantigen, at levels up to 0.05% of total soluble protein. To direct delivery of plant-synthesized insulin to the gut-associated lymphoid tissues, insulin was linked to the C-terminus of the cholera toxin B subunit (CTB). Transgenic potato tubers produced 0.1% of total soluble protein as the pentameric CTB-insulin fusion, which retained GM1-ganglioside binding affinity and native antigenicity of both CTB and insulin. Nonobese diabetic mice fed transformed potato tuber tissues containing microgram amounts of the CTB-insulin fusion protein showed a substantial reduction in pancreatic islet inflammation (insulitis), and a delay in the progression of clinical diabetes. Feeding transgenic potato tissues producing insulin or CTB protein alone did not provide a significant reduction in insulitis or diabetic symptoms. The experimental results indicate that food plants are feasible production and delivery systems for immunotolerization against this T cell-mediated autoimmune disease.
310 citations
TL;DR: Efficient expression of the cloned reporter genes by the macrophages and subsequent antigen presentation were achieved after the delivery of eukaryotic expression vectors by the attenuated suicide L. monocytogenes strain.
Abstract: Eukaryotic expression vectors can be delivered to macrophages using attenuated self-destructing Listeria monocytogenes. L. monocytogenes cells are preferentially lysed in the host cell macrophage cytosol by the production of a PactA-dependent Listeria-specific phage lysin. Efficient expression of the cloned reporter genes by the macrophages and subsequent antigen presentation were achieved after the delivery of eukaryotic expression vectors by the attenuated suicide L. monocytogenes strain. After delivery by L. monocytogenes plasmid DNAs were found to integrate into the macrophage cell's genome at a frequency of about 10(-7).
291 citations
TL;DR: Greater NOS activity in core regions could explain in part the increased vulnerability of that region to ischemia and could theoretically contribute to the progression of the infarct over time.
Abstract: Background and Purpose—The present studies examined the hypothesis that the distribution of cerebral injury after a focal ischemic insult is associated with the regional distribution of nitric oxide synthase (NOS) activity. Methods—Based on previous studies that certain anatomically well-defined areas are prone to become either core or penumbra after middle cerebral artery occlusion (MCAO), we measured NOS activity in these areas from the right and left hemispheres in a spontaneously hypertensive rat filament model. Four groups were studied: (1) controls (immediate decapitation); (2) 1.5 hours of MCAO with no reperfusion (R0); (3) 1.5 hours of MCAO with 0.5 hour of reperfusion (R0.5); and (4) 1.5 hours of MCAO with 24 hours of reperfusion (R24). Three groups of corresponding isoflurane sham controls were also included: 1.5 (S1.5) or 2 (S2.0) hours of anesthesia and 1.5 hours of anesthesia+24 hours of observation (S24). Results—Control core NOS activity for combined right and left hemispheres was 129% grea...
251 citations
TL;DR: Increased risks of incident lung cancer were associated with elevated long-term ambient concentrations of PM10 and SO2 in both genders and with O3 in males, and the gender differences for the O3 and PM10 results appeared to be partially due to gender differences in exposure.
Abstract: The purpose of this study was to evaluate the relationship of long-term concentrations of ambient air pollutants and risk of incident lung cancer in nonsmoking California adults. A cohort study of 6,338 nonsmoking, non-Hispanic, white Californian adults, ages 27-95, was followed from 1977 to 1992 for newly diagnosed cancers. Monthly ambient air pollution data were interpolated to zip code centroids according to home and work location histories, cumulated, and then averaged over time. The increased relative risk (RR) of incident lung cancer in males associated with an interquartile range (IQR) increase in 100 ppb ozone (O3) was 3.56 [95% confidence interval (CI), 1.35-9.42]. Incident lung cancer in males was also positively associated with IQR increases for mean concentrations of particulate matter <10 microm (PM10; RR = 5.21; CI, 1.94-13.99) and SO2 (RR = 2.66; CI, 1.62-4.39). For females, incident lung cancer was positively associated with IQR increases for SO2 (RR = 2.14; CI, 1.36-3.37) and IQR increases for PM10 exceedance frequencies of 50 microg/m3 (RR = 1.21; CI, 0.55-2.66) and 60 microg/m3 (RR = 1.25; CI, 0.57-2.71). Increased risks of incident lung cancer were associated with elevated long-term ambient concentrations of PM10 and SO2 in both genders and with O3 in males. The gender differences for the O3 and PM10 results appeared to be partially due to gender differences in exposure.
225 citations
TL;DR: Vegetarians have a lower risk of dying from ischaemic heart disease than non-vegetarians, and there were no significant differences between vegetarians and non- vegetarians in mortality from the other causes of death examined.
Abstract: Objective To compare the mortality rates of vegetarians and non-vegetarians. Design Collaborative analysis using original data from five prospective studies. Death rate ratios for vegetarians compared to non-vegetarians were calculated for ischaemic heart disease, cerebrovascular disease, cancers of the stomach, large bowel, lung, breast and prostate, and for all causes of death. All results were adjusted for age, sex and smoking. A random effects model was used to calculate pooled estimates of effect for all studies combined. Setting USA, UK and Germany. Subjects 76,172 men and women aged 16-89 years at recruitment. Vegetarians were those who did not eat any meat or fish (n = 27,808). Non-vegetarians were from a similar background to the vegetarians within each study. Results After a mean of 10.6 years of follow-up there were 8330 deaths before the age of 90 years, including 2264 deaths from ischaemic heart disease. In comparison with non-vegetarians, vegetarians had a 24% reduction in mortality from ischaemic heart disease (death rate ratio 0.76, 95% CI 0.62-0.94). The reduction in mortality among vegetarians varied significantly with age at death: rate ratios for vegetarians compared to non-vegetarians were 0.55 (95% CI 0.35-0.85), 0.69 (95% CI 0.53-0.90) and 0.92 (95% CI 0.73-1.16) for deaths from ischaemic heart disease at ages Conclusion Vegetarians have a lower risk of dying from ischaemic heart disease than non-vegetarians.
TL;DR: The physical basis for MRS will be presented leading to an understanding of its potential applications and limitations within the clinical research milieu, and its potential as a means of assessing the short-term effects of any CNS targeted pharmacologic interventions.
Abstract: Proton magnetic resonance spectroscopy (MRS) is an emerging technology that allows for the quantitative noninvasive assessment of regional brain biochemistry. The capacity to carry out MRS studies requires existing magnetic resonance imaging (MRI) technology platforms and the purchase of commercially available software modifications. In this review, the physical basis for MRS will be presented leading to an understanding of its potential applications and limitations within the clinical research milieu. Thus far, within pediatric neurology, proton MRS studies have been used to assist in the prediction of outcome in a variety of settings of acquired brain injuries (perinatal asphyxia, near drowning). In addition, proton MRS has been used to document disturbances in oxidative metabolism in neurometabolic disorders, assisting in defining phenotype and the response to therapeutic interventions. In epilepsy, spectroscopic studies have been useful in localizing the epileptogenic zone in intractable focal epilepsies. Future applications of proton MRS will also be highlighted. These include its use as a means of observing the transport and metabolism of various compounds in the brain, its concurrent application with other nuclear magnetic resonance techniques such as MRI and functional MRI, and finally its potential as a means of assessing the short-term effects of any CNS targeted pharmacologic interventions.
TL;DR: The associations between lung function measures and estimated 20-yr ambient concentrations of respirable particles, suspended sulfates, sulfur dioxide, ozone, and indoor particles were studied in a sample of 1,391 nonsmokers followed since 1977.
Abstract: The associations between lung function measures (spirometry and peak expiratory flow lability) and estimated 20-yr ambient concentrations of respirable particles, suspended sulfates, sulfur dioxide, ozone, and indoor particles were studied in a sample of 1,391 nonsmokers followed since 1977. Differences in air pollutants across the population were associated with decrements of lung function. An increase of 54 d/yr when particles < 10 μ m in diameter (PM10) exceeded 100 μ g/m3 was associated with a 7.2% decrement in FEV1, as percent of predicted, in males whose parents had asthma, bronchitis, emphysema, or hay fever and with increased peak expiratory flow lability of 0.8% for all females and 0.6% for all males. An increase in mean SO4 concentration of 1.6 μ g/m3 was associated with a 1.5% decrement in FEV1, as percent of predicted, in all males. An increase of 23 ppb of ozone as an 8-h average was associated with a 6.3% decrement in FEV1, as percent of predicted, in males whose parents had asthma, bronchit...
TL;DR: I.v. ketamine can be administered safely by EPs to facilitate pediatric procedures when used in a defined protocol and the sedation characteristics of the i.m. and i.V. routes appear comparable.
Abstract: OBJECTIVES To determine the safety of i.v. ketamine when administered by emergency physicians (EPs) for pediatric procedures, and to contrast the sedation characteristics of the i.v. and i.m. routes. METHODS The study was a retrospective consecutive case series of children aged < or =15 years given i.v. ketamine in the EDs of a university medical center and an affiliated county hospital over a 9-year period. A protocol for ketamine was used by treating physicians. Records were reviewed for adverse effects, indication, dosing, adjunctive drugs, inadequate sedation, and time to release. Results were contrasted with previously reported data for the i.m. route. RESULTS During the study period i.v. ketamine was administered 156 times, primarily for laceration repair and fracture reduction. Transient apnea and respiratory depression occurred in one patient each; both were quickly identified and were without sequelae. Laryngospasm or aspiration was not noted in any children. There were 6 children with emesis and 2 with mild agitation during recovery. The median time from initial dose to ED release was 103 minutes (25th to 75th percentiles 76 to 146 minutes). The i.v. and i.m. routes were comparable in terms of adverse effects, inadequate sedation, and time to release. CONCLUSION I.v. ketamine can be administered safely by EPs to facilitate pediatric procedures when used in a defined protocol. The sedation characteristics of the i.v. and i.m. routes appear comparable.
TL;DR: LimitedRevascularization of the beating heart provides long-term results comparable to full revascularization with cardiopulmonary bypass, but at the cost of a threefold increase in reinterventions.
TL;DR: The age at diagnosis of WT was determined for the largest series of patients with WT-associated syndromes reported to date, providing a basis for determining how long patients with these conditions are at risk for WT development.
Abstract: Nephrogenic rests (NR) are abnormally persistent clusters of embryonal cells, representing microscopic malformations (dysplasias) of the developing kidney. Though NR are best known as precursors of Wilms tumor (WT), many alternative fates are observed, and most rests are destined for eventual atresia. Biological and clinical distinctions between the two major NR categories, perilobar and intralobar rests (PLNR and ILNR) are emphasized. PLNR occur in fetal overgrowth and with certain overgrowth syndromes. ILNR are frequently associated with deletions or mutations of WT1. Data are presented concerning the prevalence of NR in general pediatric autopsy populations, and in selected syndromes. The age at diagnosis of WT was determined for the largest series of patients with WT-associated syndromes reported to date. These data provide a basis for determining how long patients with these conditions are at risk for WT development.
TL;DR: A cross-sectional study measuring serum levels of proinsulin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D3, 1,25-dihydroxyv vitamin D3 and several biochemical bone markers found positive correlations with bone formation markers and increased bone turnover, suggesting that diabetics without residual insulin secretion and high insulin requirement may contribute to bone loss.
Abstract: Osteopenia has been ascribed to diabetics without residual insulin secretion and high insulin requirement. However, it is not known if this is partially due to disturbances in the IGF system, which is a key regulator of bone cell function. To address this question, we performed a cross-sectional study measuring serum levels of IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, IGFBP-4 and IGFBP-5 by specific immunoassays in 52 adults with Type 1 (n=27) and Type 2 (n=25) diabetes mellitus and 100 age- and sex-matched healthy blood donors. In the diabetic patients, we further determined serum levels of proinsulin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and several biochemical bone markers, including osteocalcin (OSC), bone alkaline phosphatase (B-ALP), carboxy-terminal propeptide of type I procollagen (PICP), and type I collagen cross-linked carboxy-terminal telopeptide (ICTP). Urinary albumin excretion was ascertained as a marker of diabetic nephropathy. Bone mineral density (BMD) of hip and lumbar spine was determined by dual-energy X-ray absorptiometry. Data are presented as means+/-s.e.m. Differences between the experimental groups were determined by performing a one-way analysis of variance (ANOVA), followed by Newman-Keuls test. Correlations between variables were assessed using univariate linear regression analysis and partial correlation analysis. Type 1 diabetics showed significantly lower IGF-I (119+/-8 ng/ml) and IGFBP-3 (2590+/-104 ng/ml) but higher IGFBP-1 levels (38+/-10 ng/ml) compared with Type 2 patients (170+/-13, 2910+/-118, 11+/-3 respectively; P<0.05) or healthy controls (169+/-5, 4620+/-192, 3.5+/-0.4 respectively; P<0.01). IGFBP-5 levels were markedly lower in both diabetic groups (Type 1, 228+/-9; Type 2, 242+/-11 ng/ml) than in controls (460+/-7 ng/ml,P<0. 01), whereas IGFBP-4 levels were similar in diabetics and controls. IGF-I correlated positively with IGFBP-3 and IGFBP-5 and negatively with IGFBP-1 and IGFBP-4 in all subjects. Type 1 patients showed a lower BMD of hip (83+/-2 %, Z-score) and lumbar spine (93+/-2 %) than Type 2 diabetics (93+/-5 %, 101+/-5 % respectively), reaching significance in the female subgroups (P<0.05). In Type 1 patients, BMD of hip correlated negatively with IGFBP-1 (r=-0.34, P<0.05) and IGFBP-4 (r=-0.3, P<0.05) but positively with IGFBP-5 (r=0.37, P<0. 05), which was independent of age, diabetes duration, height, weight and body mass index, as assessed by partial correlation analysis. Furthermore, biochemical markers indicating bone loss (ICTP) and increased bone turnover (PTH, OSC) correlated positively with IGFBP-1 and IGFBP-4 but negatively with IGF-I, IGFBP-3 and IGFBP-5, while the opposite was observed with bone formation markers (PICP, B-ALP) and vitamin D3 metabolites. In 20 Type 2 patients in whom immunoreactive proinsulin could be detected, significant positive correlations were found between proinsulin and BMD of hip (r=0.63, P<0.005), IGF-I (r=0.59, P<0.01) as well as IGFBP-3 (r=0.49, P<0.05). Type 1 and Type 2 patients with macroalbuminuria showed a lower BMD of hip, lower IGFBP-5 but higher IGFBP-4 levels, suggesting that diabetic nephropathy may contribute to bone loss by a disturbed IGF system. In conclusion, the findings of this study support the hypothesis that the imbalance between individual IGF system components and the lack of endogenous proinsulin may contribute to the lower BMD in Type 1 diabetics.
TL;DR: The tissue reaction to MTA implantation was the most favorable observed at both sites; as in every specimen, it was free of inflammation (p < 0.01).
TL;DR: Findings suggest that the PFSDQ-M demonstrates initial reliability; good validity estimates, as seen with the factor analysis, and the dyspnea and activity scores appear responsive to physiologic changes in lung function over time.
TL;DR: A classification system for loss of papillary height is proposed that uses readily identifiable anatomical landmarks for reference, and sorts the degree of loss into 3 classes, allowing for a quick descriptive assessment.
Abstract: A classification system for loss of papillary height is proposed. It uses readily identifiable anatomical landmarks for reference, and sorts the degree of loss into 3 classes. The 3 broad categories allow for a quick descriptive assessment. In addition to the basic classification, it is suggested that additional and incremental description may be included to further define the defects.
TL;DR: These data are compatible with interstitial edema as a mechanism and suggest that lung size is an important determinant of the efficiency of gas exchange during exercise.
Abstract: During maximal exercise, ventilation-perfusion inequality increases, especially in athletes. The mechanism remains speculative. We hypothesized that, if interstitial pulmonary edema is involved, pr...
TL;DR: Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed and is consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg.
Abstract: Ascorbic acid is a required cofactor in the hydroxylations of lysine and proline necessary for collagen formation; its role in bone cell differentiation and formation is less well characterized. This study examines the cross-sectional relation between dietary vitamin C intake and bone mineral density (BMD) in women from the Postmenopausal Estrogen/Progestin Interventions Trial. BMD (spine and hip) was measured using dual energy X-ray absorptiometry (DXA). The PEPI participants (n = 775) included in this analysis were Caucasian and ranged in age from 45 to 64 years. At the femoral neck and total hip after adjustment for age, BMI, estrogen use, smoking, leisure physical activity, calcium and total energy intake, each 100 mg increment in dietary vitamin C intake, was associated with a 0.017 g/cm2 increment in BMD (P= 0.002 femoral neck; P= 0.005 total hip). After adjustment, the association of vitamin C with lumbar spine BMD was similar to that at the hip, but was not statistically significant (P= 0.08). To assess for effect modification by dietary calcium, the analyses were repeated, stratified by calcium intake (>500 mg/day and ≤500 mg/day). For the femoral neck, women with higher calcium intake had an increment of 0.0190 g/cm2 in BMD per 100 mg vitamin C (P= 0.002). No relation between BMD and vitamin C was evident in the lower calcium stratum. Similar effect modification by calcium was observed at the total hip: the β coefficient in the higher calcium stratum was similar to that for the total sample (β= 0.0172, P= 0.01), but no statistically significant relation between total hip BMD and vitamin C was found in the lower calcium subgroup. Although the relation between vitamin C and lumbar spine BMD was of marginal statistical significance in the total sample, among women ingesting higher calcium, a statistically significant association was observed (β= 0.0199, P= 0.024). These data are consistent with a positive association of vitamin C with BMD in postmenopausal women with dietary calcium intakes of at least 500 mg.
TL;DR: Brief training increased muscle volume in weight-stable adolescent males and, surprisingly, influenced not only IGF-I but GHBP and IGFBP-2 as well in a manner typically found in energy-deficient states.
Abstract: Insulin-like growth factor-I (IGF-I) is associated with muscle hypertrophy, and circulating IGF-I levels are correlated with fitness. To test the hypothesis that IGF-I increases with increased physical activity in adolescent males, 38 subjects (16 +/- 0.7 yr old) were randomized to control (n = 18) or increased physical activity groups for 5 wk. Before and after the intervention, we measured thigh muscle volume using magnetic resonance imaging and serum levels of mean growth hormone (GH) by overnight multiple sampling, GH binding protein (GHBP), IGF-I, and IGFBPs 1-5 by standard assays. Energy expenditure was assessed with the doubly labeled water technique toward the end of the study. In the training subjects there was 1) a significant increase in thigh muscle volume (+3.6 +/- 1%), 2) 15.5 +/- 3.3% greater energy expenditure than in controls, and 3) no evidence of weight loss (+1.44 +/- 0.4%). In contrast to our hypothesis, but similar to our recent observations in adolescent females, training decreased IGF-I (-12 +/- 4%, P < 0. 005). Moreover, training substantially reduced GHBP (-21 +/- 4%, P < 0.00002) and increased IGFBP-2 (+40 +/- 16%, P < 0.008). Brief training increased muscle volume in weight-stable adolescent males and, surprisingly, influenced not only IGF-I but GHBP and IGFBP-2 as well in a manner typically found in energy-deficient states.
TL;DR: The results suggest that AGE may be an effective antioxidant in preventing or treating disorders related to endothelial cell injury associated with free radicals.
TL;DR: It is concluded that adjunctive bicarbonate is unnecessary and potentially disadvantageous in severe pediatric DKA.
TL;DR: This review will address the molecular mechanisms of the osteogenic action of fluoride and proposes two competing models, both of which involve the mitogen activated protein kinase (MAPK) mitogenic signal transduction pathway.
Abstract: Fluoride is an effective anabolic agent to increase spinal bone density by increasing bone formation, and at therapeutically relevant (i.e., micromolar) concentrations, it stimulates bone cell proliferation and activities in vitro and in vivo. However, the fluoride therapy of osteoporosis has been controversial, in large part because of a lack of consistent antifracture efficacy. However, information regarding the molecular mechanism of action of fluoride may improve its optimum and correct usage and may disclose potential targets for the development of new second generation drugs that might have a better efficacy and safety profile. Accordingly, this review will address the molecular mechanisms of the osteogenic action of fluoride. In this regard, we and other workers have proposed two competing models, both of which involve the mitogen activated protein kinase (MAPK) mitogenic signal transduction pathway. Our model involves a fluoride inhibition of a unique fluoride-sensitive phosphotyrosine phosphatase (PTP) in osteoblasts, which results in a sustained increase in the tyrosine phosphorylation level of the key signaling proteins of the MAPK mitogenic transduction pathway, leading to the potentiation of the bone cell proliferation initiated by growth factors. The competing model proposes that fluoride acts in coordination with aluminum to form fluoroaluminate, which activates a pertussis toxin-sensitive Gi/o protein on bone cell membrane, leading to an activation of cellular protein tyrosine kinases (PTKs), which in turn leads to increases in the tyrosine phosphorylation of signaling proteins of the MAPK mitogenic signal transduction pathway, ultimately leading to a stimulation of cell proliferation. A benefit of our model, but not the other model, is that it accounts for all the unique properties of the osteogenic action of fluoride. These include the low effective fluoride dose, the skeletal tissue specificity, the requirement of PTK-activating growth factors, the sensitivity to changes in medium phosphate concentration, the preference for undifferentiated osteoblasts, and the involvement of the MAPK. Unlike fluoride, the mitogenic action of fluoroaluminate is not specific for skeletal cells. Moreover, the mitogenic action of fluoroaluminate shows several important, different characteristics than that of fluoride. Thus, it is likely that our model of a fluoride-sensitive PTP represents the actual molecular mechanism of the osteogenic action of fluoride.
TL;DR: Soy foods and soybean components have received considerable attention of late for their potential role in reducing cancer risk, but there is, at the moment, very limited support for soy exerting a protective effect against this type of cancer.
Abstract: Soy foods and soybean components have received considerable attention of late for theirpotential role in reducing cancer risk. Although the relationship between soy intake and the risk of breast and prostate cancer has been the focus of most interest, the relationship between soy intake and other cancers, including colorectal cancer, has also been studied. Several anti-carcinogens have been identified in soybeans, but most enthusiasm for the potential anti-cancer effects of soy undoubtedly stems from work involving soybean isoflavones. Isoflavones have a limited distribution in nature, and, for practical purposes, soyfoods are the only nutritionally relevant dietary source of these phytochemicals. Isoflavones are weak oestrogens but possess other potentially important biological attributes independent of their ability to bind to the oestrogen receptor. The isoflavone genistein inhibits the growth of most types of hormone-dependent and hormone-independent cancer cells in vitro, including colonic cancer cells. Several mechanisms for the in vitro anti-cancer effects of genistein have been proposed, including effects on signal transduction. A number of epidemiological studies, primarily of Asian origin, have examined the relationship between soy intake and the risk of colorectal cancer. Although these studies provide little support for a protective effect of soy, concerns have been raised about the completeness of the soy intake data, since soy was not the focus of these studies and most of this research was conducted prior to the recent interest in the anti-cancer effects of soy. The effect of soy/isoflavone intake has also been studied in rodents, but again these data are conflicting and provide only modest support for a protective effect. Although the relationship between soy intake and colonic cancer risk is certainly worthy of further investigation, there is, at the moment, very limited support for soy exerting a protective effect against this type of cancer.
TL;DR: Primary prevention programs are able to reach and influence high-risk adolescents in a nonstigmatizing manner and demonstrate significant reductions in cigarette use and alcohol use at the initial follow-up.
Abstract: OBJECTIVES: This study investigated the secondary prevention effects of a substance abuse primary prevention program. METHODS: Logistic regression analyses were conducted on 4 waves of follow-up data from sixth- and seventh-grade baseline users of cigarettes, alcohol, and marijuana taking part in a school-based program in Indianapolis. RESULTS: The program demonstrated significant reductions in cigarette use at the initial follow-up (6 months) and alcohol use at the first 2 follow-ups (up to 1.5 years). Models considering repeated measures also showed effects on all 3 substances. CONCLUSIONS: Primary prevention programs are able to reach and influence high-risk adolescents in a nonstigmatizing manner.
TL;DR: The results suggest that the role of IGFBP‐4 is mainly to sequester excess IGFs, and thus inhibit all actions, and IGF BP‐5 is capable of eliciting a dual response, possibly due to its unique ability to associate with the cell membrane.
Abstract: We have previously shown that the insulin-like growth factors (IGFs) stimulate both proliferation and differentiation of skeletal muscle cells in culture, and that these actions in L6A1 muscle cells may be modulated by three secreted IGF binding proteins (IGFBPs), IGFBP-4, -5, and -6. Since we found that the temporal expression pattern of IGFBP-4 and IGFBP-5 differed dramatically during the transition from proliferating myoblasts to differentiated myotubes, we undertook the current study to examine the effects of purified IGFBP-4 and IGFBP-5 on IGF-stimulated actions in L6A1 muscle cells. As has been shown for other cell types, we found that IGFBP-4 had only inhibitory actions, inhibiting IGF-I and IGF-II-stimulated proliferation and differentiation. In contrast, IGFBP-5 exhibited both inhibitory and stimulatory actions. When added in the presence of 30 ng/ml IGF-I, IGFBP-5 (250 ng/ml) inhibited all markers of the early proliferative response: the tyrosine phosphorylation of the cytoplasmic signaling molecules IRS-1 and Shc, the activation of the MAP kinases, ERK1 and 2, the elevation of c-fos mRNA, the early inhibition of the elevation in myogenin mRNA, and the increase in cell number. In contrast, IGFBP-5 stimulated all aspects of the myogenic response to IGF-I: the later rise in myogenin mRNA, the elevation of creatine kinase activity, and the fusion of myoblasts into myotubes. This dual response to IGFBP-5 was greatest when it was added at a molar ratio of IGFBP-5 to IGF-I of 2:1. In contrast, when IGFBP-5 was added in the presence of IGF-II, it inhibited both proliferation and differentiation. Neither IGFBP had any effect when added in the presence of R3 IGF-I, an analog with substantially reduced affinity for IGFBPs. Our results suggest that the role of IGFBP-4 is mainly to sequester excess IGFs, and thus inhibit all actions. IGFBP-5, however, is capable of eliciting a dual response, possibly due to its unique ability to associate with the cell membrane.
TL;DR: A course of oral corticosteroids in healthy young patients with subfoveal CNV in PIC or MIC may reduce subretinal vascular leakage and stabilise vision when no other proven treatment option is available.
Abstract: Purpose To investigate the role of systemic corticosteroids in the treatment of sight-threatening choroidal neovascularisation (CNV) in patients with punctate inner choroidopathy (PIC) and multifocal inner choroiditis (MIC). Methods Twelve eyes of 10 patients with evidence of PIC or MIC with recent visual symptoms were identified. All eyes had CNV within the foveal avascular zone on fundus fluorescein angiography (FFA). Systemic oral prednisolone at an initial dose of 1 mg/kg (60-80 mg) was given for 3-5 days and the dose was subsequently tapered. Changes in best corrected visual acuity and leakage on FFA were recorded during follow-up. Systemic side-effects of the corticosteroids were monitored. Results In 10 of 12 eyes vision improved or stabilised. Leakage on FFA resolved in 9 eyes and was reduced in 3. Four patients required more than one course of oral corticosteroids. One patient was maintained on low-dose oral corticosteroids for recurrent CNV activity. No systemic complications from the treatment were observed. Conclusion A course of oral corticosteroids in healthy young patients with subfoveal CNV in PIC or MIC may reduce subretinal vascular leakage and stabilise vision when no other proven treatment option is available.