Showing papers by "University of Medicine and Dentistry of New Jersey published in 1996"
1,094 citations
TL;DR: A low preoperative haemoglobin or a substantial operative blood loss increases the risk of death or serious morbidity more in patients with cardiovascular disease than in those without.
928 citations
TL;DR: This review discusses some rules for assessing the completeness of a cDNA sequence and identifying the start site for translation and includes some advice for using in vitro translation systems for the expression of cDNAs.
Abstract: This review discusses some rules for assessing the completeness of a cDNA sequence and identifying the start site for translation. Features commonly invoked-such as an ATG codon in a favorable context for initiation, or the presence of an upstream in-frame terminator codon, or the prediction of a signal peptide-like sequence at the amino terminus-have some validity; but examples drawn from the literature illustrate limitations to each of these criteria. The best advice is to inspect a cDNA sequence not only for these positive features but also for the absence of certain negative indicators. Three specific warning signs are discussed and documented: (i) The presence of numerous ATG codons upstream from the presumptive start site for translation often indicates an aberration (sometimes a retained intron) at the 5' end of the cDNA. (ii) Even one strong, upstream, out-of-frame ATG codon poses a problem if the reading frame set by the upstream ATG overlaps the presumptive start of the major open reading frame. Many cDNAs that display this arrangement turn out to be incomplete; that is, the out-of-frame ATG codon is within, rather than upstream from, the protein coding domain. (iii) A very weak context at the putative start site for translation often means that the cDNA lacks the authentic initiator codon. In addition to presenting some criteria that may aid in recognizing incomplete cDNA sequences, the review includes some advice for using in vitro translation systems for the expression of cDNAs. Some unresolved questions about translational regulation are discussed by way of illustrating the importance of verifying mRNA structures before making deductions about translation.
761 citations
TL;DR: In this article, genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380.
Abstract: Parkinson9s disease (PD) is the second most common neurodegenerative disorder after Alzheimer9s disease, affecting approximately 1 percent of the population over age 50. Recent studies have confirmed significant familial aggregation of PD and a large number of large multicase families have been documented. Genetic markers on chromosome 4q21-q23 were found to be linked to the PD phenotype in a large kindred with autosomal dominant PD, with a Zmax = 6.00 for marker D4S2380. This finding will facilitate identification of the gene and research on the pathogenesis of PD.
753 citations
TL;DR: Altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion, which may well be responsible for the increased gynecological morbidity that characterizes this period of life.
Abstract: Medical therapy for women in the perimenopausal period is controversial, in part due to varying degrees of ovarian hormone secretion characteristic of this time of life. To extend our understanding of the reproductive endocrine milieu of perimenopausal women, we studied 6 cycling women, aged 47 yr and older, for 6 months with daily collections of first morning voided urine. Five additional older reproductive aged (43-47 yr old) women were studied with daily urine and serum sampling for a single menstrual cycle; their urinary hormone data were combined with the former group for menstrual cycle comparisons. Urine was assayed for LH, FSH, estrone conjugates, and pregnanediol glucuronide and normalized for creatinine (Cr). Eleven midreproductive aged (19-38 yr old) normally cycling women, 5 women with well defined premature ovarian failure, and 5 women aged 54 yr and older who were at least 1 yr postmenopausal were used for comparison. Perimenopausal women had shorter follicular phases (11 +/- 2 days vs. 14 +/- 1 days; P = 0.031) and, hence, shorter menstrual cycles than midreproductive aged controls. FSH excretion in perimenopausal women was greater than that in younger women (range of means, 4-32 vs 3-7 IU/g Cr; P = 0.0005). LH secretion was overall greater than that in younger normal subjects (range of means, 1.4-6.8 vs. 1.1-4.2 IU/g Cr; P < 0.026). Overall mean estrone conjugate excretion was greater in the perimenopausal women compared to that in the younger women [76.9 ng/mg Cr (range, 13.1-135) vs. 40.7 ng/mg Cr (range, 22.8-60.3); P = 0.023] and was similarly elevated in both follicular and luteal phases. Luteal phase pregnanediol excretion was diminished in the perimenopausal women compared to that in younger normal subjects (range for integrated pregnanediol, 1.0-8.4 vs. 1.6-12.7 microg/mg Cr/luteal phase; P = 0.015). Compared to postmenopausal women, perimenopausal women had more overall estrone excretion (2.5-6.2 ng/mg Cr in postmenopausal women; P = 0.02) and lower mean FSH (range of means for postmenopause, 24-85 IU/g Cr; P = 0.017) and LH (range for postmenopause, 4.3-14.8 IU/g Cr; P = 0.041). Compared to women with premature menopause, perimenopausal women again had lower FSH (range of means for premature menopause, 36-82 IU/g Cr; P = 0.0022), lower LH (range of means for premature menopause, 5.5-23.8 IU/g Cr; P = 0.0092), borderline higher mean estrone conjugates (range of means for premature menopause, 4-44 ng/mg Cr; P = 0.064), and far longer periods of ovarian activity (one to two cycles in prematurely menopausal women vs. three to six cycles in perimenopausal women). We conclude that altered ovarian function in the perimenopause can be observed as early as age 43 yr and include hyperestrogenism, hypergonadotropism, and decreased luteal phase progesterone excretion. These hormonal alterations may well be responsible for the increased gynecological morbidity that characterizes this period of life.
494 citations
TL;DR: Replication fork pause (RFP) sites transiently arresting replication fork movement were mapped to transfer RNA (tRNA) genes of Saccharomyces cerevisiae in vivo, suggesting that transcription is required for RFP activity.
Abstract: Replication fork pause (RFP) sites transiently arresting replication fork movement were mapped to transfer RNA (tRNA) genes of Saccharomyces cerevisiae in vivo. RFP sites are polar, stalling replication forks only when they oppose the direction of tRNA transcription. Mutant tRNA genes defective in assembly of transcription initiation complexes and a temperature-sensitive RNA polymerase III mutant (rpc160-41) defective in initiation of transcription do not stall replication forks, suggesting that transcription is required for RFP activity.
363 citations
TL;DR: In this article, the isolation of a human RNA polymerase II complex containing a subset of the basal transcription factors and the human homologues of the yeast SRB proteins was reported.
Abstract: WE report here the isolation of a human RNA polymerase II complex containing a subset of the basal transcription factors and the human homologues of the yeast SRB (for suppressors of RNA polymerase B) proteins1–3. The complex contains transcriptional coactivators and increases the activation of transcription. In addition, some components of the RNA polymerase II complex participate in DNA repair.
348 citations
TL;DR: The requirement for CsdA in derepression of heat-shock protein synthesis is a cold shock-induced function possibly mediated by destabilization of secondary structures previously identified in the rpoH mRNA.
Abstract: A 70-kDa protein was specifically induced in Escherichia coli when the culture temperature was shifted from 37 to 15 degrees C. The protein was identified to be the product of the deaD gene (reassigned csdA) encoding a DEAD-box protein. Furthermore, after the shift from 37 to 15 degrees C, CsdA was exclusively localized in the ribosomal fraction and became a major ribosomal-associated protein in cells grown at 15 degrees C. The csdA deletion significantly impaired cell growth and the synthesis of a number of proteins, specifically the derepression of heat-shock proteins, at low temperature. Purified CsdA was found to unwind double-stranded RNA in the absence of ATP. Therefore, the requirement for CsdA in derepression of heat-shock protein synthesis is a cold shock-induced function possibly mediated by destabilization of secondary structures previously identified in the rpoH mRNA.
332 citations
TL;DR: The present analysis completes a cycle of analyses that have determined the four fundamental parameters of cell proliferation: growth fraction, lengths of cell cycle, and phases Q and P and mathematically relates the size of the initial proliferative population to the neuronal population of the adult neocortex.
Abstract: Neurons of neocortical layers II-VI in the dorsomedial cortex of the mouse arise in the pseudostratified ventricular epithelium (PVE) through 11 cell cycles over the six embryonic days 11-17 (E11-E17). The present experiments measure the proportion of daughter cells that leave the cycle (quiescent or Q fraction or Q) during a single cell cycle and the complementary proportion that continues to proliferate (proliferative or P fraction or P; P = 1 - Q). Q and P for the PVE become 0.5 in the course of the eighth cycle, occurring on E14, and Q rises to approximately 0.8 (and P falls to approximately 0.2) in the course of the 10th cycle occurring on E16. This indicates that early in neuronogenesis, neurons are produced relatively slowly and the PVE expands rapidly but that the reverse happens in the final phase of neuronogenesis. The present analysis completes a cycle of analyses that have determined the four fundamental parameters of cell proliferation: growth fraction, lengths of cell cycle, and phases Q and P. These parameters are the basis of a coherent neuronogenetic model that characterizes patterns of growth of the PVE and mathematically relates the size of the initial proliferative population to the neuronal population of the adult neocortex.
321 citations
TL;DR: Issues of clinical and technical importance with regard to blood culturing are addressed; these issues include skin antisepsis, the number and timing of blood cultures, the appropriate volume of blood for culture, culture media and additives, length and atmosphere of incubation, and interpretation of positive blood culture results.
Abstract: Since the mid-1970s there has been a number of advances in blood culture practices and technology; these advances have been based largely on well-designed controlled clinical evaluations of blood culture systems and media. Thus, a sound scientific basis for the fundamental principles of blood culturing now exists. In this article. I will address issues of clinical and technical importance with regard to blood culturing; these issues include skin antisepsis, the number and timing of blood cultures, the appropriate volume of blood for culture, culture media and additives, length and atmosphere of incubation, and interpretation of positive blood culture results. Finally, I will discuss the currently available blood culture systems, with an emphasis on the newer continuous-monitoring blood culture systems.
320 citations
Journal Article•
TL;DR: HIV entry into brain is a consequence of the ability of virus-infected and immune-activated monocytes to induce adhesion molecules on brain endothelium, and an association between macrophage infiltration and increased endothelial cell adhesion molecule was observed in encephalitic brains.
Abstract: HIV-1 penetration of the brain is a pivotal event in the neuropathogenesis of AIDS-associated dementia. The establishment of productive viral replication or up-regulation of adhesion molecule expression on brain microvascular endothelial cells (BMVEC) could permit entry of HIV into the central nervous system. To investigate the contribution of both, we inoculated primary human BMVEC with high titer macrophage-tropic HIV-1 or cocultured them with virus-infected monocytes. In both instances, BMVEC failed to demonstrate productive viral replication. Cell to cell contact between monocytes and microvascular endothelium resulted in E-selectin expression on BMVEC. BMVEC. cocultured with LPS-activated HIV-infected monocytes expressed even higher levels of E-selectin and vascular cell adhesion molecule-1 (VCAM-1). Transwell assays supported a role of soluble factors, from virus-infected monocytes, for the induction of adhesion molecules on BMVEC. To verify the in vivo relevance of these findings, levels of adhesion molecules were compared with those of proinflammatory cytokines and HIV-1 gene products in brain tissue of AIDS patients with or without encephalitis and HIV-seronegative controls. E-Selectin, and to a lesser degree VCAM-1, paralleled the levels of HIV-1 gene products and proinflammatory cytokines in brain tissue of subjects with encephalitis. Most importantly, an association between macrophage infiltration and increased endothelial cell adhesion molecules was observed in encephalitic brains. Monocyte binding to encephalitic brain tissue was blocked with Abs to VCAM-1 and E-selectin. These data, taken together, suggest that HIV entry into brain is, in part, a consequence of the ability of virus-infected and immune-activated monocytes to induce adhesion molecules on brain endothelium.
TL;DR: Camptothecin induced significant, dose-dependent cell death of postmitotic rat cortical neurons in vitro; astrocytes were more resistant and a model based on transcriptionally mediated DNA damage, a novel mechanism of action of topo-I poisons is suggested.
Abstract: Camptothecin is an S-phase-specific anticancer agent that inhibits the activity of the enzyme DNA topoisomerase-I (topo-I). Irreversible DNA double-strand breaks are produced during DNA synthesis in the presence of camptothecin, suggesting that this agent should not be toxic to nondividing cells, such as neurons. Unexpectedly, camptothecin induced significant, dose-dependent cell death of postmitotic rat cortical neurons in vitro; astrocytes were more resistant. Aphidicolin, an inhibitor of DNA polymerase alpha, did not prevent camptothecin-induced neuronal death, while death was prevented by actinomycin D and 5,6-dichloro-1-beta-D-ribofuranosyl benzimidazole as well as cycloheximide and anisomycin, inhibitors of RNA and protein synthesis, respectively. Camptothecin-induced neuronal death was apoptotic, as characterized by chromatin condensation, cytoplasmic shrinking, plasma membrane blebbing, and fragmentation of neurites. DNA fragmentation was also confirmed by the use of the in situ DNA end labeling assay. In addition, aurintricarboxylic acid, an inhibitor of the apoptotic endonuclease, partially protected against camptothecin-induced neuronal death. The toxicity of stereoisomers of a camptothecin analogue was stereospecific, demonstrating that toxicity was a result of inhibition of topo-I. The difference in sensitivity to camptothecin between neurons and astrocytes correlated with their transcriptional activity and level of topo-I protein expression. These data indicate important roles for topo-I in postmitotic neurons and suggest that topo-I inhibitors can induce apoptosis independent of DNA synthesis. We suggest a model based on transcriptionally mediated DNA damage, a novel mechanism of action of topo-I poisons.
TL;DR: Surgical and nonsurgical approaches to weight loss have been evaluated, although most studies to date suffer from methodological limitations including lack of random assignment to treatment groups, confounding of treatment interventions, absence of untreated controls and lack of adequate follow-up assessment.
Abstract: Clinic-based and epidemiological studies demonstrate a strong association between obesity and obstructive sleep apnea. However, defining the causal relationship between excess body weight and sleep-disordered breathing remains difficult. Potential mechanisms to be considered include: (1) alterations in upper airway structure; (2) alterations in upper airway function; (3) alterations in the balance between ventilatory drive and load and (4) obesity-induced hypoxemia. Additional evidence for the role of obesity in obstructive sleep apnea comes from clinical studies of weight loss in patients with sleep-disordered breathing. Significant weight loss has been reported in most studies, which has been associated with varying degrees of improvement in sleep-disordered breathing, oxygen hemoglobin saturation, sleep architecture and daytime performance. Surgical and nonsurgical approaches to weight loss have been evaluated, although most studies to date suffer from methodological limitations including lack of random assignment to treatment groups, confounding of treatment interventions, absence of untreated controls and lack of adequate follow-up assessment. Implications for research and clinical practice are discussed.
TL;DR: Women with a low mean daily folate intake had an approximately twofold greater risk of preterm delivery and infant low birth weight after maternal characteristics, energy intake, and other correlated nutrients were controlled for.
TL;DR: This study shows that the NCIclinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials.
Abstract: Background : The National Cancer Institute (NCI)-sponsored clinical trials cooperative groups place more than 25 000 American patients in treatment trials every year. Equal access and proportional representation of all races/ethnicities is desired. Purpose : Our objectives were to evaluate the inclusion of African-Americans, Hispanics, and non-Hispanic whites in NCI-sponsored treatment trials and to determine if there is proportional racial/ethnic representation. Methods : During the period of January 1, 1991, through June 30, 1994, 99 495 cancer patients were enrolled in clinical trials and declared themselves as non-Hispanic black, non-Hispanic white, or Hispanic (of any race). In the analysis, participants in NCI treatment trials were subdivided into three age groups : birth to 19 years, 20-49 years, and 50 or more years. The racial/ethnic composition of each of these age groups was compared with the racial/ethnic makeup of the American population with cancer. Estimates of the number of incident cancer cases per year were made for each racial/ethnic group within each age group using data from the Surveillance, Epidemiology, and End Results (SEER) Program and the 1990 Census. The percentage of all cancer patients who were in each racial/ethnic group were compared with the population that entered clinical trials. Comparisons are also made separately for patients with leukemia and breast, colorectal, lung, and prostate cancers. Results : Among patients 0-19 years old, 20-49 years old, and 50 years old or older there is relatively proportional representation of non-Hispanic blacks, Hispanics, and non-Hispanic whites in trials. It is noted that more than 70% of cancer patients aged 0-19 years are estimated to enter cooperative group clinical trials compared with 4.0% of cancer patients aged 20-49 years and 1.5% of patients aged 50 years or older. Conclusions : Accrual of American cancer patients to NCI-sponsored treatment trials generally parallels the incident burden of disease among non-Hispanic African-Americans, Hispanics, and non-Hispanic whites. Implications : This study shows that the NCI clinical trials are, as a whole, racially/ethnically representative of the American population and suggests that there is equal access to NCI clinical trials.
TL;DR: The biologically active metabolite of vitamin D (cholecalciferol), i.e. 1,25(OH)2D3, is known to be a principal regulator of calcium homeostasis, and it has numerous other physiological functions including inhibition of proliferation of cancer cells, effects on hormone secretion and suppression of T-cell proliferation and cytokine production.
Abstract: The biologically active metabolite of vitamin D (cholecalciferol), i.e. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a secosteroid hormone whose mode of action involves stereospecific interaction with an intracellular receptor protein (vitamin D receptor; VDR). 1,25(OH)2D3 is known to be a principal regulator of calcium homeostasis, and it has numerous other physiological functions including inhibition of proliferation of cancer cells, effects on hormone secretion and suppression of T-cell proliferation and cytokine production. Although the exact mechanisms involved in mediating many of the different effects of 1,25(OH)2D3 are not completely defined, genomic actions involving the VDR are clearly of major importance. Similar to other steroid receptors, the VDR is phosphorylated; however, the exact functional role of the phosphorylation of the VDR remains to be determined. The VDR has been reported to be regulated by 1,25(OH)2D3 and also by activation of protein kinases A and C, suggesting co-operativity between signal transduction pathways and 1,25(OH)2D3 action. The VDR binds to vitamin D-responsive elements (VDREs) in the 5' flanking region of target genes. It has been suggested that VDR homodimerization can occur upon binding to certain VDREs but that the VDR/retinoid X receptor (RXR) heterodimer is the functional transactivating species. Other factors reported to be involved in VDR-mediated transcription include chicken ovalbumin upstream promoter (COUP) transcription factor, which is involved in active silencing of transcription, and transcription factor IIB, which has been suggested to play a major role following VDR/RXR heterodimerization. Newly identified vitamin D-dependent target genes include those for Ca2+/Mg(2+)-ATPase in the intestine and p21 in the myelomonocytic U937 cell line. Elucidation of the mechanisms involved in the multiple actions of 1,25(OH)2D3 will be an active area of future research.
TL;DR: The findings show that a presumably single mutation can prodcue a heterogeneous PD phenotype, even among siblings, consistent with the hypothesis that PD in the community may in fact be caused by a mutation, but one producing a lower penetrance and older age at onset than those in this kindred.
Abstract: We performed a clinical genetic analysis of a kindred originating in the town of Contursi in Salerno province, Italy, in which 60 individuals in 5 generations are known to have had Parkinson's disease (PD). Two previously reported autopsy cases showed typical PD with Lewy bodies. The inheritance pattern is apparently autosomally dominant with a segregation ratio of 40.1% for kindred members aged 50 years and older. The mean age at PD onset is 45.6 years (standard deviation, 13.48; range, 20-85) with a mean course to death of 9.2 years (standard deviation, 4.87; range, 2-20). Otherwise, clinical characteristics of PD in the kindred, including variance in onset age and incidence of tremor and levodopa responsiveness, are similar to those of PD in the community. The presence of tremor tended to be concordant in affected parent-child pairs, but there was no parent-child correlation for age at onset or intrasibship clustering of tremor or onset age. A suggestion of anticipation disappeared after adjustment for age-related ascertainment bias. The findings show that a presumably single mutation can produce a heterogeneous PD phenotype, even among siblings. This is consistent with the hypothesis that PD in the community may in fact be caused by such a mutation, but one producing a lower penetrance and older age at onset than those in this kindred.
TL;DR: The results suggest that DHT-crosslinked collagen fibers should not be used as load-bearing implants because they may retain more native structure and should exhibit greater resistance to nonspecific proteases in vivo.
Abstract: We previously demonstrated that ultraviolet (UV) or dehydrothermal (DHT) crosslinking partially denatured fibers extruded from an insoluble type I collagen dispersion. In this study denaturation effects were evaluated by measuring collagen-fiber sensitivity to trypsin. Shrinkage-temperature measurements and sensitivity to collagenase served as indices of crosslinking. UV or DHT crosslinking increased the collagen-fiber shrinkage temperature, resistance to degradation in collagenase, and durability under load in collagenase. However, in trypsin solutions, solubility was significantly increased for UV (approximately 11%) or DHT (approximately 15%) crosslinked fibers compared with uncrosslinked fibers (approximately 4%). Size-exclusion chromatography indicated that no intact collagen alpha-chains were present in the soluble fraction of fibers exposed to trypsin (MW < 1 kD). Interestingly, UV-crosslinked collagen fibers remained intact an order of magnitude longer (4840 +/- 739 min) than DHT-crosslinked (473 +/- 39 min) or uncrosslinked (108 +/- 53 min) fibers when placed under load in trypsin solutions. These data indicate that mechanical loading during incubation in a trypsin solution measures denaturation effects not detected by the trypsin-solubility assay. Our results suggest that DHT-crosslinked collagen fibers should not be used as load-bearing implants. UV-crosslinked fibers may retain more native structure and should exhibit greater resistance to nonspecific proteases in vivo.
TL;DR: The analysis suggests that Upf1p is a multifunctional protein with separable activities that can affect mRNA turnover and nonsense suppression, and suggests that ATP binding, independent of its hydrolysis, can modulate Upf 1p:RNA complex formation for this mutant protein.
Abstract: mRNA degradation is an important control point in the regulation of gene expression and has been linked to the process of translation. One clear example of this linkage is the nonsense-mediated mRNA decay pathway, in which nonsense mutations in a gene can reduce the abundance of the mRNA transcribed from that gene. For the yeast Saccharomyces cerevisiae, the Upf1 protein (Upf1p), which contains a cysteine- and histidine-rich region and nucleoside triphosphate hydrolysis and helicase motifs, was shown to be a trans-acting factor in this decay pathway. Biochemical analysis of the wild-type Upf1p demonstrates that it has RNA-dependent ATPase, RNA helicase, and RNA binding activities. A UPF1 gene disruption results in stabilization of nonsense-containing mRNAs, leading to the production of enough functional product to overcome an auxotrophy resulting from a nonsense mutation. A genetic and biochemical study of the UPF1 gene was undertaken in order to understand the mechanism of Upf1p function in the nonsense-mediated mRNA decay pathway. Our analysis suggests that Upf1p is a multifunctional protein with separable activities that can affect mRNA turnover and nonsense suppression. Mutations in the conserved helicase motifs of Upf1p that inactivate its mRNA decay function while not allowing suppression of leu2-2 and tyr7-1 nonsense alleles have been identified. In particular, one mutation located in the ATP binding and hydrolysis motif of Upf1p that changed the aspartic and glutamic acid residues to alanine residues (DE572AA) lacked ATPase and helicase activities, and the mutant formed a Upf1p:RNA complex in the absence of ATP; surprisingly, however, the Upf1p:RNA complex dissociated as a consequence of ATP binding. This result suggests that ATP binding, independent of its hydrolysis, can modulate Upf1p:RNA complex formation for this mutant protein. The role of the RNA binding activity of Upf1p in modulating nonsense suppression is discussed.
TL;DR: The future of dietetics practice requires dietetics professionals to provide medical nutrition therapy that incorporates a person's total health needs, including oral health, which requires inclusion of both didactic and clinical practice concepts that illustrate the role of nutrition in oral health.
Abstract: It is the position of the American Dietetic Association that nutrition is an integral component of oral health. The American Dietetic Association supports the integration of oral health with nutrition services, education, and research. Collaboration between dietetics and dental professionals is recommended for oral health promotion and disease prevention and intervention. Scientific and epidemiological data suggest a lifelong synergy between nutrition and the integrity of the oral cavity in health and disease. Oral health and nutrition have a synergistic bidirectional relationship. Oral infectious diseases, as well as acute, chronic, and terminal systemic diseases with oral manifestations, impact the functional ability to eat as well as diet and nutrition status. Likewise, nutrition and diet may affect the development and integrity of the oral cavity as well as the progression of oral diseases. As we advance in our discoveries of the links between oral and nutrition health, practitioners of both disciplines must learn to provide screening, baseline education, and referral to each other as part of comprehensive client/patient care. Dietetics practice requires registered dietitians to provide medical nutrition therapy that incorporates a person's total health needs, including oral health. Inclusion of both didactic and clinical practice concepts that illustrate the role of nutrition in oral health is essential in both dental and dietetic education programs. Collaborative endeavors between dietetics and dentistry in research, education, and delineation of health provider practice roles are needed to ensure comprehensive health care. The multifaceted interactions between diet, nutrition, and oral health in practice, education, and research in both dietetics and dentistry merit continued, detailed delineation.
TL;DR: Between 1993 and 1995, 93 neuropathic diabetes mellitus patients with foot ulcers underwent a total contact cast (TCC) protocol, with results in healing of forefoot ulcer and helps prevent ulcer recurrence.
Abstract: Between 1993 and 1995, 93 neuropathic diabetes mellitus patients with foot ulcers underwent a total contact cast (TCC) protocol. A randomly chosen group of 21 patients (Group I) demonstrated ulcer healing in a mean time of 43.5 days. Despite 9 weeks of TCC, 15 patients (Group II) with forefoot ulcers failed to heal. Physical examination of Group I revealed plantarflexion/dorsiflexion range of motion of the ankle of 33.8 degrees / 1.9 degrees compared to 32.3 degrees / -10.5 degrees of Group II, demonstrating an ankle equinus deformity and limited joint motion. Group II patients underwent a correction of the equinus deformity with percutaneous tendo-Achilles lengthening (TAL), followed by a TCC. All but one ulcer (93.3%) healed within 39.4 days. Four (19.0%) ulcers recurred (at the same site) in Group I, compared to none in Group II at the latest follow up of 17.3 months. Surgical correction with percutaneous TAL and TCC results in healing of forefoot ulcer and helps prevent ulcer recurrence.
TL;DR: Evidence proposing a critical role for ERCC2 in mediating the association of CAK with core TFIIH subunits is presented, and CAK-ERCC2 can efficiently associate with core-TFIIH to reconstitute holo-TF IIH transcription activity.
Abstract: Transcription factor IIH (TFIIH) is a multisubunit complex required for transcription and for DNA nucleotide excision repair. TFIIH possesses three enzymatic activities: (i) an ATP-dependent DNA helicase, (ii) a DNA-dependent ATPase, and (iii) a kinase with specificity for the carboxyl-terminal domain of RNA polymerase II. The kinase activity was recently identified as the cdk (cyclin-dependent kinase) activating kinase, CAK, composed of cdk7, cyclin H, and MAT-1. Here we report the isolation and characterization of three distinct CAK-containing complexes from HeLa nuclear extracts: CAK, a novel CAK-ERCC2 complex, and TFIIH. CAK-ERCC2 can efficiently associate with core-TFIIH to reconstitute holo-TFIIH transcription activity. We present evidence proposing a critical role for ERCC2 in mediating the association of CAK with core TFIIH subunits.
TL;DR: The salivary sulfo- and sialomucins actively participate in the modulation of the oral mucosal calcium channel activity through the inhibition of EGF-stimulated channel protein tyrosine phosphorylation, which is of paramount importance to mucosalcium homeostasis.
Abstract: 1. Salivary mucins are well recognized as an important factor in the preservation of the health of the oral cavity. These large glycoproteins play a major role in the formation of protective coatings covering tooth enamel and oral mucosa, which act as a dynamic functional barrier capable of modulating the untoward effects of oral environment, and are of significance to the processes occurring within the epithelial perimeter of mucosal defense. 2. Based on macromolecular characteristics, the mucins in saliva fall into high (> 1000 kDa) and low (200-300 kDa) molecular weight forms. The two forms, although differ with respect to bacterial clearance ability, display virtually identical carbohydrate chain make-up, ranging in size from 3 to 16 sugar units. 3. Of the two mucin forms, the low molecular weight form more efficient in bacterial aggregation, predominates in saliva and oral mucosal mucus coat of caries-resistant individuals, while the level of the high molecular weight form is higher in caries-susceptible subjects. The saliva of caries-resistant individuals also exhibits greater activity of protease capable of conversion of the high molecular weight mucin to the low molecular weight form. 4. The bacterial aggregating activity of salivary mucins appears to be associated with sulfomucins rather than sialomucins. While the removal of sialic acid causes only partial loss in mucin aggregating capacity, a complete loss in the bacterial aggregating activity occurs following mucin desulfation. 5. The mucins in oral mucosal mucus coat interact with the epithelial surfaces through specific membrane receptors. This interaction apparently involves the carbohydrate moiety of mucin molecule and may be rendered vulnerable to disruption by opportunistic bacteria colonizing the oral mucosa. 6. Salivary sulfo- and sialomucins actively participate in the modulation of the oral mucosal calcium channel activity through the inhibition of EGF-stimulated channel protein tyrosine phosphorylation. This function of salivary mucins is of paramount importance to mucosal calcium homeostasis.
TL;DR: The finding that nigral cell loss occurs after METH treatment indicates that the METH-treated mouse may be a very relevant model of Parkinson's disease (PD).
Vanderbilt University Medical Center1, Vanderbilt University2, University of Washington3, MedStar Washington Hospital Center4, University of California, San Francisco5, University of South Carolina6, University of Colorado Denver7, Wake Forest University8, University of Medicine and Dentistry of New Jersey9
TL;DR: In pregnant trauma patients, infant viability is defined by the presence of FHTs, estimated gestational age greater than or equal to 26 weeks, and in viable infants, survival after emergency cesarean section is acceptable (75%).
Abstract: Hypothesis Emergency cesarean sections in trauma patients are not justified and should be abandoned. Setting and Design A multi-institutional, retrospective cohort study was conducted of level I trauma centers. Methods Trauma admissions from nine level I trauma centers from January 1986 through December 1994 were reviewed. Pregnant women who underwent emergency cesarean sections were identified. Demographic and clinical data were obtained on all patients undergoing a cesarean section. Fetal distress was defined by bradycardia, deceleration, or lack of fetal heart tones (FHTs). Maternal distress was defined by shock (systolic blood pressure < 90) or acute decompensation. Statistical analyses were performed. Results Of the 114,952 consecutive trauma admissions, more than 441 pregnant women required 32 emergency cesarean sections. All were performed for fetal distress, maternal distress, or both. Overall, 15 (45%) of the fetuses and 23 (72%) of the mothers survived. Of 33 fetuses delivered, 13 had no FHTs and none survived. Twenty infants (potential survivors) had FHTs and an estimated gestational age (EGA) of greater than or equal to 26 weeks, and 75% survived. Infant survival was independent of maternal distress or maternal Injury Severity Score. The five infant deaths in the group of potential survivors resulted from delayed recognition of fetal distress, and 60% of these deaths were in mothers with mild to moderate injuries (Injury Severity Score < 16). Conclusions In pregnant trauma patients, infant viability is defined by the presence of FHTs, estimated gestational age greater than or equal to 26 weeks. In viable infants, survival after emergency cesarean section is acceptable (75%). Infant survival is independent of maternal distress or Injury Severity Score. Sixty percent of infant deaths resulted from delay in recognition of fetal distress and cesarean section. These were potentially preventable. Given the definition of fetal viability, our initial hypothesis is invalid.
TL;DR: De novo mutations are generated by inherently error-prone steps in the retroviral life cycle that introduce base substitutions, frame shifts, genetic rearrangements and hypermutations.
TL;DR: The results do not support a strong relationship between shoulder subluxation and pain after stroke and Appropriate precautions should be taken to prevent range of motion limitations that may result in shoulder pain.
Abstract: OBJECTIVE Few studies have concomitantly examined shoulder subluxation and other potential causes of shoulder pain in persons who have had a stroke. This study explores whether shoulder pain after stroke is related to shoulder subluxation, age, limitations in shoulder range of motion, and upper extremity motor impairment. METHOD Shoulder pain was measured with a visual analog scale in 20 subjects admitted to a rehabilitation hospital within 6 weeks of onset of their first stroke. Degree of shoulder pain was correlated with vertical, horizontal, and total asymmetries of glenohumeral subluxation; age; shoulder flexion, abduction, and external rotation; and the upper extremity subscore of the Fugl-Meyer Motor Assessment. RESULTS Shoulder pain after stroke was not correlated with age (rk = .019, p = .916); vertical (rk = .081, p = .324), horizontal (rk = .126, p = .241), or total asymmetry (rk = -.098, p = .288); shoulder flexion (rk = .049, p = .390) or abduction (rk = -.074, p = .337); or Fugl-Meyer scores (rk = -.123, p = .257). In contrast, shoulder pain was strongly correlated with degree of shoulder external rotation (rk = -.457, p = .006). CONCLUSION These results do not support a strong relationship between shoulder subluxation and pain after stroke. Appropriate precautions should be taken to prevent range of motion limitations that may result in shoulder pain.
TL;DR: The steady‐state pharmacokinetic profile of topiramate (TPM) as a function of dose and the effects of comedication with carbamazepine with CBZ was studied.
Abstract: Summary: Purpose: We studied the steady-state pharmacokinetic profile of topiramate (TPM) as a function of dose and the effects of comedication with carbamazepine (CBZ).
Methods: We enrolled 12 patients with partial epilepsy receiving chronic stable doses of CBZ 300–800 mg every 8 h. In a 6-week period, TPM was added and doses were increased at -2-week intervals from 100 to 200 to 400 mg every 12 h and stabilized at the highest tolerated dose to as high as 400 mg every 12 h. CBZ was tapered in the next 4 weeks when possible, and TPM was maintained as monotherapy at the highest stabilized dose for 2 more weeks. Plasma and urine samples were collected before TPM dosing, after each TPM dose increase, and during TPM monotherapy.
Results: Dose-normalized results (n = 10) for TPM area under the curve from 0 to 12 h (AUC(0–12)), Cmin(0), and Cavg indicated that TPM exhibits linear plasma pharmacokinetics over the dose range of 100- to 400-mg every 12 h when administered with CBZ. Mean TPM AUC(0–12)) Cmax, Cmin(0), and Cavg values were -40% lower during CBZ treatment as compared with those during TPM monotherapy (n = 3). TPM oral and nonrenal clearance rates were approximately two- to threefold higher, whereas TPM renal clearance was unchanged during concomitant CBZ treatment (n = 3). There were no significant changes in total and unbound CBZ and CBZ-epoxide (CBZ-E) pharmacokinetics during TPM administration (n = 10). TPM pharmacokinetics during concomitant CBZ treatment were significantly different from those during TPM monotherapy, suggesting that metabolic clearance of TPM increases when CBZ is coadministered.
Conclusions: When CBZ is reduced or discontinued, TPM doses may need to be lowered to maintain equivalent plasma concentrations. Adjusting the CBZ dose for pharmacokinetic reasons when TPM is administered as adjunctive treatment does not appear to be necessary.
Journal Article•
TL;DR: It seems possible to develop coralyne and nitidine derivatives as new topo I-targeted therapeutics to overcome aspects of camptothecin-related resistance.
Abstract: Protoberberine alkaloids (coralyne and its derivatives), which exhibit antileukemic activity in animal models, have been shown to be potent inducers of topoisomerase (topo) I-DNA cleavable complexes using purified recombinant human DNA topo I Different from the structurally similar benzophenanthridine alkaloid nitidine (a dual poison of both topos I and II), coralyne and its derivatives have marginal poisoning activity against DNA topo II Yeast cells expressing human DNA topo I are shown to be specifically sensitive to killing by coralyne derivatives and nitidine, suggesting that cellular DNA topo I is their cytotoxic target Two human camptothecin-resistant cell lines, CPT-K5 and A2780/CPT-2000, which are known to express highly camptothecin-resistant topo I, are only marginally resistant to coralyne derivatives and nitidine Purification of human topo I from Escherichia coli cells overexpressing CPT-K5 recombinant topo I has demonstrated similar marginal cross-resistance to nitidine It seems possible to develop coralyne and nitidine derivatives as new topo I-targeted therapeutics to overcome aspects of camptothecin-related resistance
TL;DR: Previously unreported, or little appreciated, nonmotor "off" states include sensory dyspnea, nausea, facial flushing, cough, hunger, unilateral limb edema, proximal limb pain, and trigeminal neuralgia-like pain.
Abstract: We studied the nature and frequency of nonmotor "off" phenomena in 130 consecutive patients with Parkinson's disease (PD) with motor fluctuations. Twenty-two patients (17%) experienced nonmotor fluctuations as an end-of-dose phenomenon. Previously unreported, or little appreciated, nonmotor "off" states include sensory dyspnea, nausea, facial flushing, cough, hunger, unilateral limb edema, proximal limb pain, and trigeminal neuralgia-like pain. We attempted treatment modification in 12 of 22 patients; nonmotor "off" symptoms improved in nine of these 12 patients (75%). Recognizing these phenomena will prevent unnecessary tests and treatments.