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Showing papers by "University of Texas Health Science Center at Houston published in 1995"


Journal ArticleDOI
TL;DR: Observations suggest that Adenylate/uridylate-rich elements play a critical role in the regulation of gene expression during cell growth and differentiation and in the immune response.

1,955 citations


Journal ArticleDOI
TL;DR: In healthy adults with no serologic evidence of past infection with C. parvum, a low dose of C.Parvum oocysts is sufficient to cause infection, and there were no secondary cases of diarrhea among household contacts.
Abstract: Background Small numbers of Cryptosporidium parvum oocysts can contaminate even treated drinking water, and ingestion of oocysts can cause diarrheal disease in normal as well as immunocompromised hosts. Since the number of organisms necessary to cause infection in humans is unknown, we performed a study to determine the infective dose of the parasite in healthy adults. Methods After providing informed consent, 29 healthy volunteers without evidence of previous C. parvum infection, as determined by the absence of anti-cryptosporidium–specific antibodies, were given a single dose of 30 to 1 million C. parvum oocysts obtained from a calf. They were then monitored for oocyst excretion and clinical illness for eight weeks. Household contacts were monitored for secondary spread. Results Of the 16 subjects who received an intended dose of 300 or more oocysts, 14 (88 percent) became infected. After a dose of 30 oocysts, one of five subjects (20 percent) became infected, whereas at a dose of 1000 or more oocysts, ...

884 citations


Journal ArticleDOI
01 Jun 1995-Burns
TL;DR: By providing a dermal replacement, the grafted dermal matrix permitted the use of a thin, widely meshed autograft from the donor site, without the undesirable scarring and contracture at the wound site that commonly results from this technique.

775 citations


Journal ArticleDOI
TL;DR: A maximum likelihood approach to estimating the variation of substitution rate among nucleotide sites according to an invariant+gamma distribution, which has two parameters: the gamma parameter alpha and the proportion of invariable sites theta.
Abstract: This paper presents a maximum likelihood approach to estimating the variation of substitution rate among nucleotide sites. We assume that the rate varies among sites according to an invariant+gamma distribution, which has two parameters: the gamma parameter alpha and the proportion of invariable sites theta. Theoretical treatments on three, four, and five sequences have been conducted, and computer program have been developed. It is shown that rho = (1 + theta alpha)/(1 + alpha) is a good measure for the rate heterogeneity among sites. Extensive simulations show that (1) if the proportion of invariable sites is negligible, i.e., theta = 0, the gamma parameter alpha can be satisfactorily estimated, even with three sequences; (2) if the proportion of invariable sites is not negligible, the heterogeneity rho can still be suitably estimated with four or more sequences; and (3) the distances estimated by the proposed method are almost unbiased and are robust against violation of the assumption of the invariant + gamma distribution.

599 citations


Journal ArticleDOI
TL;DR: The mean and variance of the frequency of mutations of each size and type, and the covariance between the numbers of mutation of two different sizes and two different types are derived.

492 citations


Journal ArticleDOI
TL;DR: A systematic screening of FGFR3 to detect mutations in patients with hypochondroplasia is reported, with a singleFGFR3 mutation found in 8 out of 14 unrelated patients with HypochondroPLasia.
Abstract: Hypochondroplasia (MIM 146000) is an autosomal dominant skeletal dysplasia with skeletal features similar to but milder than those seen in achondroplasia. Within the past year, the achondroplasia locus has been mapped to 4p 16.3 (refs 5-7) and mutations in the fibroblast growth factor receptor 3 (FGFR3) gene have been identified in patients with the disorder. More than 95% of 242 cases reported so far are accounted for by a single Gly380Arg mutation. McKusick et al. proposed that achondroplasia and hypochondroplasia are allelic based on the similarities in phenotype between the two disorders and the identification of a severely dwarfed individual whose father had achondroplasia and whose mother had hypochondroplasia. There is also genetic linkage evidence that hypochondroplasia and achondroplasia map to the same locus. We therefore began a systematic screening of FGFR3 to detect mutations in patients with hypochondroplasia. We now report a single FGFR3 mutation found in 8 out of 14 unrelated patients with hypochondroplasia. This mutation causes a C to A transversion at nucleotide 1620, resulting in an Asn540Lys substitution in the proximal tyrosine kinase domain.

429 citations


Journal ArticleDOI
26 Oct 1995-Nature
TL;DR: To determine the relative permeabilities of the two junctional pathways, the distribution of biotinylated tracers across this heterologous cell assembly after injecting a single AII amacrine cell is measured and it is found that neurobiotin passed easily through both types of gap junctions, but that biotin-X cadaverine passed through AII/bipolar cell gap junitions poorly compared to AII-AII gap junications.
Abstract: The retina is sensitive to light stimuli varying over more than 12 log units in intensity. It accomplishes this, in part, by switching between rod-dominated circuits designed for maximum utilization of scarce photons and cone circuits designed for greater acuity. Rod signals are integrated into the cone pathways through AII amacrine cells, which are connected by gap junctions both to other AII amacrine cells and to cone bipolar cells. To determine the relative permeabilities of the two junctional pathways, we have measured the distribution of biotinylated tracers across this heterologous cell assembly after injecting a single AII amacrine cell. We found that neurobiotin (relative molecular mass, 286) passed easily through both types of gap junctions, but that biotin-X cadaverine (relative molecular mass, 442) passed through AII/bipolar cell gap junctions poorly compared to AII/AII gap junctions. Thus, the AII/bipolar cell channel has a lower permeability to large molecules than does the AII/AII amacrine cell channel. The two pathways are also regulated differently. Dopamine and cyclic AMP agonists, known to diminish AII-AII coupling, did not change the relative labelling intensity of AII to bipolar cells. However, nitric oxide and cGMP agonists selectively reduced labelling in bipolar cells relative to AII amacrine cells, perhaps by acting at the bipolar side of this gap junction. This suggests that increased cGMP controls the network switching between rod and cone pathways associated with light adaptation.

362 citations


Journal ArticleDOI
TL;DR: The results demonstrate that mutations in the COMP gene cause pseudochondroplasia, a well characterized dwarfing condition mapping to chromosome 19p12–13.
Abstract: Pseudoachondroplasia (PSACH) is a well characterized dwarfing condition mapping to chromosome 19p12-13.1. Cartilage oligomeric matrix protein (COMP), a cartilage specific protein, maps to the same location within a contig that spans the PSACH locus. Using single strand conformation polymorphism (SSCP) analysis and nucleotide sequencing we have identified COMP mutations in eight familial and isolated PSACH cases. All mutations involve either a single base-pair change or a three base-pair deletion in exon 17B. Six mutations delete or change a well conserved aspartic acid residue within the calcium-binding type 3 repeats. These results demonstrate that mutations in the COMP gene cause pseudochondroplasia.

355 citations


Journal ArticleDOI
TL;DR: It is proposed that characterization of odontoblasts in tissues and cultures should rely upon utilization of sets of markers for the above NCPs and their mRNAs.
Abstract: Odontoblasts are responsible for formation of predentin, which is transformed to dentin when apatite crystals are formed and the fibrillar matrix becomes mineralized. Odontoblasts are specialized cells that synthesize and secrete a unique set of non-collagenous proteins (NCPs), as well as the collagenous matrix largely comprised of type I collagen. The NCPs consist of dentin specific and mineralized tissue specific proteins, as well as other proteins that are found in a variety of tissues. Three dentin specific proteins have been recognized to date: dentin phosphoprotein (DPP), also called phosphophoryn, AG1 (dentin matrix protein 1, Dmp1) and dentin sialoprotein (DSP). DPP appears to be made by odontoblasts and appears at the mineralization front within a short time. It may be secreted via odontoblastic processes. DPP binds to collagen and potentially initiates formation of apatite crystals. A second DPP function appears to be to bind to the 100 face of growing apatite crystals and to inhibit or slow their growth; thus, DPP may play a dual role by initiating mineralization and then affecting the crystal growth and perhaps the habit of the crystals. Although no function has been ascribed to AG1 or DSP, they should prove to be important markers for the odontoblast phenotype. A recent unique finding is that two separate genes appear to code for more than one DSP mRNA; other transcripts may result from differential splicing. Examples of mineralized tissue specific proteins expressed by osteoblasts as well as odontoblasts are bone sialoprotein (BSP) and osteocalcin. Some NCPs expressed by osteoblasts, odontoblasts and several other tissues include osteopontin (OPN) and the chondroitin sulfate containing proteoglycans, decorin and biglycan. We propose that characterization of odontoblasts in tissues and cultures should rely upon utilization of sets of markers for the above NCPs and their mRNAs. Similar approaches are commonly used in investigations on osteoblasts. Finally, dentin (like bone) contains other molecules such as growth factors, and serum derived proteins, found within the matrix; no functional significance has yet been placed upon this finding. Future experiments should focus upon the elucidation of the three dimensional structures of the collagenous fibrillar network and of the NCPs to determine the relationships to mineralization. The role played by odontoblasts in controlling extracellular events, such as by selective secretory routes, will require careful exploration.

350 citations


Journal ArticleDOI
TL;DR: The role of a thrombolytic agent added to conventional medical therapies and to compare an early invasive management strategy to a more conservative early strategy in patients with unstable angina and non-Q wave myocardial infarction is investigated to find either strategy is appropriate for patient management.

339 citations


Journal ArticleDOI
TL;DR: In studies that employed randomization to provider, greater patient compliance with treatment recommendations was shown with NPs than with physicians, and patient satisfaction and resolution of pathological conditions were greater for NP patients.
Abstract: This meta-analysis was an evaluation of patient outcomes of nurse practitioners (NPs) and nurse midwives (NMs), compared with those of physicians, in primary care. The sample included 38 NP and 15 NM studies. Thirty-three outcomes were analyzed. In studies that employed randomization to provider, greater patient compliance with treatment recommendations was shown with NPs than with physicians. In studies that controlled for patient risk in ways other than randomization, patient satisfaction and resolution of pathological conditions were greater for NP patients. NPs were equivalent to MDs on most other variables in controlled studies. In studies that controlled for patient risk, NMs used less technology and analgesia than did physicians in intrapartum care of obstetric patients. NMs achieved neonatal outcomes equivalent to those of physicians. Limitations in data from primary studies precluded answering questions of why and under what conditions these outcomes apply and whether these services are cost-effective.

Journal ArticleDOI
TL;DR: The hydrophobic properties of mucus appear to be related to its lipidic constituents and specifically to the presence of phospholipid surfactants that are synthesized, stored, and secreted by GI mucus cells in a regulated fashion.
Abstract: Impressive evidence has accumulated over the past 12 years indicating that one of the potentially important biophysical characteristics of mucus relates to its hydrophobic character. This surface property is region specific and reaches high values in the stomach and colon, where barrier properties against noxious agents in the lumen are most important. The hydrophobic properties of mucus appear to be related to its lipidic constituents and specifically to the presence of phospholipid surfactants that are synthesized, stored, and secreted by GI mucus cells in a regulated fashion.

Journal ArticleDOI
TL;DR: The incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 though 1984 was 39.0/100,000 person‐years (United States 1970 population as standard).
Abstract: We determined the incidence of seizures due to acute CNS insults for residents of Rochester, Minnesota, U.S.A., from 1935 through 1984. The age-adjusted incidence rates for 1955-1984, the period of most complete case ascertainment, was 39.0/100,000 person-years (United States 1970 population as standard). The age-adjusted incidence was considerably higher in men: 52.0 as compared with 29.5 in women. The 3.6% risk of experiencing an acute symptomatic seizure in an 80-year lifespan approaches that of developing epilepsy. The major causes of acute symptomatic seizures were traumatic brain injury, cerebrovascular disease, drug withdrawal, and CNS infections. Each type of acute symptomatic seizure has age, gender, and time period patterns that reflect the occurrence of the underlying cause.

Journal ArticleDOI
TL;DR: The life expectancy of patients with Marfan Syndrome undergoing surgical repair of aortic aneurysms has improved and is consistent with increased survival, indicating Marfan syndrome is a disease involving the entire aorta.
Abstract: Background Development of surgical therapy for aortic aneurysms and dissections has led to treatment of the lifethreatening cardiovascular complications associated with Marfan syndrome. The present study determines the effect of surgical therapy on the life expectancy of patients with Marfan syndrome and the clinical course of these patients after aortic aneurysm repair. Methods and Results Medical records were reviewed on 192 patients with Marfan syndrome who underwent aortic aneurysm repair during the past 26 years; 103 patients were interviewed, and complete preoperative and postoperative medical information was obtained. Survival curves were generated, and data were analyzed. The median cumulative probability of survival was 61 years, significantly increased compared with the median survival of 47 years for patients with Marfan syndrome determined 30 years ago (P<.0006). The majority of patients (53%) had second surgeries to repair subsequent aneurysms or dissections at other sites, the vast majority of which involved the aorta. The most common pattern of aneurysm repair was proximal ascending aortic aneurysm repair, followed by descending thoracic aneurysm surgery. The following variables predicted patients requiring second vascular surgeries: presence of acute or chronic dissection at the time of the first surgery, hypertension after the first surgery, and a history of smoking. Conclusions. The life expectancy of patients with Marfan syndrome undergoing surgical repair of aortic aneurysms had improved and is consistent with increased survival. After initial repair of an ascending aortic aneurysm, a significant number of patients have subsequent surgeries at other sites throughout the aorta, indicating Marfan syndrome is a disease involving the entire aorta. Patients who had a dissection at the time of the first aortic surgery were more likely to require subsequent aortic surgery than were patients who underwent prophylactic composite graft repair of an aortic aneurysm

Journal ArticleDOI
TL;DR: The data suggest that classical diabetic cystopathy is not the most common urodynamic findings in patients with diabetes mellitus and voiding dysfunction, and in fact these patients present with variable pathophysiological findings.

Journal ArticleDOI
TL;DR: It is reported that two structurally different AREs, the c-fos ARE and the granulocyte-macrophage colony-stimulating factor ARE, both direct rapid deadenylation as the first step in mRNA degradation, but by different kinetics.
Abstract: Poly(A) tail removal is a critical first step in the decay pathway for many yeast and mammalian mRNAs. Poly(A) shortening rates can be regulated by cis-acting sequences within the transcribed portion of mRNA, which in turn control mRNA turnover rates. The AU-rich element (ARE), found in the 3' untranslated regions of many highly labile mammalian mRNAs, is a well-established example of this type of control. It represents the most widespread RNA stability determinant among those characterized in mammalian cells. Here, we report that two structurally different AREs, the c-fos ARE and the granulocyte-macrophage colony-stimulating factor (GM-CSF) ARE, both direct rapid deadenylation as the first step in mRNA degradation, but by different kinetics. For c-fos-ARE-mediated decay, the mRNA population undergoes synchronous poly(A) shortening and is deadenylated at the same rate, implying the action of distributive or nonprocessive ribonucleolytic digestion of poly(A) tails. In contrast, the population of granulocyte-macrophage colony-stimulating factor ARE-containing mRNAs is deadenylated asynchronously, with the formation of fully deadenylated intermediates, consistent with the action of processive ribonucleolytic digestion of poly(A) tails. An important general implication of this finding is that different RNA-destabilizing elements direct deadenylation either by modulating the processivity at which a single RNase functions or by recruiting kinetically distinct RNases. We have also employed targeted inhibition of translation initiation to demonstrate that the RNA-destabilizing function of both AREs can be uncoupled from translation by ribosomes. In addition, a blockade of ongoing transcription has been used to further probe the functional similarities and distinctions of these two AREs. Our data suggest that the two AREs are targets of two distinct mRNA decay pathways. A general model for ARE-mediated mRNA degradation involving a potential role for certain heterogeneous nuclear ribonucleoproteins and ARE-binding proteins is proposed.

Journal ArticleDOI
TL;DR: The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients.
Abstract: PURPOSEDiagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed.PATIENTS AND METHODSData from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test.RESULTSA primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed w...

Journal ArticleDOI
18 Oct 1995-JAMA
TL;DR: In low-seroprevalence areas, it appears possible to severely limit transmission of HIV among populations of IDUs, despite continuing risk behavior among a substantial proportion of the population.
Abstract: Objectives. —To describe prevention activities and risk behavior in cities where human immunodeficiency virus (HIV) was introduced into the local population of injecting drug users (IDUs), but where seroprevalence has nevertheless remained low ( Design and Setting. —A literature search identified five such cities: Glasgow, Scotland; Lund, Sweden; Sydney, New South Wales, Australia; Tacoma, Wash; and Toronto, Ontario. Case histories were prepared for each city, including data on prevention activities and current levels of risk behavior among IDUs. Participants. —Injecting drug users recruited from both drug treatment and non-treatment settings in each city. Interventions. —A variety of HIV prevention activities for IDUs had been implemented in each of the five cities. Results. —There were three common prevention components present in all five cities: (1) implementation of prevention activities when HIV seroprevalence was still low, (2) provision of sterile injection equipment, and (3) community outreach to IDUs. Moderate levels of risk behavior continued with one third or more of the IDUs reporting recent unsafe injections. Conclusions. —In low-seroprevalence areas, it appears possible to severely limit transmission of HIV among populations of IDUs, despite continuing risk behavior among a substantial proportion of the population. Pending further studies, the common prevention components (beginning early, community outreach, and access to sterile injection equipment) should be implemented wherever populations of IDUs are at risk for rapid spread of HIV. (JAMA. 1995;274:1226-1231)

Journal ArticleDOI
TL;DR: There was an excess of males within the entire affected population and within identified probands and the male to female ratio was unskewed in nuclear families (probands, affected sibs, and parents); the excess appears to be related to males having more severe and more frequent complications of EXT than having any primary genetic origin.
Abstract: Hereditary multiple exostosis (EXT) is an autosomal dominant disorder in which the clinical hallmark is the growth of bony protuberances from long bones and which can cause a variety of orthopedic deformities. This study sought to further delineate the natural history of EXT. In addition, since previous studies have suggested that there are deviations from Mendelelian expectations in EXT, including incomplete penetrance and a skewed sex ratio, we attempted to confirm or refute these suggestions. Both portions of the study were carried out through retrospective review of 43 affected probands and 137 of their affected relatives. Data are presented concerning frequency and severity of complications of EXT including short stature, sequelae of exostoses, occurrence of malignant degeneration of exostoses, and problems in pregnancy and delivery of affected females. Only 2.8% of the total affected population had experienced exostosis-related malignancy, an estimate which is considerably less than earlier reports would suggest. Penetrance was 100%. There was an excess of males within the entire affected population (104:76) and within identified probands (28:15). However, the male to female ratio was unskewed in nuclear families (probands, affected sibs, and parents). The excess of males appears to be related to males having more severe and more frequent complications of EXT than having any primary genetic origin. © 1995 Wiley-Liss, Inc.

Journal ArticleDOI
TL;DR: It is shown that knowledge of H. pylori transmission is limited due to lack of solid epidemiological evidence from population-based analyses that adequately consider confounding, and that a role for either waterborne or zoonotic transmission has not been ruled out.
Abstract: This paper critically reviews the reported data regarding the transmission of Helicobacter pylori. The mode of transmission remains poorly understood ; no single transmission pathway has been clearly identified. Laboratory studies have experienced difficulty in isolating this organism from material other than gastric tissue. The problematic detection of this bacterium has presented obstacles to pinpointing portals of entry and exit and to implicating or ruling out environmental reservoirs. It is shown additionally that knowledge of H. pylori transmission is limited due to lack of solid epidemiological evidence from population-based analyses that adequately consider confounding. Reported observations in general support a person-to-person mode of transmission that occurs most frequently early in life ; H. pylori is consistently linked to conditions associated with residential crowding in childhood. Laboratory studies have yielded evidence in favour of both faecal-oral and oral-oral pathways. However, a role for either waterborne or zoonotic transmission has not been ruled out. The failure of investigations to single out a mode of transmission for H. pylori signals the possibility of multiple transmission pathways.

Journal ArticleDOI
TL;DR: This study provides final proof of the association between FBN2 mutations and CCA pathology, thus establishing the role of the fibrillin-2 in extracellular matrix physiology and pathology.
Abstract: Congenital contractural arachnodactyly (CCA) is an autosomal dominant disorder that is phenotypically similar to Marfan syndrome (MFS) and characterized by arachnodactyly, dolichostenomelia, scoliosis, multiple congenital contractures and abnormalities of the external ears. In contrast to MFS, CCA does not affect the aorta or the eyes. Two closely related genes, FBN1 located on chromosome 15q15-21.3 and FBN2 located at 5q23-31, encode large fibrillin proteins found in extracellular matrix structures called microfibrils. The MFS is caused by mutations in FBN1, while CCA has been genetically linked to FBN2 (refs 2, 5, 6). We now describe a pair of FBN2 missense mutations in two CCA patients that cause substitution of distinct cysteine residues in separate epidermal growth-factor-like (EGF) repeats. Our study provides final proof of the association between FBN2 mutations and CCA pathology, thus establishing the role of the fibrillin-2 in extracellular matrix physiology and pathology.

Journal ArticleDOI
TL;DR: The absence of hemolysin, gelatinase, or the aggregation substance gene in > 45% of endocarditis E. faecalis isolates suggests that while these traits may play a role in virulence, other properties are also important.
Abstract: The presence of hemolysin, gelatinase, and aggregation substance (by use of a probe known to hybridize to most pheromone-responsive plasmids) was determined in 192 isolates of Enterococcus faecalis from patients with endocarditis or other infections and fecal isolates from hospitalized patients or healthy volunteers, and in 86 non-E. faecalis isolates. Hemolysin was more common in nonendocarditis clinical isolates and in hospital fecal isolates (37% and 31%, respectively) than among endocarditis and community fecal isolates (16% and 20%, respectively). Gelatinase and aggregation substance, respectively, were found in 54% and 52% of isolates from endocarditis, in 58% and 72% of isolates from other infections, in 62% and 56% of hospital fecal isolates, and in 27% and 30% of fecal isolates from healthy volunteers. All 86 non-E. faecalis enterococcal isolates were negative for these traits. The absence of hemolysin, gelatinase, or the aggregation substance gene in > 45% of endocarditis E. faecalis isolates suggests that while these traits may play a role in virulence, other properties are also important.

Journal ArticleDOI
TL;DR: The placement of oral implants into jaw bone has a high predictability provided an adequate bone volume surrounding the implant is present to ensure primary stability and resistance to functional loading forces after completion of osseointegration.
Abstract: The placement of oral implants into jaw bone has a high predictability provided an adequate bone volume surrounding the implant is present to ensure primary stability and resistance to functional loading forces after completion of osseointegration. In the distal area of the maxilla, an adequate bone volume is often lacking because of the proximity of the sinus cavities. The aim of this study was to evaluate histologically the simultaneous placement of endosseous implants into the sinus cavity and the surgical elevation of the sinus floor including filling the cavity with different grafting materials. In 9 sinus areas of 5 beagle dogs, 9 titanium implants (ITI Dental Implant System) were placed, and the void space of the sinus cavity was filled simultaneously with either demineralized freeze-dried human cortical bone (Musculoskeletal Transplant Foundation), resorbable hydroxyapatite (Osteogen) or natural cancelleous bovine bone mineral (Bio-Oss). To study bone formation, fluorochrome markers (tetracycline HCl and calcein green) were used at 2 and 8 weeks. Clinically, all implants healed uneventfully, and 5 months after implant placement the dogs were killed for histologic evaluation. All implants exhibited osseointegration within the pre-existing cortical bone of the sinus floor. The implants surrounded by freeze-dried bone xenografts yielded no formation of new bone, whereas the sites with hydroxyapatite or natural bovine bone mineral demonstrated newly formed bone with direct contact at the implant surface. The average extent of bone to implant contact was 25% (SD = 10.6%) and 27% (SD = 8.8%), respectively in relation to the length of the originally denuded implant surface.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: In this article, the authors studied the association of plasminogen activator inhibitor antigen (PAI-1), tissue-type PLASM activator activator antigen (TPA), and D-dimer with early atherosclerosis in a cross-sectional case-control study involving 457 pairs.
Abstract: Background Thrombosis, provoked by a rupture of an atherosclerotic plaque, plays a crucial role in precipitating a coronary heart disease event Its role at the early stage of atherosclerosis has, however, been unclear, but it has been hypothesized that thrombosis or defective fibrinolysis contributes to the progression of atherosclerotic lesions Methods and Results We studied the association of plasminogen activator inhibitor antigen (PAI-1), tissue-type plasminogen activator antigen (TPA), and D-dimer with early atherosclerosis in a cross-sectional case-control study involving 457 pairs chosen from the biracial cohort of the Atherosclerosis Risk in Communities (ARIC) Study As examined by B-mode ultrasound, patients (cases) had intima-media thickness of carotid arteries above the 90th percentile and control subjects had thickness below the 75th percentile of the ARIC cohort Persons with a history of heart disease, stroke, or claudication were excluded from the case-control selection PAI-1, TPA, and D-dimer were higher in patients than in control subjects ( P ≤001, Wilcoxon signed rank statistic) In conditional logistic regression analyses, the odds ratios of carotid atherosclerosis were, for PAI-1, for example, 122, 154, and 160 in the second, third, and fourth quartiles compared with the first quartile ( P <0001, test of linear trend, adjusting for age, systolic blood pressure, total cholesterol, acetylsalicylic acid use, and time of blood draw) Corresponding tests for D-dimer and TPA also showed an increasing trend ( P <0001) Conclusions The findings support the hypothesis that thrombosis and fibrinolysis play a role at the early stage of the atherosclerotic process

Journal ArticleDOI
TL;DR: Docetaxel administered at 100 mg/m2 intravenously every 3 weeks has notable activity against platinum-refractory non-small-cell lung cancer, with a 21% major response rate.
Abstract: PURPOSEWe conducted a phase II study to determine the response to and toxicity of docetaxel (Taxotere; Rhone-Poulenc Rorer Pharmaceuticals, Inc, Collegeville, PA) in patients with advanced non-small-cell lung cancer refractory to prior platinum-containing chemotherapy (PCC) regimens.PATIENTS AND METHODSForty-four patients with stage IIIb or IV platinum-refractory non-small-cell lung cancer were treated with 100 mg/m2 of docetaxel intravenously over 1 hour every 3 weeks. The responses of 42 of 44 patients were assessable. Most patients had a Zubrod performance status of 1; the predominant histologic type was adenocarcinoma (61%), and 91% of patients had stage IV disease.RESULTSNine of 42 assessable patients (21%) achieved a partial response to treatment. The median response duration (from response to progression) was 17 weeks, and the projected median survival duration of all patients is 42 weeks (51 weeks for adenocarcinoma and 22 weeks for nonadenocarcinoma). Grade 3/4 neutropenia occurred in 85% of pati...

Journal ArticleDOI
TL;DR: It is demonstrated that ligand activation of retinoic acid receptors is sufficient to induce differentiation, whereas ligandactivation of retinoid X receptors is essential for the induction of apoptosis in HL-60 cell lines.
Abstract: Retinoids induce myeloblastic leukemia (HL-60) cells to differentiate into granulocytes, which subsequently die by apoptosis. Retinoid action is mediated through at least two classes of nuclear receptors: retinoic acid receptors, which bind both all-trans retinoic acid and 9-cis retinoic acid, and retinoid X receptors, which bind only 9-cis retinoic acid. Using receptor-selective synthetic retinoids and HL-60 cell sublines with different retinoid responsiveness, we have investigated the contribution that each class of receptors makes to the processes of cellular differentiation and death. Our results demonstrate that ligand activation of retinoic acid receptors is sufficient to induce differentiation, whereas ligand activation of retinoid X receptors is essential for the induction of apoptosis in HL-60 cell lines.

Journal ArticleDOI
TL;DR: Within the limits of this study, replacement of single-tooth molars by implant-supported restorations was predictable; however, a high incidence of gold screw loosening was seen.
Abstract: This retrospective report presents findings on 22 patients with 24 implantsreplacing single molars with implant-supported restorations. Patients with known bruxism habits were not considered for single-molar implant replacement. The patients underwent follow-up for an average of 24 months. The cumulative success rate was 95%, which reflects the loss of one 5×6 mm wide implant. Eleven implants were placed in edentulous ridges, and 13 were placed in extraction sockets. Most of the implants were placed in type B and C bone quantity and type 2 and 3 bone quality. All implants were restored on abutments with nonrotating gold cylinders. The occlusion for all restorations was developed to minimize centric contacts and lateral interferences. The frequency of gold retaining-screw loosening was obtained for 21 patients. The gold retaining screws loosened in eight implants between one and three times (38%). No incidence of crown or implant fracture occurred. Whithin the limits of this study, replacement of single-tooth molars by implant-supported restorations was predictable; however, a high incidence of gold screw loosening was seen.

Journal ArticleDOI
TL;DR: It is suggested that ICAM‐1 plays a significant role during the neutrophil‐dependent injury phase after hepatic ischemia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure.
Abstract: The potential role of intercellular adhesion molecule-i (ICAM-1) in the pathogenesis of reperfusion injury was investigated in male Fischer rats subjected to 45 mm of hepatic ischemia and 24 h of reperfusion. ICAM-i mRNA levels increased during ischemia in the ischemic liver lobes; however, during reperfusion mRNA levels increased in both the ischemic and nonischemic lobes. Immunohistochemical evaluation indicated ICAM-i expression only on sinusoidal lining cells in controls; ischemia-reperfusion enhanced ICAM-1 expression in the sinusoids and induced some expression on hepatocytes The monoclonal anti-ICAM-i antibody iA29, but not an immunoglobulin G control antibody, administered at 1 h and 8 h of reperfusion (2 mg/kg) signifIcantly attenuated liver injury as indicated by 51% lower plasma alanine aminotransferase activities and 32-36% less hepatic necrosis at 24 h without affecting reactive oxygen forma- tion by Kupffer cells and hepatic neutrophils. Although 1A29 reduced neutrophil extravasation in a glycogen peritonitis by 60%, the antibody had no signfficant effect on hepatic neutrophil infiltration during reperfusion. These data suggest that ICAM-1 plays a significant role during the neutrophil-dependent injury phase after hepatic ischemia and reperfusion and therefore blocking this adhesion molecule may have therapeutic potential against postischemic acute liver failure J. Leukoc. Biol. 57: 368-374; 1995.

Journal ArticleDOI
TL;DR: Students' physical activity and associated variables in 293 third-grade physical education lessons in 95 schools in 4 Child and Adolescent Trial for Cardiovascular Health (CATCH) centers in California, Louisiana, Minnesota, and Texas were observed.
Abstract: Little is known about children's activity levels during physical education classes and how they relate to the national health objectives for the year 2000 (U.S. Public Health Service, 1991). We systematically observed students' physical activity and associated variables in 293 third-grade physical education lessons in 95 schools in 4 Child and Adolescent Trial for Cardio-vascular Health (CATCH) centers in California, Louisiana, Minnesota, and Texas. The influence of independent variables was assessed simultaneously by analysis of variance. Significant differences among study centers were evidenced for both physical activity and lesson context variables. Additionally, there were differences among variables for lesson location and teacher specialty, but not for teacher gender. Boys were more active than girls, but only during free play opportunities. The findings have widespread implications for educators responsible for developing and implementing health-related physical education programs, as wel...