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1.
AJNR Am J Neuroradiol ; 40(2): 334-339, 2019 02.
Article in English | MEDLINE | ID: mdl-30679213

ABSTRACT

BACKGROUND AND PURPOSE: The sensitivity of contrast-enhanced 3D-FLAIR has not been assessed in patients with idiopathic intracranial hypertension. The purpose of this study was to evaluate whether hyperintensity of the optic nerve/optic nerve head on contrast-enhanced 3D-FLAIR imaging is associated with papilledema in patients with idiopathic intracranial hypertension. MATERIALS AND METHODS: A retrospective review was conducted from 2012 to 2015 of patients with clinically diagnosed idiopathic intracranial hypertension and age- and sex-matched controls who had MR imaging with contrast-enhanced 3D-FLAIR. Two neuroradiologists graded each optic nerve/optic nerve head on a scale of 0-3. This grade was then correlated with the Frisén Scale, an ophthalmologic scale used for grading papilledema from 0 (normal) to 5 (severe edema). To estimate the correlation between the MR imaging and Frisén scores, we calculated the Kendall τ coefficient. RESULTS: Forty-six patients (3 men, 43 women) with idiopathic intracranial hypertension and 61 controls (5 men, 56 women) with normal findings on MR imaging were included in this study. For both eyes, there was moderate correlation between the 2 scales (right eye: τ = 0.47; 95% CI, 0.31-0.57; left eye: τ = 0.38; 95% CI, 0.24-0.49). Interreader reliability for MR imaging scores showed high interreader reliability (right eye: κ = 0.76; 95% CI, 0.55-0.88; left eye: κ = 0.87; 95% CI, 0.78-0.94). Contrast-enhanced 3D-FLAIR imaging correlates with the Frisén Scale for moderate-to-severe papilledema and less so for mild papilledema. CONCLUSIONS: Hyperintensity of the optic nerve/optic nerve head on contrast-enhanced 3D-FLAIR is sensitive for the detection of papilledema in patients with idiopathic intracranial hypertension, which may be useful when prompt diagnosis is crucial.


Subject(s)
Imaging, Three-Dimensional/methods , Neuroimaging/methods , Optic Disk/diagnostic imaging , Optic Nerve/diagnostic imaging , Pseudotumor Cerebri/diagnostic imaging , Adult , Algorithms , Female , Humans , Magnetic Resonance Imaging/methods , Male , Middle Aged , Optic Disk/pathology , Optic Nerve/pathology , Papilledema/diagnostic imaging , Papilledema/etiology , Pseudotumor Cerebri/complications , Pseudotumor Cerebri/pathology , Reproducibility of Results , Retrospective Studies
3.
Ann Oncol ; 23(11): 2960-2963, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22745218

ABSTRACT

BACKGROUND: Cardiac sequelae from oncologic drugs are important in early cancer drug development. Prolongation of the corrected QT interval (QTc) by noncardiac drugs is the most common cause of drug development delays, nonapprovals and postmarketing withdrawals by the US Food and Drug Administration. PATIENTS AND METHODS: We analyzed 8518 electrocardiograms (ECGs) in 525 consecutive cancer patients enrolled in 22 industry-sponsored phase I clinical trials, starting 1 January 2006. RESULTS: Seventy-four patients [14%, 95% confidence interval (CI) 11% to 17%] with normal QTc at baseline had QTc intervals above upper limit of normal after treatment initiation; 33 (6%, 95% CI 4% to 9%) had prolonged QTc intervals at baseline, and only one (3%, 95% CI 0% to 16%) worsened after dosing. Seven of 33 patients (21%, 95% CI 9% to 39%) with prolonged baseline QTc had normalization of QTc intervals after dosing. All QTc prolongations were clinically insignificant; study drugs were continued uneventfully. Two of 525 patients (0.4%, 95% CI 0% to 1%) experienced cardiac serious adverse events (myocardial infarction possibly related to drug and unstable atrial flutter related to metastatic disease). Both cardiac events were detected by clinical assessment, not surveillance ECGs. CONCLUSION: Frequent ECG monitoring provided no clinically significant information in 525 patients in early phase trials.


Subject(s)
Antineoplastic Agents/adverse effects , Electrocardiography/drug effects , Heart Rate/drug effects , Heart/drug effects , Neoplasms/drug therapy , Adolescent , Adult , Aged , Aged, 80 and over , Clinical Trials, Phase I as Topic , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical , Female , Humans , Long QT Syndrome/chemically induced , Male , Middle Aged , Young Adult
4.
Blood Coagul Fibrinolysis ; 11(3): 309-11, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10870812

ABSTRACT

The potential mechanism underlying the rapid response to vitamin K replacement in acquired deficiency states is incompletely understood. To examine vitamin K metabolism, a 10-year-old boy with autoimmune enteropathy on oral vitamin K supplementation, who presented with profuse nosebleeds and calf tenderness, was evaluated. Laboratory analyses were consistent with severe vitamin K deficiency: vitamin K dependent protein (VKDP) levels < 5%, normal vitamin K epoxide level and depressed total prothrombin antigen (carboxylated and undercarboxyated forms). Intramuscular vitamin K (10 mg) was administered. Nine hours following therapy, VKDP levels corrected completely. Total prothrombin antigen increased indicating new prothrombin synthesis. However, the increase in the prothrombin-clotting assay far exceeded the increase in total prothrombin, supporting storage of undercarboxylated prothrombin in vitamin K deficiency states, with carboxylation and secretion after vitamin K replacement. Although this mechanism is known to occur in rodents, it has not been reported in humans. Our findings suggest a new potential mechanism of prothrombin metabolism in humans.


Subject(s)
Prothrombin , Vitamin K Deficiency , Blood Coagulation , Child , Humans , Male , Vitamin K Deficiency/blood
5.
Dev Biol ; 208(2): 375-91, 1999 Apr 15.
Article in English | MEDLINE | ID: mdl-10191052

ABSTRACT

Retinoids have long been known to influence skeletogenesis but the specific roles played by these effectors and their nuclear receptors remain unclear. Thus, it is not known whether endogenous retinoids are present in developing skeletal elements, whether expression of the retinoic acid receptor (RAR) genes alpha, beta, and gamma changes during chondrocyte maturation, or how interference with retinoid signaling affects skeletogenesis. We found that immature chondrocytes present in stage 27 (Day 5.5) chick embryo humerus exhibited low and diffuse expression of RARalpha and gamma, while RARbeta expression was strong in perichondrium. Emergence of hypertrophic chondrocytes in Day 8-10 embryo limbs was accompanied by a marked and selective up-regulation of RARgamma gene expression. The RARgamma-rich type X collagen-expressing hypertrophic chondrocytes lay below metaphyseal prehypertrophic chondrocytes expressing Indian hedgehog (Ihh) and were followed by mineralizing chondrocytes undergoing endochondral ossification. Bioassays revealed that cartilaginous elements in Day 5.5, 8.5, and 10 chick embryo limbs all contained endogenous retinoids; strikingly, the perichondrial tissues surrounding the cartilages contained very large amounts of retinoids. Implantation of beads filled with retinoid antagonist Ro 41-5253 or AGN 193109 near the humeral anlagens in stage 21 (Day 3.5) or stage 27 chick embryos severely affected humerus development. In comparison to their normal counterparts, antagonist-treated humeri in Day 8.5-10 chick embryos were significantly shorter and abnormally bent; their diaphyseal chondrocytes had remained prehypertrophic Ihh-expressing cells, did not express RARgamma, and were not undergoing endochondral ossification. Interestingly, formation of an intramembranous bony collar around the diaphysis was not affected by antagonist treatment. Using chondrocyte cultures, we found that the antagonists effectively interfered with the ability of all-trans-retinoic acid to induce terminal cell maturation. The results provide clear evidence that retinoid-dependent and RAR-mediated mechanisms are required for completion of the chondrocyte maturation process and endochondral ossification in the developing limb. These mechanisms may be positively influenced by cooperative interactions between the chondrocytes and their retinoid-rich perichondrial tissues.


Subject(s)
Bone and Bones/embryology , Cartilage/embryology , Chondrocytes/cytology , Forelimb/embryology , Receptors, Retinoic Acid/biosynthesis , Retinoids/metabolism , Trans-Activators , Animals , Benzoates/pharmacology , Biological Assay , Calcification, Physiologic , Cells, Cultured , Chick Embryo , Chromans/pharmacology , Collagen/biosynthesis , Diaphyses/embryology , Hedgehog Proteins , Humerus/embryology , In Situ Hybridization , Naphthalenes/pharmacology , Protein Biosynthesis , RNA, Messenger/isolation & purification , Receptors, Retinoic Acid/genetics , Retinoids/antagonists & inhibitors , Signal Transduction , Sternum/cytology , Tissue Distribution , Ulna/embryology
6.
J Mol Biol ; 285(3): 1039-52, 1999 Jan 22.
Article in English | MEDLINE | ID: mdl-9887266

ABSTRACT

We have carried out a physicochemical and computational analysis on the stability of the intercalated structures formed by cytosine-rich DNA strands. In the computational study, the electrostatic energy components have been calculated using a Poisson-Boltzmann model, and the non-polar energy components have been computed with a van der Waals function and/or a term dependent on the solvent-accessible surface area of the molecules. The results have been compared with those obtained for Watson-Crick duplexes and with thermodynamic data derived from UV experiments. We have found that intercalated DNA is mainly stabilized by very favorable electrostatic interactions between hydrogen-bonded protonated and neutral cytosines, and by non-polar forces including the hydrophobic effect and enhanced van der Waals contacts. Cytosine protonation electrostatically promotes the association of DNA strands into a tetrameric structure. The electrostatic interactions between stacked C.C+ pairs are strongly attenuated by the reaction field of the solvent, and are modulated by a complex interplay of geometric and protonation factors. The forces stabilizing intercalated DNA must offset an entropic penalty due to the uptake of protons for cytosine protonation, at neutral pH, and also the electrostatic contribution to the solvation free energy. The latter energy component is less favorable for protonated DNA due to the partial neutralization of the negative charge of the molecule, and probably affects other protonated DNA and RNA structures such as C+-containing triplexes.


Subject(s)
Centromere/chemistry , DNA/chemistry , Nucleic Acid Conformation , Computer Simulation , Magnetic Resonance Spectroscopy , Models, Molecular , Nucleic Acid Denaturation , Static Electricity , Temperature , Thermodynamics
7.
JAMA ; 280(2): 159-65, 1998 Jul 08.
Article in English | MEDLINE | ID: mdl-9669790

ABSTRACT

CONTEXT: No pharmacological therapeutic protocol has been found effective in modifying the clinical course of acute respiratory distress syndrome (ARDS) and mortality remains greater than 50%. OBJECTIVE: To determine the effects of prolonged methylprednisolone therapy on lung function and mortality in patients with unresolving ARDS. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Medical intensive care units of 4 medical centers. PARTICIPANTS: Twenty-four patients with severe ARDS who had failed to improve lung injury score (LIS) by the seventh day of respiratory failure. INTERVENTIONS: Sixteen patients received methylprednisolone and 8 received placebo. Methylprednisolone dose was initially 2 mg/kg per day and the duration of treatment was 32 days. Four patients whose LIS failed to improve by at least 1 point after 10 days of treatment were blindly crossed over to the alternative treatment. MAIN OUTCOME MEASURES: Primary outcome measures were improvement in lung function and mortality. Secondary outcome measures were improvement in multiple organ dysfunction syndrome (MODS) and development of nosocomial infections. RESULTS: Physiological characteristics at the onset of ARDS were similar in both groups. At study entry (day 9 [SD, 3] of ARDS), the 2 groups had similar LIS, ratios of PaO2 to fraction of inspired oxygen (FIO2), and MODS scores. Changes observed by study day 10 for methylprednisolone vs placebo were as follows: reduced LIS (mean [SEM], 1.7 [0.1] vs 3.0 [0.2]; P<.001); improved ratio of PaO2 to FIO2 (mean [SEM], 262 [19] vs 148 [35]; P<.001); decreased MODS score (mean [SEM], 0.7 [0.2] vs 1.8 [0.3]; P<.001); and successful extubation (7 vs 0; P=.05). For the treatment group vs the placebo group, mortality associated with the intensive care unit was 0 (0%) of 16 vs 5 (62%) of 8 (P=.002) and hospital-associated mortality was 2 (12%) of 16 vs 5 (62%) of 8 (P=.03). The rate of infections per day of treatment was similar in both groups, and pneumonia was frequently detected in the absence of fever. CONCLUSIONS: In this study, prolonged administration of methylprednisolone in patients with unresolving ARDS was associated with improvement in lung injury and MODS scores and reduced mortality.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Methylprednisolone/therapeutic use , Respiratory Distress Syndrome/drug therapy , Adult , Cross Infection/etiology , Double-Blind Method , Female , Hospital Mortality , Humans , Intensive Care Units , Male , Middle Aged , Multiple Organ Failure/etiology , Prospective Studies , Respiratory Distress Syndrome/complications , Respiratory Function Tests , Severity of Illness Index , Survival Analysis
8.
Am J Med Sci ; 315(5): 314-6, 1998 May.
Article in English | MEDLINE | ID: mdl-9587088

ABSTRACT

The genus Citrobacter includes three species of organisms that are uncommonly associated with human infection. When they are pathogenic, there are usually one or more associated respiratory, urinary, skin-soft tissue, and central nervous system infections and neonatal sepsis. These infections occur in the wake of significant systemic illness or complicate antibiotic usage. Rarely, infection has been associated with active tuberculosis. The authors report a case of Citrobacter freundii empyema in a patient with occult pulmonary histoplasmosis.


Subject(s)
Citrobacter freundii , Empyema, Pleural/complications , Enterobacteriaceae Infections/complications , Histoplasmosis/complications , Lung Diseases, Fungal/complications , Aged , Citrobacter freundii/isolation & purification , Citrobacter freundii/pathogenicity , Empyema, Pleural/diagnosis , Empyema, Pleural/microbiology , Enterobacteriaceae Infections/diagnosis , Enterobacteriaceae Infections/microbiology , Histoplasmosis/diagnosis , Histoplasmosis/microbiology , Humans , Lung Diseases, Fungal/diagnosis , Lung Diseases, Fungal/microbiology , Male , Opportunistic Infections/complications , Opportunistic Infections/diagnosis , Opportunistic Infections/microbiology , Tomography, X-Ray Computed
9.
Ment Retard ; 35(3): 177-84, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9197119

ABSTRACT

Variation in nutrition knowledge of adults with mild or moderate mental retardation (30 obese, 27 nonobese) from four community agencies was examined as a function of their body mass and level of mental retardation. They completed a nutrition knowledge test adapted for individuals with mental retardation. Multiple regression analyses revealed significant effects of level of mental retardation and body mass on nutrition knowledge. Adults with mild mental retardation possessed greater nutrition knowledge than did those with moderate mental retardation, and obese individuals possessed more knowledge than did nonobese individuals. The unexpected relation between nutrition knowledge and degree of obesity implies an influential role for environmental factors in the development of obesity.


Subject(s)
Intellectual Disability/complications , Knowledge , Nutritional Physiological Phenomena , Obesity/complications , Residential Facilities , Adult , Female , Humans , Male , Middle Aged , Obesity/diagnosis
10.
Blood Coagul Fibrinolysis ; 8(1): 48-53, 1997 Jan.
Article in English | MEDLINE | ID: mdl-9105637

ABSTRACT

Monitoring of oral anticoagulant therapy is usually undertaken with the prothrombin time (PT), which is influenced by factors II, X, and VII. A number of studies have suggested that the prothrombin (factor II) level may be the most important determinant of the therapeutic efficacy of these drugs. Although some studies suggest that oral anticoagulants induce a similar residual level of plasma vitamin K-dependent proteins, others have called this into question. We therefore measured plasma levels of factors II, X, and VII in 50 patients undergoing chronic Warfarin therapy. The plasma levels of factors II, X, and VII were significantly different. Although the factor X levels of all plasmas were < 30%, levels of factors II and VII were > 30% in 14% and 50% of the samples, respectively. Multivariable analysis showed factor II levels to be the least significant of the three factors measured in determining the international normalized ratio of plasma or whole blood. Thus, plasma levels of the vitamin K-dependent coagulation factors are not equal in patients on chronic Warfarin therapy. If factor II (prothrombin) levels are indeed the major determinants of the therapeutic efficacy of Warfarin, alternative means of monitoring that more accurately reflects prothrombin levels should be evaluated.


Subject(s)
Anticoagulants/administration & dosage , Factor VII/analysis , Factor X/analysis , Prothrombin/analysis , Warfarin/administration & dosage , Administration, Oral , Drug Monitoring/methods , Humans , Reference Standards
11.
Exp Cell Res ; 229(1): 126-36, 1996 Nov 25.
Article in English | MEDLINE | ID: mdl-8940256

ABSTRACT

During endochondral ossification, chondrocytes progress through several stages of maturation before they are replaced by bone cells. Chondrocyte proliferation, the first step in this complex multistage process, is strictly controlled both spatially and temporally but its underlying mechanisms of regulation remain unclear. In this study we asked whether chondrocytes produce syndecan-3, a cell surface receptor for growth factors such as fibroblast growth factor 2 (FGF-2), and whether syndecan-3 may play a role in proliferation during chondrocyte maturation. We found that proliferating immature cartilage from chick embryo tibia and sternum contained significant amounts of syndecan-3 mRNA, whereas mature hypertrophic cartilage contained markedly lower transcript levels. Immunohistochemical analyses on sections of Day 18 chick embryo tibia revealed that syndecan-3 was spatially restricted and indeed detectable only in immature proliferating chondrocytes in the top zone of growth plate. These syndecan-3-rich proliferating chondrocytes lay beneath developing articular chondrocytes rich in their typical matrix protein tenascin-C, resulting in a striking boundary between these two populations of chondrocytes. Immature proliferating chondrocyte populations reared in growth-promoting culture conditions displayed strong continuous syndecan-3 gene expression; upon induction of maturation by vitamin C treatment, syndecan-3 gene expression was markedly down-regulated. Treatment with FGF-2 for 24 h stimulated both syndecan-3 gene expression and chondrocyte proliferation; this growth stimulation was counteracted by cotreatment with heparinase I or III. The results of the study indicate that syndecan-3 participates in the maturation of chondrocytes during endochondral ossification and represents a regulator of the proliferative phase of this multistage process.


Subject(s)
Cartilage, Articular/cytology , Cartilage, Articular/physiology , Fibroblast Growth Factor 2/pharmacology , Glucuronidase , Membrane Glycoproteins/physiology , Osteogenesis , Proteoglycans/physiology , Animals , Cartilage, Articular/embryology , Cell Division/drug effects , Cells, Cultured , Chick Embryo , Gene Expression Regulation, Developmental , Glycoside Hydrolases/pharmacology , Humans , Kinetics , Membrane Glycoproteins/biosynthesis , Membrane Glycoproteins/drug effects , Organ Specificity , Proteoglycans/biosynthesis , Proteoglycans/drug effects , Receptors, Fibroblast Growth Factor/physiology , Recombinant Proteins/pharmacology , Syndecan-3
12.
Thromb Res ; 83(2): 137-42, 1996 Jul 15.
Article in English | MEDLINE | ID: mdl-8837312

ABSTRACT

Laboratory evidence for the presence of lupus anticoagulants (LAs) is sought when patients experience thrombotic events or when coagulation assays are abnormal. Although a number of tests for LAs have been proposed, none detect all LAs, and laboratories may be confronted with the need to perform more than one test to confirm a suspected LA. Recently, a modification of the aPTT, performed by varying the initial time of incubation of the aPTT reagent with the patient's plasma, was reported to detect LAs. The difference in clotting times when plasma is subjected to a 1- or 10- minute incubation (called here the "Delta one minus ten" or DOT) using a particular micronized silica-based aPTT reagent was shown to provide good discrimination between normal and LA plasmas. Because of the low cost of this test and its relative ease of performance, we attempted to replicate the results of this test using previously characterized LA plasmas. The DOT of 23 normal plasmas was 5.1 +/- 2.1 seconds, with a range of 0.5 - 9.3 seconds. The DOT of 20 of 34 LA samples tested (59%) was > 11 seconds. The DOT was abnormal in 8 of 22 (36%) samples diagnosed with a dilute Russell's viper venom time. It was abnormal in 12 of 12 patients diagnosed by other criteria, prior to the use of the dilute Russell's viper venom time. The DOT performed with a kaolin or ellagic acid-based aPTT reagent failed to discriminate normal from LA plasma. We conclude that the DOT performed with a specific silica-based reagent is an apparently simple and moderately sensitive test for detecting the lupus anticoagulant that deserves further evaluation.


Subject(s)
Lupus Coagulation Inhibitor/blood , Humans , Partial Thromboplastin Time
13.
J Orthop Res ; 14(3): 403-12, 1996 May.
Article in English | MEDLINE | ID: mdl-8676253

ABSTRACT

The development of cartilaginous elements of long bone during embryogenesis and postnatal bone repair processes is a complex process that involves skeletal cells and surrounding mesenchymal periosteal cells. Relatively little is known of the mechanisms underlying these processes. Previous studies from this and other laboratories have suggested that the extracellular matrix protein tenascin-C is involved in skeletogenesis. Using in situ hybridization and immunofluorescence, we extended those studies by comparing the expression of tenascin-C with that of syndecan-3, which belongs to a family of cell surface receptors with which tenascins are known to interact. We found that syndecan-3 transcripts at first were very abundant in the presumptive periosteum surrounding the diaphysis of early chondrocytic skeletal elements in chick limb. As the elements developed further, syndecan-3 gene expression decreased in the diaphyseal periosteum, whereas it became stronger around the early epiphysis and within the forming articular cells. However, as the diaphyseal periosteum initiated osteogenesis and gave rise to the intramembranous bone collar, syndecan-3 gene expression increased again. At early stages of skeletogenesis: the tenascin-C gene exhibited patterns of expression that were similar to and temporally followed, those of the syndecan-3 gene. At later stages, however, tenascin-C gene expression was markedly reduced during intramembranous osteogenesis around the diaphysis. In addition, although syndecan-3 gene expression was low in osteoblasts and osteocytes located deep into trabecular bone, tenascin-C gene expression remained strong. Thus, tenascin-C and syndecan-3 display distinct temporal and spatial patterns of expression in periosteum and during the development of long bone. Given their multidomain structure and specific patterns of expression, these macromolecules may regulate site-specific skeletal processes, including interactions between developing periosteum and chondrocytes and delineation of the early cartilaginous skeletal elements.


Subject(s)
Membrane Glycoproteins/genetics , Periosteum/embryology , Proteoglycans/genetics , Receptors, Fibroblast Growth Factor/genetics , Tenascin/genetics , Animals , Bone Development/genetics , Chick Embryo , Fluorescent Antibody Technique , Gene Expression Regulation, Developmental/physiology , In Situ Hybridization , Periosteum/physiology , RNA, Messenger/analysis , Syndecan-3
14.
Dev Dyn ; 206(1): 59-72, 1996 May.
Article in English | MEDLINE | ID: mdl-9019247

ABSTRACT

Tooth development involves reciprocal epithelial-mesenchymal interactions, polarized growth, mesenchyme condensation, and complex morphogenetic events. Because these processes bear similarities to those occurring in the developing limb, we asked whether morphogenetic signals found in the limb also occur in the developing tooth. We grafted mouse embryo tooth germs to the anterior margin of host chick embryo wing buds and determined whether the dental tissues had polarizing activity. Indeed, the grafts induced supernumerary digits. Activity of both molar and incisor tooth germs increased from bud to cap stages and was maximal at late bell stage in newborn. With further development the polarizing activity began to decrease, became undetectable in adult molar mesenchyme but persisted in incisor mesenchyme, correlating with the fact that incisors grow throughout postnatal life while molars do not. When different portions of neonatal incisors were assayed, a clear proximo-distal gradient of activity was apparent, with maximal activity restricted to the most proximal portion where undifferentiated mesenchyme and enamel organ reside. In situ hybridizations demonstrated that prior to induction of supernumerary digits, the tooth germ grafts induced expression in host tissue of Hoxd-12 and Hoxd-13. In addition, whole-mount in situ hybridizations and immunohistochemistry showed that developing tooth germs express Sonic hedgehog (Shh). Shh expression was first detected in bud stage tooth germs; at later stages Shh transcripts were prominent in enamel knot and differentiating ameloblasts at the cuspal region. We concluded that tooth germs possess polarizing activity and produce polarizing factors such as Shh. As in the limb, these factor(s) and activity probably play key roles in establishing polarity and regulating morphogenesis during early tooth development. Given its subsequent association with differentiating ameloblasts, Shh probably participates also in cytogenetic events during odontogenesis.


Subject(s)
Animals, Newborn/growth & development , Animals, Newborn/metabolism , Body Patterning , Proteins/metabolism , Tooth/embryology , Tooth/growth & development , Trans-Activators , Aging/metabolism , Animals , Chick Embryo , Embryonic and Fetal Development , Enamel Organ/embryology , Enamel Organ/growth & development , Hedgehog Proteins , Incisor/embryology , Incisor/growth & development , Mice/embryology , Mice/growth & development , Mice, Inbred Strains , Molar/embryology , Molar/growth & development , Tooth Germ/physiology , Tooth Germ/transplantation , Wings, Animal/abnormalities , Wings, Animal/embryology
15.
Ann Epidemiol ; 4(6): 460-5, 1994 Nov.
Article in English | MEDLINE | ID: mdl-7804501

ABSTRACT

To examine the extent of infection with syphilis in an inner-city community, we determined the prevalence, incidence, and correlates of syphilis seroreactivity in a representative sample of unmarried whites, African Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. One thousand seven hundred seventy single men and women aged 20 to 44 were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Syphilitic infection was determined by testing specimens with the microhemagglutination assay for antibodies to Treponema pallidum (MHA-TP). Of blood samples available from 1262 participants from the initial survey, 32 (2.5%) were MHA-TP reactive. After adjustment for age, a reactive syphilis serology was significantly predicted (P < 0.05) by African American race, homosexual activity (men), and less education. In homosexually active men, lifetime number of male sex partners and the presence of antibody to the human immunodeficiency virus (HIV) significantly predicted syphilis seroreactivity (P < 0.01). One year later, of 841 specimens available for testing, an additional 13 (1.5%) had become MHA-TP reactive. Eleven (85%) of the new cases were in heterosexual men and women. Although San Francisco citywide incidence data indicate that syphilis may be decreasing for the city as a whole, incidence data on a community level suggests that syphilitic infection is increasing in high-risk heterosexual communities. Thus, syphilis prevention programs should rely on serologic testing at the community level to plan effective intervention strategies.


Subject(s)
Syphilis/epidemiology , Adult , Black or African American , Confidence Intervals , Female , Hispanic or Latino , Humans , Incidence , Male , Prevalence , Risk , San Francisco/epidemiology , Serologic Tests , Sexual Behavior , Syphilis/diagnosis , Syphilis/ethnology , Urban Health , White People
16.
AIDS Educ Prev ; 6(1): 12-26, 1994 Feb.
Article in English | MEDLINE | ID: mdl-8024940

ABSTRACT

We examined correlates of condom use among heterosexual whites, blacks, and Hispanics (ages 20-45 years) with an human immunodeficiency virus (HIV) risk factor in a community-based longitudinal sample (San Francisco; n = 716). Lag models were used to examine hypothesized antecedents of condom use at wave 2. High levels of condom use were associated with labeling one's sexual behavior as risky for HIV infection, high levels of condom enjoyment and commitment to use condoms, good sexual communication practices, gender (trend), and marital status. The results support the need for wide-ranging intervention programs that stimulate people to make personal risk assessments, teach basic sexual skills, and direct those in need of intensive help to appropriate agencies.


Subject(s)
Black or African American/psychology , Condoms/statistics & numerical data , HIV Infections/prevention & control , Health Behavior , Hispanic or Latino/psychology , Sexual Behavior , White People/psychology , Adult , Communication , Female , HIV Infections/epidemiology , Humans , Logistic Models , Longitudinal Studies , Male , Middle Aged , Risk Factors , San Francisco/epidemiology , Surveys and Questionnaires
17.
Dev Dyn ; 198(2): 123-34, 1993 Oct.
Article in English | MEDLINE | ID: mdl-7508293

ABSTRACT

The roles of tenascin in cartilage development and function remain unclear. Based on the observation that tenascin is particularly abundant at the epiphyseal extremities of developing cartilaginous models of long bones in chick and mouse embryo, we tested the hypothesis that tenascin is involved in articular cartilage development. Immunofluorescence analysis revealed that tenascin was first localized in the cell condensation region of Day 4 chick embryo limb buds, where the cartilaginous models form. With further development, tenascin gene expression became indeed restricted to the articular cap of the models. Tenascin persisted in the articular cartilage of postnatal chickens but appeared to decrease with age. The protein was also abundant in embryonic and adult tracheal cartilage rings which, like articular cartilage, persist throughout postnatal life. Similar patterns of tenascin expression were seen in mouse. Using monoclonal antibodies to avian tenascin variants, we found that the bulk of articular cartilage contained the shortest tenascin variant (Tn190), whereas the largest variant (Tn230) was present in tissues associated or interacting with articular cartilage (ligaments and meniscus). The protein and its mRNA, however, were undetectable in growth plate cartilage undergoing maturation and endochondral ossification. This inverse correlation between chondrocyte maturation and tenascin production was corroborated by the finding that tenascin gene expression decreased markedly during maturation of chondrocytes in culture and during formation of a secondary ossification center within the articular cap in vivo. Thus, tenascin is intimately associated with the development of articular cartilage and other permanent cartilages whereas absence or reduced amounts of this matrix protein characterize transient cartilages which undergo maturation and are replaced by bone.


Subject(s)
Cartilage, Articular/embryology , Cell Adhesion Molecules, Neuronal/physiology , Extracellular Matrix Proteins/physiology , Animals , Cartilage, Articular/chemistry , Cartilage, Articular/cytology , Cell Adhesion Molecules, Neuronal/analysis , Cell Adhesion Molecules, Neuronal/genetics , Cell Differentiation/physiology , Cells, Cultured , Chick Embryo , Extracellular Matrix Proteins/analysis , Extracellular Matrix Proteins/genetics , Fluorescent Antibody Technique , Growth Plate/cytology , Growth Plate/embryology , Immunohistochemistry , Isomerism , Mice , Osteogenesis/physiology , RNA, Messenger/analysis , RNA, Messenger/genetics , Tenascin , Trachea/chemistry , Trachea/cytology , Trachea/embryology
18.
Arch Pathol Lab Med ; 117(10): 989-92, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8215841

ABSTRACT

The purpose of this study was to investigate a family with type IV Ehlers-Danlos syndrome (EDS-IV) and platelet sensitivity to aspirin, an association that, to our knowledge, has not been reported previously. Type IV Ehlers-Danlos syndrome is a rare disorder of type III collagen metabolism characterized by bruising easily and death at an early age from exsanguination by rupture of a major viscus or artery. Previous studies have suggested an association between various types of Ehlers-Danlos syndrome and abnormal platelet function. In this family, EDS-IV is inherited in an autosomal dominant pattern. The transmission of the platelet functional disorder from the proband to only one of two children affected with EDS-IV in this family suggests that there is a genetic component to this condition that is independent of EDS-IV.


Subject(s)
Aspirin/adverse effects , Blood Coagulation/drug effects , Ehlers-Danlos Syndrome/blood , Ehlers-Danlos Syndrome/genetics , Adult , Blood Platelets/physiology , Child , Collagen/analysis , Female , Fibrinogen/analysis , Humans , Male , Pedigree , Platelet Aggregation
20.
J Adolesc Health ; 14(4): 295-300, 1993 Jun.
Article in English | MEDLINE | ID: mdl-8347641

ABSTRACT

The recent spread of crack cocaine use among inner-city teenagers has been accompanied by dramatic increases in juvenile delinquency and sexually transmitted diseases (STDs) among teenagers. This study examined the prevalence of five factors which promote STDs, including human immunodeficiency virus (HIV), among a sample of sexually active black adolescent crack users and non-users from the San Francisco Bay Area. Significant differences were observed between these groups with respect to history of engaging in sexual intercourse under the influence of drugs or alcohol, exchanging sexual favors for drugs or money, condom use in the most recent sexual encounter, and having five or more sexual partners in the last year. Approximately 63% of all respondents reported engaging in at least one of these risk behaviors. In multiple logistic regression analysis, reporting one or more of these STD/HIV risk behaviors was significantly associated with crack use and having one or more relatives who used drugs. Intervention efforts need to address both individual and environmental risk factors in order to reduce teens' risk for STDs, including HIV.


PIP: Researchers combined data from two surveys conducted in the summer of 1988 to examine the association between sexually transmitted diseases (STD) risk behaviors and crack cocaine use among sexually active, black teenagers. All of the subjects lived in an inner city neighborhood in the San Francisco Bay Area in California. The Centers for Disease Control had earlier found a large increase in gonorrhea among black teenagers in San Francisco. Crack users were more likely the nonusers to have sexual intercourse under the influence of drugs or alcohol (43% vs. 11% for boys and 46% vs. 14% for girls; p .001), to take part in sexual acts placing them at risk for STD in exchange for money or drugs (29% vs. 4% for boys and 25% vs. 0 for girls; p .001), and to have more sexual partners in the last year (11.1 vs. 5.3 partners for boys; p .01 and 4.5 vs. 2.5 partners for girls; insignificant). Female nonusers were more likely to have used a condom during last sexual intercourse than were female crack users (39% vs. 18%; p .01). For both groups of boys, condom use during the last sexual act was at the same low rate (about 25%). Approximately 63% of all adolescents admitted to having at least one sexual risk behavior. Crack cocaine use and having at least one relative who used drugs were the greatest predictors of STD risk behavior (odds ratios, 2.2 and 1.97; p .001 and .01, respectively). An urban anthropology study in the same neighborhoods showed that the teenagers lived in an area conducive to high-risk behaviors including drug use common among friends and relatives, more than one sexual partner/year, high prevalence of STDs, and low condom use. The findings from these studies indicated that public health workers planning to implement interventions to prevent or reduce the risk of teenage drug use and/or HIV infection must consider both individual and environmental influences.


Subject(s)
Adolescent Behavior , Black or African American , Crack Cocaine , Risk-Taking , Sexual Behavior , Substance-Related Disorders/epidemiology , Adolescent , Adult , Case-Control Studies , Female , Forecasting , Humans , Male , Regression Analysis , San Francisco/epidemiology , Sexually Transmitted Diseases/epidemiology , Sexually Transmitted Diseases/etiology
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