Natural history of macrovascular disease in type 2 diabetes. Role of insulin resistance.
Explore the source record for details and available documents.
Cardiovascular Diseases↗
Biomedical subjects
M Stern
Publications and source records attributed to M Stern.
Frequent 4-bp deletion in exon 9 of the SMAD4/MADH4 gene in familial juvenile polyposis patients.
Familial juvenile polyposis (FJP) is a hamartomatous polyposis syndrome characterized by the appearance of juvenile polyps in the gastrointestinal tract. Patients with this syndrome are at an increased risk for cancer of the colon, stomach, and pancreas. Recently, germline mutations in the SMAD4/DPC4 gene (official symbol MADH4) have been found in the majority of patients suffering from FJP. We have examined 11 unrelated patients with FJP for MADH4 germline mutations by direct sequencing of genomic DNA encompassing all 11 exons of the gene. Besides a novel mutation (959-960delAC at codon 277, exon 6) in one patient, we observed a 4-bp deletion (1372-1375delACAG) in exon 9 in two unrelated patients. Examination with microsatellite markers flanking MADH4 supports an independent origin of the mutation in these two families. The same 4-bp deletion in exon 9 has previously been described in three out of nine patients examined for MADH4 mutations. Our results combined with these previous data demonstrate that a unique 4-bp deletion in exon 9 of MADH4 accounts for about 25% of all FJP cases and that other MADH4 mutations occur in an additional 15% of patients. Genes Chromosomes Cancer 25:403-406, 1999.
Adenomatous Polyposis Coli↗
American Academy of Pediatrics. Pediatric Practice Action Group and Task Force on Medical Informatics. Privacy protection and health information: patient rights and pediatrician responsibilities.
Pediatricians and pediatric medical and surgical subspecialists should know their legal responsibilities to protect the privacy of identifiable patient health information. Although paper and electronic medical records have the same privacy standards, health data that are stored or transmitted electronically are vulnerable to unique security breaches. This statement describes the privacy and confidentiality needs and rights of pediatric patients and suggests appropriate security strategies to deter unauthorized access and inappropriate use of patient data. Limitations to physician liability are discussed for transferred data. Any new standards for patient privacy and confidentiality must balance the health needs of the community and the rights of the patient without compromising the ability of pediatricians to provide quality care.
Computer Security↗
Changes in the carbon balance of tropical forests: evidence from long-term plots
The role of the world's forests as a "sink" for atmospheric carbon dioxide is the subject of active debate. Long-term monitoring of plots in mature humid tropical forests concentrated in South America revealed that biomass gain by tree growth exceeded losses from tree death in 38 of 50 Neotropical sites. These forest plots have accumulated 0.71 ton, plus or minus 0.34 ton, of carbon per hectare per year in recent decades. The data suggest that Neotropical forests may be a significant carbon sink, reducing the rate of increase in atmospheric carbon dioxide.
Journal Article↗
Peaks of transforming growth factor-beta mRNA in alveolar cells of lung transplant recipients as an early marker of chronic rejection.
BACKGROUND: Chronic lung rejection (CLR) induces a fibroproliferative disorder leading to the occlusion of small airways. It has emerged as the major factor limiting the survival of lung transplant recipients. Predictive markers of CLR are lacking, and its diagnosis is generally ascertained when the fibrosis process is irreversible. METHODS: We have quantified the expression of transforming growth factor-beta (TGF-beta), a critical mediator of fibrogenesis, in alveolar cells from lung transplant recipients using a competitive reverse transcriptase polymerase chain reaction method. RESULTS: We have shown that patients with CLR presented marked peaks of TGF-beta mRNA expression, in contrast with patients without CLR. These peaks preceded the diagnosis of CLR by several months in two of three patients who died within 2 years of diagnosis. CONCLUSIONS: Our data suggest that TGF-beta expression in alveolar cells could serve as an early predictive and prognostic marker of chronic lung rejection.
Bronchoalveolar Lavage Fluid↗
Nonhepatosplenic gammadelta T-cell lymphoma: a subset of cytotoxic lymphomas with mucosal or skin localization.
Human gammadelta T lymphocytes represent a minor subset of T cells in the peripheral blood, which exhibit a limited diversity and a tissue-restricted repertoire in contrast to their broad specificity. Most postthymic neoplasms that arise from this T-cell subpopulation belong to the hepatosplenic gammadelta lymphoma entity. Only a few cases of nonhepatosplenic gammadelta lymphomas have been described in detail previously. This study presents the clinicopathologic features of 11 consecutive cases of nonhepatosplenic gammadelta lymphoma. All were characterized by mucosal or skin initial involvement: nasal cavity (n = 3), gastrointestinal tract (n = 3), skin (n = 3), lung (n = 1), larynx (n = 1). Most patients presented with B symptoms (eight of 11), without peripheral lymphadenopathy and bone marrow involvement. A past history of chronic antigen exposure was noted in six cases, and four patients had features of immune deficiency. On histology, they were classified as pleomorphic tumors. Features of epitheliotropism and angiocentrism was observed in most cases. Tumor cells had a CD2+, CD3+, T-cell receptor (TCR)delta-1+), betaF1- phenotype. They were CD5- (9 of 10) and CD4-/CD8- (9 of 10) or CD8+ (1 of 10). A clonal gamma-chain gene rearrangement was detected in all tested cases (9/9). All cases had an activated cytotoxic T-cell intracellular antigen-1 (TIA-1)+, Granzyme B+ phenotype. Epstein-Barr virus (EBV) sequences were detected in six cases by in situ hybridization (ISH). Despite an aggressive clinical course, complete remission was obtained in three patients, and one of the latter required a peripheral blood stem-cell transplantation. Nonhepatosplenic gammadelta peripheral T-cell lymphoma can be regarded as a model of activated cytotoxic lymphoma, occurring in mucosae or skin. These appear to be derived from the subpopulation of tissue-restricted gammadelta lymphocytes, which are involved in the host epithelial surface surveillance. The role of chronic antigen exposure in the pathogenesis of these rare lymphomas can be suggested, in view of the past history observed in at least some patients.
Adult↗
Specific interaction of food proteins with apical membranes of the human intestinal cell lines Caco-2 and T84.
A comparison between the intestinal epithelial cell lines Caco-2 and T84 was made to assess the influence of enterocytic differentiation on food protein binding capacities of the brush border membrane. Cell morphology and expression of brush border-associated enzymes were studied as differentiation markers. Food protein binding to isolated brush border membranes was measured with a dot blot chemiluminescence assay. Early at confluence, Caco-2 cells exhibited a more differentiated state compared to T84 cells. Brush border membranes of both cell lines bound gliadin peptides, beta-lactoglobulin and ovalbumin specifically. Binding capacities increased from gliadin peptides to ovalbumin to beta-lactoglobulin. There was correlation of membrane binding capacity with degree of cell differentiation. Due to their similarity to small intestinal epithelial cells, the colon carcinoma cell lines Caco-2 and T84 represent models for studying food protein-enterocytic brush border membrane interactions in relation to varying degrees of cell differentiation.
Caco-2 Cells↗
Biochemical analysis of ocular surface mucin abnormalities in dry eye: the canine model.
This study examines the canine model of keratoconjunctivitis sicca (KCS, 'dry eye') in order to establish the biochemical basis of altered ocular mucin secretion in this condition. It follows a previous examination of ocular mucins in the normal dog. Mucus was collected by suction from the ocular surface of dogs with KCS, and dispersed in guanidine hydrochloride containing a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation was used to separate floating 'rafts' of cell membranes from gradients containing secreted mucins. Gradient fractions were collected into pools on the basis of differential staining by Periodic Acid Schiff, Wheat Germ Agglutinin, and antibodies to MUC5AC peptide. High molecular weight glycoproteins were purified from the pooled material by gel filtration chromatography. Membrane-associated glycoproteins were also derived from the membrane rafts using octyl glucoside extraction and/or reduction and alkylation. Secreted mucins and membrane extracts from KCS samples were compared to equivalent material obtained from normal eyes. Density gradient staining profiles for normal and KCS mucus were similar over the buoyant density range typical for secreted mucins, enabling the collection of identical pools of gradient fractions for direct comparison. The following differences were observed in KCS secreted mucins compared to normal samples: an increase in the proportion of mucin with low buoyant density; a decrease in mannose content detected with Concanavalin A lectin; an increase in N-acetylglucosamine structures detected with Lycopersicon esculentum lectin; increased migration and lack of evidence for distinct subunit structure on agarose gels. In membrane extracts, the main difference was the presence of T antigen (Gal beta 1-3GalNAc) in KCS. These results demonstrate alterations in the subunit linkage of mucins in KCS, and suggest that glycosylation, core protein expression and/or post-synthetic modification of ocular surface mucins may also be changed.
Animals↗
Evaluation of three methods for culturing alginate throat swabs from cystic fibrosis patients.
Deep throat swabs are usually cultured for potential respiratory pathogens in patients with cystic fibrosis (CF) who do not produce sputum. Using alginate swabs, three methods were examined in the present study: (i) semiquantitative processing (direct plating); (ii) mere elution of swabs in Ringer's lactate followed by plating of the eluate; and (iii) complete quantitative processing (elution plus two-step dilution series). Throat swabs from 56 CF patients yielded 122 isolates of potential respiratory pathogens. Semiquantitative processing (n = 101 isolates) was not significantly inferior to elution (n = 104) and quantitative processing (n = 113; p > 0.05). Since semiquantitative processing is the simplest method, it is to be preferred, provided that alginate swabs are used.
Adolescent↗
Psychosocial adjustment in middle eastern adolescents: the relative impact of violent vs. non-violent social disorganization.
The relationship between extreme social change and the psychological adjustment of adolescents undergoing such change was examined. The impact of extreme social change relative to other conditions of catastrophic social disorganization such as chronic social conflict and violent war-like conditions was also considered. The results indicate that Bedouin adolescents in Israel, members of a community that has experienced drastic social upheaval, show elevated rates of psychopathology. Comparisons of Bedouin adolescents to Palestinian adolescents from the West Bank and Gaza suggest that for older adolescents the impact of extreme social change on mental health adjustment generally parallels that of both chronic social conflict (West Bank) and that of violent war-like conditions (Gaza). However, this pattern did not hold for younger adolescents. In the Bedouin community, younger adolescents demonstrated significantly less adverse impact on adjustment than older adolescents, while such differences did not hold in the West Bank and Gaza. Thus the findings suggest a continuum of adverse impact of the types of social disorganization examined and a possible interaction between type of social disorganization and organismic variables such as age and gender.
Adolescent↗
Postnatal maturation of rat small intestinal brush border membranes correlates with increase in food protein binding capacity.
To investigate maturational changes of membrane food protein binding capacity, we studied binding characteristics of brush border membranes isolated from small intestines of newborn and adult rats. Binding of biotinylated gliadin peptides, cow's milk proteins (alpha-casein, beta-lactoglobulin, alpha-lactalbumin, bovine serum albumin) and lectins was assessed by a sensitive chemiluminescence blot assay. We found specific food protein binding with regard to saturation and inhibition. Maximal binding of most food proteins and several lectins to brush border membranes of newborn and adult rats was comparable, whereas binding of beta-lactoglobulin was substantially less. Common or adjoining binding sites for the different food proteins tested were indicated by corresponding membrane protein binding patterns and by inhibition properties of unrelated proteins. Compared to newborns, adult membrane vesicles as well as isolated membrane proteins showed higher binding capacities. Thus postnatal maturation of small intestinal brush border membranes correlated with increased food protein binding capacity.
Animals↗
The effect of mucolytic agents on gene transfer across a CF sputum barrier in vitro.
Trials of gene transfer for cystic fibrosis (CF) are currently underway. However, direct application to the airways may be impeded by the presence of airway secretions. We have therefore assessed the effect of CF sputum on the expression of the reporter gene beta-galactosidase complexed with the cationic liposome DC-Chol/DOPE in a number of cell lines in vitro. Transfection was markedly inhibited in the presence of sputum; the effect was concentration dependent and was only partially ameliorated by removal of sputum with phosphate-buffered saline (PBS) washing before gene transfer. However, treatment of the sputum-covered cells with recombinant human DNase (rhDNase, 50 micrograms/ml) but not with N-acetylcysteine, Nacystelyn, lysine (all 20 mM) or recombinant alginase (0.5 U/ml) significantly (P < 0.005) improved gene transfer. Adenovirus-mediated gene transfer efficiency in the presence of sputum was similarly inhibited, and again, treatment with rhDNase before transfection significantly improved gene transfer (P < 0.005). Transfection of Cos 7 cells in the presence of exogenous genomic DNA alone demonstrated similar inhibition to that observed with sputum and was also ameliorated by pre-treatment of DNA-covered cells with rhDNase. In a separate series of experiments performed in the absence of added sputum or genomic DNA, increasing concentrations of rhDNase resulted in a concentration-related decline in transfection efficiency. However, even at the highest concentration (500 micrograms/ml of rhDNase), transfection efficiency remained more than 50% of control. Thus, pre-treatment of CF airways with rhDNase may be appropriate before liposome or adenovirus-mediated gene therapy.
Adenoviridae↗
The effects of jet nebulisation on cationic liposome-mediated gene transfer in vitro.
Nebulisation is currently the most acceptable and practical delivery system for repeated applications of gene therapy to the lower airways of cystic fibrosis (CF) patients. We have assessed whether this route of administration offers other benefits with regard to respiratory gene transfer. A standard jet nebuliser (Acorn System 22, Medicaid) was used to transfer the reporter gene beta-galactosidase complexed with the cationic liposome DC-Chol/DOPE to three epithelial cell lines in vitro, two non-CF and one CF, using a novel collection system. In all three cell lines, nebulisation resulted in significantly (P < 0.05) improved transfection efficiency compared with instillation. At a constant DNA: liposome ratio of 1:5 (wt:wt), transfection efficiency was inversely related to increasing concentrations of DNA-liposomes before nebulisation. This effect was not related to the amount of DNA delivered and measurements of both zeta potential and mean aerodynamic particle size before and after nebulisation did not show concentration-related differences. The increased transfection efficiency did not relate either to the physical consequences of the nebulisation processes nor the effects of nebulisation on the complexes before instillation. Significantly increased transfection efficiency was seen following nebulisation with 95% O2/5% CO2 in comparison with 21% O2/78% N2 (air); this did not relate to changes in either the pH or temperature of the solution bathing the cells. The data confirm that nebulisation is appropriate for gene delivery to the lower airways in clinical practice and points to factors that may optimise gene transfer efficiency.
Animals↗
Increased transmitter release and aberrant synapse morphology in a Drosophila calmodulin mutant.
The ubiquitous calcium-binding protein calmodulin (CaM) has been implicated in the development and function of the nervous system in a variety of eukaryotic organisms. We have generated mutations in the single Drosophila Calmodulin (Cam) gene and examined the effects of these mutations on behavior, synaptic transmission at the larval neuromuscular junction, and structure of the larval motor nerve terminal. Flies hemizygous for Cam3c1, a mutation in the first Ca2+-binding site, exhibit behavioral, neurophysiological, and neuroanatomical abnormalities. In particular, adults exhibit defects in locomotion, coordination, and flight. Larvae exhibit increased neurotransmitter release from the motor nerve terminal at low [Ca2+] in the presence of the K+ channel-blocking drug quinidine. In addition, synaptic bouton structure at motor nerve terminals is altered. These effects are distinct from those produced by altering the activity of the CaM target enzymes CaM-activated kinase II (CaMKII) and CaM-activated adenylyl cyclase (CaMAC). Furthermore, previous in vitro studies of mutant Cam3c1 demonstrated that although its Ca2+ affinity is decreased, Cam3c1 protein can activate CaMKII, CaMAC, and CaM-activated phosphatase calcineurin in a manner similar to wild-type CaM. Thus, the Cam3c1 mutation might affect Ca2+ buffering or interfere with the activation or inhibition of a CaM target distinct from CaMKII or CaMAC.
Amino Acid Sequence↗
Evolving concepts of diagnosis, pathogenesis, and therapy of Sjögren's syndrome.
Differences in diagnostic criteria for Sjögren's Syndrome (SS) have led to confusion in the research literature and in clinical practice. A particular challenge is the clinical diagnosis of the patients with sicca symptoms, fibromyalgia, chronic fatigue, vague cognitive defects, and a low titer antinuclear antibody. Until recently, many of these patients would have been classified as primary SS using the European criteria. A suggested revision of the European criteria will require inclusion of anti SS-A antibody or characteristic minor salivary gland biopsy, leading to greater agreement between European and San Diego criteria. Recent studies have emphasized that lacrimal and salivary gland flow involves an entire "functional" unit that includes the mucosal surface (the site of inflammation), efferent nerve signals sent to the midbrain (lacrimatory and salvatory nucleus), efferent neural signals from the brain, and acinal/ductal structures in the gland. Thus, symptoms of dryness or pain can result from interferences with any part of this functional unit. The initiating antigens in SS remain unknown, but immune reactivity against SS-A, SS-B, fodrin, alpha- amylase, and carbonic anhydrase have been demonstrated in patients with established disease. The inflammatory process in the gland releases metalloproteinases that alter the relationship of epithelial cells to their matrix, an interaction that is necessary for glandular function and survival. Therapies for SS remain inadequate. In SS patients with immune-mediated extraglandular manifestation (ie, lung, kidney, skin, nerve), the therapeutic approach is similar to systemic lupus erythematosus, although these therapies have relatively little effect on tear or saliva flow.
Humans↗
Hyaluronan and CD44 expression in minor salivary gland tumors.
OBJECTIVES: Hyaluronan (HA) and CD44 are most likely associated with tumor invasion and metastasis. Malignancies with different degrees of aggressiveness may express different levels and patterns of HA and CD44. The aim of this project was to examine the distribution of HA and CD44 in minor salivary gland tumors to determine if staining could be correlated with biologic behavior or tumor type. MATERIALS AND METHODS: Biotinylated hyaluronan binding protein as a probe for HA and monoclonal antibodies specific for CD44 were used to stain classic examples of the five most commonly encountered minor salivary gland tumors: monomorphic adenomas, pleomorphic adenomas, polymorphous low grade adenocarcinomas, mucoepidermoid carcinomas, and adenoid cystic carcinomas. RESULTS: Tumor cells of monomorphic adenomas were negative for both HA and CD44, and tumor capsules were intensely HA-positive. Pleomorphic adenomas exhibited HA and CD44 positivity in both mesenchymal and epithelial components, and HA in capsular tissues. All malignant salivary gland tumors expressed similar intense HA in tumor stroma. HA staining was more intense in stroma than in parenchymal cells. Tumor cells of most adenoid cystic carcinomas were HA-positive, while most polymorphous low grade adenocarcinomas were HA-negative. HA was uniformly distributed throughout supporting stroma of high and low grade malignancies, except for two polymorphous low grade adenocarcinomas (PLGAs) in which HA was more intense at the invading edge of the tumors. CD44 expression was seen only in tumor cells (not stroma) of malignancies, and was of similar intensity in both low and high grade tumors. CONCLUSIONS: Differences in the expression of HA and CD44 among different types of salivary gland tumors were noted. These findings, however, could not be correlated with known biologic behaviors of the tumor groups studied. Immunohistochemical staining of salivary gland tumors for HA and CD44 may be useful in separating monomorphic adenoma, polymorphous low grade adenocarcinoma and adenoid cystic carcinoma, lesions that may be difficult to distinguish with routine light microscopy.
Adenocarcinoma↗
Rapid and sustained efficacy of mizolastine 10 mg once daily in seasonal allergic rhinitis.
This 28-day, double-blind, randomized study in 256 patients compared the efficacy and safety of mizolastine 10 mg daily with placebo in patients with seasonal allergic rhinoconjunctivitis. All four nasal symptoms (itch, rhinorrhoea, sneezing, obstruction) and three ocular symptoms (itch, tears, redness) were rated by investigators using both a 0-3 and a 0-9 rating scale. Compared with the placebo group total, nasal and ocular scores were all significantly lower in the mizolastine-treated patients at day 14 of the study (P = 0.0002-0.0009, using the 0-9 scale) and relief was maintained throughout the 4-week study duration. Patient diary total scores showed that mizolastine was effective from the first day of treatment. The 0-9 scale appears to be more sensitive than the 0-3 scale for rating symptoms of seasonal allergic rhinitis.
Adult↗
Relapse prevention as an interventive model for HIV risk reduction in gay and bisexual men.
Despite considerable self-initiated HIV risk reduction among men who have sex with men, little is known about how to design interventions that will effectively assist individuals from this population in maintaining safer sex behaviors over time. The present study evaluated the effectiveness of a 17-session group counseling intervention that incorporated components based on a cognitive-behavioral model of relapse. Differential behavioral outcomes following treatment included an increase in the percentage of sexual activities that were protected and a decrease in unprotected oral sex. However, considerable risk reduction (e.g., increased condom use, decreased unprotected sex, and decreases in the number of male partners and in the total number of sexual acts) occurred in both treated and untreated participants. Measures of mediating attitudinal variables drawn from relapse prevention theory largely predicted behavioral changes. Over time, several of the risk reduction behaviors achieved at posttreatment were not maintained, suggesting the importance of further developing effective strategies for supporting behavior change maintenance.
Adult↗