Partial hospitalization for borderline personality disorder.
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Borderline Personality Disorder↗
Biomedical subjects
R Stern
Publications and source records attributed to R Stern.
Characterisation of a cluster of genes encoding Theileria annulata AT hook DNA-binding proteins and evidence for localisation to the host cell nucleus.
Infection of bovine leukocytes by the apicomplexan parasite Theileria annulata results in alteration of host cell gene expression and stimulation of host cell proliferation. At present, the parasite-derived factors involved in these processes are unknown. Recently, we described the characterisation of a parasite gene (TashAT2), whose polypeptide product bears AT hook DNA-binding motifs and may be transported from the parasite to the host nucleus. We now describe the isolation of a further two genes (TashAT1 and TashAT3) that are very closely related to TashAT2. All three TashAT genes are located together in a tight cluster, interspersed by two further small open reading frames, all facing head to tail. TashAT2 was shown to be expressed in all T. annulata cell lines examined, whereas TashAT1 and TashAT3 were expressed in the sporozoite stage of the parasite, and also in infected cell lines, where their expression was found to vary between different cell lines. Evidence for transport was provided by antisera raised against TashAT1 and TashAT3 that reacted with the host nucleus of T. annulata-infected cells. Reactivity was particularly strong against the host nuclei of the T. annulata-infected cloned cell line D7B12, which is attenuated for differentiation. A polypeptide in the size range predicted for TashAT3 was preferentially detected in host enriched D7B12 nuclear extracts. DNA-binding analysis demonstrated that fusion proteins containing the AT hook region of either TashAT1 or TashAT2 bound preferentially to AT rich DNA.
AT Rich Sequence↗
Total elbow replacement for complex fractures of the distal humerus. An option for the elderly patient.
The treatment of multifragmentary, intra-articular fractures of the distal humerus is difficult, even in young patients with bone of good quality, but is worse in elderly patients who have varying degrees of osteopenia. We have evaluated the functional outcome of primary total elbow replacement (TER) in the treatment of these fractures in ten elderly patients followed for a minimum of one year. There were no complications in regard to the soft tissues, bone or prosthesis. The mean range of flexion obtained was 125 degrees (110 to 140) and loss of extension was 23.5 degrees (0 to 50). The mean Mayo score was 94 points (80 to 100) and patient satisfaction was high. We feel that TER provides an alternative to open reduction and internal fixation in the management of these complicated fractures in the elderly.
Age Factors↗
Hyaluronidase activity and hyaluronidase inhibitors. Assay using a microtiter-based system.
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Animals↗
Detecting hyaluronidase and hyaluronidase inhibitors. Hyaluronan-substrate gel and -inverse substrate gel techniques.
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Animals↗
Beneficial effects of pravastatin (+/-colestyramine/niacin) initiated immediately after a coronary event (the randomized Lipid-Coronary Artery Disease [L-CAD] Study).
Secondary prevention of coronary heart disease by antilipidemic therapy beginning at > or =3 months after an acute coronary syndrome is well documented. The impact, however, of immediate initiation of antilipidemic therapy on coronary stenoses and clinical outcome in patients with acute coronary syndrome is unknown. In our study, patients were randomized, on average, 6 days after an acute myocardial infarction and/or percutaneous transluminal coronary angioplasty secondary to unstable angina, to pravastatin (combined, when necessary, with cholestyramine and/or nicotinic acid) to achieve low-density lipoprotein cholesterol levels of < or =130 mg/dl (group A, n = 70). In controls (group B, n = 56), antilipidemic therapy was determined by family physicians. Quantitative coronary angiography was performed at inclusion, and at 6- and 24-month follow-up. The combined clinical end points were total mortality, cardiovascular death, nonfatal myocardial infarction, need for coronary intervention, stroke, and new onset of peripheral vascular disease. Minimal lumen diameter in group A increased by 0.05 +/- 0.20 mm after 6 months and 0.13 +/- 0.29 mm after 24 months, whereas it decreased by 0.08 +/- 0.20 mm and 0.18 +/- 0.27 mm, respectively, in group B (p = 0.004 at 6 months and p <0.001 at 24 months). After 2 years, 29 patients of 56 patients in group B, but only 16 of 70 patients in group A, experienced a clinical end point (p = 0.005; odds ratio 0.28, confidence intervals 0.13 to 0.6). We conclude that pravastatin-based therapy initiated immediately after an acute coronary syndrome is well tolerated and safe, lessens coronary atherosclerosis, and has a pronounced clinical benefit.
Adult↗
Biosynthesis of the galactan component of the mycobacterial cell wall.
The structural core of the cell walls of Mycobacterium spp. consists of peptidoglycan bound by a linker unit (-alpha-L-Rhap-(1-->3)-D-GlcNAc-P-) to a galactofuran, which in turn is attached to arabinofuran and mycolic acids. The sequence of reactions leading to the biogenesis of this complex starts with the formation of the linker unit on a polyprenyl-P to produce polyprenyl-P-P-GlcNAc-Rha (Mikusová, K., Mikus, M., Besra, G. S., Hancock, I., and Brennan, P. J. (1996) J. Biol. Chem. 271, 7820-7828). We now establish that formation of the galactofuran takes place on this intermediate with UDP-Galf as the Galf donor presented in the form of UDP-Galp and UDP-Galp mutase (the glf gene product) and is catalyzed by galactofuranosyl transferases, one of which, the Mycobacterium tuberculosis H37Rv3808c gene product, has been identified. Evidence is also presented for the growth of the arabinofuran on this polyprenyl-P-P-linker unit-galactan intermediate catalyzed by unidentified arabinosyl transferases, with decaprenyl-P-Araf or 5-P-ribosyl-PP as the Araf donor. The product of these steps, the lipid-linked-LU-galactan-arabinan has been partially characterized in terms of its heterogeneity, size, and composition. Biosynthesis of the major components of mycobacterial cell walls is proving to be extremely complex. However, partial definition of arabinogalactan synthesis, the site of action of several major anti-tuberculosis drugs, facilitates the present day thrust for new drugs to counteract multiple drug-resistant tuberculosis.
Cell Wall↗
Evidence that the serum inhibitor of hyaluronidase may be a member of the inter-alpha-inhibitor family.
A study of the uncharacterized serum inhibitors of hyaluronidase, first described half a century ago, was undertaken. Activity was measured against bovine testicular hyaluronidase using a microtiter-based assay and reverse hyaluronan substrate gel zymography. The predominant inhibitory activity was magnesium-dependent and could be eliminated by protease or chondroitinase digestion and by heat treatment. Kinetics of inhibition were similar against hyaluronidases from testis and snake and bee venoms. The inhibitor had no effect on Streptomyces hyaluronidase, indicating that inhibition was not through protection of the hyaluronan substrate. Inhibition levels in serum were increased in mice following carbon tetrachloride or interleukin-1 injection, inducers of the acute-phase response. Reverse zymography identified a predominant band of 120-kDa relative molecular size, with two bands of greater and one of smaller size. The predominant protein was tentatively identified as a member of the inter-alpha-inhibitor family. Inhibition was also observed using either purified inter-alpha-inhibitor or an inter-alpha-inhibitor-related 120-kDa complex. Inter-alpha-inhibitor, found in the hyaluronan-rich cumulus mass surrounding mammalian ova and the coat of fibroblasts and mesothelial cells, may function to stabilize such matrices by protecting against hyaluronidase degradation. Turnover of circulating hyaluronan is extraordinarily rapid, with a half-life of 2-5 min. Prompt increases in levels of serum hyaluronan occur in patients with shock, septicemia, or massive burns, increases that can be attributed, in part, to suppression of degradation by these acute-phase reactants, the inhibitors of hyaluronidase.
Alpha-Globulins↗
HYAL1LUCA-1, a candidate tumor suppressor gene on chromosome 3p21.3, is inactivated in head and neck squamous cell carcinomas by aberrant splicing of pre-mRNA.
The hyaluronidase first isolated from human plasma, Hyal-1, is expressed in many somatic tissues. The Hyal-1 gene, HYAL1, also known as LUCA-1, maps to chromosome 3p21.3 within a candidate tumor suppressor gene locus defined by homozygous deletions and by functional tumor suppressor activity. Hemizygosity in this region occurs in many malignancies, including squamous cell carcinomas of the head and neck. We have investigated whether cell lines derived from such malignancies expressed Hyal-1 activity, using normal human keratinocytes as controls. Hyal-1 enzyme activity and protein were absent or markedly reduced in six of seven carcinoma cell lines examined. Comparative genomic and fluorescence in situ hybridization identified chromosomal deletions of one allele of HYAL1 in six of seven cell lines. Initial RT - PCR analyses demonstrated marked discrepancies between levels of HYAL1 mRNA and protein. Despite repeated sequence analyses, no mutations were found. However, two species of transcripts were identified when primers were used that included the 5' untranslated region. The predominant mRNA species did not correlate with protein translation and contained a retained intron. A second spliced form lacking this intron was found only in cell lines that produced Hyal-1 protein. Inactivation of HYAL1 in these tumor lines is a result of incomplete splicing of its pre-mRNA that appears to be epigenetic in nature. Oncogene (2000) 19, 870 - 877.
Alternative Splicing↗
Induction of resistance to diabetes in non-obese diabetic mice by targeting CD44 with a specific monoclonal antibody.
Inflammatory destruction of insulin-producing beta cells in the pancreatic islets is the hallmark of insulin-dependent diabetes mellitus, a spontaneous autoimmune disease of non-obese diabetic mice resembling human juvenile (type I) diabetes. Histochemical analysis of diabetic pancreata revealed that mononuclear cells infiltrating the islets and causing autoimmune insulitis, as well as local islet cells, express the CD44 receptor; hyaluronic acid, the principal ligand of CD44, is detected in the islet periphery and islet endothelium. Injection of anti-CD44 mAb 1 hr before cell transfer of diabetogenic splenocytes and subsequently on alternate days for 4 weeks induced considerable resistance to diabetes in recipient mice, reflected by reduced insulitis. Contact sensitivity to oxazolone was not influenced by this treatment. A similar antidiabetic effect was observed even when the anti-CD44 mAb administration was initiated at the time of disease onset: i.e., 4-7 weeks after cell transfer. Administration of the enzyme hyaluronidase also induced appreciable resistance to insulin-dependent diabetes mellitus, suggesting that the CD44-hyaluronic acid interaction is involved in the development of the disease. These findings demonstrate that CD44-positive inflammatory cells may be a potential therapeutic target in insulin-dependent diabetes.
Animals↗
Reverse hyaluronan substrate gel zymography procedure for the detection of hyaluronidase inhibitors.
Little is known of the ubiquitous inhibitors of hyaluronidase, molecules that may be important for the deposition of hyaluronan. A reverse hyaluronan-substrate gel procedure is described here that detects such inhibitors, even in crude biological extracts, and is independent of the catalytic mechanism of the target enzyme. Following electrophoresis, hyaluronan-containing gels are incubated in a hyaluronidase solution. Alcian blue-staining bands indicate hyaluronan protected from degradation and the location of hyaluronidase inhibitors. Coordinated use of hyaluronan substrate gel and reverse substrate gel procedures provides estimates of the number and relative molecular sizes of both enzymes and their inhibitors.
Animals↗
Topical hyaluronidase decreases hyaluronic acid and CD44 in human skin and in reconstituted human epidermis: evidence that hyaluronidase can permeate the stratum corneum.
Hyaluronic acid (HA), a high molecular weight glycosaminoglycan of the extracellular matrix involved in growth, inflammation and wound healing, also contributes to the hydration and plastic properties of skin. Several drug and cosmetic formulations contain HA. We have initiated investigations that explore whether it is possible, by topical application, to modulate endogenous HA levels in skin. We developed a model epidermal culture system that exhibited a differentiated stratum corneum, and expressed HA and the HA receptor CD44, in a pattern similar to that observed in intact skin. Such in vitro skin equivalents are useful models for investigating the effect of topical drugs. HA and bacterial hyaluronidase were applied to the in vitro skin equivalent and to human skin. Their effects on endogenous HA and CD44 expression were examined using histochemical analysis. Topical HA treatment had no significant effect on HA or CD44 expression in either system. However, hyaluronidase decreased HA and CD44 expression in a dose-dependent manner in both the epidermal culture system and in skin. Apparently, HA is not able to permeate the epidermal culture system or human skin to a significant degree, but bacterial hyaluronidase does permeate both human skin and the culture system, depleting HA and decreasing CD44 expression. These effects were more prominent in the dermal than in the epidermal layers, suggesting that marked differences in HA metabolism exist in these two skin compartments. The ability of hyaluronidase to permeate the stratum corneum suggests that topical application may, additionally, be useful as a clinical modality.
Adult↗
Reduced hyaluronan in keloid tissue and cultured keloid fibroblasts.
Extracellular matrix hyaluronan is prominent during wound healing, appearing at elevated levels early in the repair process. It is prevalent throughout the course of fetal wound healing, which is scar-free, but decreases late in adult wound repair, that is often marked by scarring. To determine whether aberrant hyaluronan metabolism is associated with the excessive scarring that characterizes keloids, cultured fibroblasts derived from keloids and from the dermis of normal human skin and scar were compared. Levels of hyaluronan in 48 h conditioned media of keloid-derived cultures were significantly lower than in cultures of normal skin and scar fibroblasts. Profiles of hyaluronan polymer size were comparable in these two cell types, suggesting that excessive hyaluronan degradation was not involved. Hydrocortisone decreased hyaluronan levels approximately 70% in the conditioned media of both keloid and normal fibroblasts. Diminished hyaluronan accumulation in keloid-derived cells compared with normal fibroblasts was also observed in an in vitro wound healing model. Histolocalization of hyaluronan in keloids, normal skin, and scar samples confirmed the biochemical observations that the dermis of keloids, which comprises most of the scar tissue, contained markedly diminished levels of hyaluronan. Alterations in hyaluronan in the epidermis overlying keloids, however, were also observed. A modest increase in hyaluronan staining intensity was observed in the epidermis of keloids, as well as changes in the patterns of distribution within the epidermis, compared with that in normal skin and scar. Increased hyaluronan was present in the granular and spinous layers of the keloid epidermis Abnormalities are present apparently in both the overlying epidermis as well as in the dermis of keloids. Aberrations in signaling between keloid stroma and keloid epidermis may underlie abnormalities that contribute to the excessive fibrosis characteristic of these lesions.
Adolescent↗
Diurnal, weekly and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases.
AIMS: Several studies have reported circadian and seasonal variations in acute cardiovascular disease. In addition, a weekly variation has been observed in acute myocardial infarction. The aim of our study was to determine the circadian weekly, and seasonal variations of sudden death utilizing population-based data. METHODS AND RESULTS: We analysed the emergency medical system data of Berlin (West) from 1987-1991 with respect to all consecutive sudden deaths in subjects >18 years (n=24 061). There was a marked circadian variation of sudden death, with a minimum between 0 and 6 h and a maximum between 6 and 12 h (P<0.0001) for every day of the week. A minimum of events occurred on Sundays (n=3143), and a maximum on Mondays (n=3721), corresponding to a relative increase of 18.3% (P<0.0001). The increase was more pronounced (23.6%) in patients < or =65 than in patients >65 (15.7%). In addition, we found a significant seasonal variation (P<0.0001) in events, with a maximum during winter (December to February, n=6493), and a minimum during summer (June to August, n=5472), corresponding to a relative difference of 18.7%. The seasonal variation was more pronounced in patients >65 years. CONCLUSION: The present analyses demonstrate marked variations in the occurrence of sudden death with peaks during morning hours, on Mondays, and during winter months. The findings suggest that the onset of sudden death may be associated with endogenous rhythms and external factors including climatic conditions.
Adult↗
U-Pb Geochronologic, Nd Isotopic, and Geochemical Evidence for the Correlation of the Chopawamsic and Milton Terranes, Piedmont Zone, Southern Appalachian Orogen.
We report U-Pb crystallization ages from four metavolcanic rocks and two granitic gneiss samples as well as whole-rock chemical analyses and Sm-Nd isotopic ratios from 25 metaigneous and metasedimentary rocks from the Chopawamsic and Milton terranes, southern Appalachian Orogen. A metarhyolite sample from the Chopawamsic Formation and a metabasalt sample from the Ta River Formation in the Chopawamsic terrane have indistinguishable U-Pb crystallization ages of 471.4+/-1.3 Ma and 470.0+1.3/-1.5 Ma, respectively. A sample from the Prospect granite that intruded metavolcanic rocks of the Ta River Formation yields a younger U-Pb date of 458.0+/-1 Ma. Metarhyolite and granitic gneiss samples from the northern part of the Milton terrane yield U-Pb dates of 458.5+3.8/-1.0 Ma and 450+/-1.8 Ma, respectively. Metavolcanic and metaplutonic rocks from both terranes span a range in major element composition from basalt to rhyolite. Trace element concentrations in these samples show enrichment in large-ion lithophile elements K, Ba, and Rb and depletion in high field strength elements Ti and Nb, similar to those from island arc volcanic rocks. Initial epsilon(Nd) values and T(DM) ages of the metaigneous and metasedimentary samples range from 0.2 to -7.2 and from 1200 to 1700 Ma for the Chopawamsic terrane and from 3.7 to -7.2 and from 850 to 1650 Ma for the Milton terrane. The crystallization ages for the metavolcanic and metaplutonic samples from both terranes indicate that Ordovician magmatism occurred in both. Similar epsilon(Nd) values from representative samples from both terranes suggest that both were generated from an isotopically similar source. Xenocrystic zircons from metavolcanic rocks in the Chopawamsic terrane have predominately Mesoproterozoic (207)Pb/(206)Pb ages (600-1300 Ma), but a single Archean (2.56 Ga) core was also present. The xenocrystic zircons and the generally negative epsilon(Nd) values indicate that both terranes are composed of isotopically evolved continental crust.
Journal Article↗
Evidence that hyaluronidase is not involved in tissue invasion of the protozoan parasite Entamoeba histolytica.
As previous reports suggested that a hyaluronidase is involved in tissue invasion of Entamoeba histolytica, we searched for such an activity in trophozoite extracts. A hyaluronidase activity was not detectable in long-term cultures or in amoebae freshly passaged through a gerbil liver, as evidenced by four different techniques.
Animals↗
A role for hyaluronan in macrophage accumulation and collagen deposition after bleomycin-induced lung injury.
Elevated concentrations of hyaluronan (HA) are associated with the accumulation of macrophages in the lung after injury. We have investigated the role of HA in the inflammatory and fibrotic responses to lung injury using the intratracheal instillation of bleomycin in rats as a model. After bleomycin-induced lung injury, both HA content in bronchoalveolar lavage (BAL) and staining for HA in macrophages accumulating in injured areas of the lung were maximal at 4 d. Increased HA in BAL correlated with increased locomotion of isolated alveolar macrophages. HA-binding peptide was able to specifically block macrophage motility in vitro. Importantly, systemic administration of HA-binding peptide to rats before injury not only decreased alveolar macrophage motility and accumulation in the lung, but also reduced lung collagen alpha (I) messenger RNA and hydroxyproline contents. We propose a model in which HA plays a critical role in the inflammatory response and fibrotic consequences of acute lung injury.
Amino Acid Sequence↗
Vagal changes following cancer chemotherapy: implications for the development of nausea.
Many physiological changes that occur contemporaneously with nausea are mediated by the autonomic nervous system, but the specific autonomic changes associated with nausea have not been characterized. Cardiac parasympathetic (vagal) activity as indicated by heart rate variability, measured as the standard deviation of successive differences (SDSD) in beat-to-beat intervals, was assessed in 24 women with ovarian cancer immediately prior to and accompanying nausea that occurred following anticancer chemotherapy. A progressive increase in SDSD followed infusion of the chemotherapy agent, indicating a rise in cardiac parasympathetic (vagal) activity, with onset of nausea consistently occurring after the peak activity had been reached, at a time when SDSD was decreasing. An increase in parasympathetic activity seems to set the stage for the expression of nausea but an additional stimulus is apparently needed to finally trigger the event.
Aged↗