Glandular tularemia with typhoidal features in a Manitoba child.
Explore the source record for details and available documents.
Disease Outbreaks↗
Biomedical subjects
H Jacobs
Publications and source records attributed to H Jacobs.
T cell receptor-alpha beta lacking the beta-chain V domain can be expressed at the cell surface but prohibits T cell maturation.
A TCR-beta gene lacking V domain sequences (delta V-TCR-beta) was inserted into the germline of mice. Expression of the transgene inhibited endogenous TCR-beta, but not TCR-alpha gene rearrangement and expression. The mutated TCR-beta gene affected alpha beta T cell development: the common thymocyte pool was normal in cell number, with cells expressing CD4 and CD8, but the mature, "CD3bright" population expressing either CD4 or CD8 molecules was reduced by 90%. To help understand these effects on TCR-beta gene rearrangement and T cell development, biosynthesis of the delta V-TCR-beta protein was analyzed in a tumor cell line derived from a transgenic mouse. Despite absence of the V domain, the delta V-TCR-beta chain paired with endogenous TCR-alpha chains and assembled with CD3 gamma, -delta, -epsilon, and -zeta components in the endoplasmatic reticulum, followed by transport through the Golgi complex to the plasma membrane. Therefore, assembly of the complex, and even cell surface expression, may be relevant for allelic exclusion of the TCR-beta gene. In the common thymocyte population, the CD3 components, endogenous TCR-alpha, and the delta V-TCR-beta gene product were expressed at the RNA level, but endogenous TCR-beta was not. The TCR-alpha delta beta/CD3 complex was present at the cell surface at low levels and was functional in terms of anti-CD3-induced Ca2+ mobilization. The observed arrest of alpha beta T cell development at the CD4+8+ thymocyte stage indicates that ligand recognition by the TCR, with contribution of the beta-chain V domain, is not required for transition of CD4-8- thymocytes to the CD4+8+ phenotype, but necessary for entry into the "single positive," CD3bright differentiation stage.
Animals↗
Blood compatibility of SPUU-PEO-heparin graft copolymers.
Biological responses to heparinized segmented polyurethaneurea (SPUU-PEO-Heparin) were evaluated in vitro and ex vivo. In vitro assays involved plasma protein adsorption, platelet adhesion, and release reaction studies. In addition, an ex vivo rabbit arterio-artery (A-A) shunt experiment was also performed to measure occlusion times of the heparinized surfaces. All SPUU-PEO-Heparin surfaces demonstrated less protein adsorption than Biomer and protein adsorption patterns similar to SPUU-PEO surfaces. Platelet adhesion and release studies demonstrated that both SPUU-PEO-Heparin and SPUU-PEO surfaces adsorbed less platelets and inhibited platelet release, as compared to Biomer. These findings correlated with reduction in protein adsorption observed for the modified surfaces. In low flow rate ex-vivo A-A shunt experiments, all heparinized surfaces prolonged occlusion time longer than controls. However, SPUU-PEO surfaces did not prolong occlusion time when compared to Biomer, although these surfaces suppressed protein adsorption and platelet interaction in vitro. The improved blood compatibility of SPUU-PEO-Heparin surfaces attest to the usefulness of this approach in improving the blood compatibility of blood contacting surfaces.
Adsorption↗
Collaboration of pim-1 and bcl-2 in lymphomagenesis.
Explore the source record for details and available documents.
Animals↗
A randomized placebo controlled trial on the effects of simvastatin, a HMG-CoA reductase inhibitor, on blood lipids and fibrinolytic parameters.
Coronary artery disease is frequently associated with disturbed blood lipids and with a deficient blood fibrinolytic capacity. In order to investigate a possible link between hypercholesterolemia and hypofibrinolysis, we have investigated the effect of simvastatin, a HMG-CoA reductase inhibitor, on blood lipids and fibrinolytic parameters in a double blind, randomized, placebo controlled study design. Twenty-four male patients, aged between 42 and 65 years, with angiographically confirmed coronary artery disease, were selected from a series of 731 consecutive patients on the basis of a fasting serum cholesterol level of more than 250 mg/dl and a plasma PAI-1 level of more than 60 ng/ml. Patients were randomly assigned to 20 mg of simvastatin daily (Group I), or placebo (Group II), for four weeks, followed by doubling of the dose for another four weeks. Blood samples were obtained at baseline and at 4 and 8 weeks. Groups I and II did not differ significantly at baseline. As expected, simvastatin produced a significant reduction in serum levels of total cholesterol (33 +/- 12 and 36 +/- 12 percent, mean +/- SD, after 4 and 8 weeks respectively, p less than 0.001 vs baseline), LDL-cholesterol (36 +/- 5 and 43 +/- 6 percent respectively, p less than 0.001 vs baseline) and apolipoprotein-B (20 +/- 29 and 23 +/- 30 percent respectively, p less than 0.05 vs baseline), whereas these parameters did not change significantly in the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Polycystic ovary syndrome and bulimia.
One hundred fifty-three patients classified as suffering from polycystic ovarian syndrome (PCOS) and 109 patients who were suffering from a clear organic disorder or endocrinopathy received the bulimia investigation test (Edinburgh) (BITE) questionnaire for abnormal eating behaviors. Patients with PCOS showed a significant increase in their mean BITE score for approximately a third had abnormal eating patterns, and 6% have scores suggestive of clinical bulimia compared with only 1% of women in the group with organic endocrinopathies. The work suggests that women with PCOS should be screened for abnormal eating behaviors and raises the possibility that treatment by psychological means should be considered when abnormal eating behaviors are present.
Analysis of Variance↗
Mutations in the major histocompatibility complex class I antigen-presenting groove affect both negative and positive selection of T cells.
In several transgenic mouse models T cell development was shown to be controlled by the binding of the alpha/beta T cell receptor (TcR) to ligands in the thymus. In transgenic mice expressing a male-specific TcR alpha/beta, the presence of the restricting D major histocompatibility complex (MHC) molecule plus the male specific peptide deleted thymocytes at an early stage of development. On the other hand, maturation of T cells required an interaction of the TcR with the thymic D MHC molecules in the absence of specific peptides. This could imply that negative and positive selection of this receptor are affected differently by mutations in the HY peptide-binding groove of the D MHC molecule. Such mutants have been isolated and were shown to affect the response to HY antigen in that both the bm14 (residue Glu70----Asp) and the bm13 (residue Leu114----Glu, Phe116----Tyr and Glu119----Asp) strains do not normally mount cytotoxic responses to male cells. Here we show that these mutations affect antigenicity of male cells, as well as negative and positive selection of T cells in TcR alpha/beta transgenic mice.
Animals↗
Cavernous sinus involvement in recurrent Nelson's syndrome.
Nelson's syndrome is rare and difficult to cure. The tumours in this condition may behave invasively and require multiple interventions. Two patients who had been followed up for nearly 20 years developed signs of cavernous sinus involvement, one with an empty sella. Long term follow-up for such patients is emphasized.
Adult↗
Synthesis and characterization of poly(dimethylsiloxane)-poly(ethylene oxide)-heparin CBABC type block copolymers.
Heparin and poly(ethylene oxide) were coupled to a central anchoring block of poly(dimethylsiloxane) in order to investigate its blood compatible properties. Diamino telechelic poly(dimethylsiloxane) (PDMS-(NH2)2, Mw = 20,000) was first modified to isocyanate functionalities using toluene 2,4-diisocyanate. This modified PDMS was then coupled to diamino-telechelic poly(ethylene oxide) (PEO-(NH2)2, Mw = 2000, 4000, 6000) to create BAB type copolymers having terminal free amino groups. These amino groups were covalently coupled to heparin containing terminal aldehyde groups using sodium cyanoborohydride to yield a bioactive, CBABC type block copolymer. The physical characterization of these copolymers was performed with IR, NMR, sulphur elemental analysis, Wilhelmy plate contact angle, and differential scanning calorimetry (DSC). CBABC block copolymer surfaces demonstrated heparin bioactivity in in vitro evaluation, and improved nonthrombogenic properties during ex vivo A-A shunt experiments.
Animals↗
Influence of monoclonal IgM cold agglutinins on adhesiveness, phagocytosis, and bactericidal activity on human granulocytes and monocytes.
Monoclonal IgM cold agglutinins (CA) bind and, in the presence of complement, are cytotoxic to various mammalian cells. The impact of these autoantibodies on functional capacity of phagocytes has not been studied until now. Herein we report that sera with monoclonal IgM anti-I and anti-i CA significantly reduce adhesiveness, phagocytosis, phagocytic index, and intracellular bactericidal activity of human peripheral blood polymorphonuclear cells (PMNs) at 37 degrees C and 24 degrees C. Anti-i CA were more active than anti-I. Sera with monoclonal IgMs without CA activity reduced the total number of ingested bacteria but otherwise had no effect on phagocytic functions. There was no difference in the degree of inhibition when anti-i and anti-I CA were tested against cord, maternal, and adult PMNs. Chromatographically purified a-I and a-i CA inhibited markedly phagocytosis in concentrations as low as 1 mg/ml. Phagocytic activity of peripheral blood monocytes was inhibited by CA at 18 degrees C but not at 24 degrees C or 37 degrees C. Pepsin digestion or reduction and alkylation of chromatographically pure IgM CA abolished completely their inhibitory activity. Thus, in physiological temperatures, monoclonal IgM cold agglutinins impair various phagocytic functions of human phagocytes. It may add to the susceptibility to infections in patients in which such autoantibodies are synthesized.
Agglutinins↗
The primary structure of a feline class I gene: striking similarity to HLA-A.
The sequence of a feline class I pseudogene and its comparison with class I genes from other species is presented. The gene isolated is a pseudogene because of the presence of four stop codons and two frame shift mutations in the first- and second-domain encoding exons, as well as a mutation in a splice acceptor site in the third intron. By sequence comparison with the other class I sequences determined to date, the FLA pseudogene is most closely related to the HLA-A locus products (88% nucleotide identity.
Amino Acid Sequence↗
Surface modification for improved blood compatibility.
Several surface modification techniques are currently being used to improve the biocompatibility of blood-contacting devices. These include the immobilization of bioactive materials to prevent thrombus generation and platelet activation, the incorporation of hydrophilic grafts onto practical hydrophobic surfaces (polyurethanes) to reduce protein adsorption, and the concept of microdomain-phase separated surfaces to regulate cellular and protein adhesion.
Animals↗
Phospholipase A2 activity associated with synovial fluid cells.
High activity of phospholipase A2 (PLA2) has been detected in synovial fluids (SF) in inflammatory arthritides. Since the source(s) of SF PLA2 has not been identified, we tested PLA2 content in SF cells obtained from 11 SF. Cell sonicates were prepared at 5 X 10(6) cells/ml. In the supernatants of the sonicated SF cells (n = 11), PLA2 activity ranged from 38-755 U/ml, mean 368 +/- 243 (SD) U/ml, compared to 5-64 U/ml, mean 31 +/- 15 (SD) U/ml in sonicates of normal peripheral blood PMN (n = 5) (p less than 0.0001). Spontaneous release of PLA2 from unstimulated SF cells ranged from 26-365 U/ml, mean 131 +/- 144 (SD) U/ml (n = 5), whereas spontaneous release from peripheral blood PMN was negligible. Neither 10(-8) M FMLP nor 5 X 10(-6) M dexamethasone altered extracellular PLA2 release. To assess whether PLA2 adsorbs passively to cell membranes through hydrophobic interaction, normal peripheral PMN were incubated in crude SF (n = 7) with PLA2 ranging from 4,000-24,300 U/ml, or with purified human SF PLA2 or Naja naja PLA2. We found that soluble PLA2 adsorbed to PMN membranes in a concentration dependent fashion. PLA2 activity in sonicates of PMN incubated in crude SF ranged from 185-358 U/ml compared to controls of 21-64 U/ml. Sonicates of PMN incubated with purified human SF PLA2 (5,000-30,000 U/ml) showed progressive concentration dependent increase in PLA2 from 7 +/- 4 to 212 +/- 11 (SD) U/ml (p less than 0.001). PMN incubated with Naja naja PLA2 also showed marked increase in the content of PLA2.(ABSTRACT TRUNCATED AT 250 WORDS)
Adsorption↗
Experiences with interstitial HDR afterloading therapy in genital and breast cancer.
Explore the source record for details and available documents.
Brachytherapy↗
Cryptic cold agglutinin activity of monoclonal macroglobulins.
One hundred and twenty sera with monoclonal immunoglobulin M's (IgM's) were tested for cryptic cold agglutinin activity against papain- and neuraminidase-treated adult and cord red blood cells (RBC). Fifteen sera (12.5%) agglutinated papain-treated RBC. Fourteen of these 15 sera also agglutinated neuraminidase-treated RBC. Ten additional sera agglutinated neuraminidase-treated but not papain-treated cells. Three patterns were observed among agglutinators of papain-treated RBC: either predominant agglutination of adult RBC, or of cord RBC or equal reaction, thus resembling I, i and non-Ii patterns of conventional cold agglutinins. We propose to call these patterns, tentatively, Icr (cr for cryptic), icr, and non-Iicr, respectively. Purified monoclonal IgM's retained the above patterns. Eluates from enzyme-treated cells contained monoclonal IgM's. Investigation of neuraminidase-treated RBC has shown that in distinction to T-anti-T system (Thomsen-Friedenreich receptor system), the majority of sera with monoclonal IgM's agglutinated more strongly adult RBC, and some agglutinated more strongly cord RBC. There was no loss of agglutinating activity after repeat freezing and thawing of the sera. Thus, it seems that monoclonal IgM's which react with neuraminidase-treated RBC detect antigenic determinants different from the T antigen. Cryptic CA activity of IgM's should be added to the list of antibody activities of these monoclonal immunoglobulins.
Adult↗
Nonthrombogenic bioactive surfaces.
Explore the source record for details and available documents.
Alprostadil↗
In vitro bioactivity of a synthesized prostaglandin E1-heparin conjugate.
A covalently bound conjugate of commercial grade heparin and prostaglandin E1 (PGE1) was synthesized to provide the dual pharmacological role of decreasing the extent of platelet aggregation and inhibiting fibrin formation during thrombogenesis. The compound was synthesized using a modified mixed carbonic anhydride method of amide bond formation between the carboxylic acid moiety of PGE1 and a primary amine group on heparin. Quantitation of coupling was measured spectrophotometrically by monitoring a degradation product of the prostaglandin E1-heparin conjugate (prostaglandin B1-heparin conjugate). Bioactivity tests on the conjugates (activated partial thromboplastin time and platelet aggregation) confirmed that both the anticoagulant activity of heparin and the inhibitory effect of PGE1 on platelet aggregation were maintained.
Alprostadil↗
Hemodynamic effects of high frequency ventilation in surfactant-treated preterm lambs.
We compared the hemodynamic status and left ventricular (LV) performance in 7 twin pairs of preterm lambs delivered at 124 days gestational age (83% of term gestation) and ventilated by either conventional ventilation (CV) or high frequency ventilation (HFV) at 15 Hz. The lambs were treated with suspensions of natural sheep surfactant to permit ventilation and survival, and ventilatory settings were adjusted to maintain physiologic blood gas values. The ductus arteriosus was occluded with a balloon catheter at 40-45 min of age to eliminate the variable of a left to right ductal shunt. Cineangiocardiographic, pressure, and blood flow measurements were made 1 and 2 h after ductal occlusion. At the same mean airway pressures, the heart rates, LV end-diastolic volumes, and mean arterial pressures were similar in both groups. LV stroke volumes, ejection fractions, LV outputs, and organ blood flows also did not differ between the two groups. When compared with CV, HFV provides comparable ventilation with no apparent deleterious hemodynamic effects in preterm surfactant-treated lambs with occluded ductus arteriosus.
Acid-Base Equilibrium↗