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J Thompson

Publications and source records attributed to J Thompson.

At least 73 records · Page 4Linked to original sources
PubMed2001

Plasmodium falciparum homologue of the genes for Plasmodium vivax and Plasmodium yoelii adhesive proteins, which is transcribed but not translated.

The 235-kDa family of rhoptry proteins in Plasmodium yoelii and the two reticulocyte binding proteins of P. vivax comprise a family of proteins involved in host cell selection and erythrocyte invasion. Here we described a member of the gene family found in P. falciparum (PfRH3) that is transcribed in its entirety, under stage-specific control, with correct splicing of the intron, but appears not to be translated, probably due to two reading frameshifts at the 5' end of the gene.

Amino Acid Sequence↗
PubMed2001

Regulation of the glv operon in Bacillus subtilis: YfiA (GlvR) is a positive regulator of the operon that is repressed through CcpA and cre.

Maltose metabolism and the regulation of the glv operon of Bacillus subtilis, comprising three genes, glvA (6-phospho-alpha-glucosidase), yfiA (now designated glvR), and glvC (EIICB transport protein), were investigated. Maltose dissimilation was dependent primarily upon the glv operon, and insertional inactivation of either glvA, glvR, or glvC markedly inhibited growth on the disaccharide. A second system (MalL) contributed to a minor extent to maltose metabolism. Northern blotting revealed two transcripts corresponding to a monocistronic mRNA of glvA and a polycistronic mRNA of glvA-glvR-glvC. Primer extension analysis showed that both transcripts started at the same base (G) located 26 bp upstream of the 5' end of glvA. When glvR was placed under control of the spac promoter, expression of the glv operon was dependent upon the presence of isopropyl-beta-D-thiogalactopyranoside (IPTG). In regulatory studies, the promoter sequence of the glv operon was fused to lacZ and inserted into the amyE locus, and the resultant strain (AMGLV) was then transformed with a citrate-controlled glvR plasmid, pHYCM2VR. When cultured in Difco sporulation medium containing citrate, this transformant [AMGLV(pHYCM2VR)] expressed LacZ activity, but synthesis of LacZ was repressed by glucose. In an isogenic strain, [AMGLVCR(pHYCM2VR)], except for a mutation in the sequence of a catabolite-responsive element (cre), LacZ activity was expressed in the presence of citrate and glucose. Insertion of a citrate-controlled glvR plasmid at the amyE locus of ccpA(+) and ccpA mutant organisms yielded strains AMCMVR and AMCMVRCC, respectively. In the presence of both glucose and citrate, AMCMVR failed to express the glv operon, whereas under the same conditions high-level expression of both mRNA transcripts was found in strain AMCMVRCC. Collectively, our findings suggest that GlvR (the product of the glvR gene) is a positive regulator of the glv operon and that glucose exerts its effect via catabolite repression requiring both CcpA and cre.

Bacillus subtilis↗
PubMed2001

Evidence for early local viral replication and local production of antiviral immunity upon mucosal simian-human immunodeficiency virus SHIV(89.6) infection in Macaca nemestrina.

Transmission of human immunodeficiency virus type 1 (HIV-1) is largely a result of heterosexual exposure, leading many investigators to evaluate mucosal vaccines for protection against intravaginal (i.vag.) transmission in macaque models of AIDS. Relatively little is known, however, about the dynamics of viral replication and the ensuing immune response following mucosal infection. We have utilized a simian-human immunodeficiency virus (SHIV) to study the differences in viremia, CD4 T-cell percentages, and mucosal and systemic anti-SHIV humoral and cellular immune responses during primary infection of animals infected either intravenously (i.v.) or i.vag. Positive viral cocultures, peripheral blood mononuclear cell viral load peaks, and CD4 cell declines were delayed by 1 week in the i.vag. inoculated animals compared to the animals infected i.v., demonstrating delayed viral spreading to the periphery. In contrast, mucosal anti-SHIV antibody levels were greater in magnitude and arose more rapidly and mucosal CD8(+) T-cell responses were enhanced in the i.vag. group animals, whereas both the magnitudes and times of onset of systemic immune responses for the animals in the two groups did not differ. These observations demonstrate that compartmentalization of viral replication and induction of local antiviral immunity occur in the genital tract early after i.vag. but not i.v. inoculation. Induction of mucosal immunity to target this local, contained replication should be a goal in HIV vaccine development.

Animals↗
PubMed2001

Deferoxamine toxicity in hepatoma and primary rat cortical brain cultures.

Deferoxamine is commonly used for treatment of iron intoxication. Because the usual dose is unable to chelate sufficient iron before severe injury occurs, "high-dose" deferoxamine treatment has been proposed. However, several authors have reported severe toxicity after deferoxamine therapy. Although the hemodynamic effects are well described, the cellular toxicity of deferoxamine is unknown. Accordingly, we investigated the cellular toxicity of deferoxamine using in vitro techniques in two cell lines. Brain cells were harvested from fetal rats and cultured for 14-21 days before deferoxamine exposure. Using similar techniques, rat hepatoma cells were grown until confluent. Deferoxamine was added to the cultures to achieve final concentrations of 200-800 microg/ml, corresponding to in vivo infusion rates of 15-60 mg/kg/h. Deferoxamine was removed after 3 or 6 days by changing the medium. Subtoxic FeCl3 (500 mg/dl) was concurrently added to identical cultures to determine if deferoxamine potentiated iron toxicity. Cell viability was measured by a colorimetric assay. The addition of deferoxamine (0.2, 0.4, 0.8 mg/ml) significantly decreased cell viability in both cell groups. The effect of deferoxamine on primary cortical brain cultures was similar for the three concentrations used, and was similar when examined either 72 h or 6 days later. In contrast, hepatoma cell cultures evidenced a dose- dependent cell loss that increased with the length of exposure. The addition ofsubtoxic amounts of FeCl3 (500 microg/dl) in the presence of deferoxamine was protective in all cultures, and abolished deferoxamine-induced cell loss. Interestingly, the addition of serum albumin significantly reduced the amount of iron present in cells, suggesting its potential use to treat iron toxicity. These results suggest that deferoxamine, in the absence of iron, is toxic to cortical brain and hepatoma cells in vitro.

Animals↗
PubMed2001

Disrupted amino- and carboxyl-terminal interactions of the androgen receptor are linked to androgen insensitivity.

We have compared the functional consequences of seven single-point mutations in the ligand-binding domain (LBD) of the androgen receptor (AR). The mutations span helices 3 to 11 and are present in patients suffering from androgen insensitivity syndromes (AIS) and other male-specific disorders. The mutants, except M742V, bound to androgen response elements in vivo and in vitro and showed a testosterone-dependent conformational change. With regard to functional activity, the mutant M742V had severely blunted ability to transactivate or exhibit the androgen-dependent amino/carboxyl-terminal (N/C) interaction; mutants F725L, G743V, and F754L showed reduced transactivation potential and attenuated N/C interaction; and mutants V715M, R726L, and M886V had minor functional impairments. The mutants belonging to the first two groups also displayed reduced response to coexpressed GRIP1. In addition, mutations of amino acids M894 and A896 in the putative core activation domain 2 (AF2) in helix 12 confirmed that this helix is important for N/C interactions. Thus, amino acids located between helices 3 and 4 (F725 and R726), in helix 5 (M742, G743, and F754), and in helix 12 (M894 and A896) play critical roles in mediating the N/C interaction of AR. The data also show that disrupted N/C interaction is a potential molecular abnormality in AIS cases in which LBD mutations have not resulted in markedly impaired ability to bind androgen.

Amino Acid Sequence↗
PubMed2001

HER2 testing.

Explore the source record for details and available documents.

Antibodies, Monoclonal↗
PubMed2001

Acceptability and patterns of endometrial bleeding in estradiol-based HRT regimens: a comparative study of cyclical sequential combinations of trimegestone or norethisterone acetate.

OBJECTIVE: This randomized, double-blind, multicenter study was planned to compare the efficacy and tolerance of a novel oral regimen containing estradiol (2.0 mg) sequentially combined with trimegestone, at a daily dose of either 0.25 mg or 0.5 mg, with a standard hormone replacement therapy containing estradiol and norethisterone acetate (E2 + NETA) in the treatment of climacteric symptoms. METHODS: The study was conducted over 13 cycles, each of 28 days, and involved 487 subjects, of whom 349 completed the study. RESULTS: All three treatments were equally effective in alleviating hot flushes and showed a progressive and significant reduction in the value of the Kupperman index. The treatments diminished equally effectively urogenital signs and symptoms. All treatments were well tolerated and the incidences of adverse events associated with each treatment were similar across the treatment groups. The duration of expected withdrawal bleeding was shorter in the estradiol + trimegestone 0.5 mg group than in the estradiol + trimegestone 0.25 mg or E2 + NETA group. CONCLUSION: All treatments were effective and well tolerated, providing significant relief from climacteric symptoms. Treatment with estradiol + trimegestone 0.5 mg provided the most favorable bleeding pattern.

Argentina↗
PubMed2000

Candida-specific systemic cell-mediated immune reactivities in human immunodeficiency virus-positive persons with mucosal candidiasis.

Oropharyngeal candidiasis (OPC), as opposed to vulvovaginal candidiasis (VVC), is a common opportunistic infection in human immunodeficiency virus (HIV)-positive persons that correlates with reduced CD4 T cell counts. Although cell-mediated immunity (CMI) by CD4 Th1-type cells is considered to be the predominant host defense against mucosal candidiasis, the immune factors associated with susceptibility to OPC in HIV-positive persons are not well understood. This study investigated Candida-specific systemic CMI in HIV-positive persons with OPC and/or VVC. Reductions in delayed skin test reactivity to Candida antigen were observed in HIV-positive persons with CD4 cell counts <200 cells/microL, irrespective of the presence of mucosal infection. Likewise, despite the correlate of OPC with reduced CD4 cell counts in HIV-positive persons, differences in Candida-specific peripheral blood mononuclear cell proliferation and Th1/Th2 cytokine production between HIV-positive and HIV-negative persons were not consistent in a manner to suggest that deficiencies in Candida-specific systemic CMI account solely for the susceptibility to OPC.

AIDS-Related Opportunistic Infections↗
PubMed2000

A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth.

A proliferation-inducing ligand (APRIL) is a ligand of the tumor necrosis factor (TNF) family that stimulates tumor cell growth in vitro and in vivo. Expression of APRIL is highly upregulated in many tumors including colon and prostate carcinomas. Here we identify B cell maturation antigen (BCMA) and transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI), two predicted members of the TNF receptor family, as receptors for APRIL. APRIL binds BCMA with higher affinity than TACI. A soluble form of BCMA, which inhibits the proliferative activity of APRIL in vitro, decreases tumor cell proliferation in nude mice. Growth of HT29 colon carcinoma cells is blocked when mice are treated once per week with the soluble receptor. These results suggest an important role for APRIL in tumorigenesis and point towards a novel anticancer strategy.

3T3 Cells↗
PubMed2000

Molecular interactions between Anopheles stephensi midgut cells and Plasmodium berghei: the time bomb theory of ookinete invasion of mosquitoes.

We present a detailed analysis of the interactions between Anopheles stephensi midgut epithelial cells and Plasmodium berghei ookinetes during invasion of the mosquito by the parasite. In this mosquito, P. berghei ookinetes invade polarized columnar epithelial cells with microvilli, which do not express high levels of vesicular ATPase. The invaded cells are damaged, protrude towards the midgut lumen and suffer other characteristic changes, including induction of nitric oxide synthase (NOS) expression, a substantial loss of microvilli and genomic DNA fragmentation. Our results indicate that the parasite inflicts extensive damage leading to subsequent death of the invaded cell. Ookinetes were found to be remarkably plastic, to secrete a subtilisin-like serine protease and the GPI-anchored surface protein Pbs21 into the cytoplasm of invaded cells, and to be capable of extensive lateral movement between cells. The epithelial damage inflicted is repaired efficiently by an actin purse-string-mediated restitution mechanism, which allows the epithelium to 'bud off' the damaged cells without losing its integrity. A new model, the time bomb theory of ookinete invasion, is proposed and its implications are discussed.

Actins↗
PubMed2000

An alternative interpretation of nanobacteria-induced biomineralization.

The reported isolation of nanobacteria from human kidney stones raises the intriguing possibility that these microorganisms are etiological agents of pathological extraskeletal calcification [Kajander, E. O. & Ciftçioglu, N. (1998) Proc. Natl. Acad. Sci. USA 95, 8274-8279]. Nanobacteria were previously isolated from FBS after prolonged incubation in DMEM. These bacteria initiated biomineralization of the culture medium and were identified in calcified particles and biofilms by nucleic acid stains, 16S rDNA sequencing, electron microscopy, and the demonstration of a transferable biomineralization activity. We have now identified putative nanobacteria, not only from FBS, but also from human saliva and dental plaque after the incubation of 0.45-microm membrane-filtered samples in DMEM. Although biomineralization in our "cultures" was transferable to fresh DMEM, molecular examination of decalcified biofilms failed to detect nucleic acid or protein that would be expected from growth of a living entity. In addition, biomineralization was not inhibited by sodium azide. Furthermore, the 16S rDNA sequences previously ascribed to Nanobacterium sanguineum and Nanobacterium sp. were found to be indistinguishable from those of an environmental microorganism, Phyllobacterium mysinacearum, that has been previously detected as a contaminant in PCR. Thus, these data do not provide plausible support for the existence of a previously undiscovered bacterial genus. Instead, we provide evidence that biomineralization previously attributed to nanobacteria may be initiated by nonliving macromolecules and transferred on "subculture" by self-propagating microcrystalline apatite.

Bacteria↗
PubMed2000

Phase I assessment of the pharmacokinetics, metabolism, and safety of emitefur in patients with refractory solid tumors.

PURPOSE: To determine the toxicities, dose-limiting toxicities (DLT), maximum-tolerated dose, and pharmacokinetic profile of emitefur (BOF-A2) in patients with advanced solid tumors. METHODS: This was a phase I dose-escalating trial in which cohorts of patients received BOF-A2 (cohort 1, 300 mg/m(2) orally [PO] tid; cohort 2, 200 mg/m(2) PO tid; cohort 3, 200 mg/m(2) bid; and cohort 4, 250 mg/m(2) bid) for 14 consecutive days followed by 1 week of rest (cycle 1). Pharmacokinetics, toxicity, and tumor response were monitored. RESULTS: Nineteen patients received 110 cycles (three patients in cohort 1, three patients in cohort 2, 10 patients in cohort 3, and three patients in cohort 4). DLT (grade 3 stomatitis, diarrhea, leukopenia) was observed in cohorts 1, 2, and 4. Pharmacokinetics indicated that prolonged systemic expression of fluorouracil (5-FU) is maintained after administration of BOF-A2 at a dose of 200 mg bid for 14 days. The mean steady-state concentration of plasma 5-FU was > or = 24 ng/mL, which was 184-fold greater than the minimum effective cytotoxic concentration in vitro. Lack of variation of 5-FU trough levels within a day at steady-state indicates suppression of circadian variation. One patient in cohort 3 achieved a partial response and five patients maintained stable disease in excess of 6 months. CONCLUSION: BOF-A2 at a dose of 200 mg PO bid for 14 days followed by 7 days of rest is well tolerated. Prolonged exposure to 5-FU above the predicted preclinical minimum effective concentration is maintained, without evidence of circadian variation. Furthermore, evidence of antitumor activity is suggested.

Adult↗
PubMed2000

Evaluation of a live, cold-passaged, temperature-sensitive, respiratory syncytial virus vaccine candidate in infancy.

A live-attenuated, intranasal respiratory syncytial virus (RSV) candidate vaccine, cpts-248/404, was tested in phase 1 trials in 114 children, including 37 1-2-month-old infants-a target age for RSV vaccines. The cpts-248/404 vaccine was infectious at 104 and 105 plaque-forming units in RSV-naive children and was broadly immunogenic in children >6 months old. Serum and nasal antibody responses in 1-2 month olds were restricted to IgA, had a dominant response to RSV G protein, and had no increase in neutralizing activity. Nevertheless, there was restricted virus shedding on challenge with a second vaccine dose and preliminary evidence for protection from symptomatic disease on natural reexposure. The cpts-248/404 vaccine candidate did not cause fever or lower respiratory tract illness. In the youngest infants, however, cpts-248/404 was unacceptable because of upper respiratory tract congestion associated with peak virus recovery. A live attenuated RSV vaccine for the youngest infant will use cpts-248/404 modified by additional attenuating mutations.

Antibodies, Viral↗
PubMed2000

Review of the Bethesda System atlas does not improve reproducibility or accuracy in the classification of atypical squamous cells of undetermined significance smears.

BACKGROUND: The Bethesda System (TBS) and its accompanying atlas were developed to promote uniform diagnosis and reporting of cervical and vaginal cytology, especially with respect to borderline abnormal smears. The authors assessed whether group study of TBS atlas improves the reproducibility and accuracy of the cytopathologic diagnosis of equivocal Papanicolaou smears. METHODS: One hundred "atypical" smears were divided into pretest and posttest sets containing equal numbers of negative, atypical squamous cells of undetermined significance (ASCUS), and squamous intraepithelial lesion (SIL) diagnoses based on a five-member panel review. Two comparable teams of four pathologists from George Washington University Medical Center (Washington, DC) and Kaiser Permanente (Portland, OR), each comprised of two more experienced cytopathologists and two less experienced pathologists, independently reviewed the 50 pretest slides and classified the slides according to TBS as negative, ASCUS, or SIL. The teams then conducted group study sessions using TBS atlas. After the review, the pathologists independently classified the 50 posttest slides in a similar manner. RESULTS: Pretest, pair-wise interobserver agreement ranged from 30% to 66% compared with 34-62% for posttest agreement. Absolute percent agreement of reviewers' diagnoses with a previously developed consensus diagnosis based on opinions of a five-expert panel (cytopathologic certainty scale) ranged from 44% to 62% for the pretest set and from 40% to 60% for the posttest set. Comparison of the detection of oncogenic human papilloma virus (HPV) DNA by hybrid capture tube test with smears classified as negative, ASCUS, or SIL revealed that seven of eight reviewers did not demonstrate a stronger association between HPV detection and cytologic diagnosis in the posttest set. CONCLUSIONS: Review of TBS atlas by itself does not appear to improve the reproducibility or accuracy of cytologic diagnoses. The lack of improvement was similar among the pathologists involved regardless of experience level or whether they had a close working relation. Cancer (Cancer Cytopathol)

Cervix Uteri↗
PubMed2000

Activation of NF-kappaB by PM(10) occurs via an iron-mediated mechanism in the absence of IkappaB degradation.

Exposure to particulate air pollution (PM(10)) is associated with exacerbations of respiratory diseases and increased cardiopulmonary mortality. PM(10) induces lung inflammation in rats, which has been attributed to many factors, including the ultrafine components of PM(10), endotoxins, and transition metals. In this study, we investigated in alveolar epithelial (A549) cells whether PM(10) could activate nuclear factor-kappa B (NF-kappaB), a transcription factor stimulated in response to many proinflammatory agents. Our results show that PM(10) samples from various sites within the United Kingdom cause nuclear translocation, DNA-binding, and transcriptional activation of NF-kappaB in A549 cells. Furthermore, increased NF-kappaB activity was observed in the absence of IkappaB degradation. To evaluate the role of iron, A549 cells were exposed to PM(10) previously treated with phosphate-buffered saline (PBS), deferoxamine mesylate, or deferoxamine plus ferrozine. PBS-treated and, to a lesser extent, deferoxamine-treated PM(10) were able to activate NF-kappaB, whereas this response was completely abrogated in cells exposed to PM(10) treated with both deferoxamine and ferrozine. Moreover, we studied the effects of soluble components of PM(10) on NF-kappaB activation by exposing alveolar epithelial cells to soluble fractions from PM(10) treated with PBS or the metal chelators. We found that, compared with fractions from PBS-treated PM(10) which activated NF-kappaB, fractions from PM(10) treated with deferoxamine and ferrozine did not stimulate NF-kappaB activity above background levels. Coincubation of polymixin B, an endotoxin-binding compound, and PM(10) did not inhibit NF-kappaB. In summary, PM(10) activates NF-kappaB in A549 cells by an iron-mediated mechanism in the absence of IkappaB degradation.

Adenocarcinoma↗