bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel Two-Component Regulatory System Involved in Biofilm Formation and Acid Resistance inStreptococcus mutans
Authors: Li Yung-Hua , Lau Peter C. Y. , Tang Nan , Svensäter Gunnel , Ellen Richard P. , Cvitkovitch Dennis G. 
Published: October 2002

ABSTRACTThe abilities ofStreptococcus mutansto form biofilms and to survive acidic pH are regarded as two important virulence determinants in the pathogenesis of dental caries. Environmental stimuli are thought to regulate the expression of several genes associated with virulence factors through the activity of two-component signal transduction systems. Yet, little is known of the involvement of these systems in the physiology and pathogenicity ofS. mutans. In this study, we describe a two-component regulatory system and its involvement in biofilm formation and acid resistance inS. mutans. By searching theS. mutansgenome database with tblastn with the HK03 and RR03 protein sequences fromS. pneumoniaeas queries, we identified two genes, designatedhk11andrr11, that encode a putative histidine kinase and its cognate response regulator. To gain insight into their function, a PCR-mediated allelic-exchange mutagenesis strategy was used to create thehk11(Emr) andrr11(Emr) deletion mutants fromS. mutanswild-type NG8 named SMHK11 and SMRR11, respectively. The mutants were examined for their growth rates, genetic competence, ability to form biofilms, and resistance to low-pH challenge. The results showed that deletion ofhk11orrr11resulted in defects in biofilm formation and resistance to acidic pH. Both mutants formed biofilms with reduced biomass (50 to 70% of the density of the parent strain). Scanning electron microscopy revealed that the biofilms formed by the mutants had sponge-like architecture with what appeared to be large gaps that resembled water channel-like structures. The mutant biofilms were composed of longer chains of cells than those of the parent biofilm. Deletion ofhk11also resulted in greatly diminished resistance to low pH, although we did not observe the same effect whenrr11was deleted. Genetic competence was not affected in either mutant. The results suggested that the gene product ofhk11inS. mutansmight act as a pH sensor that could cross talk with one or more response regulators. We conclude that the two-component signal transduction system encoded byhk11andrr11represents a new regulatory system involved in biofilm formation and acid resistance inS. mutans.
Regulation and Physiological Significance of ClpC and ClpP in
Streptococcus mutans
Authors: Lemos José A. C. , Burne Robert A. 
Published: October 2002

ABSTRACT

Tolerance of environmental stress, especially low pH, by
Streptococcus mutans
is central to the virulence of this organism. The Clp ATPases are implicated in the tolerance of, and regulation of the response to, stresses by virtue of their protein reactivation and remodeling activities and their capacity to target misfolded proteins for degradation by the ClpP peptidase. The purpose of this study was to dissect the role of selected
clp
genes in the stress responses of
S. mutans
, with a particular focus on acid tolerance and adaptation. Homologues of the
clpB
,
clpC
,
clpE
,
clpL
,
clpX
, and
clpP
genes were identified in the
S. mutans
genome. The expression of
clpC
and
clpP
, which were chosen as the focus of this study, was induced at low pH and at growth above 40°C. Inactivation of
ctsR
, the first of two genes in the
clpC
operon, demonstrated that CtsR acts as a repressor of
clp
and
groES-EL
gene expression. Strains lacking ClpP, but not strains lacking ClpC, were impaired in their ability to grow under stress-inducing conditions, formed long chains, aggregated in culture, had reduced genetic transformation efficiencies, and had a reduced capacity to form biofilms. Comparison of two-dimensional protein gels from wild-type cells and the
ctsR
and
clpP
mutants revealed many changes in the protein expression patterns. In particular, in the
clpP
mutant, there was an increased production of GroESL and DnaK, suggesting that cells were stressed, probably due to the accumulation of denatured proteins.
TURING UNIVERSALITY OF RECURSIVE PATTERNS FOR PARALLEL PROGRAMMING
Authors: FISCHER JÖRG , GORLATCH SERGEI 
Published: October 2002

Dijkstra's famous thesis "goto considered harmful", which paved the way for structured programming, was formally substantiated by the result of Böhm and Jacopini on the Turing universality of the three well-known basic programming constructs. We argue for a similar ideal in parallel programming — "send-receive considered harmful" — i.e. abandoning explicit send-receive statements between processors and expressing programs using a restricted set of parallel constructs. We deal with recursive patterns of parallelism, represented formally as morphisms in a suitable calculus. The aim of this paper is to study the expressive power of two morphisms – catamorphisms and anamorphisms. For a restricted program calculus based on these morphisms, we constructively prove two formal results, whose pragmatic message is: (1) A programming language based on catamorphisms is computationally equivalent to the class of primitive recursive functions; (2) A programming language based on both catamorphisms and anamorphisms is equivalent to the class of partial recursive functions and is therefore Turing-universal. We present a case study on numerical integration, demonstrating the expressive power of ana- and catamorphisms for parallel programming.
GEOMETRY AND SPACETIME
Authors: YAU SHING TUNG 
Published: October 2002

The geometry of spacetime has a deep influence on our physical world. Hence any significant understanding of our physical world gives rise to important insights into geometry. The exchange of ideas between geometry and fundamental physics have been extensive in the past twenty years. Ideas from string theory have been vital in unifying several disciplines in mathematics. In this talk, I shall discuss a few examples in geometry that are related to physics.
Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation
Authors: Storek Jan , Joseph Ansamma , Espino German , Dawson Monja A. , Douek Daniel C. , Sullivan Keith M. , Flowers Mary E. D. , Martin Paul , Mathioudakis George , Nash Richard A. , Storb Rainer , Appelbaum Frederick R. , Maloney David G. 
Published: October 2002

AbstractThe duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were assessed by flow cytometry. T-cell receptor excision circles (TRECs), markers of T cells generated de novo, were quantitated by real-time polymerase chain reaction. Immunoglobulin G2 (IgG2) and antigen-specific IgG levels were determined by enzyme-linked immunosorbent assay. Infections diagnosed 15 years after transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding respiratory tract infections, gastroenteritis, lip sores, and hepatitis C. The counts of circulating monocytes, natural killer cells, B cells, CD4 T cells, and CD8 T cells in the patients were not lower than in the donors. The counts of TREC+ CD4 T cells in transplant recipients younger than age 18 years (at the time of transplantation) were not different from the counts in their donors. In contrast, the counts of TREC+ CD4 T cells were lower in transplant recipients age 18 years or older, even in those with no history of clinical extensive chronic graft-versus-host disease, compared with their donors. The levels of total IgG2 and specific IgG against Haemophilus influenzae and Streptococcus pneumoniae were similar in patients and donors. Overall, the immunity of patients surviving 20 to 30 years after transplantation is normal or near normal. Patients who received transplants in adulthood have a clinically insignificant deficiency of de novo–generated CD4 T cells, suggesting that in these patients the posttransplantation thymic insufficiency may not be fully reversible.
Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome
Authors: Maciejewski Jaroslaw P. , Follmann Dean , Nakamura Ryotaro , Saunthararajah Yogen , Rivera Candido E. , Simonis Toni , Brown Kevin E. , Barrett John A. , Young Neal S. 
Published: October 2002

Abstract
Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)–anchored protein (AP)–deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP–deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%;z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP–deficient cells is linked to HLA and likely related to an immune mechanism.
Isolation and characterization of plasmacytoid dendritic cells from Flt3 ligand and granulocyte-macrophage colony-stimulating factor–treated mice
Authors: Björck Pia 
Published: October 2002

AbstractInterferon α/β plays an important role in the first-line defense against viral infections and can modulate cytokine responses by T-helper cells. Type 1 interferons (IFNs) are clinically important in infectious diseases and in the treatment of leukemia and lymphomas. Many different cell types have the capacity to produce IFN-α after encounter with virus and bacteria. The major, natural type 1 IFN–producing cell in humans was recently described as the plasmacytoid T cell, or pDC2, and it can differentiate into dendritic cells (DCs) on culture. This study describes the murine natural IFN-α–producing cell, or pDC2, that shares morphologic features with its human counterpart but has some distinct phenotypical characteristics. Murine plasmacytoid DCs can be differentially isolated based on their expression of CD11c, B220 (CD45R), and Thy1.2 (CD90). They lack expression of myeloid (eg, CD11b) antigens and CD8α, a marker used to isolate lymphoid DCs. Like human pDC2, murine plasmacytoid DCs exhibit their maximal type 1 IFN–producing capacity at a precursor stage; pDCs isolated from bone marrow responded to viral stimulation with higher IFN-α production than cells of the same phenotype isolated from spleen. Mobilization of mice with Flt3 ligand (Flt3L) or Flt3L and granulocyte-macrophage colony-stimulating factor, hematopoietic factors that specifically enhance DC growth, resulted in strikingly increased numbers of pDC in bone marrow and spleen. The isolation of this novel murine DC subset may serve as a useful tool in the study of viral immunobiology and for the design of treatments for murine malignancies.
Myeloma cells induce imbalance in the osteoprotegerin/osteoprotegerin ligand system in the human bone marrow environment
Authors: Giuliani Nicola , Bataille Régis , Mancini Cristina , Lazzaretti Mirca , Barillé Sophie 
Published: October 2002

AbstractAlthough osteolysis is a common complication in patients with multiple myeloma (MM), the biologic mechanisms involved in the pathogenesis of MM-induced bone disease are poorly understood. Two factors produced by stromal-osteoblastic cells seem critical to the regulation of bone resorption: osteoprotegerin (OPG) and its ligand (OPGL). OPGL stimulates osteoclast differentiation and activity, whereas OPG inhibits these processes. The present study investigated whether myeloma cells affect physiologic OPG/OPGL balance in the bone marrow (BM) environment. Ten human myeloma cell lines and myeloma cells isolated from 26 consecutive patients with MM failed to express OPGL and only rarely produced a low amount of OPG. In a coculture system, human myeloma cells up-regulated OPGL expression but strongly down-regulated OPG production in preosteoblastic (preOB) or stromal cells (BMSCs) of primary human BM at the mRNA and protein levels. This effect, which was dependent on cell-to-cell contact between myeloma cells and BMSCs or preOB, partially involved the integrin VLA-4. In addition, overexpression of OPGL mRNA occurred in ex vivo BM cultures obtained from MM patients as compared with healthy donors, and immunohistochemical staining performed on BM biopsy specimens showed an increase of OPGL and a reduction of OPG expression in MM patients as compared with healthy subjects. In summary, these data indicate that myeloma cells affect the OPG/OPGL ratio in the BM environment and tend to confirm that the OPG/OPGL system is involved in the pathogenesis of MM-induced bone disease.
Transgenic overexpression of the CC chemokine CCL21 disrupts T-cell migration
Authors: Christopherson Kent W. , Campbell James J. , Hromas Robert A. 
Published: October 2002

AbstractChemokines are a large family of cytokines that direct normal leukocyte migration. They also have been implicated in leukocyte development and in the pathogenesis of many diseases. The CC chemokine CCL21, also known as Exodus-2, SLC, 6Ckine, and TCA4 induces both the adhesion and migration of human T cells. CCL21 is hypothesized to regulate the trafficking of T cells through secondary lymphoid tissues. To test this hypothesis, a transgenic mouse model was generated that placed the expression of mouse CCL21 (mCCL21) under the control of the T cell-specific lck promoter to abrogate the concentration gradient to which T cells normally respond. Overexpression of mCCL21 in T cells resulted in defects in CCL21- and CCL19-induced T-cell chemotaxis, node T-cell subpopulations, and lymph node architecture. The regulation of T-cell trafficking in secondary lymphoid tissues by CCL21 is therefore a tightly regulated system that can be altered by changes in the level of environmental CCL21 protein.
Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies
Authors: Socié Gérard , Clift Reginald A. , Blaise Didier , Devergie Agnès , Ringden Olle , Martin Paul J. , Remberger Mats , Deeg H. Joachim , Ruutu Tapani , Michallet Mauricette , Sullivan Keith M. , Chevret Sylvie 
Published: October 2002

AbstractIn the early 1990s, 4 randomized studies compared conditioning regimens before transplantation for leukemia with either cyclophosphamide (CY) and total-body irradiation (TBI), or busulfan (Bu) and CY. This study analyzed the long-term outcomes for 316 patients with chronic myeloid leukemia (CML) and 172 patients with acute myeloid leukemia (AML) who participated in these 4 trials, now with a mean follow-up of more than 7 years. Among patients with CML, no statistically significant difference in survival or disease-free survival emerged from testing the 2 regimens. The projected 10-year survival estimates were 65% and 63% with Bu-CY versus CY-TBI, respectively. Among patients with AML, the projected 10-year survival estimates were 51% and 63% (95% CI, 52%-74%) with Bu-CY versus CY-TBI, respectively. At last follow-up, most surviving patients had unimpaired health and had returned to work, regardless of the conditioning regimen. Late complications were analyzed after adjustment for patient age and for acute and chronic graft-versus-host disease (GVHD). CML patients who received CY-TBI had an increased risk of cataract formation, and patients treated with Bu-CY had an increased risk of irreversible alopecia. Chronic GVHD was the primary risk factor for late pulmonary disease and avascular osteonecrosis. Thus, Bu-CY and CY-TBI provided similar probabilities of cure for patients with CML. In patients with AML, a nonsignificant 10% lower survival rate was observed after Bu-CY. Late complications occurred equally after both conditioning regimens (except for increased risk of cataract after CY-TBI and of alopecia with Bu-CY).
Comparison of idarubicin + ara-C–, fludarabine + ara-C–, and topotecan + ara-C–based regimens in treatment of newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts in transformation, or refractory anemia with excess blasts
Authors: Estey Elihu H. , Thall Peter F. , Cortes Jorge E. , Giles Francis J. , O'Brien Susan , Pierce Sherry A. , Wang Xuemei , Kantarjian Hagop M. , Beran Miloslav 
Published: October 2002

AbstractIt has been unclear whether regimens containing topotecan + ara-C (TA) or fludarabine + ara-C (FA) ± idarubicin are superior to regimens containing idarubicin + ara-C (IA) without either fludarabine or topotecan for treatment of newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts in transformation (RAEB-t), or RAEB. Of 1279 patients treated here for these diagnoses between 1991 and 1999, 322 received IA regimens, 600 FA regimens, and 357 TA regimens. All regimens used ara-C doses of 1 to 2 gm/m2/d, given by continuous infusion in IA, and over 2 to 4 hours in FA and TA. Complete remission (CR) rates were lower with FA (55%) and TA (59%) than with IA (77%). Both event-free survival (EFS) in CR and survival were shorter: median EFS in CR (95% confidence interval) was 63 weeks (range, 55-76 weeks) for IA, 40 (range, 31-46 weeks) for FA, and 36 (range, 27-44 weeks) for TA; median survival was 77 weeks (range, 57-88 weeks) for IA, 30 (range, 27-35 weeks) for FA, and 41 (range, 35-50 weeks) for TA. These trials were not randomized, and patients with worse prognoses were disproportionately given the FA and TA regimens. Nonetheless, after accounting for prognosis the FA and TA regimens remained highly significantly associated with lower CR rates, shorter EFS in CR, and shorter survival. Accounting for possible effects of individual trials within each of the IA, FA, and TA groups did not alter these findings. It is unlikely that, as given here, either FA or TA is, in general, superior to IA, highlighting the need for new treatments.
Decreased transfusion requirements for patients receiving nonmyeloablative compared with conventional peripheral blood stem cell transplants from HLA-identical siblings
Authors: Weissinger Florian , Sandmaier Brenda M. , Maloney David G. , Bensinger William I. , Gooley Ted , Storb Rainer 
Published: October 2002

Abstract
Red blood cell (RBC) and platelet transfusion requirements in patients given nonmyeloablative versus conventional peripheral blood stem cell (PBSC) transplants from HLA-matched siblings were compared. Between December 1997 and March 2000, 40 patients, aged 21 to 67 years (median 51), with hematologic malignancies underwent nonmyeloablative allografts after either 2 Gy total body irradiation alone (n = 30) or 2 Gy total body irradiation preceded by fludarabine 30 mg/m2/d on days −4, −3, and −2 (n = 10). All received postgrafting mycophenolate mofetil and cyclosporine. Controls included 67 concurrent patients, aged 23 to 66 years (median, 46 years), given conventional PBSC transplants following high-dose conditioning and postgrafting methotrexate and cyclosporine. Among patients given nonmyeloablative transplants, 23% required platelet transfusions compared with 100% among patients given conventional grafts (P &lt; .0001). Further, the number of platelet units given to nonmyeloablative recipients was reduced, with a median of 0 (range, 0 to 214) compared with a median of 24 (range, 4 to 358) after conventional transplantation (P &lt; .0001). Sixty-three percent of nonmyeloablative recipients required RBC transfusions compared with 96% of those with conventional grafts (P = .0001). The number of RBC units transfused was also reduced, with a median of 2 (range, 0 to 50) compared with 6 (range, 0 to 34) after conventional transplantation (P = .0001). High transfusion requirements before transplantation and donor-recipient ABO incompatibility increased transfusion requirements in both patient groups, though neither significantly influenced the outcome of the analysis. Neither patient age, splenomegaly at transplantation, development of graft-versus-host disease, nor posttransplantation cytomegalovirus antigenemia or cytomegalovirus disease had statistically significant influences on posttransplantation transfusions.
Nonablative allogeneic hematopoietic transplantation as adoptive immunotherapy for indolent lymphoma: low incidence of toxicity, acute graft-versus-host disease, and treatment-related mortality
Authors: Khouri Issa F. , Saliba Rima M. , Giralt Sergio A. , Lee Ming-Sheng , Okoroji Grace-Julia , Hagemeister Fredrick B. , Korbling Martin , Younes Anas , Ippoliti Cindy , Gajewski James L. , McLaughlin Peter , Anderlini Paolo , Donato Michele L. , Cabanillas Fernando F. , Champlin Richard E. 
Published: October 2002

Abstract
This study investigated the use of a nonablative conditioning regimen to decrease toxicity and achieve engraftment of an allogeneic blood stem cell transplant, allowing a graft-versus-malignancy effect to occur. All patients had follicular or small cell lymphocytic lymphoma after relapse from a prior response to conventional chemotherapy. Patients received a preparative regimen of fludarabine (25 mg/m2 given daily for 5 days or 30 mg/m2daily for 3 days) and intravenous cyclophosphamide (1 g/m2given daily for 2 days or 750 mg/m2 daily for 3 days). Nine patients received rituximab in addition to the chemotherapy. Tacrolimus and methotrexate were used for graft-versus-host disease (GVHD) prophylaxis. Twenty patients were studied; their median age was 51 years. Twelve were in complete remission (CR) at transplantation. All patients achieved engraftment of donor cells. The median number of days with severe neutropenia was 6. Only 2 patients required more than one platelet transfusion. The cumulative incidence of acute grade II to IV GVHD was 20%. Only one patient developed acute GVHD of greater than grade II. All patients achieved CR. None have had a relapse of disease, with a median follow-up period of 21 months. The actuarial probability of being alive and in remission at 2 years was 84% (95% confidence interval, 57%-94%). Nonablative chemotherapy with fludarabine/cyclophosphamide followed by allogeneic stem cell transplantation is a promising therapy for indolent lymphoma with minimal toxicity and myelosuppression. Further studies are warranted to compare nonablative allogeneic hematopoietic transplantation with alternative treatment strategies.