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University of Massachusetts Medical School

Women’s Health Research Faculty Publications

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T-Cell Responses To Dengue Virus In Humans, Ichiro Kurane, Takaji Matsutani, Ryuji Suzuki, Tomohiko Takasaki, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis Dec 2011

T-Cell Responses To Dengue Virus In Humans, Ichiro Kurane, Takaji Matsutani, Ryuji Suzuki, Tomohiko Takasaki, Siripen Kalayanarooj, Sharone Green, Alan L. Rothman, Francis A. Ennis

Women’s Health Research Faculty Publications

Dengue virus (DENV) is a leading cause of morbidity and mortality in most tropical and subtropical areas of the world. Dengue virus infection induces specific CD4+CD8- and CD8+CD4- T cells in humans. In primary infection, T-cell responses to DENV are serotype cross-reactive, but the highest response is to the serotype that caused the infection. The epitopes recognized by DENV-specific T cells are located in most of the structural and non-structural proteins, but NS3 is the protein that is most dominantly recognized. In patients with dengue hemorrhagic fever (DHF) caused by secondary DENV infection, T cells are highly activated ...


Host Genetic Risk Factors For West Nile Virus Infection And Disease Progression, Abigail W. Bigham, Kati J. Buckingham, Sofia Husain, Mary J. Edmond, Kathryn M. Bofferding, Heidi Gildersleeve, Ann Rutherford, Natalia M. Astakhova, Andrey A. Perelygin, Michael P. Busch, Kristy O. Murray, James J. Sejvar, Sharone Green, John Kriesel, Margo A. Brinton, Michael Bamshad Sep 2011

Host Genetic Risk Factors For West Nile Virus Infection And Disease Progression, Abigail W. Bigham, Kati J. Buckingham, Sofia Husain, Mary J. Edmond, Kathryn M. Bofferding, Heidi Gildersleeve, Ann Rutherford, Natalia M. Astakhova, Andrey A. Perelygin, Michael P. Busch, Kristy O. Murray, James J. Sejvar, Sharone Green, John Kriesel, Margo A. Brinton, Michael Bamshad

Women’s Health Research Faculty Publications

West Nile virus (WNV), a category B pathogen endemic in parts of Africa, Asia and Europe, emerged in North America in 1999, and spread rapidly across the continental U.S. Outcomes of infection with WNV range from asymptomatic to severe neuroinvasive disease manifested as encephalitis, paralysis, and/or death. Neuroinvasive WNV disease occurs in less than one percent of cases, and although host genetic factors are thought to influence risk for symptomatic disease, the identity of these factors remains largely unknown. We tested 360 common haplotype tagging and/or functional SNPs in 86 genes that encode key regulators of immune ...


Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss In Human Peripheral Blood T Lymphocytes, Joel M. O'Bryan, James A. Potts, Herbert L. Bonkovsky, Anuja Mathew, Alan L. Rothman Aug 2011

Extended Interferon-Alpha Therapy Accelerates Telomere Length Loss In Human Peripheral Blood T Lymphocytes, Joel M. O'Bryan, James A. Potts, Herbert L. Bonkovsky, Anuja Mathew, Alan L. Rothman

Women’s Health Research Faculty Publications

BACKGROUND: Type I interferons have pleiotropic effects on host cells, including inhibiting telomerase in lymphocytes and antiviral activity. We tested the hypothesis that long-term interferon treatment would result in significant reduction in average telomere length in peripheral blood T lymphocytes.

METHODS/PRINCIPAL FINDINGS: Using a flow cytometry-based telomere length assay on peripheral blood mononuclear cell samples from the Hepatitis-C Antiviral Long-term Treatment against Cirrhosis (HALT-C) study, we measured T cell telomere lengths at screening and at months 21 and 45 in 29 Hepatitis-C virus infected subjects. These subjects had failed to achieve a sustained virologic response following 24 weeks of ...


Cross-Reactivity And Expansion Of Dengue-Specific T Cells During Acute Primary And Secondary Infections In Humans, Heather L. Friberg-Robertson, Hema Sundara Bashyam, Tomoko Toyosaki-Maeda, James A. Potts, Thomas C. Greenough, Siripen Kalayanarooj, Robert V. Gibbons, Ananda Nisalak, Anon Srikiatkhachorn, Sharone Green, Henry A. F. Stephens, Alan L. Rothman, Anuja Mathew Aug 2011

Cross-Reactivity And Expansion Of Dengue-Specific T Cells During Acute Primary And Secondary Infections In Humans, Heather L. Friberg-Robertson, Hema Sundara Bashyam, Tomoko Toyosaki-Maeda, James A. Potts, Thomas C. Greenough, Siripen Kalayanarooj, Robert V. Gibbons, Ananda Nisalak, Anon Srikiatkhachorn, Sharone Green, Henry A. F. Stephens, Alan L. Rothman, Anuja Mathew

Women’s Health Research Faculty Publications

Serotype-cross-reactive memory T cells responding to secondary dengue virus (DENV) infection are thought to contribute to disease. However, epitope-specific T cell responses have not been thoroughly compared between subjects with primary versus secondary DENV infection. We studied CD8(+) T cells specific for the HLA-A*1101-restricted NS3(133) epitope in a cohort of A11(+) DENV-infected patients throughout acute illness and convalescence. We compared the expansion, serotype-cross-reactivity, and activation of these cells in PBMC from patients experiencing primary or secondary infection and mild or severe disease by flow cytometry. Our results show expansion and activation of DENV-specific CD8(+) T cells during acute ...


Epigenetic Regulation In Alcoholic Liver Disease, Pranoti Mandrekar May 2011

Epigenetic Regulation In Alcoholic Liver Disease, Pranoti Mandrekar

Women’s Health Research Faculty Publications

Alcoholic liver disease (ALD) is characterized by steatosis or fat deposition in the liver and inflammation, which leads to cirrhosis and hepatocellular carcinoma. Induction of target genes without involving changes in DNA sequence seems to contribute greatly to liver injury. Chromatin modifications including alterations in histones and DNA, as well as post-transcriptional changes collectively referred to as epigenetic effects are altered by alcohol. Recent studies have pointed to a significant role for epigenetic mechanisms at the nucleosomal level influencing gene expression and disease outcome in ALD. Specifically, epigenetic alterations by alcohol include histone modifications such as changes in acetylation and ...


Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy P. Endy, Kathryn B. Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan L. Rothman, Stephen J. Thomas, Richard G. Jarman, Daniel H. Libraty, Robert V. Gibbons Mar 2011

Determinants Of Inapparent And Symptomatic Dengue Infection In A Prospective Study Of Primary School Children In Kamphaeng Phet, Thailand, Timothy P. Endy, Kathryn B. Anderson, Ananda Nisalak, In-Kyu Yoon, Sharone Green, Alan L. Rothman, Stephen J. Thomas, Richard G. Jarman, Daniel H. Libraty, Robert V. Gibbons

Women’s Health Research Faculty Publications

BACKGROUND: Dengue viruses are a major cause of morbidity in tropical and subtropical regions of the world. Inapparent dengue is an important component of the overall burden of dengue infection. It provides a source of infection for mosquito transmission during the course of an epidemic, yet by definition is undetected by health care providers. Previous studies of inapparent or subclinical infection have reported varying ratios of symptomatic to inapparent dengue infection.

METHODOLOGY/PRINCIPAL FINDINGS: In a prospective study of school children in Northern Thailand, we describe the spatial and temporal variation of the symptomatic to inapparent (S:I) dengue illness ...


Metal-Free Als Variants Of Dimeric Human Cu,Zn-Superoxide Dismutase Have Enhanced Populations Of Monomeric Species, Anna-Karin E. Svensson, Osman Bilsel, Can Kayatekin, Jessica A. Adefusika, Jill A. Zitzewitz, C. Robert Matthews Apr 2010

Metal-Free Als Variants Of Dimeric Human Cu,Zn-Superoxide Dismutase Have Enhanced Populations Of Monomeric Species, Anna-Karin E. Svensson, Osman Bilsel, Can Kayatekin, Jessica A. Adefusika, Jill A. Zitzewitz, C. Robert Matthews

Women’s Health Research Faculty Publications

Amino acid replacements at dozens of positions in the dimeric protein human, Cu,Zn superoxide dismutase (SOD1) can cause amyotrophic lateral sclerosis (ALS). Although it has long been hypothesized that these mutations might enhance the populations of marginally-stable aggregation-prone species responsible for cellular toxicity, there has been little quantitative evidence to support this notion. Perturbations of the folding free energy landscapes of metal-free versions of five ALS-inducing variants, A4V, L38V, G93A, L106V and S134N SOD1, were determined with a global analysis of kinetic and thermodynamic folding data for dimeric and stable monomeric versions of these variants. Utilizing this global analysis ...


Sex Steroid Metabolism Polymorphisms And Mammographic Density In Pre- And Early Perimenopausal Women, Carolyn J. Crandall, Mary E. Sehl, Sybil L. Crawford, Ellen B. Gold, Laurel A. Habel, Lesley M. Butler, Mary Fran R. Sowers, Gail A. Greendale, Janet S. Sinsheimer Jul 2009

Sex Steroid Metabolism Polymorphisms And Mammographic Density In Pre- And Early Perimenopausal Women, Carolyn J. Crandall, Mary E. Sehl, Sybil L. Crawford, Ellen B. Gold, Laurel A. Habel, Lesley M. Butler, Mary Fran R. Sowers, Gail A. Greendale, Janet S. Sinsheimer

Women’s Health Research Faculty Publications

INTRODUCTION : We examined the association between mammographic density and single-nucleotide polymorphisms (SNPs) in genes encoding CYP1A1, CYP1B1, aromatase, 17beta-HSD, ESR1, and ESR2 in pre- and early perimenopausal white, African-American, Chinese, and Japanese women.

METHODS : The Study of Women's Health Across the Nation is a longitudinal community-based cohort study. We analyzed data from 451 pre- and early perimenopausal participants of the ancillary SWAN Mammographic Density study for whom we had complete information regarding mammographic density, genotypes, and covariates. With multivariate linear regression, we examined the relation between percentage mammographic breast density (outcome) and each SNP (primary predictor), adjusting for age ...


Factors Related To Declining Luteal Function In Women During The Menopausal Transition, Nanette Santoro, Sybil L. Crawford, Bill Lasley, J. L. Luborsky, Karen A. Matthews, Daniel Mcconnell, John F. Randolph, Ellen B. Gold, Gail A. Greendale, S. G. Korenman, Lynda H. Powell, Mary Fran R. Sowers, Gerson Weiss May 2008

Factors Related To Declining Luteal Function In Women During The Menopausal Transition, Nanette Santoro, Sybil L. Crawford, Bill Lasley, J. L. Luborsky, Karen A. Matthews, Daniel Mcconnell, John F. Randolph, Ellen B. Gold, Gail A. Greendale, S. G. Korenman, Lynda H. Powell, Mary Fran R. Sowers, Gerson Weiss

Women’s Health Research Faculty Publications

CONTEXT: Reproductive hormones are incompletely characterized during the menopause transition (MT). Hypothesis: Increased anovulation and decreased progesterone accompany progress through the MT.

DESIGN: The Daily Hormone Study (DHS) of the Study of Women's Health Across the Nation (SWAN) included 848 women aged 43-53 yr at baseline who collected daily urine for one cycle or up to 50 d annually for 3 yr.

MAIN OUTCOME MEASURES: LH, FSH, estrone conjugates, and pregnanediol glucuronide levels were assessed. Cycles were classified by presumed luteal (ovulatory) status and bleeding. Hormones were related to time in study, age, menopausal status, and selected variables.

RESULTS ...


Dna Polymerase Beta Is Able To Repair Breaks In Switch Regions And Plays An Inhibitory Role During Immunoglobulin Class Switch Recombination, Xiaoming Wu, Janet Stavnezer Jul 2007

Dna Polymerase Beta Is Able To Repair Breaks In Switch Regions And Plays An Inhibitory Role During Immunoglobulin Class Switch Recombination, Xiaoming Wu, Janet Stavnezer

Women’s Health Research Faculty Publications

Immunoglobulin (Ig) class switch recombination (CSR) is initiated by activation-induced cytidine deaminase (AID), which converts cytosines to uracils in switch (S) regions. Subsequent excision of dU by uracil DNA glycosylase (UNG) of the base excision repair (BER) pathway is required to obtain double-strand break (DSB) intermediates for CSR. Since UNG normally initiates faithful repair, it is unclear how the AID-instigated S region lesions are converted into DSBs rather than correctly repaired by BER. Normally, DNA polymerase beta (Polbeta) would replace the dC deaminated by AID, leading to correct repair of the single-strand break, thereby preventing CSR. We address the question ...


Impact Of Cyclooxygenase Inhibitors In The Women's Health Initiative Hormone Trials: Secondary Analysis Of A Randomized Trial, Judith Hsia, Joann E. Manson, Lewis H. Kuller, Mary B. Pettinger, John H. Choe, Robert D. Langer, Marian C. Limacher, Albert Oberman, Judith K. Ockene, Mary Jo O'Sullivan, Jennifer G. Robinson Sep 2006

Impact Of Cyclooxygenase Inhibitors In The Women's Health Initiative Hormone Trials: Secondary Analysis Of A Randomized Trial, Judith Hsia, Joann E. Manson, Lewis H. Kuller, Mary B. Pettinger, John H. Choe, Robert D. Langer, Marian C. Limacher, Albert Oberman, Judith K. Ockene, Mary Jo O'Sullivan, Jennifer G. Robinson

Women’s Health Research Faculty Publications

OBJECTIVES: We evaluated the hypothesis that cyclooxygenase (COX) inhibitor use might have counteracted a beneficial effect of postmenopausal hormone therapy, and account for the absence of cardioprotection in the Women's Health Initiative hormone trials. Estrogen increases COX expression, and inhibitors of COX such as nonsteroidal anti-inflammatory agents appear to increase coronary risk, raising the possibility of a clinically important interaction in the trials.

DESIGN: The hormone trials were randomized, double-blind, and placebo-controlled. Use of nonsteroidal anti-inflammatory drugs was assessed at baseline and at years 1, 3, and 6.

SETTING: The Women's Health Initiative hormone trials were conducted at ...


Inducible Dna Breaks In Ig S Regions Are Dependent On Aid And Ung, Carol E. Schrader, Erin K. Linehan, Sofia N. Mochegova, Robert T. Woodland, Janet Stavnezer Aug 2005

Inducible Dna Breaks In Ig S Regions Are Dependent On Aid And Ung, Carol E. Schrader, Erin K. Linehan, Sofia N. Mochegova, Robert T. Woodland, Janet Stavnezer

Women’s Health Research Faculty Publications

Class switch recombination (CSR) occurs by an intrachromosomal deletion whereby the IgM constant region gene (Cmu) is replaced by a downstream constant region gene. This unique recombination event involves formation of double-strand breaks (DSBs) in immunoglobulin switch (S) regions, and requires activation-induced cytidine deaminase (AID), which converts cytosines to uracils. Repair of the uracils is proposed to lead to DNA breaks required for recombination. Uracil DNA glycosylase (UNG) is required for most CSR activity although its role is disputed. Here we use ligation-mediated PCR to detect DSBs in S regions in splenic B cells undergoing CSR. We find that the ...


Shifts In Targeting Of Class Switch Recombination Sites In Mice That Lack Mu Switch Region Tandem Repeats Or Msh2, Irene M. Min, Lisa R. Rothlein, Carol E. Schrader, Janet Stavnezer, Erik Selsing Jun 2005

Shifts In Targeting Of Class Switch Recombination Sites In Mice That Lack Mu Switch Region Tandem Repeats Or Msh2, Irene M. Min, Lisa R. Rothlein, Carol E. Schrader, Janet Stavnezer, Erik Selsing

Women’s Health Research Faculty Publications

The mechanisms that target class switch recombination (CSR) to antibody gene switch (S) regions are unknown. Analyses of switch site locations in wild-type mice and in mice that lack the Smu tandem repeats show shifts indicating that a 4-5-kb DNA domain (bounded upstream by the Imu promoter) is accessible for switching independent of Smu sequences. This CSR-accessible domain is reminiscent of the promoter-defined domains that target somatic hypermutation. Within the 4-5-kb CSR domain, the targeting of S site locations also depends on the Msh2 mismatch repair protein because Msh2-deficient mice show an increased focus of sites to the Smu tandem ...


Deletion Of The Nucleotide Excision Repair Gene Ercc1 Reduces Immunoglobulin Class Switching And Alters Mutations Near Switch Recombination Junctions, Carol E. Schrader, Joycelyn Vardo, Erin K. Linehan, Michael Z. Twarog, Laura J. Niedernhofer, Jan H. J. Hoeijmakers, Janet Stavnezer Aug 2004

Deletion Of The Nucleotide Excision Repair Gene Ercc1 Reduces Immunoglobulin Class Switching And Alters Mutations Near Switch Recombination Junctions, Carol E. Schrader, Joycelyn Vardo, Erin K. Linehan, Michael Z. Twarog, Laura J. Niedernhofer, Jan H. J. Hoeijmakers, Janet Stavnezer

Women’s Health Research Faculty Publications

The structure-specific endonuclease ERCC1-XPF is an essential component of the nucleotide excision DNA repair pathway. ERCC1-XPF nicks double-stranded DNA immediately adjacent to 3' single-strand regions. Substrates include DNA bubbles and flaps. Furthermore, ERCC1 interacts with Msh2, a mismatch repair (MMR) protein involved in class switch recombination (CSR). Therefore, ERCC1-XPF has abilities that might be useful for antibody CSR. We tested whether ERCC1 is involved in CSR and found that Ercc1(-)(/)(-) splenic B cells show moderately reduced CSR in vitro, demonstrating that ERCC1-XPF participates in, but is not required for, CSR. To investigate the role of ERCC1 in CSR, the nucleotide ...


Mlh1 Can Function In Antibody Class Switch Recombination Independently Of Msh2, Carol E. Schrader, Joycelyn Vardo, Janet Stavnezer May 2003

Mlh1 Can Function In Antibody Class Switch Recombination Independently Of Msh2, Carol E. Schrader, Joycelyn Vardo, Janet Stavnezer

Women’s Health Research Faculty Publications

Mismatch repair proteins participate in antibody class switch recombination, although their roles are unknown. Previous nucleotide sequence analyses of switch recombination junctions indicated that the roles of Msh2 and the MutL homologues, Mlh1 and Pms2, differ. We now asked if Msh2 and Mlh1 function in the same pathway during switch recombination. Splenic B cells from mice deficient in both these proteins were induced to undergo switching in culture. The frequency of switching is reduced, similarly to that of B cells singly deficient in Msh2 or Mlh1. However, the nucleotide sequences of the Smu-Sgamma3 junctions resemble junctions from Mlh1- but not ...


American Cancer Society Guidelines For Breast Cancer Screening: Update 2003, Robert A. Smith, Debbie Saslow, Kimberly Andrews Sawyer, Wylie Burke, Mary E. Costanza, W. Phil Evans 3rd, Roger S. Foster Jr., Edward Hendrick, Harmon J. Eyre, Steven Sener May 2003

American Cancer Society Guidelines For Breast Cancer Screening: Update 2003, Robert A. Smith, Debbie Saslow, Kimberly Andrews Sawyer, Wylie Burke, Mary E. Costanza, W. Phil Evans 3rd, Roger S. Foster Jr., Edward Hendrick, Harmon J. Eyre, Steven Sener

Women’s Health Research Faculty Publications

In 2003, the American Cancer Society updated its guidelines for early detection of breast cancer based on recommendations from a formal review of evidence and a recent workshop. The new screening recommendations address screening mammography, physical examination, screening older women and women with comorbid conditions, screening women at high risk, and new screening technologies.


Role For Mismatch Repair Proteins Msh2, Mlh1, And Pms2 In Immunoglobulin Class Switching Shown By Sequence Analysis Of Recombination Junctions, Carol E. Schrader, Joycelyn Vardo, Janet Stavnezer Feb 2002

Role For Mismatch Repair Proteins Msh2, Mlh1, And Pms2 In Immunoglobulin Class Switching Shown By Sequence Analysis Of Recombination Junctions, Carol E. Schrader, Joycelyn Vardo, Janet Stavnezer

Women’s Health Research Faculty Publications

B cells from mice deficient in mismatch repair (MMR) proteins show decreased ability to undergo class switch recombination in vitro and in vivo. The deficit is not accompanied by any reduction in cell viability or alterations in the cell cycle in B cells cultured in vitro. To assess the role of MMR in switching we examined the nucleotide sequences of Smicro-Sgamma3 recombination junctions in splenic B cells induced in culture to switch to IgG3. The data demonstrate clear differences in the sequences of switch junctions in wild-type B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells. Sequences of ...


The Mu Switch Region Tandem Repeats Are Important, But Not Required, For Antibody Class Switch Recombination, Thomas M. Luby, Carol E. Schrader, Janet Stavnezer, Erik Selsing Jan 2001

The Mu Switch Region Tandem Repeats Are Important, But Not Required, For Antibody Class Switch Recombination, Thomas M. Luby, Carol E. Schrader, Janet Stavnezer, Erik Selsing

Women’s Health Research Faculty Publications

Class switch DNA recombinations change the constant (C) region of the antibody heavy (H) chain expressed by a B cell and thereby change the antibody effector function. Unusual tandemly repeated sequence elements located upstream of H chain gene exons have long been thought to be important in the targeting and/or mechanism of the switch recombination process. We have deleted the entire switch tandem repeat element (S(mu)) from the murine (mu) H chain gene. We find that the S(mu) tandem repeats are not required for class switching in the mouse immunoglobulin H-chain locus, although the efficiency of switching ...


Development Of A State Wide Tobacco Treatment Specialist Training And Certification Programme For Massachusetts, Lori Pbert, Judith K. Ockene, Beth M. Ewy, Ellen Sachs Leicher, Donna D. Warner Dec 2000

Development Of A State Wide Tobacco Treatment Specialist Training And Certification Programme For Massachusetts, Lori Pbert, Judith K. Ockene, Beth M. Ewy, Ellen Sachs Leicher, Donna D. Warner

Women’s Health Research Faculty Publications

OBJECTIVE: To describe the research conducted to structure and develop a statewide tobacco training and certification programme for tobacco treatment specialists (TTSs) in Massachusetts.

DESIGN: Qualitative research strategies were used to obtain information on certification development and opinions regarding TTS training and certification from key informants. A role definition and validation study was then conducted to determine the core competencies for TTSs. A comprehensive training programme was developed, piloted, and finalised, and a certification programme was initiated.

PARTICIPANTS: Key informants included: individuals involved in the development of their professional certification programmes; tobacco treatment providers from across Massachusetts; and national tobacco ...


Evidence For Class-Specific Factors In Immunoglobulin Isotype Switching, A. Shanmugam, M. J. Shi, L. Yauch, Janet Stavnezer, A. L. Kenter Apr 2000

Evidence For Class-Specific Factors In Immunoglobulin Isotype Switching, A. Shanmugam, M. J. Shi, L. Yauch, Janet Stavnezer, A. L. Kenter

Women’s Health Research Faculty Publications

Immunoglobulin class switch recombination (SR) occurs by a B cell-specific, intrachromosomal deletional process between switch regions. We have developed a plasmid-based transient transfection assay for SR to test for the presence of transacting switch activities. The plasmids are novel in that they lack a eukaryotic origin of DNA replication. The recombination activity of these switch substrates is restricted to a subset of B cell lines that support isotype switching on their endogenous loci and to mitogen-activated normal splenic B cells. The factors required for extrachromosomal plasmid recombination are constitutively expressed in proliferating splenic B cells and in B cell lines ...


Reduced Isotype Switching In Splenic B Cells From Mice Deficient In Mismatch Repair Enzymes, Carol E. Schrader, Winifred Edelmann, R. Kucherlapati, Janet Stavnezer Aug 1999

Reduced Isotype Switching In Splenic B Cells From Mice Deficient In Mismatch Repair Enzymes, Carol E. Schrader, Winifred Edelmann, R. Kucherlapati, Janet Stavnezer

Women’s Health Research Faculty Publications

Mice deficient in various mismatch repair (MMR) enzymes were examined to determine whether this repair pathway is involved in antibody class switch recombination. Splenic B cells from mice deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with lipopolysaccharide (LPS) to induce immunoglobulin (Ig)G2b and IgG3, LPS and interleukin (IL)-4 to induce IgG1, or LPS, anti-delta-dextran, IL-4, IL-5, and transforming growth factor (TGF)-beta1 to induce IgA. After 4 d in culture, cells were surface stained for IgM and non-IgM isotypes and analyzed by FACS((R)). B cells from MMR-deficient mice show a 35-75 ...


Characterization Of An Interleukin 4 (Il-4) Responsive Region In The Immunoglobulin Heavy Chain Germline Epsilon Promoter: Regulation By Nf-Il-4, A C/Ebp Family Member And Nf-Kappa B/P50, S. Delphin, Janet Stavnezer Jan 1995

Characterization Of An Interleukin 4 (Il-4) Responsive Region In The Immunoglobulin Heavy Chain Germline Epsilon Promoter: Regulation By Nf-Il-4, A C/Ebp Family Member And Nf-Kappa B/P50, S. Delphin, Janet Stavnezer

Women’s Health Research Faculty Publications

A large body of data indicate that antibody class switching is directed by cytokines by inducing or repressing transcription from unrearranged, or germline, CH genes. Interleukin 4 (IL-4) induces transcription of the germline C epsilon genes in activated B cells and subsequently, cells in this population will undergo switch recombination to immunoglobulin E. Furthermore, the data suggest that transcription of germline C epsilon genes is required for class switching. In this paper we define DNA elements required for induction of transcription of the germline C epsilon genes by IL-4. To do this, segments of DNA from the 5' flank of ...


Effect Of A Community Health Center Intervention On Breast Cancer Screening Among Hispanic American Women, Jane G. Zapka, Donald R. Harris, David W. Hosmer, Mary E. Costanza, Edith Mas, Robin S. Barth Jun 1993

Effect Of A Community Health Center Intervention On Breast Cancer Screening Among Hispanic American Women, Jane G. Zapka, Donald R. Harris, David W. Hosmer, Mary E. Costanza, Edith Mas, Robin S. Barth

Women’s Health Research Faculty Publications

OBJECTIVE. A multiple component intervention in a community health center is presented, and its effect on breast cancer screening participation by Hispanic American women between the ages of 45 and 75 years is discussed.

DATA SOURCES/STUDY SETTING. In 1990, data were collected through a retrospective audit (at least as far back as 1987) of community health center medical records, as well as from a client referral log. The health center, located in a small Massachusetts city, primarily serves clients of Latino heritage.

STUDY DESIGN. The study used a nonexperimental pretest-posttest intervention design to document clients' screening activities. To control ...


Impact Of A Physician Intervention Program To Increase Breast Cancer Screening, Mary E. Costanza, Jane G. Zapka, Donald R. Harris, David W. Hosmer, Robin S. Barth, Victoria P. Gaw, Harry L. Greene, Anne M. Stoddard Nov 1992

Impact Of A Physician Intervention Program To Increase Breast Cancer Screening, Mary E. Costanza, Jane G. Zapka, Donald R. Harris, David W. Hosmer, Robin S. Barth, Victoria P. Gaw, Harry L. Greene, Anne M. Stoddard

Women’s Health Research Faculty Publications

In order to improve compliance with the National Cancer Institute's breast cancer screening guidelines, we developed a multifaceted intervention designed to alter physician screening practice. A pre-post test, two-community design was used. Primary care physicians in one community served as the control. Data were collected by two mailed surveys (1987 and 1990). Response rates were 61% and 64%, respectively. The physician intervention program consisted of a hospital-based continuing medical education program and an outreach component which focused on implementing a reminder system. Outcome measures were self-reported attitudinal, knowledge, and screening practices changes. In spite of an impressive change in ...


Changes In Mammography Use: Economic, Need, And Service Factors, Jane G. Zapka, David W. Hosmer, Mary E. Costanza, Donald R. Harris, Anne M. Stoddard Oct 1992

Changes In Mammography Use: Economic, Need, And Service Factors, Jane G. Zapka, David W. Hosmer, Mary E. Costanza, Donald R. Harris, Anne M. Stoddard

Women’s Health Research Faculty Publications

OBJECTIVES. The purpose of this study was to document changes in mammography use between 1987 and 1990 and assess the relationship of use to selected economic, need, and health system factors.

METHODS. Independent random-digit-dialed telephone surveys of women between 52 and 75 years of age were conducted.

RESULTS. Between 1987 and 1990, the proportion of women who had had a mammogram in the past year increased from 31% to 51%. Though income was significantly related to overall patterns of use, it was not associated with recent mammogram use in 1990. Women with a family history of breast cancer reported greater ...


Structure Of Germline Immunoglobulin Heavy-Chain Gamma 1 Transcripts In Interleukin 4 Treated Mouse Spleen Cells, M. Xu, Janet Stavnezer Jan 1990

Structure Of Germline Immunoglobulin Heavy-Chain Gamma 1 Transcripts In Interleukin 4 Treated Mouse Spleen Cells, M. Xu, Janet Stavnezer

Women’s Health Research Faculty Publications

Antibody class switching is mediated by a DNA recombination event that replaces the C mu gene with one of the other heavy (H) chain constant region (CH) genes located 3' to the C mu gene. The regulation of this process is essential to the immune response because different CH regions provide different biological functions. Correlative evidence indicates that the isotype (class) specificity of the switch is determined by the accessibility of specific CH genes as indicated by hypomethylation and transcriptional activity. For example, RNAs transcribed from specific unrearranged CH genes are induced prior to switching under conditions that promote subsequent ...


Breast Cancer Screening By Mammography: Utilization And Associated Factors, Jane G. Zapka, Anne M. Stoddard, Mary E. Costanza, Harru L. Greene Jr. Nov 1989

Breast Cancer Screening By Mammography: Utilization And Associated Factors, Jane G. Zapka, Anne M. Stoddard, Mary E. Costanza, Harru L. Greene Jr.

Women’s Health Research Faculty Publications

The status of mammography screening experience and factors related to utilization were examined in six towns serviced by physician staffs at five hospitals. Data were collected via random digit dial telephone interview of a probability sample of 1184 women, aged 45-75 years. The results showed that 55% of the women reported ever having had a mammogram. Of those who had ever had a mammogram, 21% reported that the mammogram in the past year was their first one. Of those women who are over 50 and had ever had a mammogram, 57% reported one in the past year. Analyses demonstrated that ...