bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Characterization of Novel Superantigens from Streptococcus pyogenes
Authors: Proft Thomas , Louise Moffatt S. , Berkahn Celia J. , Fraser John D.
Published: July 2002

Three novel streptococcal superantigen genes (spe-g, spe-h, and spe-j) were identified from the Streptococcus pyogenes M1 genomic database at the University of Oklahoma. A fourth novel gene (smez-2) was isolated from the S. pyogenes strain 2035, based on sequence homology to the streptococcal mitogenic exotoxin z (smez) gene. SMEZ-2, SPE-G, and SPE-J are most closely related to SMEZ and streptococcal pyrogenic exotoxin (SPE)-C, whereas SPE-H is most similar to the staphylococcal toxins than to any other streptococcal toxin. Recombinant (r)SMEZ, rSMEZ-2, rSPE-G, and rSPE-H were mitogenic for human peripheral blood lymphocytes with half-maximal responses between 0.02 and 50 pg/ml (rSMEZ-2 and rSPE-H, respectively). SMEZ-2 is the most potent superantigen (SAg) discovered thus far. All toxins, except rSPE-G, were active on murine T cells, but with reduced potency. Binding to a human B-lymphoblastoid line was shown to be zinc dependent with high binding affinity of 15–65 nM. Evidence from modeled protein structures and competitive binding experiments suggest that high affinity binding of each toxin is to the major histocompatibility complex class II β chain. Competition for binding between toxins was varied and revealed overlapping but discrete binding to subsets of class II molecules in the hierarchical order (SMEZ, SPE-C) > SMEZ-2 > SPE-H > SPE-G. The most common targets for the novel SAgs were human Vβ2.1- and Vβ4-expressing T cells. This might reflect a specific role for this subset of Vβs in the immune defense of gram-positive bacteria.
Interleukin 2 Receptor Signaling Regulates the Perforin Gene through Signal Transducer and Activator of Transcription (Stat)5 Activation of Two Enhancers
Authors: Zhang Jin , Scordi Irinoulla , Smyth Mark J. , Lichtenheld Mathias G.
Published: July 2002

Optimal T cell differentiation into effector cells with specialized functions requires the participation of cytokine receptor signals. In T helper cells, this process is controlled by chromatin changes and distal and proximal regulatory elements as well as specific transcription factors. Analogous events during cytotoxic T lymphocyte (CTL) differentiation remain to be identified. This process is known, however, to be crucially regulated by interleukin (IL)-2 receptor (R) signals. It is accompanied by the induction of perforin expression via a mechanism that does not entail proximal regulatory elements. In this report, transgenically expressed human perforin gene locus DNAs demonstrate that IL-2R signals target two IL-2–dependent enhancers ∼15 and 1 kilobase upstream of the promoter. The most distal enhancer may also respond to TCR signals. In transient transfections, both enhancers required two identically spaced Stat-like elements for their activation, which was abolished by expression of a dominant negative signal transducer and activator of transcription (Stat)5 molecule, whereas a constitutively active Stat5 molecule bypassed the requirement for IL-2R signals. These results provide a molecular explanation for the activation of the perforin gene during CTL differentiation and complement the analysis of animals deficient in the activation of the IL-2R Stat signaling pathway by establishing perforin as a target gene.
Somatic Mutation of the Cd95 Gene in Human B Cells as a Side-Effect of the Germinal Center Reaction
Authors: Müschen Markus , Re Daniel , Jungnickel Berit , Diehl Volker , Rajewsky Klaus , Küppers Ralf
Published: July 2002

Somatic hypermutation specifically modifies rearranged immunoglobulin (Ig) genes in germinal center (GC) B cells. However, the bcl-6 gene can also acquire somatic mutations during the GC reaction, indicating that certain non-Ig genes can be targeted by the somatic hypermutation machinery. The CD95 gene, implicated in negative selection of B lymphocytes in GCs, is specifically expressed by GC B cells and was recently identified as a tumor suppressor gene being frequently mutated in (post) GC B cell lymphomas. In this study, the 5′ region (5′R) and/or the last exon coding for the death domain (DD) of the CD95 gene were investigated in naive, GC, and memory B cells from seven healthy donors. About 15% of GC and memory, but not naive, B cells carried mutations within the 5′R (mutation frequency 2.5 × 10−4 per basepair). Mutations within the DD were very rare but could be efficiently selected by inducing CD95-mediated apoptosis: in 22 apoptosis-resistant cells, 12 DD mutations were found. These results indicate that human B cells can acquire somatic mutations of the CD95 gene during the GC reaction, which potentially confers apoptosis resistance and may counteract negative selection through the CD95 pathway.
The Long Isoform of Terminal Deoxynucleotidyl Transferase Enters the Nucleus And, Rather than Catalyzing Nontemplated Nucleotide Addition, Modulates the Catalytic Activity of the Short Isoform
Authors: Benedict Cindy L. , Gilfillan Susan , Kearney John F.
Published: July 2002

During variable/diversity/joining (V[D]J) recombination, the enzyme terminal deoxynucleotidyl transferase (Tdt) adds random nucleotides at the junctions of the rearranging gene segments, increasing diversity of the antibody (Ab) and T cell receptor repertoires. Two splice variants of Tdt have been described, but only one (short isoform of Tdt [TdtS]) has been convincingly demonstrated to catalyze nontemplated (N) addition in vitro. We have expressed each splice variant of Tdt in transgenic (Tg) mice and found that the TdtS transgene catalyzes N addition on the endogenous Tdt−/− background and in fetal liver, but that the long isoform of Tdt (TdtL) transgene does neither. In contrast to previous in vitro results, both TdtS and TdtL are translocated to the nucleus in our model. Furthermore, TdtL/TdtS double Tg mice exhibit less N addition in fetal liver than do TdtS Tg mice. Whereas the TdtS transgene was shown to have functional consequences on the antiphosphorylcholine (PC) B cell repertoire, TdtL Tg mice exhibit a normal PC response, and Tdt−/− mice actually exhibit an increase in the PC response and in TEPC 15 idiotype+ Ab production. We conclude that TdtL localizes to the nucleus in vivo where it serves to modulate TdtS function.
Identification of the In Vivo Role of a Viral bcl-2
Authors: Gangappa Shivaprakash , van Dyk Linda F. , Jewett Travis J. , Speck Samuel H. , Virgin Herbert W.
Published: July 2002

Many γ-herpesviruses encode candidate oncogenes including homologues of host bcl-2 and cyclin proteins (v-bcl-2, v-cyclin), but the physiologic roles of these genes during infection are not known. We show for the first time in any virus system the physiologic role of v-bcl-2. A γ-herpesvirus v-bcl-2 was essential for efficient ex vivo reactivation from latent infection, and for both persistent replication and virulence during chronic infection of immunocompromised (interferon [IFN]-γ−/−) mice. The v-cyclin was also critical for the same stages in pathogenesis. Strikingly, while the v-bcl-2 and v-cyclin were important for chronic infection, these genes were not essential for viral replication in cell culture, viral replication during acute infection in vivo, establishment of latent infection, or virulence during acute infection. We conclude that v-bcl-2 and v-cyclin have important roles during latent and persistent γ-herpesvirus infection and that herpesviruses encode genes with specific roles during chronic infection and disease, but not acute infection and disease. As γ-herpesviruses primarily cause human disease during chronic infection, these chronic disease genes may be important targets for therapeutic intervention.
Uncharged S4 Residues and Cooperativity in Voltage-dependent Potassium Channel Activation
Authors: Smith-Maxwell Catherine J. , Ledwell Jennifer L. , Aldrich Richard W.
Published: July 2002

Substitution of the S4 of Shaw into Shaker alters cooperativity in channel activation by slowing a cooperative transition late in the activation pathway. To determine the amino acids responsible for the functional changes in Shaw S4, we created several mutants by substituting amino acids from Shaw S4 into Shaker. The S4 amino acid sequences of Shaker and Shaw S4 differ at 11 positions. Simultaneous substitution of just three noncharged residues from Shaw S4 into Shaker (V369I, I372L, S376T; ILT) reproduces the kinetic and voltage-dependent properties of Shaw S4 channel activation. These substitutions cause very small changes in the structural and chemical properties of the amino acid side chains. In contrast, substituting the positively charged basic residues in the S4 of Shaker with neutral or negative residues from the S4 of Shaw S4 does not reproduce the shallow voltage dependence or other properties of Shaw S4 opening. Macroscopic ionic currents for ILT could be fit by modifying a single set of transitions in a model for Shaker channel gating (Zagotta, W.N., T. Hoshi, and R.W. Aldrich. 1994. J. Gen. Physiol. 103:321–362). Changing the rate and voltage dependence of a final cooperative step in activation successfully reproduces the kinetic, steady state, and voltage-dependent properties of ILT ionic currents. Consistent with the model, ILT gating currents activate at negative voltages where the channel does not open and, at more positive voltages, they precede the ionic currents, confirming the existence of voltage-dependent transitions between closed states in the activation pathway. Of the three substitutions in ILT, the I372L substitution is primarily responsible for the changes in cooperativity and voltage dependence. These results suggest that noncharged residues in the S4 play a crucial role in Shaker potassium channel gating and that small steric changes in these residues can lead to large changes in cooperativity within the channel protein.
A Hot Spot for the Interaction of Gating Modifier Toxins with Voltage-Dependent Ion Channels
Authors: Winterfield Jeffrey R. , Swartz Kenton J.
Published: July 2002

The gating modifier toxins are a large family of protein toxins that modify either activation or inactivation of voltage-gated ion channels. ω-Aga-IVA is a gating modifier toxin from spider venom that inhibits voltage-gated Ca2+ channels by shifting activation to more depolarized voltages. We identified two Glu residues near the COOH-terminal edge of S3 in the α1A Ca2+ channel (one in repeat I and the other in repeat IV) that align with Glu residues previously implicated in forming the binding sites for gating modifier toxins on K+ and Na+ channels. We found that mutation of the Glu residue in repeat I of the Ca2+ channel had no significant effect on inhibition by ω-Aga-IVA, whereas the equivalent mutation of the Glu in repeat IV disrupted inhibition by the toxin. These results suggest that the COOH-terminal end of S3 within repeat IV contributes to forming a receptor for ω-Aga-IVA. The strong predictive value of previous mapping studies for K+ and Na+ channel toxins argues for a conserved binding motif for gating modifier toxins within the voltage-sensing domains of voltage-gated ion channels.
Large time asymptotics of solutions to the generalized Benjamin-Ono equation
Authors: Hayashi Nakao , Naumkin Pavel
Published: July 2002

We study the asymptotic behavior for large time of solutions to the Cauchy problem for the generalized Benjamin-Ono (BO) equation:

u

t

+
(

|

u

|

ρ
−
1

u

)

x

+

H

u

x
x

=
0

u_{t} + (|u|^{\rho -1}u)_{x} + \mathcal {H} u_{xx} = 0

, where

H

\mathcal {H}

is the Hilbert transform,

x
,
t
∈

R

x, t \in {\mathbf {R}}

, when the initial data are small enough. If the power

ρ
\rho

of the nonlinearity is greater than

3
3

, then the solution of the Cauchy problem has a quasilinear asymptotic behavior for large time. In the case

ρ
=
3

\rho =3

critical for the asymptotic behavior i.e. for the modified Benjamin-Ono equation, we prove that the solutions have the same

L

∞

L^{\infty }

time decay as in the corresponding linear BO equation. Also we find the asymptotics for large time of the solutions of the Cauchy problem for the BO equation in the critical and noncritical cases. For the critical case, we prove the existence of modified scattering states if the initial function is sufficiently small in certain weighted Sobolev spaces. These modified scattering states differ from the free scattering states by a rapidly oscillating factor.
Tame and wild kernels of quadratic imaginary number fields
Authors: Browkin Jerzy , Gangl Herbert
Published: July 2002

For all quadratic imaginary number fields

F
F

of discriminant

d
>
−
5000
,

d>-5000,

we give the conjectural value of the order of Milnor’s group (the tame kernel)

K

2

O

F

,

K_{2}O_{F},

where

O

F

O_{F}

is the ring of integers of

F
.

F.

Assuming that the order is correct, we determine the structure of the group

K

2

O

F

K_{2}O_{F}

and of its subgroup

W

F

W_{F}

(the wild kernel). It turns out that the odd part of the tame kernel is cyclic (with one exception,

d
=
−
3387

d=-3387

).
Tables of octic fields with a quartic subfield
Authors: Cohen H. , Diaz y Diaz F. , Olivier M.
Published: July 2002

We describe the computation of extended tables of degree 8 fields with a quartic subfield, using class field theory. In particular we find the minimum discriminants for all signatures and for all the possible Galois groups. We also discuss some phenomena and statistics discovered while making the tables, such as the occurrence of 11 non-isomorphic number fields having the same discriminant, or several pairs of non-isomorphic number fields having the same Dedekind zeta function.
Square integrable representations of classical p-adic groups corresponding to segments
Authors: Tadić Marko
Published: July 2002

Let

S
n

S_n

be either the group

S
p
(
n
)

Sp(n)

or

S
O
(
2
n
+
1
)

SO(2n+1)

over a

p
p

-adic field

F
F

. Then Levi factors of maximal parabolic subgroups are (isomorphic to) direct products of

G
L
(
k
)

GL(k)

and

S

n
−
k

S_{n-k}

, with

1
≤
k
≤
n

1\leq k\leq n

. The square integrable representations which we define and study in this paper (and prove their square integrability), are subquotients of reducible representations Ind

P

S
n

(
δ
⊗
σ
)
,

_P^{S_n}(\delta \otimes \sigma ),

where

δ
\delta

is an essentially square integrable representation of

G
L
(
k
)

GL(k)

, and

σ
\sigma

is a cuspidal representation of

S

n
−
k

S_{n-k}

. These square integrable representations play an important role in a construction of more general square integrable representations.
ER-Golgi Traffic Is a Prerequisite for Efficient ER Degradation
Authors: Taxis Christof , Vogel Frank , Wolf Dieter H.
Published: July 2002

Protein quality control is an essential function of the endoplasmic reticulum. Misfolded proteins unable to acquire their native conformation are retained in the endoplasmic reticulum, retro-translocated back into the cytosol, and degraded via the ubiquitin-proteasome system. We show that efficient degradation of soluble malfolded proteins in yeast requires a fully competent early secretory pathway. Mutations in proteins essential for ER-Golgi protein traffic severely inhibit ER degradation of the model substrate CPY*. We found ER localization of CPY* in WT cells, but no other specific organelle for ER degradation could be identified by electron microscopy studies. Because CPY* is degraded in COPI coat mutants, only a minor fraction of CPY* or of a proteinaceous factor required for degradation seems to enter the recycling pathway between ER and Golgi. Therefore, we propose that the disorganized structure of the ER and/or the mislocalization of Kar2p, observed in early secretory mutants, is responsible for the reduction in CPY* degradation. Further, we observed that mutations in proteins directly involved in degradation of malfolded proteins (Der1p, Der3/Hrd1p, and Hrd3p) lead to morphological changes of the endoplasmic reticulum and the Golgi, escape of CPY* into the secretory pathway and a slower maturation rate of wild-type CPY.
Identification of a Novel Light Intermediate Chain (D2LIC) for Mammalian Cytoplasmic Dynein 2
Authors: Grissom Paula M. , Vaisberg Eugeni A. , McIntosh J. Richard
Published: July 2002

The diversity of dynein's functions in mammalian cells is a manifestation of both the existence of multiple dynein heavy chain isoforms and an extensive set of associated protein subunits. In this study, we have identified and characterized a novel subunit of the mammalian cytoplasmic dynein 2 complex. The sequence similarity between this 33-kDa subunit and the light intermediate chains (LICs) of cytoplasmic dynein 1 suggests that this protein is a dynein 2 LIC (D2LIC). D2LIC contains a P-loop motif near its NH2terminus, and it shares a short region of similarity to the yeast GTPases Spg1p and Tem1p. The D2LIC subunit interacts specifically with DHC2 (or cDhc1b) in both reciprocal immunoprecipitations and sedimentation assays. The expression of D2LIC also mirrors that of DHC2 in a variety of tissues. D2LIC colocalizes with DHC2 at the Golgi apparatus throughout the cell cycle. On brefeldin A-induced Golgi fragmentation, a fraction of D2LIC redistributes to the cytoplasm, leaving behind a subset of D2LIC that is localized around the centrosome. Our results suggest that D2LIC is a bona fide subunit of cytoplasmic dynein 2 that may play a role in maintaining Golgi organization by binding cytoplasmic dynein 2 to its Golgi-associated cargo.
The Cytoplasmic Tail of Invariant Chain Regulates Endosome Fusion and Morphology
Authors: Nordeng Tommy W. , Gregers Tone F. , Kongsvik Thomas Lasker , Méresse Stéphane , Gorvel Jean-Pierre , Jourdan Fabrice , Motta Andrea , Bakke Oddmund
Published: July 2002

The major histocompatibility complex class II associated invariant chain (Ii) has been shown to inhibit endocytic transport and to increase the size of endosomes. We have recently found that this property has a significant impact on antigen processing and presentation. Here, we show in a cell-free endosome fusion assay that expression of Ii can increase fusion after phosphatidylinositol 3-kinase activity is blocked by wortmannin. In live cells wortmannin was also not able to block formation of the Ii-induced enlarged endosomes. The effects of Ii on endosomal transport and morphology depend on elements within the cytoplasmic tail. Data from mutagenesis analysis and nuclear magnetic resonance-based structure calculations of the Ii cytoplasmic tail demonstrate that free negative charges that are not involved in internal salt bridges are essential for both interactions between the tails and for the formation of enlarged endosomes. This correlation indicates that it is interactions between the Ii cytoplasmic tails that are involved in endosome fusion. The combined data from live cells, cell-free assays, and molecular dynamic simulations suggest that Ii molecules on different vesicles can promote endosome docking and fusion and thereby control endosomal traffic of membrane proteins and endosomal content.
Localized Calcium Signals along the Cleavage Furrow of theXenopusEgg Are Not Involved in Cytokinesis
Authors: Noguchi Tatsuhiko , Mabuchi Issei
Published: July 2002

It has been proposed that a localized calcium (Ca) signal at the growing end of the cleavage furrow triggers cleavage furrow formation in large eggs. We have examined the possible role of a Ca signal in cleavage furrow formation in the Xenopus laevis egg during the first cleavage. We were able to detect two kinds of Ca waves along the cleavage furrow. However, the Ca waves appeared after cleavage furrow formation in late stages of the first cleavage. In addition, cleavage was not affected by injection of dibromoBAPTA or EGTA into the eggs at a concentration sufficient to suppress the Ca waves. Furthermore, even smaller classes of Ca release such as Ca puffs and Ca blips do not occur at the growing end of the cleavage furrow. These observations demonstrate that localized Ca signals in the cleavage furrow are not involved in cytokinesis. The two Ca waves have unique characteristics. The first wave propagates only in the region of newly inserted membrane along the cleavage furrow. On the other hand, the second wave propagates along the border of new and old membranes, suggesting that this wave might be involved in adhesion between two blastomeres.
Pancreatic β-Cell Protein Granuphilin Binds Rab3 and Munc-18 and Controls Exocytosis
Authors: Coppola Thierry , Frantz Christian , Perret-Menoud Véronique , Gattesco Sonia , Hirling Harald , Regazzi Romano
Published: July 2002

Granuphilin/Slp-4 is a member of the synaptotagmin-like protein family expressed in pancreatic β-cells and in the pituitary gland. We show by confocal microscopy that both granuphilin-a and -b colocalize with insulin-containing secretory granules positioned at the periphery of pancreatic β-cells. Overexpression of granuphilins in insulin-secreting cell lines caused a profound inhibition of stimulus-induced exocytosis. Granuphilins were found to bind to two components of the secretory machinery of pancreatic β-cells, the small GTP-binding protein Rab3 and the solubleN-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)–binding protein Munc-18. The interaction with Rab3 occurred only with the GTP-bound form of the protein and was prevented by a point mutation in the effector domain of the GTPase. Structure-function studies using granuphilin-b mutants revealed that complete loss of Rab3 binding is associated with a reduction in the capacity to inhibit exocytosis. However, the granuphilin/Rab3 complex alone is not sufficient to mediate the decrease of exocytosis, suggesting the existence of additional binding partners. Taken together, our observations indicate that granuphilins play an important role in pancreatic β-cell exocytosis. In view of the postulated role of Munc-18 in secretory vesicle docking, our data suggest that granuphilins may also be involved in this process.
Risk Factors for Uterine Fibroids among Women Undergoing Tubal Sterilization
Authors: Chen Chao-Ru , Buck Germaine M. , Courey Norman G. , Perez Kimberly M. , Wactawski-Wende Jean
Published: July 2002

Uterine leiomyomas are reported to be the most common benign gynecologic tumors affecting premenopausal women, and they are often associated with considerable morbidity. The purpose of this study was to identify risk factors for uterine fibroids among women undergoing tubal sterilization. Cases comprised women aged 17–44 years whose uterine fibroids were first visualized at the time of tubal sterilization (1978–1979 or 1985–1987) or who reported a history of uterine fibroids (n = 317). Controls were randomly selected from women with no laparoscopic evidence of or history of fibroids (n = 1,268). Adjusted odds ratios were estimated using unconditional logistic regression separately for White (n = 1,235) and African-American(n = 350) women. Risk factors for White women included: age 40–44 years (odds ratio (OR) = 6.3; 95% confidence interval (CI): 3.5, 11.6), ≥5 years since last delivery (OR = 1.9; 95% CI: 1.1, 3.1), lifetime cigarette smoking of ≥1 pack/day (OR = 1.6; 95% CI: 1.1, 2.3), menstrual cycle length of >30 days (OR = 1.6; 95% CI: 1.1, 3.3), and menstrual bleeding for ≥6 days (OR = 1.4; 95% CI: 1.0, 2.0). Parous women were at reduced risk compared with nulliparous women (OR = 0.2; 95% CI: 0.1, 0.3). Advancing age was the only significant risk factor for African-American women (ages 40–44 years, OR = 27.5; 95% CI: 5.6, 83.6). Current oral contraceptive use and elective abortion were not associated with fibroids.
Invited Commentary: Studying the Epidemiology of Uterine Leiomyomata—Past, Present, and Future
Authors: Schwartz Stephen M.
Published: July 2002

Uterine leiomyomata have a substantial impact on women's reproductive health, but epidemiologists have focused relatively little energy on identifying risk factors for this condition. Only a handful of studies, most of which were not designed to address methodological challenges posed by these tumors, have been conducted. These studies focused almost exclusively on reproductive and hormonal characteristics as possible risk factors, but consistent relations have not emerged. Three new reports (from two studies) in this issue of the Journal target the paucity of information on uterine leiomyomata risk factors by testing novel hypotheses, by employing designs that incorporate subclinical tumors or account for variable management of clinically recognized disease, or by using a combination of these approaches. The success of these strategies and the contributions of the new findings are discussed. Recommendations are made for a program of research that eventually could improve our knowledge of uterine leiomyomata etiology and yield clues to the prevention of associated morbidity.
Bone Mass and the Risk of Colon Cancer among Postmenopausal Women
Authors: Zhang Yuqing , Felson David T. , Ellison R. Curtis , Kreger Bernard E. , Schatzkin Arthur , Dorgan Joanne F. , Cupples L. Adrienne , Levy Daniel , Kiel Douglas P.
Published: July 2002

Although postmenopausal estrogen use has been associated with a lower risk of colon cancer in women, some studies do not confirm such findings. No known study has examined the effect of cumulative estrogen exposure on colon cancer risk. Bone mass has been proposed as a marker of cumulative exposure to endogenous and exogenous estrogens. By using data on 1,394 Massachusetts women in the Framingham Study who underwent hand radiography in 1967–1970, the authors examined the association between bone mass (from relative areas of the second metacarpal) and colon cancer incidence. Over 27 years of follow-up, 44 incident colon cancer cases occurred. Colon cancer incidence decreased from 2.19 per 1,000 person-years among the women in the lowest age-specific tertile of bone mass to 1.59 and 1.08 among women in the middle and the highest tertiles, respectively. After adjustment for age and other potential confounding factors, the rate ratios of colon cancer were 1.0, 0.7 (95% confidence interval: 0.3, 1.3), and 0.4 (95% confidence interval: 0.2, 0.9) from the lowest to the highest tertile (p for trend = 0.033). No association was found between bone mass and rectal cancer. The findings suggest that women with higher bone mass, perhaps reflecting greater cumulative estrogen exposure, have a decreased risk of colon cancer.
Excess Incidence of Squamous Cell Esophageal Cancer among US Black Men: Role of Social Class and Other Risk Factors
Authors: Morris Brown Linda , Hoover Robert , Silverman Debra , Baris Dalsu , Hayes Richard , Swanson G. Marie , Schoenberg Janet , Greenberg Raymond , Liff Jonathan , Schwartz Ann , Dosemeci Mustafa , Pottern Linda , Fraumeni Joseph F.
Published: July 2002

Data from a population-based case-control study were used to evaluate the relation between social class factors and squamous cell esophageal cancer and the extent to which alcohol, tobacco, diet, and low income contribute to the higher incidence among Black men than among White men in the United States. A total of 347 male cases (119 White, 228 Black) and 1,354 male controls (743 White, 611 Black) were selected from three US geographic areas (Atlanta, Georgia, Detroit, Michigan, and New Jersey). Cases were residents of the study areas aged 30–79 years who had been diagnosed with histologically confirmed esophageal cancer between 1986 and 1989. The adjusted odds ratios for subjects with annual incomes less than $10,000 versus incomes of $25,000 or more were 4.3 (95% confidence interval: 2.1, 8.7) for Whites and 8.0 (95% confidence interval: 4.3, 15.0) for Blacks. The combination of all four major risk factors—low income, moderate/heavy alcohol intake, tobacco use, and infrequent consumption of raw fruits and vegetables—accounted for almost all of the squamous cell esophageal cancers in Whites (98%) and Blacks (99%) and for 99% of the excess incidence among Black men. Thus, lifestyle modifications, especially a lowered intake of alcoholic beverages, would markedly decrease the incidence of squamous cell esophageal cancer in both racial groups and would narrow the racial disparity in risk. Further studies on the determinants of social class may help to identify a new set of exposures for this tumor that are amenable to intervention.
Association of Dietary Antioxidants and Waist Circumference with Pulmonary Function and Airway Obstruction
Authors: Chen Ruoling , Tunstall-Pedoe Hugh , Bolton-Smith Caroline , Hannah Mary K. , Morrison Caroline
Published: July 2002

Dietary antioxidants, waist circumference, and pulmonary function were measured in the Fourth Scottish MONICA cross-sectional survey of 865 men and 971 women aged 25–64 years. Waist circumference was inversely related to forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), even after adjustment for age, height, weight, working status, energy intake, and smoking variables in a multiple linear regression model (men: β = −0.017 for FEV1 l/cm, p < 0.01 and β = −0.008 for FVC, p = 0.04; women: β = −0.009 for FEV1, p < 0.01 and β = −0.007 for FVC, p = 0.01). After additional adjustment for waist circumference, estimated vitamin C and β-carotene intakes were positively associated with lung function in men (vitamin C: β = 0.102 for FEV1 l/mg/day, p = 0.03; β-carotene: β = 0.073 for FVC l/μg/day, p = 0.02). Retinol and vitamin E were not significantly related to lung function for either sex. A case-control study of airway obstruction showed that waist circumference was significantly associated, while vitamin C could be protective. The study suggests that adequate intake of antioxidants and avoidance of increasing girth could help to preserve lung function.
Cryptosporidium Infection in Bedouin Infants Assessed by Prospective Evaluation of Anticryptosporidial Antibodies and Stool Examination
Authors: Robin Guy , Fraser Drora , Orr Nadav , Sela Tamar , Slepon Raphael , Ambar Ruhama , Dagan Ron , Le Blancq Sylvie , Deckelbaum Richard J. , Cohen Dani
Published: July 2002

An enzyme-linked immunosorbent assay system using oocyst lysate as antigen was used to detect serum-specific antibody responses to Cryptosporidium parvum between 1989 and 1994 in consecutive sera obtained at birth, and at the age of 6, 12, and 23 months, from 52 infants living in a Bedouin town located in the south of Israel. The serologic tests revealed high levels of immunoglobulin G anti-Cryptosporidium at birth that dropped significantly by the age of 6 months and then rose continuously to a geometric mean titer of 481 at age 23 months. The serum immunoglobulin M Cryptosporidium antibodies rose continuously from nearly undetectable levels at birth to a geometric mean titer of 471 (157-fold increase) at age 23 months. All the subjects already showed at 6 months a significant rise in immunoglobulin M. A significant rise in immunoglobulin A titers was detected in 48% and 91% of subjects at 6 and 23 months, respectively. By monthly surveillance, microscopy using the modified Ziehl-Neelsen method and confirmed by indirect immunofluorescence assay detected Cryptosporidium antigens in only 11% at age 6 months and 48% at age 23 months. The extent of exposure to Cryptosporidium immediately after birth as detected by serology is much higher than that predicted by frequent prospective assessment of stool samples.
Immunity to Poliomyelitis in the Netherlands
Authors: Conyn-van Spaendonck Marina A. E. , de Melker Hester E. , Abbink Frithjofna , Elzinga-Gholizadea Nazrin , Kimman Tjeerd G. , van Loon Ton
Published: July 2002

Despite a vaccination coverage rate of 97%, several poliomyelitis outbreaks occurred in the Netherlands during the last three decades, all among sociogeographically clustered, unvaccinated persons. Therefore, to eradicate polio, insight into poliomyelitis immunity is particularly useful. In 1995–1996, the authors conducted a population-based study and determined neutralizing antibodies against poliovirus types 1, 2, and 3 in 9,274 sera from the general population and from religious groups rejecting vaccination. In the general population, the antibody prevalence (≥1:8) was 96.6% (95% confidence interval (CI): 95.9, 97.2), 93.4% (95% CI: 92.3, 94.5), and 89.7% (95% CI: 88.3, 91.0) for poliovirus types 1, 2, and 3, respectively. Antibodies persisted for long periods in persons with natural immunity as well as in persons whose immunity was induced by inactivated polio vaccine. In Orthodox Reformed persons, the antibody prevalence of poliovirus types 1, 2, and 3 was 65.0% (95% CI: 57.2, 72.9), 59.0% (95% CI: 40.1, 77.9), and 68.7% (95% CI: 65.2, 72.2), respectively. The recent outbreaks clearly affected the seroprevalence profiles of Orthodox Reformed groups but not the general population. At present, there is an insufficient social and political basis for mandatory vaccination; therefore, global eradication of poliovirus seems to be the only way to protect these Orthodox Reformed persons against future poliomyelitis outbreaks.
Race, Anthropometric Factors, and Stage at Diagnosis of Breast Cancer
Authors: Moorman Patricia G. , Jones Beth A. , Millikan Robert C. , Hall Ingrid J. , Newman Beth
Published: July 2002

A recent study suggested that the greater prevalence of severe obesity among African-American women explained almost one third of the observed differences between African-American and White women in stage at diagnosis of breast cancer. The objective of this investigation was to attempt to replicate these findings in a second, larger population and to expand the analyses by including a measure of body fat distribution, the waist:hip ratio. The authors used data from a population-based study in North Carolina comprising 791 breast cancer cases (302 in African-American women and 489 in White women) diagnosed between 1993 and 1996. African-American women were more likely to have later-stage (TNM stage ≥II) breast cancer (odds ratio (OR) = 2.2; 95% confidence interval (CI): 1.6, 2.9). They also were much more likely to be severely obese (body mass index ≥32.3) (OR = 9.7; 95% CI: 6.5, 14.5) and to be in the highest tertile of waist:hip ratio (OR = 5.7; 95% CI: 3.8, 8.6). In multivariate logistic regression models, adjustment for waist:hip ratio reduced the odds ratio for later-stage disease in African-American women by 20%; adjustment for both waist:hip ratio and severe obesity reduced the odds ratio by 27%. These observations suggest that obesity and body fat distribution, in addition to socioeconomic and medical care factors, contribute to racial differences in stage at breast cancer diagnosis.
First Analysis of Cancer Incidence and Occupational Radiation Exposure Based on the National Dose Registry of Canada
Authors: Sont W. N. , Zielinski J. M. , Ashmore J. P. , Jiang H. , Krewski D. , Fair M. E. , Band P. R. , Létourneau E. G.
Published: July 2002

A cohort study was conducted to investigate the relation between cancer incidence and occupational exposure to ionizing radiation. Records containing dose information from 1951 to 1988 for 191,333 persons were extracted from the National Dose Registry of Canada. The records were linked to the Canadian Cancer Data Base, with incidence data from 1969 to 1988. Standardized incidence ratios were calculated using Canadian cancer incidence rates stratified by age, sex, and calendar year. Excess relative risks were obtained from internally based dose-response analyses. The following significant results were found for males and females combined: a deficit in the standardized incidence ratio for all cancers combined; elevated standardized incidence ratios for thyroid cancer and melanoma; and elevated excess relative risks for rectum, leukemia, lung, all cancers combined, all except lung, and all except leukemia. For males, cancers of the colon, pancreas, and testis also showed significantly elevated excess relative risks. The specific cancer types listed above have been implicated in previous studies on occupational exposure to ionizing radiation, except for testis, colon, and melanoma, while the findings on thyroid cancer from previous studies are inconclusive. The thyroid standardized incidence ratios in this study are highly significant, but further investigation is needed to assess the possibility of association with occupational radiation exposure.
Predictive 5-Year Survivorship Model of Cystic Fibrosis
Authors: Liou Theodore G. , Adler Frederick R. , FitzSimmons Stacey C. , Cahill Barbara C. , Hibbs Jonathan R. , Marshall Bruce C.
Published: July 2002

The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis. Such a model could help researchers and clinicians to evaluate therapies, improve the design of prospective studies, monitor practice patterns, counsel individual patients, and determine the best candidates for lung transplantation. The authors used information from the Cystic Fibrosis Foundation Patient Registry (CFFPR), which has collected longitudinal data on approximately 90% of cystic fibrosis patients diagnosed in the United States since 1986. They developed multivariate logistic regression models by using data on 5,820 patients randomly selected from 11,630 in the CFFPR in 1993. Models were tested for goodness of fit and were validated for the remaining 5,810 patients for 1993. The validated 5-year survivorship model included age, forced expiratory volume in 1 second as a percentage of predicted normal, gender, weight-for-age z score, pancreatic sufficiency, diabetes mellitus, Staphylococcus aureus infection, Burkerholderia cepacia infection, and annual number of acute pulmonary exacerbations. The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research.
Immigration and the Health of Asian and Pacific Islander Adults in the United States
Authors: Parker Frisbie W. , Cho Youngtae , Hummer Robert A.
Published: July 2002

The authors used the 1992–1995 National Health Interview Survey to examine the effect of immigrant status (both nativity and duration of residence in the United States) on the health of Asian and Pacific Islander adults by constructing models in which national origin was also specified. In logistic regression models adjusted for age, marital status, living arrangement, family size, and several socioeconomic indicators, immigrants were found to be in better health than their US-born counterparts, but their health advantages consistently decreased with duration of residence. For example, for Asian and Pacific Islander immigrants whose duration of residence was less than 5 years, 5–9 years, and 10 years or more, the odds ratios for activity limitations were 0.45 (95% confidence interval (CI): 0.33, 0.62), 0.65 (95% CI: 0.46, 0.93), and 0.73 (95% CI: 0.60, 0.90), respectively. Similar findings emerged for respondent-reported health and bed days due to illness. These results support the validity and complementarity of the migration selectivity and acculturation hypotheses. However, the picture was not uniformly positive. The health of certain Asian and Pacific Islander groups, notably Pacific Islanders and Vietnamese, was found to be less favorable than average. Finally, after adjustment for health status, immigrants seemed to have less adequate access to formal medical care.
Forearm Bone Mineral Density by Age in 7,620 Men and Women The Tromsø Study, a Population-based Study
Authors: Rosvold Berntsen Gro K. , Fønnebø Vinjar , Tollan Anne , Johanne Søgaard Anne , Magnus Jeanette H.
Published: July 2002

Population-based studies of adult forearm bone mineral density (BMD) by age are scarce, and standardized reference values are lacking. In this cross-sectional study, men aged 55–74 years, women aged 50–74 years, and representative 5–10% samples of remaining age groups between 25 and 84 years living in Tromsø, Norway, were invited for forearm BMD measurement in 1994–1995. The authors measured 3,062 men and 4,558 women (response rate, 78%) by single x-ray absoptiometry at distal and ultradistal forearm sites. Up to age 50, the mean BMD difference was –0.1% per 1-year age group in both sexes. After age 50, the mean BMD difference per 1-year age group was −0.6% in men and −1.3% (distal) and −1.5% (ultradistal) in women. The BMD by age curve was linear for men throughout senescence, but women had a slope change to −0.7% (distal) and −0.8% (ultradistal) per 1-year age group from the 65- to 69-year age group. BMD levels and BMD by age association in the general population (n = 7,620) and in the population without bone-threatening diseases or medication (n = 5,179) were similar. Only longitudinal studies can clarify whether cohort effects or longitudinal BMD development patterns explain these cross-sectional results.
Serum Triglycerides and Risk of Coronary Heart Disease among Japanese Men and Women
Authors: Iso Hiroyasu , Naito Yoshihiko , Sato Shinichi , Kitamura Akihiko , Okamura Tomonori , Sankai Tomoko , Shimamoto Takashi , Iida Minoru , Komachi Yoshio
Published: July 2002

To examine the relation of triglycerides with coronary heart disease among populations with low mean total cholesterol, the authors conducted a 15.5-year prospective study ending in 1997 of 11,068 Japanese aged 40–69 years (4,452 men and 6,616 women with mean total cholesterol = 4.73 mmol/liter and 5.03 mmol/liter, respectively), initially free of coronary heart disease or stroke. There were 236 coronary heart disease events comprising 133 myocardial infarctions, 68 angina pectoris events, and 44 sudden cardiac deaths. The coronary heart disease incidence was greater in a dose-response manner across increasing quartiles of nonfasting triglycerides for both sexes. The multivariate relative risk of coronary heart disease adjusting for coronary risk factors and time since last meal associated with a 1-mmol/liter increase in triglycerides was 1.29 (95% confidence interval (CI): 1.09, 1.53; p = 0.004) for men and 1.42 (95% CI: 1.15, 1.75; p = 0.001) for women. The trend was similar for myocardial infarction, angina pectoris, and sudden cardiac death. The relation of triglycerides with coronary heart disease was not influenced materially by total cholesterol levels or, in a subsample analysis (51% of total sample), by high density lipoprotein cholesterol levels. Nonfasting serum triglycerides predict the incidence of coronary heart disease among Japanese men and women who possess low mean values of total cholesterol. Further adjustment for high density lipoprotein cholesterol suggests an independent role of triglycerides on the coronary heart disease risk.
Multivariate Logistic Regression for Familial Aggregation of Two Disorders. II. Analysis of Studies of Eating and Mood Disorders
Authors: Hudson James I. , Laird Nan M. , Betensky Rebecca A. , Keck Paul E. , Pope Harrison G.
Published: July 2002

Family studies have suggested that eating disorders and mood disorders may coaggregate within families. Previous studies, however, have been limited by use of univariate modeling techniques and failure to account for the correlation of observations within families. To provide a more efficient analysis and to illustrate multivariate logistic regression models for familial aggregation of two disorders, the authors analyzed pooled data from two previously published family studies (conducted in Massachusetts in 1984–1986 and 1986–1987) by using multivariate proband predictive and family predictive models. Both models demonstrated a significant familial aggregation of mood disorders and familial coaggregation of eating and mood disorders. The magnitude of the coaggregation between eating and mood disorders was similar to that of the aggregation of mood disorders. Similar results were obtained with alternative models, including a traditional univariate proband predictive model. In comparison with the univariate model, the multivariate models provided greater flexibility, improved precision, and wider generality for interpreting aggregation effects.
Analysis of 13 32P-DNA Postlabeling Studies on Occupational Cohorts Exposed to Air Pollution
Authors: Peluso M. , Ceppi M. , Munnia A. , Puntoni R. , Parodi S.
Published: July 2002

Industrial and urban workers may be exposed to significant levels of air pollutants resulting from the incomplete combustion of organic matter. The authors performed a meta-analysis of 13 DNA-adduct studies (32P-DNA postlabeling technique) on occupational cohorts exposed to air pollution. The association between levels of DNA adducts and air pollution exposure was significant both in heavily exposed industrial workers and in less severely exposed urban workers. Moreover, in an analysis using the seven studies that reported measuring levels of benzo[a]pyrene (B(a)P), a typical marker of exposure, DNA adduct levels in exposed workers (versus those in referents) were significantly correlated with air levels of B(a)P. The relation between DNA adducts and B(a)P was found to be linear at low doses and sublinear at high doses, indicating that DNA adduct formation tends to reach some kind of saturation point at higher levels of exposure to the chemical mixtures present in fumes. When the authors examined the efficiency of DNA adduct production associated with increasing air pollution exposures, the production of DNA adducts per unit of exposure was significantly decreased at higher B(a)P exposure levels. These findings suggest that linear downward extrapolations based on DNA adduct levels associated with B(a)P concentrations of ≥20 ng/m3 might be affected by underestimation bias.
Multiple Chemical Sensitivity and Chronic Fatigue Syndrome in British Gulf War Veterans
Authors: Reid Steven , Hotopf Matthew , Hull Lisa , Ismail Khalida , Unwin Catherine , Wessely Simon
Published: July 2002

The objective of this study was to measure the prevalence of multiple chemical sensitivity (MCS) and chronic fatigue syndrome (CFS) in British Gulf War veterans and to investigate their association with reported exposures and psychologic morbidity. In 1997–1998, the authors undertook a cross-sectional survey of three cohorts of British military personnel comprising Gulf veterans (n = 3,531), those who had served in Bosnia (n = 2,050), and those serving during the Gulf War but not deployed there (Era cohort, n = 2,614). MCS and CFS were defined according to operational criteria. The prevalence of MCS in the Gulf, Bosnia, and Era cohorts was 1.3%, 0.3%, and 0.2%, respectively. For CFS, the prevalence was 2.1% (Gulf cohort), 0.7% (Bosnia cohort), and 1.8% (Era cohort). In Gulf veterans, MCS was strongly associated with exposure to pesticides (adjusted odds ratio = 12.3, 95% confidence interval: 5.1, 30.0). Both syndromes were associated with high levels of psychologic morbidity. These findings suggest that CFS and MCS account for some of the medically unexplained illnesses reported by veterans after deployment to the Gulf. MCS was particularly associated with Gulf deployment and self-reported exposure to pesticides, findings that merit further exploration given the controversial status of this diagnosis and the potential for recall bias in a questionnaire survey.