bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased arginase activity and endothelial dysfunction in human inflammatory bowel disease
Authors: Horowitz Scott , Binion David G. , Nelson Victoria M. , Kanaa Yasmin , Javadi Pooria , Lazarova Zelmira , Andrekopoulos Christopher , Kalyanaraman Balaraman , Otterson Mary F. , Rafiee Parvaneh
Published: January 2007

Nitric oxide (·NO) generation from conversion of l-arginine to citrulline by nitric oxide synthase isoforms plays a critical role in vascular homeostasis. Loss of ·NO is linked to vascular pathophysiology and is decreased in chronically inflamed gut blood vessels in inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis). Mechanisms underlying decreased ·NO production in IBD gut microvessels are not fully characterized. Loss of ·NO generation may result from increased arginase (AR) activity, which enzymatically competes with nitric oxide synthase for the common substrate l-arginine. We characterized AR expression in IBD microvessels and endothelial cells and its contribution to decreased ·NO production. AR expression was assessed in resected gut tissues and human intestinal microvascular endothelial cells (HIMEC). AR expression significantly increased in both ulcerative colitis and Crohn's disease microvessels and submucosal tissues compared with normal. TNF-α/lipopolysaccharide increased AR activity, mRNA and protein expression in HIMEC in a time-dependent fashion. RhoA/ROCK pathway, a negative regulator of ·NO generation in endothelial cells, was examined. The RhoA inhibitor C3 exoenzyme and the ROCK inhibitor Y-27632 both attenuated TNF-α/lipopolysaccharide-induced MAPK activation and blocked AR expression in HIMEC. A significantly higher AR activity and increased RhoA activity were observed in IBD submucosal tissues surrounding microvessels compared with normal control gut tissue. Functionally, inhibition of AR activity decreased leukocyte binding to HIMEC in an adhesion assay. Loss of ·NO production in IBD microvessels is linked to enhanced levels of AR in intestinal endothelial cells exposed to chronic inflammation in vivo.
Milnacipran, a serotonin and norepinephrine reuptake inhibitor, induces appetite-suppressing effects without inducing hypothalamic stress responses in mice
Authors: Nonogaki Katsunori , Nozue Kana , Kuboki Tomifusa , Oka Yoshitomo
Published: January 2007

Milnacipran, a selective serotonin (5-HT) and norepinephrine (NE) reuptake inhibitor, increases extracellular 5-HT and NA levels equally in the central nervous system. Here, we report that systemic administration of milnacipran (20–60 mg/kg) significantly suppressed food intake after fasting in C57BL6J mice. The appetite-suppressing effects of milnacipran were sustained for 5 h. Neither SB242084, a selective 5-HT2C receptor antagonist, nor SB224289, a selective 5-HT1B receptor antagonist, reversed the appetite-suppressing effects of milnacipran. Milnacipran suppressed food intake and body weight in wild-type mice and in Aymice, which have ectopic expression of the agouti protein. Moreover, milnacipran significantly increased hypothalamic proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) mRNA levels, while having no effect on hypothalamic neuropeptide Y, ghrelin, corticotropin-releasing hormone (CRH), and suppressor of cytokine signaling-3 mRNA levels. Interestingly, milnacipran did not increase plasma corticosterone and blood glucose levels, whereas fenfluramine, which inhibits 5-HT reuptake and stimulates 5-HT release, significantly increased plasma corticosterone and blood glucose levels in association with increased hypothalamic CRH mRNA levels. The appetite-suppressing effects of milnacipran had no effects on food intake in food-restricted, wild-type mice and Aymice. On the other hand, fenfluramine suppressed food intake in food-restricted wild-type mice, but it had no effects in food-restricted Aymice. These results suggest that inhibition of 5-HT and NA reuptake induces appetite-suppressing effects independent of 5-HT2C and 5-HT1B receptors, and increases hypothalamic POMC and CART gene expression without increasing plasma corticosterone and blood glucose levels in mice.
Effects of hyperventilation on phosphocreatine kinetics and muscle deoxygenation during moderate-intensity plantar flexion exercise
Authors: Forbes S. C. , Kowalchuk J. M. , Thompson R. T. , Marsh G. D.
Published: January 2007

The effects of controlled voluntary hyperventilation (Hyp) on phosphocreatine (PCr) kinetics and muscle deoxygenation were examined during moderate-intensity plantar flexion exercise. Male subjects ( n = 7) performed trials consisting of 20-min rest, 6-min exercise, and 10-min recovery in control [Con; end-tidal Pco2(PetCO2) ∼ 33 mmHg] and Hyp (PetCO2∼17 mmHg) conditions. Phosphorus-31 magnetic resonance and near-infrared spectroscopy were used simultaneously to monitor intramuscular acid-base status, high-energy phosphates, and muscle oxygenation. Resting intracellular hydrogen ion concentration ([H+]i) was lower ( P < 0.05) in Hyp [90 nM (SD 3)] than Con [96 nM (SD 4)]; however, at end exercise, [H+]iwas greater ( P < 0.05) in Hyp [128 nM (SD 19)] than Con [120 nM (SD 17)]. At rest, [PCr] was not different between Con [36 mM (SD 2)] and Hyp [36 mM (SD 1)]. The time constant (τ) of PCr breakdown during transition from rest to exercise was greater ( P < 0.05) in Hyp [39 s (SD 22)] than Con [32 s (SD 22)], and the PCr amplitude was greater ( P < 0.05) in Hyp [26% (SD 4)] than Con [22% (SD 6)]. The deoxyhemoglobin and/or deoxymyoglobin (HHb) τ was similar between Hyp [13 s (SD 8)] and Con [10 s (SD 3)]; however, the amplitude was increased ( P < 0.05) in Hyp [40 arbitrary units (au) (SD 23)] compared with Con [26 au (SD 17)]. In conclusion, our results indicate that Hyp-induced hypocapnia enhanced substrate-level phosphorylation during moderate-intensity exercise. In addition, the increased amplitude of the HHb response suggests a reduced local muscle perfusion in Hyp compared with Con.
Free radical-mediated skeletal muscle dysfunction in inflammatory conditions
Authors: Supinski Gerald S. , Callahan Leigh A.
Published: January 2007

Loss of functional capacity of skeletal muscle is a major cause of morbidity in patients with a number of acute and chronic clinical disorders, including sepsis, chronic obstructive pulmonary disease, heart failure, uremia, and cancer. Weakness in these patients can manifest as either severe limb muscle weakness (even to the point of virtual paralysis), respiratory muscle weakness requiring mechanical ventilatory support, and/or some combination of these phenomena. While factors such as nutritional deficiency and disuse may contribute to the development of muscle weakness in these conditions, systemic inflammation may be the major factor producing skeletal muscle dysfunction in these disorders. Importantly, studies conducted over the past 15 years indicate that free radical species (superoxide, hydroxyl radicals, nitric oxide, peroxynitrite, and the free radical-derived product hydrogen peroxide) play an key role in modulating inflammation and/or infection-induced alterations in skeletal muscle function. Substantial evidence exists indicating that several free radical species can directly alter contractile protein function, and evidence suggests that free radicals also have important effects on sarcoplasmic reticulum function, on mitochondrial function, and on sarcolemmal integrity. Free radicals also modulate activation of several proteolytic pathways, including proteosomally mediated protein degradation and, at least theoretically, may also influence pathways of protein synthesis. As a result, free radicals appear to play an important role in regulating a number of downstream processes that collectively act to impair muscle function and lead to reductions in muscle strength and mass in inflammatory conditions.
Familial Effects of BRCA1 Genetic Mutation Testing: Changes in Perceived Family Functioning
Authors: Stroup Antoinette M. , Smith Ken R.
Published: January 2007

This study expands recent research that examines how the receipt of BRCA1 genetic test results affects family adaptability and cohesion 1 year after genetic risk notification. Study participants were members of a large Utah-based kindred with an identified mutation at the BRCA1 locus. The final sample, 90 men and 132 women, contributed information before genetic testing (baseline) and 4 months and/or 1 year after receipt of genetic test results. After controlling for other factors such as family coping resources (Family Crises–Oriented Personal Evaluation Scale) and strains (Family Strains Index) and the tested individual's anxiety levels before genetic testing (state anxiety subscale), men and women reported significant declines in family cohesion 1 year after genetic risk notification (P < 0.01). There is suggestive evidence that carrier men reported increasing adaptability 1 year after risk notification (+0.21 points per month; P < 0.10). Having a carrier sister had a positive influence on women's perceived family cohesion and adaptability levels, whereas a personal history of cancer, having a great deal of caregiving involvement for a female relative with cancer, anxiety, and some types of coping resources had a negative effect on men's perceived family cohesion and adaptability levels. Although results showed that tested parents are perceiving a decline in family functioning after genetic risk notification, there is no evidence to suggest that the decline is due to carrier status. In fact, it is other life circumstances that exist at the time of the genetic testing process that seem to influence the degree to which families adjust to the experience and test results. (Cancer Epidemiol Biomarkers Prev 2007;16(1):135–41)
Haplotype-Based Analysis of Common Variation in the Growth Hormone Receptor Gene and Prostate Cancer Risk
Authors: McKay James D. , Kaaks Rudolf , Johansson Mattias , Biessy Carine , Wiklund Fredik , Bälter Katarina , Adami Hans-Olov , Boillot Catherine , Gioia-Patricola Lydie , Canzian Federico , Stattin Pär , Grönberg Henrik
Published: January 2007

The growth hormone receptor (GHR) is potentially involved in prostate cancer through its role in stimulating insulin-like growth factor I production and its cellular effects on prostate epithelium. We have used a haplotype-based tagging approach within CAncer Prostate Sweden, a large retrospective case-control study of 2,863 cases and 1,737 controls to investigate if genetic variation in the GHR gene influences prostate cancer risk. One haplotype in the 3′ region of the GHR gene was found associated with prostate cancer risk in elderly men (>65 years old at the time of diagnosis), with heterozygote haplotype carriers having an odds ratio of 1.65 (95% confidence interval, 1.21-2.16; P = 0.0009, Pcorrected = 0.03). GHR function has been implicated in the determination of body mass index. Interestingly, the same haplotype associated with risk in the 3′ end of the GHR gene was also associated with a decrease in body mass index in controls (P = 0.003, Pcorrected = 0.05), possibly indicating some functionality with this haplotype. These results suggest that whereas genetic variation in the GHR gene does not seem to play a major role in prostate cancer etiology, one haplotype in the 3′ region may be potentially relevant to cases with later onset of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(1):169–73)
A Case-Control Investigation of Immune Function Gene Polymorphisms and Risk of Testicular Germ Cell Tumors
Authors: Purdue Mark P. , Sakoda Lori C. , Graubard Barry I. , Welch Robert , Chanock Stephen J. , Sesterhenn Isabel A. , Rubertone Mark V. , Erickson R. Loren , McGlynn Katherine A.
Published: January 2007

There is reason to suspect that testicular germ cell tumor (TGCT) development may be influenced by cytokines, secreted proteins that modulate tumor immune surveillance activity as well as a variety of processes in the testis. To address this hypothesis, we conducted a case-control analysis (508 cases, 608 controls) of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5−73C>T variant was positively associated with TGCT (CT/TT versus CC: odds ratio, 1.73; 95% confidence interval, 1.01-2.95; Ptrend = 0.05); additionally, haplotypes of the assessed TGFB1 SNPs (−509C>T, 327C>T, Ex1−282C>G, and Ex5−73C>T) differed in frequency between cases and controls (all TGCT, P 0.07; seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among TGCT cases versus controls of LTA 252G (Ptrend = 0.08) and of the TNF variants −1042C (Ptrend = 0.06), −1036T (Ptrend = 0.07), and −238G (Ptrend = 0.09). Analyses of haplotypes for LTA-TNF SNPs (LTA −91C>A, LTA 252A>G, TNF −863C>A, TNF −857C>T, TNF −308G>A, and −238G>A) were similarly suggestive of an association with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21). Polymorphisms in other genes were found to be associated only with seminoma (IL2) or nonseminoma (IFNGR2 and IL10). However, none of the associations remained noteworthy after applying the false discovery rate method to control for multiple testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and LTA/TNF, and possibly other immune function genes, may influence susceptibility to TGCT. (Cancer Epidemiol Biomarkers Prev 2007;16(1):77–83)
Global DNA Methylation Level in Whole Blood as a Biomarker in Head and Neck Squamous Cell Carcinoma
Authors: Ting Hsiung Debra , Marsit Carmen J. , Houseman E. Andres , Eddy Karen , Furniss C. Sloane , McClean Michael D. , Kelsey Karl T.
Published: January 2007

Background: Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol exposures, although dietary factors, particularly folate, and human papillomavirus, are also risk factors. Epigenetic alterations are increasingly implicated in the initiation and progression of cancer. Genome-wide (global) hypomethylation seems to occur in early neoplasia and is a feature of genomic DNA derived from solid tumor tissues, including HNSCC. This study aimed to determine whether global methylation in DNA derived from whole blood, a proxy tissue, is associated with HNSCC and to assess potential modification of this property by environmental or behavioral risk factors.

Methods: Global DNA methylation levels were assessed using a modified version of the combined bisulfite restriction analysis of the LRE1 sequence in a population-based case-control study of HNSCC from the Boston area.

Results: Hypomethylation lead to a significant 1.6-fold increased risk for disease (95% confidence interval, 1.1-2.4), in models controlled for other HNSCC risk factors. Smoking showed a significant differential effect (P < 0.03) on blood relative methylation between cases and controls. Furthermore, in cases, variant genotype in the MTHFR gene and low folate intake showed relationships with decreased global methylation, whereas in controls, antibody response to human papillomavirus 16 was associated with an increased global methylation level.

Discussion: DNA hypomethylation in nontarget tissue was independently associated with HNSCC and had a complex relationship with the known risk factors associated with the genesis of HNSCC. (Cancer Epidemiol Biomarkers Prev 2007;16(1):108–14)
Type-Specific Persistence of High-Risk Human Papillomavirus Infections in the New Independent States of the former Soviet Union Cohort Study
Authors: Kulmala Satu-Maria A. , Shabalova Irena P. , Petrovitchev Nikolay , Syrjänen Kari J. , Gyllensten Ulf B. , Johansson Bo C. , Syrjänen Stina M. ,   and the New Independent States of the former Soviet Union Cohort Study Group
Published: January 2007

Background: Prospective follow-up studies have recently suggested that persistent high-risk human papillomavirus (HPV) infections play a key role in the progression of CIN lesions and in the development of cervical cancer. However, data on type-specific persistence, viral integration, and the role of multiple infections are scanty.

Materials and Methods: A cross-sectional/cohort study was conducted between 1998 and 2002 in three New Independent States of the former Soviet Union comprising a cohort of 3,187 women, of whom 854 women were followed up for a mean of 17 months (SD, 11.6). HPV genotyping was done with real-time PCR, detecting HPV types 16, 18/45, 31, 33/52/58, 35, and 39. The integration status of HPV16 was examined by using a novel Taqman-based PCR method.

Results: The mean clearance time for the individual high– risk–type infection was 16.5 months (range = 0.9-34.9 months). HPV16 and HPV31 were the most persistent infections (clearance times = 18.1 and 16.2 months, respectively), whereas HPV39 infections cleared most rapidly. The mean copies per cell in HPV18/45, HPV31, HPV33/52/58, and HPV39 infections were higher in persisting HPV infections than in HPV infections that cleared, but the difference was not significant. Integration of HPV16 was not found to correlate with HPV persistence.

Conclusions: A large proportion of women remained high-risk HPV positive after 18 months. Coinfection with multiple HPV types, viral load, or integration status did not correlate with persistence of high-risk HPV infections. (Cancer Epidemiol Biomarkers Prev 2007;16(1):17–22)
Risk for High-Grade Cervical Intraepithelial Neoplasia Associated with Variants of Human Papillomavirus Types 16 and 18
Authors: Xi Long Fu , Koutsky Laura A. , Hildesheim Allan , Galloway Denise A. , Wheeler Cosette M. , Winer Rachel L. , Ho Jesse , Kiviat Nancy B.
Published: January 2007

Background: Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intraepithelial neoplasia (CIN) have not been extensively evaluated.

Methods: Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages.

Results: Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% CI, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants.

Conclusions: The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN. (Cancer Epidemiol Biomarkers Prev 2007;16(1):4–10)
Variant in Sex Hormone-Binding Globulin Gene and the Risk of Prostate Cancer
Authors: Berndt Sonja I. , Chatterjee Nilanjan , Huang Wen-Yi , Chanock Stephen J. , Welch Robert , Crawford E. David , Hayes Richard B.
Published: January 2007

Sex hormones have been implicated in prostate carcinogenesis and are thought to modulate cell proliferation and growth. To investigate the association between polymorphisms in hormone-related genes and prostate cancer risk, we conducted a two-stage, case-control study within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Using DNA extracted from blood specimens, we initially genotyped 14 single nucleotide polymorphisms in genes involved in hormone regulation or metabolism (AKR1C3, CYP1A1, CYP1B1, CYP3A4, ESR1, GNRH1, HSD173B, HSD3B2, SHBG, and SRD5A2) in 488 prostate cancer cases and 617 matched controls. Heterozygotes at SHBG D356N were found to be associated with an increased risk of prostate cancer compared with the homozygous wild type, particularly among non-Hispanic whites (odds ratio, 1.54; 95% confidence interval, 1.13-2.09; P = 0.006). No significant associations were observed with the other polymorphisms. The SHBG D356N polymorphism, which has potential functional significance, was subsequently genotyped in additional 769 cases and 1,168 controls. Overall, SHBG D356N heterozygotes were found to have an increased risk of prostate cancer among whites (odds ratio, 1.34; 95% confidence interval, 1.10-1.63; P = 0.0007). This study suggests that genetic variation in SHBG may influence prostate cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2007;16(1):165–8)
Body Mass Index, Weight Change, and Risk of Prostate Cancer in the Cancer Prevention Study II Nutrition Cohort
Authors: Rodriguez Carmen , Freedland Stephen J. , Deka Anusila , Jacobs Eric J. , McCullough Marjorie L. , Patel Alpa V. , Thun Michael J. , Calle Eugenia E.
Published: January 2007

Background: Obesity has been associated with aggressive prostate cancer. The extent of this association, which varies by stage and grade, remains unclear. The role of recent weight change had not been previously examined.

Methods: We examined body mass index (BMI) and weight change in relation to incident prostate cancer by disease stage and grade at diagnosis among 69,991 men in the Cancer Prevention Study II Nutrition Cohort. Participants provided information on height and weight in 1982, and again at enrollment in 1992. During follow-up through June 30, 2003 (excluding the first 2 years of follow-up), we documented 5,252 incident prostate cancers. Cox proportional hazards models were used to estimate rate ratios (RR) and 95% confidence intervals (95% CI).

Results: The association between BMI in 1992 and risk of prostate cancer differed by stage and grade at diagnosis. BMI was inversely associated with risk of nonmetastatic low-grade prostate cancer (RR, 0.84; 95% CI, 0.66-1.06), but BMI was positively associated with risk of nonmetastatic high-grade prostate cancer (RR, 1.22; 95% CI, 0.96-1.55) and risk of metastatic or fatal prostate cancer (RR, 1.54; 95% CI, 1.06-2.23). Compared with weight maintenance, men who lost >11 pounds between 1982 and 1992 were at a decreased risk of nonmetastatic high-grade prostate cancer (RR, 0.58; 95% CI, 0.42-0.79).

Conclusion: Obesity increases the risk of more aggressive prostate cancer and may decrease either the occurrence or the likelihood of diagnosis of less-aggressive tumors. Men who lose weight may reduce their risk of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(1):63–9)
Catheter Lock Solutions to Prevent Bloodstream Infections in High-Risk Hemodialysis Patients
Authors: Feely Theodore , Copley Angela , Bleyer Anthony J.
Published: January 2007

Background: Antimicrobial catheter lock solutions (CLS) have been shown to prevent bacteremia in chronic hemodialysis (HD) patients with new HD catheters. However, there is little information regarding the usage of these solutions in patients who have a history of recurrent bacteremia and are at very high risk of infection. The purpose of this investigation was to identify the efficacy of these solutions in such high-risk patients. Methods: A retrospective chart review was performed to identify patients who had a history of recurrent bacteremia and had received prophylaxis with antimicrobial CLS. Results: Nine patients with recurrent bacteremia were identified. These patients had received prophylaxis with minocycline/EDTA, gentamicin/heparin, or vancomycin/heparin solutions. The catheter-related bacteremia rate was 9.13 per 1,000 catheter days prior to the use of CLS, 1.04 during use of solution, and 7.94 after the CLS were discontinued (p < 0.001). Conclusions: These results show a dramatic effect of antimicrobial CLS on the prevention of catheter-related bacteremia.
Activity of Rituximab plus Cyclophosphamide, Doxorubicin/Mitoxantrone, Vincristine and Prednisone in Patients with Relapsed MALT Lymphoma
Authors: Raderer Markus , Wöhrer Stefan , Streubel Berthold , Drach Johannes , Jäger Ulrich , Turetschek Karl , Troch Marlene , Püspök Andreas , Zielinski Christoph C. , Chott Andreas
Published: January 2007

Background: Various chemotherapeutic agents as well as the anti-CD20 antibody rituximab (R) have been tested in patients with mucosa-associated lymphoid tissue (MALT) lymphoma, but no standard chemotherapeutic regimen has emerged so far. Judging from the data obtained in various types of lymphoma, the activity of R appears to be enhanced by combination with chemotherapy. As no data on this topic exist for MALT lymphoma, we have retrospectively analysed our experience with R plus cyclophosphamide, doxorubicin/mitoxantrone, vincristine and prednisone (R-CHOP/R-CNOP) in patients with relapsed MALT lymphoma. Patients and Methods: A total of 26 patients were identified, 15 were administered R-CHOP while 11 patients were given R-CNOP due to age >65 years or pre-existing cardiac conditions. Cycles were repeated every 21 days, and restaging was performed after 4 cycles of therapy. In case of complete remission, 2 further cycles were administered for consolidation while patients achieving partial remission or stable disease after restaging were given 4 further courses. Results: A total of 170 cycles were administered to our patients (median 6, range 2–8). Twenty of the 26 patients (77%) achieved a complete remission and 6 (23%) a partial remission. Toxicities were mainly haematological, with WHO grade III/IV leukocytopenia occurring in 5 patients. After a median follow-up of 19 months (range 10–45), all patients are alive: 22 are in ongoing remission, while 4 have relapsed between 12 and 19 months after treatment. Conclusions: Our data demonstrate a high activity of R-CHOP/R-CNOP in relapsing MALT lymphoma irrespective of prior therapy.
DNA Image Cytometry Is a Useful Adjunct Tool in the Prediction of Disease Outcome in Patients with Stage II and Stage III Colorectal Cancer
Authors: Buhmeida A. , Ålgars A. , Ristamäki R. , Collan Y. , Syrjänen K. , Pyrhönen S.
Published: January 2007

Background: We assessed the prognostic value of the nuclear DNA content measured in the primary tumours of 123 patients with stage II or stage III colorectal cancer (CRC). Methods: Isolated nuclei from paraffin sections were stained with the Feulgen reaction, and DNA was measured using a computer-assisted image analysis cytometry system. We applied 4 different approaches in the analysis of DNA histograms: the ABCDE approach, histogram range, peak evaluation and DNA cut-off values. Results: Using the histogram range, the narrow range was rare (3.7%) in patients who died of disease (n = 28) as compared with 16.4% among those alive (n = 74; p = 0.017). Modal peak evaluation was a significant predictor of disease-free survival (DFS; Kaplan-Meier log-rank p = 0.0235). In the range evaluation, the 1st set (low-start gates) was a significant predictor of DFS (log-rank p = 0.0121), where disease recurrence was closely associated with the widest range (1.8–>10c; c = haploid DNA content) gates. Recurrence-free survival was 3 times better in narrow-gate histograms than wide-range histograms (p < 0.03). The 1st set also proved to be a significant predictor of disease-specific survival (DSS; log-rank p = 0.0045), which was markedly better (77.8–90.0%) among the patients with the narrow-gate histograms. Grading of the histogram range into 2 categories (with 6.0c as cut-off), was a powerful predictor of both DSS (log-rank p = 0.0092) and 5-year DFS (p = 0.0106) in the whole series, and separately in stage III (but not stage II) disease, with p = 0.0131 and p = 0.0201, respectively. Conclusion: The DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in CRC, with potential clinical implications in patient management, particularly in predicting the patients at high risk for recurrence who should be considered as candidates for adjuvant therapy.
Combination of Multiple mRNA Markers (PTTG1, Survivin, UbcH10 and TK1) in the Diagnosis of Taiwanese Patients with Breast Cancer by Membrane Array
Authors: Chen Chung-Chi , Chang Tsai-Wang , Chen Fang-Ming , Hou Ming-Feng , Hung Sung-Yu , Chong Inn-Wen , Lee Su-Chen , Zhou Tian-Hong , Lin Shiu-Ru
Published: January 2007

Objective: Early detection is a prerequisite to the effective reduction of morbidity and mortality from breast cancer. The present study intended to employ a high-throughput membrane array to detect a panel of mRNA markers expressed by circulating tumor cells (CTCs) in the peripheral blood of female patients with breast cancer. Methods: Peripheral blood was sampled from 92 breast cancer patients and 100 normal persons. CTCs were detected by using a membrane array technique. The markers used included the pituitary tumor transforming gene 1, survivin, UbcH10 and thymidine kinase 1. Results: The results showed that the membrane array could positively detect 5 cancer cells per 1 ml of peripheral blood in breast cancer cell dilution experiments. For the panel of 4 mRNA markers, sensitivity and specificity were elevated up to 86 and 88%, respectively. Furthermore, it was found that the patients’ clinicopathological characteristics tumor size (p = 0.006), histologic grade (p = 0.012), lymph node metastasis (p = 0.001) and TNM stage (p = 0.006) significantly correlated with the positive detection rate of the multimarker panel. Conclusions: These findings demonstrated that our multimarker membrane array method could detect CTCs in the circulation of breast cancer patients with considerably high sensitivity and specificity.
The Bone Morphogenetic Protein Antagonist Noggin Regulates Mammalian Cardiac Morphogenesis
Authors: Choi Murim , Stottmann Rolf W. , Yang Yu-Ping , Meyers Erik N. , Klingensmith John
Published: January 2007

Bone morphogenetic proteins (BMPs) play many roles in mammalian cardiac development. Here we address the functions of Noggin, a dedicated BMP antagonist, in the developing mouse heart. In early cardiac tissues, the Noggin gene is mainly expressed in the myocardial cells of the outflow tract, atrioventricular canal, and future right ventricle. The major heart phenotypes of Noggin mutant embryos are thicker myocardium and larger endocardial cushions. Both defects result from increased cell number. Cell proliferation is increased and cell cycle exit is decreased in the myocardium. Although we find evidence of increased BMP signal transduction in the myocardium and endocardium, we show that the cardiac defects of Noggin mutants are rescued by halving the gene dosage of
Bmp4
. In culture, BMP increases the epithelial-to-mesenchymal transformation (EMT) of endocardial explant cells. Increased EMT likely accounts for the enlarged atrioventricular cushion. In the outflow tract cushion, we observed an increased contribution of cardiac neural crest cells to the mutant cushion mesenchyme, although many cells of the cushion were not derived from neural crest. Thus the enlarged outflow tract cushion of Noggin mutants likely arises by increased contributions both of endocardial cells that have undergone EMT as well as cells that have migrated from the neural crest. These data indicate that antagonism of BMP signaling by Noggin plays a critical role in ensuring proper levels of cell proliferation and EMT during cardiac morphogenesis in the mouse.
Infant Growth and Stroke in Adult Life
Authors: Osmond Clive , Kajantie Eero , Forsén Tom J. , Eriksson Johan G. , Barker David J.P.
Published: January 2007

Background and Purpose—

People who had low birth weight are at increased risk of stroke. Little is known about the effects of early postnatal growth on stroke risk.

Methods—

We followed-up 12 439 people born in Helsinki during 1934 to 1944. Their body size was measured at birth and, on average, 9 times between birth and age 2 years; 507 of them were hospitalized with stroke or died from the disease.

Results—

Hazard ratios for stroke declined progressively with increasing gain in weight between birth and age 2 years. The hazard ratio was 0.85 (95% CI, 0.78 to 0.93;
P
=0.0004) per standard deviation increase in the difference between the weight attained at age 2 years and that predicted from birth weight. A 1-standard deviation increase in body mass index at 2 years of age was associated with a hazard ratio for stroke of 0.84 (95% CI, 0.77 to 0.92;
P
=0.0002). This association was little changed by adjustment for measures of socio-economic status. Change in body size after the age of 2 years had little effect on the risk of later stroke. People whose mothers had a small external conjugate diameter of the pelvis had an increased risk of stroke. The hazard ratio associated with a diameter of ≤18 cm was 1.62 (95% CI, 1.30 to 2.02;
P
<0.0001).

Conclusion—

Thinness during infancy is associated with an increased risk of stroke in later life. This association may be the result of maternal influences which originated in the mother’s infancy when her pelvic shape was established.
Qualitative Methods
Authors: Bennett Andrew , Elman Colin
Published: January 2007

Qualitative methods are currently undergoing a renaissance in political science, with a rich new literature developing and disseminating them and greatly increased attention to preparing scholars in their use. Although this is a discipline-wide phenomenon, at the same time political science continues to be differentiated along subfield lines. The collection of articles in this symposium describes the trajectory of qualitative methods in three of political science’s empirical subfields: comparative politics, international relations (IR), and American politics. Although much of the new literature and training is self-consciously transdisciplinary, the subfields continue to exert a strong influence. These essays investigate the three empirical subfields to uncover some of the areas in which they have made more progress and therefore have particular strengths to share, to provide some examples of applications of qualitative methods outside of readers’ own subfields, and to help make sure that future methodological opportunities offered by discipline-wide developments are not limited by subfield lacunas.
A Prospective Randomized Study of Anterior Cruciate Ligament Reconstruction
Authors: Maletis Gregory B. , Cameron Sheri L. , Tengan Joann J. , Burchette Raoul J.
Published: January 2007

Background

Debate exists regarding the optimal graft for anterior cruciate ligament reconstruction. Few studies have compared the differences in outcome after reconstruction using similar fixation methods.

Hypothesis

Similar outcomes will be seen after anterior cruciate ligament reconstruction with bone-patellar tendon-bone or quadruple-strand semitendinosus/gracilis tendons fixed with bioabsorbable interference screws.

Study Design

Randomized controlled trial; Level of evidence, 1.

Methods

Ninety-nine patients were prospectively randomized to bone-patellar tendon-bone (46 patients) or quadruple-strand semitendinosus/gracilis (53 patients) reconstruction groups. The bone-patellar tendon-bone group had slightly lower preinjury Tegner scores (6.7 vs 7.1, P = .03); otherwise, the groups were similar. All surgeries were performed by a single surgeon using an endoscopic technique with bioabsorbable interference screw fixation. Patients were evaluated at 3, 6, 12, and 24 months.

Results

Forty-six bone-patellar tendon-bone and 50 quadruple-strand semitendinosus/gracilis patients were available at 24 months (97%). No differences in International Knee Documentation Committee grade, Lysholm score, Tegner activity level, range of motion, single-legged hop test, KT-1000 arthrometer manual maximum difference, Short Form-36, or patient knee rating were found. The bone-patellar tendon-bone group had better flexion strength in the operated leg than in the nonoperated leg (102% vs 90%, P = .0001), fewer patients complaining of difficulty jumping (3% vs 17%, P = .03), and a greater number of patients returning to preinjury Tegner level (51% vs 26%, P = .01). The quadruple-strand semitendinosus/gracilis group had better extension strength in the operated leg than in the nonoperated leg (92% vs 85%, P = .04), fewer patients with sensory deficits (14% vs 83%, P = .0001), and fewer patients with difficulty kneeling (6% vs 20%, P = .04). Both groups showed significant improvement in KT-1000 arthrometer manual maximum difference, Lysholm score, Tegner activity level, International Knee Documentation Committee grade, and patient knee rating score.

Conclusions

Good outcomes were seen in both the bone-patellar tendon-bone and quadruple-strand semitendinosus/gracilis groups. Subtle differences were noted between the groups, which may help guide optimal graft choice.
Stress Distribution in the Supraspinatus Tendon after Tendon Repair
Authors: Sano Hirotaka , Yamashita Takeshi , Wakabayashi Ikuko , Itoi Eiji
Published: January 2007

Background

The stress concentration at the site of supraspinatus tendon repair, either by suture anchor fixation or by transosseous suture fixation, has not been fully clarified.

Hypothesis

Suture anchor fixation showed higher stress concentrations in the tendon than did transosseous suture fixation.

Study Design

Controlled laboratory study.

Methods

Three finite element models were developed based on a previously published model of normal supraspinatus tendon (0° abduction). Single-row fixation, double-row fixation, and transosseous suture fixation were simulated. A tensile force was applied to the proximal end of the supraspinatus tendon to simulate its contraction force.

Results

In the single-row model, the stress appeared from the site of the anchor and extended into the proximal tendon. The highest stress concentration was observed on the bursal surface of the tendon. The double-row model showed a similar pattern to the single-row model except that the stress concentration was observed only around the medial anchor. In the transosseous model, the stress appeared from the attachment site to a bony trough, which extended proximally into the tendon substance. No significant stress concentration was observed inside the tendon.

Conclusion

Both single-row and double-row fixations showed higher stress concentration inside the tendon than did transosseous suture fixation.

Clinical Relevance

A high stress concentration might be a cause of the rerupture often observed after arthroscopic cuff repair using suture anchors.
Sports after Hip Resurfacing Arthroplasty
Authors: Naal Florian-D. , Maffiuletti Nicola A. , Munzinger Urs , Hersche Otmar
Published: January 2007

Background

No information is available concerning patients’ sports activity after hip resurfacing arthroplasty.

Hypothesis

Patients treated by hip resurfacing arthroplasty will be able to achieve a high level of sports activity.

Study Design

Case series; Level of evidence, 4.

Methods

We surveyed 112 patients by postal questionnaire to determine their sporting activities at a mean of 23.5 (range, 9—40) months after hip resurfacing surgery. Data were also analyzed separately for older and younger patients and women and men, respectively.

Results

Of 112 patients, 110 participated in an average of 4.6 sport disciplines after surgery, compared with 105 patients preoperatively engaged in an average of 4.8 disciplines. About 26% performed sports 4 times per week or more—almost 60% for longer than 60 min at each session. A high proportion of our patients were still engaged in downhill skiing (51%) and in high-impact disciplines such as tennis (12%) or contact sports (22%). More than 50% of the patients commenced sports within the first 3 months after surgery. During activities, 70% were completely pain-free. The group of older patients (mean age, 60.2 years) participated in more different disciplines with a higher weekly frequency and longer session length than younger patients (mean age, 46.4 years).

Conclusion

The present study reports for the first time on the detailed sports activity and activity extent after hip resurfacing arthroplasty. Our patients could return to a high level of sports participation after surgery. Age-related differences were found that have not yet been published. Nevertheless, further follow-up is necessary to assess the influence of high-level activity on loosening and revision rates after hip resurfacing arthroplasty.
Metaphors at Work
Authors: Ollilainen Marjukka , Calasanti Toni
Published: January 2007

Self-managing teams have been predicted to break down organizational hierarchies and sex-segregated functional divisions. Based on participant observation and interviews with 39 men and women in service-oriented self-managing teams, the authors found that the metaphor of family emerged in interviews as a popular way to describe teams' interaction and social relations. The ways that team members used the family metaphor revealed that women were often perceived in familial roles that the authors argue encourage emotional labor. Although relational tasks may not directly reproduce traditional gender power relations in teams, women can face difficulties taking on more instrumental team tasks. The authors propose that the persistence of family metaphors sustains the organizational gender categorization that self-managing teams as work-based, cross-functional groups were supposed to help eliminate. To the extent that this is the case, it suggests the importance of exploring the gendered organizational cultures that exist alongside structural arrangements.
Gender and Organizational Culture
Authors: Haas Linda , Hwang C. Philip
Published: January 2007

This study explores company support for men's participation in child care in Sweden, where the government promotes gender equality. The authors investigate the influence of two ideologies about gender, the doctrine of separate spheres and masculine hegemony, on the responsiveness to fathers shown by Sweden's largest corporations. Father-friendly companies had adopted values associated with the private sphere and prioritized entrance of women into the public sphere. Companies with less masculine hegemony provided some informal but no formal support to fathers. Following social justice theory, future research could focus on how fathers come to perceive the lack of corporate responsiveness as unfair.
Negotiating Sexual Agency: Postmenopausal Women's Meaning and Experience of Sexual Desire
Authors: Wood Jill M. , Mansfield Phyllis Kernoff , Koch Patricia Barthalow
Published: January 2007

The purpose of this feminist grounded theory study was to understand the meaning and experience of postmenopausal women's sexual desire. Data collection from 22 postmenopausal women who were ongoing participants of the TREMIN Research Program on Women's Health occurred via audiotaped, telephone-based, semistructured interviews. Women's descriptions of their sexual needs and desires led to the discovery of the core category, negotiating sexual agency, which refers to women's ability to act on behalf of their sexual needs, desires, and wishes. Women negotiated their sexual agency within three main domains (or axial codes): their own sexual self, their partners, and the medical system. An important finding was women's internalization of sociocultural assumptions that privilege their male partners' sexual needs over their own. The findings of this study, especially the contexts in which women negotiate their sexual agency, are important for women, women's health care providers, and women's life partners to understand.
Men, Masculinities, and Prostate Cancer: Australian and Canadian Patient Perspectives of Communication With Male Physicians
Authors: Oliffe John , Thorne Sally
Published: January 2007

Patient-physician communication is vital in cancer care, and aspects of the patients' experiences provide insight into what constitutes effective cancer communication. Complexities inherent in prostate cancer regarding screening, treatment(s) efficacy, and side effects commonly form the basis of patient-physician discussions. However, the specificities of patient-physician communications, particularly in the male dyad, and the connections to masculinity are poorly understood. The authors used secondary analysis of data from two interview studies of 19 Canadian and 33 Australian prostate cancer survivors who were treated by male general practitioners and prostate cancer specialists. Participants acknowledged that physician expertise and compassion underpinned the development of trust, and both reassurance and humor were effective communication strategies. Participants were often self-directed in researching prostate cancer, consistently using biomedical language and numerical markers when discussing their disease. Analysis of findings enabled interpretations regarding what might be considered prostate cancer communication competencies in the male patient-physician dyad.
Spirituality in African Americans With Diabetes: Self-Management Through a Relationship With God
Authors: Polzer Rebecca L. , Miles Margaret S.
Published: January 2007

The purpose of this study was to develop a theoretical model about how the spirituality of African Americans affects their self-management of diabetes. The sample consisted of 29 African American men and women, ages 40 to 75, with type 2 diabetes. The authors used a grounded theory design and collected data using minimally structured interviews. The method of analysis was constant comparison. The core concept identified was Self-Management Through a Relationship With God. Participants fell into one of three typologies: (a) Relationship and Responsibility: God Is in Background; (b) Relationship and Responsibility: God Is in Forefront: (c) Relationship and Relinquishing of Self-Management: God Is Healer. These typologies varied according to how participants viewed their relationship with God and the impact of this relationship on their self-management. The spirituality of these African Americans was an important factor that influenced the self-management of their diabetes.
Identity and Resilience Among Persons With HIV: A Rural African American Experience
Authors: Bletzer Keith V.
Published: January 2007

In this article, the author contrasts the disruption model proposed by Becker (1997) against the life trajectories of two persons who used and sold drugs; considers the impact of engagement and discontinuation of substance use on their respective lives; and examines the process of life reorganization they put into motion after testing positive for HIV. Their departure from the world of drugs removed each from an unwanted lifestyle, facilitated the process of building resilience against the social adversity they faced in relation to their seropositivity, assisted them with securing care and services through institutional mechanisms, and generated a forum for new ideas on family continuity versus the ideal of individualism that grounds mainstream society. A process of identity reaffirmation further deepened their understanding of themselves as African Americans in the southern United States.