bluuebunny/crossref_metadata_2025 huggingface dataset:
Kidney Function After Islet Transplant Alone in Type 1 Diabetes
Authors: Maffi Paola , Bertuzzi Federico , De Taddeo Francesca , Magistretti Paola , Nano Rita , Fiorina Paolo , Caumo Andrea , Pozzi Paolo , Socci Carlo , Venturini Massimo , del Maschio Alessandro , Secchi Antonio
Published: April 2007

OBJECTIVE—Islet transplantation alone is an alternative for the replacement of pancreatic endocrine function in patients with type 1 diabetes. The aim of our study was to assess the impact of the Edmonton immunosuppressive protocol (tacrolimus-sirolimus association) on kidney function.

RESEARCH DESIGN AND METHODS—Nineteen patients with type 1 diabetes and metabolic instability received islet transplantation alone and immunosuppressive therapy according to the Edmonton protocol. Serum creatinine (sCr), creatinine clearance (CrCl), and 24-h urinary protein excretion (UPE) were assessed at baseline and during a follow-up of 339 patient-months.

RESULTS— After islet transplantation we observed 1) sCr within the normal range in all but two patients in whom sCr increased immediately after islet transplantation, and despite withdrawal of immunosuppression, patients progressed to end-stage renal disease (ESRD); 2) CrCl remained within the normal range for those patients who had normal baseline values and decreased, progressing to ESRD in two patients with a decreased baseline CrCl; and 3) 24-h UPE worsened (>300 mg/24 h) in four patients. In the two patients who progressed to ESRD, the worsening of 24-h UPE occurred immediately after islet transplantation. In one patient 24-h UPE worsening occurred at 18 months, and, after withdrawal of immunosuppression, it returned to the normal range. In another patient 24-h UPE increased at 24 months and remained stable while immunosuppression was continued.

CONCLUSIONS—In type 1 diabetic patients receiving islet transplantation alone, the association of tacrolimus and sirolimus should be used only in patients with normal kidney function. Alternative options for immunosuppressive treatment should be considered for patients with even a mild decrease of kidney function.
Whole-Body Glycolysis Measured by the Deuterated-Glucose Disposal Test Correlates Highly With Insulin Resistance In Vivo
Authors: Beysen Carine , Murphy Elizabeth J. , McLaughlin Tracey , Riiff Timothy , Lamendola Cindy , Turner Holly C. , Awada Mohamad , Turner Scott M. , Reaven Gerald , Hellerstein Marc K.
Published: April 2007

OBJECTIVE—The purpose of this study was to compare an in vivo test of whole-body glycolysis, the deuterated-glucose disposal test (2H-GDT), with insulin sensitivity measured by the euglycemic-hyperinsulinemic glucose clamp and the steady-state plasma glucose (SSPG) test.

RESEARCH DESIGN AND METHODS—The 2H-GDT consists of an oral glucose challenge containing deuterated glucose, followed by measurement of heavy water (2H2O) production, which represents whole-body glycolytic disposal of the glucose load. 2H2O production is corrected for ambient insulin concentration as an index of tissue insulin sensitivity. The 2H-GDT was compared with euglycemic-hyperinsulinemic glucose clamps in healthy lean subjects (n = 8) and subjects with the metabolic syndrome (n = 9) and with the SSPG test in overweight (n = 12) and obese (n = 6) subjects.

RESULTS—A strong correlation with the clamp was observed for the 75-g and 30-g 2H-GDT (r = 0.95, P < 0.0001 and r = 0.88, P < 0.0001, respectively). The 2H-GDT and clamp studies revealed marked insulin resistance in subjects with metabolic syndrome compared with lean control subjects. The correlation with the clamp was maintained in each group (lean, r = 0.86, P < 0.01; metabolic syndrome, r = 0.81, P < 0.01) for the 75-g test. The 2H-GDT also correlated strongly with the SSPG test (r = −0.87, P < 0.0001) in overweight and obese subjects.

CONCLUSIONS—The 2H-GDT, which measures whole-body glycolysis in humans in a quantitative manner, correlates highly with the euglycemic-hyperinsulinemic glucose clamp and the SSPG test. Impaired insulin-mediated whole-body glycolysis is a feature of insulin resistance, which provides a means of assessing insulin sensitivity in vivo.
Glucose Homeostasis and Genotype-Phenotype Interplay in Cystic Fibrosis Patients With CFTR Gene ΔF508 Mutation
Authors: Preumont Vanessa , Hermans Michel P. , Lebecque Patrick , Buysschaert Martin
Published: April 2007

OBJECTIVE—We sought to determine the clinical phenotype of adolescent/adult patients with cystic fibrosis, according to heterozygosity or homozygosity for cystic fibrosis transmembrane regulator (CFTR) ΔF508 mutation, and to analyze their characteristics according to glucose tolerance status.

RESEARCH DESIGN AND METHODS—A total of 76 cystic fibrosis patients with CFTR ΔF508 mutation (33 heterozygous and 43 homozygous) stratified according to normal glucose tolerance (NGT) (n = 51) or abnormal glucose homeostasis (AGH) (impaired fasting glucose, impaired glucose tolerance, or diabetes; n = 25) had their homeostasis model assessment (HOMA) of β-cell function and of insulin sensitivity and hyperbolic product (β-cell function × insulin sensitivity [B × S]) measured. Pancreatic exocrine insufficiency was inferred from pancreatine requirements. Clinical effects of insulin therapy on weight and lung function were recorded.

RESULTS—AGH was observed in 24 and 40% of heterozygous and homozygous subjects, respectively. AGH patients were older than NGT patients (mean ± SD age 29 ± 10 vs. 23 ± 8 years, P = 0.006), and their β-cell function was lower (93 ± 49 vs. 125 ± 51%, P = 0.011). Insulin sensitivity values were comparable in NGT and AGH patients. A lower B × S product was observed in AGH, although it was nonsignificant when adjusted for error propagation. Pancreatic insufficiency was observed in 52 and 100% of heterozygous and homozygous patients (P = 0.001).

CONCLUSIONS—Pre-diabetes and diabetes represent frequent comorbidities in CFTR ΔF508 mutation in the homozygous or heterozygous states. Impairment of insulin secretion, as shown by HOMA, is an important determinant when compared with the magnitude of compensation from insulin sensitivity. Given the high prevalence of abnormal glucose tolerance, screening for (pre-)diabetes is mandatory. Insulin supplementation in diabetic subjects with CFTR ΔF508 mutation seems a rational therapy for consideration, although this does not preclude that therapy directed toward insulin resistance could also interact.
Clustering of Risk Factors in Parents of Patients With Type 1 Diabetes and Nephropathy
Authors: Thorn Lena M. , Forsblom Carol , Fagerudd Johan , Pettersson-Fernholm Kim , Kilpikari Riika , Groop Per-Henrik ,   on behalf of the FinnDiane Study Group
Published: April 2007

OBJECTIVE—To assess the impact of parental risk factors for diabetic nephropathy.

RESEARCH DESIGN AND METHODS—This cross-sectional study included 2,355 type 1 diabetic patients from the FinnDiane (Finnish Diabetic Nephropathy) study. Diabetic nephropathy was defined as macroalbuminuria (urinary albumin excretion rate >200 μg/min or >300 mg/24 h) or end-stage renal disease. Information was available from 4,676 parents. Parental scores were calculated based on the number of various traits in the parents.

RESULTS—Patients with diabetic nephropathy, compared with those without diabetic nephropathy, had a higher prevalence of maternal (41 vs. 35%, P = 0.046) and parental (62 vs. 55%, P = 0.044) hypertension, maternal stroke (7.6 vs. 5.1%, P = 0.044), and maternal (1.4 vs. 0.7%, P = 0.058) and parental (4.3 vs. 2.9%, P = 0.030) type 1 diabetes. If both, compared with none, of the parents had hypertension, the adjusted odds ratio (OR) for diabetic nephropathy in offspring was 1.56 (95% CI 1.13–2.15). The adjusted OR for diabetic nephropathy was 2.13 (1.36–3.33) for the parental hypertension–diabetes score (3–4 vs. 0 points) and 2.13 (1.37–3.33) for the parental hypertension–cardiovascular disease (CVD)–diabetes score (4–6 vs. 0 points). Fathers of patients with diabetic nephropathy, compared with those without diabetic nephropathy, had reduced overall survival (log-rank P = 0.04) and reduced cardiovascular survival (log-rank P = 0.03).

CONCLUSIONS—A cluster of parental hypertension, CVD, and diabetes is associated with diabetic nephropathy in type 1 diabetes, as is paternal mortality.
Benefits of Information Technology–Enabled Diabetes Management
Authors: Bu Davis , Pan Eric , Walker Janice , Adler-Milstein Julia , Kendrick David , Hook Julie M. , Cusack Caitlin M. , Bates David W. , Middleton Blackford
Published: April 2007

OBJECTIVE—To determine the financial and clinical benefits of implementing information technology (IT)-enabled disease management systems.

RESEARCH DESIGN AND METHODS—A computer model was created to project the impact of IT-enabled disease management on care processes, clinical outcomes, and medical costs for patients with type 2 diabetes aged >25 years in the U.S. Several ITs were modeled (e.g., diabetes registries, computerized decision support, remote monitoring, patient self-management systems, and payer-based systems). Estimates of care process improvements were derived from published literature. Simulations projected outcomes for both payer and provider organizations, scaled to the national level. The primary outcome was medical cost savings, in 2004 U.S. dollars discounted at 5%. Secondary measures include reduction of cardiovascular, cerebrovascular, neuropathy, nephropathy, and retinopathy clinical outcomes.

RESULTS—All forms of IT-enabled disease management improved the health of patients with diabetes and reduced health care expenditures. Over 10 years, diabetes registries saved $14.5 billion, computerized decision support saved $10.7 billion, payer-centered technologies saved $7.10 billion, remote monitoring saved $326 million, self-management saved $285 million, and integrated provider-patient systems saved $16.9 billion.

CONCLUSIONS—IT-enabled diabetes management has the potential to improve care processes, delay diabetes complications, and save health care dollars. Of existing systems, provider-centered technologies such as diabetes registries currently show the most potential for benefit. Fully integrated provider-patient systems would have even greater potential for benefit. These benefits must be weighed against the implementation costs.
A1C and Survival in Maintenance Hemodialysis Patients
Authors: Kalantar-Zadeh Kamyar , Kopple Joel D. , Regidor Deborah L. , Jing Jennie , Shinaberger Christian S. , Aronovitz Jason , McAllister Charles J. , Whellan David , Sharma Kumar
Published: April 2007

OBJECTIVE—The optimal target for glycemic control has not been established in diabetic dialysis patients.

RESEARCH DESIGN AND METHODS—To address this question, the national database of a large dialysis organization (DaVita) was analyzed via time-dependent survival models with repeated measures.

RESULTS—Of 82,933 patients undergoing maintenance hemodialysis (MHD) in DaVita outpatient clinics over 3 years (July 2001 through June 2004), 23,618 diabetic MHD patients had A1C measurements at least once. Unadjusted survival analyses indicated paradoxically lower death hazard ratios (HRs) with higher A1C values. However, after adjusting for potential confounders (demographics, dialysis vintage, dose, comorbidity, anemia, and surrogates of malnutrition and inflammation), higher A1C values were incrementally associated with higher death risks. Compared with A1C in the 5–6% range, the adjusted all-cause and cardiovascular death HRs for A1C ≥10% were 1.41 (95% CI 1.25–1.60) and 1.73 (1.44–2.08), respectively (P < 0.001). The incremental increase in death risk for rising A1C values was monotonic and robust in nonanemic patients (hemoglobin >11.0 g/dl). In subgroup analyses, the association between A1C >6% and increased death risk was more prominent among younger patients, those who had undergone dialysis for >2 years, and those with higher protein intake (>1 g · kg−1 · day−1), blood hemoglobin (>11 g/dl), or serum ferritin values (>500 ng/ml).

CONCLUSIONS—In diabetic MHD patients, the apparently counterintuitive association between poor glycemic control and greater survival is explained by such confounders as malnutrition and anemia. All things equal, higher A1C is associated with increased death risk. Lower A1C levels not related to malnutrition or anemia appear to be associated with improved survival in MHD patients.
Knowledge on Inpatient Diabetes Among Fourth-Year Medical Students
Authors: Lansang M. Cecilia , Harrell Heather
Published: April 2007

OBJECTIVE—The importance of proper management of inpatient hyperglycemia is increasingly being recognized. However, the curriculum for 4th-year medical students has lagged behind current clinical recommendations. The aim of this study was to assess the baseline knowledge of medical subinterns on inpatient diabetes.

RESEARCH DESIGN AND METHODS—In the 2005–2006 school year, subinterns were given a pretest on inpatient diabetes. Descriptive analysis was used.

RESULTS—Students frequently recommended the sole use of sliding scale for diabetes management. Hyperglycemia in patients not known to have diabetes is less likely to be recognized. The students were more likely to provide appropriate management for chest pain than diabetes. Students were otherwise knowledgable about the recognition of type of diabetes and the pharmacology of the medications.

CONCLUSIONS—This study demonstrates the gaps in knowledge about inpatient diabetes that exist before internship and residency. The findings can be used to design a curriculum appropriately targeted to the level of 4th-year medical students.
Chromium Treatment Has No Effect in Patients With Type 2 Diabetes in a Western Population
Authors: Kleefstra Nanne , Houweling Sebastiaan T. , Bakker Stephan J.L. , Verhoeven Simon , Gans Rijk O.B. , Meyboom-de Jong Betty , Bilo Henk J.G.
Published: April 2007

OBJECTIVE—Chromium treatment has been reported to improve glycemic control in patients with type 2 diabetes. However, concern exists about the possible toxic effects of chromium picolinate. The aim of this study was to determine the effect of chromium treatment in the form of chromium yeast on glycemic control in a Western population of patients with type 2 diabetes who were being treated with oral hypoglycemic agents.

RESEARCH DESIGN AND METHODS—In this 6-month, double-blind study, patients with moderate glycemic control, being treated with oral hypoglycemic agents, were randomly assigned to receive either a placebo or treatment with 400 μg of chromium daily in the form of chromium yeast. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, body fat, and insulin resistance.

RESULTS—No differences were found for the change in A1C between the intervention and placebo groups, nor were any differences found between the groups for the secondary end points.

CONCLUSIONS—There is no evidence that chromium in the form of chromium yeast is effective in improving glycemic control in Western patients with type 2 diabetes who are taking oral hypoglycemic agents.
Identification of Distinct Self-Management Styles of Adolescents With Type 1 Diabetes
Authors: Schneider Stefan , Iannotti Ronald J. , Nansel Tonja R. , Haynie Denise L. , Simons-Morton Bruce , Sobel Douglas O. , Zeitzoff Linda , Clark Loretta , Plotnick Leslie P.
Published: April 2007

OBJECTIVE—Using a profile-based approach to the assessment of diabetes management, the purpose of this study was to identify and evaluate an empirically derived classification system of distinct self-management styles.

RESEARCH DESIGN AND METHODS—Youth with type 1 diabetes (n = 156) aged 10–16 years and their parents were administered a modified version of the Diabetes Self-Management Profile (DSMP). Cluster analyses were performed independently on parent and youth report forms to categorize patients based on their patterns of scores in five diabetes self-management areas.

RESULTS—Cluster analyses revealed three self-management styles that emerged from both youth and parent report: a “methodical style” (33%) with an emphasis on careful meal planning and correct insulin administration; an “adaptive style” (46%), characterized by high rates of blood glucose testing, exercise, and self-care adjustments; and an “inadequate style” (21%) with moderate rates of self-care adjustments and otherwise low DSMP scores. Convergence between parent and youth report classifications was moderate (Cohen's κ = 0.47, P < 0.0001). A1C was 1.6% higher in the inadequate style group than in both other groups (P < 0.0001), and the classification significantly accounted for differences in A1C above what was explained by an overall DSMP score.

CONCLUSIONS—The findings provide support for recognizing subgroups of patients with unique multidimensional patterns of self-care behaviors. The assessment of self-management styles may prove useful for customized treatments that are targeted directly to the patients’ needs.
Androgenicity of Progestins in Hormonal Contraceptives and the Risk of Gestational Diabetes Mellitus
Authors: Hedderson Monique M. , Ferrara Assiamira , Williams Michelle A. , Holt Victoria L. , Weiss Noel S.
Published: April 2007

OBJECTIVE—There is some evidence that use of hormonal contraceptives, particularly the more androgenic formulations, can alter a woman's glucose tolerance. We examined the association between hormonal contraceptive use, categorized by the androgenicity of the progestin component, and risk of gestational diabetes mellitus (GDM) in a nested case-control study.

RESEARCH DESIGN AND METHODS—Case (n = 356) and control (n = 368) subjects were selected from a multiethnic cohort of 14,235 women who delivered a singleton live birth between 1 January 1996 and 30 June 1998, who were screened for GDM at 24–28 gestational weeks, and who were members of Kaiser Permanente for at least 5 years before pregnancy. GDM was defined using the National Diabetes Data Group plasma glucose cutoffs. Information concerning hormonal contraceptive use during the 5 years before pregnancy was obtained from medical charts and some pharmacy data.

RESULTS—There was a suggestion that compared with no hormonal contraceptive use, use of a low-androgen hormonal contraceptive before pregnancy was associated with a slight reduction in risk of GDM (odds ratio 0.84 [95% CI 0.58–1.22]), whereas use of a high-androgen hormonal contraceptive was associated with a modest increase in GDM risk (1.43 [0.92–2.22]).

CONCLUSIONS—The effects of hormonal contraceptive use on GDM risk may vary by the androgenicity of the progestin component.
Prevalence of Nonalcoholic Fatty Liver Disease and Its Association With Cardiovascular Disease Among Type 2 Diabetic Patients
Authors: Targher Giovanni , Bertolini Lorenzo , Padovani Roberto , Rodella Stefano , Tessari Roberto , Zenari Luciano , Day Christopher , Arcaro Guido
Published: April 2007

OBJECTIVE—To determine the prevalence of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetic population and to compare the prevalence of cardiovascular disease (CVD) and its risk factors between people with and without NAFLD.

RESEARCH DESIGN AND METHODS—The entire sample of type 2 diabetic outpatients (n = 2,839) who regularly attended our clinic was screened. Main outcome measures were NAFLD (by patient history and liver ultrasound) and manifest CVD (by patient history, review of patient records, electrocardiogram, and echo-Doppler scanning of carotid and lower limb arteries).

RESULTS—The unadjusted prevalence of NAFLD was 69.5% among participants, and NAFLD was the most common cause (81.5%) of hepatic steatosis on ultrasound examination. The prevalence of NAFLD increased with age (65.4% among participants aged 40–59 years and 74.6% among those aged ≥60 years; P < 0.001) and the age-adjusted prevalence of NAFLD was 71.1% in men and 68% in women. NAFLD patients had remarkably (P < 0.001) higher age and sex-adjusted prevalences of coronary (26.6 vs. 18.3%), cerebrovascular (20.0 vs. 13.3%), and peripheral (15.4 vs. 10.0%) vascular disease than their counterparts without NAFLD. In logistic regression analysis, NAFLD was associated with prevalent CVD independent of classical risk factors, glycemic control, medications, and metabolic syndrome features.

CONCLUSIONS—NAFLD is extremely common in people with type 2 diabetes and is associated with a higher prevalence of CVD. Follow-up studies are needed to determine whether NAFLD predicts the development and progression of CVD.
High Circulating Retinol-Binding Protein 4 Is Associated With Elevated Liver Fat but Not With Total, Subcutaneous, Visceral, or Intramyocellular Fat in Humans
Authors: Stefan Norbert , Hennige Anita M. , Staiger Harald , Machann Jürgen , Schick Fritz , Schleicher Erwin , Fritsche Andreas , Häring Hans-Ulrich
Published: April 2007

OBJECTIVE—Retinol-binding protein 4 (RBP4) is an adipokine that induced insulin resistance in mice, and high plasma RBP4 levels were associated with insulin-resistant states in humans. To determine which fat compartments are associated with elevated RBP4 levels in humans, we measured circulating RBP4 in 75 healthy subjects and used state-of-the-art measurements of body fat distribution.

RESEARCH DESIGN AND METHODS—Total body, visceral, and subcutaneous abdominal fat were determined by magnetic resonance tomography and liver fat and intramyocellular fat by localized proton magnetic resonance spectroscopy. Insulin sensitivity was measured by the euglycemic-hyperinsulinemic clamp and, together with insulin clearance, estimated from the oral glucose tolerance test (OGTT).

RESULTS—Adjusted circulating RBP4 correlated negatively with insulin sensitivity (clamp: r = −0.33, P = 0.005; OGTT: r = −0.36, P = 0.002) and positively with parameters in the fasting state as insulin levels (r = 0.35, P = 0.003) and homeostasis model assessment of insulin resistance (r = 0.34, P = 0.004). In addition, circulating RBP4 correlated negatively with hepatic insulin clearance (r = −0.25, P = 0.04). Circulating RBP4 was not associated with total body, visceral, or subcutaneous abdominal fat (all P ≥ 0.29). Plasma RBP4 levels were also not associated with intramyocellular fat or circulating adiponectin or leptin. In contrast, plasma RBP4 levels correlated positively with liver fat in cross-sectional (r = 0.27, P = 0.03) and longitudinal (r = 0.37, P = 0.04) analyses.

CONCLUSIONS—Circulating RBP4 is not associated with the amount of fat in the classical depots or in the ectopic depots in muscle. However, it correlates positively with liver fat. Furthermore, metabolic parameters support the close relationship between circulating RBP4 with liver fat and, presumably, hepatic insulin resistance.
Noninvasive Type 2 Diabetes Screening
Authors: Maynard John D. , Rohrscheib Mark , Way Jeffrey F. , Nguyen Catriona M. , Ediger Marwood N.
Published: April 2007

OBJECTIVE—This study compared the performance of a novel noninvasive technology to fasting plasma glucose (FPG) and A1C tests for detecting undiagnosed diabetes and impaired glucose tolerance.

RESEARCH DESIGN AND METHODS—The design was a head-to-head evaluation in a naïve population. Consented subjects received FPG and A1C tests and an oral glucose tolerance test (OGTT). Subjects were also measured by a noninvasive device that detects the fluorescence of skin advanced glycation end products. A total of 351 subjects participated.

RESULTS—Subjects with 2-h OGTT values ≥140 mg/dl defined the positive screening class. A total of 84 subjects (23.9% prevalence) screened positive. The performances of the noninvasive device, FPG, and A1C were evaluated for sensitivity and specificity against this classification. At the impaired fasting glucose threshold (FPG =100 mg/dl), the FPG testing sensitivity was 58% and the specificity was 77.4%. At that same specificity, the sensitivity for A1C testing was 63.8%, while the noninvasive testing sensitivity was 74.7%. The sensitivity advantage of the noninvasive device over both blood tests for detecting diabetes and precursors was statistically significant (P < 0.05).

CONCLUSIONS—The noninvasive technology showed clinical performance advantages over both FPG and A1C testing. The sensitivity differential indicated that the noninvasive device is capable of identifying 28.8% more individuals in the OGTT-defined positive screening class than FPG testing and 17.1% more than A1C testing. The combination of higher sensitivity and greater convenience—rapid results with no fasting or blood draws—makes the device well suited for opportunistic screening.
Procaspase-9 is attached to the mitochondrial outer membrane in the early stages of apoptosis
Authors: Milisav Irina , Šuput Dušan
Published: April 2007

Procaspase-9 is the zymogen form of one of the apoptosis initiators, caspase-9. Its cellular location may differ depending on the cell type; it is found throughout the cytosol, although some of it may be associated with the mitochondria. Procaspase-9 relocates from the cytosol to the mitochondria shortly after the triggering of apoptosis in rat hepatocytes. We investigated whether the mitochondrial protein import machineries import procaspase-9. The combined results of protein import analyses, mitochondrial fractionation and protease treatments of intact and swollen mitochondria imply that procaspase-9 attaches to the outer surface of the mitochondrial outer membrane.
Two new cryptogonimid genera (Digenea, Cryptogonimidae) from Lutjanus bohar (Perciformes, Lutjanidae): analyses of ribosomal DNA reveals wide geographic distribution and presence of cryptic species
Authors: Miller Terrence , Cribb Thomas
Published: April 2007

We describe three new species of Cryptogonimidae belonging to two new genera, Caulanus gen. nov. and Latuterus gen. nov., from the large piscivorous reef fish Lutjanus bohar Forsskål, 1775, recovered from Heron and Lizard Islands off the Great Barrier Reef and Rasdhoo Atoll, Maldives. To support our morphologically based taxonomic approach, three nuclear ribosomal DNA regions (28S, ITS1 and ITS2) were sequenced and analysed to explore the geographic distribution and integrity of the putative species recovered from these widespread localities. Sequencing of the rDNA regions included multiple replicates and revealed three distinct genotypes. Two of the observed genotypes were associated with phenotypically similar specimens of Latuterus, but were each restricted to a single locality, Lizard Island, GBR or Rasdhoo Atoll, Maldives. A posteriori analysis of the associated morphotypes revealed distinct morphological differences and these consistent differences, in combination with the consistent genetic differences led to the recognition of two distinct species in the system. Caulanus is distinguished by having oral spines, caeca which open via ani at the posterior end of the body, tandem testes and uterus that extends from the posterior end of the body to the pharynx. Latuterus is distinguished by lacking oral spines, having multiple/follicular testes, a uterus that is extensive in both fore-and hindbody and vitelline follicles which are confined to the region from the pharynx to oral sucker. Caulanus thomasi sp. nov. had identical sequences for all of the rDNA regions examined from specimens recovered from all three localities, indicating that this species has a wide Indo-Pacific distribution. The species reported here are evidently restricted to Lutjanus bohar because they were never found in large numbers of other lutjanid species sampled at the same localities.
Terahertz imaging: a new non-destructive technique for the quality control of plastic weld joints
Authors: Wietzke S. , Jördens C. , Krumbholz N. , Baudrit B. , Bastian M. , Koch M.
Published: April 2007

We present the first investigation of plastic weld joints using terahertz waves. Terahertz time-domain spectroscopy clearly reveals contaminations like metal or sand within the weld joint of two high-density polyethylene sheets. Furthermore, areas can be identified where the welding process has failed and the parts to be joined are separated by a small air gap. We show that a three layer structure of polyethylene-air-polyethylene has a characteristic, frequency-dependent transmission behaviour. This allows for a distinction between welded and non-welded material as well as for the calculation of the air layer thickness from the relative transmission spectrum. Consequently, terahertz time-domain spectroscopy provides a promising new non-destructive and even contactless technique, which is desired by the plastics industry for detecting a variety of deviations from the ideal welding process.
A Poly(3,4‐alkylenedioxythiophene) Electrochromic Variable Optical Attenuator with Near‐Infrared Reflectivity Tuned Independently of the Visible Region
Authors: Dyer A. L. , Grenier C. R. G. , Reynolds J. R.
Published: April 2007

Disubstituted poly(3,4‐propylenedioxythiophene)s (PProDOTs) exhibit large electrochromic contrasts in the near infrared (NIR) while showing essentially no color change in the visible region when incorporated into a reflective device platform. The source of this is attributed to a conductive front that propagates through the insulating polymer film, extending from the polymer/electrode interface to the top of the polymer film. A utility of the large contrasts seen in the NIR region is demonstrated with application of the device as an electrochromic variable optical attenuator modulating fiber‐optic signals for optical telecommunications. With bis(ethylhexyloxy)‐substituted PProDOT as the active electrochromic polymer in the device, an optical attenuation of 11 dB at the telecommunications wavelengths of 1.31 and 1.55 μm is achieved with only a 0.1–0.2 dB optical loss in the bleached state. Other favorable properties include optical memory in the absorbing state, switching speeds of under 1 s, a low operating voltage of ±1.2 V, and an improved processability that allows spray‐casting from organic solvents.
Cover Picture: UV‐Light‐Induced Swelling and Visible‐Light‐Induced Shrinking of a TiO2‐Containing Redox Gel (Adv. Mater. 9/2007)
Authors: Tatsuma T. , Takada K. , Miyazaki T.
Published: April 2007

Polyacrylate gels containing Ag+ and TiO2 nanoparticles are shown to swell under UV light and shrink under visible light in water. In work reported by Tetsu Tatsuma and co‐workers on p. 1249, the TiO2 absorbs UV light and reduces the Ag+, whereas the deposited Ag absorbs visible light and dissolves itself. These redox reactions change the interactions between the polymer chains and eventually the volume of the gel, as shown on the cover.
A novel VEGFR3 mutation causes Milroy disease
Authors: Butler Matthew G. , Dagenais Susan L. , Rockson Stanley G. , Glover Thomas W.
Published: April 2007

Milroy disease, also known as primary congenital lymphedema, is a hereditary form of lymphedema with autosomal dominant inheritance. Individuals with Milroy disease are typically characterized by congenital onset of lymphedema of the lower limbs due to hypoplasia of the lymphatic vessels. The genetic basis of most cases of Milroy disease has not been established, although mutations in the vascular endothelial growth factor receptor VEGFR3 (FLT‐4) are responsible for some cases with 17 mutations described to date. In this report, we describe a novel VEGFR3 mutation in exon 22 in a four‐generation family in which congenital lymphedema segregates in an autosomal dominant manner. In addition to lymphedema, affected family members had other clinical manifestations associated with Milroy disease including hydrocele, ski jump toenails, large caliber veins, and subcutaneous thickening. We screened VEGFR3 for mutations which revealed a novel 3059A > T transversion in exon 22 resulting in Q1020L missense mutation in the second tyrosine kinase domain of VEGFR3. This mutant allele segregated with lymphedema among affected individuals with incomplete penetrance. This is the first report of an exon 22 mutation in Milroy disease. © 2007 Wiley‐Liss, Inc.
Parameters affecting the grafting reaction and side reactions involved in the free‐radical melt grafting of maleic anhydride onto high‐density polyethylene
Authors: Sheshkali H. R. Z. , Assempour H. , Nazockdast H.
Published: April 2007

The parameters affecting the grafting reaction and side reactions in free‐radical melt grafting of maleic anhydride (MA) onto high‐density polyethylene with the aid of 2,5‐dimethyl‐2,5‐di(t‐butyl peroxy)hexane peroxide(DTBPH) have been studied using an internal mixer. MA grafting degree of the maleated samples was measured with titrometry and FTIR spectroscopy methods. The extent of chain‐branching/crosslinking side reactions was evaluated with gel content and MFI determination. The flow behavior and melt viscoelastic properties of the samples were measured using a rheometric mechanical spectrometer. DTBPH and MA concentrations, reaction temperature, rotor speed, the type and concentration of coagents were among the studied parameters. The results show that MA and DTBPH concentration has a major role on the grafting reaction, chain‐branching/crosslinking side reactions and also the grafts microstructure in the final product. The reaction temperature has a complex effect on the maleation reaction. Increasing the rotor speed causes an increase in MA grafting degree of the samples and reduces the competitive side reactions. By using Gaylord additives, gel formation reduces at the expense of a dramatic decrease in the grafting degree. MA grafting degree is increased by the use of comonomers in the reaction and this is accompanied with a decrease in crosslinking side reaction when the vinyl type styrene comonomer is used. The results of processing torque in combination with the measurements of the melt viscoelastic property and gel content of the samples provide a great insight into understanding the gel formation mechanism. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Analysis of the effect of the amount and type of montmorillonite on the supermolecular structure, porosity, and properties of polyimidoamide fibres
Authors: Mikołajczyk Teresa , Rabiej Stanisław , Olejnik Magdalena
Published: April 2007

The effect of the amount and type of montmorillonite (MMT) on the supermolecular structure, porosity, and properties of polyimidoamide (PIA) fibres has been investigated. An increase in the quantity of nanoadditive incorporated into the fiber‐forming polymer from 1 to 5% results in a decrease in the strength properties of fibers. The level of the sorption parameters of PIA nanocomposite fibers depends not only on the nanoadditive content, but also on the type of modifier used to change the MMT properties from hydrophilic to organophilic. It has been found that the exfoliation of MMT depends on the chemical structure of its modifier. The exfoliation takes place when MMT is modified with aminododecane acid. © 2007 Wiley Periodicals, Inc. J Appl Polym Sci, 2007
Some antiphospholipid antibodies recognize conformational epitopes shared by β2‐glycoprotein I and the homologous catalytic domains of several serine proteases
Authors: Lin Wei‐Shiang , Chen Pei‐Chih , Yang Cheng‐De , Cho EunJung , Hahn Bevra H. , Grossman Jennifer , Hwang Kwan‐Ki , Chen Pojen P.
Published: April 2007

Objective

To test the hypothesis that some antiphospholipid antibodies (aPL) in patients with the antiphospholipid syndrome (APS) recognize a conformational epitope shared by β2‐glycoprotein I (β2GPI; the major autoantigen for the antiphospholipid antibodies) and the homologous catalytic domains of several serine proteases (such as thrombin, activated protein C [APC], and plasmin) involved in hemostasis.

Methods

We generated 4 new IgG monoclonal aPL (2 screened against β2GPI, 1 against thrombin, and 1 against protein C) from 2 APS patients. The monoclonal antibodies (mAb) were analyzed for binding to β2GPI, thrombin, APC, and plasmin, as well as for anticardiolipin antibody (aCL) activity. To demonstrate a shared epitope between β2GPI and a serine protease, 1 mAb was studied by cross‐inhibition analysis.

Results

Both of the IgG anti‐β2GPI mAb bound to thrombin, APC, and plasmin. On the other hand, the 1 anti‐thrombin mAb and the 1 anti–protein C mAb also bound to β2GPI. Moreover, the binding of 1 cross‐reactive mAb to β2GPI was inhibited by α‐thrombin (which contains only the catalytic domain of thrombin). All 4 mAb displayed aCL activity.

Conclusion

Taken together with the findings that some aCL bind to several serine proteases that participate in hemostasis and share homologous catalytic domains, these data demonstrate that some aCL in APS patients recognize one or more conformational epitopes shared by β2GPI and the catalytic domains of disease‐relevant serine proteases.
Plasmacytoid dendritic cells in inflamed muscle of patients with juvenile dermatomyositis
Authors: López de Padilla Consuelo M. , Vallejo Abbe N. , McNallan Kelly T. , Vehe Richard , Smith Stephen A. , Dietz Allan B. , Vuk‐Pavlovic Stanimir , Reed Ann M.
Published: April 2007

Objective

To examine whether dendritic cells (DCs) are constituents of muscle inflammation in juvenile dermatomyositis (DM).

Methods

The types, numbers, and activation state of DC subsets in inflamed muscle tissue from patients with juvenile DM and in noninflamed muscle tissue from control subjects were examined by multicolor immunofluorescence. Chemokine expression of the muscle‐infiltrating cells was examined by laser capture microdissection and quantitative polymerase chain reaction.

Results

Plasmacytoid DCs were the predominant component of the inflamed muscle tissue from patients with juvenile DM. These cells were identified by coexpression of CD4 and CD123, but not CD11c, and also expressed CD83, indicating maturity of the cells. In contrast, in noninflamed muscle, plasmacytoid DCs were scarce and did not express CD83. Mononuclear cells surrounding the blood vessels of inflamed muscle contained abundant transcripts of CCL19 and CCL21, but very little CCL18 transcripts. In contrast, cells from noninflamed muscle contained negligible amounts of CCL19 and CCL21, but had high amounts of CCL18. Both the inflamed and noninflamed muscle tissue had equivalent levels of CXCL12 transcripts, but inflamed muscle contained more transcripts of the CXCL12 receptor CXCR4.

Conclusion

These findings are consistent with the idea that plasmacytoid DCs are mediators of muscle inflammation in juvenile DM. The abundance of CD83+ plasmacytoid DCs in perivascular areas and the overexpression of CCL19 and CCL21 in perivascular cellular foci suggest that in situ activation and maturation of resident plasmacytoid DCs are central to the initiation and perpetuation of muscle inflammation in juvenile DM.
The innate immune component ficolin 3 (Hakata antigen) mediates the clearance of late apoptotic cells
Authors: Honoré Christian , Hummelshoj Tina , Hansen Bjarke E. , Madsen Hans O. , Eggleton Paul , Garred Peter
Published: April 2007

Objective

Ficolin 3 (Hakata antigen), a collagen‐like defense molecule, is a known autoantigen in patients with systemic lupus erythematosus (SLE). Recent studies have shown that other collagen‐like defense molecules, such as C1q, mannose‐binding lectin (MBL) and ficolin 2, bind to apoptotic cells and mediate their clearance by phagocytic cells. Dysfunction in this mechanism is regarded as an important contributor to the pathophysiology of SLE. Thus, we sought to determine whether ficolin 3 participates in the clearance of apoptotic cells.

Methods

A Jurkat T cell line was used as the source of dying host cells. The cells were rendered apoptotic or necrotic by incubation with etoposide or by heat shocking, respectively. Binding of ficolin 3 to the cells was analyzed by flow cytometry. The apoptotic cells were incubated with human monocyte‐derived macrophages, and the effect of ficolin 3 on the adhesion/uptake was examined by flow cytometry.

Results

Ficolin 3 bound to a population of late apoptotic cells, while a strong and uniform binding to necrotic cells was observed. The binding properties differed from those of MBL and ficolin 2. Ficolin 3 binding to late apoptotic cells resulted in a significant increase in adhesion/uptake by macrophages.

Conclusion

Ficolin 3 mediates the clearance of late apoptotic cells, which suggests that this protein is involved in the maintenance of tissue homeostasis and might play a protective role against the development of autoimmunity.
Differential recognition of heat‐shock protein dnaJ–derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis
Authors: Massa Margherita , Passalia Maristella , Manzoni Silvia Magni , Campanelli Rita , Ciardelli Laura , Yung Gisella Puga , Kamphuis Sylvia , Pistorio Angela , Meli Valentina , Sette Alessandro , Prakken Berent , Martini Alberto , Albani Salvatore
Published: April 2007

Objective

To identify epitopes on Escherichia coli heat‐shock protein (HSP) dnaJ or on homologous human HSP dnaJ involved in the induction/modulation of autoimmune inflammation in patients with oligoarticular juvenile idiopathic arthritis (JIA).

Methods

We used a proliferation assay and cytokine production to evaluate the immune responses of synovial fluid mononuclear cells (SFMCs) to pan–HLA–DR binder peptides derived from either homologous or nonhomologous regions on bacterial and human HSP dnaJ. Cytofluorometric analysis was performed in order to phenotype and sort Treg cells. Sorted cells were then analyzed for the expression of the forkhead box P3 (FoxP3) transcription factor, and their regulatory capacity was tested in coculture assays.

Results

T cell responses to E coli HSP dnaJ–derived peptides were eminently proinflammatory. Conversely, peptides derived from human HSP dnaJ induced interleukin‐10 (IL‐10) production from SFMCs of patients with oligoarticular JIA. A positive correlation was found between disease with a better prognosis (persistent oligoarticular JIA) and recognition of 3 human HSP dnaJ–derived peptides. The recognition of the human peptide H134–148 also induced a significantly greater amount of IL‐10 in patients with persistent oligoarticular JIA than in those with extended oligoarticular JIA (P = 0.0012). Incubation of SFMCs from patients with persistent oligoarticular JIA with this human epitope increased the percentage of Treg cells and FoxP3 expression. It also induced the recovery of suppressor activity by Treg cells.

Conclusion

This is the first description of a self‐regulating immune modulator circuit active during autoimmune inflammation through recognition of HSP epitopes with different functional properties. These epitopes induce T cells with regulatory function. Such induction correlates with disease severity and prognosis.
Impact of oral cyclophosphamide on health‐related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study
Authors: Khanna Dinesh , Yan Xiaohong , Tashkin Donald P. , Furst Daniel E. , Elashoff Robert , Roth Michael D. , Silver Richard , Strange Charlie , Bolster Marcy , Seibold James R. , Riley David J. , Hsu Vivien M. , Varga John , Schraufnagel Dean E. , Theodore Arthur , Simms Robert , Wise Robert , Wigley Fredrick , White Barbara , Steen Virginia , Read Charles , Mayes Maureen , Parsley Ed , Mubarak Kamal , Connolly M. Kari , Golden Jeffrey , Olman Mitchell , Fessler Barri , Rothfield Naomi , Metersky Mark , Clements Philip J. ,   Scleroderma Lung Study Group
Published: April 2007

Objective

To assess the impact of cyclophosphamide (CYC) on the health‐related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment.

Methods

One hundred fifty‐eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF‐36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference‐based measure, the SF‐6D. The differences in the HRQOL between the 2 groups at 12 months were calculated using a linear mixed model. Responsiveness was evaluated using the effect size. The proportion of subjects in each treatment group whose scores improved at least as much as or more than the minimum clinically important difference (MCID) in HRQOL measures was assessed.

Results

After adjustment for baseline scores, differences in the HAQ DI, SF‐36 role physical, general health, vitality, role emotional, mental health scales, and SF‐36 mental component summary (MCS) score were statistically significant for CYC versus placebo (P< 0.05). Effect sizes were negligible (<0.20) for all of the scales of the SF‐36, HAQ DI, and SF‐6D at 12 months. In contrast, a higher proportion of patients who received CYC achieved the MCID compared with placebo in the HAQ DI score (30.9% versus 14.8%), transitional dyspnea index score (46.4% versus 12.7%), SF‐36 MCS score (33.3% versus 18.5%), and SF‐6D score (21.3% versus 3.8%).

Conclusion

One year of treatment with CYC leads to an improvement in HRQOL in patients with scleroderma lung disease.
Involvement of the constitutive complex formation of c‐Ski/SnoN with smads in the impaired negative feedback regulation of transforming growth factor β signaling in scleroderma fibroblasts
Authors: Jinnin Masatoshi , Ihn Hironobu , Mimura Yoshihiro , Asano Yoshihide , Tamaki Kunihiko
Published: April 2007

Objective

The principal effect of transforming growth factor β1 (TGFβ1) on mesenchymal cells is its stimulation of extracellular matrix synthesis. Previous reports indicated the significance of the autocrine TGFβ loop in the pathogenesis of scleroderma. The aim of this study was to examine c‐Ski and SnoN, principal molecules in the negative regulation of TGFβ signaling, to further understand the autocrine TGFβ loop in scleroderma.

Methods

Levels of expression of c‐Ski/SnoN on cultured normal and scleroderma fibroblasts were determined by Western blotting, Northern blotting, and immunohistochemical staining. To determine the protein–protein interaction between c‐Ski/SnoN, Smads, and p300, immunoprecipitation was performed. A transient transfection assay was performed to measure promoter activity of the α2(I) collagen gene and the 3TP‐Lux plasmid construct.

Results

Scleroderma fibroblasts exhibited increased c‐Ski/SnoN levels compared with normal fibroblasts, both in vivo and in vitro. Although c‐Ski/SnoN constitutively formed a complex with Smads by immunoprecipitation, the inhibitory effect of c‐Ski/SnoN on the promoter activity of human α2(I) collagen and 3TP‐Lux was impaired in scleroderma fibroblasts. Immunoprecipitation analyses also revealed that overexpressed c‐Ski/SnoN could not compete with p300 in these cells.

Conclusion

These results indicate that impaired competition with p300 is the possible cause of dysfunction of c‐Ski/SnoN in scleroderma fibroblasts and that this might contribute to maintenance of the autocrine TGFβ loop in this disease.