bluuebunny/crossref_metadata_2025 huggingface dataset:
Genes of Cholesterol Metabolism in Human Atheroma
Authors: Forcheron Fabien , Legedz Liliana , Chinetti Guiletta , Feugier Patrick , Letexier Dominique , Bricca Giampierro , Beylot Michel
Published: June 2005

Objective—

Accumulation of cholesterol in foam cells of atheroma plaques depends on the balance between uptake and efflux of cholesterol. It may also depend on proteins surrounding lipid droplets, adipophilin, and perilipins. They favor triglyceride storage in adipocytes and could play a similar role for cholesterol in atheroma.

Methods and Results—

We measured in human atheroma and nearby macroscopically intact tissue (MIT) the expression of perilipin, adipophilin, and regulatory factors of cholesterol metabolism. We identified perilipin A in human arterial wall. Its expression was largely increased in atheroma compared with MIT, and perilipin was present in macrophages and vascular smooth muscle cells. Adipophilin, ACAT1, and CD36 were also overexpressed in atheroma. mRNA levels of low-density lipoprotein receptor, 3-hydroxy-3-methylglutaryl coenzyme A reductase, and SREBP-2 were unchanged. With respect to efflux of cholesterol, the mRNA levels of NCEH and ABCA-1 were unchanged, whereas CLA-1 mRNA was slightly higher in atheroma. Importantly, immunoblotting of ABCA-1 showed a dramatic decrease of ABCA1 protein, the key molecule of cholesterol efflux, in atheroma compared with MIT.

Conclusion—

We show the presence and induction of perilipin in atheroma. This overexpression and the coordinated modifications of expression of key regulatory factors for cholesterol metabolism could favor cholesterol accumulation.
An Oral ApoJ Peptide Renders HDL Antiinflammatory in Mice and Monkeys and Dramatically Reduces Atherosclerosis in Apolipoprotein E–Null Mice
Authors: Navab Mohamad , Anantharamaiah G.M. , Reddy Srinivasa T. , Van Lenten Brian J. , Wagner Alan C. , Hama Susan , Hough Greg , Bachini Eugene , Garber David W. , Mishra Vinod K. , Palgunachari Mayakonda N. , Fogelman Alan M.
Published: June 2005

Objective—

To determine the properties of a peptide synthesized from D-amino acids corresponding to residues 113 to 122 in apolipoprotein (apo) J.

Methods and Results—

In contrast to D-4F, D- [113–122]apoJ showed minimal self-association and helicity in the absence of lipids. D-4F increased the concentration of apoA-I with pre-β mobility in apoE-null mice whereas D- [113–122]apoJ did not. After an oral dose D- [113–122]apoJ more slowly associated with lipoproteins and was cleared from plasma much more slowly than D-4F. D- [113–122]apoJ significantly improved the ability of plasma to promote cholesterol efflux and improved high-density lipoprotein (HDL) inflammatory properties for up to 48 hours after a single oral dose in apoE-null mice, whereas scrambled D- [113–122]apoJ did not. Oral administration of 125 μg/mouse/d of D- [113–122]apoJ reduced atherosclerosis in apoE-null mice (70.2% reduction in aortic root sinus lesion area,
P
=4.3×10
−13
; 70.5% reduction by en face analysis,
P
=1.5×10
−6
). In monkeys, oral D- [113–122]apoJ rapidly reduced lipoprotein lipid hydroperoxides (LOOH) and improved HDL inflammatory properties. Adding 250 ng/mL of D-[113–122]apoJ (but not scrambled D- [113–122]apoJ) to plasma in vitro reduced LOOH and increased paraoxonase activity.

Conclusions—

Oral D- [113–122]apoJ significantly improves HDL inflammatory properties in mice and monkeys and inhibits lesion formation in apoE-null mice.
Overexpression of Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Induces Intramyocardial Vasculopathy in Apolipoprotein E–Null Mice
Authors: Inoue Kazuhiko , Arai Yuji , Kurihara Hiroki , Kita Toru , Sawamura Tatsuya
Published: June 2005

Endothelial dysfunction induced by oxidized low-density lipoprotein (OxLDL) has been implicated in the pathogenesis of atherosclerosis and vasculopathy. Increased expression of lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), the receptor for OxLDL in endothelial cells, has been demonstrated in the atherosclerotic plaques from experimental atherosclerotic animal models and human clinical samples. In vitro, activation of LOX-1 alters the expression of several endothelial cell genes that are involved in endothelial dysfunction. To investigate the role of LOX-1 in terms of both endothelial dysfunction and resultant vascular changes, we generated mice overexpressing LOX-1 (LOXtg) in C57BL/6 and apolipoprotein E–null mice (apoEKO) backgrounds. We found that the expression of the transgene was prominent in coronary vessels and cardiomyocytes. The enhancement of OxLDL uptake in LOXtg mice was consistent with the expression level of LOX-1. Under hyperlipidemic conditions, both OxLDL and 8-hydroxy-2′-deoxyguanosine accumulated in the coronary arteries of LOXtg/apoEKO mice. The expression of ICAM-1 and VCAM-1, as well as the number of macrophages around blood vessels, were significantly increased in LOXtg/apoEKO mice compared with control littermates. There were no differences in either the hemodynamic profile or the plasma lipid profile between the 2 groups of animals. LOXtg/apoEKO mice displayed accelerated intramyocardial vasculopathy, and the atheroma-like lesion area was increased 10-fold in the LOXtg/apoEKO mice compared with nontransgenic littermates after 3-weeks on the high-fat diet. Thus, it is demonstrated that LOX-1 overexpression promotes inflammatory intramyocardial vasculopathy in a hyperlipidemic mouse model, and this effect is probably mediated through the endothelial dysfunction induced by overexpression of LOX-1.
Houston Paramedic and Emergency Stroke Treatment and Outcomes Study (HoPSTO)
Authors: Wojner-Alexandrov Anne W. , Alexandrov Andrei V. , Rodriguez Diana , Persse David , Grotta James C.
Published: June 2005

Background and Purpose—

Establishment of stroke centers, combined with accurate paramedic diagnosis and rapid transport, is essential to deliver acute stroke therapy. We wanted to measure and improve paramedic and hospital performance through implementation of the Brain Attack Coalition and American Stroke Association guidelines.

Methods—

Pre-intervention and active-intervention phases with parallel data measurement points were used. The study involved six hospitals comprising the majority of acute-stroke admissions in Houston, Tex. Hospital, paramedic, and patient data were collected prospectively pre-intervention and during the active-intervention phase on all suspected acute-stroke patients admitted by Houston Fire Department-Emergency Medical Services. A multilevel educational intervention included paramedic, hospital, and community education. Paramedic diagnostic accuracy, hospital-performance efficiency, and thrombolytic treatment rates were the main outcome measures of the study.

Results—

Four hundred forty-six patients (74 per month) were transported in the pre-intervention phase to participating hospitals (59.8% of all suspected stroke patients transported city wide by Houston Fire Department—Emergency Medical Services), compared with 1072 patients (89 per month, or 68.7%) transported in the active-intervention phase (
P
<0.001). Accuracy of paramedic diagnosis of stroke increased from 61% to 79%. Admission within 2 hours of symptom onset increased from 58% to 62% (
P
=0.002). Thrombolysis rates increased in 4 of 6 centers, with 1 post- tissue plasminogen activator hemorrhage (3.7%) reported.

Conclusions—

A multilevel educational program improves rapid hospitalization and paramedic diagnostic accuracy and increases the number of patients presenting for evaluation within the 3-hour tissue plasminogen activator window. Stroke center development supports safe thrombolytic practice in community settings.
Life Versus Disease in Difficult Diabetes Care: Conflicting Perspectives Disempower Patients and Professionals in Problem Solving
Authors: Zoffmann Vibeke , Kirkevold Marit
Published: June 2005

Conflicts in problem solving are known from diabetes research on patients with good glycemic control but have rarely been studied in the care of patients with poor glycemic control. Equally, the different perspectives of health care providers and patients have not been a focus in previous studies. The authors studied the interactions between health care providers and 11 diabetes patients with poor glycemic control in a grounded theory study at a Danish university hospital. Keeping Life and Disease Apart was identified as a core category. It involved a pattern of conflicts both between and within patients and health professionals, which disempowered them in problem solving. Three approaches to problem solving were identified: A compliance-expecting approach kept the pattern unchanged, a failure-expecting approach deadlocked the pattern, and a mutuality-expecting approach appeared to neutralize the conflict.
Older Stroke Patients’ Negotiations Within the Hierarchic Medical Context
Authors: LÖFmark Ulrika , HammarstrÖM Anne
Published: June 2005

A stroke can affect a person’s whole being and make him or her feel helpless and insecure. In this study, the authors aimed to analyze from a gender perspective how elderly women and men responded to treatment and care after stroke in the acute care setting. They used a strategic selection procedure in this qualitative follow-up interview study, in which 7 women and 5 men aged 75 to 83 participated. Personal interviews were performed, tape-recorded, transcribed verbatim, and analyzed in accordance with grounded theory. In the hierarchic medical context, the participants used four kinds of negotiations. These negotiations were either resistant (striving for autonomy and criticizing the care) or adjustive (following the rules and building alliances) to the hierarchic structure. The authors discuss how the concepts of power from above versus power from below can be applied in the hierarchic medical context.
Cooperating cancer-gene identification through oncogenic-retrovirus–induced insertional mutagenesis
Authors: Du Yang , Spence Sally E. , Jenkins Nancy A. , Copeland Neal G.
Published: June 2005

Multiple cooperating mutations that deregulate different signaling pathways are required to induce cancer. Identifying these cooperating mutations is a prerequisite for developing better combinatorial therapies for treating cancer. Here we show that cooperating cancer mutations can be identified through oncogenic-retrovirus-induced insertional mutagenesis. Among 13 myeloid leukemias induced by transplanting into mice bone marrow cells infected in vitro with a replication-defective retrovirus carrying the Sox4 oncogene, 9 contained insertional mutations at known or suspected cancer genes. This likely occurred because rare bone marrow cells, in which the oncogenic retrovirus happened to integrate and in which it mutated a cooperating cancer gene, were selected because the host harbored a cooperating cancer mutation. Cooperativity between Sox4 and another gene, Mef2c, was subsequently confirmed in transplantation studies, in which deregulated Mef2c expression was shown to accelerate the myeloid leukemia induced by Sox4. Insertional mutagenesis of cooperating cancer genes by a defective oncogenic retrovirus provides a new method for identifying cooperating cancer genes and could aid in the development of better therapies for treating cancer. (Blood. 2005;106:2498-2505)
SCL/TAL1 expression level regulates human hematopoietic stem cell self-renewal and engraftment
Authors: Reynaud Damien , Ravet Emmanuel , Titeux Monique , Mazurier Frédéric , Rénia Laurent , Dubart-Kupperschmitt Anne , Roméo Paul-Henri , Pflumio Françoise
Published: June 2005

The fate of hematopoietic stem cells (HSCs) is regulated through a combinatorial action of proteins that determine their self-renewal and/or their commitment to differentiation. Stem cell leukemia/T-cell acute lymphoblastic leukemia 1 (SCL/TAL1), a basic helix-loop-helix (bHLH) transcription factor, plays key roles in controlling the development of primitive and definitive hematopoiesis during mouse development but its function in adult HSCs is still a matter of debate. We report here that the lentiviral-mediated enforced expression of TAL1 in human CD34+ cells marginally affects in vitro the differentiation of committed progenitors, whereas in vivo the repopulation capacity of the long-term SCID (severe combined immunodeficient) mouse–repopulating cells (LT-SRCs) is enhanced. As a consequence, the production of SRC-derived multipotent progenitors as well as erythroid- and myeloid-differentiated cells is increased. Looking at the lymphoid compartment, constitutive TAL1-enforced expression impairs B- but not T-cell differentiation. Expression of a mutant TAL1 protein that cannot bind DNA specifically impairs human LT-SRC amplification, indicating a DNA-binding dependent effect of TAL1 on primitive cell populations. These results indicate that TAL1 expression level regulates immature human hematopoietic cell self-renewal and that this regulation requires TAL1 DNA-binding activity.
Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice
Authors: Gunshin Hiromi , Starr Carolyn N. , DiRenzo Cristina , Fleming Mark D. , Jin Jie , Greer Eric L. , Sellers Vera M. , Galica Stephanie M. , Andrews Nancy C.
Published: June 2005

Mammalian nonheme iron absorption requires reduction of dietary iron for uptake by the divalent metal ion transport system in the intestine. This was thought to be mediated by duodenal cytochrome b (Cybrd1), a ferric reductase enzyme resident on the luminal surface of intestinal absorptive cells. To test its importance in vivo, we inactivated the murine Cybrd1 gene and assessed tissue iron stores in Cybrd1-null mice. We found that loss of Cybrd1 had little or no impact on body iron stores, even in the setting of iron deficiency. We conclude that other mechanisms must be available for the reduction of dietary iron. (Blood. 2005;106: 2879-2883)
Insulin resistance in adolescents with Down syndrome: a cross-sectional study
Authors: Fonseca Cristina T , Amaral Daniela M , Ribeiro Márcia G , Beserra Izabel CR , Guimarães Marília M
Published: June 2005

Background

The prevalence of diabetes mellitus is higher in individuals with Down syndrome (DS) than in the general population; it may be due to the high prevalence of obesity presented by many of them. The aim of this study was to evaluate the insulin resistance (IR) using the HOMA (Homeostasis Model Assessment) method, in DS adolescents, describing it according to the sex, body mass index (BMI) and pubertal development.

Methods

15 adolescents with DS (8 males and 7 females) were studied, aged 10 to 18 years, without history of disease or use of medication that could change the suggested laboratory evaluation. On physical examination, the pubertal signs, acanthosis nigricans (AN), weight and height were evaluated. Fasting plasma glucose and insulin were analysed by the colorimetric method and RIA-kit LINCO, respectively. IR was calculated using the HOMA method. The patients were grouped into obese, overweight and normal, according to their BMI percentiles. The EPIINFO 2004 software was used to calculate the BMI, its percentile and Z score.

Results

Five patients were adults (Tanner V or presence of menarche), 9 pubertal (Tanner II – IV) and 1 prepubertal (Tanner I). No one had AN. Two were obese, 4 overweight and 9 normal. Considering the total number of patients, HOMA was 1.7 ± 1.0, insulin 9.3 ± 4.8 μU/ml and glucose 74.4 ± 14.8 mg/dl. The HOMA values were 2.0 ± 1.0 in females and 1.5 ± 1.0 in males. Considering the nutritional classification, the values of HOMA and insulin were: HOMA: 3.3 ± 0.6, 2.0 ± 1.1 and 1.3 ± 0.6, and insulin: 18.15 ± 1.6 μU/ml, 10.3 ± 3.5 μU/ml and 6.8 ± 2.8 μU/ml, in the obese, overweight and normal groups respectively. Considering puberty, the values of HOMA and insulin were: HOMA: 2.5 ± 1.3, 1.4 ± 0.6 and 0.8 ± 0.0, and insulin: 13.0 ± 5.8 μU/ml, 7.8 ± 2.9 μU/ml and 4.0 ± 0.0 μU/ml, in the adult, pubertal and prepubertal groups respectively.

Conclusion

The obese and overweight, female and adult patients showed the highest values of HOMA and insulin.
Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)-1 expression in human mononuclear leukocytes
Authors: Naldini Antonella , Bernini Claudia , Pucci Annalisa , Carraro Fabio
Published: June 2005

Thrombin, the key enzyme of the coagulation cascade, exerts cellular effects through activation of the protease-activated receptors (PARs). Interleukin (IL)-10, besides its anti-inflammatory properties, is considered a major denominator of the immunosuppressive effect during human endotoxemia. We have recently shown that thrombin inhibits IL-12 production in human mononuclear cells and that such inhibition is accompanied by IL-10 up-regulation. To our knowledge, there are no data available to show that thrombin mediates IL-10 production by its interactions with PAR-1. We here report that human α-thrombin enhances IL-10 expression in human peripheral blood mononuclear cells and in established monocytic cell lines and that this up-regulation requies PAR-1 expression. The use of proteolytically inactive thrombin reveals that such enhancement requires thrombin proteolytic activity. Addition of PAR-1 agonist peptides, such as SFLLRN, results in a significant increase of IL-10 production. PAR-1 expression is required for thrombin-induced IL-10 production, as shown by experiments performed with antisense or sense PAR-1 oligonucleotides. Treatment with thrombin or SFLLRN of monocytic cell lines, such as U937 and Mono Mac-6, results in an increased IL-10 production. This suggests that the observed IL-10 up-regulation may be the result of a direct interaction with monocytes. The observation that thrombin-mediated up-regulation of IL-10 may require the expression of the PAR-1 receptor identifies a new, functional link between inflammation and coagulation. Our results may also contribute to better design therapeutic strategies to treat several disorders, characterized by the presence of inflammatory as well as coagulant responses.
Cellular and Molecular Regulation of Hematopoietic and Intestinal Stem Cell Behavior
Authors: HE XI C. , ZHANG JIWANG , LI LINHENG
Published: June 2005

Abstract: Two fundamental questions in stem cell research are what controls stem cell number in vivo and which signal pathways regulate self‐renewal. Here we summarize our recent studies regarding the role of BMP signaling in regulation of stem cell behavior in both the hematopoietic and intestinal systems. These studies provide evidence to show that BMP signaling plays an important role in controlling stem cell number, at least in these two stem cell compartments. However, the BMP signal utilizes different mechanisms to fulfill this purpose: in the hematopoietic stem cell compartment it controls stem cell number through regulation of the niche size; in the intestinal stem cell compartment it directly controls self‐renewal of stem cells through restriction of/Wnt/β‐catenin activity. The Bmpr1a mutant mouse provided an elegant model which allowed us to identify the HSC niche, an enigma for more than 25 years. Our work provided more evidence to demonstrate the essential function of the niche in maintenance of stem cells and showed that multiple signals are required to maintain a balanced control of stem cell self‐renewal.
Neural Progenitor Cell Transplants into the Developing and Mature Central Nervous System
Authors: SAKAGUCHI D.S. , Van HOFFELEN S J. , GROZDANIC S D. , KWON Y H. , KARDON R H. , YOUNG M J.
Published: June 2005

Abstract: When developing cell transplant strategies to repair the diseased or injured central nervous system (CNS), it is essential to consider host‐graft interactions and how they may influence the outcome of the transplants. Recent studies have demonstrated that transplanted neural progenitor cells (NPCs) can differentiate and integrate morphologically into developing mammalian retinas. Is the ability to differentiate and to undergo structural integration into the CNS unique to specific progenitor cells, or is this plasticity a function of host environment, or both? To address these issues we have used the developing retina of the Brazilian opossum and have compared the structural integration of brain and retinal progenitor cells transplanted into the eyes at different developmental stages. The Brazilian opossum, Monodelphis domestica, is a small pouchless marsupial native to South America. This animal's lack of a pouch and fetal‐like nature at birth circumvents the need for in utero surgical procedures, and thus provides an ideal environment in which to study the interactions between developing host tissues and transplanted NPCs. To test whether NPCs affect visual function we transplanted adult hippocampal progenitor cells (AHPCs) into normal, healthy adult rat eyes and performed noninvasive functional recordings. Monitoring of the retina and optic nerve over time by electroretinography and pupillometry revealed no severe perturbation in visual function in the transplant recipient eyes. Taken together, our findings suggest that the age of the host environment can strongly influence NPC differentiation and that transplantation of neural progenitor cells may be a useful strategy aimed at treating neurodegeneration and pathology of the CNS.
Magnetic Resonance Tracking of Implanted Adult and Embryonic Stem Cells in Injured Brain and Spinal Cord
Authors: SYKOVÁ EVA , JENDELOVÁ PAVLA
Published: June 2005

Abstract: Stem cells are a promising tool for treating brain and spinal cord injury. Magnetic resonance imaging (MRI) provides a noninvasive method to study the fate of transplanted cells in vivo. We studied implanted rat bone marrow stromal cells (MSCs) and mouse embryonic stem cells (ESCs) labeled with iron‐oxide nanoparticles (Endorem®) and human CD34+ cells labeled with magnetic MicroBeads (Miltenyi) in rats with a cortical or spinal cord lesion. Cells were grafted intracerebrally, contralaterally to a cortical photochemical lesion, or injected intravenously. During the first week post transplantation, transplanted cells migrated to the lesion. About 3% of MSCs and ESCs differentiated into neurons, while no MSCs, but 75% of ESCs differentiated into astrocytes. Labeled MSCs, ESCs, and CD34+ cells were visible in the lesion on MR images as a hypointensive signal, persisting for more than 50 days. In rats with a balloon‐induced spinal cord compression lesion, intravenously injected MSCs migrated to the lesion, leading to a hypointensive MRI signal. In plantar and Basso‐Beattie‐Bresnehan (BBB) tests, grafted animals scored better than lesioned animals injected with saline solution. Histologic studies confirmed a decrease in lesion size. We also used 3‐D polymer constructs seeded with MSCs to bridge a spinal cord lesion. Our studies demonstrate that grafted adult as well as embryonic stem cells labeled with iron‐oxide nanoparticles migrate into a lesion site in brain as well as in spinal cord.
Restoration of Mitochondrial Function in Cells with Complex I Deficiency
Authors: BAI YIDONG , PARK JEONG SOON , DENG JIAN‐HONG , LI YOUFEN , HU PEIQING
Published: June 2005

Abstract: The mammalian mitochondrial NADH dehydrogenase (complex I) is the major entry point for the electron transport chain. It is the largest and most complicated respiratory complex consisting of at least 46 subunits, 7 of which are encoded by mitochondrial DNA (mtDNA). Deficiency in complex I function has been associated with various human diseases including neurodegenerative diseases and the aging process. To explore ways to restore mitochondrial function in complex I‐deficient cells, various cell models with mutations in genes encoding subunits for complex I have been established. In this paper, we discuss various approaches to recover mitochondrial activity, the complex I activity in particular, in cultured cells.
Potential Mechanism of Blood Vessel Protection by Resveratrol, a Component of Red Wine
Authors: HUANG HUEI‐MEI , LIANG YU‐CHIH , CHENG TZU‐HURNG , CHEN CHENG‐HEIEN , JUAN SHU‐HUI
Published: June 2005

Abstract: Resveratrol‐mediated heme oxgenase‐1 (HO‐1) induction has been shown to occur in primary neuronal cultures and has been implicated as having potential neuroprotective action. Further, antioxidant properties of resveratrol have been reported to protect against coronary heart disease. We attempted to examine the HO‐1 inducing potency of resveratrol and the regulatory mechanism of its induction in rat aortic smooth muscle cells (RASMC). We showed that resveratrol‐induced HO‐1 expression was concentration‐ and time‐dependent. The level of HO‐1 expression and its promoter activity mediated by resveratrol was attenuated by nuclear factor‐kappa B (NF‐κB) inhibitors, but not by mitogen‐activated protein kinase (MAPK) inhibitors. Deletion of NF‐κB binding sites in the promoter region strongly reduced luciferase activity. Collectively, we suggest that resveratrol‐mediated HO‐1 expression occurs, at least in part, through the NF‐κB pathway.
Randomized Phase II/III Trial of Interferon Alfa-2a With and Without 13-cis-Retinoic Acid in Patients With Progressive Metastatic Renal Cell Carcinoma: The European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group (EORTC 30951)
Authors: Aass Nina , De Mulder Pieter H.M. , Mickisch Gerald H.J. , Mulders Peter , van Oosterom Allan T. , van Poppel Hein , Fossa Sophie D. , de Prijck Linda , Sylvester Richard J.
Published: June 2005

Purpose

A randomized phase II/III trial was conducted to determine whether combination treatment with 13-cis-retinoic acid (13-CRA) plus interferon alfa-2a (IFN-α-2a) was superior to IFN-α-2a alone in patients with progressive metastatic renal cell carcinoma.

Patients and Methods

Three hundred twenty patients were randomly assigned to treatment with IFN-α-2a plus 13-CRA or to IFN-α-2a alone. IFN-α-2a was given daily subcutaneously, starting at a dose of 3 million units (MU). The dose was escalated every 7 days from 3 to 9 MU by increments of 3 MU. Patients randomly assigned to combination therapy received oral 13-CRA 1 mg/kg/d plus IFN-α-2a.

Results

Median time to progression was 5.1 months for patients treated with the combination and 3.4 months for patients on IFN-α-2a alone (P = .008). Progression-free survival rates at 6 months were 43% for patients receiving combined therapy and 30% for patients on IFN-α-2a, and at 12 months, 27% and 17%, respectively. Median overall survival was 17.3 months for patients on IFN-α-2a and 13-CRA, and 13.2 months for patients treated with IFN-α-2a (P = .048). Twenty-two percent of the patients receiving the combination stopped treatment due to toxicity, as compared with 16% on IFN-α-2a.

Conclusion

Progression-free and overall survival for patients with progressive metastatic renal cell carcinoma treated with IFN-α-2a plus 13-CRA were significantly longer compared with patients on IFN-α-2a alone (P = .007 and P = .048, respectively). Improvement in efficacy in the combination arm was accompanied by increased, though not serious, toxicity.
Use of Magnetic Resonance Imaging to Assess Blood-Brain/Blood-Glioma Barrier Opening During Conformal Radiotherapy
Authors: Cao Yue , Tsien Christina I. , Shen Zhou , Tatro Daniel S. , Ten Haken Randall , Kessler Marc L. , Chenevert Thomas L. , Lawrence Theodore S.
Published: June 2005

Purpose

For chemotherapy to act synergistically and safely with radiation against high-grade gliomas, drugs must pass the endothelial junctions of the blood-tumor barrier (BTB) to reach all tumor cells, and should not pass the blood-brain barrier (BBB) to cause toxicity to normal brain. The objective of this study was to assess BBB/BTB status using magnetic resonance imaging (MRI) during a course of radiotherapy of high-grade gliomas.

Patients and Methods

Sixteen patients with grade 3 or 4 supratentorial malignant glioma receiving conformal radiotherapy (RT) underwent contrast-enhanced MRI before, during, and after completion of RT. A gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) uptake index was analyzed with respect to the tumor and RT dose received.

Results

In the nonenhanced tumor region, contrast uptake increased significantly after the receipt of approximately 10 Gy (P < .01), and reached a maximum after the receipt of approximately 30 Gy. In the initially contrast-enhanced tumor region, contrast uptake decreased over the course of RT and became significant after completion of RT in patients without progressive disease. The healthy brain showed only nonsignificant changes during and after irradiation.

Conclusion

Contrast MRI reveals increases in Gd-DTPA uptake in the initially nonenhanced tumor region but not in the remaining brain during the course of RT, suggesting opening of the BTB. This finding suggests that the effect of conformal radiation is more selective on the BTB than the BBB, and there may be a window extending from 1 week after the initiation of radiotherapy to 1 month after the completion of treatment during which a pharmaceutical agent has maximum access to high-grade gliomas.
Orexin Expression and Function: Glucocorticoid Manipulation, Stress, and Feeding Studies
Authors: Ford Gemma K. , Al-Barazanji Kamal A. , Wilson Shelagh , Jones Declan N. C. , Harbuz Michael S. , Jessop David S.
Published: June 2005

We investigated the effects of glucocorticoid manipulation on orexin-A-induced feeding and prepro-orexin mRNA levels in the lateral hypothalamic area (LHA) of the rat brain. Adrenalectomy (ADX) reduced orexin-A-induced feeding over 4 h by about 60%, compared with shams, an effect that was reversed by corticosterone (CORT) replacement. ADX had no effect on prepro-orexin mRNA levels in the LHA in either the morning or the evening; however, message was up-regulated by CORT in the morning but not the evening. An increased number of emulsion grains per cell in the LHA suggests that this is a specific increase in prepro-orexin mRNA and is not due to an increased number of cells expressing message. Prepro-orexin mRNA levels in the LHA were elevated 4 h after injection of lipopolysaccharide, compared with saline-injected controls. Partial but not complete abolition of orexin-A-induced feeding by ADX suggests that orexin-A-induced feeding may be mediated through glucocorticoid-dependent and glucocorticoid-independent pathways. In the morning increased prepro-orexin mRNA after CORT replacement demonstrates that orexin expression is sensitive to increased concentrations of glucocorticoids. However, the lack of effect of ADX on prepro-orexin mRNA levels suggests that endogenous glucocorticoids are not involved in tonic regulation of basal prepro-orexin expression. Overall our data constitute a body of evidence for an integrated relationship between central orexin expression, stress, glucocorticoid manipulation, and feeding patterns in the rat.
An investigation of a novel cooling system for chilled food display cabinets
Authors: Maidment G. G. , Missenden J. F. , Karayiannis T. G. , Wang F
Published: June 2005

The modern retail cabinets that are used for chilling and displaying food in shops are described in this paper. The deficiencies of the purely convective heat transfer mechanism used to cool food in modern cabinets are highlighted. A novel heat transfer system that provides an integrated conductive/convective cooling mechanism is then proposed. A purpose-developed finite difference model and its application in the study of the novel cooling system are presented in this paper. The model was used to evaluate the performance of the mechanism compared with the conventional convective system. The results indicate that the proposed novel system can provide improved heat transfer, which contributes to lower core food temperatures of approximately 2.5−3.5 K. This can lead to significant reductions in energy and capital costs as well as improvements in food quality and shelf-life. Furthermore, the use of this cooling system could avoid the requirement for electric defrost, which is energy-intensive.
New Reference Intervals for Thyrotropin and Thyroid Hormones Based on National Academy of Clinical Biochemistry Criteria and Regular Ultrasonography of the Thyroid
Authors: Kratzsch Juergen , Fiedler Georg Martin , Leichtle Alexander , Brügel Matthias , Buchbinder Susanne , Otto Lothar , Sabri Osama , Matthes Gert , Thiery Joachim
Published: June 2005

Background: The aim of our present study was to establish new reference intervals for thyrotropin (TSH) and thyroid hormones based on National Academy of Clinical Biochemistry (NACB) criteria and regular thyroid ultrasonography. We also assessed the effect of potentially confounding factors to modulate the limits of these intervals.

Methods: We investigated 870 apparently healthy persons and excluded, step by step, those with a family history of thyroid disease, pathologic thyroid ultrasonography results, and increased anti-thyroid peroxidase or anti-thyroglobulin antibodies. Accordingly, only 453 of the 870 persons in the entire group were finally included as reference collective. We measured serum concentrations of TSH, total and free thyroxine (T4 and FT4), and total and free triiodothyronine (T3 and FT3) of the whole and the reference collective on the ELECSYS system assays (Roche Diagnostics) and calculated the 2.5th and 97.5th percentiles for comparison.

Results: The calculated lower limit for TSH differed significantly between the reference intervals for healthy persons with an assessed normal thyroid gland vs the nonselected group of healthy blood donors. Age was the only independent factor and was significantly inversely associated with TSH (P <0.0001). Use of oral contracep-tives was a significant predictor for variation in T4 concentrations (P <0.001). Age and oral contraceptives were independently associated with T3 variations (P <0.05). For FT4 vs FT3 variation, gender and (inversely) age (P <0.01) were independent modulating factors.

Conclusions: The selection of healthy persons according to NACB criteria combined with sonographic confirmation of a normal thyroid gland provide a valid basis for the reference interval for TSH. Factors indicating a preclinical disease state, such as family history, pathologic ultrasonography result, or increased anti-thyroid peroxidase and anti-thyroglobulin antibodies, can be associated with normal hormone concentrations. Additionally, patient age and gender as well as use of contraceptives should be considered in diagnostic evaluation of thyroid diseases.
Concept of chemical immaturity in body composition estimates: Implications for estimating the prevalence of obesity in childhood and youth
Authors: Lohman T. G. , Gonig S. B. , Slaughter M. H. , Boileau R. A.
Published: June 2005

This paper estimates the prevalence of obesity in 6–8‐year‐old children, 13–15‐year‐old youth, and 18–19‐old adults by using skinfold data of the National Nutrition and Health Examination Survey. Obesity is defined as above 25% fat in males and above 32% fat in females. Skinfold equations used to estimate the fat cotent at each age were based on a multicompontent approach that used body density, body water, and bone mineral. The prevalence of obesity in the U.S. population was found to be much lower in children than in youth and young adults and to increase from 1 in 20 in childhood to 1 in 5 in adulthood.
Amyotrophic lateral sclerosis and parkinsonism‐dementia of Gaum: Clinical, epidemiological, and genetic patterns
Authors: Garruto Ralph M.
Published: June 2005

The strikingly high incidence of amyotrophic lateral sclerosis (ALS) and parkinsonism‐dementia (PD), two uniformly fatal neurodegenerative disorders which often occur in the same families and occasionally in the same individual, was recognized on Guam more than three decades ago. Since the first systematic observations began, nearly 800 Guamanian Chamorro patients have been clinically diagnosed as having either disease. The original incidence rates for ALS and PD accounted for one in five deaths among Chamorros over ago 25. During the past 30 years, however, the incidence and mortality rates have dramatically declined and today the risk to Guamanian chamorros is only several‐fold higher than that for non‐Chamorro residents of the continental United States. The accumulating epidemiological and genetic data strongly suggest that environmental factors are primarily involved in the etiology and pathogenesis of these disorders. The high incidence focus of ALS and PD on Guam and similar, but less well‐studied, foci in West New Guinea and the Kii Peninsula of Japan represent natural paradigms of chronic degenerative disease that have provided new information and insights for understanding not only ALS and PD, but other neurological disorders such as classical ALS, Parkinson disease, Alzheimer disease, and early neuronal aging, insights that might otherwise not have been forthcoming from studies of low incidence sporadic disease in large cosmopolitan Western communities.
Do reproductive patterns affect maternal nutritional status?: An analysis of maternal depletion in Lesotho
Authors: Miller Jane E. , Huss‐Ashmore Rebecca
Published: June 2005

Poor pregnancy outcomes in developing countries have often been blamed on maternal depletion or on the cumulative nutritional drain of many closely spaced pregnancies. Despite its widespread acceptance, the maternal depletion hypothesis remains unproven. This study examines nutritional status and fertility history for 873 women in highland Lesotho. Parity, age, pregnancy status, length of last closed birth interval, open interval, and median birth interval were used to predict nutritional status (BMI, triceps skinfold, arm muscle area). While there is evidence that both short‐term and long‐term nutritional depletion are related to lactation and pregnancy spacing, both BMI and triceps fat increase with parity. For this population, then, the assumption of cumulative depletion due simply to high fertility is not supported.
X‐linked pattern of inheritance for serial measures of weight/stature2
Authors: Byard Pamela J. , Siervogel Roger M. , Roche Alex F.
Published: June 2005

The pattern of family resemblance for long‐term serial measures of weight/stature2 (W/S2) in approximately 500 individuals from the Fels Longitudinal Growth Study suggests that X‐linked genes may be contributing to the variability in this trait among children, particularly during the prepubertal age range of 2–9 years. In this data set, W/S2 was measured serially at the same ages in all family members. Thus, a parent‐child correlation at a specific age can be determined even though the measurements were made on the child a generation later than on the parent. The pattern of family resemblance at each annual age up to 10 years and at ages 14–18 years is consistent with the presence of an X‐linked genetic effect. Opposite‐sex parent‐child pairs are more similar than same‐sex pairs, and sister‐sister pairs are more similar than brother‐brother or brother‐sister pairs at these ages. Furthermore, when the distribution of W/S2 is examined separately in boys and girls, there is evidence of commingling in the distribution of boys from 5 to 8 years of age but not in girls. This is consistent with the existence of a major X‐linked gene with a frequency of about 3%. This pattern of family resemblance and commingling suggestive of partial X‐linkage for W/S2 has not been detected previously because cross‐sectional family studies generally compare individuals at different stages of growth.
Semai Senoi fertility and population dynamics: Two‐census method
Authors: Fix Alan G.
Published: June 2005

The fertility and parameters of population growth of the Semai Senoi of Malaysia are studied by using a two‐census method based on nonstable population theory. Semai fertility is shown to be moderately high; female completed fertility is 7.42 children and the crude birth rate is greater than 0.050. Previous estimates of Semai mortality rates are also moderately high but are insufficient to balance birth; thus, the overall rate of growth is presently nearly 2%. Compared with an earlier description of the pre‐1969 Semai population, fertility has increased markedly leading to a nearly threefold increase in the annual growth rate.
Semai Senoi mortality: Two‐census method
Authors: Fix Alan G.
Published: June 2005

The mortality pattern of a subpopulation of Semai Senoi of Malaysia is studied by using a two‐census method. The method yields abridged life tables for both sexes as well as an estimate of the birth rate. The life tables show that Semai mortality is reduced compared to estimates based on stable population methods for the population prior to 1969. Increased health care availability seems to account for this lower mortality.
Sibling correlations for skeletal age assessments by the Fels method
Authors: Xi Huanjiu , Roche Alex F. , Guo Shumei
Published: June 2005

Sibling correlations are reported for Fels skeletal ages from 2,622 mixed longitudinal hand‐wrist radiographs of 285 boys and 276 girls. Because the observed correlations were irregular across age, they were smoothed by using kernel regression. The brother‐sister correlations were generally lower than those for the other types of silbling pairs, but they were similar to the brother‐brother correlations after 11 years. The sister‐sister correlations were considerably higher than the brother‐brother and brother‐sister correlations after 12 years. The present data do not provide clear evidence of involvement of the X chromosome in the timing of skeletal maturation, but after 12 years the present data suggest such an involvement.
Relationship of disease characteristics and nutritional status to patterns of growth in children with Crohn disease
Authors: Cronk Christine E. , Stallings Virginia A.
Published: June 2005

Crohn disease is one type of inflammatory bowel disease with frequent occurrence before maturity. Many children with Crohn disease experience linear growth retardation. However, the prevalence and contribution of various factors to growth failure have not been adequately investigated. The purpose of the present study was to estimate the prevalence of growth deficiency by using multiple criteria based on longitudinal data and to simulatneously evaluate the contribution of disease, demographic, and treatment characteristics to the growth failure in this group of children.

A sample of 78 patients assessed retrospectively and 41 patients followed prospectively were drawn from the Children's Hospital of Philadelphia Division of Gastroenterology and Nutrition. Data on growth, nutritional status (hematocrit and albumin levels), disease characteristics (severity, site, duration, and age of onset), and steroid dosage were collected for both groups. For the prospective sample, measurements of height, weight, and four skinfold thicknesses were taken. A 24 hour recall and 3 day food record estimated kcal intake. Parental size was taken by report from the accompanying caregiver.

When three criteria were used, prevalence of growth retardation was 67% in the retrospective group, higher than most available figures. In the prospective sample, reductions in height adjusted for midparental size were greater than those for weight, and depletion of lower body fat was greater than that of upper body fat.

Multiple regression analyses showed that degree of growth retardation as measured by the parent adjusted z score for height was associated with higher steroid dosage and later age of disease onset, but not disease severity or the anatomical site of the disease. Of the nutritional status variables, degree of growth retardation was most closely associated with degree of reduction in lower body fat stores.
Technical error of mesiodistal diameters for the permanent and deciduous dentition
Authors: Buschang Peter H. , Demirjian Arto
Published: June 2005

Method errors and reliabilities are given for mesiodistal measurements of the permanent and deciduous dentitions. Method errors, describing random measurement error, range between 0.04 and 0.12 mm. Reliabilities, describing the proportion of true variance to true plus error variance, are lowest for measurements taken on the canines. Mesiodistal measurements of the incisors are more reliable than those taken on the (pre)molars. The different reliability estimates reflect disparities in true rather than error variance. The method error and reliability statistics serve different purposes and lead to different interpretations.
Selective neutrality of surname, distribution in an immigrant indian community of Houston, Texas
Authors: Chakraborty Ranajit , Schwartz Robert J.
Published: June 2005

From survey data on surnames in an immigrant community of Indians in Houston, Texas, it is shown that the family size distribution and the distribution of the number of male children per family are independent of the surnames of the parents. This provides a direct test of selective neutrality of surname distributions. A genetic theory of sampling distribution of neutral alleles is employed to estimate the parameter of the surname distribution, and analytical results for the expectation and variance of the frequencies of surnames with a different number of copies in a sample are provided. It is also shown that the surname distribution may indicate presence of mixture in a sample, which can be examined by such theoretical approaches. The transition of surname distributions in two successive generations is shown to follow the pattern predicted by random extinction of surnames.
Stresses of conquest: A study of Wilson bands and enamel hypoplasias in the Maya of Lamanai, Belize
Authors: Wright Lori E.
Published: June 2005

This paper examines the prevalence of Wilson bands and hypoplasias in the dental enamel of a sample of Postclassic and Historic Maya Indian remains from the archaeological site of Lamanai, Belize. Mandibular canines were removed from 23 individuals from the two periods. The surface of a polished, acid etched, longitudinal section of each canine was examined with scanning electron microscopy for the presence of enamel malformations.

A large number of Wilson bands and shallow hypoplasias were identified; however, more severe macroscopic hypoplasias were rare. The two kinds of defects were found to be temporally associated in only 25–50% of instances, indicating that circumstances leading to their formation are likely distinct.

The mean number of both Wilson bands and shallow hypoplasias was found to be significantly different between samples, indicating an increase in developmental stress in the Historic occupation. As dietary differences have not been detected between the occupations, the observed differences in enamel defect prevalence can be attributed to the effects of changing epidemiological patterns following the Spanish conquest.
Commingling analysis of blood pressure in the Tecumseh community health study
Authors: Province M. A. , Keller J. , Higgins M. , Rao D. C.
Published: June 2005

A commingling analysis of the distribution of systolic and diastolic blood pressure was performed on measurements from 9,226 individuals living in Tecumseh, Michigan during 1962–1965. Even after correcting for skewness in the distributions, multiple normal distributions fit the data significantly better than a single normal one, suggesting some level of commingling. The exact nature of the components differed depending on the phenotype, and the number of components entertained, suggesting a possibly complex etiology, but with some definite qualitative effects. Segregation analysis under the mixed model is needed to address the nature of blood pressure in this community more definitively.