bluuebunny/crossref_metadata_2025 huggingface dataset:
Relation Between Progression and Regression of Atherosclerotic Left Main Coronary Artery Disease and Serum Cholesterol Levels as Assessed With Serial Long-Term (≥12 Months) Follow-Up Intravascular Ultrasound
Authors: von Birgelen Clemens , Hartmann Marc , Mintz Gary S. , Baumgart Dietrich , Schmermund Axel , Erbel Raimund
Published: November 2003

Background—

The relation between serum lipids and risk of coronary events has been established, but there are no data demonstrating directly the relation between serum low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol versus serial changes in coronary plaque dimensions.

Methods and Results—

We performed standard analyses of serial intravascular ultrasound (IVUS) studies of 60 left main coronary arteries obtained 18.3±9.4 months apart to evaluate progression and regression of mild atherosclerotic plaques in relation to serum cholesterol levels. Overall, there was (1) a positive linear relation between LDL cholesterol and the annual changes in plaque plus media (P&M) cross-sectional area (CSA) (
r
=0.41,
P
<0.0001) with (2) an LDL value of 75 mg/dL as the cutoff when regression analysis predicted on average no annual P&M CSA increase; (3) an inverse relation between HDL cholesterol and annual changes in P&M CSA (
r
=−0.30,
P
<0.02); (4) an inverse relation between LDL cholesterol and annual changes in lumen CSA (
r
=−0.32,
P
<0.01); and (5) no relation between LDL and HDL cholesterol and the annual changes in total arterial CSA (remodeling). Despite similar baseline IVUS characteristics, patients with an LDL cholesterol level ≥120 mg/dL showed more annual P&M CSA progression and lumen reduction than patients with lower LDL cholesterol.

Conclusions—

There is a positive linear relation between LDL cholesterol and annual changes in plaque size, with an LDL value of 75 mg/dL predicting, on average, no plaque progression. HDL cholesterol shows an inverse relation with annual changes in plaque size.
Angiotensin-Converting Enzyme Is Involved in Outside-In Signaling in Endothelial Cells
Authors: Kohlstedt Karin , Brandes Ralf P. , Müller-Esterl Werner , Busse Rudi , Fleming Ingrid
Published: November 2003

Not all of the cardiovascular effects of angiotensin-converting enzyme (ACE) inhibitors can be attributed to changes in angiotensin II and bradykinin levels. Because the cytoplasmic tail of ACE is phosphorylated, we determined whether ACE inhibitors affect the phosphorylation of ACE and whether ACE possesses the characteristics of a signal transduction molecule. The ACE inhibitors ramiprilat and perindoprilat, and the substrate bradykinin (but not angiotensin I), enhanced the activity of ACE-associated CK2 and the phosphorylation of ACE Ser
1270
in cultured endothelial cells. Mitogen-activated protein kinase kinase 7 and c-Jun N-terminal kinase (JNK) coprecipitated with ACE, and stimulation of endothelial cells with ACE inhibitors increased the activity of ACE-associated JNK and elicited the accumulation of phosphorylated c-Jun in the nucleus. Ramiprilat was however unable to activate JNK or to stimulate the nuclear accumulation of c-Jun in endothelial cells expressing a S1270A ACE mutant or in ACE-deficient cells. Because the ACE inhibitor–induced increase in ACE expression has been linked to the formation of c-Jun homodimers, we investigated whether ACE signaling via JNK contributes to this response in vitro and in vivo. Prolonged ramiprilat treatment increased ACE expression in primary cultures of human endothelial cells and in vivo (mouse lung), a response that was prevented by pretreatment with the JNK inhibitor SP600125. Thus, ACE is involved in outside-in signaling in endothelial cells and “ACE signaling” may be an important cellular mechanism contributing to the beneficial effects of ACE inhibitors.
Cholesterol and the Risk of Ischemic Stroke
Authors: Bowman Thomas S. , Sesso Howard D. , Ma Jing , Kurth Tobias , Kase Carlos S. , Stampfer Meir J. , Gaziano J. Michael
Published: November 2003

Background and Purpose—

Large epidemiological studies have not established cholesterol levels as a risk factor for ischemic stroke, but recent clinical trials have demonstrated a reduction in the ischemic stroke rate for patients taking HMG-CoA reductase inhibitors (“statins”). The goal of this study was to evaluate whether total cholesterol (TC), high-density lipoprotein (HDL), triglycerides, and the TC:HDL ratio are risk factors for ischemic stroke in apparently healthy men enrolled in the Physicians’ Health Study.

Methods—

We used a nested case-control study design and matched 296 ischemic stroke cases with an equal number of controls on age, tobacco use, and follow-up time. At baseline, TC, HDL, and triglyceride levels were measured. We calculated odds ratios (ORs) and their 95% confidence intervals (CIs) using conditional logistic regression, adjusting for major risk factors for ischemic stroke.

Results—

Compared with the reference lowest quartile, the highest quartile for TC had an adjusted OR of 1.56 (95% CI, 0.84 to 2.92), the highest quartile of HDL had an adjusted OR of 0.75 (95% CI, 0.43 to 1.30), and the highest quartile of triglycerides had an adjusted OR of 1.07 (95% CI, 0.63 to 1.82). Although the highest quartile of the TC:HDL ratio had an adjusted OR of 1.62 (95% CI, 0.93 to 2.82), the risk of ischemic stroke was not a linear relationship.

Conclusions—

After adjustment, TC, HDL, and triglycerides were not significantly associated with ischemic stroke risk, and for the TC:HDL ratio, a suggestion of increased risk of ischemic stroke was limited to those with the highest levels.
Disruption of Gene for Inducible Nitric Oxide Synthase Reduces Progression of Cerebral Aneurysms
Authors: Sadamasa Nobutake , Nozaki Kazuhiko , Hashimoto Nobuo
Published: November 2003

Background and Purpose—

The rupture of a cerebral aneurysm is a major cause of subarachnoid hemorrhage, but the mechanism of its development remains unclear. Inducible nitric oxide synthase (iNOS) is expressed in human and rat cerebral aneurysms, and aminoguanidine, a relatively selective inhibitor of iNOS, can decrease the number of the aneurysms in rats. In this study we applied our new mouse model of cerebral aneurysms to the iNOS gene knockout mice and observed experimental cerebral aneurysms in these animals to elucidate the role of iNOS in the process of cerebral aneurysm formation.

Methods—

Eight C57/Bl6 mice and 16 iNOS knockout mice received a cerebral aneurysm induction procedure. Four months after the operation, the mice were killed, their cerebral arteries were dissected, and the region of the bifurcation of the anterior cerebral artery/olfactory artery was examined histologically and immunohistochemically.

Results—

No significant difference was seen in the incidence of cerebral aneurysms between iNOS+/+ and iNOS−/− mice. However, the size of advanced cerebral aneurysms and the number of apoptotic smooth muscle cells were significantly greater in iNOS+/+ mice than in iNOS−/− mice.

Conclusions—

Inducible NOS is not necessary for the initiation of cerebral aneurysm. However, the results of this study suggest that regulation of iNOS may have therapeutic potential in the prevention of the progression of cerebral aneurysms.
Functional Outcome of Ischemic and Hemorrhagic Stroke Patients After Inpatient Rehabilitation
Authors: Paolucci Stefano , Antonucci Gabriella , Grasso Maria Grazia , Bragoni Maura , Coiro Paola , De Angelis Domenico , Fusco Francesca Romana , Morelli Daniela , Venturiero Vincenzo , Troisi Elio , Pratesi Luca
Published: November 2003

Background and Purpose—

The goal of this study was to assess the specific influence of stroke etiology on rehabilitation results.

Methods—

This was a case-control study of 270 inpatients with sequelae of first stroke who were enrolled in homogeneous subgroups and matched for stroke severity, basal disability, age (within 1 year), sex, and onset admission interval (within 3 days) who were different only in terms of stroke origin, infarction versus hemorrhage. We compared the groups’ length of stay, efficiency and effectiveness of treatment, and percentage of low and high responder patients. Odds ratios of dropouts and of low and high therapeutic response were also quantified.

Results—

Compared with ischemic patients, hemorrhagic patients had significantly higher Canadian Neurological Scale and Rivermead Mobility Index scores at discharge; higher effectiveness and efficiency on the Canadian Neurological Scale, Barthel Index, and Rivermead Mobility Index; and a higher percentage of high responders on the Barthel Index. Hemorrhagic patients showed a probability of a high therapeutic response on the Barthel Index that was ≈2.5 times greater than that of ischemic patients (odds ratio, 2.48; 95% confidence interval, 1.19 to 5.20; accuracy on prediction, 87.06%).

Conclusions—

The results of this study provide further evidence of better functional prognosis in stroke survivors with hemorrhagic stroke.
High incidence of somatic mutations in the AML1/RUNX1 gene in myelodysplastic syndrome and low blast percentage myeloid leukemia with myelodysplasia
Authors: Harada Hironori , Harada Yuka , Niimi Hiromasa , Kyo Taiichi , Kimura Akiro , Inaba Toshiya
Published: November 2003

A high incidence of somatically acquired point mutations in the AML1/RUNX1 gene has been reported in poorly differentiated acute myeloid leukemia (AML, M0) and in radiation-associated and therapy-related myelodysplastic syndrome (MDS) or AML. The vast majority of AML1 mutations identified in these diseases were localized in the amino (N)–terminal region, especially in the DNA-binding Runt homology domain. In this report, we show that AML1 point mutations were found in 26 (23.6%) of 110 patients with refractory anemia with excess blasts (RAEB), RAEB in transformation (RAEBt), and AML following MDS (defined these 3 disease categories as MDS/AML). Among them, 9 (8.2%) mutations occurred in the carboxy (C)–terminal region, which were exclusively found in MDS/AML and were strongly correlated with sporadic MDS/AML. All patients with MDS/AML with an AML1 mutation expressed wild-type AML1 protein and had a significantly worse prognosis than those without AML1 mutations. Most AML1 mutants lost trans-activation potential, regardless of their DNA binding potential. These data suggested that AML1 point mutation is one of the major driving forces of MDS/AML, and these mutations may represent a distinct clinicopathologic-genetic entity.
Long chain polyunsaturated fatty acids are required for efficient neurotransmission in C. elegans
Authors: Lesa Giovanni M. , Palfreyman Mark , Hall David H. , Clandinin M. Thomas , Rudolph Claudia , Jorgensen Erik M. , Schiavo Giampietro
Published: November 2003

The complex lipid constituents of the eukaryotic plasma membrane are precisely controlled in a cell-type-specific manner, suggesting an important, but as yet, unknown cellular function. Neuronal membranes are enriched in long-chain polyunsaturated fatty acids (LC-PUFAs) and alterations in LC-PUFA metabolism cause debilitating neuronal pathologies. However, the physiological role of LC-PUFAs in neurons is unknown. We have characterized the neuronal phenotype of C. elegans mutants depleted of LC-PUFAs.

The C. elegans genome encodes a single Δ6-desaturase gene (fat-3), an essential enzyme for LC-PUFA biosynthesis. Animals lacking fat-3 function do not synthesize LC-PUFAs and show movement and egg-laying abnormalities associated with neuronal impairment. Expression of functional fat-3 in neurons, or application of exogenous LC-PUFAs to adult animals rescues these defects. Pharmacological, ultrastructural and electrophysiological analyses demonstrate that fat-3 mutant animals are depleted of synaptic vesicles and release abnormally low levels of neurotransmitter at cholinergic and serotonergic neuromuscular junctions. These data indicate that LC-PUFAs are essential for efficient neurotransmission in C. elegans and may account for the clinical conditions associated with mis-regulation of LC-PUFAs in humans.
Reciprocal walking orthosis with composite material body brace: Initial development
Authors: Stallard J , McLeod N , Woollam P J , Miller K
Published: November 2003

Reciprocal walking orthoses are routinely used by thoracic lesion patients for ambulation using crutches. A primary reason for their prescription is to provide therapeutic benefit and improved independence. To achieve this, maximum efficiency of walking and acceptance of the device is necessary to promote long-term compliance. Lateral rigidity in the orthosis influences walking efficiency, but the structural properties of conventional techniques for producing a sufficiently rigid body brace makes them unattractive. Currently patients and clinicians are forced to choose between greater efficiency or cosmesis of the orthosis.

Composite materials have the potential to permit the required rigidity in a structure that is less obtrusive. However, their material properties could lead to unsafe forms of failure unless suitable manufacturing methods are devised. It is therefore inappropriate to supply prototypes to patients for field evaluation until laboratory investigation of innovative production methods has ensured that the orthosis is safe. A production technique has been devised that is ostensibly suitable. Prototype body braces have been tested and have been shown to have improved structural properties and safe failure modes. A test programme implemented on a complete concept orthosis has confirmed that improved lateral rigidity can be achieved with a less obtrusive body brace, and that it will behave safely for long enough to permit field evaluation.
Signaling Strategies in Competitive Interaction: Building Reputations and Hiding the Truth
Authors: Prabhu Jaideep , Stewart David W.
Published: November 2003

The authors develop a conceptual framework of how managers interpret competitors' signals over time in various market contexts. From the framework, the authors generate hypotheses about the relative effectiveness of signaling strategies used by firms in different market contexts. The authors conducted two empirical studies involving a repeated entry-pricing game to test the hypotheses. The results of Study 1 show that the entrant's perceptions of the aggressiveness of the incumbent depend on the focus and strength of the incumbent's signals. The results of Study 2 show that the strength of the entrant's responses to the incumbent's signals depends on the incumbent's use of bluffs and the cost of information about the factors driving the incumbent's signals. The implications of these findings for how firms should signal to achieve such strategic objectives as revealing or concealing information, developing a desired reputation, and influencing competitors' responses over time are discussed. The authors conclude by discussing the limitations of the article and its implications for further research.
Treatment of postrenal transplantation lymphoproliferative disease manifesting as plasmacytoma with nonmyeloablative hematopoietic stem cell transplantation from the same kidney donor
Authors: Au W.Y. , Lie A.K.W. , Chan E.C. , Pang A. , Ma S.K. , Choy C. , Kwong Y.L.
Published: November 2003

Posttransplantation lymphoproliferative disease (PTLD) presenting as an Epstein‐Barr‐virus (EBV)–related nasal plasmacytoma developed in a renal‐allograft recipient 13 years after transplantation. Systemic dissemination occurred despite immunosuppression withdrawal, surgery, irradiation, and chemotherapy. A nonmyeloablative hematopoietic‐stem‐cell‐transplantation (HSCT) with peripheral blood HSC from the kidney donor was performed. With the onset of graft‐versus‐host disease, resolution of the systemic disease was demonstrated clinically and molecularly by serial quantification of plasma EBV‐DNA. Isolated relapse occurred in the central nervous system (CNS), a known tumour sanctuary site, ultimately leading to death. Nonmyeloablative HSCT might be considered a cellular therapy for PTLD, but possible CNS relapse must be effectively tackled. Am. J. Hematol. 74:283–286, 2003. © 2003 Wiley‐Liss, Inc.
Imatinib mesylate in idiopathic and postpolycythemic myelofibrosis
Authors: Hasselbalch Hans Carl , Bjerrum Ole Weiss , Jensen Bjarne Anker , Clausen Nielsaage Tøffner , Hansen Per Boye , Birgens Henrik , Therkildsen Marianne Hamilton , Ralfkiær Elisabeth
Published: November 2003

Imatinib mesylate targets the adenosine triphosphate (ATP)‐binding sites of the protein tyrosine kinase domains associated with Bcr‐abl, the platelet‐derived growth factor (PDGF) and c‐kit. In idiopathic myelofibrosis (IMF) PDGF is considered to be one of the growth factors responsible for the development of bone marrow fibrosis. Recently, it has been shown that imatinib has antifibrogenic effect on bone marrow fibrosis in chronic myelogenous leukemia. Treatment with imatinib alone in IMF has been associated with significant side effects. In this study, the safety and efficacy of imatinib therapy in IMF, either administered as a single agent or in combination with hydroxyurea (HU) and/or alpha‐interferon (IFN‐α) are evaluated. Eleven patients (median age, 63 years; range, 33–82 years) with IMF (n = 8) or postpolycythemic myelofibrosis (PPMF) (n = 3) were studied All patients had been treated with HU (n = 9) and/or IFN (n = 7) before study entry. In all but one patient, treatment with these agents was discontinued when imatinib therapy was instituted. One patient continued IFN when treatment with imatinib was started. Imatinib was given at a dose of 400 mg/day. Nine patients were in an advanced disease phase. The patients have been followed for a median period of 2 months (range, 0.5–12 months). Treatment with imatinib has been stopped in six patients (55%), because of overt side effects (n = 4), recurrence of transitory dizziness and visual defects owing to a rising platelet count (n = 1), or the occurrence of an acute subdural hemorrhage that was evacuated without neurological deficits (n = 1). In nine patients imatinib treatment was followed by a rise in leukocyte and platelet counts that required combination with HU or IFN. The combined treatment modalities were followed by a rapid decrease in cell counts and were well tolerated apart from IFN side effects. A beneficial effect of imatinib was documented in three patients. It is concluded that leukocytosis and thrombocytosis are seen in most patients with myelofibrosis during treatment with imatinib. Combination therapy with HU or IFN seems safe and well tolerated and followed by a decrease in disease activity. A subgroup of patients in an early disease phase might benefit from imatinib therapy alone. Am. J. Hematol. 74:238–242, 2003. © 2003 Wiley‐Liss, Inc.
Occupational exposures to extremely low frequency magnetic fields and postmenopausal breast cancer
Authors: Labrèche France , Goldberg Mark S. , Valois Marie‐France , Nadon Louise , Richardson Lesley , Lakhani Ramzan , Latreille Benoit
Published: November 2003

Background

The association between occupational exposure to extremely low frequency magnetic fields (ELF‐MF) and risk of postmenopausal breast cancer was assessed in a case‐control study.

Methods

Breast cancer cases were compared to cancer controls. Interviewers elicited information on risk factors and on lifetime work history. Industrial hygienists assigned to each job average duration of exposure to ELF‐MF at four levels of intensities (“none,” <0.2 μT; “low,” 0.2–<0.5μT; “medium,” 0.5–<1μT; “high,” ≥1–10μT). Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI).

Results

A total number of 608 cases and 667 controls participated. Adjusting for accepted breast cancer risk factors, we found an OR of 1.13 for lifetime occupational exposure to ELF‐MF at medium or high intensities. Risks were larger for exposures before age 35 (OR = 1.40), and statistically significant for exposures before 35 among cases with progesterone receptor positive tumors (OR = 1.56, 95% CI=1.02–2.39).

Conclusions

There appears to be a small increased risk for breast cancer among postmenopausal women exposed occupationally to ELF‐MF. Am. J. Ind. Med. 44:643–652, 2003. © 2003 Wiley‐Liss, Inc.
Occupational cancer among women: Where have we been and where are we going?
Authors: Zahm Shelia Hoar , Blair Aaron
Published: November 2003

Studies of occupational exposures have been a fruitful area of research for identifying carcinogens. Some of the early observations, such as increased risk of breast cancer among nuns and bone cancer among radium dial workers, were made among women. Recent research on cancer among women has shown increased risks of cancer in many industries and occupations. Estimates that 1% of cancer among women is attributable to occupation are based on research conducted mainly in the 1970s among men in developed countries. These studies do not reflect the dramatic changes in the participation of women in the workplace or the patterns of employment of women in developing countries. The proportion of women in the paid workforce, the amounts and types of unpaid labor, the distribution of women by economy sector, the scale of the workplaces, the allowable exposure levels in the workplace, and implementation of controls have changed over time and vary internationally. Occupational cancer researchers need to expand their focus on women, increase activities in developing countries, include newly created industries, use sophisticated exposure assessment methods, and, where appropriate, incorporate molecular epidemiologic techniques to discover new occupational carcinogens and to identify where better control measures are needed. Am. J. Ind. Med. 44:565–575, 2003. Published 2003 Wiley‐Liss, Inc.
Mortality and cancer morbidity experience of female workers at the British Nuclear Fuels Sellafield plant, 1946–1998
Authors: McGeoghegan D. , Gillies M. , Riddell A.E. , Binks K.
Published: November 2003

Background

Studies of nuclear workers have focused mainly on the experience of male workers. To date, little has been published specifically on the experience of female workers in the nuclear industry.

Methods

We report on the mortality, cancer morbidity, and tracing experience of the 6,376 females ever employed at the British Nuclear Fuels Ltd. plant at Sellafield to the end of 1998. These workers have accumulated 142,337 person‐years of experience.

Results

Radiation workers were exposed to low doses of radiation. No statistically significant associations were noted between mortality or cancer morbidity and cumulative assessed organ‐specific internal plutonium dose or cumulative external whole body radiation dose overall, or for any of the individual disease groupings examined. The power of the study was insufficient to detect the risks indicated in other radiation studies.

Conclusion

This study offers reassurance that there is no detrimental effect on the health of the female workers from occupational exposures at Sellafield. Am. J. Ind. Med. 44:653–663, 2003. © 2003 Wiley‐Liss, Inc.
Falls in workers during pregnancy: Risk factors, job hazards, and high risk occupations
Authors: Dunning Kari , LeMasters Grace , Levin Linda , Bhattacharya Amit , Alterman Toni , Lordo Kathy
Published: November 2003

Background

Although falls are a major source of trauma during pregnancy and 70% of pregnant women are employed, information on falls among pregnant workers is lacking. Study objectives were to estimate fall prevalence and risk factors among pregnant workers.

Methods

This retrospective cohort study used birth certificates to identify recently pregnant women. Data were collected via phone, internet, and mail surveys. The primary outcome investigated was a fall at work during pregnancy. Adjusted odds ratios (aOR) and confidence intervals (CI) were calculated.

Results

Of the 2,847 employed women, 26.6% (757) fell during their pregnancy and 6.3% (179) fell at work. Walking on slippery floors, hurrying, or carrying an object occurred in 66.3% of work falls.

Conclusion

The service and teaching industry should be evaluated for risk reduction. Future research should determine if counseling during pregnancy will reduce falls in the workplace. Am. J. Ind. Med. 44:664–672, 2003. © 2003 Wiley‐Liss, Inc.
MAP kinase activation in cells exposed to a 60 Hz electromagnetic field
Authors: Nie K. , Henderson A.
Published: November 2003

This research provides evidence that mitogen‐activated protein kinase or extracellular signal‐regulated kinase (MAPK/ERK) is activated in HL‐60 human leukemia cells, MCF‐7 human breast cancer cells, and rat fibroblast 3Y1 cells exposed to a 60 Hertz (Hz), 1 Gauss (G) electromagnetic field (EMF). The effects of EMF exposure were compared to those observed using 12‐O‐tetradecanoylphorbal‐13‐acetate (TPA) treatment. The level of MAPK activation in cells exposed to EMF was approximately equivalent to that in cells treated with 0.1–0.5 ng/ml of TPA. A role for protein kinase C (PKC) in the process leading to MAPK activation in EMF exposed cells is also suggested by the results. MAPK activation is negated by an inhibitor to PKCα, but not PKCδ inhibitors, in cells subjected to EMF exposure or TPA treatment. Thus, similarities between the effects of EMF exposure and TPA treatment are supported by this investigation. This provides a possible method for revealing other participants in EMF–cell interaction, since the TPA induction pathway is well documented. © 2003 Wiley‐Liss, Inc.
Antisteroidogenic actions of hydrogen peroxide on rat leydig cells
Authors: Tsai Shiow‐Chwen , Lu Chien‐Chen , Lin Chiu‐Shuang , Wang Paulus S.
Published: November 2003

It has been well known that reactive oxygen species (ROS) are produced in the steroidogenic pathway and spermatozoa. H2O2, one of ROS produced by spermatozoa, appears to be a primary toxic agent. In the present study, we examined the effects of H2O2 on the basal and evoked‐testosterone release from primary Leydig cells, the protein expressions of cytochrome P450 side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein were also investigated. Our preparation was found to contain approximately 87% Leydig cells and very few macrophages. The results demonstrated that H2O2 (>1 × 10−4 M) significantly inhibited the basal and hCG‐stimulated testosterone release. H2O2 abolished forskolin‐ or 8‐Br‐cAMP‐evoked testosterone release. In the presence of pregnenolone, progesterone, or androstenedione, the inhibitory effect of H2O2 on testosterone release was prevented. H2O2 also inhibited pregnenolone production in the presence of trilostane (an inhibitor of 3β‐hydroxysteroid dehydrogenase), therefore diminished the activity of P450scc in Leydig cells. In addition to the inhibition of hormone secretion, H2O2 also regulated steroidogenesis by diminishing protein expression of StAR. These results suggest that H2O2 acts directly on rat Leydig cells to diminish testosterone production by inhibiting P450scc activity and StAR protein expression. © 2003 Wiley‐Liss, Inc.
Age‐dependent changes in thymic macrophages and dendritic cells
Authors: Varas Alberto , Sacedón Rosa , Hernandez‐López Carmen , Jiménez Eva , García‐Ceca Javier , Arias‐Díaz Javier , Zapata Agustín G. , Vicente Angeles
Published: November 2003

Aging is characterized by the decline and deregulation of several physiological systems, especially the immune system. The involution of the thymus gland has been identified as one of the key events that precedes the age‐related decline in immune function. Whereas the decrease in thymocyte numbers and in the thymic output during thymus atrophy has been analyzed by various authors, very little information is available about the age‐associated modifications in thymic macrophages and dendritic cells. Here we present evidence that these thymic stromal cell components are only slightly affected by age. Microsc. Res. Tech. 62:501–507, 2003. © 2003 Wiley‐Liss, Inc.
Apoptosis in primary lymphoid organs with aging
Authors: Sainz Rosa M. , Mayo Juan C. , Reiter R.J. , Tan D.X. , Rodriguez C.
Published: November 2003

Age‐associated changes in the immune system are responsible for an increased likelihood of infection, autoimmune diseases, and cancer in the elderly. Immunosenescence is characterized by reduced levels of the peripheral naive T cell pool derived from thymus and the loss of immature B lineage cells in the bone marrow. Primary lymphoid organs, i.e., bone marrow and thymus, exhibit a loss of cellularity with age, which is especially dramatic in the thymus. A summary of major changes associated with aging in primary lymphoid organs is described in this article. The participation of apoptosis in cell loss in the immune system, a change associated with age, as well as a description of molecular machinery involved, is presented. Finally, the involvement of different hormonal and non‐hormonal agents in counteracting apoptosis in thymus and bone marrow during aging is explained. Here, we underlie the important role of glucocorticoids as immunodepressors and melatonin as an immunostimulatory agent. Microsc. Res. Tech. 62:524–539, 2003. © 2003 Wiley‐Liss, Inc.
Herpes simplex type 1 shedding is associated with reduced hospital survival in patients receiving assisted ventilation in a tertiary referral intensive care unit
Authors: Ong G.M. , Lowry K. , Mahajan S. , Wyatt D.E. , Simpson C. , O'Neill H.J. , McCaughey C. , Coyle P.V.
Published: November 2003

The impact of shedding of herpes simplex virus type 1 (HSV‐1) on hospital survival of patients receiving assisted ventilation in an adult tertiary referral, acute trauma intensive care unit was assessed. The study was designed to address a clinical impression linking HSV‐1 recovery with poor survival. Two hundred and forty‐one males and 152 females were enrolled into a longitudinal cohort study. Combined throat swabs and tracheal secretions were tested for HSV‐1 shedding using a nested nucleic acid amplification protocol; patients were ranked as nonshedders, shedders, and high‐level shedders. Nonparametric analysis assessed the impact of shedding on hospital survival and logistic regression measured the confounding influence of sex, age, and the Acute Physiology, Age and Chronic Health Evaluation (APACHE II) score. Linear‐by‐linear association determined the influence of the level of shedding on hospital survival. The observed mortality rate was 113/393 (28.8%). Patients shedding HSV‐1 106/393 (27%) had a significant reduction in hospital survival 66/106 (62%) in HSV‐1 shedders compared with 217/287 (75.6%) in nonshedders (P = 0.002). This difference remained significant when adjusted for age and sex (P = 0.026). Respective mortality figures for HSV‐1 shedders and nonshedders were 43/106 (40.6%) and 70/287 (24.4%) (P = 0.002). HSV‐1 shedding was associated with a significant reduction in hospital survival amongst patients receiving assisted ventilation. Hospital mortality in HSV‐1 shedders was increased by 16.2% over nonshedders. The role of HSV‐1 in this setting needs to be addressed. J. Med. Virol. 72:121–125, 2004. © 2004 Wiley‐Liss, Inc.
Comparison of human herpesvirus 8 and Epstein–Barr virus seropositivity among children in areas endemic and non‐endemic for Kaposi's sarcoma
Authors: Martro E. , Bulterys M. , Stewart J.A. , Spira T.J. , Cannon M.J. , Thacher T.D. , Bruns R. , Pellett P.E. , Dollard S.C.
Published: November 2003

Human herpesvirus 8 (HHV‐8) is the etiologic agent of Kaposi's sarcoma (KS). Several studies indicate horizontal HHV‐8 transmission among children in areas where KS is endemic, but few studies have assessed acquisition of HHV‐8 by children in low seroprevalence areas. Antibody screening was carried out for HHV‐8 and Epstein–Barr virus (EBV) on 787 serum specimens from children living in two areas where HHV‐8 is not endemic, the United States (US) and Germany, and on 184 specimens from children living in a KS‐endemic area (Nigeria). For children in the US and Germany, the results showed low HHV‐8 seroprevalence rates (3–4%). However, US children aged 6 months to 5 years had higher HHV‐8 antibody titers than did 6–17‐year‐old children (P < 0.01), a finding consistent with more recent infections being detected in the younger children. Compared with seroprevalence rates and antibody titers in US and German children, those in Nigerian children were significantly higher, and seroprevalence increased with age. There was no evidence of cross‐reactivity between assays for HHV‐8 and EBV, despite the genetic similarity of these two herpesviruses. The data indicate that HHV‐8 transmission among children where HHV‐8 is not endemic occurs, but is uncommon. The findings also suggest that HHV‐8 antibodies, as measured by current tests, may not persist for long periods in populations at low risk for KS and that vertical transmission is rare, although longitudinal studies are necessary to address directly these issues. J. Med. Virol. 72:126–131, 2004. © 2004 Wiley‐Liss, Inc.
Role of actin filaments in targeting of Crimean Congo hemorrhagic fever virus nucleocapsid protein to perinuclear regions of mammalian cells
Authors: Andersson Ida , Simon Melinda , Lundkvist Åke , Nilsson Mikael , Holmström Anna , Elgh Fredrik , Mirazimi Ali
Published: November 2003

Crimean‐Congo hemorrhagic fever virus is the causative agent of a severe disease throughout Africa, Europe, and Asia. Like other members of the genus Nairovirus, the Crimean‐Congo hemorrhagic fever virus contains three genomic RNA segments, the small (S), medium (M), and large (L) segments. The S segment encodes the viral nucleocapsid protein (NP), while the M and L segments encode the glycoproteins and the RNA‐dependent RNA polymerase, respectively. In this study, the site of expression and assembly of Crimean‐Congo hemorrhagic fever virus NP in mammalian cells have been investigated. It was found that the NP is localized in the perinuclear region of infected cells. By using the Semliki forest virus expression system, it was shown that the Crimean‐Congo hemorrhagic fever virus NP is targeted to the perinuclear region of cells in the absence of native RNA segments and virally encoded glycoproteins. It was also demonstrated that the Crimean‐Congo hemorrhagic fever virus NP was not expressed as a Golgi‐membrane associated protein. By using Cytochalasin D, an agent that disrupts actin filaments, it was found that actin filaments are involved in targeting the viral NP to perinuclear regions. We also demonstrated that disruption of actin filaments reduced the assembly of infectious Crimean‐Congo hemorrhagic fever virus up to 97%. Furthermore, we showed that the NP of Crimean‐Congo hemorrhagic fever virus NP interacts with actin. J. Med. Virol. 72:83–93, 2004. © 2004 Wiley‐Liss, Inc.
Nucleotide variation in the VP7 gene affects PCR genotyping of G9 rotaviruses identified in Italy
Authors: Martella Vito , Terio Valentina , Arista Serenella , Elia Gabriella , Corrente Marialaura , Madio Anna , Pratelli Annamaria , Tempesta Maria , Cirani Antonio , Buonavoglia Canio
Published: November 2003

A modified (aFT9m) and a degenerate (aFT9d) version of the rotavirus G9‐specific primer (aFT9) allowed strains that were previously untypable, because of point mutations accumulating at the primer binding site, to be G typed by reverse transcription‐polymerase chain reaction. The strains were collected during 2001–2002 in Italy in hospitals of the Apulia region, from children affected by severe rotavirus‐associated enteritis. Using a wide selection of G9 rotaviruses detected worldwide, sequencing of the G9 untypable strains, sequence comparison, and phylogenetic analysis showed that the Italian strains have strong genetic similarity (≤99.4%) to G9 rotaviruses identified recently in many parts of the world and different from the old G9 strains identified during the 1980s (less than 90%). Genetic variation of G9 rotaviruses explains the constraints encountered in the typing assays and presumably accounts, together with genetic reassortment events, for the emergence on a global scale of the G9 serotype. J. Med. Virol. 72:143–148, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of the NCEP–NCAR reanalysis in terms of synoptic‐scale phenomena: a case study from the Midwestern USA
Authors: Schoof J. T. , Pryor S. C.
Published: November 2003

We evaluate the ability of the National Centers for Environmental Prediction (NCEP)–National Center for Atmosphere Research (NCAR) reanalysis to represent the synoptic‐scale climate of the Midwestern USA relative to radiosonde data. Independent, automated synoptic classifications, based on rotated principal component analysis (PCA) of 500 hPa geopotential heights, 850 hPa air temperatures, and 200 hPa wind speeds and a two‐step clustering algorithm, result in a 15‐type NCEP–NCAR synoptic classification and a 14‐type radiosonde classification. The classifications are examined in terms of similarities and differences in the modes of variance manifest in the PCA solutions, the spatial patterns and variability of input variables within each weather type, and the temporal variability of the occurrence of each weather type. The classifications are then compared in terms of these characteristics and the degree of mutual class occupancy. Although the classifications identify a number of the same weather types (in terms of the input data, PCA solution, and mutual occupancy), the correspondence is imperfect. To assess whether the differences in the classifications are due to errant assignment of data to clusters or to differences in the fundamental modes present in the data sets as represented by the PC loadings and scores, a third targeted classification is undertaken that categorizes the NCEP–NCAR reanalysis data according to the radiosonde PCA solution. This classification exhibits a higher degree of similarity to that derived using the radiosonde data (in terms of both interpretability and mutual class occupancy), but the solutions still exhibit considerable differences. It is probable that the discrepancies are partly a function of the differing data structures and densities, but they may also reflect differences in the intensity of synoptic‐scale phenomena as manifest in the data sets. Copyright © 2003 Royal Meteorological Society
Comparison of three infrared satellite techniques to estimate accumulated rainfall over the Iberian Peninsula
Authors: Tarruella R. , Jorge J.
Published: November 2003

The potential of three infrared satellite‐based techniques to estimate accumulated rainfall is tested, and the techniques are compared and contrasted. The tests are conducted in the western Mediterranean area and for the first time in the Iberian Peninsula. The well‐known Arkin and the Negri–Adler–Wesley techniques are applied, as well as the Autoestimator technique during the autumn of 1994. Because the aim of this work is to automate the process of extracting the data inferred in a large number of satellite images for as long as possible (only 4368 images have been analysed in this paper), no assisted preselection is recommended. The correlation coefficients obtained for the three methods in comparisons at specific points are near 0.6; and even better results were obtained for wide areas. The Iberian Peninsula is divided into three zones, which present different climatic characteristics. Tests conducted in the north and northwest yielded the worst results, probably due to the predominance of stratiform rain and the associated orographic effects. Tests conducted in Mediterranean coastal areas gave the best results, probably due to the convective nature of precipitation predominant in this zone. Various modifications are introduced in the methods, in order to adapt them to the target area. Copyright © 2003 Royal Meteorological Society
Conserved structural elements in glutathione transferase homologues encoded in the genome of Escherichia coli
Authors: Rife Chris L. , Parsons James F. , Xiao Gaoyi , Gilliland Gary L. , Armstrong Richard N.
Published: November 2003

Multiple sequence alignments of the eight glutathione (GSH) transferase homologues encoded in the genome of Escherichia coli were used to define a consensus sequence for the proteins. The consensus sequence was analyzed in the context of the three‐dimensional structure of the gst gene product (EGST) obtained from two different crystal forms of the enzyme. The enzyme consists of two domains. The N‐terminal region (domain I) has a thioredoxin‐like α/β‐fold, while the C‐terminal domain (domain II) is all α‐helical. The majority of the consensus residues (12/17) reside in the N‐terminal domain. Fifteen of the 17 residues are involved in hydrophobic core interactions, turns, or electrostatic interactions between the two domains. The results suggest that all of the homologues retain a well‐defined group of structural elements both in and between the N‐terminal α/β domain and the C‐terminal domain. The conservation of two key residues for the recognition motif for the γ‐glutamyl‐portion of GSH indicates that the homologues may interact with GSH or GSH analogues such as glutathionylspermidine or α‐amino acids. The genome context of two of the homologues forms the basis for a hypothesis that the b2989 and yibF gene products are involved in glutathionylspermidine and selenium biochemistry, respectively. Proteins 2003;53:777–782. © 2003 Wiley‐Liss, Inc.
The C‐terminal module of Chi1 from Aeromonas caviae CB101 has a function in substrate binding and hydrolysis
Authors: Wang F.P. , Li Q. , Zhou Y. , Li M.G. , Xiao X.
Published: November 2003

The chitinase gene chi1 of Aeromonas caviae CB101 encodes an 865‐amino‐acid protein (with signal peptide) composed of four domains named from the N‐terminal as an all‐β‐sheet domain ChiN, a triosephosphate isomerase (TIM) catalytic domain, a function‐unknown A region, and a putative chitin‐binding domain (ChBD) composed of two repeated sequences. The N‐terminal 563‐amino‐acid segment of Chi1 (Chi1ΔAΔChBD) shares 74% identity with ChiA of Serratia marcescens. By the homology modeling method, the three‐dimensional (3D) structure of Chi1ΔAΔChBD was constructed. It fit the structure of ChiA very well. To understand fully the function of the C‐terminal module of Chi1 (from 564 to 865 amino acids), two different C‐terminal truncates, Chi1ΔChBD and Chi1ΔAΔChBD, were constructed, based on polymerase chain reaction (PCR). Comparison studies of the substrate binding, hydrolysis capacity, and specificity among Chi1 and its two truncates showed that the C‐terminal putative ChBD contributed to the insoluble substrate–protein binding and hydrolysis; the A region did not have any function in the insoluble substrate–protein binding, but it did have a role in the chitin hydrolysis: Deletion of the A region caused the enzyme to lose 30–40% of its activity toward amorphous colloidal chitin and soluble chitin, and around 50% toward p‐nitrophenyl (pNP)‐chitobiose pNP‐chitotriose, and its activity toward low‐molecular‐weight chitooligomers (GlcNAc)3–6 also dropped, as shown by analysis of its digestion processes. This is the first clear demonstration that a domain or segment without a function in insoluble substrate–chitinase binding has a role in the digestion of a broad range of chitin substrates, including low‐molecular‐weight chitin oligomers. The reaction mode of Chi1 is also described and discussed. Proteins 2003. © 2003 Wiley‐Liss, Inc.
Biosynthetic uniform 13C,15N‐labelling of zervamicin IIB. Complete 13C and 15N NMR assignment
Authors: Ovchinnikova Tatyana V. , Shenkarev Zakhar O. , Yakimenko Zoya A. , Svishcheva Natalia V. , Tagaev Andrey A. , Skladnev Dmitry A. , Arseniev Alexander S.
Published: November 2003

Zervamicin IIB is a member of the α‐aminoisobutyric acid containing peptaibol antibiotics. A new procedure for the biosynthetic preparation of the uniformly 13C‐ and 15N‐enriched peptaibol is described. This compound was isolated from the biomass of the fungus‐producer Emericellopsis salmosynnemata strain 336 IMI 58330 obtained upon cultivation in the totally 13C,15N‐labelled complete medium. To prepare such a medium the autolysed biomass and the exopolysaccharides of the obligate methylotrophic bacterium Methylobacillus flagellatus KT were used. This microorganism was grown in totally 13C,15N‐labelled minimal medium containing 13C‐methanol and 15N‐ammonium chloride as the only carbon and nitrogen sources. Preliminary NMR spectroscopic analysis indicated a high extent of isotope incorporation (>90%) and led to the complete 13C‐ and 15N‐NMR assignment including the stereospecific assignment of Aib residues methyl groups. The observed pattern of the structurally important secondary chemical shifts of 1Hα, 13CO and 13Cα agrees well with the previously determined structure of zervamicin IIB in methanol solution. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
The peptaibol antiamoebin as a model ion channel: similarities to bacterial potassium channels
Authors: O'Reilly Andrias O. , Wallace B. A.
Published: November 2003

Antiamoebin (AAM) is a polypeptide antibiotic that is capable of forming ion channels in phospholipid membranes; planar bilayer studies have suggested the channels are octamers. The crystal structure of a monomeric form of AAM has provided the basis for molecular modelling of an octameric helical bundle channel. The channel model is funnel‐shaped due to a substantial bend in the middle of the polypeptide chain caused by the presence of several imino acids. Inter‐monomer hydrogen bonds orientate a ring of glutamine side chains to form a constriction in the pore lumen. The channel lumen is lined both by side chains of Gln11 and by polypeptide backbone carbonyl groups. Electrostatic calculations on the model are compatible with a channel that transports cations across membranes.

The AAM channel model is compared with the crystal structures of two bacterial (KcsA and MthK) potassium channels. AAM and the potassium channels exhibit common functional features, such as cation‐selectivity and similar single channel conductances. Common structural features include being multimers, each formed from a bundle of eight transmembrane helices, with lengths roughly comparable to the thickness of lipid bilayers. In addition, they all have aromatic amino acids that lie at the bilayer interfaces and which may aid in the stabilization of the transmembrane helices, as well as narrower constrictions that define the ion binding sites or selectivity filters in the pore lumen. The commonality of structural and functional features in these channels thus suggests that antiamoebin is a good, simple model for more complex bacterial and eukaryotic ion channels, capable of providing insight into details of the mechanisms of ion transport and multimeric channel stability. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Synthesis of the protected 6–16 segment of zervamicin II‐2, an application of the azirine/oxazolone method
Authors: Pradeille Nicolas , Heimgartner Heinz
Published: November 2003

The protected 11 amino acid segment (6–16) of the peptaibol zervamicin II‐2 was synthesized by using the ‘azirine/oxazolone method’ for the introduction of all Aib residues. Whereas a 2,2‐dimethyl‐2H‐azirin‐3‐amine was used as the building block for Aib(7), methyl 2,2‐dimethyl‐2H‐azirine‐3‐prolinate and ‐3‐(3‐hydroxyprolinate) proved to be ideally suited as dipeptide synthons for the introduction of Aib‐Pro and Aib‐Hyp, respectively. The coupling of Z‐protected amino acids or peptide acids with the 2H‐azirin‐3‐amines were performed in 75% to quantitative yield. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.