bluuebunny/crossref_metadata_2025 huggingface dataset:
Passive mechanics of muscle tendinous junction of canine diaphragm
Authors: Hwang Willy , Kelly Neil G. , Boriek Aladin M.
Published: March 2005

The diaphragmatic muscle tendon is a biaxially loaded junction in vivo. Stress-strain relations along and transverse to the fiber directions are important in understanding its mechanical properties. We hypothesized that 1) the central tendon possesses greater passive stiffness than adjacent muscle, 2) the diaphragm muscle is anisotropic, whereas the central tendon near the junction is essentially isotropic, and 3) a gradient in passive stiffness exists as one approaches the muscle-tendinous junction (MTJ). To investigate these hypotheses, we conducted uniaxial and biaxial mechanical loading on samples of the MTJ excised from the midcostal region of dog diaphragm. We measured passive length-tension relationships of the muscle, tendon, and MTJ in the direction along the muscle fibers as well as transverse to the fibers. The MTJ was slack in the unloaded state, resulting in a J-shaped passive tension-strain curve. Generally, muscle strain was greater than that of MTJ, which was greater than tendon strain. In the muscular region, stiffness in the direction transverse to the fibers is much greater than that along the fibers. The central tendon is essentially inextensible in the direction transverse to the fibers as well as along the fibers. Our data demonstrate the existence of more pronounced anisotropy in the muscle than in the tendon near the junction. Furthermore, a gradient in muscle stiffness exists as one approaches the MTJ, consistent with the hypothesis of continuous passive stiffness across the MTJ.
NAD(P)H fluorescence imaging of mitochondrial metabolism in contractingXenopusskeletal muscle fibers: effect of oxygen availability
Authors: Hogan Michael C. , Stary Creed M. , Balaban Robert S. , Combs Christian A.
Published: March 2005

The blue autofluorescence (351 nm excitation, 450 nm emission) of single skeletal muscle fibers from Xenopus was characterized to be originating from mitochondrial NAD(P)H on the basis of morphological and functional correlations. This fluorescence signal was used to estimate the oxygen availability to isolated single Xenopus muscle fibers during work level transitions by confocal microscopy. Fibers were stimulated to generate two contractile periods that were only different in the Po2of the solution perfusing the single fibers (Po2of 30 or 0–2 Torr; pH = 7.2). During contractions, mean cellular NAD(P)H increased significantly from rest in the low Po2condition with the core (inner 10%) increasing to a greater extent than the periphery (outer 10%). After the cessation of work, NAD(P)H decreased in a manner consistent with oxygen tensions sufficient to oxidize the surplus NAD(P)H. In contrast, NAD(P)H decreased significantly with work in 30 Torr Po2. However, the rate of NAD(P)H oxidation was slower and significantly increased with the cessation of work in the core of the fiber compared with the peripheral region, consistent with a remaining limitation in oxygen availability. These results suggest that the blue autofluorescence signal in Xenopus skeletal muscle fibers is from mitochondrial NAD(P)H and that the rate of NAD(P)H oxidation within the cell is influenced by extracellular Po2even at high extracellular Po2during the contraction cycle. These results also demonstrate that although oxygen availability influences the rate of NAD(P)H oxidation, it does not prevent NAD(P)H from being oxidized through the process of oxidative phosphorylation at the onset of contractions.
Role of Nitric Oxide and α-Adrenergic Receptor Responsiveness in Exercising Skeletal Muscle
Authors: Kamper Adriaan M. , de Craen Anton J. M.
Published: March 2005

The production of nitric oxide is the putative mechanism for the attenuation of sympathetic vasoconstriction (sympatholysis) in working muscles during exercise. We hypothesized that nitric oxide synthase blockade would eliminate the reduction in α-adrenergic-receptor responsiveness in exercising skeletal muscle. Ten mongrel dogs were instrumented chronically with flow probes on the external iliac arteries of both hindlimbs and a catheter in one femoral artery. The selective α1-adrenergic agonist (phenylephrine) or the selective α2-adrenergic agonist (clonidine) was infused as a bolus into the femoral artery catheter at rest and during mild and heavy exercise. Before nitric oxide synthase inhibition with NG-nitro-l-arginine methyl ester l-NAME), intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of −91 ± 3, −80 ± 5, and −75 ± 6% (means ± SE) at rest, 3 miles/h, and 6 miles/h and 10% grade, respectively. Intra-arterial clonidine reduced vascular conductance by −65 ± 6, −39 ± 4, and −30 ± 3%. After l-NAME, intra-arterial infusions of phenylephrine elicited reductions in vascular conductance of −85 ± 5, −85 ± 5, and −84 ± 5%, whereas clonidine reduced vascular conductance by −67 ± 5, −45 ± 3, and −35 ± 3%, at rest, 3 miles/h, and 6 miles/h and 10% grade. α1-Adrenergic-receptor responsiveness was attenuated during heavy exercise. In contrast, α2-adrenergic-receptor responsiveness was attenuated even at a mild exercise intensity. Whereas the inhibition of nitric oxide production eliminated the exercise-induced attenuation of α1-adrenergic-receptor responsiveness, the attenuation of α2-adrenergic-receptor responsiveness was unaffected. These results suggest that the mechanism of exercise sympatholysis is not entirely mediated by the production of nitric oxide.
Regression of capillary network in atrophied soleus muscle induced by hindlimb unweighting
Authors: Fujino Hidemi , Kohzuki Hisaharu , Takeda Isao , Kiyooka Takahiko , Miyasaka Takehiro , Mohri Satoshi , Shimizu Juichiro , Kajiya Fumihiko
Published: March 2005

Little is known about the mechanisms responsible for the adaptation and changes in the capillary network of hindlimb unweighting (HU)-induced atrophied skeletal muscle, especially the coupling between functional and structural alterations of intercapillary anastomoses and tortuosity of capillaries. We hypothesized that muscle atrophy by HU leads to the apoptotic regression of the capillaries and intercapillary anastomoses with their functional alteration in hemodynamics. To clarify the three-dimensional architecture of the capillary network, contrast medium-injected rat soleus muscles were visualized clearly using a confocal laser scanning microscope, and sections were stained by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling (TUNEL) and with anti-von Willebrand factor. In vivo, the red blood cell velocity of soleus muscle capillaries were determined with a pencil-lens intravital microscope brought into direct contact with the soleus surface. After HU, the total muscle mass, myofibril protein mass, and slow-type myosin heavy chain content were significantly lower. The number of capillaries paralleling muscle fiber and red blood cells velocity were higher in atrophied soleus. However, the mean capillary volume and capillary luminal diameter were significantly smaller after HU than in the age-matched control group. In addition, we found that the number of anastomoses and the tortuosity were significantly lower and TUNEL-positive endothelial cells were observed in atrophied soleus muscles, especially the anastomoses and/or tortuous capillaries. These results indicate that muscle atrophy by HU generates structural alterations in the capillary network, and apoptosis appears to occur in the endothelial cell of the muscle capillaries.
Electrophysiological Properties of Neurons in the Basal Ganglia of the Domestic Chick: Conservation and Divergence in the Evolution of the Avian Basal Ganglia
Authors: Farries Michael A. , Meitzen John , Perkel David J.
Published: March 2005

Although the basal ganglia of birds and mammals share an enormous number of anatomical, histochemical, and electrophysiological characteristics, studies in songbirds have revealed some important differences. Specifically, a specialized region of songbird striatum (the input structure of the basal ganglia) has an anatomical projection and a physiologically defined cell type that are characteristic of the globus pallidus. At present, it is not clear if these differences result from adaptations specific to songbirds and perhaps a few other avian taxa or are common to all birds. We shed some light on this issue by characterizing the morphology and electrophysiological properties of basal ganglia neurons in an avian species that is only distantly related to songbirds: the domestic chick. We recorded neurons in chick basal ganglia in a brain slice preparation, using the whole cell technique. We found that chick striatum, like songbird striatum, contains a pallidum-like cell type never reported in mammalian striatum, supporting the hypothesis that this feature is common to all birds. We also discovered that spiny neurons, the most common cell type in the striatum of all amniotes, possess a diverse set of physiological properties in chicks that distinguish them from both mammals and songbirds. This study revealed an unexpectedly complex pattern of conservation and divergence in the properties of neurons recorded in avian striatum.
Ion Channels in Mesangial Cells: Function, Malfunction, or Fiction
Authors: Ma Rong , Pluznick Jennifer L. , Sansom Steven C.
Published: March 2005

Ion channels in glomerular mesangial cells from humans, rats, and mice have been studied by electrophysiological, molecular, and gene-knockout methods. Two channels, a large, Ca2+-activated K+channel (BK) and a store-operated Ca2+channel (SOCC), can be defined with respect to molecular structure and function. Human BK, comprised of a pore-forming α-subunit and an accessory β1-subunit, operate as Ca2+-sensing feedback modulators of contractile tone. SOCC have also been characterized in a mouse cell line; they are comprised of molecules belonging to the transient receptor potential subfamily.
SGK1: A Rapid Aldosterone-Induced Regulator of Renal Sodium Reabsorption
Authors: McCormick James A. , Bhalla Vivek , Pao Alan C. , Pearce David
Published: March 2005

Recently, substantial progress has been made in understanding the mechanisms by which aldosterone rapidly stimulates sodium transport in the distal nephron and other tight epithelia. Serum- and glucocorticoid-regulated kinase 1 (SGK1) has been identified as an important mediator of this process. Its physiological relevance has been revealed through heterologous expression in cultured cells and generation of SGK1 knockout mice.
Fine mapping of a QTL region with large effects on growth and fatness on mouse chromosome 2
Authors: Jerez-Timaure Nancy C. , Eisen Eugene J. , Pomp Daniel
Published: March 2005

We combined the use of a congenic line and recombinant progeny testing (RPT) to characterize and fine map a previously identified region of distal mouse chromosome 2 (MMU2) harboring quantitative trait loci (QTL) with large effects on growth and fatness. The congenic line [M16i.B6-( D2Mit306- D2Mit52); MB2] was created using an inbred line (M16i) derived from a line that had undergone long-term selection for rapid weight gain (M16) as the recipient for an ∼38-cM region on MMU2 from the inbred line C57BL/6J. A large F2cohort (1,200 mice) originating from a cross between MB2 and M16i was created, and 40 F2males with defined recombinations within the QTL region were used to produce 665 segregating progeny. Linkage analysis of the F2population detected QTL with very large effects on body weight, body fat, lean tissue mass, bone mineral density, and liver weight. Confidence intervals of the QTL were narrowed to regions of 1.5–4.5 cM. Analysis of progeny of the recombinant F2males confirmed the existence of the QTL and further contributed to localization of their map positions. These efforts confirmed the presence of QTL with major effect on MMU2, narrowed the estimated region harboring the QTL from 38 to 12 cM, and further characterized phenotypic effects of the QTL, effectively culminating in a significantly decreased pool of positional candidate genes potentially representing these genes controlling predisposition to growth and fatness.
Gene expression profiling demonstrates that TGF-β1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-β signaling
Authors: Karlsson Göran , Liu Yingchun , Larsson Jonas , Goumans Marie-José , Lee Ju-Seog , Thorgeirsson Snorri S. , Ringnér Markus , Karlsson Stefan
Published: March 2005

Transforming growth factor-β1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (TβRII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of TβRII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5−/− cells show them to be completely unaffected by TGF-β. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5−/− or TGF-β-stimulated Alk5+/+ MEFs with unstimulated Alk5+/+ cells. Our results demonstrate that, in MEFs, TGF-β signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes.
Genetics and Global Health Care
Authors: Raeburn S.
Published: March 2005

Objectives: To examine an alternative model for funding genetic health care, on a global basis. Methods: Internet-based national data on gross domestic product (GDP) per capita, health care funding, and public and private elements of health care costs. Results: Wide variation in GDP per capita and in the proportion available for health care funding. Insufficient funds are available in developing countries. Conclusions: Health care provision for people with genetic disorders is unlikely to be fully funded unless a different approach to management costs is undertaken. Rare genetic disorders could be funded by an insurance model which may be more equitable and which could be developed to cover the total global health care costs of the genetic disorder.
Attitudes toward Genetic Counseling in the United Arab Emirates
Authors: Al-Gazali L.I.
Published: March 2005

Aims: To assess the level of understanding of genetic advice given in the Genetic Clinic and attitudes toward consanguineous marriages, and prenatal, abortion and preconception diagnoses. Methods: One hundred couples underwent structured interviews, and various social and educational data, reason for referral and diagnosis and advice given were recorded. Three months later, the couples were asked open-ended questions about the perceived causation of the disease, recurrence risk, plans for births, and prenatal, abortion and preconception diagnoses. Results: Half of the couples acknowledged a genetic basis for their child’s condition but only 10 remembered the risk given to them. There was a high correlation between educational level and remembering the risk, and the number of healthy children and future plans for further children. Almost half preferred consanguineous marriages and only 10% agreed with prenatal diagnosis and abortion, while 75% agreed with carrier screening and preconception diagnosis in affected families. Conclusion: Effective genetic counseling in this community requires an informed educated population and introduction of carrier screening and preconception diagnosis in affected families.
A Family Study in Oman: Large, Consanguineous, Polygamous Omani Arab Pedigrees
Authors: Hassan M.O. , Albarwani S. , Al Yahyaee S. , Al Haddabi S. , Rizwi S. , Jaffer A. , Al-Lawati J. , Cai G. , Comuzzie Anthony G. , Bayoumi R.A.
Published: March 2005

Objective: To establish a suitable human model for the study of the genetics of complex diseases. Methods: We have selected an Omani Arab population to provide the statistical power required to study the genetics of complex diseases with confidence. This model consists of five multigenerational highly inbred pedigrees, descending from a small number of founders just a few generations ago with environmental homogeneity, restricted geographical distribution, detailed records and well-ascertained and -validated pedigrees. Stringent criteria were adopted for defining the phenotypes of hypertension, diabetes mellitus, dyslipidemias and obesity. The SOLAR genetic software package was used to draw the pedigree structure. Results: Outstanding statistical power to detect susceptibility loci was obtained. Conclusions: This model represents a large homogeneous human family-based population for the study of genetic and environmental factors contributing to complex diseases.
Histological Evaluation of a Topically Applied Retinol-Vitamin C Combination
Authors: Seité S. , Bredoux C. , Compan D. , Zucchi H. , Lombard D. , Medaisko C. , Fourtanier A.
Published: March 2005

Two double-blind studies versus vehicle were carried out to investigate the effects of a topically applied retinol plus vitamin C combination on epidermal and dermal compartments of aged or photoaged human skin. The two studies were performed on postmenopausal women who were selected for treatment based on the mild level of elastosis of their facial skin. At completion of treatment, skin biopsies were collected and processed for classical histology and immunohistochemistry. In the first study (aged skin), 8 volunteers applied the retinol- and vitamin C-containing preparation on the ventral side of one elbow and the vehicle on the other elbow twice daily for 3 months. After the 3-month treatment we observed histological changes mainly within the epidermis. The stratum corneum was thinner with a compact pattern, whereas the epidermal proliferation increased, resulting in a thickening of the viable epidermis. Moreover, the interdigitation index was increased. In the second study (photoaged skin), 11 volunteers were divided in two groups; one applied the retinol- and vitamin C-containing preparation and the other one the vehicle on their face twice daily for 6 months. Facial skin samples presented histologic hallmarks of photoaging, i.e. accumulation of elastotic material in the papillary dermis. After the 6-month topical treatment, the observed histological changes were mainly concentrated at the dermal level. Both treated and control groups showed the same distribution pattern of type I procollagen, however, the high level of type III procollagen originally observed in photoaged skin was reduced in the retinol- and vitamin C-treated group, resulting in a lower type III-to-type I procollagen ratio. Furthermore, a wide band of eosinophilic material just beneath the epidermis, devoid of oxytalan fibers and forming the ‘grenz zone’, appeared more frequently and was larger in the retinol- and vitamin C-treated group. In conclusion, our results show that repeated topical application of a preparation containing both retinol and vitamin C is able to reverse, at least in part, skin changes induced by both chronologic aging and photoaging.
Pharmacology of Alzheimer’s Disease: Appraisal and Prospects
Authors: Sellal François , Nieoullon André , Michel Géraldine , Michel Bernard François , Lacomblez Lucette , Geerts Hugo , Delini Stula Alexandra , Bordet Régis , Bentué-Ferrer Danièle , Allain Hervé
Published: March 2005

Ten years after the introduction of the first drug, tacrine, in the treatment of Alzheimer’s disease, it seems appropriate to reappraise the pharmacological processes of innovation in the research field of dementia. The aim of this review is to pinpoint concrete improvements achieved in this field, regarding experimental methods and clinical evaluation of the compounds, as well as the neurochemistry of the disease and cellular targets to consider in priority. This review deals with this objective in three parts: (1) assessment of current therapeutics, (2) discussion of the experimental models and clinical practices and (3) prospective drugs of the future. The implementation of considered strategies will require the involvement and close cooperation between political decisions, pharmaceutical companies and the scientific community.
Selective Suppression of an Endothelin and Platelet-Derived Growth Factor Containing Vesicular System in Endothelium of Rat Saphenous Vein by Long-Term Orthostasis
Authors: Raffai Gábor , Fehér Erzsébet , Nádasy György , Paku Sándor , Pogány Gábor , Tímár Ferenc , Szende Béla , Monos Emil
Published: March 2005

Electron-dense vesicles were observed in rat vascular endothelium. The purpose of this study was to characterize their content(s), venous-arterial distribution and response to chronic orthostatic stress in extremity vessels. Saphenous and brachial vessels – saphenous vein (SV), saphenous artery (SA), brachial vein, brachial artery – were prepared for electron microscopy to quantitate the vesicle area within the endothelium following immunohistochemical and immunocytochemical identification. The effect of long-term orthostasis was assessed by exposure to head-up tilt for 2 weeks. The vesicular area in relation to the total cross-sectional area of the endothelial cells in the SV and SA of normal and confined control groups was 3.88 ± 0.38 versus 0.89 ± 0.06% (p < 0.05) and 4.92 ± 0.25 versus 1.09 ± 0.47% (p < 0.05), respectively. Head-up tilt suppressed the vesicle content of the SV to 2.26 ± 0.39% (p < 0.05), but it remained low in the SA (1.29 ± 0.45%), brachial vein (0.45 ± 0.12%) and brachial artery (0.59 ± 0.17%). Endothelin and platelet-derived growth factor, but not acidic phosphatase activity or lipid content, could be identified in the vesicles. Plasma endothelin levels were unchanged. We conclude that dense vesicles in the endothelium of extremity vessels are not cell degradation products. They may represent a vesicular secretory or storage system for endothelin and platelet-derived growth factor which participates in regional vascular adaptation to long-term orthostatic load.
Peripheral Blood Mononuclear Cells Acquire Myofibroblast Characteristics in Granulation Tissue
Authors: Jabs Alexander , Moncada Gustavo A. , Nichols Christopher E. , Waller Edmund K. , Wilcox Josiah N.
Published: March 2005

Background: Bone marrow-derived cell populations possess progenitor cell capacities. Emerging evidence also suggests significant plasticity of differentiated mononuclear cell lineages. We therefore assessed the distribution of transplanted peripheral blood mononuclear cells (PBMCs) in granulation tissue formation, and evaluated their possible transdifferentiation into myofibroblasts. Methods: Silastic tubes were inserted into the peritoneal cavity of rats, followed by injection of PKH26-labelled PBMCs isolated from donor animals. At 3, 14 and 21 days, the distribution of PKH26+ cells as well as their colocalization with myofibroblast/smooth muscle cell [α-smooth muscle (α-SM) actin] or macrophage markers (ED1/ED2) were determined. Results: Round-shaped PKH26+ cells accumulated around the implants at 3 days, while myofibroblasts were rare. Later, peritoneal granulation tissue constituted an inner, multilayered capsule primarily comprising α-SM actin+ cells that was surrounded by more loosely organized inflammatory connective tissue. PKH26-labelled, spindle-shaped cells were abundantly found in tissue capsules. As a key finding, granulation tissue at 14 and 21 days contained cells with both PKH26 and α-SM actin labelling. Accordingly, a subpopulation of cells staining positive for macrophage markers showed a spindle-shaped morphology and α-SM actin expression. Conclusions: Transplanted PBMCs contribute to granulation tissue, and acquire myofibroblast characteristics during de novo tissue formation. Mononuclear cells may transdifferentiate into myofibroblast-like cells within an inflammatory environment.
Adult Height in Patients Treated for Isolated Growth Hormone Deficiency: Role of Birth Weight
Authors: Di Cesare Merlone Alessandra , Bozzola Elena , Castelnovi Claudia , Chiabotto Patrizia , Costante Laura , De Sanctis Luisa , Tinelli Carmine , Bozzola Mauro
Published: March 2005

To evaluate the effect of growth hormone (GH) administration on adult height (AH) in two groups of isolated GH-deficient (IGHD) children born either small (birth weight below –2 SD) or appropriate (birth weight above –2 SD) for gestational age (GA). Out of 35 prepubertal IGHD children, 14 small for GA (SGA, group A) and 21 appropriate for GA (AGA, group B) were examined. All patients received continuous GH treatment at a median dose of 0.028 mg/kg/day (range 0.023–0.032) in group A and 0.024 (range 0.023–0.028) in group B. GH treatment was administered for a period of 67.0 months (range 42.37–96.05) in group A and 54.31 months (range 47.14–69.31) in group B. All children were measured using a Harpenden stadiometer every 6 months until they reached AH (growth velocity <1 cm/year). The patients underwent a retesting a few months after stopping GH therapy. A significant difference was found between group A and B as expected for birth weight SD, –2.70 (range –2.87 to –2.29) and –0.73 (range –1.30 to 0.14) respectively (p < 0.000001) and interestingly also for body mass index SDS (BMI SDS) at retesting, 0.08 (range 0.30 to –1.51) and 0.61 (range 0.73 to –1.10) respectively (p < 0.04). We observed no significant differences between groups A and B in height (expressed as the SDS for chronological age, height SDS) at diagnosis (p = 0.75), height SDS at start of puberty (p = 0.51), height SDS at retesting (p = 0.50), target height SDS (TH SDS) (p = 0.47), AH SDS (p = 0.92), corrected height SDS (height SDS – TH SDS) (p = 0.60), BMI SDS at diagnosis (p = 0.25), GH dosage (p = 0.34) and therapy duration (p = 0.52). GH treatment with a standard dose in short IGHD children leads to a normalization of AH without any significant difference between SGA and AGA patients.
Dextran or Polyethylene Glycol Added to Curosurf for Treatment of Meconium Lung Injury in Rats
Authors: Lu Karen W. , Robertson Bengt , Taeusch H. William
Published: March 2005

Background: In experimental lung injuries, improvement of lung function after treatment with surfactant/polymer mixtures may depend on both type of polymer and the specific surfactant. In vitro studies suggest that dextran is more effective when mixed with Curosurf, and polyethylene glycol (PEG) is more effective when mixed with Survanta. We therefore wanted to find out whether these results held true in an animal model of acute lung injury. Objective:To compare the response to therapy of PEG vs. dextran when added to Curosurf after meconium lung injury. Methods:Lung injury was produced by intratracheal instillation of meconium (30 and 4 ml/kg). One hour after injury, Curosurf (35 mg/ml) with or without 5% dextran (68 kDa) or 5% PEG (10 kDa) was given. Arterial blood gases and peak inspiratory pressures were measured for 3 h after treatment while animals were supported by volume-regulated ventilation. Then animals were sacrificed and pressure volume relationships, lung wet/dry weights, and histology were assessed. Results:Initially, improved PaO2 and inspiratory pressure occurred for both Curosurf/PEG and Curosurf/dextran groups compared with Curosurf, but at three hours, peak inspiratory pressure and PaO2 remained significantly improved for the Curosurf/dextran but not for Curosurf/PEG groups when compared with Curosurf alone. Total lung capacity at the end of the experiment was also significantly increased in the Curosurf/dextran group, but not the Curosurf/PEG group when compared with Curosurf. Conclusion:Under these experimental conditions, Curosurf/dextran mixtures provided a better therapeutic response than Curosurf/PEG or Curosurf.
The Role of Bisphosphonates in the Management of Advanced Cancer with a Focus on Non-Small-Cell Lung Cancer
Authors: Saba Nabil , Khuri Fadlo
Published: March 2005

Newer-generation intravenous bisphosphonates have resulted in the reduction of skeletal-related complications, i.e. skeletal-related events (SREs) such as pain, hypercalcemia, pathologic fractures and spinal cord and nerve compression, as well as improvements in the quality of life in patients with metastatic bone disease who are likely to have a prolonged clinical course. Highly potent, nitrogen-containing bisphosphonates such as zoledronic acid reduce SREs in patients with bone metastases from other solid tumors (including lung cancer). Part one of our review discussed the mechanisms of action by bisphosphonates as well as potential roles for bone markers and imaging in lung cancer. In this article, part two of our review, we examine the economic and clinical impact of bisphosphonates in lung cancer, with a focus on the potential role of newer-generation bisphosphonates in the management of advanced, metastatic bone disease of lung cancer.
The Melting Layer: A Laboratory Investigation of Ice Particle Melt and Evaporation near 0°C
Authors: Oraltay R. G. , Hallett J.
Published: March 2005

Melting, freezing, and evaporation of individual and aggregates of snow crystals are simulated in the laboratory under controlled temperature, relative humidity, and air velocity. Crystals of selected habit are grown on a vertical filament and subsequently melted or evaporated in reverse flow, with the velocity adjusted for appropriate fall speed to reproduce conditions of the melting layer. Nonequilibrium conditions are simulated for larger melting ice particles surrounded by smaller drops at a temperature up to +5°C or growth of an ice crystal surrounded by freezing ice particles down to −5°C. Initial melting of well-defined faceted crystals, as individuals or in combination, occurs as a water layer >10 μm thick. For larger (>100 μm) crystals the water becomes sequestered by capillary forces as individual drops separated by water-free ice regions, often having quasiperiodic locations along needles, columns, or arms from evaporating dendrites. Drops are also located at intersections of aggregate crystals and dendrite branches, being responsible for the maximum of the radar scatter. The drops have a finite water–ice contact angle of 37°–80°, depending on ambient conditions. Capillary forces move water from high-curvature to low-curvature regions as melting continues. Toward the end of the melting process, the ice separating the drops becomes sufficiently thin to fracture under aerodynamic forces, and mixed-phase particles are shed. Otherwise ice-free drops are shed. The melting region and the mechanism for lowering the melting layer with an increasing precipitation rate are associated with smaller ice particle production capable of being lofted in weaker updrafts.
Wavelet Analysis of Variability, Teleconnectivity, and Predictability of the September–November East African Rainfall
Authors: Mwale Davison , Gan Thian Yew
Published: March 2005

By applying wavelet analysis and wavelet principal component analysis (WPCA) to individual wavelet-scale power and scale-averaged wavelet power, homogeneous zones of rainfall variability and predictability were objectively identified for September–November (SON) rainfall in East Africa (EA). Teleconnections between the SON rainfall and the Indian Ocean and South Atlantic Ocean sea surface temperatures (SST) were also established for the period 1950–97. Excluding the Great Rift Valley, located along the western boundaries of Tanzania and Uganda, and Mount Kilimanjaro in northeastern Tanzania, EA was found to exhibit a single leading mode of spatial and temporal variability. WPCA revealed that EA suffered a consistent decrease in the SON rainfall from 1962 to 1997, resulting in 12 droughts between 1965 and 1997. Using SST predictors identified in the April–June season from the Indian and South Atlantic Oceans, the prediction skill achieved for the SON (one-season lead time) season by the nonlinear model known as artificial neural network calibrated by a genetic algorithm (ANN-GA) was high [Pearson correlation ρ ranged between 0.65 and 0.9, Hansen–Kuipers (HK) scores ranged between 0.2 and 0.8, and root-mean-square errors (rmse) ranged between 0.4 and 0.75 of the standardized precipitation], but that achieved by the linear canonical correlation analysis model was relatively modest (ρ between 0.25 and 0.55, HK score between −0.05 and 0.3, and rmse between 0.4 and 1.2 of the standardized precipitation).
Women and Migration in Contemporary China
Authors: Davin Delia
Published: March 2005

This paper shows that the huge numbers of rural migrants who have left the Chinese countryside in recent years to go to work in the newly industrialising coastal areas have included a substantial minority of women. It discusses the gender-specific aspects of migration and the occupations taken up by female migrants. It also considers issues such as female autonomy, fertility and prostitution in relation to migration. It contends that since the state restricts permanent settlement in the urban areas, rural to urban migration in China is characterised by a high level of circulation. The result is that successive waves of migrants return to the rural areas to marry and have families bringing with them new ideas about gender relations and family roles. Migration, especially female migration, thus presents a challenge to the traditional patriarchal family in the countryside and offers rural women the chance to negotiate more power and choice in their lives.
Unani medicine in the nineteenth-century public sphere
Authors: Alavi Seema
Published: March 2005

Unani medicine’s encounter with Western medicine in nineteenth-century north India generated a rich corpus of Unani medical texts in the vernacular Urdu. A new Unani and a new hakim (practitioner of Unani) evolved with an emphasis less on the mastery of the theory and more on the practice of medicine. Urdu newspapers, particularly the Oudh Akhbar, pushed the issues generated by texts on Unani into the public sphere, and it was here that the inevitable tensions between the old family-centred Unani and the new hakim were fought out. Through an engagement with Western medicine in order to contain the threat posed by it, Unani dramatically reshaped and redefined itself as an Indian medical system.
Ethics
Authors: S.K. Chakraborty
Published: March 2005

This article comprises deep structure clues to ethical issues in our lives drawn from the wisdom writings of Tagore, Vivekananda, Gandhi and Aurobindo. All of them had recognized frankly the negative tendencies of man-as-he-is. This fault at the base needs systematic correction and restoration. For, the positive spiritual potential of man-as-he-could-be requires a fault-free baseline as the runway. All of them readily accept the classical word ‘character’ as signifying such a base. Illustrations from various walks of life, small or big, have been interspersed in the article to indicate the essential connections of principle to reality. It is hoped that we might consent to draw sustenance for ethics from our very roots despite inevitable failures or slippages. Ethics is too precious to gain or preserve without persistent battles with one’s own self. Codes and laws are but thin layers of icing on the ethical cake.
Menstrual Practices and Reproductive Problems
Authors: Khanna Anoop , R.S. Goyal  , Bhawsar Rahul
Published: March 2005

This article sheds light on some important issues related to menstrual practices and its association with reproductive morbidity among girls. The study indicates that a significantly large proportion of girls were not aware of menstruation when they first experienced it. Mothers, sisters and friends were found to be the major source of information. Much of this information imparted to a young girl is in the form of restrictions on her movements and behaviour. More than three-fourths reported using old cloth during menstruation, and a large proportion of them were reusing the same during subsequent periods. Regression analysis in this study identified schooling, residential status, occupation of father, caste and exposure to media to be the major predictors of safe menstrual practices among adolescent girls in Rajasthan. Importantly, this study found a significantly strong relationship between practices during menstruation and prevalence (reported symptoms) of RTIs. The prevalence of RTIs was more than three times higher among girls having unsafe menstrual practices. The article makes a strong case that ignorance, false perceptions and unsafe practices regarding menstruation are not uncommon among adolescents in the study area, having serious implications for reproductive and sexual health. Further, the study demonstrates that among the determinants for reproductive morbidity, practices during menstruation appear to be the most dominant factor. These findings reinforce the need to bring them out of traditional beliefs, misconceptions and restrictions, and encourage safe and hygienic practices.
Women’s Reproductive Health, Sociocultural Context and AIDS Knowledge in Northern India
Authors: Pallikadavath Saseendran , A.A. Jayachandran  , Stones R. William
Published: March 2005

This paper identifies sociocultural and reproductive health correlates of knowledge about HIV among ever-married women using 1998–99 National Family Health Survey data from two low HIV prevalence Indian states, Madhya Pradesh (MP) and Uttar Pradesh (UP). Logistic regressions were undertaken modelling women’s awareness of HIV, of whether the disease can be avoided and of effective means of protection. In MP 22.7 per cent women were aware of HIV; 56.4 per cent (of 22.7 per cent) knew that the disease can be avoided; and 47.5 per cent (of 56.4 per cent) possessed correct knowledge about effective means of protection. In UP 20.7 per cent women had awareness of HIV; 59.2 per cent (of 20.7 per cent) knew that the disease can be avoided; and 45.7 per cent (of 59.2 per cent) were informed about effective means of protection. In both states older, uneducated, rural, poor, those not exposed to television, and those who had never used a modern family planning method were less likely to possess HIV awareness. However, for women who were aware of HIV, acquisition of further knowledge about it had fewer socioeconomic barriers. These barriers were state specific so interventions to overcome them need to be highly focused.
Managing Change
Authors: H.K. Kassean  , D. Vythilingum
Published: March 2005

Innovations in high-tech medicine are significantly improving the chances of survival of many patients. However, the importance of basic nutritional needs should not be overlooked. The frail and elderly are a vulnerable group and often rely on nurses’ support to meet their nutritional requirements. This paper addresses the topic of developing and implementing a teaching programnme for nurses in Ward A2 at the Dr. A.G. Jeetoo Hospital to enhance nurses’ knowledge and skills in nutritional care for elderly patients. A survey carried out in November 2003 in A2 suggests that the elderly patients’ nutritional needs are not being met adequately and this represents the major group of patients admitted to our hospitals and is expanding rapidly. Using appropriate management tools and techniques and proper planning, this programme was successfully implemented in Ward A2 and has improved the morale of staff and patients alike. The challenge now is to keep this momentum going and extend this innovation to other important aspects of care of the elderly in order to make it more holistic and bring a significant improvement in their quality of life.
AML-associated Flt3 kinase domain mutations show signal transduction differences compared with Flt3 ITD mutations
Authors: Choudhary Chunaram , Schwäble Joachim , Brandts Christian , Tickenbrock Lara , Sargin Bülent , Kindler Thomas , Fischer Thomas , Berdel Wolfgang E. , Müller-Tidow Carsten , Serve Hubert
Published: March 2005

Activating mutations of Flt3 are found in approximately one third of patients with acute myeloid leukemia (AML) and are an attractive drug target. Two classes of Flt3 mutations occur: internal tandem duplications (ITDs) in the juxtamembrane and point mutations in the tyrosine kinase domain (TKD). We and others have shown that Flt3-ITD induced aberrant signaling including strong activation of signal transducer and activator of transcription 5 (STAT5) and repression of CCAAT/estradiol-binding protein α (c/EBPα) and Pu.1. Here, we compared the signaling properties of Flt3-ITD versus Flt3-TKD in myeloid progenitor cells. We demonstrate that Flt3-TKD mutations induced autonomous growth of 32D cells in suspension cultures. However, in contrast to Flt3-ITD and similar to wild-type Flt3 (Flt3-WT), Flt3-TKD cannot support colony formation in semisolid media. Also, in contrast to Flt3-ITD, neither Flt3-WT nor Flt3-TKD induced activation or induction of STAT5 target genes. Flt3-TKD also failed to repress c/EBPα and Pu.1. No significant differences were observed in receptor autophosphorylation and the phosphorylation of Erk-1 and -2, Akt, and Shc. Importantly, TKD but not ITD mutations were a log power more sensitive toward the tyrosine kinase inhibitor protein kinase C 412 (PKC412) than Flt3-WT. In conclusion, Flt3-ITD and Flt3-TKD mutations display differences in their signaling properties that could have important implications for their transforming capacity and for the design of mutation-specific therapeutic approaches.
DC-NK cell cross talk as a novel CD4+ T-cell–independent pathway for antitumor CTL induction
Authors: Adam Christian , King Susan , Allgeier Thomas , Braumüller Heidi , Lüking Carolin , Mysliwietz Josef , Kriegeskorte Anja , Busch Dirk H. , Röcken Martin , Mocikat Ralph
Published: March 2005

It is generally accepted that priming of antitumor CD8+ cytotoxic T lymphocytes (CTLs) needs help that can be provided by CD4+ T cells. We show that interactions between dendritic cells (DCs) and natural killer (NK) cells can bypass the T helper arm in CTL induction. Bone marrow–derived DCs caused rejection of the A20 lymphoma and induced tumor-specific long-term memory, although they were not loaded with tumor-derived antigen. Experiments using CD40- knock-out mice and cell depletion showed that this effect did not require CD4+ cells. Both primary rejection and long-term CTL memory were the result of NK cell activation by DCs. NK cytotoxicity, which was necessary for primary rejection, was dependent on expression of natural killer group 2 D (NKG2D) ligands on tumor cells. Blocking of these ligands using NKG2D tetramers abrogated tumor killing in vitro and in vivo. The long-term response was due to CTLs directed against antigen(s) expressed on A20 and in vitro–differentiated DCs. The mechanism leading to CD4+ helper cell–independent CTL responses was elucidated as a cascade that was initiated by NK cell activation. This pathway was dependent on inter-feron-γ expression and involved priming endogenous DCs for interleukin-12 production. Our data suggest a novel pathway linking innate and adaptive immunity.
p85α subunit of class IA PI-3 kinase is crucial for macrophage growth and migration
Authors: Munugalavadla Veerendra , Borneo Jovencio , Ingram David A. , Kapur Reuben
Published: March 2005

Macrophages play an essential role in defending against invading pathogens by migrating to the sites of infection, removing apoptotic cells, and secreting inflammatory cytokines. The molecular mechanisms whereby macrophages regulate these processes are poorly understood. Using bone marrow–derived macrophages (BMMs) deficient in the expression of p85α-subunit of class IA phosphatidylinositol 3 (PI-3) kinase, we demonstrate 50% reduction in proliferation in response to macrophage–colony-stimulating factor (M-CSF) as well as granulocyte macrophage–colony-stimulating factor (GM-CSF) compared with wild-type controls. Furthermore, p85α–/– BMMs demonstrate a significant reduction in migration in a wound-healing assay compared with wild-type controls. The reduction in migration due to p85α deficiency in BMMs is associated with reduced adhesion and directed migration on fibronectin and vascular cell adhesion molecule-1. In addition, deficiency of p85α in BMMs also results in defective phagocytosis of sheep red blood cells. Biochemically, loss of p85α in BMMs results in reduced activation of Akt and Rac, but not Erk (extracellular signal-related kinase) mitogen-activated protein (MAP) kinase. Taken together, our results provide genetic evidence for the importance of p85α in regulating both actin- and growth-based functions in macrophages, and provide a potential therapeutic target for the treatment of diseases involving macrophages, including inflammation.
The role of endothelial PI3Kγ activity in neutrophil trafficking
Authors: Puri Kamal D. , Doggett Teresa A. , Huang Ching-Yu , Douangpanya Jason , Hayflick Joel S. , Turner Martin , Penninger Josef , Diacovo Thomas G.
Published: March 2005

Phosphoinositide 3-kinase gamma (PI3Kγ) in neutrophils plays a critical role in the directed migration of these cells into inflamed tissues. In this study, we demonstrate the importance of the endothelial component of PI3Kγ activity relative to its leukocyte counterpart in supporting neutrophil interactions with the inflamed vessel wall. Despite the reconstitution of class-Ib PI3K function in neutrophils of p110γ–/– mice, we observed a 45% reduction in accumulation of these cells in an acute lung injury model. Mechanistically, this appears to result from a perturbation in selectin-mediated adhesion as manifested by a 70% reduction in wild-type (WT) neutrophil attachment to and 17-fold increase in rolling velocities on p110γ–/– microvessels in vivo in response to tumor necrosis factor alpha (TNFα). This alteration in adhesion was further augmented by a deficiency in p110δ, suggesting that the activity of both catalytic subunits is required for efficient capture of neutrophils by cytokine-stimulated endothelium. Interestingly, E-selectin–mediated adhesion in p110γ–/– mice was impaired by more than 95%, but no defect in nuclear factor kappa B (NF-κB)–induced gene expression was observed. These findings suggest a previously unrecognized partnership between class-I PI3Ks expressed in leukocytes and endothelium, the combination of which is required for the efficient trafficking of immunocompetent cells to sites of inflammation.
Both heterozygous and homozygous α+ thalassemias protect against severe and fatal Plasmodium falciparum malaria on the coast of Kenya
Authors: Williams Thomas N. , Wambua Sammy , Uyoga Sophie , Macharia Alex , Mwacharo Jedidah K. , Newton Charles R. J. C. , Maitland Kathryn
Published: March 2005

Although the α+ thalassemias almost certainly confer protection against death from malaria, this has not been formally documented. We have conducted a study involving 655 case patients with rigorously defined severe malaria and 648 controls, frequency matched on area of residence and ethnic group. The prevalence of both heterozygous and homozygous α+ thalassemia was reduced in both case patients with severe malaria (adjusted odds ratios [ORs], 0.73 and 0.57; 95% confidence intervals [95% CIs], 0.57-0.94 and 0.40-0.81; P = .013 and P = .002, respectively, compared with controls) and among the subgroup of children who died after admission with severe malaria (OR, 0.60 and 0.37; 95% CI, 0.37-1.00 and 0.16-0.87; P = .05 and P = .02, respectively, compared with surviving case patients). The lowest ORs were seen for the forms of malaria associated with the highest mortality—coma and severe anemia complicated by deep, acidotic breathing. Our study supports the conclusion that both heterozygotes and homozygotes enjoy a selective advantage against death from Plasmodium falciparum malaria.