bluuebunny/crossref_metadata_2025 huggingface dataset:
Fifteen‐year secondary leukaemia risk observed in 761 patients with Hodgkin's disease prospectively treated by MOPP or ABVD chemotherapy plus high‐dose irradiation
Authors: Delwail Vincent , Jais Jean‐Philippe , Colonna Pierre , Andrieu Jean‐Marie
Published: September 2002

Summary. Between 1972 and 1988, 869 adult patients received MOPP (mechlorethamine, vincristine, procarbazine and prednisone; 462 patients) or ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine; 373 patients) and subsequent high‐dose irradiation for Hodgkin's disease. Nine patients developed a leukaemia after MOPP and four after ABVD; 11 patients were diagnosed as acute non‐lymphoblastic leukaemia (ANLL) and two as acute lymphoblastic leukaemia (ALL). Both cases of ALL were observed after ABVD and were associated with a 11q23 translocation. The 15‐year actuarial risk of secondary leukaemia was 2·4% for the whole group of patients, 3·4% after MOPP and 1·3% after ABVD. For the MOPP subgroup, the risk of leukaemia was significantly associated with the extent of irradiation: 2·4% for limited irradiation and 13·9% for extended irradiation (P < 0·001). For the ABVD subgroup, this risk remained low (1·3%) whatever the type of irradiation. Concerning ANLL, the MOPP regimen was significantly associated with a higher risk: 3·4% versus 0·7% for ABVD (P≤0·05). The 15‐year risk of ALL was 0·6 after ABVD regimen. This study demonstrated that ABVD induced less ANLL than MOPP. However, a low risk of ALL with a 11q23 translocation related to topoisomerase II inhibitors was observed.
Mutations in coagulation factor XIII A gene in three Turkish patients: two novel mutations and a known insertion
Authors: Birben Esra , Öner Reyhan , Öner Cihan , Gümrük Fatma , Altay Çiğdem , Gürgey Aytemiz
Published: September 2002

Summary.  Molecular analysis of factor XIII A gene on three unrelated Turkish families identified two novel and one known mutations. One novel mutation is a substitution of cytidine by guanine at codon 541 in exon 12, β barrel 1 domain of the coagulation factor XIII A subunit gene resulting in the conversion of asparagine to lysine. The mutation alters the restriction site of the enzyme MboII. The second novel mutation, a 4 bp (–CAAA) deletion located in a direct repetitive sequence (CAAACAAA) between codons 466–469, results in premature termination of translation at codon 474. The third mutation is a previously reported single nucleotide (cytidine) insertion at codon 400 in exon 9 of the factor XIII gene.
All‐trans retinoic acid prevents apoptosis of human marrow CD34+ cells deprived of haematopoietic growth factors
Authors: Herault Olivier , Domenech Jorge , Georget Marie Therese , Clement Nathalie , Colombat Philippe , Binet Christian
Published: September 2002

Summary. The regulation of apoptosis plays a key role in haematopoiesis. It has been demonstrated that haematopoietic progenitor cells progressively undergo apoptotic cell death in the absence of appropriate growth factors. We studied the effects of pharmacological doses of all‐transretinoic acid (ATRA) on the apoptosis of human adult marrow CD34+ progenitor cells cultured for 7 d in a serum‐free medium. We quantified CD34+ cells, clonogenic progenitors and 5 week colony‐forming cells (CFC) before and after ATRA exposure. Moreover, we defined the apoptotic status of the CD34+ cell fraction by analysis of phosphatidylserine externalization (using annexin V), the relative membrane permeability to 7‐aminoactinomycin D (7AAD) and the mitochondrial membrane potential [using 3,3′‐dihexyloxacarbocyanine iodide, DiOC6(3)]. In the drastic experimental conditions used, a decrease in viable CD34+ cells, granulocyte–macrophage colony‐forming units (CFU‐GM), erythroid burst‐forming units (BFU‐E) and 5 week CFC were observed. Exposure to ATRA partially prevented the decrease in viable CD34+, without a concomitant effect on the clonogenic and more immature progenitors. ATRA‐treated CD34+ cells displayed changes in apoptotic status compared with control cultures, particularly in lower annexin V‐binding. These results were confirmed using 7AAD and DiOC6(3). Our results demonstrate that ATRA exerts a protective effect on CD34+ cells exposed to such apoptotic stress.
Prolonged administration of erythropoietin increases erythroid response rate in myelodysplastic syndromes: a phase II trial in 281 patients
Authors: Terpos Evangelos , Mougiou Athina , Kouraklis Alexandra , Chatzivassili Aria , Michalis Evridiki , Giannakoulas Nicholas , Manioudaki Eleni , Lazaridou Anna , Bakaloudi Vassiliki , Protopappa Maria , Liapi Dimitra , Grouzi Elisavet , Parharidou Agapi , Symeonidis Argyris , Kokkini Garoufalia , Laoutaris Nikolaos P. , Vaipoulos George , Anagnostopoulos Nikolaos I. , Christakis John I. , Meletis John , Bourantas Konstantinos L. , Zoumbos Nicholas C. , Yataganas Xenophon , Viniou for The Greek MDS Study Group Nora‐Athina
Published: September 2002

Summary. Treatment with recombinant human erythropoietin (rHuEpo) improves anaemia in approximately 20% of patients with myelodysplastic syndromes (MDS). We investigated the potential advantage of a prolonged administration of rHuEpo to achieve higher erythroid response rates (RR) in 281 MDS patients: 118 with refractory anaemia (RA), 77 with refractory anaemia and ringed sideroblasts (RARS), 59 with refractory anaemia with excess of blasts and blast count < 10% (RAEB‐I), and 27 with RAEB and blast count between 11–20% (RAEB‐II). rHuEpo was given subcutaneously at a dose of 150 U/kg thrice weekly, for a minimum of 26 weeks. Response to treatment was evaluated after 12 and 26 weeks of therapy. The overall RR was 45·1%; the RR for RA, RARS, RAEB‐I and RAEB‐II were 48·3%, 58·4%, 33·8% and 13% respectively. A significant increase in RR was observed at week 26 in RA, RARS and RAEB‐I patients, as the response probability increased with treatment duration. The RR was higher in the good cytogenetic prognostic group and serum Epo level of > 150 U/l at baseline predicted for non‐response. The median duration of response was 68 weeks and the overall risk of leukaemic transformation was 21·7%. These results suggest that prolonged administration of rHuEpo produces high and long‐lasting erythroid RR in MDS patients with low blast counts, particularly in those with pretreatment serum Epo levels of < 150 U/l and good cytogenetic prognosis.
The co‐expression of CD117 (c‐kit) and osteocalcin in activated bone marrow stem cells in different diseases
Authors: Huss Ralf , Moosmann Sabine
Published: September 2002

Summary. It is still difficult to identify a potential stem cell in the bone marrow which can give rise to haematopoiesis and mesenchymal cells. In the past, the stem cells for both tissues were considered to be from different stem cell pools, but it has been shown recently in vitro and in vivo that there is an unexpected plasticity at least among early haemopoietic progenitors which can give rise also to mesenchymal tissue. In an attempt to identify stem cells in the bone marrow, which are common precursors to both lineages, we observed that fibroblast‐like periosteal cells changed their morphology towards an osteoblastic differentiation with a more cuboidal or triangular morphology especially close to metastatic infiltrates. As a marker for haemopoietic progenitors, we used an antibody against the tyrosine kinase receptor c‐kit (CD117) and an anti‐osteocalcin antibody to stain mesenchymal cells with a osteoblastic potential. Normal bone marrow specimens only showed a discrete expression pattern of CD117 and osteocalcin, but periosteal stem cells, which strongly co‐express the applied haemopoietic and mesenchymal markers, were found particularly in the bone marrow of patients with infiltrates of malignant lymphoma or metastasis from prostate or breast cancer. The evaluation of bone marrow specimens from patients with an aplastic syndrome or myelodysplastic syndrome showed a more heterogenous expression pattern. Our results show that a stem cell candidate common to haematopoiesis and mesenchymal progeny can be detected in bone marrow specimens after activation, as demonstrated by the co‐expression of CD117 and osteocalcin, which also seems to be associated with haematological diseases or metastatic infiltration in the bone marrow.
Impact of stem cell source and conditioning regimen on erythrocyte recovery kinetics after allogeneic haematopoietic stem cell transplantation from an ABO‐incompatible donor
Authors: Kanda Yoshinobu , Tanosaki Ryuji , Nakai Kunihisa , Saito Takeshi , Ohnishi Mutsuko , Niiya Hironari , Chizuka Aki , Yakushijin Kimikazu , Urahama Norinaga , Ueda Kyoji , Iijima Kimiko , Ando Toshihiko , Matsubara Hiroshi , Kami Masahiro , Makimoto Atsushi , Kobayashi Yukio , Tobinai Kensei , Mineishi Shin , Takaue Yoichi
Published: September 2002

Summary. We evaluated erythrocyte recovery in 121 allogeneic haematopoietic stem cell transplantation (HSCT) recipients. There were 35 major and minor ABO‐incompatible transplants, respectively, including 10 bi‐directionally ABO‐incompatible transplants. The use of peripheral blood stem cells facilitated erythrocyte recovery, regardless of the presence or absence of major ABO‐incompatibility, and was associated with a frequent detection of anti‐host isohaemagglutin early after minor ABO‐incompatible transplantation, which was not associated with clinically relevant haemolysis. The use of a reduced‐intensity regimen combining a purine analogue and busulphan did not delay erythrocyte recovery after major ABO‐incompatible transplantation, suggesting this regimen had a strong activity against host plasma cell.
Increased risk of adverse maternal and infant outcomes among women with renal disease
Authors: Fink Jeffrey C. , Schwartz Stephen M. , Benedetti Thomas J. , Stehman‐Breen Catherine O.
Published: September 2002

We conducted a retrospective population‐based study to estimate the risk of adverse maternal and neonatal outcomes in women with a diagnosis of renal disease during pregnancy. One hundred and sixty‐nine women with renal disease who gave birth to a singleton infant between 1987 and 1993 were identified through linked Washington State hospital discharge and birth certificate databases. For comparison, 506 women without renal disease matched for year of delivery were selected. Women with renal disease were at increased risk of pre‐eclampsia [OR = 7.2, 95% CI 4.2–12.5], preterm labour [OR = 7.9, 95% CI 1.9–32.6], dysfunctional labour [OR = 3.6, 95% CI 1.1–11.5], and caesarean section [OR = 3.1, 95% CI 2.0–4.8]. They were also at increased risk of delivering infants who were small for gestational age [OR = 5.3, 95% CI 2.8–10.0], preterm [OR = 6.1, 95%CI 3.3–11.3], and had 5‐minute Apgar scores of less than 7 [OR = 3.9, 95% CI 1.1–14.6]. These associations persisted in analyses restricted to women without chronic hypertension. Women with renal disease and their infants also had median hospital charges that were more than twice those of women without renal disease and were more likely to be hospitalised longer. These data demonstrate that, independent of chronic hypertension, women with underlying renal disease are at increased risk of adverse maternal and perinatal outcomes and use more resources than women without renal disease.
Allergen‐Induced Synthesis of Interleukin‐5, but not of IgE, is a Key Mechanism Linked to Symptomatic Episodes of Seasonal Allergic Rhinitis in Sensitized Individuals
Authors: Ohashi  , Nakai  , Tanaka  , Kakinoki  , Masamoto  , Kato  , Washio  , Yamada  , Hayashi  , Ohmoto
Published: September 2002

Some individuals with detectable levels of Japanese cedar (Criptomeria japonica) pollen‐specific immunoglobulin (Ig)E in serum have no apparent nasal symptoms during the pollen season. The response of CD4+ T‐helper (Th) cells to the pollen allergen might differ fundamentally between asymptomatic and symptomatic individuals who are already sensitized to the pollen. The aim of this study was to discern the possible differences in responses of peripheral blood mononuclear cells (PBMCs) to the pollen allergen between asymptomatic and symptomatic subjects who have been sensitized to the pollen. This study included 20 non‐atopic healthy volunteers (non‐atopic group) and 48 patients who had detectable levels of the pollen‐specific IgE before the pollen season in 1997. In the review of nasal symptoms during the pollen season 1997, 24 patients had typical symptoms of seasonal allergic rhinitis (symptomatic group), and the remainder had no seasonal aggravation of nasal symptoms (asymptomatic group). Peripheral blood mononuclear cells (1.0 × 107 cells/well) were obtained from each individual during the pollen season and cultured in the absence or presence of 12.5 μg of Cry j 1 for 4 days. The concentrations of IgE, interleukin‐5 (IL‐5), and interferon‐gamma (IFN‐γ) in the culture supernatants were measured. The levels of IgE produced by Cry j 1‐stimulated PBMCs of the asymptomatic and symptomatic groups were significantly higher than those of the non‐atopic group, but did not differ between the asymptomatic and symptomatic groups. The levels of IL‐5 produced by Cry j 1‐stimulated PBMCs did not differ significantly between the non‐atopic group and the asymptomatic group, but the levels of IL‐5 were significantly higher in the symptomatic group than in the asymptomatic group as well as the non‐atopic group. The levels of IFN‐γ produced by Cry j‐1 stimulated PBMCs did not differ significantly among the three groups. In conclusion, our study has suggested that Japanese cedar pollen‐induced synthesis of IL‐5, but not of IgE or IFN‐γ, is likely to be a key mechanism linked to the symptomatic episode of seasonal allergic rhinitis in individuals sensitized to the pollen.
Advances in the understanding and future therapy of COPD
Authors: Fabbri L. , Rennard S. , Leff A. , O'Connor B.
Published: September 2002

Chronic obstructive pulmonary disease (COPD) is an enormous public health problem, which currently causes about 5% of all deaths worldwide. The main feature of COPD is a progressive loss of lung function as a result of structural changes in the airways and lung parenchyma. It is predominantly a disease of smokers, although only about 15% of smokers are thought to develop severe enough disease to be symptomatic. The reasons why some smokers are more susceptible to the disease than others are not clear, and are the subject of extensive research. Characteristically, inflammation is central to the pathophysiology of COPD, and it is clear that the inflammation of COPD differs from that seen in asthma. The most important treatment for COPD is smoking cessation, as other current treatments do not alter the course of the disease. Recent research into the cellular and molecular mechanisms underlying chronic obstructive pulmonary disease has provided potential new avenues for the development of rationally designed drugs, which may improve the outlook for patients with this debilitating condition. It is likely that different therapeutic approaches will be needed in different patients, because of the heterogeneity of the disease.
Allergic rhinitis: current and future treatments
Authors: Naclerio R. , Rosenwasser L. , Ohkubo K.
Published: September 2002

Allergic rhinitis is a highly prevalent respiratory disease, affecting up to 40% of the population in some countries, and has an important impact on quality of life. Although a number of different drug types are available for treating allergic rhinitis, antihistamines are currently considered first‐line therapy. Newer antihistamines, such as fexofenadine, are very effective in suppressing symptoms and are largely free of side‐effects. In addition, they have been shown to improve patient's quality of life. Some patients have residual symptoms despite the use of antihistamines and other available treatments. Moreover, most current treatments only relieve symptoms, and do not modify the course of the disease. Current research into the pathophysiology of the disease is opening many promising new avenues for improved treatments. Such possibilities include improving methods of immunotherapy, based on our greater understanding of the balance between Th1 and Th2 cells and of the cytokines that they produce; and targeting and blocking the effects of bradykinin, substance P, leukotrienes, IgE antibody, tryptase, platelet‐activating factor and prostaglandins. Refinements of immunotherapy are particularly promising, as they may provide a permanent cure for the disease in an increasing number of patients. Furthermore, recent evidence has shown that early intervention in children with allergic rhinitis, by antihistamine treatment or immunotherapy, can reduce the risk of developing asthma. Improved understanding of the links between allergic rhinitis and asthma is likely to advance the treatment of both diseases.
Effect of burn injury on corticosteroid‐binding globulin levels in plasma and wound fluid
Authors: Garrel Dominique R. , Zhang Limin , Zhao Xian‐F. , Hammond Geoffrey L.
Published: September 2002

Corticosteroids exert inhibitory effects on wound healing. They circulate, largely bound to corticosteroid‐binding globulin, and the plasma concentrations of this protein determine their bioavailability. The amount of corticosteroid‐binding globulin in wounds and the related effects of burn injury are not known. We have therefore measured corticosteroid‐binding globulin in serum and wound fluid obtained from subcutaneously implanted sponges, retrieved 1, 3, and 10 days after insertion in rats. The effect of burning was studied by comparing rats that had a small scald burn with sham‐burned control rats. In serum, corticosteroid‐binding globulin levels were lower in burned rats than in control animals: the difference was 22%, 28%, and 37% for days 1, 3, and 10, respectively (p < 0.05 for each comparison), and values at day 1 were lower than at days 3 and 10 in control rats (p < 0.05) but not in burned rats. In wound fluid, corticosteroid‐binding globulin levels were lower in burned rats than in control animals: the difference was 23%, 24%, and 34% for days 1, 3, and 10, respectively (p < 0.01 for all comparisons), and the values were significantly higher (p < 0.05) at day 1 when compared with values at day 10 in both groups. We therefore conclude that a small burn injury has significant effects on levels of corticosteroid‐binding globulin on serum and wound fluid corticosteroid‐binding globulin. The decreased concentration of wound fluid corticosteroid‐binding globulin at day 10 versus day 1, with a concomitant increase in serum corticosteroid‐binding globulin, suggests an accelerated degradation of the protein within the wound; this phenomenon is exaggerated by the burn injury. This is supported by Western blot analysis, which revealed the appearance of a small polypeptide that reacts with an antiserum against rat corticosteroid‐binding globulin in wound fluid at day 10.
Development of a new wound dressing with antimicrobial delivery capability
Authors: Kuroyanagi Yoshimitsu , Shiraishi Akihiko , Shirasaki Yoshiteru , Nakakita Nobuaki , Yasutomi Yoshiaki , Takano Yasuo , Shioya Nobuyuki
Published: September 2002

A bilaminar wound dressing composed of an outer membrane and an inner three‐dimensional matrix of a fabric or a sponge may be considered to constitute an ideal structure that promotes wound healing: the outer membrane prevents body fluid loss, controls water evaporation, and protects the wound surface from bacterial invasion, and the inner matrix encourages adherence by tissue growth into the matrix. Using this concept, we developed a biosynthetic wound dressing with a drug delivery capability. This medicated wound dressing is composed of a spongy sheet of a chitosane derivative and collagen mixture that is laminated to an antimicrobial‐impregnated polyurethane membrane. In this study, a gentamycin sulfate—impregnated wound dressing was prepared and evaluated. The antimicrobial efficacy of this wound dressing was examined on an agar plate seeded with Pseudomonas aeruginosa. Also, the cytotoxicity of an antimicrobial released from this wound dressing was examined in an in vitro system with cultured skin substitutes. Both in vitro tests have shown that this wound dressing is capable of suppressing bacterial growth and minimizing cellular damage. In addition, in the treatment of wounds inflicted on rats and rabbits, this wound dressing was shown to be efficacious in covering full‐thickness and split‐thickness skin defects. Finally, the efficacy of this wound dressing was evaluated in a nonrandomized open‐label study of 31 clinical cases. In 31 cases treated with this wound dressing, good or excellent wound healing was achieved.
The hairless mouse ear: an in vivo model for studying wound neovascularization
Authors: Barker John H. , Kjolseth Dorthe , Kim Michael , Frank Johannes , Bondar Imre , Uhl Eberhard , Kamler Markus , Messmer Konrad , Tobin Gordon R. , Weiner Leonard J.
Published: September 2002

Microvascular ingrowth into damaged tissue is an essential component of the normal healing process. In fact, wound therapy is often aimed at promoting neovascularization. However, little is known about the mechanisms that regulate microvascular ingrowth into a healing wound. This limited knowledge is largely due to the lack of adequate models in which microvascular ingrowth can be quantitatively analyzed throughout the healing process. To address this deficiency, we developed a model in which a wound was created on the ear of the hairless mouse—a well established model for directly viewing and measuring skin microcirculation. While the animals were under ketamine and xylazine anesthesia, 2.25 mm diameter full‐thickness wounds were created on the dorsum of hairless mouse ears down to but not including the cartilage (0.125 mm depth). With the use of video microscopy and computer‐assisted digitized planimetry, the precise epithelial and neovascular wound edge was viewed and measured regularly throughout healing. Therefore, this model can provide objective data on wound epithelialization and neovascularization throughout healing. This model was used to examine the effect of topical wound agents on epithelialization and neovascularization. Differential effects by these anti‐microbial agents on these two processes were observed, which suggests clinical implications for their use.
Excessive scarring as a consequence of healing
Authors: Ladin Daniel A. , Garner Warren L. , Smith David J.
Published: September 2002

Synthesis and degradation of collagen is an essential component of wound healing. In most persons, this deposition of collagen results in the formation of a fine line scar which restores much of the tensile strength to the injured tissue and is cosmetically acceptable. However, in certain individuals, the result of wound healing is the excessive accumulation of collagen, resulting in a hypertrophic scar or keloid. The precise origin of this abnormal collagen deposition is unknown, but recent studies have begun to identify potential mechanisms for these disfiguring and painful lesions. This article will review the clinical and laboratory findings pertinent to understanding the origin and treatment of excessive scarring.
The role of transforming growth factor‐β in the conversion from “scarless” healing to healing with scar formation
Authors: Houghton Pamela E. , Keefer Kerry A. , Krummel Thomas M.
Published: September 2002

The objective of this study was to elucidate mediators responsible for conversion of “scarless” wound healing seen in wounded, day 14 fetal mouse limbs to healing with scar formation seen in wounded, day 18 fetal mouse limbs. Wounded, day 14 limbs were grown in a serum‐free organ culture system in which either phosphate‐buffered saline solution or human recombinant transforming growth factor beta‐1 (1 µg/ml) was added daily. Wounded, day 18 limbs were also maintained in the same organ culture system with either phosphate‐buffered saline solution or neutralizing antibody to transforming growth factor‐β (1 µg/ml) treatment. Limb cross sections were examined qualitatively with Masson's Trichrome stain and quantitatively by spectrophotometric analysis of Sirius Red and Fast Green dyes which bind to collagen and noncollagenous protein, respectively. Both qualitative and quantitative analyses showed the following: there was greater collagen deposition in day 18 versus day 14 limbs by 7 days after wounding, scar formation in day 18 limbs was attenuated by the addition of anti‐transforming growth factor‐β, and there was the addition of transforming growth factor‐β‐augmented collagenous scar formation in wounded regions of day 14 limbs. These results strongly suggest that transforming growth factor‐β present in the local wound environment is, at least in part, responsible for the conversion of “scarless” healing occurring in wounded, day 14 limbs to scar formation present in wounded, day 18 limbs.
Effect of vibriolysin, an enzymatic debriding agent, on healing of partial‐thickness burn wounds
Authors: Nanney Lillian B. , Fortney Don Z. , Durham Don R.
Published: September 2002

Vibriolysin, a new agent for enzymatic debridement, was recently shown to rapidly and thoroughly hydrolyze burn wound eschar within full‐thickness wounds. The safety of this agent and its subsequent effect on wound healing processes have yet to be established and are addressed in this study. Within the context of a porcine partial‐thickness burn wound model, the enzyme was shown to digest desiccated eschar after two applications, whereas four applications of another enzymatic preparation were required. Computerized morphometric analysis of dermal and epidermal growth from histologic sections on wounds harvested at day 7 and 10 was used to assess wound healing. The data indicate that wounds treated with Vibriolysin exhibited significant dose‐responsive stimulation of granulation tissue (neodermis) as compared with control treatment groups. Repeated protease applications did not convert partial‐thickness burns to full‐thickness wounds, and no adverse inflammatory responses were detected between 1 and 10 days. The results suggest that in addition to its documented efficacy in the debridement of burn eschar, Vibriolysin may have beneficial effects on dermal reparative events.
Wound contraction and scar synthesis during development of the amphibian Rana catesbeiana
Authors: Yannas Ioannis V. , Colt Jude , Wai Yolanda C.
Published: September 2002

Certain characteristics of skin wound healing in the North American bullfrog, Rana catesbeiana, were studied grossly and histologically at various stages of development. The contraction kinetics of excisional skin wounds were monitored for 50 days in animals from four larval developmental stages (tadpoles) and from adults (frogs). The percentage of original wound area which remained after contraction had stopped in the four larval groups decreasing steadily from 59.2%± 6.8% for the least developed larvae to 9.9%± 2.3% for the most developed ones. Wounds in adults contracted at a much lower rate than for larvae and the percentage of original wound area remaining after 50 days was less than 10%. The morphologic features characterizing the intact dermis and epidermis outside the wound bed in the larvae were also observed in qualitatively similar detail inside the wound bed. In the adults, the subepidermal connective tissue inside the wound bed was distinctly different from the physiologic dermis outside and was classified as amphibian scar. We conclude that, during larval development, wound contraction increasingly displaced skin regeneration as a mechanism for wound closure. Adults closed skin wounds by a combination of contraction and synthesis of scar tissue. It is hypothesized that the mechanism for synthesis of scar in this amphibian is established during metamorphosis from larva to adult.
Growth hormone increases the biomechanical strength and collagen deposition rate during the early phase of skin wound healing
Authors: Jørgensen Peter H. , Oxlund Hans
Published: September 2002

The effects of biosynthetic human growth hormone on the biomechanical properties and collagen deposition rate of wound healing were investigated in rat skin incisional wounds after 4 days of healing. Biosynthetic human growth hormone induced a pronounced, ≤94%, and dose‐dependent increase in the mechanical strength of wounds in the dose range of 0.125 to 2 mg/kg/day. A new method for in vivo studies of the collagen deposition rate in granulation tissue of the wound cleft was applied. The production of 3H‐hydroxy‐l‐proline was measured by injecting 3H‐proline intravenously into the rats with a large flooding dose of unlabeled proline which reduces reutilization of 3H‐proline and reduces the influence of de novo synthesis of proline. Extractable collagens, which are not bound in the wound tissue and therefore do not contribute mechanical strength to it, were removed from the samples. Labeled and unlabeled proline were determined simultaneously by reverse‐phase high‐performance liquid chromatography with ultraviolet detection and flow scintillation counting of these amino acids. At day 4 the collagen deposition rate in the incisional wound zone, 0.4 mm wide containing the wound cleft, was 1.8% per hour of the collagen present in the wound zone. The collagen deposition rate was increased by 149% by biosynthetic human growth hormone 2 mg/kg/day compared with the control group. This result indicates that the increased biomechanical strength of the skin incisional wounds of the groups treated with biosynthetic human growth hormone was produced by an increased deposition of collagen in the wound cleft.
Regulation of wound healing from a connective tissue perspective
Authors: Ehrlich H. Paul , Krummel Thomas M.
Published: September 2002

Tissue injury resulting in irreversible tissue loss initiates the repair process. The restoration of dermal loss is by scarring, where a new cell population resides in a new connective tissue matrix. The chemical composition of a scar is similar to normal dermis, but the organization of that tissue is altered. The inability of the organism to reassemble collagen into a normal dermal pattern is an attribute of a scar, but in most cases it restores normal function. With impaired scarring, wound dehiscence or chronic wounds arise, whereas the overproduction of scar tissue results in keloid or hypertrophic scarring. In both situations a catastrophic end point occurs. The volume of scar tissue deposited, as well as its organization, is critical for determining the scar's integrity, stability, and restoration of function. The maturation of scar depends on the character of its resident cell populations, the quality of deposited connective tissue, and the interactions between those components. In this Perspective article, the focus will be on the repair process in terms of collagen fiber organization. As our knowledge of cell‐cell and cell‐matrix interactions in the repair process increases, we may be able to direct the pattern of scar collagen fibers to resemble that of dermis and thereby provide better wound care to the patient of the future.
Pressure ulcers in older persons: a preventive approach
Authors: Conlin Shaw Mary M.
Published: September 2002

Strategies for the prevention of pressure ulcers are presented on the basis of the Agency for Health Care Policy and Research guidelines. A broad, holistic approach to care of the elderly, focusing on rehabilitative and restorative measures is introduced. Topics include the effects of bed rest and deconditioning, nutrition, and mobility issues. A broad approach to care, involving the expertise of multiple disciplines, is advocated.
A simple method to assess the relative amount of collagen deposition in wounded fetal mouse limbs
Authors: Houghton Pamela E. , Keefer Kerry A. , Diegelmann Robert F. , Krummel Thomas M.
Published: September 2002

A modification of the Sirius red and fast green dye staining technique which binds selectively to collagen and noncollagenous proteins, respectively, has been used to quantify the amount of collagen deposition occurring in wounded fetal mouse limbs. Wounded day 14 and 18 fetal mouse limbs were grown in serum‐free organ culture for 1 to 7 days, fixed in formalin, embedded in paraffin, and sectioned. The sections were stained with Sirius red and fast green dyes, and those sections obtained from either wounded or unwounded tissue were identified microscopically. The sections were then scraped off microscopic slides. Dye bound to the tissue sections was then eluted with a mixture of sodium hydroxide and methanol, and the optical densities were determined spectrophotometrically. There was a 98.5% correlation between the absorbance of Sirius red dye (collagen) and fast green dye (noncollagenous proteins) of eluted stain and hydroxyproline and leucine content, respectively, as determined by high‐performance liquid chromatography. In addition, there was a greater collagen/protein ratio in wounded compared with unwounded sections of day 18 limbs at 7 days after wounding (p = 0.005). However, no difference in the collagen/protein ratio was detected between wounded and unwounded regions of day 14 limbs at either day 1 or 7 after wounding. These results are consistent with previous histologic observations indicating greater collagen deposition in wounded regions of day 18 compared with day 14 limbs at 7 days after wounding. With the use of this technique, it is now possible to quantify the effects of putative fibrogenic agents on collagen deposition in wounded embryonic tissue.
Reversal of the wound healing deficit in diabetic rats by combined basic fibroblast growth factor and transforming growth factor‐β1 therapy
Authors: Davidson Jeffrey M. , Broadley Kenneth N. , Quaglino Daniela
Published: September 2002

Wound healing is impaired in the diabetic state because of, at least in part, low expression of growth factors. Individual growth factors can partially activate healing, yet the actual wound environment presents a dynamic continuum of multiple cellular signals. Complex interactions among growth factors and target cells can have synergistic effects, and several examples of combinatorial, in vivo activity are evident in the literature. In this study, the implantation of a combination of basic fibroblast growth factor and transforming growth factor‐β in rats induced fivefold to sevenfold increases in granulation tissue formation in comparison with implantation of each growth factor alone. Diabetes was induced in adult, male Sprague‐Dawley rats with streptozotocin. Incisional wounds and sponge granulation tissue were produced in separate groups and then treated with an injection of 2 µg transforming growth factor‐β1 combined with 10 µg basic fibroblast growth factor on day 3. DNA, collagen, and protein were analyzed in granulation tissue on days 7 and 9, and biomechanical properties of incisions were tested on days 7, 14, and 21. The combination of transforming growth factor‐β1 and basic fibroblast growth factor had marked, positive effects on biochemical parameters of wound healing and reversed the tensile strength deficit of diabetic wounds. Nonradioactive in situ hybridization showed increased expression of messenger RNA for type I and III procollagen and transforming growth factor‐β1 in normal and diabetic wounds, whereas ultrastructural examination showed a marked reorganization of collagen fibrils. These findings reinforce the concept that appropriate mixtures of cytokines rather than individual cytokines may more adequately stimulate tissues in cases of impaired wound healing.
Patterns and Significance of Floral Development in Whytockia (Gesneriaceae)
Authors: Wang Y.‐Z. , Möller M. , Hong D.‐Y.
Published: September 2002

Abstract: The floral development of Whytockia W. W. Smith has been studied in order to explore the developmental basis for the arrangement and differentiation patterns of floral organs, and the evolutionary relationship between Whytockia and allies in floral development. The descending imbricate aestivations in both calyx and corolla have remarkably different ontogenetic patterns between calyx and corolla which are derivative with respect to the development of the valvate aestivations in the four‐stamened Rhynchoglossum. Both corolla lobes and stamens are initiated simultaneously from the same ring meristem. However, the five stamens remarkably precede the initiation of the five corolla lobes. Also, the adaxial stamen is suppressed after initiation to become a staminode, concomitant with retardation of its adjacent organs during development. This situation, together with the non‐acropetal order among whorls of floral organs in Whytockia, is possibly related to a late expression and a remarkably different expression pattern of cycloidea‐like genes as compared to Antirrhinum. Furthermore, the axile placentation in the bilocular ovary of Whytockia is formed by an involute closure of carpels rather than derived from a secondary fusion of two intrusive parietal placentae.
Definition and Evaluation of the Spatio‐Temporal Variations in Chlorophyll Fluorescence during the Phases of CAM and during Endogenous Rhythms in Continuous Light, in Thick Leaves of Kalanchoë daigremontiana5
Authors: Maddess T. , Rascher U. , Siebke K. , Lüttge U. , Osmond B.
Published: September 2002

Abstract: We used chlorophyll fluorescence imaging to examine the homogeneity of photosynthetic metabolism during CAM in the thick leaves of Kalanchoë daigremontiana Hamet et Perrier de la Bǎthie. Intense, persistent fluorescence from a DCMU treated thin leaf of Clematis sp placed beneath a K. daigremontiana leaf was readily detected through the thick leaf. Evidently reabsorption of fluorescence was qualitatively unimportant in the system used. Chlorophyll fluorescence images from 7 mm tissue discs excised from Kalanchoë leaves were collected at 60 s intervals during 20 min transients elicited by red excitation light. Information about patchiness and subsurface processes was gained by statistical factor analysis and Fourier transform. Although small, highly resolved rings of bright chlorophyll fluorescence surrounding discs of low fluorescence were observed from cells near the surface, no independent regional temporal variation in fluorescence was evident in the surface‐biased images. Temporally independent chlorophyll fluorescence was present in images biased towards sub‐epidermal sources, in most phases of CAM, and during endogenous rhythm. These asynchronous changes were several millimetres apart. This patchy fluorescence was confirmed when attached leaves were excited with blue light in a leaf chamber while CO2 and H2O exchange was monitored. Large spatio‐temporal variations in the efficiency of photosystem II were always observed during phases II and IV of CAM, when both CO2 fixation cycles are active, and during the maximum rate of CO2 fixation during the endogenous rhythm in continuous light. These data are discussed in terms of metabolic isolation in the thick but uniform tissues in which gas diffusion may be largely confined to wet cell walls, thereby rendering the tissue functionally heterobaric. Prolonged, but in some instances, reversible alterations in PSII efficiency could be produced by injection of metabolic inhibitors, confirming that patchy fluorescence may reflect the differing energy costs of photosynthesis in different CAM phases.
Long-range ordering of methylidyne on Pt{110}(1×2)
Authors: Petersen M. A. , Watson D. T. P. , Jenkins S. J. , King D. A.
Published: September 2002

A c(2×4) LEED pattern is observed for methylidyne (CH) chemisorbed on Pt{110}(1×2) at a saturation coverage of 0.25 ML. Density functional calculations reveal that methylidyne is preferentially adsorbed in the fcc three-fold hollow site on the {111} microfacet of the reconstructed surface. A structure for the ordered overlayer is thus proposed, and both through-metal and through-space interactions are considered as possible causes for this unexpected long-range coherence. We argue that entropic effects may be implicated.
Insights into the stability of silicon cluster ions: Reactive etching with O2
Authors: Bergeron D. E. , Castleman A. W.
Published: September 2002

Oxygen etching reactions of silicon cluster cations and anions are studied with a fast-flow reaction apparatus. Ions incorporating silicon oxides are not observed as products in either the cation or anion studies. Magic clusters are identified as n=4, 6, 9, 13, 14, and 23 for the cations. For the anions, where there are no previous studies of oxygen etching reactions, magic clusters are found at n=18, 21, 24, 25, and 28. We note good overall agreement with past experimental findings in the case of cations, and with theoretically predicted structures for both anions and cations.
Radial electric field in the biasing experiments and effective conductivity in a tokamak
Authors: Rozhansky V. , Kaveeva E. , Voskoboynikov S. , Coster D. , Bonnin X. , Schneider R.
Published: September 2002

The biasing experiments and the problem of the effective perpendicular conductivity in a tokamak are studied both analytically and numerically. The simulations were performed by means of the B2SOLPS5.0 transport code [V. A. Rozhansky et al., Nucl. Fusion 41, 387 (2001)] where the fluid set of equations is solved for the real divertor geometry. It is demonstrated that there exist three regimes, which correspond to the different values of the effective perpendicular conductivity and to different profiles of the radial electric field and toroidal and poloidal rotations. Simulation results are compared with existing and developed analytical models.
Multisymplectic geometry and multisymplectic Preissman scheme for the KP equation
Authors: Liu Tingting , Qin Mengzhao
Published: September 2002

The multisymplectic structure of the KP equation is obtained directly from the variational principal. Using the covariant De Donder–Weyl Hamilton function theories, we reformulate the KP equation to the multisymplectic form which was proposed by Bridges. From the multisymplectic equation, we can derive a multisymplectic numerical scheme of the KP equation which can be simplified to the multisymplectic 45 points scheme.
Equilibrium of self-organized electron spiral toroids
Authors: Guss W. C. , Chen Chiping
Published: September 2002

Cold-fluid magnetohydrodynamics equilibrium equations are solved for an infinite aspect-ratio, electron spiral torus (EST). The electrons follow approximately azimuthal orbits outside an interior ion cloud. The ion mass is assumed finite, and both electrons and ions are assumed collisionless. It is found that self-organized solutions for the electron shell and the ions exist when the EST is immersed in a neutral gas. The ion flow velocity profile is not rigid rotor. Examples of two different electron densities are examined. In each example, solutions exist for neutral gas pressure p above a critical level pc and are independent of an applied axial magnetic field. For the low-density example, the critical neutral pressure corresponds to the value observed in experiments. The equilibrium ion rotational flow velocity and self-magnetic field scale as p1/2.
First principles simulations of SiGe for the liquid and amorphous states
Authors: Ko Eunjung , Jain Manish , Chelikowsky James R.
Published: September 2002

We report results for ab initio molecular-dynamics simulations of SiGe liquid alloy (l-SiGe) near its melting point, and the amorphous alloy (a-SiGe) near absolute zero. The structural and electronic properties of l-SiGe and a-SiGe, diffusion constants for Si and Ge atoms in the liquid state, and dielectric functions for a-SiGe are presented and compared to previous calculations and to experiment. We find l-SiGe has a predominantly random structure with a slight phase separation of Si–Si and Ge–Ge bonds. Also, it is shown that the conductivity of l-SiGe has a metallic character and a-SiGe has a semiconductor-type conductivity. We predict diffusion constants for Si and Ge in l-SiGe near the melting point to be DSi≅1.9×10−4 cm2/s and DGe≅1.5×10−4 cm2/s. Upon cooling, the structure of l-SiGe changes significantly from a more close packedlike structure to an open tetrahedral arrangement of atoms with more Si–Si and Ge–Ge association than in the melt. Our total pair correlation function for a-SiGe agrees well with available experiment.
Biaxial testing of nanoscale films on compliant substrates: Fatigue and fracture
Authors: Alaca B. Erdem , Selby John C. , Saif M. T. A. , Sehitoglu Huseyin
Published: September 2002

Two problems of technological importance for microelectromechanical systems (MEMS) and microelectronics industry are addressed: fatigue of thin films and nanoscale film cracking. A device is described that can (1) conduct biaxial fatigue tests on thin films and (2) be utilized to study fracture patterns in nanoscale coatings under biaxial stress state. Thin-film specimens, in the form of circular membranes, are exposed to cyclic pressures between two fixed pressure limits. Corresponding pressure and specimen deflection are measured. Experimental results, including hysteresis loops spanning deflections of 15–50 μm are presented for 4.6-μm-thick polyimide films. Furthermore, the evolution of crack patterns in a 150-nm-thick Al film deposited on a polyimide substrate is studied. Critical mode I stress intensity factor for Al is extracted from experimental results.
Large-eddy simulations of turbulent heat transfer in stationary and rotating square ducts
Authors: Pallares Jordi , Davidson Lars
Published: September 2002

Turbulent heat transfer at low Reynolds numbers in stationary and rotating straight square ducts was simulated using the large-eddy simulation technique. For the rotating square duct flows, the rotation axis was parallel to two opposite walls of the duct. The pressure-driven flow was assumed to be hydrodynamically and thermally fully developed. A constant and uniform heat flux distribution in the axial direction was applied at the four smooth walls of the forced and mixed convection flows. Two boundary conditions for the thermal energy equation were examined: constant peripheral wall temperature and uniform peripheral wall heat flux. Computations were carried out using a second-order finite volume code with a localized one-equation dynamic subgrid scale model. For the simulated nonrotating flows, there were significant differences of about 16% in the overall Nusselt numbers, depending on the type of thermal boundary condition applied at the walls. This was because of the presence of the corners. Simulations of mixed convection arising from the centrifugal buoyancy effect showed that the turbulence level of the flow was strongly influenced by the centrifugal buoyancy effect. At the rotation rate considered, the overall Nusselt numbers and the turbulence levels of the flow were not greatly affected by the type of boundary conditions for temperature applied at the walls. However, temperature fluctuation intensities noticeably increased when a uniform peripheral heat flux was imposed at the walls.