bluuebunny/crossref_metadata_2025 huggingface dataset:
Biostimulative effects of ND:YAG q‐switch dye on normal human fibroblast cultures: Study of a new chemosensitizing agent for the ND:YAG laser
Authors: Castro Dan J. , Ward Paul H. , Saxton Romaine E. , Castro Donna J. , Fetterman Harold R.
Published: October 2006

Kodak Q‐switch II® is a new chemical with an absorption maxima at 1,051 nm, designed to be used as an Nd:YAG dye laser. The potential for this dye as a new chemosensitizing agent in the treatment of connective tissue diseases and wound healing with low energy Nd:YAG laser was examined. Two normal fibroblast cell lines were tested for sensitivity to various levels of this dye in vitro. These cells were exposed to Q‐switch II dye at concentrations of 0.01, 0.1, 1, 10, 50, and 100 μg/ml for 1 and 24 hours. Cell viability was assessed by the trypan blue exclusion test. Cell duplication and DNA synthesis were measured by the incorporation of [3H]‐thymidine at 6 and 24 hours postexposure to Q‐switch II dye. At concentrations up to 10 μg/ml, both cell lines tested showed no changes in cell viability. However, at concentrations equal or higher than 50 μg/ml, more than 40% of the fibroblasts incorporated trypan blue after 24 hours of exposure to this dye, indicating significant cell destruction. The results indicate that Q‐switch II dye is nontoxic to normal human fibroblast cultures and showed significant biostimulative effects on cell duplication at concentrations equal to or lower than 10 μg/ml. Further studies will be required to determine the usefulness of Q‐switch EC dye as a new photochemosensitizing agent for potential biostimulation of wound healing and/or treatment of connective tissue diseases with the Nd:YAG laser (near infrared, 1,060 nm) at “nonthermal” levels of energies.
Open‐set word recognition with the duren/cologne extracochlear implant
Authors: Tyler Richard S.
Published: October 2006

The author visited Duren, West Germany and evaluated the performance of five patients implanted with the extracochlear Duren/Cologne implant who achieved better word recognition levels. Word and sentence speech reception tests were presented live‐voice by a familiar German speaker. Performance ranged from 1% to 80% correct word recognition with sentence material, 0% to 63% correct word recognition with word lists, and 13% to 86% correct recognition for phonemes in words. One patient achieved high‐level, open‐set word recognition without visual cues, using single‐channel, extracochlear stimulation. Preimplant auditory thresholds in her implanted ear were 60, 65, 90, and 105 dB HL at octave frequencies from 125 to 1,000 Hz, respectively. There was no measurable hearing at higher audiometric frequencies.
Murine subrenal capsule assay: Prediction of chemoresponsiveness in head and neck cancer
Authors: Panje William R. , Mccormick Kenneth J.
Published: October 2006

If chemotherapy is to be used with the greatest efficacy in head and neck cancer, a predictive test that will indicate tumor sensitivity or resistance in individual patients may be desirable. This report demonstrates that the in vivo murine subrenal capsule assay was an efficient, sensitive method for retrospectively predicting the clinical response of squamous cell carcinomas of the head and neck to chemotherapy. Twenty‐five courses of chemotherapy in 22 patients were compared to responses in the in vivo assay. The assay correctly identified sensitivity to chemotherapy in 86% of clinically responding patients. The specificity of the assay was 78%. A 60% efficiency for predicting clinical response and a 93% efficiency for predicting clinical resistance were demonstrated. Eighty percent of the results were correctly classified. The murine subrenal capsule assay has potential in planning of chemotherapy for selected patients.
Thrombolysis with systemically administered t‐PA in a new venous thrombosis model
Authors: Hayden Richard E. , Mclear Patrick W. , Phillips John G. , Dawson Steven M.
Published: October 2006

Early thrombosis of either the arterial or venous supply of a free flap or island pedicle flap results in total flap necrosis. Until very recently, the only option for flap salvage was surgical intervention and, often, revision of the vascular pedicle. Current advances in the pharmacologic treatment of coronary artery and deep leg vein thrombosis have kindled interest in the field of reconstructive surgery for pharmacologic treatment of thromboses that compromise flaps.

In the past, there has been research on the local and systemic administration of thrombolytic agents for lysis of experimentally induced thrombi in various animal models. A new venous inversion graft thrombosis model is presented here, which possesses many advantages over previously employed research models. This study demonstrates thrombolysis with systemically administered tissue plasminogen activator (t‐PA) in this model.
Primary squamous cell carcinoma of the parotid gland
Authors: Sterman Bruce M. , Kraus Dennis H. , Sebek Bruce A. , Tucker Harvey M.
Published: September 2006

Primary squamous cell carcinoma of the parotid gland is an uncommon malignancy. It can be diagnosed only after squamous cell carcinoma metastatic to the parotid gland has been excluded. Histologic evaluation must differentiate primary squamous cell carcinoma from high‐grade muco‐epidermoid carcinoma or adenocarcinoma. Retrospective review of parotid gland neoplasms seen in the Department of Otolaryngology and Communicative Disorders between 1972 and 1987 identified eight cases for an incidence of 1.8%. The majority of these patients had advanced disease and were treated with both surgery and radiation therapy. Fifty percent of the cases demonstrated no evidence of disease at an average follow‐up of 29 months.
The neurofasciocutaneous radial forearm flap in head and neck reconstruction: A preliminary report
Authors: Urken Mark L. , Weinberg Hubert , Vickery Carlin , Biller Hugh F.
Published: September 2006

The radial forearm free flap has achieved considerable popularity as a reconstructive technique due to its thin, pliable tissue and long vascular pedicle. The successful use of this flap as a carrier of a vascularized nerve to bridge motor nerve gaps and as a sensate flap has not been previously reported in head and neck reconstruction. The superficial branch of the radial nerve was used as a vascularized nerve graft to bridge a facial nerve defect following radical parotidectomy. The medial and lateral antebrachial cutaneous nerves were used to re‐establish sensation in a reconstructed pharyngeal mucosal defect. The published clinical and experimental studies on vascularized nerves and sen‐sate flaps are reviewed in detail.
Squamous carcinoma of the head and neck in organ transplant recipients: Possible role of oncogenic viruses
Authors: Bradford Carol R. , Hoffman Henry T. , Wolf Gregory T. , Carey Thomas E. , Baker Shan R. , Mcclatchey Kenneth D.
Published: September 2006

A consistently increased incidence of malignancies in renal transplant recipients has been attributed to the effect of chronic immunosuppression required to prevent transplant rejection. Tumors arising in such patients offer a unique opportunity to study the interactions of the immune system and tumor development. A series of three cases of head and neck squamous cell carcinoma arising in patients after renal, cardiac, or bone marrow transplantation are reported. Patient ages at tumor diagnosis were 18, 29, and 53 years, respectively. Time from transplant to diagnosis of tumor ranged from 7 months to 12 years. Only the youngest patient lacked a history of exposure to the traditional predisposing factors of tobacco and alcohol use. Histo‐pathologic examination in all three tumors showed features of koilocytosis with hyperkeratosis and parakeratosis suggestive of papillomavirus infection. Squamous carcinoma cells from one of these patients have been successfully established in cell culture. Immune system impairments secondary to the use of antirejection drugs could allow the expression of oncogenic viruses. A recent report of human papillomavirus (HPV) DNA in a primary and metastatic perianal squamous cell carcinoma from a renal transplant recipient, as well as the reported presence of HPV in benign and malignant neoplasms of the upper aerodigestive tract suggests that HPV infection could play a role in the development of squamous carcinomas in transplant recipients. Further studies of HPV invection in cultured cell lines derived from head and neck tumors occurring in immunosup‐pressed patients are needed to define this relationship.
Clinical and radiological outcome of total hip replacement five years after pamidronate therapy
Authors: Shetty N. , Hamer A. J. , Stockley I. , Eastell R. , Willkinson J. M.
Published: September 2006

Bisphosphonates reduce peri-prosthetic bone loss in the short term after total hip replacement but the mid- and longer term effects are not known. The aims of this randomised trial were to examine the effect of a single dose of 90 mg of pamidronate on the clinical and radiological outcome and peri-prosthetic bone mineral density in 50 patients (56 hips) over a five-year period, following total hip replacement.

At five years, 37 patients (42 hips) returned for assessment. The Harris hip scores were similar in the pamidronate and placebo groups throughout the study. Also at five years, four patients, two from each group had osteolytic lesions on plain radiography. These were located around the acetabular component in three patients and in the femoral calcar in one. The femoral and acetabular peri-prosthetic bone mineral density in the pamidronate group and the control group was similar at five years.

Pamidronate given as a single post-operative dose does not appear to influence the clinical outcome or prevent the development of osteolytic lesions at five years after total hip replacement.
Treatment of idiopathic club foot using the Ponseti method
Authors: Changulani M. , Garg N. K. , Rajagopal T. S. , Bass A. , Nayagam S. N. , Sampath J. , Bruce C. E.
Published: September 2006

We report our initial experience of using the Ponseti method for the treatment of congenital idiopathic club foot.

Between November 2002 and November 2004 we treated 100 feet in 66 children by this method. The standard protocol described by Ponseti was used except that, when necessary, percutaneous tenotomy of tendo Achillis were performed under general anaesthesia in the operating theatre and not under local anaesthesia in the out-patient department. The Pirani score was used for assessment and the mean follow-up time was 18 months (6 to 30).

The results were also assessed in terms of the number of casts applied, the need for tenotomy of tendo Achillis and recurrence of the deformity. Tenotomy was required in 85 of the 100 feet. There was a failure to respond to the initial regimen in four feet which then required extensive soft-tissue release. Of the 96 feet which responded to initial casting, 31 (32%) had a recurrence, 16 of which were successfully treated by repeat casting and/or tenotomy and/or transfer of the tendon of tibialis anterior. The remaining 15 required extensive soft-tissue release. Poor compliance with the foot-abduction orthoses (Denis Browne splint) was thought to be the main cause of failure in these patients.
A score for predicting salvage and outcome in Gustilo type-IIIA and type-IIIB open tibial fractures
Authors: Rajasekaran S. , Babu J. Naresh , Dheenadhayalan J. , Shetty A. P. , Sundararajan S. R. , Kumar M. , Rajasabapathy S.
Published: September 2006

Limb-injury severity scores are designed to assess orthopaedic and vascular injuries. In Gustilo type-IIIA and type-IIIB injuries they have poor sensitivity and specificity to predict salvage or outcome.

We have designed a trauma score to grade the severity of injury to the covering tissues, the bones and the functional tissues, grading the three components from one to five. Seven comorbid conditions known to influence the management and prognosis have been given a score of two each. The score was validated in 109 consecutive open injuries of the tibia, 42 type-IIIA and 67 type-IIIB. The total score was used to assess the possibilities of salvage and the outcome was measured by dividing the injuries into four groups according to their scores as follows: group I scored less than 5, group II 6 to 10, group III 11 to 15 and group IV 16 or more.

A score of 14 to indicate amputation had the highest sensitivity and specificity. Our trauma score compared favourably with the Mangled Extremity Severity score in sensitivity (98% and 99%), specificity (100% and 17%), positive predictive value (100% and 97.5%) and negative predictive value (70% and 50%), respectively. A receiver-operating characteristic curve constructed for 67 type-IIIB injuries to assess the efficiency of the scores to predict salvage, showed that the area under the curve for this score was better (0.988 (± 0.013 sem)) than the Mangled Extremity Severity score (0.938 (± 0.039 sem)). All limbs in group IV and one in group III underwent amputation. Of the salvaged limbs, there was a significant difference in the three groups for the requirement of a flap for wound cover, the time to union, the number of surgical procedures required, the total days as an in-patient and the incidence of deep infection (p < 0.001 for all). The individual scores for covering and functional tissues were also found to offer specific guidelines in the management of these complex injuries.

The scoring system was found to be simple in application and reliable in prognosis for both limb-salvage and outcome measures in type-IIIA and type-IIIB open injuries of the tibia.
Principles of fixation of osteoporotic fractures
Authors: Giannoudis P. V. , Schneider E.
Published: September 2006

Despite advances in the prevention and treatment of osteoporotic fractures, their prevalence continues to increase. Their operative treatment remains a challenge for the surgeon, often with unpredictable outcomes. This review highlights the current aspects of management of these fractures and focuses on advances in implant design and surgical technique.
A custom-made prosthesis attached to an existing femoral component for the treatment of peri- and sub-prosthetic fracture
Authors: Tillman R. , Kalra S. , Grimer R. , Carter S. , Abudu A.
Published: September 2006

Peri- and sub-prosthetic fractures, or pathological fractures below an existing well-fixed femoral component, with or without an ipsilateral knee replacement, present a difficult surgical challenge.

We describe a simple solution, in which a custom-made prosthesis with a cylindrical design is cemented proximally to the stem of an existing, well-fixed femoral component. This effectively treats the fracture without sacrificing the good hip. We describe five patients with a mean age of 73 years (60 to 81) and a mean follow-up of 47 months (6 to 108).

The mean overlap of the prosthesis over the femoral component was 7.5 cm (5.5 to 10). There have been no mechanical failures, no new infections and no re-operations. We suggest that in highly selected cases, in which conventional fixation is not feasible, this technique offers a durable option and avoids the morbidity of a total femoral replacement.
Comparison between external fixation and sliding hip screw in the management of trochanteric fracture of the femur in Nepal
Authors: Karn N. K. , Singh G. K. , Kumar P. , Shrestha B. , Singh M. P. , Gowda M. Jayaram
Published: September 2006

We conducted a randomised controlled trial to compare external fixation of trochanteric fractures of the femur with the more costly option of the sliding hip screw. Patients in both groups were matched for age (mean 67 years, 50 to 100) and gender. We excluded all pathological fractures, patients presenting at more than one week, fractures with subtrochanteric extension or reverse obliquity, multiple fractures or any bone and joint disease interfering with rehabilitation. The interval between injury and operation, the duration of surgery, the amount of blood loss, the length of hospital stay and the cost of treatment were all significantly higher in the sliding hip screw group (p < 0.05). The time to union, range of movement, mean Harris hip scores and Western Ontario and McMaster University knee scores were comparable at six months. The number of patients showing shortening or malrotation was too small to show a significant difference between the groups. Pin-track infection occurred in 18 patients (60%) treated with external fixation, whereas there was a single case of wound infection (3.3%) in the sliding hip screw group.
Isolated tuberculosis of the coccyx
Authors: Kumar A. , Varshney M. K. , Trikha V. , Khan S. A.
Published: September 2006

Vertebral disease constitutes approximately 50% of all skeletal tuberculosis. We describe a patient who developed a discharging sinus at the tip of the coccyx. Extensive examination revealed isolated tuberculosis of the coccyx. Although rare, the condition should be suspected in patients presenting with a chronic sinus in the sacrococcygeal area and a lytic lesion in the coccyx on CT or MRI, particularly in the developing world.
Obesity and joint replacement
Authors: Horan F.
Published: September 2006

There has been considerable discussion as to the influence of obesity on the indications for, and the outcome after, joint replacement. Attempts have been made to withhold funding for such procedures in those who are overweight. What is the justification for this? This editorial examines the current evidence concerning the influence of obesity on joint replacement and suggests that it is only in the morbidly obese, with a body mass index > 40 kg/m2, that significant contraindications to operation are present.
Bio Imaging of Intracellular NO Production in Single Bone Cells After Mechanical Stimulation
Authors: Vatsa Aviral , Mizuno Daisuke , Smit Theo H , Schmidt Christoph F , MacKintosh Fred C , Klein-Nulend Jenneke
Published: September 2006

We show the intracellular upregulation of NO production after mechanical stimulation, an essential chemical signal in bone remodeling. This is done in real time using the fluorescent chromophore DAR-4M AM. Differences in cellular response to mechanical stimulation of different regions of a single cell were observed.

Introduction: Osteocytes are the most abundant bone cells that are believed to be the mechanosensors of bone, responding to mechanical stresses in interstitial fluid flow through the canaliculi. Under mechanical load, chemical signals such as NO play a key role in the activity of osteoblasts/osteoclasts that regulate bone remodeling. Despite the importance of NO in signaling, its real-time detection has proved challenging. This is largely because of the short NO half-life (typically ∼0.1–5 s). Here, we show the upregulation of intracellular NO production in single osteocytes under localized mechanical stimulation.

Materials and Methods: We used the chromophore DAR-4M AM for NO detection. This is loaded into surface-attached MLO-Y4 osteocyte-like and MC3T3-E1 osteoblast-like cells that are subjected to a localized mechanical stimulation using optical tweezers or a microneedle tip. DAR-4M AM is membrane-permeable and chelates NO, forming a stable, fluorescent compound, which is visible with a rhodamine filter.

Results: Nonstimulated MLO-Y4 and MC3T3-E1 cells showed basal NO production levels, as indicated by a gradual increase in their fluorescence intensity. Localized mechanical stimulation of single MC3T3-E1 cells and MLO-Y4 cells by optical tweezers (150–550 pN, 0.5–3 Hz, 1 minute) showed a nearly 15–30% increase, whereas MLO-Y4 cells stimulated by a microneedle (10–20 nN, 1 minute) showed nearly 15–16% increase relative to their nonstimulated state. Furthermore, stimulation of a single cell process by a microneedle resulted in a 2–10% increase in the fluorescence intensity.

Conclusions: NO is essential for mechanically induced bone remodeling and is a meaningful parameter for measuring bone cell activation after mechanical loading. Here we show NO upregulation in individual bone cells after a localized mechanical stimulation. We also show that both the cell body and the cell processes might be involved in mechanosensing. This technique allows characterization of the mechanosensitivity of different parts of a single osteocyte. This opens up the possibility to uncover the complexities and function of single osteocytes in the dynamic process of bone remodeling.
PTH-Induced Actin Depolymerization Increases Mechanosensitive Channel Activity to Enhance Mechanically Stimulated 2+ Signaling in Osteoblasts*
Authors: Zhang Jinsong , Ryder Kimberly D , Bethel Jody A , Ramirez Raymund , Duncan Randall L
Published: September 2006

Disruption of the actin cytoskeleton with cytochalasin D enhanced the mechanically induced increase in intracellular Ca2+ ([Ca2+]i) in osteoblasts in a manner similar to that of PTH. Stabilization of actin with phalloidin prevented the PTH enhanced [Ca2+]i response to shear. Patch-clamp analyses show that the MSCC is directly influenced by alterations in actin integrity.

Introduction: PTH significantly enhances the fluid shear-induced increase in [Ca2+]i in osteoblasts, in part, through increased activation of both the mechanosensitive, cation-selective channel (MSCC) and L-type voltage-sensitive Ca2+ channel (L-VSCC). Both stimuli have been shown to produce dynamic changes in the organization of the actin cytoskeleton. In this study, we examined the effects of alterations in actin polymerization on [Ca2+]i and MSCC activity in MC3T3-E1 and UMR-106.01 osteoblasts in response to shear ± PTH pretreatment.

Materials and Methods: MC3T3-E1 or UMR-106.01 cells were plated onto type I collagen–coated quartz slides, allowed to proliferate to 60% confluency, and mounted on a modified parallel plate chamber and subjected to 12 dynes/cm2. For patch-clamp studies, cells were plated on collagen-coated glass coverslips, mounted on the patch chamber, and subjected to pipette suction. Modulators of actin cytoskeleton polymerization were added 30 minutes before the experiments, whereas channel inhibitors were added 10 minutes before mechanical stimulation. All drugs were maintained in the flow medium for the duration of the experiment.

Results and Conclusions: Depolymerization of actin with 1–5 μM cytochalasin D (cyto D) augmented the peak [Ca2+]i response and increased the number of cells responding to shear, similar to the increased responses induced by pretreatment with 50 nM PTH. Stabilization of actin with phalloidin prevented the PTH enhanced [Ca2+]i response to shear. Inhibition of the MSCC with Gd3+ significantly blocked both the peak Ca2+ response and the number of cells responding to shear in cells pretreated with either PTH or cyto D. Inhibition of the L-VSCC reduced the peak [Ca2+]i response to shear in cells pretreated with PTH, but not with cyto D. Patch-clamp analyses found that addition of PTH or cyto D significantly increased the MSCC open probability in response to mechanical stimulation, whereas phalloidin significantly attenuated the PTH-enhanced MSCC activation. These data indicate that actin reorganization increases MSCC activity in a manner similar to PTH and may be one mechanism through which PTH may reduce the mechanical threshold of osteoblasts.
Effects of Strontium on Bone Strength, Density, Volume, and Microarchitecture in Laying Hens
Authors: Shahnazari Mohammad , Sharkey Neil A , Fosmire Gary J , Leach Roland M
Published: September 2006

Strontium has been reported to have beneficial effects on bone. Treatment of laying hens, which are susceptible to osteoporosis and bone fracture, with strontium increased DXA measurements of BMD and BMC and μCT measurements of bone volume and microarchitecture and improved the mechanical performance of whole bone, but had no effect on the estimated material properties of the bone tissue.

Introduction: Strontium (Sr) has been reported to dissociate bone remodeling and have positive influences on bone formation. We supplemented the diet of laying hens, which are susceptible to osteoporosis and bone fracture, with Sr to study the capacity of the element to improve bone mechanical integrity and resistance to fracture.

Materials and Methods: Increasing dosages of Sr (0, 3000, 4500, and 6000 ppm) were fed to 196 13-week-old pullets for 11 months. BMD and BMC, as measured by conventional and DXA methods, microarchitectural parameters derived from μCT, and structural and material properties as determined by three-point bending test, were studied. Calcium (Ca), phosphorus (P), and Sr levels in plasma and bone, as well as egg output, shell quality, and composition, were assessed.

Results: Sr concentrations in plasma and bone increased in a dose-dependent manner without affecting Ca and P. Treatment with Sr increased BMD and BMC as measured by DXA, increased cortical and medullary bone volume, trabecular thickness, number, and surface, and improved whole bone ultimate load, but had no effect on the estimated material properties of diaphyseal bone. Sr also increased the ash content of eggshells and did not affect egg output and shell quality.

Conclusions: Sr supplementation induced large positive effects on bone density, volume, and microarchitecture as measured by radiographic methods. Sr treatment also improved the structural strength of diaphyseal bone but had no effect on the estimated material properties of the bone tissue.
RANKL Treatment Releases the Negative Regulation of the Poly(ADP-Ribose) Polymerase-1 on Tcirg1 Gene Expression During Osteoclastogenesis
Authors: Beranger Guillaume E , Momier David , Rochet Nathalie , Quincey Danielle , Guigonis Jean-Marie , Samson Michel , Carle Georges F , Scimeca Jean-Claude
Published: September 2006

The Tcirg1 gene encodes the osteoclast-specific a3 isoform of the V-ATPase a subunit. Using the mouse osteoclastic model RAW264.7 cells, we studied Tcirg1 gene expression, and we identified PARP-1 as a transcriptional repressor negatively regulated by RANKL during osteoclastogenesis.

Introduction: The TCIRG1 gene encodes the a3 isoform of the V-ATPase a subunit, and mutations at this locus account for ∼60% of infantile malignant osteopetrosis cases. Using RAW264.7 cells as an osteoclastic differentiation model, we undertook a transcriptional study of the mouse Tcirg1 gene focused on the 4-kb region upstream of the transcription starting point.

Materials and Methods: The promoter activity of serial-deletion fragments of the Tcirg1 gene promoter was monitored throughout the RAW264.7 cell differentiation process. We next performed EMSA, UV cross-linking, affinity purification, mass spectrometry analysis, gel supershift, and siRNA transfection experiments to identify the factor(s) interacting with the promoter.

Results: The −3946/+113 region of the mouse Tcirg1 gene displayed a high basal promoter activity, which was enhanced by RANKL treatment of RAW264.7 cells. Constructs deleted up to −1589 retained this response to RANKL. A deletion up to −1402 induced a 3-fold enhancement of the basal activity, whereas RANKL response was not affected. EMSA experiments led us to identify within the −1589/−1402 region, a 10-nucleotide sequence, which bound a nuclear protein present in nondifferentiated RAW264.7 cells. This interaction was lost using nuclear extracts derived from RANKL-treated cells. Affinity purification followed by mass spectrometry analysis and gel supershift assay allowed the identification of poly(ADP-ribose) polymerase-1 (PARP-1) as this transcriptional repressor, whereas Western blot experiments revealed the cleavage of the DNA-binding domain of PARP-1 on RANKL treatment. Finally, both PARP-1 depletion after siRNA transfection and RAW264.7 cell treatment by an inhibitor of PARP-1 activity induced an increase of a3 mRNA expression.

Conclusions: We provide evidence that the basal transcription activity of the Tcirg1 gene is negatively regulated by the binding of PARP-1 protein to its promoter region in mouse pre-osteoclast. On RANKL treatment, PARP-1 protein is cleaved and loses its repression effect, allowing an increase of Tcirg1 gene expression that is critical for osteoclast function.
Enhanced Osteoclastogenesis in 4-1BB—Deficient Mice Caused by Reduced Interleukin-10
Authors: Shin Hyun-Hee , Lee Ji-Eun , Lee Eun A , Kwon Byoung Se , Choi Hye-Seon
Published: September 2006

Enhanced osteoclastogenesis was observed in bone marrow—derived macrophage cells from 4-1BB—deficient mice than in those from wildtype mice. 4-1BB and 4-1BB ligand interaction may play a role at a certain stage of osteoclast formation through increased level of IL-10, a negative regulator of osteoclastogenesis.

Introduction: 4-1BB is an inducible T-cell costimulatory molecule and a member of the TNF receptor family. The expression pattern of 4-1BB and 4-1BB ligand (4-1BBL) has suggested that 4-1BB plays a role not only in various responses related to innate immunity but also in bone metabolism.

Materials and Methods: Osteoclast formation was evaluated in bone marrow—derived macrophage cells (BMMs) from wildtype and 4-1BB—deficient (4-1BB−/−) mice. Expression of interleukin-10 (IL-10) during osteoclast formation was analyzed at the mRNA and protein levels.

Results: Expression of IL-10 was higher in RANKL-stimulated wildtype BMMs than 4-1BB−/− BMMs. When 4-1BBL was stimulated with 4-1BB—Fc fusion protein, the expression of IL-10 in BMMs increased. Neutralization of IL-10 was not as effective in preventing inhibition by IL-10 of osteoclast differentiation in 4-1BB−/− BMMs as in wildtype BMMs. When IL-10 was added to the culture medium, osteoclast formation was inhibited more efficiently in the 4-1BB−/− BMMs than in the wildtype BMMs.

Conclusions: Interaction of 4-1BB and 4-1BBL stimulates IL-10 production through 4-1BBL signaling. 4-1BBL plays a role at a certain stage of osteoclast formation, and IL-10 may mediate this effect. The elevated level of osteoclastogenesis in 4-1BB−/− BMMs may thus be caused, in part, by a lower level of IL-10.
Volumetric BMD and Vascular Calcification in Middle-Aged Women: The Study of Women's Health Across the Nation
Authors: Farhat Ghada N , Cauley Jane A , Matthews Karen A , Newman Anne B , Johnston Janet , Mackey Rachel , Edmundowicz Daniel , Sutton-Tyrrell Kim
Published: September 2006

The association of spine vBMD with AC and CAC was studied in a biracial cohort of 490 middle-aged women in the Study of Women's Health Across the Nation. Lower vBMD was related to high AC, but not to CAC, independent of age and shared risk factors between osteoporosis and cardiovascular disease.

Introduction: This analysis studied the association of spine volumetric BMD (vBMD) with aortic (AC) and coronary artery (CAC) calcification in middle-aged women and evaluated whether such associations were independent of age and shared risk factors between osteoporosis and cardiovascular disease (CVD) or explained by endogenous estradiol levels.

Materials and Methods: Vascular calcification and trabecular vBMD of the spine were measured using electron-beam CT in 490 women free from clinical CVD in the Study of Women's Health Across the Nation. Women were 45–58 years of age, 61% were white, and 64% were perimenopausal. Calcification scores were categorized into three levels (no AC, N =146; moderate AC, scores =1–74, N =221; high AC, N =123; no CAC, N =256; moderate CAC, score =1–7.54, N =111; high CAC, N =123). The highest categories were set at the 75th percentiles. Multinomial logistic regression was used to assess the association between vBMD (per SD) and the AC and CAC levels, with no calcification as the reference group.

Results: AC and CAC were detected in 70% and 48% of the population, respectively. Mean vBMD was 161.6 ± 37.2 (SD) mg/ml. vBMD was associated with high AC in unadjusted, age-adjusted, and risk factor—adjusted analysis. Per 1 SD decrease in vBMD, the adjusted odds of high AC compared with no AC was significantly increased by 68% (95% CI, 1.06–2.68). Estradiol did not influence this association. vBMD was related to high CAC in unadjusted (OR =1.35; 95% CI, 1.08–1.70) but not adjusted models. No associations of vBMD with moderate AC or CAC were observed.

Conclusion: Lower vBMD was related to high AC, but not to CAC, in a biracial cohort of healthy middle-aged women independent of age and shared risk factors between osteoporosis and CVD. Further research should study possible pathophysiological links between the two conditions and the potential for common preventive and therapeutic interventions.
Size-Corrected BMD Decreases During Peak Linear Growth: Implications for Fracture Incidence During Adolescence
Authors: Faulkner Robert A , Davison K Shawn , Bailey Donald A , Mirwald Robert L , Baxter-Jones Adam DG
Published: September 2006

Peak adolescent fracture incidence at the distal end of the radius coincides with a decline in size-corrected BMD in both boys and girls. Peak gains in bone area preceded peak gains in BMC in a longitudinal sample of boys and girls, supporting the theory that the dissociation between skeletal expansion and skeletal mineralization results in a period of relative bone weakness.

Introduction: The high incidence of fracture in adolescence may be related to a period of relative skeletal fragility resulting from dissociation between bone expansion and bone mineralization during the growing years. The aim of this study was to examine the relationship between changes in size-corrected BMD (BMDsc) and peak distal radius fracture incidence in boys and girls.

Materials and Methods: Subjects were 41 boys and 46 girls measured annually (DXA; Hologic 2000) over the adolescent growth period and again in young adulthood. Ages of peak height velocity (PHV), peak BMC velocity (PBMCV), and peak bone area (BA) velocity (PBAV) were determined for each child. To control for maturational differences, subjects were aligned on PHV. BMDsc was calculated by first regressing the natural logarithms of BMC and BA. The power coefficient (pc) values from this analysis were used as follows: BMDsc =BMC/BApc.

Results: BMDsc decreased significantly before the age of PHV and then increased until 4 years after PHV. The peak rates in radial fractures (reported from previous work) in both boys and girls coincided with the age of negative velocity in BMDsc; the age of peak BA velocity (PBAV) preceded the age of peak BMC velocity (PBMCV) by 0.5 years in both boys and girls.

Conclusions: There is a clear dissociation between PBMCV and PBAV in boys and girls. BMDsc declines before age of PHV before rebounding after PHV. The timing of these events coincides directly with reported fracture rates of the distal end of the radius. Thus, the results support the theory that there is a period of relative skeletal weakness during the adolescent growth period caused, in part, by a draw on cortical bone to meet the mineral demands of the expanding skeleton resulting in a temporary increased fracture risk.
Premedication for Nonemergent Neonatal Intubations: A Randomized, Controlled Trial Comparing Atropine and Fentanyl to Atropine, Fentanyl, and Mivacurium
Authors: Roberts Kari D. , Leone Tina A. , Edwards William H. , Rich Wade D. , Finer Neil N.
Published: October 2006

OBJECTIVE. The purpose of this work was to investigate whether using a muscle relaxant would improve intubation conditions in infants, thereby decreasing the incidence and duration of hypoxia and time and number of attempts needed to successfully complete the intubation procedure.

PATIENTS/METHODS. This was a prospective, randomized, controlled, 2-center trial. Infants requiring nonemergent intubation were randomly assigned to receive atropine and fentanyl or atropine, fentanyl, and mivacurium before intubation. Incidence and duration of hypoxia were determined at oxygen saturation thresholds of ≤85%, ≤75%, ≤60%, and ≤40%. Videotape was reviewed to determine the time and number of intubation attempts and duration of action of mivacurium.

RESULTS. Analysis of 41 infants showed that incidence of oxygen saturation ≤60% of any duration was significantly less in the mivacurium group (55% vs 24%). The incidence of saturation level of any duration ≤85%, 75%, and 40%; cumulative time ≥30 seconds; and time below the thresholds were not significantly different. Total procedure time (472 vs 144 seconds) and total laryngoscope time (148 vs 61 seconds) were shorter in the mivacurium group. Successful intubation was achieved in ≤2 attempts significantly more often in the mivacurium group (35% vs 71%).

CONCLUSIONS. Premedication with atropine, fentanyl, and mivacurium compared with atropine and fentanyl without a muscle relaxant decreases the time and number of attempts needed to successfully intubate while significantly reducing the incidence of severe desaturation. Premedication including a short-acting muscle relaxant should be considered for all nonemergent intubations in the NICU.
N-Cadherin Is Expressed by Putative Stem/Progenitor Cells and Melanocytes in the Human Limbal Epithelial Stem Cell Niche
Authors: Hayashi Ryuhei , Yamato Masayuki , Sugiyama Hiroaki , Sumide Taizo , Yang Joseph , Okano Teruo , Tano Yasuo , Nishida Kohji
Published: September 2006

Corneal epithelial stem cells are known to be localized to the basal layer of the limbal epithelium, providing a model system for epithelial stem cell biology; however, the mechanisms regarding the maintenance of these stem cells in their specialized niche remain poorly understood. N-cadherin is a member of the classic cadherin family and has previously been demonstrated to be expressed by hematopoietic stem cells. In the present study, we demonstrate that N-cadherin is expressed by putative stem/progenitor cells, as well as melanocytes, in the human limbal epithelial stem cell niche. In addition, we demonstrate that upon in vitro culture using 3T3 feeder layers, loss of N-cadherin expression occurs with cell proliferation. These results indicate that N-cadherin may be a critical cell-to-cell adhesion molecule between corneal epithelial stem/progenitor cells and their corresponding niche cells in the limbal epithelium.
The Cell Surface Glycosphingolipids SSEA-3 and SSEA-4 Are Not Essential for Human ESC Pluripotency
Authors: Brimble Sandii N. , Sherrer Eric S. , Uhl Elizabeth W. , Wang Elaine , Kelly Samuel , Merrill Alfred H. , Robins Allan J. , Schulz Thomas C.
Published: September 2006

Pluripotent cells can be isolated from the human blastocyst and maintained in culture as self-renewing, undifferentiated, human ESCs (hESCs). These cells are a valuable model of human development in vitro and are the focus of substantial research aimed at generating differentiated populations for cellular therapies. The extracellular markers that have been used to characterize hESCs are primarily carbohydrate epitopes on proteoglycans or sphingolipids, such as stage-specific embryonic antigen (SSEA)-3 and -4. The expression of SSEA-3 and -4 is tightly regulated during preimplantation development and on hESCs. Although this might imply a molecular function in undifferentiated cells, it has not yet been tested experimentally. We used inhibitors of sphingolipid and glycosphingolipid (GSL) biosynthesis to block the generation of SSEA-3 and -4 in hESCs. Depletion of these antigens and their precursors was confirmed using immunostaining, flow cytometry, and tandem mass spectroscopy. Transcriptional analysis, immunostaining, and differentiation in vitro and in teratomas indicated that other properties of pluripotency were not noticeably affected by GSL depletion. These experiments demonstrated that the GSLs recognized as SSEA-3 and -4 do not play critical functional roles in maintaining the pluripotency of hESCs, but instead suggested roles for this class of molecules during cellular differentiation.
Basal Cells of the Human Adult Airway Surface Epithelium Retain Transit-Amplifying Cell Properties
Authors: Hajj Rodolphe , Baranek Thomas , Le Naour Richard , Lesimple Pierre , Puchelle Edith , Coraux Christelle
Published: September 2006

In numerous airway diseases, such as cystic fibrosis, the epithelium is severely damaged and must regenerate to restore its defense functions. Although the human airway epithelial stem cells have not been identified yet, we have suggested recently that epithelial stem/progenitor cells exist among both human fetal basal and suprabasal cell subsets in the tracheal epithelium. In this study, we analyzed the capacity of human adult basal cells isolated from human adult airway tissues to restore a well-differentiated and functional airway epithelium. To this end, we used the human-specific basal cell markers tetraspanin CD151 and tissue factor (TF) to separate positive basal cells from negative columnar cells with a FACSAria cell sorter. Sorted epithelial cells were seeded into epithelium-denuded rat tracheae that were grafted subcutaneously in nude mice and on collagen-coated porous membranes, where they were grown at the air-liquid interface. Sorted basal and columnar populations were also analyzed for their telomerase activity, a specific transit-amplifying cell marker, by the telomeric repeat amplification protocol assay. After cell sorting, the pure and viable CD151/TF-positive basal cell population proliferated on plastic and adhered on epithelium-denuded rat tracheae, as well as on collagen-coated porous membranes, where it was able to restore a fully differentiated mucociliary and functional airway epithelium, whereas viable columnar negative cells did not. Telomerase activity was detected in the CD151/TF-positive basal cell population, but not in CD151/TF-negative columnar cells. These results demonstrate that human adult basal cells are at least airway surface transit-amplifying epithelial cells.
A description of long‐term environmental monitoring and assessment programs at two U.S. Department of Energy sites
Authors: Gray Robert H.
Published: October 2006

The U.S. Department of Energy's Hanford Site was established in southeastern Washington during the 1940s to produce plutonium, and the Pantex plant in Texas (used to load conventional ammunition shells and bombs) was rehabilitated in the 1950s to assemble nuclear weapons using the plutonium produced at Hanford. Current concentrations of airborne radionuclides around the perimeters of both sites are below applicable guidelines. Concentrations of radionuclides and nonradiological water quality in the Columbia River at Hanford and radiological and nonradiological water quality in the Ogallala Aquifer beneath the Pantex plant are also in compliance with applicable standards. Foodstuffs irrigated with river water downstream from Hanford show levels of radionuclides similar to those in foodstuffs from control areas. Levels of 137Cs and 90Sr in some on‐site Hanford wildlife samples and concentrations of radionuclides in soils and vegetation on and off site at both locations are typical of naturally occurring radioactivity and worldwide fallout. The potential dose received by a maximally exposed individual at both sites in 1994 was ≤0.05 mrem; the average per capita dose was ≤0.002 mrem. By virtue of its size, restricted access, and conservative use of undeveloped land, the Hanford Site has become a sanctuary for plant and animal populations that have been eliminated from, or greatly reduced on, surrounding agricultural and range lands. The Hanford Reach of the Columbia River and its islands and the Pantex Plant with its playas serve as refuges for raptorial birds and migratory waterfowl. In addition, the Hanford Reach serves as a migration route for several species of salmon, and chinook salmon and steelhead trout spawn there. Bald eagles congregate along the Hanford Reach in the fall and winter to feed on the spawned‐out carcasses of salmon and wintering waterfowl.
Adsorption–desorption of trichlorophenol in water–soil systems
Authors: Sabbah Isam , Rebhun Menahem
Published: October 2006

Adsorption‐desorption of trichlorophenol (TCP) on calcium montmorillonite (pure clay), prepared montmorillonite‐humic complexes, and natural soils were investigated. Adsorption followed a Freundlich‐type isotherm between 5 and 30 mg/L of TCP, and linear adsorption isotherms were obtained for equilibrium concentrations up to 7 mg/L. Linear correlations were obtained between sorption constants (Kp) and organic carbon (foc) and clay‐mineral content (fm). In the montmorillonite and montmorillonite‐humic complex systems, adsorption and desorption isotherms coincided and no hysteresis was observed. Strong hysteresis was observed in adsorption‐desorption in natural soils. The different behavior in adsorption‐desorption was explained by the different nature of organic matter, its different structure, and interaction with the mineral fraction. Because trichlorophenol is a weak acid, adsorption highly depended on pH and could be predicted by combining the adsorption constant of undissociated TCP and the dissociation constant of phenol‐phenolate.
Nitrogen fixation in an aerated stabilization basin treating bleached kraft mill wastewater
Authors: Clark Thomas A. , Dare Peter H. , Bruce Mary E.
Published: October 2006

Pulp and paper mill wastewaters normally contain very low concentrations of nitrogen, but many pulp mill aerated stabilization basin (ASB) treatment systems are operated with no supplemental nitrogen, while achieving high biochemical oxygen demand (BOD5) removal. A nutrient mass‐balance study, undertaken across one of the aerated lagoons in such an ASB system, found that a substantial input of nitrogen was occurring within this pond, amounting to approximately 600 kg nitrogen per day. Direct measurement of acetylene reduction (nitrogen fixation), both in the pond and in a laboratory simulation, showed that bacterial nitrogen fixation was responsible for the input of nitrogen. Most of the nitrogen for bacterial growth within the lagoon was supplied by atmospheric nitrogen fixation, and, consequently, nitrogen fixation was critical to overall system effectiveness. It appears that elevated dissolved oxygen concentrations may inhibit fixation. This may be an important constraint on the operation of such ASB systems, especially for the first lagoon, and represents a potential change to current thinking. The implications of bacterial nitrogen fixation, with respect to the effective operation and control of kraft mill ASB systems, are discussed.
Study of the decomposition of four commercially available hydrogen peroxide solutions by Fenton's reagent
Authors: Aldershof Brian K. , Dennis Ronald M. , Kunitsky Craig J.
Published: October 2006

Four commercially available hydrogen peroxide solutions were decomposed by Fenton's reagent under nonadiabatic conditions to determine whether their decomposition rates would vary because of differences in the types and amounts of proprietary stabilizers added. The experimental plan used a 22 factorial design for each solution with two factors—concentration of hydrogen peroxide and ratio of hydrogen peroxide to ferrous iron—and two levels, high and low. Peroxide decomposition rates were modeled using Weibull survival curves, and the shape and scale parameters of these curves were estimated using nonlinear least‐squares regression. Estimates were then used in a multivariate analysis of covariance (MANCOVA) to determine whether there were any statistically significant differences among the decomposition rates of the four hydrogen peroxide solutions. The results of this analysis showed that there were none.