bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane‐associated estrogen receptor and caveolin‐1 are present in central nervous system myelin and oligodendrocyte plasma membranes
Authors: Arvanitis Dina N. , Wang Huimin , Bagshaw Richard D. , Callahan John W. , Boggs Joan M.
Published: February 2004

The estrogen receptor (ER) is a member of a superfamily of ligand‐regulated transcription factors that were thought to localize primarily to the nucleus; however, a membrane‐associated ER that can initiate rapid non‐genomic cell‐signaling events has been identified recently in various cells. The presence of the ER in myelin has not been reported although the nuclear form has been detected in oligodendrocytes. We have shown that an ER with similarities to ERβ is present in isolated central nervous system (CNS) myelin, the myelin sheath in spinal cord and brain sections, and the oligodendrocyte plasma membrane using two‐dimensional (2D) PAGE, mass spectrometry, peptide mass fingerprinting, Western blotting of 1D and 2D gels, and confocal microscopy. Caveolin‐1 was also shown to be present in isolated CNS myelin and oligodendrocyte plasma membranes, where it was partially colocalized with ER. After Triton X‐100 extraction of myelin, the ER was present in an insoluble low‐density glycosphingolipid‐enriched fraction and even more in a higher density fraction also containing caveolin and cytoskeletal elements, suggesting that the membrane form of ER may be associated with caveolin or the radial component of myelin. The discovery of the ER in the oligodendrocyte plasma membrane and within the myelin sheath indicates a potential role for estrogen in myelin maintenance or functions. © 2004 Wiley‐Liss, Inc.
High K+ and IGF‐1 protect cerebellar granule neurons via distinct signaling pathways
Authors: Zhong Jin , Deng Jixian , Huang Su , Yang Xianlin , Lee Wei‐Hua
Published: February 2004

In culture, cerebellar granule neurons die of apoptosis in serum‐free media containing a physiologic level of K+ but survive in a depolarizing concentration of K+ or when insulin‐like growth factor 1 (IGF‐1) is added. Both Akt/PKB activation and caspase‐3 inhibition were implicated as the underlying neuroprotective mechanisms. The duration of high K+, however, induced survival effects that outlasted its transient activation of Akt, and granule neurons derived from caspase‐3 knockout mice died to the same extent as did those from wild‐type mice, suggesting that additional mechanisms are involved. To delineate these survival mechanisms, we compared the activities of two major survival pathways after high K+‐induced depolarization or IGF‐1 stimulation. Although IGF‐1 promoted neuronal survival by activating its tyrosine kinase receptor, high K+ depolarization provided the same effect by increasing the Ca2+ influx through the L Ca2+ channel. Moreover, high K+‐induced depolarization resulted in sustained activation of MAP kinase, whereas IGF‐1 activated Akt in 4 hr. Inhibition of MEK (MAP kinase kinase) by either PD98059 or UO126 abolished the protective effect of high K+‐induced depolarization, but not that of IGF‐1, suggesting that activation of the MAP kinase pathway is necessary for high K+ neuroprotective effects. We demonstrated also that high K+‐induced depolarization, but not IGF‐1, increased phosphorylation of cAMP‐response element‐binding protein (CREB) and protein synthesis, both of which can be blocked by UO126. Overall, our findings suggested that high K+‐induced depolarization, unlike IGF‐1, promoted neuronal survival via activating MAP kinase, possibly by increasing CREB‐dependent transcriptional activation of specific proteins that promote neuronal survival. © 2004 Wiley‐Liss, Inc.
Characterization of a fast transient outward current in neocortical neurons from epilepsy patients
Authors: Rüschenschmidt C. , Köhling R. , Schwarz M. , Straub H. , Gorji A. , Siep E. , Ebner A. , Pannek H.W. , Tuxhorn I. , Wolf P. , Speckmann E.‐J.
Published: February 2004

A‐type currents powerfully modulate discharge behavior and have been described in a large number of different species and cell types. However, data on A‐type currents in human brain tissue are scarce. Here we have examined the properties of a fast transient outward current in acutely dissociated human neocortical neurons from the temporal lobe of epilepsy patients by using the whole‐cell voltage‐clamp technique. The A‐type current was isolated with a subtraction protocol. In addition, delayed potassium currents were reduced pharmacologically with 10 mM tetraethylammonium chloride. The current displayed an activation threshold of about −70 mV. The voltage‐dependent activation was fitted with a Boltzmann function, with a half‐maximal conductance at −14.8 ± 1.8 mV (n = 5) and a slope factor of 17.0 ± 0.5 mV (n = 5). The voltage of half‐maximal steady‐state inactivation was −98.9 ± 8.3 mV (n = 5), with a slope factor of −6.6 ± 1.9 mV (n = 5). Recovery from inactivation could be fitted monoexponentially with a time constant of 18.2 ± 7.5 msec (n = 5). At a command potential of +30 mV, application of 5 mM 4‐aminopyridine or 100 μM flecainide resulted in a reduction of A‐type current amplitude by 35% or 22%, respectively. In addition, flecainide markedly accelerated inactivation. Current amplitude was reduced by 31% with application of 500 μM cadmium. All drug effects were reversible. In conclusion, neocortical neurons from epilepsy patients express an A‐type current with properties similar to those described for animal tissues. © 2004 Wiley‐Liss, Inc.
Lymphoscintigraphic and intraoperative detection of the sentinel lymph node in breast cancer patients: The nuclear medicine perspective
Authors: Mariani Giuliano , Erba Paola , Villa Giuseppe , Gipponi Marco , Manca Gianpiero , Boni Giuseppe , Buffoni Ferdinando , Castagnola Franca , Paganelli Giovanni , Strauss H. William
Published: February 2004

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini‐invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. 99mTc‐labeled colloids with most of the particles in the 100–200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re‐examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94–97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T1a‐b breast cancers, with size ≤1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long‐term clinical outcome of patients. J. Surg. Oncol. 2004;85:112–122. © 2004 Wiley‐Liss, Inc.
Sentinel lymph node biopsy in breast cancer patients: The medical oncology perspective
Authors: Catzeddu Tiziana , Bertelli Gianfilippo , Del Mastro Lucia , Venturini Marco
Published: February 2004

Recent data indicates that the sentinel lymph node biopsy (SLNB) is a possible alternative to axillary lymph node dissection (ALND) in early breast cancer patients, with minimal risk of complications.

From the medical oncologist's point of view, the impact of SLNB on the management of patients should consider if SLNB is useful to choose adjuvant treatment, if it is adequate to provide local control, and what is the significance of lymph node micrometastases on treatment and staging. Lymph node involvement has always been recognised as the most important prognostic factor in early‐stage breast cancer, even if many other parameters have been evaluated in recent years. However, the lack of knowledge of nodal status in patients with false‐negative SLNB seems to result in an undertreatment in a very low percentage of patients. Adjuvant chemotherapy and hormonal therapy with tamoxifen are associated with an absolute reduction of the risk of recurrence and death both in node‐positive and in node‐negative patients, then if patients are treated with modern adjuvant systemic therapy, any effect associated with false negative SLN should be minimised.

The impact of axillary treatment on survival is still controversial, but in recent times axillary lymph node positivity is considered as an indicator for high risk of systemic diffusion of the disease rather than a possible origin of systemic metastases.

The significance of occult sentinel lymph node metastases detected by immunohistochemistry (IHC) or molecular biology on prognosis is still uncertain. The new version of the staging system of breast cancer has recognised the need for a standard diagnostic approach and of a nomenclature system which also takes SLNB into account. J. Surg. Oncol. 2004;85:129–132. © 2004 Wiley‐Liss, Inc.
Pathologic analysis of sentinel lymph nodes in melanoma patients: Current and future trends
Authors: Roberts Alice A. , Cochran Alistair J.
Published: February 2004

Sentinel lymph node dissection (SLND) has become the standard of care for the staging of clinically‐node negative melanomas and breast cancers. A large literature documents the efficacy of SLND in the staging of melanoma and breast cancer. The SLND has lower associated patient morbidity in comparison to elective node dissections that remove the closest regional‐draining node group. SLND has improved accuracy over traditional regional node dissection for the staging of melanoma. Currently, several multicenter trials are evaluating the prognostic significance of melanoma micrometastases in SLN detected by immunohistochemical and molecular methods. Pending trial outcome analysis, SLND has no proven effect on mortality. However, given the current oncologic emphasis on detection and removal of nodal tumor metastases, the technique has an important role in minimizing the invasiveness of tumor staging for melanoma and breast cancer. As long as lymph node metastases are used for staging solid malignancies, surgical pathologists are likely to encounter SLN excisional biopsies as a part of their routine practice. J. Surg. Oncol. 2004;85:152–161. © 2004 Wiley‐Liss, Inc.
Sentinel lymph node biopsy in melanoma patients: the medical oncologist's perspective
Authors: Queirolo Paola , Taveggia Paola , Gipponi Marco , Sertoli Mario Roberto
Published: February 2004

With the advent of sentinel node (sN) biopsy in melanoma patients, elective lymph node dissection (ELND) can be considered an exceeded procedure. Regardless of the possible therapeutic benefits, sN biopsy efficiently predicts prognosis avoiding the morbidity rate of ELND. The importance of the sN is underlined by multivariate analyses, which show that the sN status represents the most important prognostic factor influencing disease‐free and distant disease‐free survival in patients with stage I and II melanoma. Moreover, sN biopsy provides a minimally invasive method for identifying those patients with subclinical nodal metastasis who actually have stage III disease, with a very high risk of occult distant metastases and who may benefit by adjuvant therapy. J. Surg. Oncol. 2004;85:162–165. © 2004 Wiley‐Liss, Inc.
Prognostic value of sentinel lymph node biopsy in the pathologic staging of colorectal cancer patients
Authors: Bertoglio Sergio , Sandrucci Sergio , Percivale Pierluigi , Goss Matteo , Gipponi Marco , Moresco Luciano , Mussa Baudolino , Mussa Antonio
Published: February 2004

Background and Objectives

Over the last decade, lymphatic mapping and sentinel lymph node (sN) biopsy have greatly increased the possibility of identifying nodal metastasis in clinically node‐negative patients with melanoma and breast cancer, thus improving the accuracy of pathologic staging. Recently, sN biopsy has been applied also in colorectal cancer. This prospective study aimed to assess its feasibility and accuracy in predicting regional lymph nodes metastases in colorectal cancer patients as well as the impact on treatment decision‐making.

Materials and Methods

Lymphatic mapping was accomplished by means of blue dye, which was intraoperatively injected into the subserosa overlying the tumor site in 26 patients undergoing colorectal cancer surgery. Following bowel resection, the operative specimen was inspected to identify each blue‐stained node, the sN, which was sent separately to the pathologist. One half of each sN was examined by multiple 200 μm sections, while the second half was examined by standard bi‐valving technique with hematoxylin‐eosin (H&E) staining; all the other regional non‐sentinel nodes were routinely examined by standard bi‐valving technique and H&E staining.

Results

At least one sN was detected in 24 of 26 patients (92.3%); two patients with rectal cancer had no sN identified. Overall, 70 sN were retrieved into the operative specimens, with a mean of 2.9 sNs/patient, and 19 sNs were tumor‐positive. An agreement between sN and regional lymph‐node status was observed in 20 of 24 patients (83.4%). The sN was histologically negative in two of nine patients with positive regional nodes (sensitivity = 77.8%; false‐negative rate of 22.2%); in two of seven patients with tumor‐positive sN (28.6%), the sN was the exclusive site of regional nodal metastasis. The negative predictive value was 88.2% (15 of 17 patients), and the overall accuracy was 91.7% (22 of 24 patients). As regards the contribution to the detection of nodal metastasis according to the pathologic technique, standard H&E bi‐valving technique detected 16 of 19 tumor‐positive sNs (84.2%) while, by means of serial sectioning, metastases were detected in the remaining 3 of 19 sNs (15.8%).

Conclusions

The sN biopsy proved feasible, with a rather short learning curve. The focused analysis of the sN by means of serial sectioning improved the detection rate of nodal metastasis compared to standard bi‐valving examination, so that a more accurate nodal staging should be expected; finally, an elective localization of metastasis within the sN was observed in almost one third of regional node‐positive patients. J. Surg. Oncol. 2004;85:166–170. © 2004 Wiley‐Liss, Inc.
Rate constants for reaction of 1,2‐dimethylimidazole with benzyl bromide in ionic liquids and organic solvents
Authors: Skrzypczak A. , Neta P.
Published: February 2004

The rate constant for the Menschutkin reaction of 1,2‐dimethylimidazole with benzyl bromide to produce 3‐benzyl‐1,2‐dimethylimidazolium bromide was determined in a number of ionic liquids and molecular organic solvents. The rate constants in 12 ionic liquids are in the range of (1.0–3.2) × 10−3 L mol−1 s−1 and vary with the solvent anion in the order (CF3SO2)2 N− < PF6− < BF4−. Variations with the solvent cation (butylmethylimidazolium, octylmethylimidazolium, butyldimethylimidazolium, octyldimethylimidazolium, butylmethylpyrrolidinium, and hexyltributylammonium) are minimal. The rate constants in the ionic liquids are comparable to those in polar aprotic molecular solvents (acetonitrile, propylene carbonate) but much higher than those in weakly polar organic solvents and in alcohols. Correlation of the rate constants with the solvatochromic parameter ET(30) is reasonable within each group of similar solvents but very poor when all the solvents are correlated together. Better correlation is obtained for the organic solvents by using a combination of two parameters, π* (dipolarity/polarizibility) and α (hydrogen bond acidity), while additional parameters such as δ (cohesive energy density) do not provide any further improvement. © 2004 Wiley Periodicals, Inc.*

This article is a US Government work and, as such, is in the public domain of the United States of America.

Int J Chem Kinet 36: 253–258, 2004
Gas‐phase radical–radical recombination reactions of nitroxides with substituted phenyl radicals
Authors: Heidbrink J. L. , Amegayibor F. S. , Kenttämaa H. I.
Published: February 2004

Fourier‐transform ion cyclotron resonance mass spectrometry has been used to examine gas‐phase reactions of four different nitroxide free radicals with eight positively charged pyridyl and phenyl radicals (some containing a Cl, F, or CF3 substituent). All the radicals reacted rapidly (near collision rate) with nitroxides by radical–radical recombination. However, some of the radicals were also able to abstract a hydrogen atom from the nitroxide. The results establish that the efficiency (kreaction/kcollision) of hydrogen atom abstraction varies with the electrophilicity of the radical, and hence is attributable to polar effects (a lowering of the transition‐state energy by an increase in its polar character). The efficiency of the recombination reaction is not sensitive to substituents, presumably due to a very low reaction barrier. Even so, after radical–radical recombination has occurred, the nitroxide adduct was found to fragment in different ways depending on the structure of the radical. For example, a cationic fragment was eliminated from the adducts of the more electrophilic radicals via oxygen anion abstraction by the radical (i.e., the nitroxide adduct cleaves heterolytically), whereas adducts of the less electrophilic radicals predominantly fragmented via homolytic cleavage (oxygen atom abstraction). Therefore, differences in the product branching ratios were found to be attributable to polar factors. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 216–229 2004
First‐order stochastic cellular automata simulations of the lindemann mechanism
Authors: Hollingsworth Chad A. , Seybold Paul G. , Kier Lemont B. , Cheng Chao‐Kun
Published: February 2004

The Lindemann mechanism explains how apparent unimolecular chemical reactions arise from bimolecular collisions. In this mechanism an ingredient M activates reactants A through collisions, and the resulting activated species A* can either decay to products P or be deactivated back to A, again via collisions with M. A first‐order stochastic cellular automata model described previously [Seybold, Kier, and Cheng, J Chem Inf Comput Sci 1997, 37, 386] has been modified to simulate this mechanism. It is demonstrated that this model accurately reflects the salient features of the Lindemann mechanism, including the normal second‐order kinetic behavior at low [M] and apparent first‐order kinetics at high [M]. At low [M] the mechanism is equivalent to a rate‐limited sequential process, whereas at high [M] it becomes a preequilibrium with leakage to products. The model also allows an examination of the validity of the steady‐state approximation normally employed in a deterministic analysis of this mechanism, and it is seen that this approximation is not well justified under reasonable conditions. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 230–237 2004
Investigation of the correlation of sensitivity vectors of hydrogen combustion models
Authors: Zádor Judit , Zsély István Gy. , Turányi Tamás
Published: February 2004

A well‐established method for the analysis of large reaction mechanisms is the calculation and interpretation of the sensitivity of the kinetic model output Yi to parameter changes. Comparison of the sensitivity vectors si = {∂ Yi/∂p} belonging to different model outputs is a new tool for kinetic analysis. The relationship of the sensitivity vectors was investigated in homogeneous explosions, freely propagating and burner‐stabilized laminar flames of hydrogen–air mixtures, using either calculated adiabatic or constrained temperature profiles, for fuel‐to‐air ratios φ = 0.5–4.0. Sensitivity vectors are called locally similar, if the relationship si = λijsj is valid, where λij is a scalar. In many systems, only approximate local similarity of the sensitivity vectors exists and the extent of it can be quantified by using an appropriate correlation function. In the cases of adiabatic explosions and burner‐stabilized flames, accurate local similarity was present in wide ranges of the independent variable (time or distance), and the correlation function indicated that the local similarity was not valid near the concentration extremes of the corresponding species. The regions of poor similarity were studied further by cobweb plots. The correlation relationships found could be interpreted by the various kinetic processes in the hydrogen combustion systems. The sensitivity vector of the laminar flame velocity is usually considered to be characteristic for the whole combustion process. Our investigations showed that the flame velocity sensitivity vector has good correlation with the H and H2O concentration sensitivities at the front of the adiabatic flames, but there is poor correlation with the sensitivity vectors of all concentrations in homogeneous explosions. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 238–252 2004
A 308‐nm excimer laser for the treatment of scalp psoriasis
Authors: Taylor Charles R. , Racette Ashley L.
Published: February 2004

Background and Objectives

Scalp psoriasis is a frustrating disorder whose treatments can all too often be cumbersome and ineffective. Our objective was to test a combination device involving the 308‐nm excimer laser in tandem with a hair blower for treating scalp psoriasis.

Study Design/Materials and Methods

Adult subjects with scalp psoriasis unresponsive to class I topical steroids used in conjunction with medicated shampoos were treated with 308‐nm excimer laser pulses in conjunction with a hair blower that parted the obstructing hair twice a week for up to 15 weeks. Half of the scalp served as a control. Starting doses were based on standard minimal erythema dose (MED)'s with subsequent increments of up to 20%.

Results

Thirteen subjects completed the study without adverse events. Two were dropped due to lack of compliance. At the end of the investigation, the difference in the mean modified PASI scores between the control and treated sites was 4.0 (<0.0001).

Conclusions

The air blower device in conjunction with the 308‐nm excimer laser can safely and effectively treat otherwise refractory scalp psoriasis. Lasers Surg. Med. 34:136–140, 2004. © 2004 Wiley‐Liss, Inc.
The depth measuring videomicroscope (DMV): A non‐invasive tool for the assessment of capillary vascular malformations
Authors: Sivarajan Vivek , Mackay Iain R.
Published: February 2004

Background and Objectives

The response of capillary vascular malformations (CVMs) to laser treatment is believed to be due to the pattern of capillary ectasia, the depth, diameter, and flow through these capillaries and the amount of competing chromophores within the skin. Videomicroscopy has successfully been used to determine CVM capillary pattern and diameter of vessels. The depth measuring videomicroscope (DMV) allows the depth of capillaries to be measured also. The aim of this study is to examine how capillary depths within a CVM are affected by dye laser treatment using DMV.

Study Design/Materials and Methods

Thirteen previously untreated patients were examined in a temperature‐controlled room. A DMV examination was carried out prior to and 6 weeks following a treatment with pulsed dye laser. A further cohort of 11 resistant CVM patients, who had all received over five treatments, was also examined for comparison.

Results

Using a Wilcoxon Signed rank test, the results showed that the remaining vessels within the CVM as measured using DMV were more deeply located and smaller (P < 0.01 and P < 0.02 respectively), following the laser treatment. Also in the resistant patients the vessels were again more deeply placed and smaller.

Conclusions

The hypothesis that smaller and more deeply placed CVM vessels respond poorest to laser treatment is supported by these findings. Moreover, the DMV provides a simple non‐invasive technique for demonstrating this. Lasers Surg. Med. 34:193–197, 2004. © 2004 Wiley‐Liss, Inc.
Design and evaluation of a novel portable erythema‐melanin‐meter
Authors: Dolotov L.E. , Sinichkin Yu.P. , Tuchin V.V. , Utz S.R. , Altshuler G.B. , Yaroslavsky I.V.
Published: February 2004

Background and Objectives

Objective evaluation of the pigmentation index (PI) and the eythema index (EI) of human skin is a prerequisite for successful optimization of laser‐ and intense‐pulsed‐light (IPL)‐based treatment modalities in dermatology.

Study Design/Materials and Methods

We describe a three‐wavelength technique for determining PI and EI as well as its particular implementation using LEDs operating at wavelengths of 560, 650, and 710 nm and a large‐area photodiode. The instrument has been evaluated both in vitro and in vivo.

Results

In vitro, good correlation between the measured indices and results obtained with commercially available techniques has been observed. In addition, linearity of the PI with melanin concentration in the phantom medium up to 7 × 10−3 nm−1 (defined as a slope of the optical density spectrum) has been established. In vivo, feasibility of using the technique for predicting the minimal erythema dose (MED), minimal phototoxic dose (MPD), and the threshold of epidermal damage in a photothermal treatment has been demonstrated.

Conclusions

The data suggest that the technique has a substantial potential as a method of pre‐treatment diagnostics for photochemical and photothermal procedures. Lasers Surg. Med. 34:127–135, 2004. © 2004 Wiley‐Liss, Inc.
Evaluation of cryogen spray cooling exposure on in vitro model human skin
Authors: Kao Bunsho , Kelly Kristen M. , Aguilar Guillermo , Hosaka Yoshiaki , Barr Ronald J. , Nelson J. Stuart
Published: February 2004

Background and Objectives

Cryogen spray cooling (CSC) is commonly used during dermatologic laser surgery. The epidermal and dermal effects of CSC have not been adequately evaluated. To study the potential for epidermal and dermal injury after CSC using an in vitro model of human skin (RAFT).

Study Design/Materials and Methods

RAFT specimens were exposed to continuous CSC spurt durations of 10, 20, 40, 80, 100, 200, or 500 milliseconds. Biopsies were taken acutely, 3 and 7 days post‐CSC exposure. Sections were stained with hematoxylin and eosin for evaluation of possible injury, Ki‐67 to determine keratinocyte viability, and Melan‐A, to identify and evaluate melanocytes.

Results

Minimal, transient epidermal changes were noted in specimens exposed to continuous CSC spurts of 80 milliseconds or less. Keratinocytes and melanocytes remained viable. Continuous CSC spurts of 100, 200, or 500 milliseconds (much longer than recommended for clinical use) resulted in significant epidermal injury acutely, with partial or full thickness epidermal necrosis at 7 days. Only the 500 milllisecond specimen demonstrated dermal change, decreased fibroblast proliferation at 3 days.

Conclusions

Continuous CSC spurts of 80 milliseconds or less induce minimal, if any, epidermal or dermal damage and are unlikely to produce cryo‐injury when used during dermatologic laser surgery. Lasers Surg. Med. 34:146–154, 2004. © 2004 Wiley‐Liss, Inc.
Facial photo rejuvenation using two different intense pulsed light (IPL) wavelength bands
Authors: Bjerring Peter , Christiansen Kåre , Troilius Agneta , Dierickx Christine
Published: February 2004

Background and Objectives

Intense pulsed light (IPL) systems are increasingly used for treatment of photo damaged skin. In the present study, we investigated the clinical efficacy and safety of two different wavelength bands generated by the same IPL device.

Study Design/Materials and Methods

An IPL device was equipped with either a 555–950 nm filter (VL), or a 530–750 nm filter (PR).

Results

Fair, good or excellent clearance of visible telangiectasias was obtained in 81.8% of the patients (PR) and in 58.8% (VL). In the treatment of diffuse erythema, fair, good or excellent clearance was obtained in 72.7% (PR) and in 35.0% (VL). The PR filter was more efficient (P = 0.025) in reduction of diffuse erythema. The average number of treatments was 1.75 (PR) and 1.82 (VL). For the treatment of irregular pigmentation, fair, good or excellent clearance was obtained in 54.5% (PR) and in 61.9% (VL). Multiple treatments of irregular pigmentation were also evaluated. Using the VL filter more than two treatments did not induce further clinical improvement. The patients also scored their over‐all satisfaction. Either fair, good or excellent results were reported by 66.7% (PR) and by 76.2% (VL). No skin atrophy, scarring or pigment disturbances were noted after the treatments. Swelling and erythema were registered by 2/3 (PR) and 1/3 (VL) of the patients.

Conclusions

The two IPL wavelength bands were both found to be effective in the treatment of photo damaged facial skin. The clinical efficacy and safety of the two different treatment procedures were comparable to those reported in earlier studies, and finally treatment with these filter combinations required less than half the fluence, no active cooling and fewer treatments. Lasers Surg. Med. 34:120–126, 2004. © 2004 Wiley‐Liss, Inc.
Pulsed dye laser and non‐ablative wrinkle reduction
Authors: Reynolds Nick , Thomas Kay , Baker Lynn , Adams Cathy , Kenealy John
Published: February 2004

Background and Objectives

Non‐ablative wrinkle reduction is currently an issue, which is being widely discussed in the literature and at academic meetings worldwide. We present the findings of our randomized within patient controlled clinical trial into periorbital wrinkle reduction with a 595 nm pulsed dye laser.

Study Design/Materials and Methods

Twenty‐six volunteers, 25 female and 1 male were enrolled into our study. The study was set up as a randomized within patient controlled clinical trial. Subjects received one treatment to the periorbital wrinkles around one eye, using the other as the control. They were then observed at 3 and 6 months post treatment. They then received three treatments spaced 4 weeks apart and were again observed at 3 and 6 months. The author and one blinded assessor reviewed them independently. At the end of the trial a panel of three blinded assessors scored photographs of the subjects independently. The Fitzpatrick wrinkle score was used to score the subjects. All data was subjected to statistical analysis using non‐parametric t‐tests.

Results

Statistical analysis revealed no significant differences in the wrinkle scores of the patients upon completion of the trial protocols.

Conclusions

The 595 nm pulsed dye laser set at 0.5 millisecond pulse width is not an effective means of achieving sub‐purpuric non‐ablative periorbital wrinkle reduction. Lasers Surg. Med. 34:109–113, 2004. © 2004 Wiley‐Liss, Inc.
Chronic UVB exposure enhances in vitro percutaneous penetration of 5‐aminulevulinic acid in hairless mouse skin
Authors: van den Akker Johanna T.H.M. , Holroyd J. Andrew , Vernon David I. , Sterenborg Henricus J.C.M. , Brown Stanley B.
Published: February 2004

Background and Objectives

(Pre)cancerous skin lesions accumulate more protoporphyrin IX (PpIX) upon topical application of 5‐aminolevulinic acid (ALA) than the surrounding normal skin. This might be the result of a higher percutaneous penetration of ALA into (pre)cancerous skin.

Study Design/Materials and Methods

ALA penetration through (1) healthy skin with intact stratum corneum, (2) healthy skin with reduced stratum corneum (i.e. tape stripped skin) and (3) diseased skin with dysplastic and thickened epidermis (chronically UVB‐exposed skin) was determined in an in vitro model with hairless mouse skin.

Results

More ALA had penetrated through chronically UVB‐exposed skin than through normal non‐exposed skin after 8 hours ALA application. The amount of ALA penetrated through chronically UVB‐exposed skin was smaller than through tape stripped skin.

Conclusions

The stratum corneum barrier function is less effective in chronically UVB‐exposed skin than in normal non‐exposed skin, but more effective than in tape stripped skin. A higher penetration rate of ALA into (pre)cancerous lesions may be (partly) responsible for the greater accumulation of PpIX in such lesions. Lasers Surg. Med. 34:141–145, 2004. © 2004 Wiley‐Liss, Inc.
Full face laser resurfacing: Therapy and prophylaxis for actinic keratoses and non‐melanoma skin cancer
Authors: Iyer Shilesh , Friedli Andre , Bowes Leyda , Kricorian Greg , Fitzpatrick Richard E.
Published: February 2004

Background

Although there are many effective treatment modalities for individual actinic keratoses (AKs), widespread lesions on the photoaged face pose a challenge due to inefficient and ineffective therapy resulting in high rates of recurrence after local destruction. Full face laser resurfacing offers an effective and efficient treatment option that successfully reduces the number of AK's on diffusely damaged skin and may show a prophylactic benefit for preventing non‐melanoma skin cancers.

Objective

To assess the efficacy of full face laser resurfacing in reducing the number of facial AK's by comparing preoperative and postoperative numbers of lesions present and to observe the incidence of non‐melanoma skin cancer after full face laser resurfacing.

Study Design

A retrospective chart review of 24 patients with widespread facial AK's (greater than 30) treated with full face UPCO2 and/or Er:Yag laser resurfacing was performed. All patients were a minimum of 1 year post‐operative following facial laser resurfacing. The recurrence of AK's and the occurrence of facial non‐melanoma skin cancers in these patients was assessed through chart analysis.

Results

Widespread AK's were effectively eliminated in all patients. Twenty‐one patients (87%) remained lesion free for at least 1 year. Fourteen of the 24 patients (58.3%) showed no new lesions during a 2‐year follow‐up. There was an overall 94% reduction in total number of AK's. Adverse effects included transient perioral scarring in one patient, S. aureus infection in two patients, and dyschromia in two patients.

Conclusions

Full face laser resurfacing provides long‐term effective prophylaxis against AKs and may reduce the incidence of AK related squamous cell carcinoma. Lasers Surg. Med. 34:114–119, 2004. © 2004 Wiley‐Liss, Inc.
Selective electro‐thermolysis in aesthetic medicine: A review
Authors: Sadick Neil S. , Makino Yuriko
Published: February 2004

The use of radiofrequency (RF) for selective electro‐thermolysis has been found to produce a highly efficient thermal effect on biological tissue. Different from optical energy, RF energy is dependent on the electrical properties of the tissue rather than on concentration of chromophores in the skin for selective thermal destruction of targeted sites. Good results have been obtained with systems that use RF current alone for skin resurfacing, with efficacy comparable to laser resurfacing but with potentially more rapid healing. A related adverse effect is pain accompanying the procedure, due to a high depth of penetration. Another technology integrates RF energy together with optical energy (using lower energies of both forms of energies). These systems have shown efficacy in hair removal for all hair colors and skin types, as well as wrinkle reduction; and may reduce the risk of side effects associated with either RF or optical treatments alone. This article discusses the properties of electrical current in medicine and reviews the studies to date that have evaluated RF energy for dermatological applications. Lasers Surg. Med. 34:91–97, 2004. © 2004 Wiley‐Liss, Inc.
Supramolecular Hydrogel Formation Based on Inclusion Complexation Between Poly(ethylene glycol)‐Modified Chitosan and α‐Cyclodextrin
Authors: Huh Kang Moo , Cho Yong Woo , Chung Hesson , Kwon Ick Chan , Jeong Seo Young , Ooya Tooru , Lee Won Kyu , Sasaki Shintaro , Yui Nobuhiko
Published: February 2004

Summary: Supramolecular hydrogels have been prepared on the basis of polymer inclusion complex (PIC) formation between poly(ethylene glycol) (PEG)‐modified chitosans and α‐cyclodextrin (α‐CD). A series of PEG‐modified chitosans were synthesized by coupling reactions between chitosan and monocarboxylated PEG using water‐soluble carbodiimide (EDC) as coupling agent. With simple mixing, the resultant supramolecular assembly of the polymers and α‐CD molecules led to hydrogel formation in aqueous media. The supramolecular structure of the PIC hydrogels was confirmed by differential scanning calorimetry (DSC), X‐ray diffraction, and 13C cross‐polarized/magic‐angle spinning (CP/MAS) NMR characterization. The PEG side‐chains on the chitosan backbones were found to form inclusion complexes (ICs) with α‐CD molecules, resulting in the formation of channel‐type crystalline micro‐domains. The IC domains play an important role in holding together hydrated chitosan chains as physical junctions. The gelation property was affected by several factors including the PEG content in the polymers, the solution concentration, the mixing ratio of host and guest molecules, temperature, pH, etc. All the hydrogels in acidic conditions exhibited thermo‐reversible gel‐sol transitions under appropriate conditions of mixing ratio and PEG content in the mixing process. The transitions were induced by supramolecular association and dissociation. These supramolecular hydrogels were found to have phase‐separated structures that consist of hydrophobic crystalline PIC domains, which were formed by the host‐guest interaction between α‐CD and PEG, and hydrated chitosan matrices below the pKa.

The formation of inclusion complexes between α‐cyclodextrin and PEG‐modified chitosan leads to the formation of hydrogels that can undergo thermo‐reversible supramolecular dissociation.

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The formation of inclusion complexes between α‐cyclodextrin and PEG‐modified chitosan leads to the formation of hydrogels that can undergo thermo‐reversible supramolecular dissociation.
Dye Affinity Hollow Fibers for Albumin Purification
Authors: Yavuz Handan , Denizli Adil
Published: February 2004

Summary: Reactive Green HE 4BD was immobilized on polyamide (PA) hollow fibers for human serum albumin (HSA) adsorption from both aqueous solutions and human plasma. Different amounts of Reactive Green HE 4BD were incorporated on the PA hollow fibers by changing the dye attachment conditions, i.e. the initial dye concentration and the addition of sodium carbonate and sodium chloride. The maximum amount of dye attachment was obtained as 39.4 μmol · g−1 when the hollow fibers were treated with 3 M HCl for 30 min before performing the dye attachment. HSA adsorption onto unmodified and dye‐attached hollow fibers was investigated batchwise. The non‐specific adsorption of HSA was low (6.0 mg/g hollow fiber). Dye attachment onto the hollow fibers significantly increased the HSA adsorption (86.7 mg/g). The maximum HSA adsorption was observed at pH 5.0. Higher HSA adsorption was observed from human plasma (198 mg HSA/g). The desorptions were performed by adding 0.1 M Tris/HCl buffer containing 0.5 M NaSCN or 1.0 M NaCl to the HSA solutions in which adsorption equilibria had been reached. The desorption results demonstrated that the adsorption of HSA to the adsorbent was reversible.

Chemical structure of Reactive Green HE‐4BD.

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Chemical structure of Reactive Green HE‐4BD.
Characterization of Riboflavin‐Photosensitized Changes in Aqueous Solutions of Alginate by Dynamic Light Scattering
Authors: Kjøniksen Anna‐Lena , Baldursdóttir Stefania G. , Nyström Bo
Published: February 2004

Summary: The effect of irradiation, in the wavelength range of 310–800 nm, on aqueous solutions (pH = 7.4) of alginate in the presence of the photosensitizer riboflavin (RF) has been investigated with the aid of dynamic light scattering (DLS). Under aerobic conditions light irradiation of RF causes scission of the polymer chains which affects the polymer dynamics. The time correlation data obtained from DLS experiments showed at all conditions the existence of two relaxation modes: one single exponential at short times, followed by a stretched exponential at longer times. The slow relaxation time revealed, over the whole considered concentration range, lower values for the alginate/RF system, whereas no effect of photochemical degradation was observed for the fast relaxation time in the semidilute regime. The results suggest that the photochemically induced fragmentation of alginate affects the slow relaxation mode, associated with disengagement relaxation of individual chains or cluster relaxation, in a similar way as the zero‐shear viscosity. These findings provide detailed insight into the dynamics of the polymer matrix, and this knowledge can be useful in the context of controlled‐release delivery of drugs.

The chemical units of alginate (M = mannuronic acid and G = guluronic acid).

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The chemical units of alginate (M = mannuronic acid and G = guluronic acid).
Ethanol and aloe emodin alter the p53 mutational spectrum in ultraviolet radiation–induced murine skin tumors
Authors: Badgwell Donna B. , Walker Christopher M. , Baker Whitney T. , Strickland Faith M.
Published: February 2004

Mutations in the p53 tumor‐suppressor gene contribute to the development of skin cancer, and the spectrum of mutations in this gene correlates with specific physical and chemical carcinogens in the environment. Cosmetics may contain alcohols and/or aloe emodin (AE). Although these compounds are not carcinogenic when applied to the skin, they may increase the carcinogenicity of ultraviolet (UV) radiation. We investigated whether ethanol (EtOH) and AE alone or combined with UV radiation cause mutations in the p53 gene. In the absence of UV radiation, C3H/HeN mice chronically treated for up to 33 wk with AE in 25% EtOH‐in‐water vehicle or vehicle alone failed to develop tumors and had no mutations in exons 4–8 of the p53 gene. UV radiation alone induced skin tumors, which had mutations predominantly in p53 exons 5 and 8. In contrast, mutations arising in UV + EtOH–or UV + AE–treated groups were more broadly distributed throughout the p53 gene. Mutations were found in exons 4, 6, and 7, as well as in exons 5 and 8. This altered distribution of mutations across the p53 DNA sequence more closely resembles the pattern observed in TP53 from human skin tumors at sun‐exposed sites than that in the p53 gene of mice treated with UV alone. Thus, treatment with UV radiation in combination with two chemicals not thought to be carcinogenic, alcohol, and AE results in a broader distribution of mutations in a critical tumor‐suppressor gene. © 2004 Wiley‐Liss, Inc.
Intronic polymorphism (1541‐1542delGT) of the constitutive heat shock protein 70 gene has functional significance and shows evidence of association with lung cancer risk
Authors: Rusin Marek , Zientek Helena , Krześniak Małgorzata , Małusecka Ewa , Zborek Anna , Krzyżowska‐Gruca Stefania , Butkiewicz Dorota , Vaitiekunaite Rasa , Lisowska Katarzyna , Grzybowska Ewa , Krawczyk Zdzisław
Published: February 2004

Somatic mutations of 11q23.3‐linked constitutive heat shock protein 70 gene (HSPA8 alias HSC70) are detected by others in breast carcinomas. To examine whether intragenic, somatic mutations of HSPA8 occur in lung carcinomas, we sequenced its exons 2–8, with adjacent intronic sequences, in a series of DNA samples from non‐small‐cell lung cancers (NSCLC). Twenty‐one polymorphisms were detected, but no somatic mutation. However, we observed an association between the HSC70 1541‐1542delGT genotype and the immunohistochemical staining pattern of HSC70 protein. Tumors with weak (+) HSC70 protein staining were more frequent in the carriers of the polymorphic 1541‐1542delGT allele than in the homozygotes of the major allele (20% vs. 6%, P = 0.05 by Fisher's exact test). This statistically significant association prompted us to test the polymorphism functionally. The method we developed for the functional evaluation of intronic sequence alterations showed that the HSPA8 intron 2 with the deleted GT dinucleotide was associated with noticeable (approximately 20%) and statistically significant (P = 0.005) reduction of the reporter gene activity. Our case‐control analysis showed that the 1541‐1542delGT heterozygous genotype was associated with significantly decreased risk for lung cancer (crude odds ratio (OR) = 0.44; 95% confidence interval (CI): 0.23–0.84). To the best of our knowledge, this is the first report on the association between a polymorphism of a gene coding for the chaperone protein and lung cancer risk. Moreover, the simple method reported here, based on the dual‐luciferase reporter assay system, can be useful for testing functional significance of polymorphisms located in introns of other genes. © 2004 Wiley‐Liss, Inc.
Increase in DNA methylation downregulates conceptus interferon‐tau gene expression
Authors: Nojima Hisashi , Nagaoka Kentaro , Christenson Ronald K. , Shiota Kunio , Imakawa Kazuhiko
Published: February 2004

Expression of ovine interferon‐tau (oIFNτ) genes, essential for the maternal recognition of pregnancy in ruminant ungulates, is restricted to the trophoblast and is not detected in any other cell types or tissues. Substantial secretion of oIFNτ starts on day 12–13 of pregnancy (day 0 = day of estrus), reaches the highest on day 16–17, and then declines rapidly. Ovine IFNτ mRNA, on the other hand, reaches the highest level on day 14 of pregnancy, 2–3 days before peak production of the protein. In this study, day 14 and 17 conceptuses treated with 5‐aza‐2′‐deoxycytidine, an inhibitor of DNA methylation, were cultured in vitro and only day 17, not day 14, conceptuses resulted in upregulation of oIFNτ gene expression. To gain insight into the molecular mechanism of oIFNτ gene downregulation, the methylation status within 1 kb of the 5′‐flanking region of oIFNτ‐o10 gene was investigated: CpG dinucleotides of this gene in day 14 ovine conceptuses were hypomethylated compared to day 20 conceptuses or other tissues. In vitro methylation of oIFNτ‐o10‐reporter constructs caused suppression of reporter activity in transient transfections. Cotransfection of methyl‐CpG‐binding protein (MeCP2) with the reporter construct elicited further suppression of the reporter activity. In electrophoretic mobility shift assay (EMSA), patterns of shifted bands did not show much difference between methylated and unmethylated probes in distal regions, but exhibited differences in the proximal region of upstream sequences of the oIFNτ gene. These results provide evidence that changes in the degree of DNA methylation could be one of the major mechanisms leading to downregulation of the oIFNτ‐o10 gene during early gestation, and possibly its silencing in nonconceptus tissues. Mol. Reprod. Dev. 67: 396–405, 2004. © 2004 Wiley‐Liss, Inc.