bluuebunny/crossref_metadata_2025 huggingface dataset:
Adjuvant irradiation for cervical lymph node metastases from melanoma
Authors: Ballo Matthew T. , Bonnen Mark D. , Garden Adam S. , Myers Jeffrey N. , Gershenwald Jeffrey E. , Zagars Gunar K. , Schechter Naomi R. , Morrison William H. , Ross Merrick I. , Kian Ang K.
Published: March 2003

BACKGROUND

The risk of regional disease recurrence after surgery alone for lymph node metastases from melanoma is well documented. The role of adjuvant irradiation remains controversial.

METHODS

The medical records of 160 patients with cervical lymph node metastases from melanoma were reviewed retrospectively. Of these, 148 (93%) presented with clinically palpable lymph node metastases. All patients underwent surgery and radiation to a median dose of 30 grays (Gy) at 6 Gy per fraction delivered twice weekly. Surgical resection was either a selective neck dissection in 90 patients or local excision of the lymph node metastasis in 35 patients. Only 35 patients underwent a radical, modified radical, or functional neck dissection.

RESULTS

At a median follow‐up of 78 months, the actuarial local, regional, and locoregional control rates at 10 years were 94%, 94%, and 91%, respectively. Univariate analysis of patient, tumor, and treatment characteristics failed to reveal any association with the subsequent rate of local or regional control. The actuarial disease‐specific (DSS), disease‐free, and distant metastasis‐free survival (DMFS) rates at 10 years were 48%, 42%, and 43%, respectively. Univariate and multivariate analyses revealed that patients with four or more involved lymph nodes had a significantly worse DSS and DMFS. Nine patients developed a treatment‐related complication requiring medical management, resulting in a 5‐year actuarial complication‐free survival rate of 90%.

CONCLUSIONS

Adjuvant radiotherapy resulted in a 10‐year regional control rate of 94%. Complications for all patients were rare and manageable when they did occur. The authors recommend adjuvant irradiation for patients with extracapsular extension, lymph nodes measuring 3 cm in size or larger, the involvement of multiple lymph nodes, recurrent disease, or any patient having undergone a selective therapeutic neck dissection. Cancer 2003;97:1789–96. © 2003 American Cancer Society.

DOI 10.1002/cncr.11243
Author reply
Authors: Ferrara Gerardo , Argenziano Giuseppe , Cerroni Lorenzo , Soyer H. Peter
Published: March 2003

DOI 10.1002/cncr.11244
Clinical importance of molecular determinations in gynecologic patients with multiple tumors
Authors: Dinjens Winand N. M. , van der Burg Maria E. L. , Chadha Savi , Sleddens Hein F. B. M. , Burger Curt W. , Ewing Patricia C.
Published: March 2003

BACKGROUND

The prognosis and treatment of patients with multiple tumors may depend on the correlation between tumors: multiple primary tumors, or recurrent tumors, and metastatic disease. The authors investigated whether the detection of molecular aberrations in multiple gynecologic tumors in individual patients provided clinically useful information on the correlation between the tumors.

METHODS

Between 1999 and 2001, molecular analyses were performed on tissue from 15 gynecologic patients, all with multiple tumors. The molecular analyses included loss of heterozygosity determinations at eight DNA loci and mutation analyses of p53 exons 5–8 using the single‐strand conformation polymorphism method. Previously, it was not possible to use routine diagnostic histopathology to determine accurately the correlation between multiple lesions in patients with gynecologic malignancies, information that may have an impact on clinical decision‐making and prognosis.

RESULTS

Molecular results were obtained from all tumors from each of the 15 patients. The DNA alterations detected provided evidence that two patients had second primary tumors, nine patients had a single tumor with metastases, and four patients had two independent primary tumors as well as metastatic disease. The results provided additional diagnostic information and contributed to clinical decision‐making.

CONCLUSIONS

The authors demonstrated that, by comparing DNA alterations in multiple tumors within an individual patient, evidence about correlations between the tumors can be obtained. These investigations can be performed on routinely processed tissues, and the results may be of clinical importance in helping to determine the management or prognosis of patients with gynecologic malignancies. Cancer 2003;97:1766–74. © 2003 American Cancer Society.

DOI 10.1002/cncr.11249
Diagnostic value and prognostic significance of protein S‐100β, melanoma‐inhibitory activity, and tyrosinase/MART‐1 reverse transcription‐polymerase chain reaction in the follow‐up of high‐risk melanoma patients
Authors: Garbe Claus , Leiter Ulrike , Ellwanger Ulf , Blaheta Hans‐Juergen , Meier Friedegund , Rassner Gernot , Schittek Birgit
Published: March 2003

BACKGROUND

Cutaneous melanoma is the most aggressive form of skin carcinoma in humans, frequently with a rapid progression of disease. To detect early developing metastasis, laboratory tests to determine levels of lactate dehydrogenase (LDH) and alkaline phosphatase (AP) form part of the regular follow‐up, but often cannot discover recurrent disease at a sufficiently early stage.

METHODS

To evaluate the diagnostic accuracy of protein S‐100β (S‐100β), melanoma‐inhibitory activity (MIA), LDH, AP, and tyrosinase/MART‐1 reverse transcription‐polymerase chain reaction (RT‐PCR), the authors included 296 consecutive AJCC Stage II or III clinically disease‐free melanoma patients. Follow‐up examinations were performed every 3 months and blood samples were drawn to determine the levels of these tumor markers.

RESULTS

Metastasis occurred in 41 of the 296 patients during a median follow‐up period of 19 months (range, 1–33 months). The sensitivity to detect new metastases was 29% for protein S‐100β, 22% for MIA, 2% for LDH, 17% for AP, and 24% for RT‐PCR. The diagnostic accuracy was best for MIA (86%) and S‐100β (84%), whereas AP (79%), LDH (77%), and RT‐PCR (72%) demonstrated lower values. Elevated values of S‐100β and MIA during follow‐up examinations were associated with decreased survival rates in the further course of the disease, but pathologic findings of the other tumor markers showed no prognostic impact.

CONCLUSIONS

To the authors' knowledge, the current study is the first comparison of the diagnostic accuracy of currently available tumor markers in the follow‐up of high‐risk melanoma patients. Protein S‐100β and MIA demonstrated a higher sensitivity, specificity, and diagnostic accuracy in the diagnosis of newly occurring metastasis compared with to the tumor markers AP, LDH, and RT‐PCR diagnostics. Therefore, the tumor markers S‐100β and MIA may be useful in the follow‐up of disease‐free Stage II and III melanoma patients. Cancer 2003;97:1737–45. © 2003 American Cancer Society.

DOI 10.1002/cncr.11250
Outpatient, sequential, parenteral‐oral antibiotic therapy for lower risk febrile neutropenia in children with malignant disease
Authors: Paganini Hugo , Gómez Sandra , Ruvinsky Silvina , Zubizarreta Pedro , Latella Antonio , Fraquelli Lidia , Iturres Alejandro Santillán , Casimir Lidia , Debbag Roberto
Published: March 2003

BACKGROUND

Recent reports and previous randomized trials conducted at the authors' institution suggested that children with lower risk febrile neutropenic (LRFN) may benefit from substitution of oral antibiotic therapy for parenteral therapy. The objective of this study was to determine the efficacy of parenteral‐oral outpatient therapy in the management of children with LRFN who were receiving treatment for malignant disease.

METHODS

From August 2000 to April 2002, 135 children with a median age of 7.5 years (range, 1.6–15.8 years) who had a total of 177 episodes of LRFN were included in a prospective, randomized, single‐institution trial. Children with LRFN received a single dose of ceftriaxone and amikacin and completed a risk‐assessment work‐up. All patients were discharged immediately and, at 24 hours, were allocated randomly to two groups: Group A (89 episodes) received oral ciprofloxacin, and Group B (88 episodes) received intravenous ceftriaxone.

RESULTS

Most patients (61% in Group A and 51% in Group B) were receiving treatment for leukemia (P value not significant [NS]). Twenty‐eight children (31%) in Group A and 22 children (25%) in Group B displayed unexplained fever (P value NS). No significant differences in sites of initial infection were found between the two groups. The median duration of neutropenia was 4.2 days and 4.7 days for Group A and Group B, respectively (P value NS); the median duration of fever was 2.3 days and 2.6 days, respectively (P value NS); and the median duration of antibiotic treatment was 4.5 days and 4.8 days, respectively (P value NS). The overall results of the study were excellent. Only four treatment failures in Group A (5%) and 6 treatment failures in Group B (7%) were observed. These patients were readmitted to the hospital and did well with appropriate treatment.

CONCLUSIONS

In children with LRFN who are receiving treatment for malignant disease, outpatient oral ciprofloxacin after 24 hours of a single dose of intravenous ceftriaxone and amikacin was as safe and efficacious as parenteral ceftriaxone. Outpatient management and early antibiotic withdrawal were safe for both groups. Cancer 2003;97:1775–80. © 2003 American Cancer Society.

DOI 10.1002/cncr.11251
Textbook of cancer epidemiology
Authors: Bondy Melissa , Newman Lisa A.
Published: March 2003

DOI 10.1002/cncr.11252
Spectroscopic detection and evaluation of morphologic and biochemical changes in early human oral carcinoma
Authors: Müller Markus G. , Valdez Tulio A. , Georgakoudi Irene , Backman Vadim , Fuentes Cesar , Kabani Sadru , Laver Nora , Wang Zimmern , Boone Charles W. , Dasari Ramachandra R. , Shapshay Stanley M. , Feld Michael S.
Published: March 2003

BACKGROUND

Understanding the development and progression of head and neck squamous cell carcinoma is key in the quest for the early diagnosis and prevention of this type of malignancy. The current study correlated early biochemical and histologic changes in oral tissue with spectral features in fluorescence, reflectance, and light scattering spectra acquired in vivo to diagnose early stages of oral malignancies.

METHODS

A total of 91 tissue sites from 15 patients with varying degrees of malignancy (normal, dysplastic, and cancerous sites) and 8 healthy volunteers were analyzed with 3 spectroscopic techniques. Direct biochemical information regarding oral tissue native fluorophores was obtained with intrinsic fluorescence spectroscopy by fitting a linear combination of collagen and the reduced form of nicotinamide adenine dinucleotide (NADH) fluorescence spectra to the intrinsic tissue fluorescence spectra excited with 337 nanometer (nm) and 358‐nm laser light. Diffuse reflectance spectroscopy was used to provide information regarding tissue absorption and structure, such as hemoglobin concentration and stroma density, by measuring the wavelength‐dependent absorption and scattering coefficients. By subtracting the diffusely reflected component from the measured reflectance, light scattering spectroscopy (LSS) information resulting from single backscattering from epithelial cell nuclei was obtained. LSS provides information concerning the size distribution of cell nuclei.

RESULTS

These optically extracted tissue parameters provide biochemical or structural information in vivo without the need for tissue excision, and can be used to diagnose tissue abnormalities. By combining the information provided by the three techniques, a method known as trimodal spectroscopy, a sensitivity and specificity of 96% and 96%, respectively, in distinguishing cancerous/dysplastic (mild, moderate, and severe) from normal tissue was achieved. In addition, the authors were able to distinguish dysplastic from cancerous tissue with a sensitivity of 64% and a specificity of 90%.

CONCLUSIONS

The results of the current study demonstrated that Trimodal spectroscopy is a highly sensitive and specific technique with which to diagnose tissue abnormalities. Cancer 2003;97:1681–92. © 2003 American Cancer Society.

DOI 10.1002/cncr.11255
Odorant receptor expression as a function of neuronal maturity in the adult rodent olfactory system
Authors: Iwema Carrie L. , Schwob James E.
Published: March 2003

Odorant receptors (ORs) are expressed in a spatially restricted manner in the mammalian olfactory epithelium (OE), and this patterning probably contributes to innervation specificity within the olfactory bulb (OB). Furthermore, glomerular targeting appears to be contingent on receptor choice. Central to the mechanism by which ORs influence axonal specificity is the timing of OR expression during the life cycle of the olfactory sensory neurons (OSNs). Data indicate that OSNs express ORs in the absence of the OB but do not address whether OR expression is an early event in OSN differentiation. Accordingly, we evaluated whether ORs are expressed in mature [olfactory marker protein (OMP+)] and/or immature [growth‐associated protein of 43 kDa m.w. (GAP‐43+)] OSNs by assessing the expression of the P2 OR subtype via immunostaining for β‐gal and concurrent OMP or GAP‐43 expression in P2‐IRES‐tauLacZ mice. Nearly 90% of P2+ OSNs expressed OMP, whereas approximately 10% expressed GAP‐43. One month after unilateral bulb ablation, the number of P2+ OSNs decreased on the lesioned side; however, the percent of P2+/GAP‐43+ OSNs dramatically increased. We also determined that onset of P2 OR expression is slightly delayed when evaluated in the context of neuronal differentiation. Additionally, we defined the expression of OR+ OSNs in the OE of rats via in situ hybridization with a panel of eight ORs followed by OMP immunostaining. All eight ORs were found in neurons situated throughout the height of the OE, including those OSNs deep to OMP staining, thus demonstrating definitively that ORs are expressed prior to the maturational state defined by OMP expression. J. Comp. Neurol. 459:209–222, 2003. © 2003 Wiley‐Liss, Inc.
Functional organization of vasodilator neurons in pelvic ganglia of female guinea pigs: Comparison with uterine motor neurons
Authors: Jobling Phillip , Gibbins Ian L. , Morris Judy L.
Published: March 2003

Neurons producing vasodilation during reproductive activity constitute a large population of neurons in pelvic autonomic ganglia. We used intracellular recording, dye‐filling and multiple‐labeling immunohistochemistry to determine the morphology and electrophysiological properties of, and number of synaptic inputs to, vasodilator pelvic neurons in female guinea pigs. Vasodilator neurons, identified by their immunoreactivity for vasoactive intestinal peptide (VIP) and their location in paracervical ganglia, had simple dendritic arbors (1 primary dendrite) compared with nonvasodilator neurons (3 dendrites). Vasodilator neurons had more depolarized resting membrane potentials (−47 mV) than other paracervical neurons (−55 mV) and had smaller apparent cell capacitances (65 pF vs. 110 pF). Vasodilator and nonvasodilator neurons could not be distinguished on the basis of their action potential discharge characteristics or current voltage relationships. Most pelvic neurons (∼70%) had tonic (slowly adapting) discharges. Fifty‐five percent of vasodilator and 60% of nonvasodilator neurons showed inward rectification when hyperpolarized below −90 mV. Around 65% of neurons showed evidence of M‐current. Both vasodilator and nonvasodilator neurons (∼80%) expressed an A‐like current. Vasodilator neurons and nonvasodilator neurons received 1–2 fast synaptic inputs following stimulation of pelvic or hypogastric nerve trunks. Most neurons received a least one strong synaptic input. These results indicate that vasodilator neurons and neighboring neurons projecting to other pelvic targets, primarily in the myometrium, express a similar range of ionic conductances and integrate few synaptic inputs. The similarities between these two populations of neurons may be related to their coactivation as part of spinal somato‐pelvic reflexes. Vasodilation and uterine contraction during reproductive behavior in female guinea pigs are likely to involve input from preganglionic neurons at both lumbar and sacral spinal levels. J. Comp. Neurol. 459:223–241, 2003. © 2003 Wiley‐Liss, Inc.
Neurogranin expression by cerebellar neurons in rodents and non‐human primates
Authors: Singec Ilyas , Knoth Rolf , Ditter Margarethe , Frotscher Michael , Volk Benedikt
Published: March 2003

Neurogranin (NG) is a brain‐specific protein kinase C substrate involved in the regulation of calcium signaling and neuronal plasticity. A rostrocaudal expression profile, with large amounts in telencephalic brain regions and low expression levels in phylogenetically older brain structures, was reported previously. In the cerebellum, expression of NG has not been described. By using immunocytochemistry and in situ hybridization, we found that NG is expressed in the mouse (C57Bl/6), rat (Wistar), and monkey (Cercopithecus aetiops) cerebella. In the mouse cerebellum, Golgi cells were strongly immunoreactive for NG, whereas other cerebellar neurons were devoid of this protein. Cell counts showed 1.6‐fold more immunopositive Golgi cells in the hemispheres (61.1 ± 8.0 cells/mm2) than in the vermis (37.5 ± 3.3 cells/mm2). Developmental studies showed detectable NG in the mouse cerebellum as early as on postnatal day 10 (P10). In contrast to the mouse, in the rat cerebellum we found only a few Golgi cells containing NG (hemispheres, 2.4 ± 0.5 cells/mm2; vermis, 1.5 ± 0.3 cells/mm2). In the monkey cerebellum, unipolar brush cells, localized in the granular layer, were heavily labeled, whereas Golgi cells were devoid of NG. This study demonstrated that NG is strongly expressed in specific γ‐aminobutyric acidergic neurons in the rodent cerebellum. In addition, NG expression in the primate cerebellum by brush cells, which are excitatory, showed remarkable cell type‐specific and species‐specific expression patterns of a postsynaptic protein mediating calcium signaling mechanisms. J. Comp. Neurol. 459:278–289, 2003. © 2003 Wiley‐Liss, Inc.
GABA and glutamate in mating‐activated cells in the preoptic area and medial amygdala of male gerbils
Authors: Simmons Danielle A. , Yahr Pauline
Published: March 2003

The posterodorsal medial amygdala (MeApd), the posterodorsal preoptic nucleus (PdPN), and the medial cell group of the sexually dimorphic preoptic area (mSDA) contain cells that are activated specifically at ejaculation as assessed by Fos expression. The mSDA also expresses Fos early in the mating context. Because little is known about the neurotransmitters of these activated cells, the possibility that they use γ‐aminobutyric acid (GABA) or glutamate was assessed. Putative glutamatergic cells were visualized with immunocytochemistry (ICC) for glutamate and its neuron‐specific transporter. Their distributions were compared with those of GABAergic cells visualized with ICC for the 67‐kDa form of glutamic acid decarboxylase (GAD67) and in situ hybridization for GAD67 messenger RNA (mRNA). Colocalization of Fos and GAD67 mRNA in recently mated males indicated that half of the activated cells in the PdPN, mSDA, and lateral MeApd are GABAergic. Colocalization of Fos and glutamate suggested that a quarter of the activated mSDA and lateral MeApd cells are glutamatergic. The PdPN does not appear to have glutamatergic cells. In the lateral MeApd, the percentage of activated cells that are GABAergic (45%) matches the percentage that project to the principal part of the bed nucleus of the stria terminalis (BST; 43%), and the percentage likely to be glutamatergic (27%) matches the percentage projecting to the mSDA (27%). The latter could help to trigger ejaculation. The distribution of GABAergic and putative glutamatergic cells in the caudal preoptic area, caudal BST, and medial amygdala of male gerbils is also described. J. Comp. Neurol. 459:290–300, 2003. © 2003 Wiley‐Liss, Inc.
Immunohistochemical localization of citrullinated proteins in adult rat brain
Authors: Nicholas Anthony P. , King Jeffrey L. , Sambandam Thiagarajan , Echols Joshua D. , Gupta Kiran B. , McInnis Carey , Whitaker John N.
Published: March 2003

By using hybridoma technology, an IgM monoclonal antibody (F95) against multiple citrullinated synthetic and natural peptides was recently developed and used to stain immunohistochemically subsets of astrocytes and myelin basic protein (MBP) from selected regions of human brain (Nicholas and Whitaker [2002] Glia 37:328–336). With this antibody, the present study provides a more detailed localization of citrullinated epitopes in the central nervous system (CNS) by examining immunohistochemical staining patterns for F95 in the normal adult rat brain. Thus, immunohistochemical labeling for citrullinated epitopes was seen in white matter areas consistent with myelin staining; however, in general, it was more prominent and uniform in the caudal CNS (spinal cord, medulla oblongata, pons, and cerebellum) than in more rostral areas. F95 staining was also seen in cells and fibers often intimately associated with blood vessels and/or ventricular surfaces. By using dual‐color immunofluorescence, the vast majority of this latter staining was colocalized within a subset of astrocytes also immunoreactive for glial fibrillary acidic protein (GFAP). By using Western blot analysis of rat brain proteins, multiple GFAP‐ and MBP‐immunoreactive proteins and peptide fragments were seen, and many of them were also reactive with the F95 antibody. Thus, the present study not only demonstrates that citrullinated epitopes in normal rat brain are most concentrated in subsets of myelin and astrocytes but also provides evidence that GFAP, like MBP, may be present as multiple citrullinated isoforms. J. Comp. Neurol. 459:251–266, 2003. © 2003 Wiley‐Liss, Inc.
Efferent connections of the dorsomedial thalamic nuclei of the domestic chick (Gallus domesticus)
Authors: Montagnese Catherine M. , Mezey Szilvia E. , Csillag András
Published: March 2003

Small iontophoretic injections of the anterograde tracerPhaseolus vulgarisleucoagglutinin were placed in the thalamic anterior dorsomedial nucleus (DMA) of domestic chicks. The projections of the DMA covered the rostrobasal forebrain, ventral paleostriatum, nucleus accumbens, septal nuclei, Wulst, hyperstriatum ventrale, neostriatal areas, archistriatal subdivisions, dorsolateral corticoid area, numerous hypothalamic nuclei, and dorsal thalamic nuclei. The rostral DMA projects preferentially on the hypothalamus, whereas the caudal part is connected mainly to the dorsal thalamus. The DMA is also connected to the periaqueductal gray, deep tectum opticum, intercollicular nucleus, ventral tegmental area, substantia nigra, locus coeruleus, dorsal lateral mesencephalic nucleus, lateral reticular formation, nucleus papillioformis, and vestibular and cranial nerve nuclei. This pattern of connectivity is likely to reflect an important role of the avian DMA in the regulation of attention and arousal, memory formation, fear responses, affective components of pain, and hormonally mediated behaviors. J. Comp. Neurol. 459:301–326, 2003. © 2003 Wiley‐Liss, Inc.
No further loss of dorsal root ganglion cells after axotomy in p75 neurotrophin receptor knockout mice
Authors: Sørensen Bodil , Tandrup Trine , Koltzenburg Martin , Jakobsen Johannes
Published: March 2003

The role of the p75 neurotrophin receptor for neuronal survival after nerve crush was studied in L5 dorsal root ganglia (DRG) of knockout mice and controls with assumption‐free stereological methods. Numbers of neuronal A‐ and B‐cells were obtained using the optical fractionator and optical disector techniques. At birth, the total number of DRG neurons was 10,000 ± 2,600 in control mice compared with 5,100 ± 1,300 in p75 knockout mice. During postnatal development, 1,400 neuronal B‐cell bodies were lost in p75 knockouts (2P < 0.05) and 1,100 in controls (NS), whereas the A‐cell population remained stable. After a sciatic nerve crush, the total neuron loss in controls was 15.4% ± 3.5% (2P < 0.05) and 22.7% ± 5.1% (2P < 0.05) at days 14 and 42, respectively. In contrast, there was no loss in total number of neurons after crush in p75 knockout mice. Neuronal A‐cell number was unchanged after the crush in p75 knockouts as well as in controls at both times. At 14 days, the population of B‐cells was reduced by 24.8% ± 3.6% in controls and by 6.1% ± 3.5% in p75 knockouts, this difference being significant (2P < 0.001). At 42 days, the B‐cell loss was 29.6% ± 5.5% in controls and 4.2% ± 6.4% in p75 knockouts (2P < 0.001). In conclusion, the lack of the p75 receptor results in neuronal DRG cells that are resistant to nerve injury, pointing to a role for the receptor in apoptosis. J. Comp. Neurol. 459:242–250, 2003. © 2003 Wiley‐Liss, Inc.
Effects of an Added Iodine Source (C2H5I) on Ru Metal–Organic Chemical Vapor Deposition
Authors: Kim J.J. , Kim M.S. , Yoon D.Y.
Published: March 2003

The effects of an iodine source (C2H5I) on ruthenium (Ru) films grown on TiN/Ti/Si wafers by metal–organic (MO)CVD using Ru(EtCp)2 as a precursor were investigated. When an additional step of adsorbing iodine source was inserted during the Ru MOCVD process, the films became smoother and the root mean square (rms) surface roughness of the 30 nm thick Ru film became less than 10 % of the film thickness, as low as 1.71 nm. Moreover, the surface reaction‐limited regime was extended to 400 °C, causing a wide process window.
Chemical Vapor Infiltration of Rhenium
Authors: King H.C. , Renier M.C. , Ellzey K.E. , Lackey W.J.
Published: March 2003

Rhenium is of interest as a matrix material and fiber coating for high‐temperature structural composites. Despite prior success in the CVD of rhenium, there have been no studies on the chemical vapor infiltration (CVI) of this metal. The current work investigates the CVI of rhenium via the pyrolytic decomposition of ReCl5, prepared both by chlorination of rhenium metal and the sublimation of ReCl5. The feasibility of the CVI of rhenium was demonstrated for both methods. Statistical analyses showed that the amount of rhenium deposited increased for higher chlorine flow rates and lower preform temperatures, 750 °C vs. 900 °C, for the chlorination and sublimation processes, respectively.
Structure and Thermal Properties of Thin Film Poly(α‐methylstyrene) Deposited via Plasma‐Enhanced Chemical Vapor Deposition
Authors: Burkey D.D. , Gleason K.K.
Published: March 2003

Plasma‐enhanced (PE) CVD from α‐methylstyrene is a dry method for synthesizing directly patternable sacrificial materials for generating pores or air dielectric layers. Films deposited at low power excitation (40 W) decompose between 65 °C and 75 °C, leave minimal residue following a 400 °C anneal for 2 h, and have spectroscopic signatures of linear poly(α‐methylstyrene) (PaMS) as determined by nuclear magnetic resonance (NMR) spectroscopy and Fourier transform infrared (FTIR) spectroscopy. Increased plasma excitation power leads to cross‐linking and increased residue after annealing. All films also contain hydroxyl and carbonyl groups after exposure to air. Significant C–O–C inclusion occurs under continuous plasma excitation but not under pulsed‐plasma conditions.
A Kinetic Model for Step Coverage by Atomic Layer Deposition in Narrow Holes or Trenches
Authors: Gordon R.G. , Hausmann D. , Kim E. , Shepard J.
Published: March 2003

Highly conformal coatings can be deposited inside narrow features, such as holes, using complementary self‐limiting reactions of two vapors with a surface. A simple theory is developed for the conditions needed to deposit coatings with uniform thickness in narrow holes of arbitrary cross section. Two conditions are found to be necessary: 1) certain minimum amounts of vapor must be supplied, and 2) a certain minimum product of vapor pressure and its exposure time at the entrance to the hole. The theory is in good agreement with data from the reaction of hafnium dimethylamide vapor and water vapor to form hafnium dioxide films that are completely conformal in holes with an aspect ratio of 43. The theory provides simple scaling laws to predict the conditions needed to coat holes with other aspect ratios.
Chemical Vapor Deposition of TixSi1–xO2 Films: Precursor Chemistry Impacts Films Composition
Authors: Smith R.C. , Hoilien N. , Dykstra C. , Campbell S.A. , Roberts J.T. , Gladfelter W.L.
Published: March 2003

Thin films of composition TixSi1–xO2 were grown by low‐pressure (LP) CVD on silicon (100) substrates using tetraethyl orthosilicate (TEOS), [Si(OC2H5)4], and either titanium isopropoxide (TTIP), [Ti(O‐iPr)4], or anhydrous titanium tetranitrate (TN), [Ti(NO3)4], as the sources of SiO2 and TiO2, respectively. The substrate temperature was varied between 300 °C and 535 °C, and the individual precursor delivery rates ranged from 5 sccm to 100 sccm. Under these conditions, growth rates ranging from 0.6 nm min–1 to 90.0 nm min–1 were observed. As‐deposited films were amorphous to X‐rays, and cross‐sectional transmission electron microscopy (TEM) images showed no compositional inhomogeneity. Rutherford backscattering (RBS) spectrometry revealed that the relative concentration of TiO2 and SiO2 was dependent upon the choice of TiO2 precursor. Possible multi‐precursor deposition scenarios are presented and discussed in relation to the observed variation of film stoichiometry. For the TTIP–TEOS pair, the systematic variation of Ti content with deposition conditions could be accounted for by a growth scenario that limits SiO2 growth to TiO2 sites within the composite film. For the case of TN–TEOS the Ti content remained close to 50 % for all conditions studied. A specific chemical reaction between TN and TEOS prior to film deposition accounts for the observed composition.
The Metal–Organic Chemical Vapor Deposition of Lanthanum Nickelate Electrodes for Use in Ferroelectric Devices
Authors: Lane P.A. , Crosbie M.J. , Wright P.J. , Donohue P.P. , Hirst P.J. , Reeves C.L. , Anthony C.J. , Jones J.C. , Todd M.A. , Williams D.J.
Published: March 2003

Lanthanum nickelate layers have been deposited onto 100 mm diameter silicon/silicon dioxide and (0001) sapphire substrates by liquid‐delivery metal–organic (MO) CVD using the precursors La(thd)3 and Ni(thd)2 (thd = 2,2,6,6‐tetramethyl‐3,5‐heptanedionato) dissolved in tetrahydrofuran and heptane. The LaNiO3 (LNO) was deposited at 630 °C in an oxidizing atmosphere, and the as‐grown layers were highly crystalline and highly (110)‐oriented on Si/SiO2. Electrical resistivity studies were performed and showed a dependence on the La/Ni ratio, the substrate used, and the post‐deposition annealing conditions. A minimum electrical resistivity value of 300 μΩ cm was measured for LNO deposited on (0001) sapphire and rapidly annealed at 750 °C. The resistivity values of the LNO layers deposited onto silicon/silicon dioxide were higher, with a minimum value of 1 mΩ cm. The rapid annealing at 750 °C resulted in cracking of some of the LNO layers deposited onto the silicon substrates. However, the layers that were nickel‐rich withstood the annealing treatment better and showed little evidence of cracking.
Deposition of Compositionally Graded Mullite/Alumina Coatings from Mixtures of SiCl4, AlCl3, CO2 and H2
Authors: Nitodas S.F. , Sotirchos S.V.
Published: March 2003

Using CVD, compositionally graded coatings of mullite (3 Al2O3·2 SiO2) and alumina (Al2O3) were deposited on Si‐coated substrates from mixtures of silicon tetrachloride, aluminum trichloride, carbon dioxide, and hydrogen. The coatings were compositionally graded, with the Al/Si ratio increasing towards the outer layer of the coatings. The preparation of the coatings was carried out in a vertical, hot‐wall CVD reactor. The results of previous experimental studies on the deposition of aluminosilicate species have been used to identify operating conditions where deposition of coatings with alumina content equal to, or greater than, that corresponding to stoichiometric mullite was possible. The scheme for the preparation of the graded mullite/alumina coatings was based on utilizing the positive effect of decreasing the residence time of the reactive mixture in the reactor, and of increasing the Al/Si ratio in the feed on the incorporation of Al2O3 in the deposit.
Comparison of reagents for shape analysis of fixed cells by automated fluorescence microscopy
Authors: Elliott John T. , Tona Alessandro , Plant Anne L.
Published: March 2003

Background

Cell size and shape have been implicated as potentiators of intracellular signaling events and as indicators of abnormal cell behavior. Automated microscopy and image analysis can provide quantitative information about the size and shape of cultured cells, but it requires that the edge of a cell be clearly identified. Generating adequate contrast at the edge of thin well‐spread cells can be challenging.

Methods

We compared six (five chemically reactive and one lipophilic) fluorescent molecules—5‐chloromethyl fluorescein diacetate (CMFDA, CellTracker green), fluorescein‐5‐maleimide, fluorescein‐5‐isothiocyanate (FITC), 5‐iodoacetamidofluorescein, 5(6)‐carboxy fluorescein‐N‐hydroxysuccinimidyl ester, and N‐fluorescein‐1,2‐dihexadecanoyl‐sn‐glycerol‐3‐phosphoethanolamine—for their effectiveness as stains for automated morphology analysis of fixed cells.

Results

Formaldehyde‐fixed rat aortic smooth muscle cells stained with fluorescein‐5‐maleimide or FITC exhibited an average intensity that was at least twofold greater than cells stained with CMFDA even when subjected to a 25‐fold shorter exposure time. Cell area determined with the higher intensity stains was less sensitive to threshold settings during automated cell morphology analysis.

Conclusion

A procedure that includes the use of fluorescein‐5‐maleimide or FITC for staining fixed cell provides sensitivity sufficient to permit rapid, automated, morphologic analysis of well‐spread fixed cells. Cytometry Part A 52A:90–100, 2003. Published 2003 Wiley‐Liss, Inc.
Leukocyte apoptosis in whole blood involves platelet‐dependent coaggregation
Authors: Hartz S. , Menart B. , Tschoepe D.
Published: March 2003

Background

Activated leukocytes and platelet–leukocyte interaction are involved in the pathogenesis of thrombotic and inflammatory events. Because apoptosis is a prerequisite for the successful resolution of an inflammatory response, we investigated the amount of apoptotic peripheral blood leukocytes (PBLs) in whole blood and their possible functional relation with the platelet–leukocyte interaction by a flow cytometric assay using APO 2.7 antibody for the detection of apoptosis

Methods

Thirty healthy subjects volunteered for the study. PBL apoptosis in seven volunteers was induced by phorbol 12‐myristate 13‐acetate or while standing at rest.

Results

Apoptosis was observed in all types of leukocytes (0.7% neutrophils, 1.5% monocytes, and 0.3% lymphocytes). Apoptosis was found predominantly in platelet and leukocyte coaggregates (<1% of nonaggregated leukocytes vs. 9% of platelet and leukocyte coaggregates). This phenomenon was even more pronounced after induction of leukocyte apoptosis in vitro (66% of platelet and leukocyte coaggregates).

Conclusions

Apoptosis and platelet–leukocyte interaction seemed to be closely related phenomena, and apoptotic leukocytes seemed to trigger adhesion and, hence, activation of platelets. Because platelet–leukocyte interaction is involved in the pathogenesis of thrombotic events, apoptotic leukocytes may constitute an additional prothrombotic trigger. Cytometry Part A 52A:117–121, 2003. © 2003 Wiley‐Liss, Inc.
Chronology of cellular alterations during 7‐ketocholesterol–induced cell death on A7R5 rat smooth muscle cells: Analysis by time lapse‐video microscopy and conventional fluorescence microscopy
Authors: Zahm Jean‐Marie , Baconnais Sonia , Monier Serge , Bonnet Noël , Bessède Ginette , Gambert Philippe , Puchelle Edith , Lizard Gérard
Published: March 2003

Background

Time‐lapse video microscopy was used to determine whether mitochondrial and nuclear changes (decrease in mitochondrial transmembrane potential, condensation, and/or fragmentation of the nuclei, morphologic features typical of apoptosis) occurring during 7‐ketocholesterol–induced cell death on A7R5 rat smooth muscle cells took place before or after the loss of cell adhesion. In addition, changes in actin organization were followed by conventional fluorescence microscopy.

Methods

Morphologic, functional, and spatial changes at the mitochondrial level were investigated with 3,3′‐dihexyloxacarbocyanine iodide and/or MitoTracker Red, and nuclear morphology was characterized by staining with Hoechst 33342. Actin fibers, which are major components of the filament network of the cytoskeleton, were visualized with phalloidin linked to fluorescein. The numbers of adherent and nonadherent cells were determined by cell counting.

Results

7‐Ketocholesterol–induced cell death was associated with a rapid alteration of actin fibers, a loss of intercellular junctions, and cell shape modifications. Analysis of mitochondrial transmembrane potential showed successively a hyperpolarization and a more or less pronounced progressive decrease followed by a dramatic drop associated with an increase in Hoechst 33342 staining, reflecting chromatin condensation and morphologic changes in the nuclei.

Conclusions

During cell death induced by 7‐ketocholesterol in A7R5 rat smooth muscle cells, the different methods of microscopy allowed us to establish that alterations of actin fibers and mitochondrial dysfunctions occurred before condensation and/or fragmentation of the nuclei, which preceded the loss of cell adhesion. Cytometry Part A 52A:57–69, 2003. © 2003 Wiley‐Liss, Inc.
DNA content, chromatin texture and nuclear morphology in benzo[a]pyrene‐transformed human breast epithelial cells after microcell‐mediated transfer of chromosomes 11 and 17
Authors: Mello Maria Luiza S. , de Campos Vidal Benedicto , Lareef Mohamed H. , Hu Yun F. , Yang Xiaoqi , Russo Jose
Published: March 2003

Background

A relation between the changes in DNA content and chromatin supra‐organization and the expression of gradual steps of tumorigenesis has been assessed by image analysis in human breast epithelial cells (MCF‐10F) treated with benzo[a]pyrene (BP) (cell lines BP1, BP1‐E, BP1‐Tras, and others).

Methods

Because abnormal chromosomes 11 and 17 have been associated with neoplastic progression in BP‐transformed MCF‐10F cells, image analysis of Feulgen‐stained tumorigenic BP1‐E cells with the microcell‐mediated chromosome transfer of normal chromosomes 11 and 17 was carried out.

Results

A tendency of DNA amount distribution and nuclear size restoration to values typical of non‐transformed MCF‐10F cells was demonstrated, especially after the transfer of chromosome 17. No reversion in chromatin texture was found after the transfer of chromosome 11 or 17.

Conclusions

Although the presence of a normal chromosome 17 should be considered among the necessary steps for tumorigenic human breast epithelial cells to recover their normality, a more complex genome balance is required for the entire nuclear chromatin of these cells to recover its totally normal supra‐organization and expression. Cytometry Part A 52A:70–76, 2003. © 2003 Wiley‐Liss, Inc.
Effect of anti‐CD20 monoclonal antibody, Rituxan, on cynomolgus monkey and human B cells in a whole blood matrix
Authors: Vugmeyster Yulia , Howell Kathy , Bakshl Anahid , Flores Clarissa , Canova‐Davis Eleanor
Published: March 2003

Background

Cynomolgus monkeys are widely used animal models in biomedical research. The differences between cynomolgus monkey and human B cells are not completely understood. However, these differences are of crucial importance for interpretation of data from studies on new therapeutic agents aimed at B‐cell depletion, such as anti‐CD20 monoclonal antibodies.

Methods

Multicolor fluorescence‐activated cell sorting analysis of peripheral blood B cells was performed on samples treated ex vivo with the anti‐CD20 therapeutic monoclonal antibody, Rituxan, in a whole blood matrix.

Results

In contrast to humans, cynomolgus monkeys had two distinct B‐cell subsets, CD20highCD40lowCD21− and CD20lowCD40highCD21+. These B‐cell subsets had a 2.5‐fold difference in the EC50 for Rituxan binding and differed significantly in their in vitro susceptibility to Rituxan depletion. Human B cells were similar to the CD20lowCD40highCD21+ cynomolgus monkey B cells with regard to their EC50 for Rituxan and response to Rituxan in a whole blood matrix assay. CD21 was upregulated, whereas CD40 was downregulated at incubation with Rituxan in the CD20lowCD40highCD21+ monkey and human B cells in a concentration‐dependent manner.

Conclusions

These findings have direct implications for in vivo studies of therapeutic agents that target B cells in cynomolgus monkeys and for extrapolation of the results to humans. In addition, our data are consistent with the model in which CD20, CD21, and CD40 exist in a supramolecular complex that is affected by anti‐CD20 monoclonal antibodies. Cytometry Part A 52A:101–109, 2003. © 2003 Wiley‐Liss, Inc.
Measuring containment of viable infectious cell sorting in high‐velocity cell sorters
Authors: Perfetto Stephen P. , Ambrozak David R. , Koup Richard A. , Roederer Mario
Published: March 2003

Background

With the advent of high‐speed sorters, aerosols are a considerable safety concern when sorting viable infectious materials. We describe a four‐part safety procedure for validating the containment.

Methods

This procedure includes aerosol containment, physical barriers, environmental controls, and personal protection. The Aerosol Management System (AMS) produces a negative pressure within the sort chamber, where aerosols are forced through a HEPA filter. Physical barriers include the manufacturer's standard plastic shield and panels. The flow cytometer was contained within a BSL‐3 laboratory for maximum environmental control, and the operator was protected by a respiratory system. Containment was measured by using highly fluorescent Glo‐Germ particles under the same conditions as the cell sort.

Results

Escaping aerosols were vacuumed for 10 min onto a glass slide and examined. With the AMS active and the cytometer producing the maximum aerosols possible, Glo‐Germ particles remained within the sort chamber. Measurements taken directly outside the door averaged fewer than one particle per slide, and those taken at 2 ft away and on top of the sorter were completely negative.

Conclusions

With this monitoring system in place, aerosols can be efficiently measured, thus reducing the risk to the operator while sorting viable infectious cells. Cytometry Part A 52A:122–130, 2003. Published 2003 Wiley‐Liss, Inc.
Anxiolytic effects of acute tryptophan depletion in anorexia nervosa
Authors: Kaye Walter H. , Barbarich Nicole C. , Putnam Karen , Gendall Kelly A. , Fernstrom John , Fernstrom Madelyn , McConaha Claire W. , Kishore Anita
Published: March 2003

Objective

Recent studies have raised the question as to whether a dysregulation of the neurotransmitter serotonin may contribute to the alterations in mood seen in anorexia nervosa (AN). People with AN tend to be anxious, obsessional, perfectionistic, and harm avoidant. These traits are premorbid and persist after recovery. It has been suggested that increased activity of brain serotonin systems could contribute to this pathologic condition. Dieting in AN, which serves to reduce plasma levels of tryptophan (TRP), may serve to reduce symptoms of dysphoric mood.

Method

Fourteen women currently symptomatic with AN (ILL AN), 14 women recovered from AN (REC AN), and 15 healthy control women (CW) underwent acute tryptophan depletion (ATD). Measures of psychological state were self‐assessed at baseline and hourly after ATD to determine whether ATD would reduce negative mood.

Results

ILL AN and REC AN had significantly higher mean baseline TRP/LNAA (tryptophan/large neutral amino acids) ratios compared with CW. In contrast to placebo, the ATD challenge demonstrated a significantly greater reduction in the TRP/LNAA ratio for ILL AN (−95%) and REC AN (−84%) compared with CW (−70 %). Both the ILL AN and REC AN had a significant reduction in anxiety on the ATD day compared with the placebo day.

Discussion

These data demonstrate that a dietary‐induced reduction of TRP, the precursor of serotonin, is associated with decreased anxiety in people with AN. Restricting dietary intake may represent a mechanism through which individuals with AN modulate a dysphoric mood. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 257–267, 2003.
Comparison of group and individual cognitive‐behavioral therapy for patients with bulimia nervosa
Authors: Chen Eunice , Touyz Stephen W. , Beumont Pierre J.V. , Fairburn Christopher G. , Griffiths Rosalyn , Butow Phyllis , Russell Janice , Schotte David E. , Gertler Robert , Basten Christopher
Published: March 2003

Objective

The clinical effectiveness of group and individual cognitive‐behavioral therapy (CBT) for bulimia nervosa (BN) was compared.

Method

Sixty BN patients from hospitals and general practitioners in Sydney, Australia, were allocated randomly to group or individual CBT. Forty‐four completed treatment (n = 22 in group CBT and n = 22 in individual CBT). Patients were assessed at pretreatment, posttreatment, and at 3 and 6 months follow‐up with the Eating Disorder Examination‐12 and self‐report questionnaires examining weight and shape attitudes (Eating Disorder Inventory‐2), social adjustment (Socail Adjustment Scale‐Modified), self‐esteem (Rosenberg Self‐Esteem Scale), and general psychopathology (Symptom Checklist 90R).

Results

The effects of group and individual CBT were equivalent on most measures. However, a significantly greater proportion of individual CBT patients than group CBT patients were abstinent from bulimic behaviors at posttreatment, but not at follow‐up.

Discussion

This has implications for the delivery of cost‐effective and clinically effective treatment for BN. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 241–254, 2003.
The nature of body image disturbance in patients with binge eating disorder
Authors: Masheb Robin M. , Grilo Carlos M.
Published: March 2003

Objective

This study examined the distinction between body dissatisfaction and self‐evaluation unduly influenced by body shape and weight, and their longitudinal relationships to depressive symptomatology and self‐esteem in patients with binge eating disorder (BED).

Method

Ninety‐seven patients with BED completed measures tapping these constructs at baseline and again 4 weeks later.

Results

Change in body dissatisfaction was significantly correlated with both change in depressive symptomatology and change in self‐esteem over time, whereas change in self‐evaluation was significantly correlated only with change in self‐esteem. In addition, change in shape concern, but not change in weight concern, was significantly correlated with change in self‐esteem only.

Discussion

These findings suggest that self‐evaluation unduly influenced by body shape is a more useful indicator for BED than body dissatisfaction or self‐evaluation unduly influenced by weight. © 2003 by Wiley Periodicals, Inc. Int J Eat Disord 33: 333–341, 2003.