bluuebunny/crossref_metadata_2025 huggingface dataset:
Endometrial‐type cells in cervico‐vaginal smears: Clinical significance and cytopathologic correlates
Authors: Karim Baktiar O. , Burroughs Frances H. , Rosenthal Dorothy L. , Ali Syed Z.
Published: October 2004

This study assessed the significance of endometrial‐type cells (ETC) in cervico‐vaginal (CV) smears in patients 45 yr and older by evaluating quantitatively and qualitatively the relationship of ETC to subsequent endometrial pathology. In a 3‐yr period (1997–1999) at the Johns Hopkins Cytopathology Laboratory, 1,162 CV smears with ETC were found in patients 45 yr and older. In all cases with positive follow‐up by tissue biopsy/resection, i.e., endometrial hyperplasia (EHP) and endometrial adenocarcinoma (EACA), the CV smears were reevaluated and compared to the control group (i.e., patients with normal endometrial biopsies). The following cytologic characteristics were recorded: quantity of ETC, type of ETC (epithelial, stromal/histiocyte‐type, or mixed), cellular atypism, presence of inflammation, smear background, and associated estrogen effect. Of the 1,162 patients with ETC, 432 cases (37%) had tissue follow‐up as follows: EACA, 18 (4.2%); EHP, 20 (4.6%); leiomyomata, 17 (3.9%); endometrial polyp, 21 (4.9%); benign/within normal limits (WNL), 339 (78.5%); nondiagnostic, 17 (3.9%). Cytologic characteristics of ETC showed subtle but definite quantitative and qualitative differences in the major pathologic groups examined. All instances of cancers and hyperplasia occurred in postmenopausal (PM) women. Abnormal vaginal bleeding was the presenting complaint in 66.7% of EACA, 45% of EHP, and 28.6% of benign endometrium. ETC in PM CV smears are associated with significant endometrial lesions (carcinoma, hyperplasia) in less than 9% of the patients. It is concluded that the distinction between EACA and EHP can be difficult. The presence of a large number of ETC, predominantly of epithelial or a mixed (epithelial and stromal) type, is more often associated with EACA or EHP than with benign endometrium. The presence of cytologic atypia and/or diathesis is additionally helpful for the diagnosis of EACA. Diagn. Cytopathol. 2002;26:123–127; DOI 10.1002/dc.10062 © 2002 Wiley‐Liss, Inc.
Breast masses in males: Multi‐institutional experience on fine‐needle aspiration
Authors: Siddiqui Momin T. , Zakowski Maureen F. , Ashfaq Raheela , Ali Syed Z.
Published: October 2004

Male breast masses are uncommon pathologic findings. They are rarely aspirated, resulting in limited cytopathologic experience. The following study describes the cytopathology of male breast lesions from data collected for a period of 10 yr from three large institutions. A total of 14,026 breast aspirations were performed of which 614 were from male patients. All cases were reviewed and correlated with the appropriate clinicopathologic follow‐up. The FNA diagnoses were as follows: benign, 427 cases (gynecomastia 353, fat necrosis 21, miscellaneous 53); malignant, 32 cases (ductal carcinoma nos 15, metastatic tumors 17); and atypical/suspicious, 61 cases. Ninety‐four cases were nondiagnostic due to scant cellularity. Male breast aspirates accounted for 4.3% of the total breast FNAs performed. The clinicopathologic follow‐up in both the benign and malignant categories showed 100% correlation. The overall sensitivity was 95.3%, specificity was 100%, and diagnostic accuracy was 98%. A relatively high specimen unsatisfactory rate was seen (>15%). The commonest cytopathologic diagnosis was gynecomastia, followed by ductal carcinoma. Florid duct atypia in gynecomastia may mimic adenocarcinoma, necessitating a higher threshold for cytopathologic interpretation for malignancy in males. Diagn. Cytopathol. 2002;26:87–91; DOI 10.1002/dc.10066 © 2002 Wiley‐Liss, Inc.
Analysis of two distinct retinoic acid response elements in the homeobox gene Hoxb1 in transgenic mice
Authors: Huang Danyang , Chen Siming W. , Gudas Lorraine J.
Published: October 2004

Expression of vertebrate Hox genes is regulated by retinoids such as retinoic acid (RA) in cell culture and in early embryonic development. Retinoic acid response elements (RAREs) have been identified in Hox gene regulatory regions, suggesting that endogenous retinoids may be involved in the direct control of Hox gene patterning functions. Previously, two RAREs located 3′ of the murine Hoxb1 gene, a DR2 RARE and a DR5 RARE, have been shown to regulate Hoxb1 mRNA expression in the neural epithelium and the foregut region, respectively; the foregut develops into the esophagus, liver, pancreas, lungs, and stomach. We have now examined the functional roles of these two types of 3′ RAREs in regulating Hoxb1 expression at different stages of gestation, from embryonic day 7.5 to 13.5, in transgenic mice carrying specific RARE mutations. We demonstrate that the DR5 RARE is required for the regulation of Hoxb‐1 transgene region‐specific expression in the gut and extraembryonic tissues, as well as for the RA‐induced anteriorization of Hoxb‐1 transgene expression in the gut. In contrast, expression of the Hoxb1 transgene in the neural epithelium requires only the DR2 RARE. By in situ hybridization, we have identified a new site of Hoxb1 expression in the developing forelimbs at approximately day 12.5, and we show that, in transgenic embryos, expression in the forelimb buds requires that either the DR2 or the DR5 RARE is functional. Attainment of a high level of Hoxb1 transgene expression in other regions, such as in rhombomere 4 (r4) and in the somites, requires that both the DR2 and DR5 RAREs are functional. In addition, our transgenic data indicate that the Hoxb1 gene is expressed in other tissues such as the hernia gut, genital eminence, and lung. Our analysis shows that endogenous retinoids act through individual DR2 and DR5 RAREs to regulate Hoxb1 expression in different regions of the embryo and that functional redundancy between these DR2 and DR5 RAREs does not exist with respect to neural epithelium and the gut Hoxb1 expression. © 2002 Wiley‐Liss, Inc.
Broadband and low‐profile Yagi–Uda antenna composed of inverted‐F and inverted‐L shaped elements
Authors: Taguchi Yujiro , Chen Qiang , Sawaya Kunio
Published: October 2004

A broadband Yagi–Uda antenna composed of an excited inverted‐F element and two parasitic inverter‐L elements, which is used for the antennas of the SSR (secondary surveillance radar) and equipped on an airplane, is proposed. By locating a director close to the excited inverted‐F element, such as about 0.05λ0 for the array space between these elements, an antenna having a performance of the bandwidth of 18.8% and unidirectional pattern in this bandwidth is obtained with a total dimension of about 0.1λ0 (height) × 0.4λ0 (length). The validity of the calculated values is experimentally confirmed. © 2001 Scripta Technica, Electron Comm Jpn Pt 1, 85(1): 43–48, 2002
Response speed and optical investigation of inGaN/gaN multiple quantum well light‐emitting diodes (LED)
Authors: Morita Yosuke , Wakita Koichi
Published: October 2004

Transmission experiments for a local area network (LAN) using blue‐light‐emitting diodes (LEDs) with InGaN/GaN multiple quantum well (MQW) and plastic optical fibers (POFs) have been conducted. Audio analog signals have been transmitted up to 1800 kHz, which corresponds to an optical 1.5 dB bandwidth of LED response. The response speed of these diodes has been investigated by varying the operating conditions: dc bias, pulse amplitude, and pulse shape. The LED rise time is reduced from 0.26 μs to 0.19 μs by changing the electrical pulse amplitude from 0.5 V to 1.2 V, whereas the fall time (0.20 μs) does not change. On the other hand, the fall time is reduced from 0.20 μs to 0.14 μs by adding negative pulses after the applied positive pulses. It is shown that the direct‐modulation speed of these diodes is limited by the time constant associated with device capacitance. Electroluminescence and photocurrent spectra of the LEDs were also investigated; blueshifts were observed for both peaks in the spectra. © 2001 Scripta Technica, Electr Eng Jpn, 137(3): 47–51, 2001
Expression of fractalkine (CX3CL1) and its receptor, CX3CR1, during acute and chronic inflammation in the rodent CNS
Authors: Hughes Paula Marie , Botham Michelle Sandra , Frentzel Stefan , Mir Anis , Perry Victor Hugh
Published: October 2004

In this study, we investigate the expression of fractalkine (CX3CL1) and the fractalkine receptor (CX3CR1) in the naive rat and mouse central nervous system (CNS). We determine if the expression of this chemokine and its receptor are altered during chronic or acute inflammation in the CNS. In addition, we determine if CX3CL1, which has been reported to be chemoattractant to leukocytes in vitro, is capable of acting as a chemoattractant in the CNS in vivo. Immunohistochemistry was performed using primary antibodies recognizing soluble and membrane‐bound CX3CL1 and the N‐terminus of the CX3CR1. We found that neurons in the naive rodent brain are immunoreactive for CX3CL1 and CX3CR1, both showing a perinuclear staining pattern. Resident microglia associated with the parenchyma and macrophages in the meninges and choroid plexus constituitively express CX3CR1. In a prion model of chronic neurodegeneration and inflammation, CX3CL1 immunoreactivity is upregulated in astrocytes and CX3CR1 expression is elevated on microglia. In surviving neurons, expression of CX3CL1 appears unaltered relative to normal neurons. There is a decrease in neuronal CX3CR1 expression. Acute inflammatory responses in the CNS, induced by stereotaxic injections of lipopolysaccharide or kainic acid, results in activation of microglia and astrocytes but no detectable changes in the glial expression of CX3CL1 or CX3CR1. The expression of CX3CL1 and CX3CR1 by glial cells during inflammation in the CNS may be influenced by the surrounding cytokine milieu, which has been shown to differ in acute and chronic neuroinflammation. GLIA 37:314–327, 2002. © 2002 Wiley‐Liss, Inc.
Efficient recolonisation of progenitor‐depleted areas of the CNS by adult oligodendrocyte progenitor cells
Authors: Chari Divya M. , Blakemore William F.
Published: October 2004

A widely quoted hypothesis for the failure of remyelination in multiple sclerosis (MS) is the exhaustion of the oligodendrocyte progenitor cell (OPC) pool that is strongly implicated as the source of remyelinating oligodendrocytes in demyelinating lesions. Despite this, little is known about the responses of adult OPCs to adjacent areas of the CNS from which their numbers are depleted. We have developed an experimental model to study the pattern and rate of repopulation of OPC‐depleted zones, by endogenous OPCs in the adult rat spinal cord. By X‐irradiating short lengths of the spinal cord with 40 Gy of X‐irradiation, we were able to produce a highly localised depletion of OPCs that allowed us to study the responses of cells located in adjacent normal areas, to this local depletion. Using both NG2 immunohistochemistry and PDGFαR in situ hybridisation to identify OPCs, we demonstrate that endogenous OPCs repopulated the depleted areas slowly, but completely. This repopulation occurred at the rate of approximately 0.5 mm/week in the first month. Most cells at the leading edge of repopulation had complex, branching morphologies. The repopulation process was capable of restoring the density of progenitors in repopulated areas to that of normal tissue and was not associated with a secondary progenitor loss in tissue from which progenitor cells were generated. These findings indicate that depletion of the OPC population around lesions is not likely to be the primary explanation for remyelination failure in MS. GLIA 37:307–313, 2002. © 2002 Wiley‐Liss, Inc.
Stable transfection of cDNAs targeting specific steps of glycogen metabolism supports the existence of active gluconeogenesis in mouse cultured astrocytes
Authors: Bernard‐Hélary Katy , Ardourel Maryvonne , Magistretti Pierre , Hévor Tobias , Cloix Jean‐François
Published: October 2004

In order to assess the participation of astrocytic gluconeogenesis in the synthesis of glycogen, mouse astrocytes were stably transfected with antisense cDNA of fructose‐1,6‐bisphosphatase (FBPase) and with sense and antisense cDNAs of glycogen synthase (GS). The antisenses of FBPase and GS have similar significant effect in decreasing astrocyte glycogen content by 60%, while sense GS significantly increased glycogen content by 100%. The FBPase activity was decreased by all three cDNAs used, while glycogen phosphorylase was not altered. The activity of GS was decreased by the antisense GS and increased by the sense GS. These data demonstrate that the gluconeogenesis in astrocytes is involved in the glycogenesis modulation. GLIA 37:379–382, 2002. © 2002 Wiley‐Liss, Inc.
BK channels in human glioma cells have enhanced calcium sensitivity
Authors: Ransom Christopher B. , Liu Xiaojin , Sontheimer Harald
Published: October 2004

We have previously demonstrated the expression of large‐conductance, calcium‐activated potassium (BK) channels in human glioma cells. In the present study, we characterized the calcium sensitivity of glioma BK channels in excised membrane patches. Channels in inside‐out patches were activated at −60 mV by 2.1 × 10−6 M cytosolic Ca2+, were highly K+‐selective, and had a slope conductance of ≈210 pS. We characterized the Ca2+ sensitivity of these channels in detail by isolating BK currents in outside‐out patches with different free [Ca2+]i. The half‐maximal voltage for channel activation, V0.5, of glioma BK currents in outside‐out patches was +138 mV with 0 Ca2+/10 EGTA. V0.5 was shifted to +81 mV and −14 mV with free [Ca2+]i of 1.5 × 10−7 M and 2.1 × 10−6 M, respectively. These results suggest that glioma BK channels have a higher Ca2+ sensitivity than that described in many other human preparations. Data obtained from a cloned BK channel (hbr5) expressed in HEK cells support the conclusion that glioma BK channels have an unusually high sensitivity to calcium. In addition, the sensitivity of glioma BK channels to the BK inhibitor tetrandrine suggests the expression of BK channel auxiliary β‐subunits by glioma cells. Expression of the auxiliary β‐subunit of BK channels by glioma cells may relate to the high Ca2+ sensitivity of glioma BK channels. GLIA 38:281–291, 2002. © 2002 Wiley‐Liss, Inc.
Life imaging of peroxynitrite in rat microglial and astroglial cells: Role of superoxide and antioxidants
Authors: Possel Heiko , Noack Heiko , Keilhoff Gerburg , Wolf Gerald
Published: October 2004

Free radicals, such as superoxide and nitric oxide, are known to play a role in a number of inflammatory and degenerative brain diseases, in which resident microglia upregulate the inducible nitric oxide synthase (iNOS) and thus produce large amounts of nitric oxide. Simultaneously, microglia generate superoxide mainly via NADPH‐oxidase, which reacts at a diffusion‐limited rate with nitric oxide to form the powerful oxidant peroxynitrite. We used mixed astroglial/microglial cultures to study the effects of iNOS induction by lipopolysaccharide and interferon‐γ on free radical formation. Using the fluorogenic compound 2,7‐dihydrodichlorofluorescein diacetate, we monitored cellular peroxynitrite formation by confocal laser microscopy. Peroxynitrite formation in continuously nitric oxide‐producing microglial cells was rather limited. However, activation of the superoxide‐generating enzyme NADPH‐oxidase dramatically increased DCF fluorescence within a few minutes. We conclude that superoxide is the limiting factor for peroxynitrite formation. Since the formation and oxidant activity of peroxynitrite depends strongly on the availability of cellular antioxidants, we investigated the capacity of several compounds to influence peroxynitrite formation. Among the substances under investigation in this study, glutathione and the synthetic compound ebselen had a major effect on preventing peroxynitrite formation, whereas ascorbate failed to decrease peroxynitrite levels. GLIA 38:339–350, 2002. © 2002 Wiley‐Liss, Inc.
RhoA inhibition is a key step in pituicyte stellation induced by A1‐type adenosine receptor activation
Authors: Rosso Lia , Peteri‐Brunbäck Brigitta , Vouret‐Craviari Valérie , Deroanne Christophe , Troadec Jean‐Denis , Thirion Sylvie , Van Obberghen‐Schilling Ellen , Mienville Jean‐Marc
Published: October 2004

Pituicyte stellation in vitro represents a useful model with which to study morphological changes that occur in vivo in these cells during times of high neurohypophysial hormone output. This model has helped us establish the hypothesis of a purinergic regulation of pituicyte morphological plasticity. We first show that ATP induces stellation in 37% of pituicytes, an effect that is secondary to the metabolism of ATP to adenosine. Adenosine‐induced stellation of pituicytes appears to be mediated by A1‐type receptors. The effect is independent of intracellular calcium and does not involve the mitogen‐activated protein kinase pathway. The basal (nonstellate) state of pituicytes depends on tonic activation of a Rho GTPase because both C3 transferase (a Rho inhibitor) and Y‐27632 (an inhibitor of p160Rho kinase) can induce stellation. Lysophosphatidic acid, a Rho activator, blocks the morphogenic effect of adenosine dose‐dependently. Using a specific RhoA pull‐down assay, we also show that downregulation of activated RhoA is the key event coupling A1 receptor activation to pituicyte stellation, via F‐actin depolymerization and microtubule reorganization. Finally, both vasopressin and oxytocin can prevent or reverse adenosine‐induced stellation. The effects of vasopressin, and those of high concentrations of oxytocin, are mediated through V1a receptors. Placed within the context of the relevant literature, our data suggest the possibility of a purinergic regulation of pituicyte morphological plasticity and subsequent modulation of hormone release, with these hormones providing a negative feedback mechanism. GLIA 38:351–362, 2002. © 2002 Wiley‐Liss, Inc.
Combined endovascular and surgical treatment of head and neck paragangliomas—A team approach
Authors: Persky Mark S. , Setton Avi , Niimi Yasunari , Hartman Jonathan , Frank Douglas , Berenstein Alex
Published: October 2004

Background

Paragangliomas are highly vascular tumors of neural crest origin that involve the walls of blood vessels or specific nerves within the head and neck. They may be multicentric, and they are rarely malignant. Surgery is the preferred treatment, and these tumors frequently extend to the skull base. There has been controversy concerning the role of preoperative angiography and embolization of these tumors and the benefits that these procedures offer in the evaluation and management of paragangliomas.

Methods

Forty‐seven patients with 53 paragangliomas were treated from the period of 1990–2000. Initial evaluation usually included CT and/or MRI. All patients underwent bilateral carotid angiography, embolization of the tumor nidus, and cerebral angiography to define the patency of the circle of Willis. Carotid occlusion studies were performed with the patient under neuroleptic anesthesia when indicated. The tumors were excised within 48 hours of embolization.

Results

Carotid body tumors represented the most common paraganglioma, accounting for 28 tumors (53%). All patients underwent angiography and embolization with six patients (13%), demonstrating complications (three of these patients had embolized tumor involving the affected nerves). Cerebral angiography was performed in 28 patients, and 5 of these patients underwent and tolerated carotid occlusion studies. The range of mean blood loss according to tumor type was 450 to 517 mL. Postoperative cranial nerve dysfunction depended on the tumor type resected. Carotid body tumor surgery frequently required sympathetic chain resection (21%), with jugular and vagal paraganglioma removal frequently resulting in lower cranial nerve resection. These patients required various modes of postoperative rehabilitation, especially vocal cord medialization and swallowing therapy.

Conclusions

The combined endovascular and surgical treatment of paragangliomas is acceptably safe and effective for treating these highly vascular neoplasms. Adequate resection may often require sacrifice of one or more cranial nerves, and appropriate rehabilitation is important in the treatment regimen. © 2002 Wiley Periodicals, Inc.
In vitro degradation and fracture toughness of multilayered porous poly(propylene fumarate)/β‐tricalcium phosphate scaffolds
Authors: Wolfe Michael S. , Dean David , Chen Jeffrey E. , Fisher John P. , Han Seungho , Rimnac Clare M. , Mikos Antonios G.
Published: October 2004

This study investigated the in vitro degradation of poly(propylene fumarate)/β‐tricalcium phosphate (PPF/β‐TCP) scaffolds in pH 7.4 phosphate‐buffered saline at 37°C. Scaffold design consisted of three layers: two solid layers about a central layer of porous PPF foam. Solid PPF with molecular weights of 810 and 1450 Da was crosslinked under UV light. PPF foam was prepared by a photocrosslinking, porogen‐leaching method with an initial porogen content of 80 wt % and two sizes, 150–300 and 300–500 μm. Comparison of initial and residual weights demonstrated a 14.3 ± 2.0% loss of mass at 3 weeks and a 16.6 ± 1.8% loss of mass at 6 weeks. Observed pH values for all constructs remained stable (7.15–7.40) throughout the 3 to 6 weeks. Scanning electron micrographs of these scaffolds revealed some loss of foam material between 3 and 6 weeks; however, foam microarchitecture was intact. Solid PPF fracture toughness was tested for high and low molecular weight PPF, 0.376 ± 0.004 and 0.134 ± 0.015 MPa(m)1/2, respectively. These values are roughly one magnitude less than human cortical bone. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 159–164, 2002
Transmission electron microscopic visualization of the degradation and phagocytosis of a poly‐L‐lactide screw in cancellous bone: A long‐term experimental study
Authors: Laitinen Outi , Pihlajamäki Harri , Sukura Antti , Böstman Ole
Published: October 2004

The increasing clinical use of biodegradable implants in orthopedic surgery makes it necessary to determine their long‐term behavior in tissues. In this study, a biodegradable screw made of poly‐L‐lactide (PLLA) was inserted axially into the right distal femur in 18 rabbits. The degradation and phagocytosis process of PLLA was assessed histologically and by transmission electron microscopy (TEM). The follow‐up times were 3 and 4.5 years for groups of nine and eight animals, respectively. Abundant birefringent polymeric material was still present in the center of the implant channel in all specimens in both follow‐up groups. The PLLA material studied appeared to be a biologically relatively inert material, with only sparse reactive cellular activity at the tissue–implant boundary. In the TEM specimens, polymeric particles of an average area of 2 μm2 were seen to be located intracellularly within phagocytic cells. The spheric and polygonal particles were membrane‐bound and to a great extent filled up each phagocyte. In the 4.5‐year specimens, the size of the polymeric particles, measured as area and perimeter, was significantly smaller (p < 0.02) than that of the 3‐year specimens. The findings indicate that the ultimate degradation process of PLLA is much longer than it previously was thought to be. Complete degradation probably still would have taken years after the 4.5‐year span of this study. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 33–39, 2002
Detection of microscopic cracks in dental ceramic materials by fluorescent penetrant method
Authors: Fischer Horst , Karaca Fatma , Marx Rudolf
Published: October 2004

Ceramic materials are used as implants and prostheses because of their excellent biocompatibility and in the dental field beyond that, because of esthetic advantages and the little plaque accumulation. A disadvantage is their sensitivity to microscopic cracks because of their brittleness. Strength‐deteriorating microscopic cracks can be introduced into the ceramic surface by the manufacturing process. The objective of this study was to evaluate three methods on their efficiency to detect microscopic surface cracks of clinical relevance in dental ceramic materials. These methods were light‐optical microscopy, fluorescent microscopy after penetration with a fluorescent liquid, and scanning electron microscopy (SEM). It was found that microscopic cracks of critical sizes can be detected using the fluorescent penetrant method, which was not to be proven by light‐optical microscopy and even not by SEM. We conclude from our study that the fluorescent penetrant method could help to decrease clinical failures of dental ceramic components that are caused by surface microscopic cracks from the manufacturing process, if this method was routinely performed before the clinical use of the ceramic components. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 153–158, 2002
Biomaterial implants induce the inflammation marker CRP at the site of implantation
Authors: Löbler Marian , Saß Marko , Kunze Carmen , Schmitz Klaus‐Peter , Hopt Ulrich T.
Published: October 2004

Following implantation of biomaterial patches into the gastrointestinal tract, we analyzed the host's response towards the foreign material. Asymmetric patches of polydioxanone covered Vicryl or poly‐3‐hydroxybutyrate were sutured onto the rat stomach. Tissue samples were generated at distinct time intervals after surgery, and RNA profiles were compared by Differential Display. RT‐PCR analysis of gene candidates that seemed differentially expressed showed that vitamin D binding protein mRNA was induced in stomach tissue after implantation of the biomaterial patches. In parallel, the amount of C‐reactive protein mRNA was found to be increased transiently as well. Implants induce a tissue response that is specific for a given material. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 165–167, 2002
Improved sample preparation of biomaterials for in vitro genotoxicity testing using reference materials
Authors: Müller Boris P. , Ensslen Silke , Dott Wolfgang , Hollender Juliane
Published: October 2004

New biomaterial related reference materials with known genotoxic properties were produced in order to study the sample preparation and in vitro genotoxicity testing of biomaterials. We incorporated genotoxic substances like benzo[a]pyrene into the biomaterial Tecoflex®, a polyurethane frequently used for catheters and other applications. We demonstrated that the model compound benzo[a]pyrene is sufficiently extracted by organic solvents, whereas cell culture medium only extracts very limited quantities. By changing the medium several times during extraction the extracted amount was augmented. Using higher amounts of organic solvent in relation to the reference material's surface led to a higher recovery of extracted benzo[a]pyrene. For the in vitro genotoxicity testing using the Mammalian Cell Gene Mutation Test (HPRT test), Mammalian Chromosome Aberration Test, and bacterial umu‐ and SOS‐tests, concentration of extracts is a prerequisite because of the low sensitivity of the test systems. Often cytotoxicity interferes with the evaluation of genotoxic effects. We demonstrated that some recommendations of the ISO 10993‐Part 3 and 12,1, 2 dealing with the biological evaluation of medical devices, seem to be insufficient, and new rules for the in vitro genotoxicity testing of biomaterials have to be established. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 83–90, 2002
Experimental studies on bone induction using low‐molecular‐weight poly (DL‐lactide‐co‐glycolide) as a carrier for recombinant human bone morphogenetic protein‐2
Authors: Bessho K. , Carnes D. L. , Cavin R. , Ong J. L.
Published: October 2004

An appropriate carrier acting as a slow delivery vehicle for the BMPs is required for maximal clinical effectiveness of these bone‐inductive proteins. The purpose of this study was to evaluate a low‐molecular‐weight PLGA copolymer as a synthetic, biodegradable carrier for rhBMP‐2 implantation in vivo. Two, 10, or 50 μg of recombinant human BMP‐2 were mixed with 10 mg of a poly (DL‐lactide‐co‐glycolide) (PLGA) 50:50 copolymer and implanted into the calf muscles of Wistar rats. Soft X‐ray analysis and histologic examination indicated that new bone formation occurred at all rhBMP‐2‐implanted sites within 3 weeks after implantation. Correlation of rhBMP‐2 concentration with the amount of bone induction was confirmed by specific alkaline phosphatase activity and calcium content assay. In vitro analysis indicated that 78.5% of the PLGA copolymer was degraded to smaller molecular weight material after 14 days in PBS solution. It is suggested that rhBMP‐2 was released in an active form at the implant site during the degradation of the copolymer, resulting in the induction of new bone formation. Thus this low‐molecular‐weight PLGA copolymer material represents a promising delivery vehicle for BMPs, and possibly other growth factors, around dental and orthopedic implants. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 61: 61–65, 2002
Conformational analysis of thiopeptides: derivation of sp2 sulfur parameters for the CFF91 force field
Authors: Tran Tran Trung , Treutlein Herbert , Burgess Antony W.
Published: October 2004

When a sulfur atom is used to substitute for the oxygen in peptide bonds, its bulkiness should restrict the conformational space available to an amino acid. This conformational restriction as well as the ability to confer resistance to enzymatic degradation in the body means that thio‐substituted amino acids are potentially useful building blocks for drug design. To simulate the effects of thio substitution, force field parameters for sp2 sulfur are required. In this article, parameters for the thioamide group have been derived for the molecular mechanics CFF91 force field (available at http://www.ludwig.edu.au/archive/tran). The bond increment charges were obtained by fitting to ab initio charges and dipoles. The van der Waals parameters were obtained by fitting to high‐resolution crystallographic data, and the nonbonded parameters were verified by comparing with experimentally derived lattice energy. The bonded parameters were derived by least‐square fits to the ab initio calculated energy surfaces, i.e., conformational energy as well as their first and second derivatives of seven model thioamide molecules. When the sp2 sulfur parameters were tested on a set of seven X‐ray crystallographic structures from the Cambridge Structural Database, they satisfactorily reproduced the bond lengths, bond angles, torsional angles, and nonbonded distances of all the crystal structures. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1010–1025, 2001
Conformational analysis of thiopeptides: (ϕ,ψ) maps of thio‐substituted dipeptides
Authors: Tran Tran Trung , Treutlein Herbert , Burgess Antony W.
Published: October 2004

Noncoded amino acids such as isobutyric acid have been used extensively in the process of drug design and protein engineering. This article focuses on a noncoded amino acid where the oxygen in the peptide unit is replaced with a sp2 sulfur. It was hypothesized that the conformational space as well as the conformational preferences of thiopeptides will be more restricted and altered by the bulkier atom with different electrostatic properties. In vacuo conformational minima as well as associated energies for the thio‐substituted alanine dipeptides were calculated at the ab initio HF/6‐31G* level. When the bulkier sulfur atom acts as a hydrogen bond acceptor in the C5 conformation or in the C\documentclass{article}\pagestyle{empty}\begin{document}$^{\mathrm{axial}}_{7}$\end{document} and C\documentclass{article}\pagestyle{empty}\begin{document}$^{\mathrm{equatorial}}_{7}$\end{document} conformations, the hydrogen bond lengths are much longer than that of normal peptides. Consequently, the ϕ, ψ dihedral angles of the C5, C\documentclass{article}\pagestyle{empty}\begin{document}$^{\mathrm{axial}}_{7}$\end{document}, and C\documentclass{article}\pagestyle{empty}\begin{document}$^{\mathrm{equatorial}}_{7}$\end{document} conformations change to accommodate the longer hydrogen bonds. The thiopeptide group is a poorer hydrogen bond acceptor and a better hydrogen bond donor than the normal peptide group. Therefore, thio‐substitution at the amino terminal leads to disfavoring of the C7 conformations relative to the C5 conformations and thio‐substitution at the carboxyl terminal leads to favoring of the C7 conformations relative to the C5 conformation. To simulate the conformations in solution, (ϕ,ψ) conformational energy maps were calculated for the glycine and alanine dipeptides at various dielectric constants using the CFF91 force field with our previously derived parameters for the thioamide group. The results show that thio‐substitution does restrict the conformations available to amino acids residues in peptides. Thio substitution at the amino terminal introduces unfavorable interactions near ϕ=−120 and 120, where there are increased overlaps between Sn−1Hβ, and Sn−1Cβ atoms, respectively. Thio substitution at the carboxyl terminal restricts the conformations near ψ=60, −60, and 180, which correspond with increase overlaps between SnCβ, SnHβ′ and SnNn atoms, respectively. The effects of dithio substitutions of either the alanine or the glycine dipeptides are similar to the combined effects of the two single thio substitutions. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1026–1037, 2001
Repeated‐annealing sampling combined with multicanonical algorithm for conformational sampling of bio‐molecules
Authors: Kamiya Narutoshi , Higo Junichi
Published: October 2004

A novel conformational sampling method (repeated‐annealing sampling method) is proposed to execute an efficient conformational sampling at a reasonable computational cost. In the method, a molecular dynamics simulation is done with repeating an elemental process. An elemental process consists of four subprocesses: high‐temperature run, annealing, room‐temperature run, and fast heating. The sampling is done automatically according to a temperature‐control schedule. The room‐temperature run is treated with the multicanonical algorithm, and the other subprocesses are done with the conventional molecular dynamics algorithm. The method, differing from the generalized ensemble methods recently developed, is not warrantable to give the canonical ensemble because of the nonphysical process in the annealing. However, we observed that the slower the annealing and the longer the high‐temperature run, the closer the sampled conformations to those of the canonical ensemble. A test was performed with tri‐N‐acetyl‐D‐glucosamine in vacuo, and the results were compared with those from the conventional multicanonical simulation. Not only the reweighted canonical distribution function but also the energy landscape were in good agreement with those from the conventional multicanonical simulation. The potential of mean force also showed a fairly good agreement with that from the conventional multicanonical simulation in the room‐temperature region. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1098–1106, 2001
Ab initio study of C4H3 potential energy surface and reaction of ground‐state carbon atom with propargyl radical
Authors: Le Trung Ngoc , Mebel Alexander M. , Kaiser Ralf I.
Published: October 2004

The potential energy surface for the reaction of the ground‐state carbon atom [C(3Pj)] with the propargyl radical [HCCCH2(X2B1)] is investigated using the G2M(RCC,MP2) method. Numerous local minima and transition states for various isomerization and dissociation pathways of doublet C4H3 are studied. The results show that C(3Pj) attacks the π system of the propargyl radical at the acetylenic carbon atom and yields the n‐C4H3(2A′) isomer i3 after an 1,2‐H atom shift. This intermediate either splits a hydrogen atom and produces singlet diacetylene, [HCCCCH (p1)+H] or undergoes (to a minor amount) a 1,2‐H migration to i‐C4H3(2A′) i5, which in turn dissociates to p1 plus an H atom. Alternatively, atomic carbon adds to the triple CC bond of the propargyl radical to form a three‐member ring C4H3 isomer i1, which ring opens to i3. Diacetylene is concluded to be a nearly exclusive product of the C(3Pj)+HCCCH2 reaction. At the internal energy of 10.0 kcal/mol above the reactant level, Rice–Ramsperger–Kassel–Marcus calculations show about 91.7% of HCCCCH comes from fragmentation of i3 and 8.3% from i5. The other possible minor channels are identified as HCCCC+H2 and C2H+HCCH. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1522–1535, 2001
B3LYP calculations on bishomoaromaticity in substituted semibullvalenes*
Authors: Hrovat David A. , Williams Richard Vaughan , Goren Alan C. , Borden Weston Thatcher
Published: October 2004

B3LYP/6‐31G* calculations on the degenerate rearrangements of substituted semibullvalenes spuriously predict the relative enthalpies of the bishomoaromatic TSs to be lower than the experimental values. However, the calculations do make the useful and experimentally testable prediction that the two cyano and two phenyl substituents in 2,6‐dicyano‐4,8‐diphenylsemibullvalene (9d) are more likely than four cyano substituents in 2,4,6,8‐tetracyanosemibullvalene (9f) or the four phenyl substituents in 2,4,6,8‐tetraphenylsemibullvalene (9g) to produce a semibullvalene that has a bishomoaromatic equilibrium geometry in the gas phase. The major reason for the surprising finding that 9d is more likely to be bishomoaromatic than 9g is shown to be steric interactions between the phenyl groups at C‐2 and C‐8 and at C‐4 and C‐6 in bishomoaromatic structure 10g. These interactions inhibit the conjugative stabilization of 10g; but they are absent in bishomoaromatic structure 10d, where cyano groups replace the phenyl groups at C‐2 and C‐6 in 10g. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1565–1573, 2001
Observations of sibling interactions in violent families
Authors: Waddell Janice , Pepler Debra , Moore Timothy
Published: October 2004

This study examined sibling relationships of children from violent and non‐violent families. Participants included 20 children (10 dyads) who were shelter residents and their mothers and 40 children (20 dyads) from the community and their mothers. Mothers reported on children's behavior problems, sibling conflict resolution strategies, and the quality of the sibling relationship. Children reported on the quality of their sibling relationships. Sibling interactions were observed during both cooperative and competitive tasks. Shelter children had more internalizing problems than comparison children did. Mothers reported that siblings from violent homes used less verbal and physical aggression than the comparison group. Siblings in the shelter group were supportive. There were no significant differences in observed conflictual behavior. The importance of the sibling relationship and implications for intervention are discussed. © 2001 John Wiley & Sons, Inc.
Addressing cultural sensitivity in a smoking cessation intervention: Development of the Kick It at Swope project
Authors: Harris Kari Jo , Ahluwalia Jasjit S. , Okuyemi Kolawole S. , Turner Janice R. , Woods Malaika N. , Backinger Cathy L. , Resnicow Ken
Published: October 2004

There are marked and growing disparities in the health status among different racial/ethnic groups. Most researchers and practitioners agree health interventions that are tailored for specific populations are ethically important and more likely to succeed, yet there are few models for how to tailor interventions. This article outlines three phases and eight activities conducted to increase the cultural sensitivity of a clinical trial assessing the efficacy of bupropion for smoking cessation among African Americans. Early in the project development (Phase I) a strong partnership was built with a community‐based clinic, two Advisory Boards were formed (Community and Scientific), and materials were developed. Formative research (Phase II) included a survey to assess smoking cessation needs of clinic patients and exploratory focus groups. Through pilot testing (Phase III), clinic patients tested the intervention components and, in follow‐up focus groups, discussed their experiences. Over 13 months the project successfully recruited 523 African Americans into a randomized trial, and preliminary analysis suggest acceptable follow‐up rates. Successful recruitment and retention suggests the activities are promising and potentially generalizable. Discussions of these activities illustrate concrete steps researchers and practitioners can take to increase the cultural sensitivity of health promotion and prevention interventions and clinical trials. © 2001 John Wiley & Sons, Inc.
The spirit and substance of community psychology: Reflections
Authors: Gregory Robert J.
Published: October 2004

Community psychology began with a spirit of participation, social change, and excitement in the mid‐1960s. However, the substance of community psychology, whether measured by impacts on prevention, empowerment, social inclusion, or otherwise, appears to be minimal in comparison with the needs evident today and the needs emerging. From the perspective of members of the discipline and field, a great deal of effort has already resulted in many meaningful changes. However, from the views of people at large, a new field such as community psychology has relatively little tangible effect on existing communities, societies, or civilizations. The spirit of community psychology might be present, but that may not result in the massive social changes needed in the 2000s. If community psychologists could focus their efforts, become catalysts, and act firmly and forcefully, then a revitalization and renaissance for “the people” and our collective future, could be initiated. © 2001 John Wiley & Sons, Inc.
Sonographic diagnosis of a solitary intramuscular cysticercal cyst
Authors: Mani N. B. S. , Kalra Naveen , Jain Manoj , Sidhu Ravinder
Published: October 2004

We present a rare case of a solitary cysticercal cyst that involved the anterior abdominal wall musculature and was diagnosed with sonography. Sonograms revealed a small, well‐defined, elliptical cystic lesion with an eccentric hyperechoic area within it. An eccentric, echogenic, pedunculated structure was seen within the cystic area of the lesion. No calcification was apparent. The lesion was surrounded by inflammation in the muscle. Hypervascularity in the surrounding muscle was noted on color Doppler imaging. If lesions with similar morphologic characteristics are encountered in the musculature or subcutaneous tissues during sonographic examination for another condition, one should suspect cysticercosis. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:472–475, 2001.
Pharmacological properties of nicotinic acetylcholine receptors in isolated Locusta migratoria neurones
Authors: Jackson Charles , Bermudez Isabel , Beadle David J.
Published: October 2004

Mechanically dissociated neuronal cell bodies from the thoracic ganglia of Locusta migratoria were viable in culture conditions for up to 2 days and were voltage‐clamped to record the effects of GABAergic drugs and physostigmine on the membrane conductance and ACh responses of the dissociated cells. Bicuculline, hydrastine, and gabazine inhibited the EC50 ACh responses of the cells. Both bicuculline and hydrastine were full inhibitors of the ACh responses but gabazine behaved as a partial inhibitor. Bicuculline, hydrastine, and gabazine inhibited the ACh responses in a non‐competitive and voltage‐independent fashion, suggesting that they are allosteric inhibitors of locust nicotinic ACh receptors. Physostigmine activated currents when applied onto isolated locust neurones. The responses activated by physostigmine were inhibited competitively by tubocurarine, which indicates that physostigmine interacts with the ACh site of locust nicotinic ACh receptors. However, maximal concentrations of physostigmine elicited currents of smaller amplitudes to those evoked by maximal ACh concentrations. Single‐channel recordings suggest that the partial efficacy of physostigmine may reflect the low frequency of opening of physostigmine‐induced single currents relative to that of ACh‐single currents. Microsc. Res. Tech. 56:249–255, 2002. © 2002 Wiley‐Liss, Inc.
Impact of descending brain neurons on the control of stridulation, walking, and flight in orthoptera
Authors: Heinrich Ralf
Published: October 2004

Orthopteran insects (crickets, bushcrickets, and acridid grasshoppers) are preferred preparations for the study of the central nervous mechanisms that underlie behavior. Many of their behaviors are based on central rhythm‐generating circuits located in the ganglia of the ventral nerve cord. Activities of these circuits must be coordinated and adapted to the behavioral context by sensory information, which can derive from proprioceptive or exteroceptive inputs. Information from various sensory modalities converges in yet unidentified “higher brain centers” that integrate and transform it into activity patterns across populations of descending brain neurons (DBNs). Transmission of “decisions” to the thoracic motor centers leads to adjustment of their functions in order to fit the sensory situation encountered. A number of unique DBNs has been identified by morphological and physiological criteria and their role in controlling aspects of specific behaviors has been the subject of various studies. Their functions range from “switch‐like” transmitters of brain output to complex integration units for sensory inputs of various modalities and their appropriate insertion into the ongoing activities of the thoracic rhythm generators. This paper highlights some of the characteristics of DBNs by focussing on three motor behaviors: stridulation, a stereotyped behavior that seems to be mainly controlled by command‐like DBNs; walking, a plastic behavior whose various parameters must continuously be adjusted to a changing sensory environment; and flight, in which the information for course corrections encoded for by different types of DBNs is transformed to match the rhythmic activity of the flight oscillators before it affects the respective motoneurons. Microsc. Res. Tech. 56:292–301, 2002. © 2002 Wiley‐Liss, Inc.
Cytochemical techniques for zinc and heavy metals localization in nerve cells
Authors: López‐García Carlos , Varea Emilio , Palop Jorge J. , Nacher Juan , Ramirez Carmen , Ponsoda Xavier , Molowny Asunción
Published: October 2004

Zinc is one of the most abundant oligoelements in the living cell. It appears tightly bound to metallothioneins, loosely bound to some metalloproteins and nucleic acids, or even as free ion. Small amounts of zinc ions (in the nanomolar range) regulate a plentitude of enzymatic proteins, receptors, and transcription factors; thus, cells need accurate homeostasis of zinc ions. Some neurons have developed mechanisms to accumulate zinc in specific membrane compartments (“vesicular zinc”) which can be revealed using histochemical techniques. This article is a short report on the different direct–indirect experimental approaches for zinc and heavy metal detection in neurons. Substances giving a bright color or emitting fluorescence when in contact with divalent metal ions are currently used to detect them inside cells; their use leads to the so called “direct” methods. The fixation and precipitation of metal ions as insoluble salt precipitates, their maintenance along the histological process, and their demonstration after autometallographic development are essential steps for other methods, the so‐called “indirect methods” (Timm and Danscher Neo‐Timm methods). Microsc. Res. Tech. 56:318–331, 2002. © 2002 Wiley‐Liss, Inc.