bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlinear analysis of EEG during NREM sleep reveals changes in functional connectivity due to natural aging
Authors: Terry John R. , Anderson Clare , Horne James A.
Published: June 2004

The spatial organization of nonlinear interactions between different brain regions during the first NREM sleep stage is investigated. This is achieved via consideration of four bipolar electrode derivations, Fp1F3, Fp2F4, O1P3, O2P4, which are used to compare anterior and posterior interhemispheric interactions and left and right intrahemispheric interactions. Nonlinear interdependence is detected via application of a previously written algorithm, along with appropriately generated surrogate data sets. It is now well understood that the output of neural systems does not scale linearly with inputs received and, thus, the study of nonlinear interactions in EEG is crucial. This approach also offers significant advantages over standard linear techniques, in that the strength, direction, and topography of the interdependencies can all be calculated and considered. Previous research has linked delta activity during the first NREM sleep stage to performance on frontally activating tasks during waking hours. We demonstrate that nonlinear mechanisms are the driving force behind this delta activity. Furthermore, evidence is presented to suggest that the aging brain calls upon the right parietal region to assist the pre‐frontal cortex. This is highlighted by statistically significant differences in the rates of interdependencies between the left pre‐frontal cortex and the right parietal region when comparing younger subjects (<23 years) with older subjects (>60 years). This assistance has been observed in brain‐imaging studies of sleep‐deprived young adults, suggesting that similar mechanisms may play a role in the event of healthy aging. Additionally, the contribution to the delta rhythm via nonlinear mechanisms is observed to be greater in older subjects. Hum. Brain Mapping 23:73–84, 2004. © 2004 Wiley‐Liss, Inc.
Alcohol continues to affect sleepiness related driving impairment, when breath alcohol levels have fallen to near‐zero
Authors: Barrett P. R. , Horne J. A. , Reyner L. A.
Published: June 2004

Epidemiological findings point to very low blood alcohol levels heightening the risk of sleep‐related fatal road crashes. This was further assessed using a full sized interactive car simulator. Twenty, sleep restricted, healthy young men underwent a 2 h simulated afternoon monotonous drive, having previously consumed nil alcohol or 3 units >90 min previously, and having near‐zero breath alcohol (BrACs) at the start of the drive. In a repeated measures, double‐blind, balanced design, driving performance, subjective sleepiness and EEG were monitored throughout. Compared with nil alcohol, the alcohol condition initially increased sleepiness‐related driving impairment. However, this was not mirrored by subjective sleepiness or EEG. An unexpected reversal (i.e. improvement) in driving impairment occurred with the alcohol group, in the second hour of the drive. This was supported by a trend for improved subjective alertness. Alcohol continued to interact with sleepiness‐related driving impairment after BrACs had reached zero. However, a lack of subjective perception of increased sleepiness, at this time, further points to the dangerous combination of even modest alcohol intake and sleepiness, and confirms the road crash findings. BrACs are a poor guide to driver impairment. Copyright © 2004 John Wiley & Sons, Ltd.
Proliferation and differentiation of osteoblasts on Biocement D modified with collagen type I and citric acid
Authors: Hempel U. , Reinstorf A. , Poppe M. , Fischer U. , Gelinsky M. , Pompe W. , Wenzel K. W.
Published: June 2004

In this study, the proliferation and differentiation of rat calvarial osteoblasts cultured on either (1) calcium‐phosphate bone cement Biocement D, (2) Biocement D with 2.5% (w/w) mineralized collagen type I, or (3) Biocement D with 2.5% (w/w) mineralized collagen type I and 3% (w/w) citric acid were investigated. Incubation of the composites in cell‐culture medium resulted in a fast decrease of pH and calcium concentration as well as in an increase of phosphate concentration. Although these effects occurred with all investigated materials, the lowest extent could be observed for the citric‐acid‐containing composites. As shown by scanning‐electron microscopy, osteoblasts adhered to the composite surfaces. Proliferation and differentiation of the cells grown on the composites were found to be reduced compared to cells grown on tissue‐culture polystyrene. Cells cultured in the vicinity of the composites but without direct contact also exhibited a reduced rate of proliferation, reduced alkaline phosphatase activity, and reduced mineralization. Simulating the changes in calcium and phosphate concentration occasioned by the composites through exposing cells to EGTA and phosphate gives rise to the same effects of reducing proliferation, ALP activity, and mineralization. No indication for apoptosis in cells exposed to low calcium and high phosphate concentrations was found. The number of necrotic cells, however, increased after incubation with EGTA and phosphate. For assessment of cell‐composite interactions and the success of the composites in vivo, as well as for more effective material development, it seems to be important to know how changes in microenvironmental pH and ion composition of the material affect cellular proliferation and differentiation. © 2004 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 71B: 130–143, 2004
Expression and function of periostin‐isoforms in bone
Authors: Litvin Judith , Selim Abdul‐Hafez , Montgomery Michael O. , Lehmann Kiyoko , Rico Mario C. , Devlin Hugh , Bednarik Daniel P. , Safadi Fayez F.
Published: June 2004

Periostin was originally identified in MC3T3‐E1 osteoblast‐like cells. We have identified an isoform of periostin referred to as periostin‐like‐factor (PLF). It is homologous to other proteins such as fasciclin I (fas I), MPB70, βIG‐H3, and Algal‐CAMs. All of these proteins are implicated in regulating cell adhesion. PLF and the other isoforms of periostin differ in their C‐terminal sequences. PLF and periostin differ in two specific regions, between 673 and 699 amino acids (aa) and 785–812 aa. Periostin isoforms are expressed in vivo and in vitro during the stages of osteoblast differentiation and maturation. Their mRNAs are present in pre‐osteoblast cells as detected by in situ hybridization, and the proteins are between 86 and 93 kD in size as determined by Western blot analysis. Antisense oligonucleotides and antibodies directed against the isoforms of periostin were used to block the activity of these proteins. In both cases, the levels of osteoblast‐specific‐differentiation markers were markedly reduced suggesting a role for these proteins in osteoblast differentiation. © 2004 Wiley‐Liss, Inc.
In situ non‐invasive spectral discrimination between bone cell phenotypes used in tissue engineering
Authors: Notingher Ioan , Jell Gavin , Lohbauer Ulrich , Salih Vehid , Hench Larry L.
Published: June 2004

Raman micro‐spectroscopy was used to discriminate between different types of bone cells commonly used in tissue engineering of bone, with the aim of developing a method of phenotypic identification and classification. Three types of bone cells were analysed: human primary osteoblasts (HOB), retroviral transfected human alveolar bone cells with SV40 large T antigen (SV40 AB), and osteoblast‐like human osteosarcoma derived MG63 cell line. Unsupervised principal component analysis (PCA) and linear discriminant analysis (LDA) of the Raman spectra succeeded in discriminating the osteosarcoma derived MG63 cells from the non‐tumour cells (HOB and SV40 AB). No significant differences were observed between the Raman spectra of the HOB and SV40 AB cells, confirming the biochemical similarities between the two cell types. Difference spectra between tumour and non‐tumour cells suggested that the spectral discrimination is based on the fact that MG63 osteosarcoma derived cells are characterised by lower concentrations of nucleic acids and higher relative concentrations of proteins compared to the non‐tumour bone cells. A supervised classification model (LDA) was built and showed high cross‐validation sensitivity (100%) and specificity (95%) for discriminating the MG63 cells and the non‐tumour cells, with 96% of the cells being correctly classified either as tumour or non‐tumour derived cells. This study proves the feasibility of using Raman spectroscopy to identify in situ phenotypic differences in living cells. © 2004 Wiley‐Liss, Inc.
Effect of DNA loop anchorage regions (LARs) and microinjection timing on expression of β‐galactosidase gene injected into one‐cell rabbit embryos
Authors: Goldman Igor L. , Razin Sergey V. , Kadulin Sergey G. , Vassetzky Yegor S.
Published: June 2004

The conditions favoring expression of a reporter gene microinjected into a male pronucleus of naturally ovulated and fertilized rabbit eggs have been studied. Injection of the reporter gene during S phase of the cell‐cycle allows the highest level of expression of the gene. Incorporation of DNA loop anchorage regions (LARs) into constructs upstream and/or downstream of the reporter gene significantly increased the efficiency of expression. In all cases the expression of the microinjected gene started after a period of transcriptional quiescence, i.e., together with the expression of the host genome. Correct targeting of microinjected constructs within the nuclei via interaction of LAR elements with receptor sites on the nucleoskeleton may facilitate expression of injected DNA constructs as well as their integration into host cell DNA. © 2004 Wiley‐Liss, Inc.
Locus of fragility in robust breast cancer system
Authors: Radisavljevic Ziv
Published: June 2004

Functional heterogeneous redundancy of breast cancer makes this tumor to be robust. Signaling mechanisms which control cancer responses are crucial for controlling robustness. Identification of locus of fragility in cancer represents basic mechanism to target robustness. The goal of this prospect is to present locus of fragility in breast cancer robust system, and how disruption of this locus induces failure of robustness. My recent research show, that locus of fragility in breast cancer cells is suppression of nitric oxide (NO). When it was targeted, dynamics of cancer to generate robustness failed that it blocked cancer cell proliferation dependent on the NO/Rb pathway, blocked cell migration and angiogenesis dependent on the VEGF/PI3K/AKT/NO/ICAM‐1 pathway, and induced breast cancer cell apoptosis through the NO/ROCK/FOXO3a signaling pathway. This tiny and trivial perturbation in breast cancer cells such as suppression of NO represents locus of fragility (weakness) and new approach for breast cancer chemotherapy. © 2004 Wiley‐Liss, Inc.
Vasopressin phosphorylates HSP27 in aortic smooth muscle cells
Authors: Akamatsu Shigeru , Nakajima Keiichi , Ishisaki Akira , Matsuno Hiroyuki , Tanabe Kumiko , Takei Mariko , Takenaka Motoki , Hirade Kouseki , Yoshimi Naoki , Suga Hidetaka , Oiso Yutaka , Kato Kanefusa , Kozawa Osamu
Published: June 2004

Administration of arginine vasopressin (AVP) time‐dependently induced the phosphorylation of heat shock protein 27 (HSP27) at Ser‐15 and Ser‐85 in smooth muscle of aorta in vivo. The AVP‐induced phosphorylation of HSP27 at Ser‐15 and Ser‐85 was inhibited by a V1a receptor antagonist but not by a V2 receptor antagonist. In cultured aortic smooth muscle A10 cells, AVP markedly stimulated the phosphorylation of HSP27 at Ser‐15 and Ser‐85. The AVP‐induced phosphorylation of HSP27 was attenuated by SB203580 and PD169316, inhibitors of p38 mitogen‐activated protein (MAP) kinase, but not by PD98059, a MEK inhibitor. These results strongly suggest that AVP phosphorylates HSP27 via p38 MAP kinase in aortic smooth muscle cells. © 2004 Wiley‐Liss, Inc.
Volvariella volvacea lectin activates mouse T lymphocytes by a calcium dependent pathway
Authors: Sze S.C.W. , Ho J.C.K. , Liu W.K.
Published: June 2004

The immunomodulatory lectin, Volvariella volvacea lectin (VVL), isolated from the edible mushroom, Volvariella volvacea, has been shown to stimulate the expression of Th1 cytokines and the proliferative activity of mouse splenocytes (She et al. [1998]: Biochem Biophys Res Comm 247:106–111). In order to elucidate the mechanisms underlying these activities, we conducted a kinetic analysis of the early and late activation markers in mouse T lymphocytes: (1) flow cytometric analysis of calcium influx, (2) induction of activation molecules (CD25 and CD69), (3) expression and DNA‐binding activity of the nuclear factor of activated T cells (NFAT), NFκB, and activation protein‐1 (AP‐1), (4) translational production of cytokines (interleukin‐2 (IL‐2) and interferon‐γ (IFNγ)), and (5) cell proliferation by expression of proliferating cell nuclear antigen (PCNA) and tritiated thymidine incorporation. All results showed that VVL induced a rapid expression of CD69, CD25, NFAT, IL‐2, and PCNA in a dose‐ and time‐dependent manner, leading to lymphocyte proliferation. These effects brought about by VVL were more potent than those stimulated by equimolar concentrations of mitogenic lectin, concanavalin A (Con A). Cell activation and proliferation were mediated through a calcium‐dependent pathway as demonstrated by a VVL‐induced increase of intracellular calcium influx, and a proliferation inhibition by the Ca‐dependent phosphatase calcineurin blocker—cyclosporin A (CsA). Taken all data together, VVL is a lectin which activates lymphocyte through successive calcium influx, nuclear localization of NFAT transcription factor, induction of activation markers, CD25 and CD69, intracellular cytokine production, and cell proliferation. © 2004 Wiley‐Liss, Inc.
Daxx deletion mutant (amino acids 501–625)‐induced apoptosis occurs through the JNK/p38‐Bax‐dependent mitochondrial pathway
Authors: Song Jae J. , Lee Yong J.
Published: June 2004

Death‐associated protein (Daxx) deletion mutant (aa 501–625) has been known to be an inducer of apoptosis. In this study, we observed that the Bax‐dependent mitochondrial death signaling pathway plays an important role in Daxx501–625‐induced apoptosis. Daxx fragment‐induced activation of caspase‐9 and ‐3 was mediated through the apoptosis signal‐regulating kinase 1 (ASK1)–MEK–c‐Jun‐N‐terminal kinase (JNK)/p38–Bax pathway. By overexpressing JNK‐binding domain (JBD) of JIP1, a JNK‐inhibitory protein, and treatment with SB203580, a specific p38 inhibitor, DU‐145 cells were made resistant to Daxx501–625‐induced apoptosis. Capase‐3 deficiency, Bax deficiency, or overexpression of a dominant‐negative caspase‐9 mutant prevented apoptosis, even though the Daxx501–625 fragment still activated the ASK1–MEK–MAPK pathway. Interestingly, Daxx501–625‐induced Bcl‐2 interacting domain (Bid) cleavage was suppressed in the dominant‐negative caspase‐9 mutant cells, whereas Bim was still phosphorylated in these cells. These results suggest that cleavage of Bid occurs downstream of caspase‐9 activation. In contrast, phosphorylation of Bim is upstream of caspase‐9 activation. Taken together, our results suggest that Daxx501–625‐induced apoptosis is mediated through the ASK1–MEK–JNK/p38–Bim–Bax‐dependent caspase pathway. © 2004 Wiley‐Liss, Inc.
Differential control of apoptosis by DJ‐1 in prostate benign and cancer cells
Authors: Hod Yaacov
Published: June 2004

DJ‐1 is a conserved protein reported to be involved in diverse cellular processes ranging from cellular transformation, control of protein–RNA interaction, oxidative stress response to control of male infertility, among several others. Mutations in the human gene have been shown to be associated with an autosomal recessive, early onset Parkinson's disease (PARK7). The present study examines the control of DJ‐1 expression in prostatic benign hyperplasia (BPH‐1) and cancer (PC‐3) cell lines in which DJ‐1 abundance differs significantly. We show that while BPH‐1 cells exhibit low basal level of DJ‐1 expression, stress‐inducing agents such as H2O2 and mitomycin C markedly increase the intracellular level of the polypeptide. In contrast, DJ‐1 expression is relatively high in PC‐3 cells, and incubation with the same cytotoxic drugs does not modulate further the level of the polypeptide. In correlation with the expression of DJ‐1, both cytotoxic agents activate the apoptotic pathway in the prostatic benign cells but not in PC‐3 cells, which are resistant to their action. We further demonstrate that incubation of BPH‐1 cells with TNF‐related‐apoptosis‐inducing‐ligand/Apo‐2L (TRAIL) also enhances DJ‐1 expression and that TRAIL and H2O2 act additively to stimulate DJ‐1 accumulation but synergistically in the activation of the apoptotic pathway. Time‐course analysis of DJ‐1 stimulation shows that while DJ‐1 level increases without significant lag in TRAIL‐treated cells, there is a delay in H2O2‐treated cells, and that the increase in DJ‐1 abundance precedes the activation of apoptosis. Unexpectedly, over‐expression of DJ‐1 de‐sensitizes BPH‐1 cells to the action of apoptotic‐inducing agents. However, RNA‐interference‐mediated silencing of DJ‐1 expression results in sensitization of PC‐3 cells to TRAIL action. These results are consistent with a model in which DJ‐1 is involved in the control of cell death in prostate cell lines. DJ‐1 appears to play a differential role between cells expressing a low but inducible level of DJ‐1 (e.g., BPH‐1 cells) and those expressing a high but constitutive level of the polypeptide (e.g., PC‐3 cells). © 2004 Wiley‐Liss, Inc.
A fourth‐order accurate, Numerov‐type, three‐point finite‐difference discretization of electrochemical reaction‐diffusion equations on nonuniform (exponentially expanding) spatial grids in one‐dimensional space geometry
Authors: Bieniasz Lesław K.
Published: June 2004

The validity for finite‐difference electrochemical kinetic simulations, of the extension of the Numerov discretization designed by Chawla and Katti [J Comput Appl Math 1980, 6, 189–196] for the solution of two‐point boundary value problems in ordinary differential equations, is examined. The discretization is adapted to systems of time‐dependent reaction‐diffusion partial differential equations in one‐dimensional space geometry, on nonuniform space grids resulting from coordinate transformations. The equations must not involve first spatial derivatives of the unknowns. Relevant discrete formulae are outlined and tested in calculations on two example kinetic models. The models describe potential step chronoamperometry under limiting current conditions, for the catalytic EC, and Reinert‐Berg CE reaction mechanisms. Exponentially expanding space grid is used. The discretization considered proves the most accurate and efficient, out of all the three‐point finite‐difference discretizations on such grids, that have been used thus far in electrochemical kinetics. Therefore, it can be recommended as a method of choice. © 2004 Wiley Periodicals, Inc. J Comput Chem 25: 1515–1521, 2004
Sonographic appearance of congenital arteriovenous fistula of the hand
Authors: Özdemir Hüseyin , Gündoğdu Sadi , Mahmutyazicioğlu Kamran , Büyükateş Mustafa , Turan Akın , Altınyazar Cevdet
Published: June 2004

Congenital arteriovenous fistula of the hand is uncommon. We report a case of unusual congenital arteriovenous fistula forming multiple fistulous communications between the arteries and veins in the right hand. Clinical findings were confirmed by color Doppler sonography and digital subtraction angiography. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:312–315, 2004
Doppler sonography in the diagnosis of urinary tract obstruction by stone
Authors: Akçar Nevbahar , Özkan I. Ragıp , Adapınar Baki , Kaya Tamer
Published: June 2004

Purpose

This study was conducted to evaluate the accuracy of Doppler sonography in renal colic due to obstruction and to assess whether the resistance index (RI) and interrenal RI difference (ΔRI) are time‐dependent parameters.

Subjects and Methods

Obstructed and unobstructed contralateral kidneys in 28 patients with renal colic and normal kidneys in 27 control subjects were prospectively evaluated with Doppler sonography. Mean RI, mean ΔRI, and duration of pain were evaluated. Statistical analysis was done using paired and independent t‐tests.

Results

Mean RIs of the control‐group, obstructed, and contralateral kidneys were 0.60, 0.71, and 0.61, respectively; mean ΔRI values of the obstructed and control‐group kidneys were 0.10 and 0.03, respectively. Differences in mean RI between obstructed and contralateral or control‐group kidneys were statistically significant (p < 0.001). There was a statistically significant difference in ΔRI between patients and controls (p < 0.001). The difference between the RI values of kidneys with low‐grade (0.70) and high‐grade obstructions (0.72) was not statistically significant. The difference between the ΔRI values of kidneys with low‐grade (0.08) and high‐grade obstructions (0.13) was statistically significant (p < 0.05). Differences in the mean RI and mean ΔRI values between 3 groups of patients categorized according to the duration of pain were not statistically significant.

Conclusions

Along with gray‐scale sonography and intravenous urography, Doppler sonography can be used in the evaluation of renal obstruction. RI and ΔRI are not time‐dependent parameters. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:286–293, 2004
Sonographic findings in tuberculous epididymo‐orchitis
Authors: Türkvatan Aysel , Kelahmet Esra , Yazgan Çisel , Ölçer Tülay
Published: June 2004

Genitourinary tuberculosis is the most common manifestation of extrapulmonary tuberculosis. The epididymides, the seminal vesicles, and the prostate are the most commonly infected sites. The testes are rarely involved. We describe the unusual sonographic findings in a case of tuberculous epididymo‐orchitis that presented with multiple small, hypoechoic nodules within the testis. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:302–305, 2004
High‐sensitivity power Doppler imaging of normal superficial lymph nodes
Authors: Stramare Roberto , Tregnaghi Alberto , Fittà Claudio , Torraco Antonio , Khadivi Yeaganeh , Rossi C.R. , Rubaltelli Leopoldo
Published: June 2004

Purpose

This study was conducted to describe the various patterns of vascularity of the normal superficial lymph nodes detected using high‐sensitivity power Doppler imaging according to the dimension and anatomic location of the nodes.

Subjects and Methods

A total of 712 lymph nodes (416 in the neck, 205 in the groin, and 91 in the axilla) were studied in 118 patients with high‐sensitivity Power doppler. Three categories of vascularity were defined: absence of vascularity (type 1), hilar and perihilar vascularity (type 2), and vascularity in the entire node (type 3). The 3 types of vascularity were correlated with the anatomic location and the dimension (maximum transverse diameter) of the nodes.

Results

Type 3 vascularity was found in all lymph nodes with a maximum transverse diameter > 6 mm, in the 67.9% (133/196) of lymph nodes between 4 and 6 mm in diameter, and in 45.7% (42/92) of lymph nodes between 2 and 4 mm in diameter. In lymph nodes with transverse diameters of 2–6 mm, type 3 vascularity was detected in 80.7% (46/57) of the axillary nodes, in 69.0% (87/126) of the inguinal nodes, and in 40.0% (42/105) of the cervical nodes. Type 2 vascularity was seen in 14.2% (101/712) of all examined lymph nodes. The absence of vascularity (type 1) was noted in only 1.9% (8/416) of cervical and 2.0% (4/205) of inguinal nodes.

Conclusions

State‐of‐the‐art power Doppler equipment can demonstrate type 3 vascularity in a high percentage of normal superficial lymph nodes. This pattern of intense, extensive—but harmonious—vascularity must be considered as an indicator of benignity. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:273–276, 2004
Sonographic findings in complications of cosmetic breast augmentation with autologous fat obtained by liposuction
Authors: Kwak Jin Young , Lee Seung Hee , Park Hai‐Lin , Kim Ji‐Young , Kim Sung Eun , Kim Eun‐Kyung
Published: June 2004

A 37‐year‐old woman presented with breast pain after breast augmentation utilizing autologous fat obtained by liposuction. Mammography and sonography demonstrated fat necrosis in the right breast and a solid inflammatory mass in the left breast. The diagnoses were confirmed by biopsy. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:299–301, 2004
Sonographically guided core needle biopsy of soft tissue neoplasms
Authors: Liu Juhn‐Cherng , Chiou Hong‐Jen , Chen Wei‐Ming , Chou Yi‐Hong , Chen Tain‐Hsiung , Chen Winby , Yen Chueh‐Chuan , Chiu See‐Ying , Chang Cheng‐Yen
Published: June 2004

Purpose

This study was conducted to evaluate the usefulness of sonography (US)‐guided needle biopsy in the diagnosis of soft tissue masses.

Patients and Methods

Thirty‐seven patients with a mean age of 49 years were enrolled in the study. The size of the biopsy needle was selected according to the kind of tumor suspected (ie, primary or metastatic). In patients with suspected metastases, smaller biopsy needles were used; in patients with suspected primary tumors, larger needles were used so that larger specimens could be obtained. Prebiopsy color Doppler sonography (CDUS) was routinely used to guide the cutting needle to areas of the lesion showing sufficient vascularity. From 3 to 6 cores were obtained, depending on their quality. We compared the diagnoses yielded by the core biopsy and the final histopathologic analysis of the resected tumor by classifying the results as “concordant” or “discordant.”

Results

A total of 37 tumors were examined. Final diagnoses were 24 malignant tumors (6 metastases and 18 primary tumors) and 13 benign tumors. The lesions were diagnosed correctly as either benign or malignant in 35 of the 36 cases for which needle biopsy specimens were adequate, with only 1 misdiagnosis. The diagnoses were concordant in 33 cases (17 primary malignant tumors, 6 metastatic tumors, and 10 benign tumors) and were discordant diagnosis in the other 4 cases (1 primary malignant tumor and 3 benign tumors). No complications were attributable to the needle biopsy.

Conclusions

US‐guided percutaneous core needle biopsy of soft tissue neoplasms is an easy, safe, and useful procedure. It can be considered a first‐line procedure for the acquisition of tissue specimens adequate for histopathologic diagnosis. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:294–298, 2004
Leiomyoma arising from the tunica albuginea of the testis: Sonographic findings
Authors: Mak Chee‐Wai , Tzeng Wen‐Sheng , Chou Chung‐Kuao , Chen Chin‐Yu , Chang Jinn‐Ming , Tzeng Ching‐Cherng
Published: June 2004

Leiomyomas are benign neoplasms that may arise from any structure or organ containing smooth muscle. The majority of genitourinary leimyomas are found in the renal capsule, but this tumor has also been reported in the epididymis, spermatic cord, and tunica albuginea. Sonography is the imaging modality of choice for evaluating intrascrotal pathology, but the sonographic appearance of leiomyomas arising from the tunica albuginea have rarely been reported. We report a case of such a leiomyoma that was diagnosed sonographically. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:309–311, 2004
Fourier transformation of arterial Doppler waveforms of the lower extremity
Authors: Lee Hong Gi , Yum Myung‐Kul
Published: June 2004

Purpose

Although it is well known that the normal, triphasic pulsatile arterial Doppler waveform changes in shape as flow is impaired, interpretation of the waveform has largely been subjective. We aimed to describe the Doppler waveforms of the lower extremity objectively using Fourier transformation.

Methods

Sixty‐eight zero‐crossing detector arterial recordings from 25 lower extremities were grouped as follows: group 1, no ischemic symptoms with an ankle‐brachial index (ABI) > 0.9 (n = 17, 8 limbs); group 2, no ischemic symptoms with ABI < 0.9 (n = 18, 5 limbs); group 3, symptoms of claudication (n = 19, 7 limbs); group 4, rest pain or tissue loss (n = 14, 5 limbs). The waveforms were Fourier transformed and their amplitudes and phases were compared up to the third harmonic (H3).

Results

Amplitudes of both the fundamental (H1) and second harmonic (H2) were predominant in group 1. In contrast, amplitudes of the H2 and H3 decreased with altered flow (p < 0.0001 for group 1 versus others). The phases of the H1 and H2 were delayed with altered flow (p < 0.05 for group 1 versus others). Phases of the H1 were different between group 2 and 4 (p < 0.05). The difference of phase between the H3 and H1 was shortened with altered flow (p < 0.05 for group 1 or 2 versus group 4). Multivariate analysis revealed that the relative amplitudes of the H2 and H3, the phases of the H1 and H2, and the relative phase of the H3 were significant discriminators among the groups.

Conclusion

Abnormal waveforms could be characterized by the predominant amplitude of the H1, phase delay of the H1 and H2, and shortening of the relative phase of the H3. These parameters may be useful in the evaluation of Doppler waveforms in patients with peripheral arterial disease. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:277–285, 2004
Statistical genetics of molar cusp patterning in pedigreed baboons: Implications for primate dental development and evolution
Authors: Hlusko Leslea J. , Maas Mary‐Louise , Mahaney Michael C.
Published: June 2004

Gene expression and knock‐out studies provide considerable information about the genetic mechanisms required for tooth organogenesis. Quantitative genetic studies of normal phenotypic variation are complementary to these developmental studies and may help elucidate the genes and mechanisms that contribute to the normal population‐level phenotypic variation upon which selection acts. Here we present the first quantitative genetic analysis of molar cusp positioning in mammals. We analyzed quantitative measures of molar cusp position in a captive pedigreed baboon breeding colony housed at the Southwest National Primate Research Center in San Antonio, Texas. Our results reveal complete pleiotropy between antimeric pairs of traits – i.e., they are influenced by the same gene or suite of genes. Mandibular morphological homologues in the molar series also exhibit complete pleiotropy. In contrast, morphological homologues in maxillary molar series appear to be influenced by partial, incomplete pleiotropic effects. Variation in the mandibular mesial and distal molar loph orientation on the same molar crown is estimated to be genetically independent, whereas the maxillary molar mesial and distal loph orientation is estimated to have partially overlapping genetic affects. The differences between the maxillary and mandibular molar patterning, and the degree of genetic independence found between lophs on the same molar crown, may be indicative of previously unrecognized levels of modularity in the primate dentition. J. Exp. Zool. (Mol. Dev. Evol.) 302B:268–283, 2004. © 2004 Wiley‐Liss, Inc.
Thomas Henry Huxley (1825–1895) puts us in our place
Authors: Weiss Kenneth M.
Published: June 2004

Thomas Huxley was one of the 19thcentury's most active defenders of Darwin's idea that life has evolved through natural processes. An anatomist and paleontologist, he extended his energies to science and education policy, the democratization of science, and the broad societal implications of evolution. Since his time the fossil record has greatly improved and the genetic ‘revolution’ has occurred, deepening our understanding of primate and human evolution in ways that would please Huxley: improved systematics relies heavily on genetic data, and molecular technologies are opening our understanding of the genetic basis of complex traits of traditional anthropological interest—but in ways that are thoroughly dependent on the fact of evolution. A more unified biological synthesis is forming that unites genes, developmental process, structure, and inheritance. But the tempo and mode of evolution remain unresolved. Huxley was one of many who have had trouble accepting Darwin's gradual natural selection as the central evolutionary mechanism, and views spanning the antipodes of gradualism and saltation find advocates even in our genetic era.J. Exp. Zool. (Mol. Dev. Evol.) 302B:196–206, 2004.© 2004 Wiley‐Liss, Inc.
Craniofacial variability and modularity in macaques and mice
Authors: Hallgrímsson Benedikt , Willmore Katherine , Dorval Curtis , Cooper David M.L.
Published: June 2004

Evolutionary developmental biology of primates will be driven largely by the developmental biology of the house mouse. Inferences from how known developmental perturbations produce phenotypic effects in model organisms, such as mice, to how the same perturbations would affect craniofacial form in primates must be informed by comparisons of phenotypic variation and variability in mice and the primate species of interest. We use morphometric methods to compare patterns of cranial variability in homologous datasets obtained for two strains of laboratory mice and rhesus macaques. C57BL/6J represents a common genetic background for transgenic models. A/WySnJ mice exhibit altered facial morphology which results from reduction in the growth of the maxillary process during formation of the face. This is relevant to evolutionary changes in facial prognathism in nonhuman primate and human evolution. Rhesus macaques represent a nonhuman primate about which a great deal of phenotypic and genetic information is available. We find significant similarities in covariation patterns between the C57BL/6J mice and macaques. Among‐trait variation in genetic and phenotypic variances are fairly concordant among the three groups, but among‐trait variation in developmental stability is not. Finally, analysis of modularity based on phenotypic and genetic correlations did not reveal a consistent pattern in the three groups. We discuss the implications of these results for the study of evolutionary developmental biology of primates and outline a research strategy for integrating mouse genomics and developmental biology into this emerging field.J. Exp. Zool. (Mol. Dev. Evol.) 302B:207–225, 2004.© 2004 Wiley‐Liss, Inc.
Modularity and integration in the hominoid scapula
Authors: Young Nathan
Published: June 2004

In this paper, several hypotheses of morphological integration within the hominoid (ape) scapula are tested. In particular, whether the scapula represents a set of developmental tissues sharing tight correlations between constituent parts (i.e., highly integrated) or is more modularly organized (i.e., covariation is greater within regions than between) is tested. Whether the patterns of integration in the scapula have changed over phylogenetic time or in response to selective forces is also examined. Results from two different analyses (matrix correlations and edge deviance) indicate traits comprising the blade and acromion, and to a weaker degree the glenoid, correlate highly with each other. The coracoid exhibits more independence from other parts of the scapula, perhaps reflecting its distinct evolutionary developmental history. Overall, similarity in species‐specific patterns of correlation was high between all taxa. Correlation matrix similarity was significantly correlated with functional similarity and morphological distance, but not with phylogenetic distance. These results are congruent with other studies of integration that suggest correlation patterns remain stable over evolutionary time. There are changes associated with phylogeny, but the tight link between functional similarity and phylogenetic distance at this level of comparison presents possible challenges to interpretation. Overall similarities in the pattern of integration in all taxa might be better interpreted as relative strengthening or weakening of trait correlations rather than broadscale changes in the pattern of relationship between developmental regions. Larger sample sizes with greater taxonomic/functional breadth, and finer scale analyses of patterns of correlation are needed to test these hypotheses further. J. Exp. Zool. (Mol. Dev. Evol.) 302B:226–240, 2004. © 2004 Wiley‐Liss, Inc.
Testing hypotheses about tinkering in the fossil record: the case of the human skull
Authors: Lieberman Daniel E. , Krovitz Gail E. , McBratney‐Owen Brandeis
Published: June 2004

Efforts to test hypotheses about small‐scale shifts in development (tinkering) that can only be observed in the fossil record pose many challenges. Here we use the origin of modern human craniofacial form to explore a series of analytical steps with which to propose and test evolutionary developmental hypotheses about the basic modules of evolutionary change. Using factor and geometric morphometric analyses of craniofacial variation in modern humans, fossil hominids, and chimpanzee crania, we identify several key shifts in integration (defined as patterns of covariation that result from interactions between components of a system) among units of the cranium that underlie the unique shape of the modern human cranium. The results indicate that facial retraction in modern humans is largely a product of three derived changes: a relatively longer anterior cranial base, a more flexed cranial base angle, and a relatively shorter upper face. By applying the Atchley‐Hall model of morphogenesis, we show that these shifts are most likely the result of changes in epigenetic interactions between the cranial base and both the brain and the face. Changes in the size of the skeletal precursors to these regions may also have played some role. This kind of phenotype‐to‐genotype approach is a useful and important complement to more standard genotype‐to‐phenotype approaches, and may help to identify candidate genes involved in the origin of modern human craniofacial form. J. Exp. Zool. (Mol. Dev. Evol.) 302B:284–301, 2004. © 2004 Wiley‐Liss, Inc.
Kinematics of cranial ontogeny: Heterotopy, heterochrony, and geometric morphometric analysis of growth models
Authors: Zollikofer Christoph Peter Eduard , Ponce De León Marcia Silvia
Published: June 2004

In this paper, we examine the relationship between the classical concepts of heterotopy, heterochrony and ontogenetic allometry as descriptive and as explanatory categories in the investigation of evolutionary developmental novelty in the hominid skull. We use concepts of kinematic analysis of locomotion to propose a methodological framework for the kinematic analysis of cranial form change during ontogeny. We argue that a combination of geometric‐morphometric methods with graphics visualization tools currently represents the most adequate means to analyze the kinematics of ontogeny. Using cranial growth models, we simulate how evolutionary modifications of developmental processes impinge on morphological patterns of ontogeny, and explore how differences in ontogenetic patterns can tentatively be traced back to underlying process differences. Our analyses indicate that minor alterations in growth parameters elicit complex patterns of ontogenetic modification that are difficult to describe with the standard repertoire of heterochronic terminology. The proposed kinematic and model‐based approach is used in a comparative analysis of cranial ontogeny in Neanderthals and anatomically modern humans, indicating that early ontogenetic modification of a small set of growth parameters is a major source of evolutionary novelty during hominid evolution.J. Exp. Zool. (Mol. Dev. Evol.) 302B:322‐340, 2004.© 2004 Wiley‐Liss, Inc.
The anthropoid postcranial axial skeleton: Comments on development, variation, and evolution
Authors: Pilbeam David
Published: June 2004

Within‐species phenotypic variation is the raw material on which natural selection acts to shape evolutionary change, and understanding more about the developmental genetics of intraspecific as well as interspecific phenotypic variation is an important component of the Evo‐Devo agenda. The axial skeleton is a useful system to analyze from such a perspective. Its development is increasingly well understood, and between‐species differences in functionally important developmental parameters are well documented. I present data on intraspecific variation in the axial postcranial skeleton of some Primates, including hominoids (apes and humans). Hominoid species are particularly valuable, because counts of total numbers of vertebrae, and hence original somite numbers, are available for large samples. Evolutionary changes in the axial skeleton of various primate lineages, including bipedal humans, are reviewed, and hypotheses presented to explain the changes in terms of developmental genetics. Further relevant experiments on model organisms are suggested in order to explore more fully the differences in developmental processes between primate species, and hence to test these hypotheses. J. Exp. Zool. (Mol. Dev. Evol.) 302B:241–267, 2004. © 2004 Wiley‐Liss, Inc.
Accurate assessment of the arterial input function during high‐dose myocardial perfusion cardiovascular magnetic resonance
Authors: Gatehouse Peter D. , Elkington Andrew G. , Ablitt Nicholas A. , Yang Guang‐Zhong , Pennell Dudley J. , Firmin David N.
Published: June 2004

Purpose

To develop a method for accurate measurement of the arterial input function (AIF) during high‐dose, single‐injection, quantitative T1‐weighted myocardial perfusion cardiovascular magnetic resonance (CMR).

Materials and Methods

Fast injection of high‐dose gadolinium with highly T1 sensitive myocardial perfusion imaging is normally incompatible with quantitative perfusion modeling because of distortion of the peak of the AIF caused by full recovery of the blood magnetization. We describe a new method that for each cardiac cycle uses a low‐resolution short‐axis (SA) image with a short saturation‐recovery time immediately after the R‐wave in order to measure the left ventricular (LV) blood pool signal, which is followed by a single SA high‐resolution image with a long saturation‐recovery time in order to measure the myocardial signal with high sensitivity. Fifteen subjects were studied. Using the new method, we compared the myocardial perfusion reserve (MPR) with that obtained from the dual‐bolus technique (a low‐dose bolus to measure the blood pool signal and a high‐dose bolus to measure the myocardial signal).

Results

A small significant difference was found between MPRs calculated using the new method and the MPRs calculated using the dual‐bolus method.

Conclusion

This new method for measuring the AIF introduced no major error, while removing the practical difficulties of the dual‐bolus approach. This suggests that quantification of the MPR can be achieved using the simple high‐dose single‐bolus technique, which could also image multiple myocardial slices. J. Magn. Reson. Imaging 2004;20:39–45. © 2004 Wiley‐Liss, Inc.
Biolistic expression of the macrophage colony stimulating factor receptor in organotypic cultures induces an inflammatory response
Authors: Mitrasinovic Olivera M. , Robinson Christopher C. , Tenen Daniel G. , Lee Yuen Ling , Poon Clara , Murphy Greer M.
Published: June 2004

The receptor for macrophage colony‐stimulating factor (M‐CSFR; c‐fms) is expressed at increased levels by microglia in Alzheimer's disease (AD) and in mouse models for AD. Increased expression of M‐CSFR on cultured microglia results in a strong proinflammatory response, but the relevance of this cell culture finding to intact brain is unknown. To determine the effects of increased microglial expression of M‐CSFR in a complex organotypic environment, we developed a system for biolistic transfection of microglia in hippocampal slice cultures. The promoter for the Mac‐1 integrin α subunit CD11b is active in cells of myeloid origin. In the brain, CD11b expression is restricted to microglia. Constructs consisting of the promoter for CD11b and a c‐fms cDNA or an enhanced green fluorescent protein (EGFP) cDNA were introduced into monotypic cultures of microglia, neurons, and astrocytes. Strong CD11b promoter activity was observed in microglia, whereas little activity was observed in other cell types. Biolistic transfection of organotypic hippocampal cultures with the CD11b/c‐fms construct resulted in expression of the c‐fms mRNA and protein that was localized to microglia. Furthermore, biolistic overexpression of M‐CSFR on microglia resulted in significantly increased production by the hippocampal cultures of the proinflammatory cytokines interleukin (IL)‐1α macrophage inflammatory protein (MIP‐1α), and trends toward increased production of IL‐6 and M‐CSF. These findings demonstrate that microglial overexpression of M‐CSFR in an organotypic environment induces an inflammatory response, and suggest that increased microglial expression of M‐CSFR could contribute to the inflammatory response observed in AD brain. © 2004 Wiley‐Liss, Inc.
Constitutive Ras activity induces hippocampal hypertrophy and remodeling of pyramidal neurons in synRas mice
Authors: Gärtner Ulrich , Alpár Alán , Reimann Frank , Seeger Gudrun , Heumann Rolf , Arendt Thomas
Published: June 2004

The small G protein Ras, which is involved critically in neurotrophic signal transduction, has been implicated in neuronal plasticity of both the developing and the adult nervous systems. In the present study, the cumulative effects of constitutive Ras activity from early in postnatal development into the adult upon the morphology of hippocampal pyramidal neurons were investigated in synRas mice overexpressing Val12‐Ha‐Ras postmitotically under the control of the rat synapsin I promoter. In synRas mice, stereologic investigations revealed hypertrophy of the hippocampus associated with an increase in perikaryal size of pyramidal neurons within the CA2/CA3 region and the gyrus dentatus. Morphometric analyses of Lucifer Yellow‐filled CA1 pyramidal neurons, in addition, demonstrated considerable expansion of dendritic arbors. The increase in basal dendritic size was caused primarily by alterations of intermediate and distal segments and was associated with an enlarged dendritic surface. Apical dendrites showed similar but more moderate changes, which were attributed mainly to elongation of terminal segments. Sholl analyses illustrated higher complexity of both basal and apical trees. Despite significant morphologic alterations, dendritic arbors preserve their major design principles. The synaptic density within the stratum radiatum of CA1 remained unchanged; however, increases in the total hippocampal volume and in apical dendritic size imply an increment in the absolute number of synaptic contacts. The data presented here suggest a critical involvement of Ras dependent signaling in morphoregulatory processes during the maturation and in the maintenance of hippocampal pyramidal neurons. © 2004 Wiley‐Liss, Inc.
A sulfatase regulating the migratory potency of oligodendrocyte progenitor cells through tyrosine phosphorylation of β‐catenin
Authors: Kakinuma Yoshihiko , Saito Fumiji , Ohsawa Shizue , Furuichi Teiichi , Miura Masayuki
Published: June 2004

By using cDNA subtraction, we identified an extracellular sulfatase (RsulfFP1) from rat oligodendrocyte progenitor cells (OPCs) whose mRNA expression is down‐regulated by tumor necrosis factor‐α. RsulfFP1 mRNA was expressed specifically in the floor plate and the ventral portion of the rat spinal cord at E15. The expression pattern of RsulfFP1 overlapped with the OPCs, which are also located at the ventral region of the ventricular zone. After this stage, RsulfFP1 expression was attenuated, and the OPCs efficiently migrated throughout the spinal cord. The modification of CG‐4 cells, a cell line established from rat O2A cells, by RsulfFP1 activated canonical Wnt signaling. Furthermore, the deletion of RsulfFP1 expression by an antisense oligonucleotide caused impairment of OPC migration in rat spinal cord slice culture. Modification of cells by RsulfFP1 resulted in the increased tyrosine phosphorylation of immunoprecipitated β‐catenin, suggesting that sulfation of the extracellular matrix induced by this sulfatase might be responsible for an increase in Wnt signaling that is involved in the migration of OPCs. Thus, the present study revealed that a sulfatase is responsible for the migration of OPCs and activates intracellular mechanisms that regulate migration. © 2004 Wiley‐Liss, Inc.