bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and effectiveness of stent implantation without predilation for small coronary arteries
Authors: Caputo Ronald P. , Flately Michael , Ho Kalon K.L. , Baim Donald S.
Published: July 2003

The purpose of this study was to examine the safety and effectiveness of stenting without predilation (direct stenting) in small (< 2.5 mm) coronary arteries. Clinical and angiographic data from the multicenter randomized PREDICT trial was examined. Direct stenting was performed on 42 small and 158 large vessels. Predilation was performed prior to stenting for 37 small vessels. In the small‐vessel group, mean reference vessel diameter was 2.24 ± 0.19 mm for direct stenting vs. 2.24 ± 0.22 mm for predilation (P = NS). Mean reference vessel diameter was 3.17 ± 0.48 mm in the large‐vessel group. Device success for direct stenting was similar for small vs. large vessels (90.5% vs. 92.4%; P = NS). At 180 days, a trend toward increased MACE between small vs. large vessels in the direct‐stenting group was observed (26.8% vs.16.7%; P = NS), and significantly higher target lesion revascularizations (TLRs) in the small‐vessel group (19.5% vs.7.7%; P = 0.03) were observed. In small vessels, differences in device success rate (90.5% vs. 100 %; P = NS) and lesion success rate (100% vs. 100%; P = NS) for direct stenting vs. predilation were not significant. At 180 days, no differences between direct stenting and predilation for MACE (26.8% vs. 29.7%; P = NS) or TLR (22.0% vs. 21.6%; P = NS) were seen in small vessels, although binary angiographic restenosis rate tended to be higher in direct‐stenting group (38.2% vs. 18.5%; P = NS). Direct stenting of small vessels can be performed safely and successfully in selected cases. Restenosis rates may be higher for small vessel treated by direct stenting compared to predilation. Cathet Cardiovasc Intervent 2003;59:455–458. © 2003 Wiley‐Liss, Inc.
The VB‐1 catheter: A novel catheter for peripheral arterial revascularization
Authors: Kandzari David E. , Zidar James P. , Behar Victor S.
Published: July 2003

Despite recent advances in catheter‐based technologies for peripheral arterial revascularization, adequate guide catheter positioning and support remains a leading procedural challenge. This report describes the adaptation of the Behar Internal Mammary VB‐1 catheter for peripheral revascularization procedures in patients with complex anatomy not amendable to other conventional peripheral guide catheters. Cathet Cardiovasc Intervent 2003;59:514–517. © 2003 Wiley‐Liss, Inc.
Assessment of the trackability, flexibility, and conformability of coronary stents: A comparative analysis
Authors: Rieu Régis , Barragan Paul , Garitey Vincent , Roquebert Pierre O. , Fuseri Jean , Commeau Philippe , Sainsous Joel
Published: July 2003

The efficacy and safety of coronary stent implantation depend on the mechanical features of these devices when deployed in atheromatous lesions of various morphologies. We evaluated the trackability, flexibility, and conformability of 17 coronary stents using specific mechanical bench tests. The quantifications used a dynamometer for assessment of trackability (maximal strength) and flexibility (stiffness) and a 3D optical gauging machine for assessment of conformability (distance between stent and arterial wall in a curvature). The maximal strength (measuring the trackability) ranged respectively from 0.24 ± 0.06 and 0.38 ± 0.03 N (Seaquest) to 1.31 ± 0.42 and 1.34 ± 0.35 N (Carbostent), concerning respectively curvatures of 90° (P < 0.0001) and 135° (P < 0.0001). The stiffness (measuring the flexibility) ranged from 0.53 ± 0.16 (Seaquest) to 1.28 ± 0.10 N/mm (NIR Royal; P < 0.0001). The mean distance between stent and external curvature (external conformability) ranged from 0.15 ± 0.06 mm (S7) to 0.57 ± 0.4 mm (NIR Royal; P < 0.0001). The mean distance between stent and internal curve (internal conformability) ranged from 0.26 ± 0.13 (S7) to 0.44 ± 0.12 mm (S670; P < 0.0001). These results may influence the choice of a particular stent adapted to a specific coronary anatomy. Cathet Cardiovasc Intervent 2003;59:496–503. © 2003 Wiley‐Liss, Inc.
Radial loop and extreme vessel tortuosity in the transradial approach: Advantage of hydrophilic‐coated guidewires and catheters
Authors: Barbeau Gérald R.
Published: July 2003

Between October 2000 and October 2001, all transradial cases performed by the author necessitating radial and upper arm angiography because of difficult advancement of standard guidewires or catheters were analyzed retrospectively. Fourteen of 594 (2.4%) transradial cases met the study criteria. Radial loops or stenosis and tortuosity in the subclavian or innominate artery were responsible for the difficult access. Several examples of patients with access problems are presented. A technique using a hydrophilic‐coated guidewire and a new hydrophilic‐coated guiding catheter is described. Cathet Cardiovasc Intervent 2003;59:442–450. © 2003 Wiley‐Liss, Inc.
Clinical course and management strategies for hemolysis after transcatheter closure of patent arterial ducts
Authors: Anil Sivadasan Radha , Sivakumar Kothandam , Philip Ancil Kora , Francis Edwin , Kumar R. Krishna
Published: July 2003

Residual flows following transcatheter coil or device closure of the patent ductus arteriosus (PDA) can result in hemolysis. Of 611 patients who underwent transcatheter PDA closure at our institution, 5 patients (age, 6–63 years) developed overt hemolysis (after coil occlusion in 4 and Amplazter device closure in 1). All had ducts > 3 mm and residual flows after the procedure. In one patient, hemolysis occurred 3 months after coil occlusion following a period of uncontrolled hypertension. The occurrence of hemolysis correlated significantly with both age as well as duct size (P < 0.00001). Hemolysis was associated with a fall in hemoglobin of 3–6 g/100 ml (n = 3), jaundice (n = 2), and renal failure (n = 1). Hemolysis subsided spontaneously in one patient and four patients required flow elimination. Deploying additional coils in three patients eliminated residual flows. In one patient (after Amplatzer device closure for 12.5 mm duct with aneurysm), flow persisted after 25 additional coils, transient balloon occlusion, and gel foam instillation. Flow elimination was eventually achieved through thrombin instillation after balloon occlusion of the ampulla. All patients recovered completely and were well on follow‐up. Although hemolysis after duct occlusion is rare (0.8% in this series), residual flow at the end of the procedure merits careful monitoring. Aggressive elimination of residual flows is often necessary to control hemolysis. Cathet Cardiovasc Intervent 2003;59:538–543. © 2003 Wiley‐Liss, Inc.
Rotaglide‐facilitated stent delivery: Mission accomplished
Authors: Chan Albert W. , Ramee Stephen R. , Collins Tyrone , Quintana Hugo , White Christopher J.
Published: July 2003

Percutaneous coronary interventions are performed with a high success rate, though failures still occur. Inability to deliver stents to the target lesion is the most common cause for failures. We present two cases using Rotaglide applied on the stents to enable delivery, showing that Rotaglide is effective in improving stent delivery. Cathet Cardiovasc Intervent 2003;59:477–481. © 2003 Wiley‐Liss, Inc.
Disassembly of a rotablator: Getting out of a trap
Authors: Prasan Ananth M. , Patel Manish , Pitney Mark R. , Jepson Nigel S.
Published: July 2003

The rotablator burr rarely becomes trapped within calcified lesions. Manual traction can be ineffective and dangerous. We report a case that illustrates a novel technique involving use of a percutaneous snare in conjunction with partial disassembly of the rotablator device to remove a trapped burr without need for open surgical intervention. Cathet Cardiovasc Intervent 2003;59:463–465. © 2003 Wiley‐Liss, Inc.
Epithelioid variant of gastrointestinal stromal tumor: Diagnosis by fine‐needle aspiration
Authors: Dong Qun , McKee Grace , Pitman Martha , Geisinger Kim , Tambouret Rosemary
Published: July 2003

Epithelioid gastrointestinal stromal tumors (GISTs) may cause significant diagnostic confusion on fine‐needle aspiration (FNA) with carcinomas, neuroendocrine tumors, and melanoma, particularly when metastatic. This study characterizes the cytologic features of nine cases of epithelioid GISTs that were obtained by computerized tomographic guidance in five, by endoscopic ultrasound in three, and from an excised liver tumor in one. Six cases presented as liver masses, one as a perisplenic mass, one as an abdominal mass, and one as a gastric mass. The aspirates revealed mainly single or small clusters of epithelioid cells with a moderate amount of granular to clear cytoplasm, small uniform nuclei with mild to marked nuclear envelope irregularities. Binucleation and intranuclear inclusions were frequent findings. Collagenous stroma was seen in most cases. In three cases, a neuroendocrine tumor was the initial diagnosis. Immunocytochemical staining for c‐kit (CD117) was performed on cellblocks in six cases and was positive in five cases. On the subsequent surgical specimen, CD117 was positive in the c‐kit‐negative cytology case. The diagnosis of GIST should be considered in aspirates of the gastrointestinal tract, liver, mesentery, or abdominal wall mass lesions when epithelioid cells are the predominant cell type. Ancillary studies such as immunohistochemical stains are usually helpful in making a definitive diagnosis. Diagn. Cytopathol. 2003;29:55–60. © 2003 Wiley‐Liss, Inc.
Metastatic islet cell carcinoma to the umbilicus: Diagnosis by fine‐needle aspiration
Authors: Zhang Yanlong , Selvaggi Suzanne M.
Published: July 2003

Internal malignancies rarely metastasize to the umbilical region. The gastrointestinal tract and female genital tract are the most common primary sites. Although the pancreas is frequently involved, the majority of these metastases are adenocarcinoma. Here, we present a case of umbilical metastasis from an islet cell carcinoma diagnosed by fine‐needle aspiration in a young woman 2 yr after distal pancreatectomy. This finding led to further radiological studies and surgical intervention, which revealed intraabdominal tumor spread. Neuroendocrine tumors represent a rare tumor type that can give rise to umbilical metastases. Only two cases of carcinoid tumor metastasizing to the umbilicus have been reported. Diagn. Cytopathol. 2003;29:91–94. © 2003 Wiley‐Liss, Inc.
Flow cytometry as an adjunct to cytomorphologic analysis of serous effusions
Authors: Czader Magdalena , Ali Syed Z.
Published: July 2003

The role of flow cytometry (FC) in the diagnosis of lymphoid lesions by fine‐needle aspiration (FNA) is well established. However, studies evaluating the usefulness of FC in serous cavity effusions (SCE) are few. We performed a retrospective review of 115 consecutive SCE with concurrent FC analysis, comparing the provisional cytopathologic diagnosis (PCD), i.e., before the FC results were added, with final diagnoses as modified by subsequent FC immunophenotyping. The predominant clinical indication for the FC analysis was the presence of a spontaneous SCE in a patient with a history of malignant lymphoma. Three‐ or four‐color analysis was performed using antibodies against CD45, CD71, CD33, CD22, CD19, CD20, κ, λ, CD5, CD3, and CD56. The PCD was benign in 47%, atypical in 16%, and malignant in 37% of cases. The latter category consisted mostly of malignant lymphoma (n = 32), but also included acute lymphoblastic leukemia (1 case), T‐cell lymphoma/leukemia (2 cases), acute myelogenous leukemia (1 case), multiple myeloma (1 case), Hodgkin's lymphoma (1 case), sarcoma (1 case), and adenocarcinoma (4 cases). In 18 cases (16%), the PCD was later modified by the FC results from atypical/suspicious to benign (8) and from benign or atypical/suspicious to malignant (10 cases). The latter group included acute natural killer (NK) cell leukemia (1 case), chronic lymphocytic leukemia (1 case), mantle cell lymphoma (2 cases), follicular lymphoma (3 cases), angioimmunoblastic lymphoma (1 case), large cell lymphoma (1 case), and multiple myeloma (1 case). As expected, FC was noncontributory in cases of Hodgkin's lymphoma and nonlymphoid malignancies. In summary, immunophenotyping by FC modified the PCD significantly in 16% of SCE, permitting appropriate cancer staging and management. The above data underscore the importance of FC as an adjunct to cytomorphology in SCE. Diagn. Cytopathol. 2003;29:74–78. © 2003 Wiley‐Liss, Inc.
Aspiration cytology of ameloblastic fibroma: A diagnostic challenge
Authors: Kumar Neeta , Jain Shyama
Published: July 2003

Ameloblastic fibroma of the jaw is a rare, benign mixed odontogenic tumor, having little tendency for local invasion and a low recurrence rate. Cytologic distinction from ameloblastoma, ameloblastic fibrosarcoma, and intraosseous adenoid cystic carcinoma is necessary, in view of the different biologic behavior. A painful, slow‐growing swelling of the jaw in a 5‐yr‐old child clinicoradiologically considered as a benign cystic lesion was aspirated. Sheets of small monomorphic epithelial cells with peripheral palisading by columnar cells were seen on cytology smears. The striking feature was central hyaline globules in some tubules. A cytologic possibility of adenomatoid odontogenic tumor was suggested. Histopathology, however, confirmed it to be an ameloblastic fibroma. Diagn. Cytopathol. 2003;29:101–104. © 2003 Wiley‐Liss, Inc.
Cellular schwannoma: Report of a case diagnosed intraoperatively with the aid of cytologic imprints
Authors: Laforga Juan B.
Published: July 2003

The diagnosis of cellular schwannoma in intraoperative consultation is difficult because of the hypercellularity and deep location, which may lead to errors. The recognition of cytologic features together with the histological appearance are of great importance to make the correct diagnosis. An accurate diagnosis of this variant of schwannoma is important because other spindle cell tumors display differences in treatment and clinical behavior. We report a demonstrative case of cellular schwannoma arising in retroperitoneum of a 52‐yr‐old woman in which the cytologic imprints were useful to make an accurate diagnosis intraoperatively. Briefly, the differential diagnosis is discussed. Diagn. Cytopathol. 2003;29:95–100. © 2003 Wiley‐Liss, Inc.
Detection of a subset of CD30+ anaplastic large cell lymphoma by interphase fluorescence in situ hybridization
Authors: Shin Hyung Ju C. , Thorson Phataraporn , Gu Jun , Katz Ruth L.
Published: July 2003

T/null‐cell anaplastic large cell lymphoma (ALCL) is a morphologically and clinically heterogeneous group of non‐Hodgkin's lymphoma; to date several morphologic variants have been described on histologic specimens. However, the cytologic features of these variants in the fine‐needle aspiration (FNA) specimens have not been well evaluated. The t(2;5)(p23;q35) has been identified in a subset of T/null‐ALCL and is known to be associated with a favorable prognosis. We reviewed the cytomorphologic characteristics in 24 FNA specimens of ALCL. In all cases, the diagnosis was confirmed on histologic specimens, and immunohistochemical studies for anaplastic lymphoma kinase (ALK) protein expression were performed on the aspirates. The presence of ALK breakpoints were evaluated in nine cases, using a DNA break‐apart probe on chromosome 2 covering the ALK gene by fluorescence in situ hybridization (FISH) techniques. Two hundred cells per case were examined. The results were expressed as the percentage of cells containing more than two signals of chromosome 2 to the total number of cells counted. FNA sites included lymph nodes (20), lung (2), breast (1), and soft tissue (1). The median age of the patients was 56 yr (range, 17–75 yr). Twenty cases had systemic involvement; in four cases, skin was the primary site with secondary involvement of the lymph nodes. All cases were CD30+ by immunohistochemistry; 20 were of T‐cell phenotype and 4 were null cell type. The cytologic evaluation revealed typical anaplastic morphology (common type) with many “hallmark cells” in 16 (67%) cases. Other morphologic variants identified were small cell pattern in five cases, monomorphic pattern in two cases, and lymphohistiocytic pattern in one case. FISH studies showed that six (66.7%) of nine cases had at least two signals of chromosome 2, consistent with ALK breakpoints. With careful cytomorphologic evaluation in conjunction with appropriate immunohistochemical studies, a diagnosis of ALCL can be confidently made in the FNA specimens in the cellular aspirates and its morphologic variants also can be recognized. Furthermore, the FNA specimen is suitable in detecting ALK breakpoints by FISH study, permitting rapid identification of a subset of patients with ALCL, who may have a favorable prognosis. Using a commercially available probe, detection of ALK breakpoints in the FNA specimens is simple and can be a useful diagnostic adjunct in cases where distinction from other lymphomas or lymphoid lesions is morphologically difficult. Diagn. Cytopathol. 2003;29:61–66. © 2003 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of giant cell tumor of tendon sheath
Authors: Iyer Venkateswaran K. , Kapila Kusum , Verma Kusum
Published: July 2003

Giant cell tumor of tendon sheath (GCTTS) is a unique soft tissue lesion of the hands and feet. As the cytomorphological features of this lesion are rarely documented, the spectrum of cytomorphological features in 20 cases of GCTTS seen in fine‐needle aspiration (FNA) smears are presented. Patients were in the 12–64‐yr age group with an equal sex ratio. Fingers or thumb were the commonest site (16 cases), followed by foot (3 cases) and palm (1 case). FNA smears were cellular and composed of varying proportions of stromal and giant cells. Stromal cells showed a dispersed arrangement and were polygonal to spindle shaped. Nuclear grooves and convolutions were found in some of the stromal cells in all cases. Intranuclear cytoplasmic inclusions were occasionally seen. Polygonal cells with round nuclei and nucleoli having abundant cytoplasm, along with binucleate forms, were also found in all cases. Histological sections were available in 10 cases and corroborated the cytological features. Hemosiderin‐laden macrophages (11 of 20 cases) and abundant foamy vacuolation of stromal cells (3 of 20 cases) were also observed in FNA smears. In tissue sections, both features were seen in all cases, but with a patchy distribution. The cytological features of GCTTS are uniform, and FNA cytodiagnosis is possible. Diagn. Cytopathol. 2003;29:105–110. © 2003 Wiley‐Liss, Inc.
Urine cytology in renal glomerular disease and value of G1 cell in the diagnosis of glomerular bleeding
Authors: Nguyen Gia‐Khanh
Published: July 2003

The objectives of the present study were to evaluate the cytology of urine sediments in patients with glomerular diseases, as well as the value of G1 dysmorphic erythrocytes (G1DE) or G1 cells in the detection of renal glomerular hematuria. Freshly voided urine samples from 174 patients with glomerular diseases were processed according to the method used for semiquantitative cytologic urinalysis. G1DEs (distorted erythrocytes with doughnut‐like shape, target configuration with or without membranous protrusions or blebs), non‐G1DEs (distorted erythrocytes without the above‐mentioned morphologic changes), normal erythrocytes (NEs), and renal tubular cells (RTCs) were evaluated. Erythrocytic casts (ECs) were counted and graded as abundant (>1 per high‐power field) or rare (1 per 5 high‐power fields). G1DE/total erythrocyte ratios were calculated by counting 200 erythrocytes including G1DEs, non‐G1DEs, and NEs. Only abundant NEs were found in 13 cases; abundant G1DEs, non‐G1DEs, NEs, and no ECs in 95 cases; abundant NEs, non‐G1DEs, and ECs and no G1DEs in 31 cases; and abundant NEs, G1DEs and non‐G1DEs, and rare ECs in 35 cases. In 130 cases in which G1DEs were present, the G1DE/total erythrocyte ratios varied from 10% to 100%. This parameter was greater or equal to 80%, 50%, 20%, and 10% in 58 (44.6%), 29 (22.3%), 28 (21.5%), and 15 (11.5%) patients, respectively. In all cases, the number of RTCs was within normal limits or slightly increased, and a variable number of non‐G1DEs were present in 161 cases. Thus, abundant ECs and/or G1DEs with a G1DE/total erythrocyte ratio of 10–100% proved to be specific urinary markers for renal glomerular diseases. Diagn. Cytopathol. 2003;29:67–73. © 2003 Wiley‐Liss, Inc.
Case of adrenal lymphangioma with atypical lymphocytes in aspirate cytology
Authors: Satou Takao , Uesugi Tadao , Nakai Yuka , Hayashi Yoshiyuki , Imano Motohiro , Hashimoto Shigeo
Published: July 2003

Cytological diagnosis of adrenal cysts is becoming more important, with the increase in cases identified due to the widespread use of imaging modalities. Adrenal cysts have been classified into four main groups: endothelial, epithelial, parasitic, and pseudocyst, with endothelial cysts further classified as lymphangiomatous or angiomatous. We report on a case of adrenal lymphangioma with atypical lymphocytes found in the intraoperative aspirate, suggesting an inconclusive diagnosis, although immunohistochemical study led us to suppose their B‐cell origin. This case provided important cytological findings that may assist in the prevention of cytological overdiagnosis. Diagn. Cytopathol. 2003;29:87–90. © 2003 Wiley‐Liss, Inc.
Fractal dimensions of breast lesions on cytology smears
Authors: Dey Pranab , Mohanty Sambit K.
Published: July 2003

In the present study, box‐counting fractal dimensions of benign and malignant cells of breast tumors on cytology material were measured and compared. We selected fine‐needle aspiration cytology smears of 14 cases of histopathology‐proven infiltrating duct carcinomas and 7 cases of fibroadenoma of the breast. Five cells were randomly selected from each case. Box‐counting fractal dimensions of all cells were measured with the help of an image cytometer (Leica, Cambridge, UK), using Quantimet 600 software (Leica). In total, 70 malignant cells and 35 benign cells were studied. The mean fractal dimensions of malignant cells and benign cells were 0.9571 ± 0.1265 and 0.8354 ± 0.1367, respectively. There was significant difference in the fractal dimension of malignant and benign cells (P = 0.006, Mann‐Whitney nonparametric test). The measurement of fractal dimension may be helpful in discriminating malignant from benign cells. This may be another discriminating feature of malignant cells, along with classic image morphometry based on Euclidean geometry. Diagn. Cytopathol. 2003;29:85–86. © 2003 Wiley‐Liss, Inc.
Accuracy of cytological grading of spindle‐cell sarcomas
Authors: Mathur Sandeep , Kapila Kusum , Verma Kusum
Published: July 2003

Spindle‐cell sarcomas constitute an important component of soft‐tissue sarcomas, where accurate grading may be more important than histologic subtype in order to plan treatment strategies and determine prognosis. To evaluate the applicability and accuracy of grading spindle‐cell sarcomas on fine‐needle aspiration cytology (FNAC) smears, 54 cases of histologically documented spindle‐cell sarcomas, consisting of synovial sarcomas (20 cases), neurofibrosarcomas (12 cases), leiomyosarcomas (9 cases), dermatofibrosarcoma protuberans (DFSP; 6 cases), fibrosarcomas (3 cases), hemangiopericytomas (2 cases), and spindle‐cell sarcomas, unclassified (2 cases), were graded according to a three‐tier system proposed earlier for FNAC smears, while the histological sections were graded using the French Federation of National Cancer Centers (FNCLCC) grading system. The cytological grading was correlated with the histological grade. There was an overall cytologic and histologic concordance in 40/54 (74%) cases, and concordance in 9/13 (69%) grade I, 19/25 (76%) grade II, and 12/16 (75%) grade III cases. Analysis of grading of individual sarcomas revealed a concordance in 92% of neurofibrosarcomas, 78% of leiomyosarcomas, 70% of synovial sarcomas, 67% of dermatofibrosarcoma protuberans, 67% of fibrosarcomas, 50% of hemangiopericytomas, and 50% of cases of malignant mesenchymal tumors, spindle‐cell type unclassified. Major noncorrelation was seen in 10/54 (18.5%) cases. Minor noncorrelation was seen in 4/54 (7.4%) cases. Thus it is possible to accurately predict the grade in 74% of cases of spindle‐cell sarcomas. The cytological and histological concordance was better (75%) in high‐grade (grades II and III) as compared to grade I sarcomas (69%). Sampling errors due to morphologic heterogeneity in sarcomas may cause noncorrelation in a few cases. Diagn. Cytopathol. 2003;29:79–83. © 2003 Wiley‐Liss, Inc.
Pap test discrepancies and follow‐up histology
Authors: Stelow Edward B. , Skeate Robert , Wahi Monika M. , Kjeldahl Klint , McKeon Dan , Larkin Stephen , Woronzoff Kristine , Pambuccian Stefan E.
Published: July 2003

Papanicolaou (Pap) test discrepancy rates between cytotechnologists (CTs) and cytopathologists (CPs) are often kept to evaluate the performance of individual CTs. This is based on the unproven assumption that the CP's diagnoses are more likely to be correct. We investigated this assumption using data from our discrepancy files and comparing them to follow‐up histology. All Pap test discrepancies were noted between January 1, 2001–December 31, 2001. Surgical pathology files were then searched for follow‐up histology within 9 mo of the Pap test. Histologic diagnoses were compared with the previous CT and CP diagnoses, and then judged regarding accuracy. In total, 63,376 Pap tests were evaluated between January 1, 2001–December 31, 2001. There were 795 discrepancies throughout this period (1.25%). One hundred and sixty‐six cases with discrepancies had follow‐up histology within 9 mo of the Pap test (20.9%). Of downgraded cases (103), CPs were more correct in 51 cases (49.5%), whereas CTs were more correct in 52 cases (50.5%). Of upgraded cases (63), CPs were more correct in 19 cases (30.2%), whereas CTs were more correct in 44 cases (69.8%). Our results suggest that CPs are not more likely to be correct than CTs when there is a discrepancy with the diagnosis of a Pap test, especially when CPs upgrade CT diagnoses. This suggests that discrepancy data may be helpful for evaluating the performance of both CPs and CTs. It may also be of educational use for both CPs and CTs to know the follow‐up histology in these cases. Diagn. Cytopathol. 2003;29:111–115. © 2003 Wiley‐Liss, Inc.
Developmentally regulated expression of Netrin‐1 and ‐3 in the embryonic mouse molar tooth germ
Authors: Løes Sigbjørn , Luukko Keijo , Hals Kvinnsland Inger , Salminen Marjo , Kettunen Päivi
Published: July 2003

The Netrins form a small, conserved family of laminin‐related signaling proteins regulating axon guidance in the developing nervous system. Here, we analyzed the roles of Netrin‐1 and ‐3 in trigeminal axon guidance to the first lower molar of the embryonic mouse. Netrin‐1 showed a restricted epithelial expression domain buccal to the tooth germ, toward which the pioneer tooth axons initially appear to navigate. Later, before birth, transcripts were colocalized with nerve fibers around the bell stage tooth germ. Analysis of Netrin‐1–deficient mice, however, did not reveal any obvious disturbances in the axon growth or pattern of tooth innervation. In contrast, Netrin‐3 showed a prominent, distinct expression in the axon pathway and target field mesenchyme around the tooth. Hence, it is possible that Netrin‐3 may regulate pioneer axon growth toward and within the embryonic tooth target field. Developmental Dynamics 227:573–577, 2003. © 2003 Wiley‐Liss, Inc.
Morphogenesis of blood vessels in the head muscles of avian embryo: Spatial, temporal, and VEGF expression analyses
Authors: Ruberte Jesus , Carretero Ana , Navarro Marc , Marcucio Ralph S. , Noden Drew
Published: July 2003

Adult skeletal muscle is a highly vascularized tissue, but the development of intramuscular endothelial networks has not been well studied. In quail embryos, QH1‐positive angioblasts are present and moving throughout myogenic head mesoderm before the onset of primary myotube formation. On day 5 of incubation, concurrent with early myotube formation and aggregation, angioblasts establish a transient vascular plexus surrounding the myogenic condensations. Between days 5 and 9, the intramuscular vessels form an irregular network of endothelial cords and patent channels and only later are the parallel arrays of capillaries characteristic of adult muscles established. Microinjections using India ink, QH1, and Mercox resin reveal that these intramuscular capillaries are typically not connected to systemic vessels of the head until day 10, which is near the end of primary myogenesis and corresponds to the onset of muscular function. Morphometric analyses performed during primary myogenesis stages show a decrease in muscle cell density but no significant changes in intramuscular vascular density between days 5 and 9. This finding was surprising, as it is generally assumed that muscle growth requires elevated oxygen and nutrient levels. Moreover, there are no significant morphometric differences in vascular supply to embryonic fast and slow muscles. Endothelial tissue density is similar in slow muscles (oculorotatory, e.g., lateral rectus), fast muscles (mandibular depressor), and mixed muscles, in which the fiber types can be interspersed (jaw adductors) or segregated (branchiomandibular). Vascular endothelial growth factor (VEGF) protein is abundant in myotubes but not endothelial cells within both fast and slow head muscles at days 7 and 9. However, in some mixed muscles, only a minority of myotubes, which do not correspond to one specific fiber type, express VEGF. These results document a dynamic set of intramuscular and perimuscular angiogenic reorganizations during avian head myogenesis. Thus far, no vasculogenic distinctions between fast and slow muscles have been observed, although muscle heterogeneity in VEGF expression is evident. Developmental Dynamics 227:470–483, 2003. © 2003 Wiley‐Liss, Inc.
In vivo regulation of the chicken cardiac troponin T gene promoter in zebrafish embryos
Authors: Tidyman William E. , Sehnert Amy J. , Huq Anja , Agard Jennifer , Deegan Fiona , Stainier Didier Y.R. , Ordahl Charles P.
Published: July 2003

The chicken cardiac troponin T (cTnT) gene is representative of numerous cardiac and skeletal muscle‐specific genes that contain muscle‐CAT (MCAT) elements within their promoters. We examined the regulation of the chicken cTnT gene in vivo in zebrafish embryos, and in vitro in cardiomyocyte, myoblast, and fibroblast cultures. Defined regions of the cTnT promoter were linked to the green fluorescent protein (GFP) gene for in vivo analysis, and the luciferase gene for in vitro analysis. Injection of the cTnT promoter constructs into fertilized zebrafish eggs resulted in GFP expression in both heart and skeletal muscle cells reproducing the pattern of expression of the endogenous cTnT gene in the chicken embryo. Promoter deletion analysis revealed that the cis‐regulatory regions responsible for cardiac and skeletal muscle‐specific expression functioned in an equivalent manner in both in vitro and in vivo environments. In addition, we show that mutation of the poly‐ADP ribose polymerase‐I (PARP‐I) binding site adjacent to the distal MCAT element in the chicken cTnT promoter produced a non–cell‐specific promoter in vitro and in the zebrafish. Thus, the PARP‐I transcriptional regulatory mechanism that governs muscle specificity of the chicken cTnT promoter is conserved across several chordate classes spanning at least 350 million years of evolution. Developmental Dynamics 227:484–496, 2003. © 2003 Wiley‐Liss, Inc.
Selective control of neuronal cluster size at the forebrain/midbrain boundary by signaling from the prechordal plate
Authors: Tallafuß Alexandra , Adolf Birgit , Bally‐Cuif Laure
Published: July 2003

Within the vertebrate embryonic neural plate, the first neuronal clusters often differentiate at the border of patterning identities. Whether the information inherent in the intersection of patterning identities alone controls all aspects of neuronal cluster development (location, identity, and size) is unknown. Here, we focus on the cluster of the medial longitudinal fascicle (nMLF) and posterior commissure (nPC), located at the forebrain/midbrain (fore/mid) boundary, to address this issue. We first identify expression of the transcription factor Six3 as a common and distinct molecular signature of nMLF and nPC neurons in zebrafish, and we use this marker to monitor mechanisms controlling the location and number of nMLF/nPC neurons. We demonstrate that six3 expression is induced at the fore/mid boundary in pax2.1/no‐isthmus and smoothened/slow muscle omitted mutants, where identities adjacent to the six3 cluster are altered; however, in these mutants, the subpopulation of six3‐positive cells located within the mispatterned territory is reduced. These results show that induction of the six3 cluster is triggered by the information derived from the intersection in patterning identities alone, whereas correct cluster size depends, in a modular manner, on the identities themselves. The size of the six3 cluster is also controlled independently of neural tube patterning: we demonstrate that the prechordal plate (PCP) is impaired in mixer/bonnie and clyde mutants and that this phenotype secondarily results in an increased production of six3‐positive cells at the fore/mid boundary, without correlatively affecting patterning in this area. Thus, a signaling process originating from the PCP distinguishes between neural patterning and the control of six3 cluster size at the fore/mid junction in vivo. Together, our results suggest that a combination of patterning‐related and ‐unrelated mechanisms specifically controls the size of individual early neuronal clusters within the anterior neural plate. Developmental Dynamics 227:524–535, 2003. © 2003 Wiley‐Liss, Inc.
Zebrafish atonal homologue zath3 is expressed during neurogenesis in embryonic development
Authors: Wang Xukun , Emelyanov Alexander , Korzh Vladimir , Gong Zhiyuan
Published: July 2003

Basic helix‐loop‐helix (bHLH) transcriptional activators function in development of various cell lineages, including the central nervous system. One of the bHLH proteins, Math3/Xath3/NeuroM, was suggested to act as a late proneural gene in the mouse, Xenopus, and chick. Here, we isolated a zebrafish homologue, named zath3, and analyzed its expression pattern in zebrafish embryos. In the neural plate, zath3 is expressed first in the primordia of the tegmentum and trigeminal ganglia and three classes of primary neurons: sensory neurons, interneurons, and motor neurons. During later development, zath3 transcripts were localized along the boundaries of the optic tectum in the midbrain and rhombomeres of the hindbrain. Analyses of zath3 expression in three mid‐hindbrain boundary mutants, acerebellar, no isthmus, and spiel‐ohne‐grensen, indicated that distribution of zath3 mRNAs in the midbrain and hindbrain was dramatically disturbed. In addition, these mutants also affect expression of zath3 in the neuroretina. Developmental Dynamics 227:587–592, 2003. © 2003 Wiley‐Liss, Inc.
Embryonic stem cell and tissue‐specific expression of a novel conserved gene, asrij
Authors: Mukhopadhyay Arpita , Das Debjani , Inamdar Maneesha S.
Published: July 2003

We have identified a novel gene expressed in murine embryonic stem (ES) cells and in a restricted, tissue‐specific pattern during mouse development. The gene is also expressed in blood vessels; hence, we have named it asrij (Sanskrit; asRˆij = blood). The gene encodes a novel conserved, predicted transmembrane protein of 247 amino acids, which is localized to lysosomes and endosomes. During ES cell‐derived blood vessel formation in vitro, Asrij expression precedes and partially overlaps with the vascular markers Flk‐1 and PECAM. During development, Asrij is expressed predominantly in mouse embryonic blood vessels. The asrij transcript is alternatively spliced, and its expression is regulated in a tissue‐specific manner. An asrij splice variant that is enriched in the adult mouse brain encodes a protein of 196 amino acids. Asrij can serve as an early stem cell marker that is down‐regulated in nonvascular tissues. Our data indicate that Asrij belongs to a novel class of conserved proteins with a complex developmental profile and suggests multiple functions for the gene. Development Dynamics 227:578–586, 2003. © 2003 Wiley‐Liss, Inc.
Wnt11 and Wnt7a are up‐regulated in association with differentiation of cardiac conduction cells in vitro and in vivo
Authors: Bond Jacqueline , Sedmera David , Jourdan Jane , Zhang Yuhua , Eisenberg Carol A. , Eisenberg Leonard M. , Gourdie Robert G.
Published: July 2003

The heart beat is coordinated by a precisely timed sequence of action potentials propagated through cells of the conduction system. Previously, we have shown that conduction cells in the chick embryo are derived from multipotent, cardiomyogenic progenitors present in the looped, tubular heart. Moreover, analyses of heterogeneity within myocyte clones and cell birth dating have indicated that elaboration of the conduction system occurs by ongoing, localized recruitment from within this multipotent pool. In this study, we have focused on a potential role for Wnt signaling in development of the cardiac conduction system. Treatment of embryonic myocytes from chick with endothelin‐1 (ET‐1) has been shown to promote expression of markers of Purkinje fiber cells. By using this in vitro model, we find that Wnt11 are Wnt7a are up‐regulated in association with ET‐1 treatment. Moreover, in situ hybridization reveals expression, although not temporal coincidence of, Wnt11 and Wnt7a in specialized tissues in the developing heart in vivo. Specifically, whereas Wnt11 shows transient and prominent expression in central elements of the developing conduction system (e.g., the His bundle), relative increases in Wnt7a expression emerge at sites consistent with the location of peripheral conduction cells (e.g., subendocardial Purkinje fibers). The patterns of Wnt11 and Wnt7a expression observed in vitro and in the embryonic chick heart appear to be consistent with roles for these two Wnts in differentiation of cardiac conduction tissues. Development Dynamics 227:536–543, 2003. © 2003 Wiley‐Liss, Inc.
Pigment cell organization in the hypodermis of zebrafish
Authors: Hirata Masashi , Nakamura Kei‐ichiro , Kanemaru Takaaki , Shibata Yosaburo , Kondo Shigeru
Published: July 2003

Zebrafish have a characteristic horizontal‐stripe pigment pattern made by a specific distribution of three types of pigment cells: melanophores, xanthophores, and iridophores. This pattern is a valuable model to investigate how the spatial patterns form during animal development. Although recent findings suggest that the interactions among the pigment cells play a key role, the particular details of these interactions have not yet been clarified. In this report, we performed transmission electron microscopic study to show the distribution, conformation, and how the cells contact with each other in the hypodermis. We found that the pigment cells form complex but ordered, layered structures in both stripe and interstripe regions. The order of the layered structures is kept strictly all through the hypodermal regions. Our study will provide basic information to investigate the mechanism of pigment pattern formation in zebrafish. Developmental Dynamics 227:497–503, 2003. © 2003 Wiley‐Liss, Inc.
Evidence for an extracellular matrix bridge guiding proepicardial cell migration to the myocardium of chick embryos
Authors: Nahirney Patrick C. , Mikawa Takashi , Fischman Donald A.
Published: July 2003

During heart development, the proepicardium (PE) gives rise to cells of the epicardial epithelium, connective tissue of the subepicardium and the myocardium, and smooth muscle, endothelium, and connective tissue of the coronary arteries. The PE arises as an outgrowth of the pericardial serosa at embryonic day 2 (Hamburger and Hamilton stage [HH] 14) of chick development. Between stages HH14 and HH17, multicellular villous projections extend from the PE toward the dorsal aspect of the lesser curvature of the myocardium. On reaching the atrioventricular (AV) junction, the cells spread over the myocardium, eventually enveloping the complete heart surface as a simple squamous epithelium. Although the lineage of the PE cells is well established, it remains uncertain how cells of the PE reach the myocardial surface and specifically target the AV junction. By using a combination of serial section reconstructions, immunofluorescence, and electron microscopy, we have identified an extracellular matrix bridge (ECMB) spanning the coelomic cavity between the PE and the myocardium. The ECMB is first detectable at HH14 and persists until the PE contacts the bare myocardial surface. This ECMB stains intensely with ruthenium red and Alcian blue, contains heparan sulfate and fibronectin, and exhibits both fibrillar and globular ultrastructure, reminiscent of proteoglycans. After PE attachment to the myocardium (HH16–HH17), the subepicardium exhibited strong staining for heparan sulfate. Heparinase injection into the pericardial coelom at HH15 resulted in aberrant development of the primordial epicardium. On the basis of these studies, we suggest that the ECMB may participate in migration and targeting of the PE to the myocardium. Developmental Dynamics 227:511–523, 2003. © 2003 Wiley‐Liss, Inc.
Induction of neurogenin‐1 expression by sonic hedgehog: Its role in development of trigeminal sensory neurons
Authors: Ota Mitsunori , Ito Kazuo
Published: July 2003

We have examined the roles of signaling molecules in the mechanisms underlying the induction of neurogenin (ngn)‐1 expression. ngn‐1 is a basic helix‐loop‐helix (bHLH) transcription factor, which is essential for the specification of trigeminal sensory neurons. Semiquantitative reverse transcriptase‐polymerase chain reaction using cranial explants in organ cultures showed that sonic hedgehog (Shh) promotes ngn‐1 expression. This promoting activity was not observed in other signaling molecules examined. The promotion of ngn‐1 expression by Shh, furthermore, was inhibited by cyclopamine, a specific inhibitor of Shh signaling. Shh did not affect the expression of ngn‐2, a bHLH transcription factor that plays an important role in the specification of epibranchial placode‐derived sensory neurons. The expression levels of ngn‐1 and ngn‐2 decreased after fibroblast growth factor‐2 treatment. These results suggest that Shh induces ngn‐1 expression specifically and that expression of ngn‐1 and ngn‐2 is regulated by different mechanisms. The induction of ngn‐1 expression by Shh suggests that this signaling molecule participates in the specification of trigeminal sensory neurons. We therefore examined the effect of Shh on the development of these neurons. Immunostaining using anti–ngn‐1 demonstrated that Shh promotes ngn‐1 expression in trigeminal neural crest cells. Trigeminal neural crest cells are derived from the posterior mesencephalon and the most‐anterior rhombencephalon, and they contain a subset of precursors of trigeminal sensory neurons. Moreover, a subpopulation of trigeminal neural crest cells expressed the Shh receptor Patched. The number of cells that express Brn3a, a POU‐domain transcription factor that plays an important role in differentiation of sensory neurons, also increased with Shh treatment. Our data suggest that Shh signaling is involved in the specification of trigeminal sensory neurons through the induction of ngn‐1 expression. Furthermore, Shh promotes the differentiation of neural crest cells into trigeminal sensory neurons. Developmental Dynamics 227:554–551, 2003. © 2003 Wiley‐Liss, Inc.
Pluripotency of reprogrammed somatic genomes in embryonic stem hybrid cells
Authors: Tada Masako , Morizane Asuka , Kimura Hironobu , Kawasaki Hiroshi , Ainscough Justin F.X. , Sasai Yoshiki , Nakatsuji Norio , Tada Takashi
Published: July 2003

Somatic nuclei can be epigenetically reprogrammed by factors present in undifferentiated embryonic stem (ES) cells. The acquisition of pluripotency by somatic genomes could render such cells a viable source of personalized cell type(s) for therapeutic application, avoiding the need for controversial therapeutic cloning. To investigate this possibility, we first determined the origin of transcripts in teratomas generated from mouse (ES × somatic cell) hybrid clones. Transcription of markers from the somatic genome demonstrated efficient in vivo differentiation down independent lineages. The induction of dopaminergic neurons by coculture with stromal PA6 feeder cells also demonstrated efficient capacity to differentiate in vitro. Hybrid clone‐derived neurons expressed appropriate markers, and transcription of Pitx3 from the somatic genome was confirmed. When transplanted into mouse brains, the dopaminergic neurons were successfully integrated and expressed tyrosine hydroxylase. Thus, it should be possible to produce personalized ES‐like cells with the reprogrammed somatic genomes. Developmental Dynamics 227:504–510, 2003. © 2003 Wiley‐Liss, Inc.
Establishment of a ventral cell fate in the spinal cord
Authors: Moghadam Kaveh S. , Chen Aileen , Heathcote R. David
Published: July 2003

The neural plate is induced during gastrulation when the organizer affects the ectoderm around it. Recent experiments show that axial mesoderm can stimulate formation of specific ventral cell types in the spinal cord, including floor plate, motor neurons, and several types of interneurons. We have eliminated or disrupted axial mesoderm by using a variety of methods to show that ventral columns of intermittent dopaminergic neurons in the frog Xenopus also appear to be induced by axial mesoderm. Inversion of the dorsal‐ventral neural axis by splitting the presumptive neural plate in vivo, produced two spinal cords with ectopic dopaminergic neurons. The location and number of neurons suggest that even a brief association with axial mesoderm can specify the identity of the first or primary dopaminergic neurons and that notochord retains the ability to induce cells to become secondary dopaminergic neurons. Developmental Dynamics 227:552–562, 2003. © 2003 Wiley‐Liss, Inc.
Progranulin (acrogranin/PC cell‐derived growth factor/granulin‐epithelin precursor) is expressed in the placenta, epidermis, microvasculature, and brain during murine development
Authors: Daniel Rachael , Daniels Eugene , He Zhiheng , Bateman Andrew
Published: July 2003

The growth factor progranulin (acrogranin/PC‐derived growth factor/granulin‐epithelin precursor) promotes onset of blastocyst cavitation and is required for neonatal hypothalamic sexual differentiation. Little is known, however, of the range of developmental processes in which it is involved. We used in situ hybridization to investigate progranulin expression in murine embryos. Progranulin mRNA is expressed in maternal and embryonic components during early establishment of pregnancy. Abundant expression is observed in the early decidualizing uterine stroma and glands. In the embryo, the trophoblast giant cells at the interface of placental exchange sites (both choriovitelline and chorioallantoic placenta) show strong expression. The gastrulating epiblast and mesenchyme (intraembryonic and extraembryonic mesenchyme) all revealed activity. The allantois and yolk sac mesenchyme (site of early hemopoiesis) were positive, as were later phases of active vessel formation (pia mater of brain, epicardium of the heart). In the urogenital system, it was expressed in Sertoli cells and in kidney tubules. It was highly expressed in proliferating epidermal cells. During epidermal appendage formation, the early epithelial bud was positive, but the forming duct and differentiating adjacent mesenchyme was negative. It is widely distributed during central nervous system development and the peripheral nervous system (dorsal root ganglia and sympathetic ganglia). Based on the pattern of progranulin gene expression, we propose proliferative and developmental roles for progranulin in establishing pregnancy, during gastrulation, and during embryonic development of the epidermis, nervous system, blood vessel, formation, and spermatogenesis. Developmental Dynamics 593–599, 2003. © 2003 Wiley‐Liss, Inc.