bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in professional conceptions of suicide prevention among psychologists: using a conceptual model
Authors: Upanne Maila
Published: August 2002

This prospective follow‐up study monitored the evolution of psychologists' conceptions of suicide prevention over the course of their participation in psychological autopsy studies that constituted the first phase of the National Suicide Prevention Project in Finland. Another purpose of the study was to consider the feasibility of an earlier suicide prevention model. Ideas on prevention were compared in two different situations and items were categorized using descriptive and conceptual criteria of prevention. They could be classified into a typology of four categories: care approach, cultural‐educational approach, conditions approach, and critical approach. The follow‐up suggested that the model is a feasible method for analysing conceptions of suicide prevention, and that it was possible to interpret conceptions in a theoretically adequate manner. In addition, ideas could be compared with certain known theoretical models of prevention. The model could thus be used in further research and for practical purposes. Experiences of psychological autopsy studies definitely had an impact on the psychologists' views; conceptions altered towards emphasizing the care approach and individual risk factors. Nonetheless, the overall structure of the prevention paradigm remained multifactorial, stressing multistage influencing. Surprisingly, the priority of acute suicide risk as a preventive target did not increase. Promotive aims remained the most important aim category. Copyright © 2002 John Wiley & Sons, Ltd.
Mixing theory with real‐time analysis: a look at an online music distributor
Authors: Vibert Conor
Published: August 2002

Although in its infancy, the practice of Web‐based analysis is dramatically altering the way corporations approach the discipline of competitive intelligence (CI). The same can be said for the impact of the World Wide Web on business strategy research and instruction. This article outlines an innovative approach to understanding agency theory, and offers the case of MP3.com to illustrate the use of Web‐based online evidence as both a research and teaching tool for experienced and budding analysts. © 2001 John Wiley & Sons, Inc.
Transient concentration of a γ‐tubulin‐related protein with a pericentrin‐related protein in the formation of basal bodies and flagella during the differentiation of Naegleria gruberi
Authors: Suh Mi Ra , Han Ji Woong , No Yi Ran , Lee JooHun
Published: August 2002

The distribution of two proteins in Naegleria gruberi, N‐γTRP (Naegleria γ‐tubulin‐related protein) and N‐PRP (Naegleria pericentrin‐related protein), was examined during the de novo formation of basal bodies and flagella that occurs during the differentiation of N. gruberi. After the initiation of differentiation, N‐γTRP and N‐PRP began to concentrate at the same site within cells. The percentage of cells with a concentrated region of N‐γTRP and N‐PRP was maximal (68%) at 40 min when the synthesis of tubulin had just started but no assembled microtubules were visible. When concentrated tubulin became visible (60 min), the region of concentrated N‐γTRP and N‐PRP was co‐localized with the tubulin spot and then flagella began to elongate from the region of concentrated tubulin. When cells had elongated flagella, the concentrated N‐γTRP and N‐PRP were translocated to the opposite end of the flagellated cells and disappeared. The transient concentration of N‐γTRP coincided with the transient formation of an F‐actin spot at which N‐γTRP and α‐tubulin mRNA were co‐localized. The concentration of N‐γTRP and formation of the F‐actin spot occurred without the formation of microtubules but were inhibited by cytochalasin D. These observations suggest that the regional concentration of N‐γTRP and N‐PRP is mediated by actin filaments and might provide a site of microtubule nucleation for the assembly of newly synthesized tubulins into basal bodies and flagella. Cell Motil. Cytoskeleton 52:66–81, 2002. © 2002 Wiley‐Liss, Inc.
Growth cones contain myosin II bipolar filament arrays
Authors: Bridgman Paul C.
Published: August 2002

Nonmuscle myosin II is among the most abundant forms of myosin in nerve growth cones. At least two isoforms of myosin II (A and B) that have overlapping but distinct distributions are found in growth cones. It appears that both myosin IIA and IIB may be necessary for normal nerve outgrowth and motility, but the molecular interactions responsible for their activity remain unclear. For instance, it is unknown if these myosin II isoforms produce bipolar “minifilaments” in growth cones similar to those observed in other nonmuscle cells. To determine if minifilaments are present in growth cones, we modified the electron microscopy preparative procedures used to detect minifilaments in other cell types. We found structures that appeared very similar to bipolar minifilaments found in noneuronal cells. They also labeled with antibodies to either myosin IIA or IIB. Thus, the activity of myosin II in growth cones is likely to be similar to that in other nonmuscle cells. Bipolar filaments interacting with oppositely oriented actin filaments will produce localized contractions or exert tension on actin networks. This activity will be responsible for the myosin II dependent motility in growth cones. Cell Motil. Cytoskeleton 52:91–96, 2002. © 2002 Wiley‐Liss, Inc.
Regulation of monomeric dynein activity by ATP and ADP concentrations
Authors: Shiroguchi Katsuyuki , Toyoshima Yoko Y.
Published: August 2002

Axonemal dyneins are force‐generating ATPases that produce ciliary and flagellar movement. A dynein has large heavy chain(s) in which there are multiple (4–6) ATP‐binding consensus sequences (P‐loops) as well as intermediate and light chains, constituting a very large complex. We purified a monomeric form of dynein (dynein‐a) that has at least three light chains from 14S dyneins of Tetrahymena thermophila and characterized it. In in vitro motility assays, dynein‐a rotated microtubules around their longitudinal axis as well as translocated them with their plus‐ends leading. ATPase activity at 1 mM ATP was doubled in the presence of a low level of ADP (≥ 20 μM). Both ATPase activity and translocational velocities in the presence of ADP (≥ 20 μM) fit the Michaelis‐Menten equation well. However, in the absence of ADP (< 0.1 μM), neither of the activities followed the Michaelis‐Menten‐type kinetics, probably due to the effect of two ATP‐binding sites. Our results also indicate that dynein‐a has an ATP‐binding site that is very sensitive to ADP and affects ATP hydrolysis at the catalytic site. This study shows that a monomeric form of a dynein molecule regulates its activity by direct binding of ATP and ADP to itself, and thus the dynein molecule has an intramolecular regulating system. Cell Motil. Cytoskeleton 49:189–199, 2001. © 2001 Wiley‐Liss, Inc.
Hyperpolarized3He gas production and MR imaging of the lung
Authors: Leawoods Jason C. , Yablonskiy Dmitriy A. , Saam Brian , Gierada David S. , Conradi Mark S.
Published: August 2002

Optical polarization of3He generates large nuclear spin magnetizations, allowing MR imaging of the gas spaces of human and animal lungs despite the low number density of spins in the gas. The atomic physics of optical pumping and spin exchange is explained; the hardware for polarizing, transporting, and imaging is detailed. Pulse sequences for optimum use of the nonrenewable magnetization require a different imaging strategy than traditional proton MRI. Examples are discussed for static lung images, diffusion images for characterization of the local alveolar structure, and high temporal resolution images. © 2001 John Wiley & Sons, Inc. Concepts Magn Reson 13: 277–293, 2001
Primary pleuropulmonary synovial sarcoma
Authors: Essary Lydia R. , Vargas Sara O. , Fletcher Christopher D. M.
Published: August 2002

BACKGROUND

Primary pleuropulmonary synovial sarcoma (SS) is a rare neoplasm and a recently recognized anatomic subset. Its clinicopathologic attributes are not yet well defined.

METHODS

In this study, the clinical and histopathologic features of 12 SS arising in the lung and/ or pleura were analyzed.

RESULTS

The neoplasms occurred in 7 men and 5 women, 20–72 years old (median, 31 years), were well circumscribed with a mean size of 7.2 cm, and involved either lung (9 cases), pleura (2 cases), or both (1 case). All the tumors were of monophasic type. Nine showed a classic spindle cell pattern, and three showed predominantly poorly differentiated features. All but one case showed at least focal positivity for epithelial membrane antigen (EMA), a finding characteristic of this tumor. The lack of EMA staining in one case, proven by electron microscopy to be SS, was attributed to the scarcity of material available for immunohistochemical stains. The diagnosis was proven cytogenetically in three cases. Within 2 years, local recurrence developed in 8 patients (75%), 3 of whom developed metastasis (25%). Five patients died of their disease within 2.5 years, 4 of them from uncontrolled local disease.

CONCLUSIONS

The authors conclude that pleuropulmonary SS, although rare, represents a distinct anatomic subset having pathologic features similar to those of its soft tissue counterpart. Its clinical behavior appears more aggressive, perhaps because of relatively later presentation combined with the difficulty in obtaining a wide surgical margin. Cancer 2002;94:459–69. © 2002 American Cancer Society.
Clinical usefulness of color doppler ultrasound in patients with endometrial hyperplasia and carcinoma
Authors: Emoto Makoto , Tamura Riko , Shirota Kyoko , Hachisuga Toru , Kawarabayashi Tatsuhiko
Published: August 2002

BACKGROUND

The objective of this study was to examine the usefulness of transvaginal color Doppler ultrasound (TV‐CDU) in differentiating between endometrial hyperplasia (EH) and endometrial carcinoma (EC) and in predicting tumor spread in patients with EC.

METHODS

Seventy‐one postmenopausal patients were enrolled with either EH or EC that had been diagnosed by endometrial biopsy. The presence or absence of intratumoral blood flow was assessed by TV‐CDU. The intratumoral blood flow characteristics were analyzed using the resistance index (RI), pulsatility index (PI), and peak systolic velocity (PSV). The endometrial thickness also was measured in all patients by gray‐scale sonography. The correlation of these sonographic findings with histologic type, tumor grade, surgical stage, myometrial invasion, or the presence or absence of pelvic lymph node metastasis was then evaluated in patients with EC.

RESULTS

Although there were no patients with EC with endometrial thickness measuring < 5 mm, no significant difference was found in the mean value of endometrial thickness between patients with EH (n = 18 patients; 16.2 mm ± 15.9 mm) and patients with EC (n = 53 patients; 18.7 mm ± 17.1 mm). Intratumoral blood flow was detected in significant numbers of patients who had EC (71.7%; 38 of 53 patients) compared with patients who had EH (5.6%; 1 of 18 patients; P < 0.0001). Thus, no patients with EH showed any blood flow in the endometrial lesions, except for one patient who had EH complicated by pyometra. In patients with EC, the positive rate of intratumoral blood flow was correlated significantly with myometrial invasion, tumor grade, and pelvic lymph node metastasis (P < 0.05; Cochran–Armitage trend test). No associations were found between RI, PI, or PSV and the clinicopathologic parameters examined, including surgical stage.

CONCLUSIONS

TV‐CDU may be more useful in differentiating between EH and EC than measuring endometrial thickness by transvaginal gray‐scale sonography. For patients with EC, the detection of intratumoral blood flow may be helpful in distinguishing between low‐grade and high‐grade tumors and predicting myometrial invasion. However, intratumoral blood flow analysis using RI, PI, or PSV may not be useful for predicting tumor spread before surgery. Cancer 2002;94:700–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10208
Ten‐year survival with chemotherapy and radiotherapy in patients with squamous cell carcinoma of the esophagus
Authors: Bidoli Paolo , Bajetta Emilio , Stani Simonetta C. , De Candis Daniela , Santoro Armando , Valente Maurizio , Zucali Roberto , Valagussa Pinuccia , Ravasi Gianni , Bonadonna Gianni
Published: August 2002

BACKGROUND

The effects of multimodality treatment on the survival of patients with esophageal carcinoma are unclear. The authors performed a prospective, Phase II study to assess the long‐term results of chemotherapy plus radiotherapy (RT) on patients with esophageal squamous cell carcinoma.

METHODS

Of 106 consecutive patients who were recruited between 1985 and 1992, 101 patients were evaluable. Cisplatin (100 mg/m2per day) on Day 1 and fluorouracil (1000 mg/m2per day) on Days 1–4 were given for two cycles, with concomitant RT (30 grays [Gy] in 15 fractions) over 19 days. Patients with potentially resectable tumors were then assessed for curative surgery; the other patients received two more courses of chemotherapy and further RT (20 Gy in 10 fractions).

RESULTS

Of 40 patients who were candidates for surgery, 32 patients underwent surgery, and 24 patients had complete resection; 8 patients (25%) had no residual tumor in the specimen, and 12 patients (37%) had microscopic foci only. Surgical mortality was high (22%). Of 61 nonsurgical patients, 37 patients (61%) achieved complete clinical remission, and 14 patients (23%) achieved partial remission. The median survival for the entire series was 15 months (range, 1–136 months). The overall survival rate was 22% at 5 years and 12% at 10 years. At 10 years, freedom from disease progression was similar in the two groups (24%), whereas the median survival (22 months vs. 12 months) and the overall survival rates (17% vs. 9%) were better in nonsurgical patients compared with surgical patients, respectively, probably in relation to high surgical mortality. The larynx was preserved in 28% of 32 patients with cervical disease sites, with a 10‐year disease free survival rate of 31%. Three deaths were attributed to nonsurgical treatments.

CONCLUSIONS

Careful multidisciplinary pretreatment evaluation can identify patients who are ineligible for surgery without compromising long‐term results. For patients with inoperable disease, chemoradiotherapy can produce relatively good long‐term results. The combined approach without surgery can permit laryngeal preservation in a useful fraction of patients. Cancer 2002;94:352–61. © 2002 American Cancer Society.
Chromosomal imbalances detected by comparative genomic hybridization are associated with outcome of patients with hepatocellular carcinoma
Authors: Kusano Noriyoshi , Okita Kiwamu , Shirahashi Hitoshi , Harada Tomohiko , Shiraishi Kei , Oga Atsunori , Kawauchi Shigeto , Furuya Tomoko , Sasaki Kohsuke
Published: August 2002

BACKGROUND

Biologic characteristics of tumors are greatly affected by genetic aberrations. However, to the authors' knowledge there is no study that shows that cytogenetic information is useful for estimating prognosis of patients with hepatocellular carcinoma (HCC).

METHODS

Comparative genomic hybridization (CGH) analysis was performed in 41 HCCs to examine whether the analysis of cytogenetic aberrations allows us to estimate biologic behavior of HCC.

RESULTS

Tumor recurrence was linked to the loss at 13q (P = 0.0027) and to the number of DNA copy number aberrations (DCNAs; P = 0.0003). The decrease in DNA copy number at 8p and 13q and amplification at 11q13 were significantly associated with unfavorable outcome of patients (P = 0.017, P = 0.012, and P = 0.00081, respectively). The number of DCNAs was significantly different between favorable and poor prognosis patients with HCC; 5.78 ± 2.7 versus 11.13 ± 4.8 (P = 0.004), and it was an independent prognostic marker in HCCs.

CONCLUSIONS

The current study indicates that cytogenetic information provided by CGH is useful for estimating prognosis of patients with HCC. Cancer 2002;94:746–51. © 2002 American Cancer Society.

DOI 10.1002/cncr.10254
Relevance of biologic markers in colorectal carcinoma
Authors: Barozzi Chiara , Ravaioli Matteo , D'Errico Antonia , Grazi Gian Luca , Poggioli Gilberto , Cavrini Giulia , Mazziotti Alighieri , Grigioni Walter Franco
Published: August 2002

BACKGROUND

Although pathologic stage is currently the main prognostic indicator for patients with colorectal carcinoma (CRC), mounting evidence suggests that, in its current form, it is insufficient to predict clinical outcome. To assess biologic markers of primary CRC that may improve clinical staging and provide useful information for the application of novel therapeutic strategies, the authors investigated a panel of markers that included transforming growth factor‐α (TGF‐α), epithelial growth factor receptor (EGF‐R; the protein product of the c‐erb B2/HER‐2 oncogene), matrix metalloproteinase 2 (MMP‐2), insulin‐like growth factor II (IGF‐II), vascular endothelial growth factor (VEGF), and angiogenesis, as evaluated by microvessel density (MVD).

METHODS

Two groups of CRC were studied: 1) surgical samples from patients who achieved a disease free survival of at least 6 years (CRC‐M0) and 2) surgical specimens of both primary tumors and synchronous or metachronous liver metastases (CRC‐M1).

RESULTS

Chi‐square analysis revealed that expression levels of TGF‐α, c‐erb B2/HER‐2, MMP‐2, IGF‐II, VEGF, and MVD (but not EGF‐R) were significantly higher in CRC‐M1 samples compared with CRC‐M0 samples (P < 0.001, P < 0.05, P < 0.001, P < 0.001, P < 0.01, and P < 0.001, respectively). Logistic regression analysis showed that TGF‐α, IGF‐II, and MMP‐2 had significantly greater expression in CRC‐M1 samples independent of the other variables (including tumor classification, histologic grade, and patient age). If all three markers had ≥ 25% expression, then the probability of developing liver metastasis was 99.5%.

CONCLUSIONS

Based on the evidence of this study, TGF‐α MMP‐2, and IGF‐II seem suitable candidates for a selective panel of markers designed to provide significant additional information with respect to the current pathologic staging system for patients with colorectal carcinoma. Cancer 2002;94:647–57. © 2002 American Cancer Society.

DOI 10.1002/cncr.10277
Pathologic analysis of tumor size and lymph node status in multifocal/multicentric breast carcinoma
Authors: Andea Aleodor A. , Wallis Tracie , Newman Lisa A. , Bouwman David , Dey Jyotirmoy , Visscher Daniel W.
Published: August 2002

BACKGROUND

For unifocal invasive breast carcinoma, increasing tumor diameter predictably correlates with a greater frequency of lymph node involvement, thereby facilitating treatment decisions. In invasive breast tumors presenting with multiple nodules, however, it is unclear whether tumor size correlates with lymph node dissemination in a similar manner.

METHODS

The authors analyzed a series of 101 invasive breast carcinomas presenting with multiple macroscopically apparent lesions (2 foci: n = 77; 3: n = 20; 4: n = 4). Two different assessments of the tumor size (diameter of largest focus and combined diameter of all the foci) were then correlated with the status of axillary lymph nodes. For comparison with unifocal tumors, the authors used both external and internal control series (the latter consisting of 469 patients from their institution). The associations between lymph node status, tumor size, and multifocality were modeled using univariate and multivariate logistic regression, for each modality of tumor size assessment.

RESULTS

The logistic curves for multifocal and unifocal tumors were significantly different when the largest diameter was used as a tumor size estimate. Multifocal cases had higher frequencies of lymph node involvement than unifocal lesions of similar size category. In a multivariate logistic regression, the odds ratio of positive lymph node status in multifocal versus unifocal cases was 2.8 using largest diameter as a tumor size estimate (P < 0.0001). When the combined diameter assessment was used, however, the regression curve of multifocal cases was similar to that of unifocal cases, and the frequency of lymph node positivity was not significantly different in multifocal versus unifocal cases of the same size (odds ratio, 1.4; P = 0.13).

CONCLUSIONS

The authors' results show that, if aggregate diameters are used, unifocal and multifocal breast carcinomas are similar with respect to frequency of regional lymph node metastasis. Currently used algorithms, which use the diameter of the largest nodule, result in understaging of multifocal breast carcinomas due to underestimation of actual tumor size. Cancer 2002;94:1383–90. © 2002 American Cancer Society.

DOI 10.1002/cncr.10331
Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome‐related burkitt lymphoma/leukemia
Authors: Cortes Jorge , Thomas Deborah , Rios Adan , Koller Charles , O'Brien Susan , Jeha Sima , Faderl Stefan , Kantarjian Hagop
Published: August 2002

BACKGROUND

Patients with acquired immunodeficiency syndrome (AIDS)‐associated lymphoma/leukemia have a poor prognosis and are frequently treated with low‐intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper‐CVAD), a dose‐intensive chemotherapy regimen, in patients with AIDS‐associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients.

METHODS

Thirteen patients with AIDS‐associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper‐CVAD alternating with high‐dose methotrexate and ara‐C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32–55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18–137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/μL (range, 9–544); only one patient had a count > 200/μL.

RESULTS

Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7–45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7–45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non‐HIV patients with Burkitt lymphoma/leukemia treated with the same regimen.

CONCLUSIONS

Hyper‐CVAD is an effective regimen for patients with AIDS‐associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper‐CVAD and HAART is associated with long‐term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically. Cancer 2002;94:1492–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10365
Expression of UDP‐N‐acetyl‐α‐D‐galactosamine–polypeptide galNAc N‐acetylgalactosaminyl transferase‐3 in relation to differentiation and prognosis in patients with colorectal carcinoma
Authors: Shibao Kazunori , Izumi Hiroto , Nakayama Yoshifumi , Ohta Ryo , Nagata Naoki , Nomoto Minoru , Matsuo Ken‐ichi , Yamada Yuji , Kitazato Kenji , Itoh Hideaki , Kohno Kimitoshi
Published: August 2002

BACKGROUND

Tumor development usually is accompanied by alterations of O‐glycosylation. Initial glycosylation of mucin‐type, O‐linked proteins is catalyzed by one of the UDP‐GalNAc–polypeptide N‐acetyl‐galactosaminyl transferases, such as GalNAc‐T3, which is expressed in adenocarcinoma cells. The authors investigated whether such expression influenced tumor differentiation or prognosis in patients with colorectal carcinoma.

METHODS

The expression of GalNAc‐T3 was evaluated immunohistochemically in 106 paraffin embedded samples from surgically resected colorectal carcinomas and was related to patient and tumor characteristics. Western blot analysis was performed on seven samples of frozen tissue.

RESULTS

Strong tumor expression of GalNAc‐T3 predicted 5‐year survival in patients with colorectal carcinoma (67.2% vs. 43.6% for weak expression;P= 0.017). GalNAc‐T3 expression was not associated with age, gender, tumor size, tumor location, or disease stage but was related to histologic differentiation (P= 0.049) and depth of invasion (P= 0.031). Univariate analysis showed that strong GalNAc‐T3 expression significantly enhanced the likelihood of survival. Multivariate Cox survival analysis identified enzyme expression as an independent prognostic factor that was second only to TNM stage.

CONCLUSIONS

GalNAc‐T3 expression is a novel and useful indicator of tumor differentiation, disease aggressiveness, and prognosis in patients with colorectal carcinoma. Cancer 2002;94:1939–46. © 2002 American Cancer Society.

DOI 10.1002/cncr.10423
Fertility‐preserving treatment in young patients with endometrial adenocarcinoma
Authors: Wang Chen‐Bin , Wang Chin‐Jung , Huang Huei‐Jean , Hsueh Swei , Chou Hung‐Hsueh , Soong Yung‐Kuei , Lai Chyong‐Huey
Published: August 2002

BACKGROUND

Hormone therapy alone for early‐stage, low‐grade endometrial carcinoma arising in young women has been reported occasionally in case reports or small series. However, a comprehensive guideline for selection, treatment, and follow‐up is not available as yet.

METHODS

In the current study, the authors' evaluated the outcome of a cohort of young women with clinically diagnosed endometrial adenocarcinoma Stage IA, Grade 1 who were selected for fertility‐preserving treatment by stringent staging procedures and treated in a standard protocol using combinations of megestrol acetate, tamoxifen, and gonadotropin‐releasing hormone analog (GnRHa).

RESULTS

Nine eligible patients were treated between 1991 and 1999. The median age of the patients was 32 years (range, 30–39 years). Of the 9 patients, 8 (88.9%) achieved complete remission after hormone therapy. Four patients had ever conceived (two patients had three term pregnancies and underwent consolidation hysterectomy after completion of family planning). Only one patient underwent hysterectomy for failure to respond, whose tumor was estrogen receptor (ER)/progesterone receptor (PgR) positive by immunostaining but negative by ligand‐binding method. Another patient, whose tumor was ER negative/PgR positive, had residual carcinoma on the first assessment and achieved complete remission after replacement of tamoxifen with a GnRHa. Four responders later developed recurrent endometrial carcinoma. One underwent immediate hysterectomy. Two were successfully re‐treated with hormone therapy, but the other did not respond and underwent hysterectomy. All nine patients have been alive without evidence of disease 25–113 (median, 69) months from initial diagnosis.

CONCLUSIONS

The treatment strategy described in the current study is feasible. A larger multicenter trial of fertility‐preserving treatment is warranted for nulliparous young patients with well selected Stage I, Grade 1, endometrial adenocarcinoma. Cancer 2002;94:2192–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10435
Prognostic value of nuclear grading in patients with intracapsular (pT1‐pT2) renal cell carcinoma
Authors: Minervini Andrea , Lilas Leon , Minervini Riccardo , Selli Cesare
Published: August 2002

BACKGROUND

The TNM classification system considers tumor size and, in particular tumor, greatest dimension as the only prognostic indicator for intracapsular renal cell carcinoma (RCC). The objective of the current study was to evaluate the role of nuclear grading and its importance as a prognostic indicator in patients with intracapsular (T1‐T2) RCC.

METHODS

A retrospective study was performed on 213 patients with RCC limited to the kidney who were free from distant metastases at the time of diagnosis and who underwent radical nephrectomy from January 1990 to November 1999. All patients were staged according to the 1997 TNM classification system. Nuclear grading was determined according to the criteria proposed by Fuhrman et al. The patients' status was evaluated last in November 2000. The mean follow‐up was 52 months (range, 12–130 months). The probability of survival was estimated by using the Kaplan‐Meier method, with the log‐rank test used to estimate differences among levels of the analyzed variables. A multivariate Cox proportional hazards model was performed to estimate the relative importance of the variables in predicting survival.

RESULTS

The 5‐year disease specific survival rates for patients with pT1 and pT2 tumors were 93.5% and 61.1%, respectively. The 5‐year disease specific survival rates for patients with Grade 1, Grade 2, and Grade 3–4 tumors were 95.9%, 86.8%, and 60.1%, respectively. A comparison of the survival curves both by stage and grade showed a statistically significant difference. For patients with pT1 lesions, the 5‐year disease specific survival rate was 94.2% for patients with Grade 1–2 disease and 89.8% for patients with Grade 3–4 disease. For patients with pT2 lesions, the 5‐year disease specific survival rate was 72.2% for patients with Grade 1–2 disease and 20% for patients with Grade 3–4 disease.

CONCLUSIONS

Within intracapsular tumors that measure > 7.0 cm in greatest dimension, nuclear grade is an important morphologic variable for predicting long‐term survival. Identification of patients with nuclear Grade 3–4 tumors is important prognostically to determine the metastatic potential of pT2 tumors, because this subgroup of patients may benefit from adjuvant immunotherapy. Cancer 2002;94:2590–5. © 2002 American Cancer Society.

DOI 10.1002/cncr.10510
Clinical trial participation among patients enrolled in the Glioma Outcomes Project
Authors: Chang Susan M. , Barker Fred G. , Schmidt Meic H. , Sloan Andrew E. , Kasper Rachel , Phillips Leslie , Shih Karen , Hariharan Subramanian , Berger Mitchel S. ,   The Glioma Outcomes Investigators
Published: August 2002

BACKGROUND

Patient participation in well‐designed and conducted clinical trials enables researchers to test new therapies. An understanding of the variables that possibly influence patient enrollment may help in patient recruitment for future trials. The authors evaluated factors that influenced patient enrollment in clinical trials using a prospective, large, multi‐institutional registry of patients with malignant glioma.

METHODS

Data were examined from 708 patients who underwent first or second surgery for a malignant glioma who were enrolled in the Glioma Outcomes Project, which is a prospective observational data base that captures clinical practice patterns. The frequency of clinical trial participation and the variables that may have been associated with trial participation were evaluated. These variables included age, gender, race, household income, educational level, first versus second craniotomy, histology, and whether the patient was treated at an academic institution.

RESULTS

One hundred fifty‐one of 708 patients (21.3%) participated in a clinical trial, which was higher than the participation reported typically for patients with other types of primary malignancies. In univariate analysis, race, histology, and first craniotomy were significant between the two groups, with Caucasian patients and patients with glioblastoma histology showing higher participation rates. In a multivariate logistic regression model, significant predictors included young age and glioblastoma multiforme histology.

CONCLUSIONS

The authors present information on factors that may influence clinical trial participation among patients with malignant glioma and compare their data with information described previously on patients with other types of malignant disease. The percent of participation among the patients in the current study was greater than among patients with other primary tumor sites. Strategies should be implemented to improve recruitment to neuro‐oncology trials, especially in elderly and minority populations. Cancer 2002;94:2681–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10536
Visceral region in the rat primary somatosensory cortex identified by vagal evoked potential
Authors: Ito Shin‐Ichi
Published: August 2002

Recent noninvasive human studies have reconfirmed the presence of a viscerally responsive region in the most lateral part of the primary somatosensory cortex (S1). The present electrophysiological study identified the corresponding area in rats as a vagal afferent projection region and examined the cytoarchitecture. Electrical stimulation of the cervical vagus nerve elicited a field potential comparable in waveform, latency, and amplitude to the simultaneously evoked potential in the insular visceral sensory cortex. The potential field adjoined the S1 trigeminal region without overlap, and was rostroventral to the lip representation barrel field, which was identified histochemically, and rostrodorsal to the tongue representation region, which was identified electrophysiologically. The vagal potential underwent a phase reversal in the middle layers; thus, the current sink site was cytoarchitectonically identified as the most rostral part of the parietal granular cortex or the S1, where no somatosensory input has previously been demonstrated. The rat S1 contains a region representing general visceral information, topographically located as if the visceral organs protruded from the mouth. J. Comp. Neurol. 444:10–24, 2002. © 2002 Wiley‐Liss, Inc.
Comparison of the basal ganglia in rats, marmosets, macaques, baboons, and humans: Volume and neuronal number for the output, internal relay, and striatal modulating nuclei
Authors: Hardman Craig Denis , Henderson Jasmine Monica , Finkelstein David Isaac , Horne Malcolm Kenneth , Paxinos George , Halliday Glenda Margaret
Published: August 2002

This study compares the basal ganglia of rats, marmosets, macaques, baboons, and humans. It uses established protocols to estimate the volume and number of neurons within the output nuclei (internal globus pallidus, IGP; and nondopaminergic substantia nigra, SNND), two internal relay and modulating nuclei (subthalamic nucleus, STh; and external globus pallidus, EGP), and a modulator of the striatum (dopaminergic substantia nigra, SND). Nuclear boundaries were defined by using immunohistochemistry for striatal afferents. Total numbers of Nissl‐stained and parvalbumin‐immunoreactive neurons were calculated by using the fractionator technique. Comparisons between species were standardized relative to brain mass (rats < marmosets < macaques < baboons < humans). The EGP consistently had more neurons relative to the IGP, STh, and SND, which had similar neuronal numbers within each species. The SNND had proportionally more neurons in rats than in primates (especially humans). The distribution of SND neurons varied substantially between rats and primates (very few ventrally located neurons in rats) with humans containing fewer SND neurons than other primates. The reduction in SND neurons in humans suggests less dopaminergic regulation of the basal ganglia system compared with other species. The consistency in the number of IGP neurons across all species, combined with the reduction in SNND neurons in humans, suggests a greater emphasis on output pathways through the IGP and that there are proportionally more STh and EGP neurons in humans. J. Comp. Neurol. 445:238–255, 2002. © 2002 Wiley‐Liss, Inc.
Topographic organization and neurochemical identity of dorsal raphe neurons that project to the trigeminal somatosensory pathway in the rat
Authors: Kirifides Michael L. , Simpson Kimberly L. , Lin Rick C.‐S. , Waterhouse Barry D.
Published: August 2002

The primary goals of this study were to: 1) examine the distribution of neurons within the dorsal raphe (DR) nucleus that project to cortical and subcortical sites along the trigeminal somatosensory pathway in rat; 2) determine the extent to which different regions within this ascending sensory system receive collateral projections from the same DR neuron; and 3) identify the putative transmitters contained within these DR projection neurons. Long‐Evans hooded rats received pressure injections of various combinations of retrograde fluorescent tracers; into the whisker‐related regions of the primary somatosensory cortex (barrel field cortex [BC]), ventral posterior medial thalamus (VPM), and principal nucleus of the trigeminal complex (PrV). The distribution of retrogradely labeled neurons within the DR was examined by fluorescence microscopy. The major finding was that cortically projecting neurons were located within the midline regions of the rostral portion of the DR, whereas cells projecting to subcortical trigeminal somatosensory structures were distributed bilaterally in the lateral wing regions of the DR as well as in the midline portions of the nucleus. Single neurons that send axon collaterals to multiple cortical and subcortical trigeminal somatosensory targets were observed in the dorsomedian and ventromedian regions of the DR. DR neurons that projected to cortical and subcortical sites contained serotonin but not tyrosine hydroxylase, the marker enzyme for catecholamine transmitters. Taken together, these findings provide further evidence of neurochemical specificity and functional anatomical organization within the DR efferent projection system. J. Comp. Neurol. 435:325–340, 2001. © 2001 Wiley‐Liss, Inc.
Distribution of ionotropic glutamate receptor subunit mRNAs in the rat hypothalamus
Authors: Eyigor Ozhan , Centers Adrian , Jennes Lothar
Published: August 2002

The excitatory amino acid neurotransmitter glutamate participates in the control of most (and possibly all) neuroendocrine systems in the hypothalamus. This control is exerted by binding to two classes of membrane receptors, the ionotropic and metabotropic receptor families, which differ in their structure and mechanisms of signal transduction. To gain a better understanding about the precise sites of action of glutamate and the subunit compositions of the receptors involved in the glutamatergic neurotransmission in the hypothalamus and septum, in situ hybridization was used with 35S‐labeled cRNA probes for the different ionotropic receptor subunits, including glutamate receptor subunits 1–4 (GluR1–GluR4), kainate‐2, GluR5–GluR7, N‐methyl‐D‐aspartate (NMDA) receptor 1 (NMDAR1), and NMDAR2A–NMDAR2D. The results showed that subunits of α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole‐propionate‐preferring, kainate‐preferring, and NMDA‐preferring receptor subunits are distributed widely but heterogeneously and that the GluR1, GluR2, kainate‐2, NMDAR1, NMDAR2A, and NMDAR2B subunits are the most abundant in the hypothalamus. Thus, GluR1 subunit mRNA was prominent in the lateral septum, preoptic area, mediobasal hypothalamus, and tuberomammillary nucleus, whereas kainate‐2 subunit mRNA was abundant in the medial septum‐diagonal band, median and anteroventral preoptic nuclei, and supraoptic nuclei as well as the magnocellular portion of the posterior paraventricular nucleus. Regions that contained the highest levels of NMDAR1 subunit mRNA included the septum, the median preoptic nucleus, the anteroventral periventricular nucleus, and the supraoptic and suprachiasmatic nuclei as well as the arcuate nucleus. Together, the extensive distribution of the different GluR subunit mRNAs strengthen the view that glutamate is a major excitatory neurotransmitter in the hypothalamus. The overlap in the distribution of the various subunit mRNAs suggests that many neurons can express GluR channels that belong to different families, which would allow a differential regulation of the target neurons by glutamate. J. Comp. Neurol. 434:101–124, 2001. © 2001 Wiley‐Liss, Inc.
Development of laminar organization in the mushroom bodies of the cockroach: Kenyon cell proliferation, outgrowth, and maturation
Authors: Farris Sarah M. , Strausfeld Nicholas J.
Published: August 2002

The mushroom bodies of the insect brain are lobed integration centers made up of tens of thousands of parallel‐projecting axons of intrinsic (Kenyon) cells. Most of the axons in the medial and vertical lobes of adult cockroach mushroom bodies derive from class I Kenyon cells and are organized into regular, alternating pairs (doublets) of pale and dark laminae. Organization of Kenyon cell axons into the adult pattern of laminae occurs gradually over the course of nymphal development. Newly hatched nymphs possess tiny mushroom bodies with lobes containing a posterior lamina of ingrowing axons, followed by a single doublet, which is flanked anteriorly by a γ layer composed of class II Kenyon cells. Golgi impregnations show that throughout nymphal development, regardless of the number of doublets present, the most posterior lamina serves as the “ingrowth lamina” for axons of newborn Kenyon cells. Axons of the ingrowth lamina are taurine‐ and synaptotagmin‐immunonegative. They produce fine growth cone tipped filaments and long perpendicularly oriented collaterals along their length. The maturation of these Kenyon cells and the formation of a new lamina are marked by the loss of filaments and collaterals, as well as the onset of taurine and synaptotagmin expression. Class I Kenyon cells thus show plasticity in both morphology and transmitter expression during development. In a hemimetabolous insect such as the cockroach, juvenile stages are morphologically and behaviorally similar to the adult. The mushroom bodies of these insects must be functional from hatching onward, while thousands of new neurons are added to the existing structure. The observed developmental plasticity may serve as a mechanism by which extensive postembryonic development of the mushroom bodies can occur without disrupting function. This contrasts with the more evolutionarily derived holometabolous insects, such as the honey bee and the fruit fly, in which nervous system development is accomplished in a behaviorally simple larval stage and a quiescent pupal stage. J. Comp. Neurol. 430:331–351, 2001. © 2001 Wiley‐Liss, Inc.
Connexin26 in adult rodent central nervous system: Demonstration at astrocytic gap junctions and colocalization with connexin30 and connexin43
Authors: Nagy James I. , Li Xinbo , Rempel Jeremy , Stelmack Gerald , Patel Daywin , Staines William A. , Yasumura Thomas , Rash John E.
Published: August 2002

The connexin family of proteins (Cx) that form intercellular gap junctions in vertebrates is well represented in the mammalian central nervous system. Among these, Cx30 and Cx43 are present in gap junctions of astrocytes. Cx32 is expressed by oligodendrocytes and is present in heterologous gap junctions between oligodendrocytes and astrocytes as well as at autologous gap junctions between successive myelin layers. Cx36 mRNA has been identified in neurons, and Cx36 protein has been localized at ultrastructurally defined interneuronal gap junctions. Cx26 is also expressed in the CNS, primarily in the leptomeningeal linings, but is also reported in astrocytes and in neurons of developing brain and spinal cord. To establish further the regional, cellular, and subcellular localization of Cx26 in neural tissue, we investigated this connexin in adult mouse brain and in rat brain and spinal cord using biochemical and immunocytochemical methods. Northern blotting, western blotting, and immunofluorescence studies indicated widespread and heterogeneous Cx26 expression in numerous subcortical areas of both species. By confocal microscopy, Cx26 was colocalized with both Cx30 and Cx43 in leptomeninges as well as along blood vessels in cortical and subcortical structures. It was also localized at the surface of oligodendrocyte cell bodies, where it was coassociated with Cx32. Freeze‐fracture replica immunogold labeling (FRIL) demonstrated Cx26 in most gap junctions between cells of the pia mater by postnatal day 4. By postnatal day 18 and thereafter, Cx26 was present at gap junctions between astrocytes and in the astrocyte side of most gap junctions between astrocytes and oligodendrocytes. In perinatal spinal cord and in five regions of adult brain and spinal cord examined by FRIL, no evidence was obtained for the presence of Cx26 in neuronal gap junctions. In addition to its established localization in leptomeningeal gap junctions, these results identify Cx26 as a third connexin (together with Cx30 and Cx43) within astrocytic gap junctions and suggest a further level of complexity to the heterotypic connexin channel combinations formed at these junctions. J. Comp. Neurol. 441:302–323, 2001. © 2001 Wiley‐Liss, Inc.
Discontinuous Galerkin methods for flow and transport problems in porous media
Authors: Rivière Béatrice , Wheeler Mary F.
Published: August 2002

This work presents a new scheme based on discontinuous approximation spaces for solving the miscible displacement problem in porous media. Numerical comparisons are made between this scheme and the well‐known mixed finite element and higher‐order Godunov methods. The simulations clearly show the advantages of the discontinuous Galerkin methods for stable or unstable flow. Copyright © 2001 John Wiley & Sons, Ltd.
Interface tracking finite volume method for complex solid–fluid interactions on fixed meshes
Authors: Udaykumar H. S. , Mittal R. , Rampunggoon P.
Published: August 2002

We present a numerical technique for computing flowfields around moving solid boundaries immersed in fixed meshes. The mixed Eulerian–Lagrangian framework treats the immersed boundaries as sharp solid–fluid interfaces and a conservative finite volume formulation allows boundary conditions at the moving surfaces to be exactly applied. A semi‐implicit second‐order accurate spatial and temporal discretization is employed with a fractional‐step scheme for solving the flow equations. A multigrid accelerator for the pressure Poisson equations has been developed to apply in the presence of multiple embedded solid regions on the mesh. We present applications of the method to two types of problems: (a) solidification in the presence of flows and particles, (b) fluid–structure interactions in flow control. In both these problems, the sharp interface method presents advantages by being able to track arbitrary interface motions, while capturing the full viscous, unsteady dynamics. Copyright © 2001 John Wiley & Sons, Ltd.
Moderate deviations for longest increasing subsequences: The upper tail
Authors: Löwe Matthias , Merkl Franz
Published: August 2002

We derive the upper‐tail moderate deviations for the length of a longest increasing subsequence in a random permutation. This concerns the regime between the upper‐tail large‐deviation regime and the central limit regime. Our proof uses a formula to describe the relevant probabilities in terms of the solution of the rank 2 Riemann‐Hilbert problem (RHP); this formula was invented by Baik, Deift, and Johansson [3] to find the central limit asymptotics of the same quantities. In contrast to the work of these authors, who apply a third‐order (nonstandard) steepest‐descent approximation at an inflection point of the transition matrix elements of the RHP, our approach is based on a (more classical) second‐order (Gaussian) saddle point approximation at the stationary points of the transition function matrix elements. © 2001 John Wiley & Sons, Inc.