bluuebunny/crossref_metadata_2025 huggingface dataset:
Hair‐forming activity of human lymphocyte specific protein 1 requires cooperation between its caldesmon‐like domains and the villin headpiece‐like domains
Authors: Zhang Qihong , Li Yao , Howard Thomas H.
Published: August 2002

LSP1 is an F‐actin binding with multiple F‐actin binding domains. Overexpression of LSP1 in NAD 47/89 patient's neutrophils created hair‐like projections on the patient's neutrophil cell surfaces and inhibited neutrophil cell motility and transfection of LSP1 in serial cell lines recreate the NAD 47/89 phenotype and produce branching hair‐like surface projections. Although LSP1 contains hair‐forming ability and LSP1 F‐actin binding domains have been defined, the LSP1 domains responsible for its hair‐forming activity, the relationship to the F‐actin binding domains, and the required domain interactions, if any, for hair formation are not well understood. To define the hair‐forming domains of LSP1, the relationship to the known F‐actin binding domains, and binding domain interactions, LSP1 truncates, which include or exclude the different F‐actin binding domains, were created by PCR. LSP1 mutants were created by site‐directed mutagenesis to define the amino acids important for hair formation. Sf9 cells were infected with recombinant baculovirus expressing the cDNA of LSP1 truncates and mutants, and the morphology of infected Sf9 cells was documented by DIC optics. Results show that (1) the hair‐forming activity of LSP1 is localized to the basic C‐terminal half of the molecule, which contains all of the F‐actin binding domains; (2) both the caldesmon‐like domains and the villin headpiece‐like domains are required for the hair‐forming activity of LSP1; (3) basic amino acids in the villin headpiece regions are crucial for the hair‐forming activity of LSP1 molecule. The results suggest cooperation between the caldesmon‐like domains and the villin headpiece‐like domains are required for the hair‐forming activity of human LSP1 in cells. Cell Motil. Cytoskeleton 49:179–188, 2001. © 2001 Wiley‐Liss, Inc.
The World Health Organization histologic classification system reflects the oncologic behavior of thymoma
Authors: Okumura Meinoshin , Ohta Mitsunori , Tateyama Hisashi , Nakagawa Katsuhiro , Matsumura Akihide , Maeda Hajime , Tada Hiroto , Eimoto Tadaaki , Matsuda Hikaru , Masaoka Akira
Published: August 2002

BACKGROUND

Although the histologic classification of thymic epithelial tumors has been confusing and controversial, an agreement on the universal classification system for thymic epithelial tumors was achieved by the World Health Organization (WHO) in 1999. The authors previously reported that the WHO histologic classification system reflects invasiveness and immunologic function of thymic epithelial tumors. In this subsequent study, they examined the prognostic significance of this classification system.

METHODS

Clinical features as well as postoperative survival of patients with thymoma, but not thymic carcinoma, were examined with reference to WHO histologic classification based on an experience with 273 patients over a 44‐year period.

RESULTS

There were 18 type A tumors, 77 type AB tumors, 55 type B1 tumors, 97 type B2 tumors, and 26 type B3 tumors. In patients with type A, AB, B1, B2, and B3 tumors, the respective proportions of invasive tumor were 11.1%, 41.6%, 47.3%, 69.1%, and 84.6%; the respective proportions of tumors with involvement of the great vessels were 0%, 3.9%, 7.3%, 17.5%, and 19.2%; and the respective 20‐year survival rates were 100%, 87%, 91%, 59%, and 36%. According to the Masaoka staging system, the 20‐year survival rates were 89%, 91%, 49%, 0%, and 0% in patients with Stage I, II, III, IVa, and IVb disease, respectively. By multivariate analysis, the Masaoka staging system and the WHO histologic classification system were significant independent prognostic factors, whereas age, gender, association with myasthenia gravis, completeness of resection, or involvement of the great vessels were not significant independent prognostic factors.

CONCLUSIONS

This study showed that histologic appearance reflects the oncologic behavior of thymoma when the WHO classification system is adopted. The WHO classification system may be helpful in clinical practice for the assessment and treatment of patients with thymoma. Cancer 2002;94:624–32. © 2002 American Cancer Society.

DOI 10.1002/cncr.10225
National Cancer Data Base report on malignant paragangliomas of the head and neck
Authors: Lee John H. , Barich Frank , Karnell Lucy Hynds , Robinson Robert A. , Zhen Weining K. , Gantz Bruce J. , Hoffman Henry T. ,   American College of Surgeons Commission on Cancer and the American Cancer Society
Published: August 2002

BACKGROUND

Malignant paragangliomas of the head and neck are rare, with previous reports limited to nine or fewer patients. The current review included 59 cases extracted from the National Cancer Data Base that were diagnosed between 1985–1996.

METHODS

The primary criterion for inclusion in the current study was verified metastatic spread from a paraganglioma of the head and neck. Patterns of presentation and treatment as well as clinically relevant associations were demonstrated in contingency tables. Relative survival was used for analysis of outcome.

RESULTS

The average patient age at presentation was 44 years, and gender distribution was equivalent. Metastases were confined to regional lymph nodes in the majority of cases (68.6%), with carotid body tumors found to have an even higher rate of regional confinement (93.8%). Surgery was the most common treatment (76.3%). The use of adjuvant irradiation for regionally confined disease increased across time, from 27% (1985–1990) to 46% (1991–1996). The 5‐year relative survival rate was 59.5% (76.8% for regionally confined carcinoma and 11.8% for distant metastasis). Among patients who were followed until death, those treated with adjuvant irradiation had a longer median survival (45 months) compared with those patients who were treated with surgery alone (12 months).

CONCLUSIONS

Malignant paraganglioma represents metastatic spread of a tumor type that, when restricted to the site of origin, is considered benign. Metastases from malignant paragangliomas of the head and neck usually are regionally confined. The primary management of a recognized malignancy should be directed toward complete surgical removal of the primary tumor and regional lymph nodes. Postoperative irradiation may be beneficial in slowing the progression of residual disease. Cancer 2002;94:730–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10252
CD3‐ζchain expression of intratumoral lymphocytes is closely related to survival in gastric carcinoma patients
Authors: Ishigami Sumiya , Natsugoe Shoji , Tokuda Koki , Nakajo Akihiro , Higashi Hiroshi , Iwashige Hirohumi , Aridome Kuniaki , Hokita Shuichi , Aikou Takashi
Published: August 2002

BACKGROUND

Impaired or reduced CD3 zeta chain (CD3‐ζ) expression in T cells has been identified in various cancers and may be associated with an ineffective immune response. The clinical significance of CD3‐ζ chain expression in tumor‐infiltrating lymphocytes (TILs) in gastric carcinoma remains unclear.

METHODS

The authors immunohistochemically investigated CD3‐ζ expression in TILs in 185 patients who had undergone curative gastrectomy. CD3‐ζ/CD3 epsilon (CD3‐ϵ) ratios were calculated. Patients were divided into two groups: a normal CD3‐ζ group (n = 121) and a reduced CD3‐ζ group (n = 64). Patients with a zeta per epsilon ratio of greater than 66% were placed in the normal CD3‐ζ group.

RESULTS

Patients in the normal CD3‐ζ group had fewer lymph node metastasis (P < 0.01) and a shallower depth of invasion (P < 0.05) than those in the reduced CD3‐ζ group. The 5‐year survival rate was 72% in the normal CD3‐ζ group, which was significantly better than that in the reduced CD3‐ζ group (55%; P < 0.01). When stratified according to clinical stage, the prognostic value was significantly different only in Stage IV patients. Multivariate analysis showed that CD3‐ζ expression was an independent prognostic factor (P = 0.03) next to depth of invasion and lymph node involvement.

CONCLUSIONS

Reduced CD3‐ζ expression in TILs was strongly correlated with progressive disease in gastric carcinomas. CD3‐ζ expression in TILs is considered an immunologic, independent prognostic marker in gastric carcinoma patients. CD3‐ζ normalization with cytokine treatment may lead to prolonged survival in advanced gastric carcinoma patients. Cancer 2002;94:1437–42. © 2002 American Cancer Society.

DOI 10.1002/cncr.10346
Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colon carcinoma
Authors: Fata Farid , Mirza Ayoub , Craig Wood G. , Nair Suresh , Law Amy , Gallagher James , Ellison Neil , Bernath Albert
Published: August 2002

BACKGROUND

Although the benefit from adjuvant chemotherapy has been established clearly in patients with Stage III colon carcinoma, the degree to which elderly patients with colon carcinoma can tolerate such therapy generally has remained unknown.

METHODS

The authors reviewed all patients in their Tumor Registry with Stage II and Stage III adenocarcinoma of the colon who underwent potentially curative resection for their disease at the Geisinger Medical Center between January 1990 and September 2000. One hundred twenty patients underwent complete resection of their colon carcinoma and received 5‐fluorouracil‐based (5‐FU) adjuvant chemotherapy.

RESULTS

The 5‐year disease free survival rate for patients age ≥ 65 years (Group A) was 70% compared with 56% for patients age < 65 years (Group B) (P = 0.085). The 5‐year overall survival rate for patients in Group B was 77% compared with 62% for the patients in Group A (P = 0.143). In a Cox regression model, age was not a predictor of disease free survival (P = 0.633) or overall survival (P = 0.900) when it was analyzed as a continuous variable. Only 19 patients were age > 75 years, and the disease free and overall survival rates for this group were similar but were underpowered compared with the rates for the patients ages between 65–75 years. When gender and disease stage were included in the model, age remained a nonsignificant variable (P = 0.400 for disease free survival; P = 0.615 for overall survival). Nine of 56 patients in Group A (16%) experienced Grade 3–4 toxicity compared with 14 of 64 patients in Group B (22%) (P = 0.420). The lack of a correlation between toxicity and age was maintained after controlling for disease stage and patient gender (P = 0.343). There were no correlations between preoperative carcinoembryonic antigen level, tumor grade, or lymph node involvement and patient age (P = 0.258, P = 0.256, and P = 0.519, respectively).

CONCLUSIONS

Elderly patients with Stage II and Stage III colon carcinoma benefit from 5‐FU‐based adjuvant therapy without a significant increase in toxicity compared with their younger counterparts. Adjuvant chemotherapy should be presented to elderly patients with high‐risk, resected colon carcinoma. The data regarding age cannot be generalized to patients age > 75 years. Cancer 2002;94:1931–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10430
Correlation between MIB‐1 and other proliferation markers
Authors: Spyratos Frédérique , Ferrero‐Poüs Magali , Trassard Martine , Hacène Kamel , Phillips Edelmira , Tubiana‐Hulin Michèle , Le Doussal Viviane
Published: August 2002

BACKGROUND

Cell proliferation is a major determinant of the biologic behavior of breast carcinoma. MIB‐1 monoclonal antibody is a promising tool for determining cell proliferation on routine histologic material. The objectives of this study were to compare MIB‐1 evaluation to other methods of measuring cell proliferation, with a view to refining the cutoff used to classify tumors with low and high proliferation rates in therapeutic trials.

METHODS

One hundred eighty‐five invasive breast carcinomas were evaluated for cell proliferation by determining monoclonal antibody MIB‐1 staining, histologic parameters (Scarff–Bloom–Richardson grade and mitotic index) on paraffin sections, S‐phase fraction (SPF) by flow cytometry, and thymidine‐kinase (TK) content of frozen samples.

RESULTS

There was a high correlation (P = 0.0001) between the percentage of MIB‐1 positive tumor cells and SPF, TK, histologic grade, and the mitotic index. Multivariate analyses including MIB‐1 at 5 different cutoffs (10%, 15%, 17% [median], 20%, 25%) and the other proliferative markers showed that the optimal MIB‐1 cutoff was 25% and that the mitotic index was the proliferative variable that best discriminated between low and high MIB‐1 samples. A MIB‐1 cutoff of 25% adequately identified highly proliferative tumors. Conversely, with a MIB‐1 cutoff of 10%, few tumors with low proliferation were misclassified.

CONCLUSIONS

The choice of MIB‐1 cutoff depends on the following clinical objective: if MIB‐1 is used to exclude patients with slowly proliferating tumors from chemotherapeutic protocols, a cutoff of 10% will help to avoid overtreatment. In contrast, if MIB‐1 is used to identify patients sensitive to chemotherapy protocols, it is preferable to set the cutoff at 25%. The MIB‐1 index should be combined with some other routinely used proliferative markers, such as the mitotic index. Cancer 2002;94:2151–9. © 2002 American Cancer Society.

DOI 10.1002/cncr.10458
The value of breast lumpectomy margin assessment as a predictor of residual tumor burden in ductal carcinoma in situ of the breast
Authors: Neuschatz Andrew C. , DiPetrillo Thomas , Steinhoff Margaret , Safaii Homa , Yunes Michael , Landa Marcia , Chung Maureen , Cady Blake , Wazer David E.
Published: August 2002

BACKGROUND

Margin width is considered the most important risk factor for local recurrence in ductal carcinoma in situ (DCIS) of the breast. The purpose of this report is to assess the predictive utility of lumpectomy specimen margin assessment for the presence and extent of residual DCIS.

METHODS

Specimens from 253 DCIS cases with lumpectomy and reexcision were studied to determine to the probability of residual DCIS on reexcision. The probability of residual tumor was evaluated with respect to tumor size, margin status, nuclear grade, presence of necrosis, patient age, and the extent of specimen processing (number of sections/volume tissue). Lesions were grouped by size: less than or equal to 2 mm, greater than 2–15 mm, greater than 15–40 mm, or greater than 40 mm. Margin width was recorded as the distance of DCIS to the closest specimen edge or, for positive margins, scored as: extensive (margin involvement in ≥8 sections or >4 low‐power fields [LPFs]), moderate (5–7 sections or 2–4 LPFs), minimal (2–4 sections or 1 LPF), or focal (1 section, single focus). The amount of residual tumor was graded by maximum dimension on a semiquantitative basis.

RESULTS

Initial excision margin significantly predicted for the presence of residual tumor on reexcision. Residual tumor was found on reexcision in 85% of extensively positive, 68% of moderately positive, 46% of minimally positive, 30% of focally positive, 41% of greater than 0–1 mm, 31% of greater than 1–2 mm, and 0% of greater than 2 mm margins (P < 0.0001). On univariate analysis, margin width and lesion size of initial excision specimens significantly predicted for the presence of residual DCIS on reexcision. Age, grade, necrosis, and extent of specimen processing were not significant prognostic factors. On multivariate analysis, both initial margin width (P < 0.0001) and lesion size (P = 0.02) significantly predicted for residual DCIS. As for amount of residual tumor, margin width and initial lesion dimension both significantly predicted for medium to large residuum, whereas age 45 years or younger was of borderline significance on univariate analysis. On multivariate analysis, margin width and lesion size on initial excision both remained significant predictors of larger volume residual tumor.

CONCLUSIONS

The margin status of a DCIS lumpectomy specimen is the most important predictive factor for both the presence and amount of residual disease. Cancer 2002;94:1917–24. © 2002 American Cancer Society.

DOI 10.1002/cncr.10460
Clinical and screening implications of the I1307K adenomatous polyposis coli gene variant in Israeli Ashkenazi Jews with familial colorectal neoplasia
Authors: Rozen Paul , Naiman Tova , Strul Hana , Taussky Philipp , Karminsky Nataly , Shomrat Ruth , Samuel Ziona , Yaron Yuval , Orr‐Urtreger Avi
Published: August 2002

BACKGROUND

The authors previously found the I1307K adenomatous polyposis coli (APC) gene variant in 5% of Ashkenazi control participants, in 15.4% of those who had familial colorectal neoplasia, but also in 1.6% of non‐Ashkenazi control participants. In this study, they evaluated its use in a screening program for familial colorectal neoplasia and examined for a founder effect.

METHODS

Consecutive Ashkenazim with a personal and/or family history of colorectal neoplasia had the DNA test. Markers flanking the APC gene were examined in Ashkenazi and non‐Ashkenazi I1307K carriers and noncarriers.

RESULTS

Among 718 persons, I1307K occurred in 6.2% of Ashkenazi participants, in 1.5% of non‐Ashkenazi control participants (P = 0.02), and in 10.7% of Ashkenazim with familial neoplasia (relative risk, 1.73 [not significant compared with controls]; 95% confidence interval, 0.7–3.2). Colorectal neoplasia was detected in carriers at a younger age (P < 0.05) without excess risk for multiple colorectal neoplasia or noncolorectal neoplasia. I1307K attributable risk for colorectal neoplasia was 0.5–0.6%. Compared with noncarriers, both Ashkenazi and non‐Ashkenazi I1307K carriers had similar flanking polymorphic alleles (P < 0.01).

CONCLUSIONS

I1307K is a low‐penetrance genetic variant that indicates a 1.7 relative risk for neoplasia in carriers who have familial carcinoma, clinically equivalent to obtaining a family history of sporadic colorectal neoplasia and promoting early screening. I1307K is a founder genetic variant in Jews of different ethnic origin, mainly Ashkenazim, but it explains only partially their higher incidence of colorectal carcinoma. Cancer 2002;94:2561–8. © 2002 American Cancer Society.

DOI 10.1002/cncr.10529
Ribosomal DNA methylation in patients with endometrial carcinoma
Authors: Powell Matthew A. , Mutch David G. , Rader Janet S. , Herzog Thomas J. , Huang Tim Hui‐Ming , Goodfellow Paul J.
Published: August 2002

BACKGROUND

Surgery is curative for the majority of patients with endometrial carcinoma: Consequently, the use of adjuvant therapy has been controversial. More effective methods to identify patients who are at risk for recurrence and who would benefit from adjuvant therapy are needed. The objective of this study was to investigate the prognostic significance of ribosomal DNA (rDNA) methylation in patients with endometrial carcinoma.

METHODS

rDNA methylation was assessed in 215 endometrial tumors by Southern blot analysis of HpaII‐digested DNA using a probe corresponding to the 5.8 and 28S ribosomal subunits. Tumor rDNA methylation status was correlated with patient outcome.

RESULTS

The majority of tumors demonstrated high levels of rDNA methylation (rDNA‐high; 74%). Both disease free survival and overall survival were significantly worse for patients with low‐level rDNA methylation (rDNA‐low; P < 0.0001). African‐American patients were more likely to have rDNA‐low tumors than Caucasian patients (P = 0.002). Among the subpopulation of patients with endometrial carcinoma for whom the use of adjuvant therapy is most controversial (148 women with Stage I–II endometrioid tumors), survival was significantly worse for the patients with rDNA‐low tumors (P < 0.0001); and, using multivariate analyses, tumor rDNA level was the only significant prognostic factor for both disease free survival and overall survival (hazard ratios, 11.0 and 26.3, respectively; P < 0.01 for both).

CONCLUSIONS

rDNA methylation is an independent prognostic indicator for patients with endometrial carcinoma that may serve to identify women with early‐stage disease at who are at high risk for recurrence. Racial differences in DNA methylation may explain the historically observed disparity in survival between African‐American patients and Caucasian patients. Cancer 2002;94:2941–52. © 2002 American Cancer Society.

DOI 10.1002/cncr.10559
Paget disease of the nipple
Authors: Kothari Ashutosh S. , Beechey‐Newman Nicolas , Hamed Hisham , Fentiman Ian S. , D'Arrigo Corrado , Hanby Andrew M. , Ryder Ken
Published: August 2002

BACKGROUND

The treatment of Paget disease by mastectomy has been challenged recently in favor of breast‐conserving techniques. A large series of patients treated with mastectomy has been reviewed to assess the feasibility of less radical surgery.

METHODS

The cases of 70 women with a clinical diagnosis of Paget disease were reviewed. The type, grade, receptor and node status, and the mammographic and pathologic extent of the underlying breast malignancy were determined. The survival of patients with invasive disease was compared with matched controls without Paget disease.

RESULTS

The underlying malignancy was invasive in 58% of cases. Despite the fact that only one third of women presented with a palpable mass, the malignancy was frequently extensive, being confined to the retroareolar region in only 25% of cases. The true extent of the disease was underestimated by mammography in 43% of cases. Of the patients with ductal in situ carcinoma, 96.5% had high‐grade carcinomas and 100% had invasive carcinomas of high cytonuclear grade. Overexpression of the c‐erb‐B2 oncogene was detectable in 83% of cases. Patients with Paget disease had a significantly worse survival than matched controls, but this difference was eliminated if they were also matched for c‐erb‐B2 status.

CONCLUSIONS

Paget disease is often associated with extensive underlying malignancy, which is difficult to assess accurately either clinically or mammographically. As a consequence, cone excision of the nipple would have resulted in incomplete excision in 75% of cases. The underlying disease is of high grade and is frequently c‐erb‐B2 positive with a resulting poor prognosis. Aggressive local and systemic treatment would seem to be merited. Cancer 2002;95:1–7. © 2002 American Cancer Society.

DOI 10.1002/cncr.10638
Differential expression of α3 and α6 integrins in the developing mouse inner ear
Authors: Davies Dawn , Holley Matthew C.
Published: August 2002

The development of the mammalian inner ear involves a complex series of cell‐cell and cell‐extracellular matrix interactions. These interactions are likely to be mediated by families of adhesion molecules, including the integrins. We have studied the expression of three integrin subunits known to be expressed on epithelia in a number of tissues (namely, α3, α6, and β4) during the development of the murine inner ear. At E10.5, both α3 and α6 were expressed in the epithelial layers of the otocyst. The expression of α6 was concentrated in an anterioventral region of the epithelium and in a proportion of the cells forming the cochlear‐vestibular and facial ganglia. By E12.5, α6 showed a more restricted expression, confined mainly to the pro‐sensory epithelia and the neural processes from the cochlear‐vestibular ganglion. In contrast, α3 was expressed in epithelia adjacent to the pro‐sensory areas. This reciprocal expression pattern was maintained until birth. Between birth and P6, a switch in expression occurred such that α3 was upregulated and α6 was downregulated in the sensory epithelia of both the auditory and vestibular systems. At this stage, α3 was expressed in all the epithelia lining the scala media, thus defining the endolymph compartment. The expression of β4 was restricted to epithelial/mesenchymal borders throughout the developmental stages studied, suggesting that α6 expression observed within the epithelium and neuronal tissue was α6β1. The early expression and changing pattern of α3 and α6 integrins during development of the mammalian inner ear suggests that they may be involved in the molecular processes that define epithelial boundaries and guide sensory innervation. J. Comp. Neurol. 445:122–132, 2002. © 2002 Wiley‐Liss, Inc.
Digital atlases of the antennal lobe in two species of tobacco budworm moths, the oriental Helicoverpa assulta (male) and the American Heliothis virescens (male and female)
Authors: Berg Bente G. , Galizia C. Giovanni , Brandt Robert , Mustaparta Hanna
Published: August 2002

The antennal lobe of the moth brain is the primary olfactory center processing information about pheromones and plant odors. We present here a digital atlas of the glomerular antennal lobe structures in the male of Helicoverpa assulta and the male and female of Heliothis virescens, based on synaptic antibody staining combined with confocal microscopy. The numbers of the glomeruli in the three specimens were similar, 65, 66, and 62, respectively. Whereas the male antennal lobe has a macroglomerular complex consisting of three and four units in the two species, the female lobe has two enlarged glomeruli at a corresponding position, near the entrance of the antennal nerve. Another large glomerulus, showing homology in the three specimens, is ventrally located. The small size of the heliothine moths is advantageous for confocal microscopy because the entire brain can be visualized as a single image stack. The maps are freely accessible on the internet, and the digital form of the data allows each atlas to be rotated and sectioned at any angle, providing for the identification of glomeruli in different preparations. J. Comp. Neurol. 446:123–134, 2002. © 2002 Wiley‐Liss, Inc.
Vocal–acoustic circuitry and descending vocal pathways in teleost fish: Convergence with terrestrial vertebrates reveals conserved traits
Authors: Goodson James L. , Bass Andrew H.
Published: August 2002

Vocal behavior is multifaceted and requires that vocal‐motor patterning be integrated at multiple brain levels with auditory, neuroendocrine, and other social behavior processes (e.g., courtship and aggression). We now provide anatomical evidence for an extensive vocal network in teleost fishes (Batrachoididae:Porichthys notatus;Opsanus beta) that is strongly integrated with neuroendocrine and auditory pathways and that exhibits striking similarities to the vocal‐acoustic circuitry known for mammals. Biotin compound injections into neurophysiologically identified vocal regions of the forebrain (preoptic area and anterior hypothalamus) and of the midbrain (periaqueductal gray and paralemniscal tegmentum) reveal extensive connectivity within and between these regions, as well as reciprocal relationships with the auditory thalamus and/or auditory midbrain (torus semicircularis). Thus, specific components of the basal forebrain and midbrain are here designated as theforebrain vocal‐acoustic complex(fVAC) andmidbrain vocal‐acoustic complex(mVAC), respectively. Biotin injections into the mVAC and a previously identified hindbrain vocal pattern generator likewise provide anatomical evidence for a distributed network of descending projections to the vocal pacemaker‐motoneuron circuitry. Together, the present experiments establish a vocal‐auditory‐neuroendocrine network in teleost fish that links the forebrain and midbrain to the hindbrain vocal pattern generator (i.e., fVAC → mVAC → pattern generator) and provides an anatomical framework for the previously identified neuropeptide modulation of vocal activity elicited from the forebrain and midbrain, which contributes to the expression of sex‐ and male morph‐specific behavior. We conclude with a broad comparison of these findings with those for other vertebrate taxa and suggest that the present findings provide novel insights into the structure of conserved behavioral regulatory circuits that have led to evolutionary convergence in vocal‐acoustic systems. J. Comp. Neurol. 448:298–322, 2002. © 2002 Wiley‐Liss, Inc.
Differential expression of catecholamine biosynthetic enzymes in the rat ventrolateral medulla
Authors: Phillips Jacqueline K. , Goodchild Ann K. , Dubey Ratna , Sesiashvili Erekle , Takeda Mamoru , Chalmers John , Pilowsky Paul M. , Lipski Janusz
Published: August 2002

Adrenergic (C1) neurons located in the rostral ventrolateral medulla are considered a key component in the control of arterial blood pressure. Classically, C1 cells have been identified by their immunoreactivity for the catecholamine biosynthetic enzymes tyrosine hydroxylase (TH) and/or phenylethanolamine N‐methyltransferase (PNMT). However, no studies have simultaneously demonstrated the expression of aromatic L‐amino acid decarboxylase (AADC) and dopamine β‐hydroxylase (DBH) in these neurons. We examined the expression and colocalization of all four enzymes in the rat ventrolateral medulla using immunohistochemistry and reverse transcription‐polymerase chain reaction (RT‐PCR) analysis. Retrograde tracer injected into thoracic spinal segments T2–T4 was used to identify bulbospinal neurons. Using fluorescence and confocal microscopy, most cells of the C1 group were shown to be double or triple labeled with TH, DBH, and PNMT, whereas only 65–78% were immunoreactive for AADC. Cells that lacked detectable immunoreactivity for AADC were located in the rostral C1 region, and approximately 50% were spinally projecting. Some cells in this area lacked DBH immunoreactivity (6.5–8.3%) but were positive for TH and/or PNMT. Small numbers of cells were immunoreactive for only one of the four enzymes. Numerous fibres that were immunoreactive for DBH but not for TH or PNMT were noted in the rostral C1 region. Single‐cell RT‐PCR analysis conducted on spinally projecting C1 neurons indicated that only 76.5% of cells that contained mRNA for TH, DBH, and PNMT contained detectable message for AADC. These experiments suggest that a proportion of C1 cells may not express all of the enzymes necessary for adrenaline synthesis. J. Comp. Neurol. 432:20–34, 2001. © 2001 Wiley‐Liss, Inc.
Immunotoxic destruction of distinct catecholamine subgroups produces selective impairment of glucoregulatory responses and neuronal activation
Authors: Ritter Sue , Bugarith Kishor , Dinh Thu T.
Published: August 2002

The toxin‐antibody complex anti‐dβh‐saporin (DSAP) selectively destroys dβh‐containing catecholamine neurons. To test the role of specific catecholamine neurons in glucoregulatory feeding and adrenal medullary secretion, we injected DSAP, unconjugated saporin (SAP), or saline bilaterally into the paraventricular nucleus of the hypothalamus (PVH) or spinal cord (T2–T4) and subsequently tested rats for 2‐deoxy‐D‐glucose (2DG)‐induced feeding and blood glucose responses. Injections of DSAP into the PVH abolished 2DG‐induced feeding, but not hyperglycemia. 2DG‐induced Fos expression was profoundly reduced or abolished in the PVH, but not in the adrenal medulla. The PVH DSAP injections caused a nearly complete loss of tyrosine hydroxylase immunoreactive (TH‐ir) neurons in the area of A1/C1 overlap and severe reduction of A2, C2, C3 (primarily the periventricular portion), and A6 cell groups. Spinal cord DSAP blocked 2DG‐induced hyperglycemia but not feeding. 2DG‐induced Fos‐ir was abolished in the adrenal medulla but not in the PVH. Spinal cord DSAP caused a nearly complete loss of TH‐ir in cell groups A5, A7, subcoeruleus, and retrofacial C1 and a partial destruction of C3 (primarily the ventral portion) and A6. Saline and SAP control injections did not cause deficits in 2DG‐induced feeding, hyperglycemia, or Fos expression and did not damage catecholamine neurons. DSAP eliminated dβh immunoreactivity but did not cause significant nonspecific damage at injection sites. The results demonstrate that hindbrain catecholamine neurons are essential components of the circuitry for glucoprivic control of feeding and adrenal medullary secretion and indicate that these responses are mediated by different subpopulations of catecholamine neurons. J. Comp. Neurol. 432:197–216, 2001. © 2001 Wiley‐Liss, Inc.
Conservation of neuronal number and size in the entorhinal cortex of behaviorally characterized aged rats
Authors: Merrill David A. , Chiba Andrea A. , Tuszynski Mark H.
Published: August 2002

Despite abundant evidence of behavioral and electrophysiological dysfunction of the rodent hippocampal formation with aging, the structural basis of age‐related cognitive decline remains unclear. Recently, unbiased stereological studies of the mammalian hippocampus have found little evidence to support the dogma that cellular loss accompanies hippocampal aging, thereby supporting an alternative hypothesis that aging is marked by widespread conservation of neuronal number. However, to date, the effects of aging have not been reported in another key component of memory systems in the rodent brain, the entorhinal cortex. In the present study, we stereologically estimated total neuronal number and size (cross‐sectional area and cell volume) in the subdivisions and cellular layers of the rat entorhinal cortex, using the optical fractionator and nucleator, respectively. Comparisons were made among Fischer 344 rats that were young, aged‐impaired, and aged‐unimpaired (based on functional analysis in the Morris water maze). No significant differences in cell number or size were observed in any of the entorhinal subdivisions or laminae examined in each group. Thus, aging is associated with widespread conservation of neuronal number, despite varying degrees of cognitive decline, in all memory‐related systems examined to date. These data suggest that mechanisms of age‐related cognitive decline are to be found in parameters other than neuronal number or size in the cortex of the mammalian brain. J. Comp. Neurol. 438:445–456, 2001. © 2001 Wiley‐Liss, Inc.
Volume and time doubling of graphs and random walks: The strongly recurrent case
Authors: Telcs András
Published: August 2002

This paper proves upper and lower off‐diagonal, sub‐Gaussian transition probability estimates for strongly recurrent random walks under sufficient and necessary conditions. Besides the known conditions, volume doubling and the elliptic Harnack inequality, a new property is introduced: time doubling. © 2001 John Wiley & Sons, Inc.
Comparing Windows NT, Linux, and QNX as the basis for cluster systems
Authors: Kavas Avi , Feitelson Dror G.
Published: August 2002

Clusters use commodity hardware and software components to provide an environment for high‐performance parallel processing. A major issue in the development of a cluster system is the choice of the operating system that will run on each node. We compare three alternatives: Windows NT, Linux, and QNX—a real‐time microkernel. The comparison is based on expressive power, performance, and ease‐of‐use metrics. The result is that none of these systems has a clear advantage over the others in all the metrics, but that each has its strong and weak points. Thus any choice of a base system will involve some technical compromises, but not major ones. Copyright © 2001 John Wiley & Sons, Ltd.
Applying developmental theory to the assessment and treatment of childhood disorders: does it make a difference?
Authors: Ollendick Thomas H. , Grills Amie E. , King Neville J.
Published: August 2002

In this paper, we examine the role of developmental theory in the assessment and treatment of child behaviour disorders, with special reference to the anxiety disorders. Following a brief review of the tenets of developmental psychology and developmental psychopathology, we illustrate the role of developmental theory in clinical research and practice. We suggest that developmental theory guides us in the selection and use of developmentally sensitive assessment strategies. Moreover, we indicate that use of developmental theory assists us in the treatment of children and adolescents by helping us determine when a behaviour problem is significant and when to initiate treatment, how to determine the goals of treatment and to select targets for treatment outcome, which treatment strategies to select for intervention, and how to determine the context of intervention. We conclude that the importance of developmental theory is axiomatic when working with children and adolescents. Still, considerable more work is needed before we can conclude that we have fully integrated developmental theory into our ongoing clinical research and practice with children. Copyright © 2001 John Wiley & Sons, Ltd.
A step‐by‐step approach to compute a consistent initialization for the MNA
Authors: Estévez Schwarz D.
Published: August 2002

One of the difficulties of the numerical integration methods for differential–algebraic equations (DAEs) is the computation of consistent initial values before starting the integration, i.e. calculating values that satisfy the given algebraic constraints as well as the hidden constraints if higher index problems are considered.

This paper presents an approach to calculate consistent initial values for index‐2 DAEs starting up from possibly inconsistent ones for systems arising from modified nodal analysis (MNA) in circuit simulation. This article is based on the results from Estévez Schwarz and Tischendorf, International Journal of Circuit Theory and Applications 2000; 28: 131–162. Several of the denotations and results that we use were introduced there in more detail. Copyright © 2001 John Wiley & Sons, Ltd.
Near‐infrared dyes for six‐color immunophenotyping by laser scanning cytometry
Authors: Gerstner Andreas O.H. , Lenz Dominik , Laffers Wiebke , Hoffman Robert A. , Steinbrecher Michael , Bootz Friedrich , Tárnok Attila
Published: August 2002

Background

To adequately analyze the complexity of the immune system and reduce the required sample volume for immunophenotyping in general, more measurable colors for the discrimination of leukocyte subsets are necessary. Immunophenotyping by the laser scanning cytometer (LSC), a slide‐based cytometric technology, combines cell detection based on multiple colors with their subsequent visualization without the need for physical cell sorting. In the present study, the filter setting of the LSC was adapted for the measurement of the far‐red emitting dye cyanine 7 (Cy7), thereby increasing the number of measurable commercially available fluorochromes.

Methods

The optical filters of the LSC were replaced—photomultiplier (PMT) 3/allophycocyanin (APC): 740‐nm dichroic long pass, and 670‐/55‐nm bandpass; PMT 4/Cy7: 810‐/90‐nm bandpass. Peripheral blood leukocytes were stained directly by fluorochrome‐labeled antibodies or by indirect staining. The tandem dyes of Cy7 (phycoerythrin [PE]‐Cy7, APC‐Cy7) and the fluorochromes fluorescein isothiocyanate (FITC), PE, PE‐Cy5, and APC were tested alone and in different combinations.

Results

With the new filter combination and tandem fluorochromes, Cy7 was measurable at 488‐nm (argon laser) or 633‐nm (helium‐neon laser) excitation. Resolution was in the range of FITC for PE‐Cy7 but approximately 30% lower for APC‐Cy7; spillover into the respective donor fluorochrome channel for both tandem dyes was prominent. A six‐color panel for leukocyte subtyping was designed.

Conclusions

With this adaptation, it is possible to measure the tandem conjugates PE‐Cy7 and APC‐Cy7. This new setup opens the way for six‐color immunophenotyping by LSC. Cytometry 48:115–123, 2002. © 2002 Wiley‐Liss, Inc.
Fine‐needle aspiration cytology of pulmonary rheumatoid nodule: Case report and review of the major cytologic features
Authors: Filho Jorge Sergio Reis , Soares Maria Fernanda , Wal Raquel , Christmann Romy Beatriz , Liu Christian Bark , Schmitt Fernando C.
Published: August 2002

Patients with rheumatoid disease may develop extra‐articular lesions, affecting viscera and soft tissues. Pulmonary rheumatoid nodules show morphologic features reminiscent of a necrotizing inflammation of rheumatoid synovitis and differ from subcutaneous rheumatoid nodules only by their location, extension, and size. Although cytologic studies on pleural effusions in rheumatoid disease have long been performed, there are no more than three reports concerning the fine‐needle aspiration (FNA) diagnosis of pulmonary rheumatoid nodules. The authors report on a case of a 62‐yr‐old woman with rheumatoid disease in whom a FNA diagnosis of pulmonary rheumatoid nodule was successfully performed. The authors highlight the main cytologic features of the entity and emphasise the high index of clinical and pathologic suspicions needed to be able to diagnose this lesion. Diagn. Cytopathol. 2002;26:150–153; DOI 10.1002/dc.10007 © 2002 Wiley‐Liss, Inc.
Cytology of primary central nervous system neoplasms in cerebrospinal fluid specimens
Authors: Chhieng David C. , Elgert Paul , Cohen Jean‐Marc , Jhala Nirag C. , Cangiarella Joan F.
Published: August 2002

Although two‐thirds of tumors occurring in the central nervous system (CNS) are primary neoplasms, only 10% of positive cerebrospinal fluid (CSF) specimens are from primary CNS tumors. In this study, we reviewed the cytologic findings of 21 positive CSF specimens from primary CNS tumors. A computer search identified 21 cases of positive CSF specimens from patients with primary CNS tumors from the archives. Follow‐up included review of medical charts and histologic correlation. The specimens were from 20 patients (9 females and 11 males). Their ages ranged from 6–83 yr, old with a mean of 30 yr. The cases included 9 medulloblastomas, 7 gliomas (3 glioblastoma multiformes, 2 anaplastic astrocytomas, and 2 ependymomas), 2 germinomas, 2 non‐Hodgkin's large B‐cell lymphomas, and 1 ganglioneurocytoma. Two cases were classified as suspicious and the remaining as positive for malignancy. Immunocytochemistry was employed in 3 cases to support the cytologic diagnosis. These cases included one large‐cell lymphoma (leukocyte‐common antigen‐positive), one germinoma (placental alkaline phosphatase‐positive), and the ganglioneurocytoma (neuron‐specific enolase‐ and synaptophysin‐positive). There were no false‐positive cases. Our results suggest that positive CSF cytology in patients with a primary CNS tumor is a reliable indicator of malignancy and reflects leptomeningeal involvement. The use of immunocytochemistry is helpful in confirming the cytologic impression in some cases. Diagn. Cytopathol. 2002;26:209–212. © 2002 Wiley‐Liss, Inc.
Atypical glandular cells of undetermined significance (AGUS): Clinical considerations and cytohistologic correlation
Authors: Nasuti Joseph F. , Fleisher Seth R. , Gupta Prabodh K.
Published: August 2002

The diagnoses of atypical glandular cells of undetermined significance (AGUS) made upon evaluation of cervical/vaginal (Pap) smears is examined to ascertain salient clinical and cytologic features that may lead to better characterization of the true nature of these lesions. Prior history of squamous dysplasia, age of the patient, and the occurrence of abnormal microbiopsy tissue fragments are investigated to determine their value in the proper evaluation of AGUS specimens. Of the 86,234 Pap smears submitted to our laboratory during a period of 2 yr, 187 (0.2%) were diagnosed as AGUS. Available follow‐up in 128 (69%) cases revealed 54 (42%) significant tissue proven abnormalities, the majority (55%, 30 patients) of which were diagnosed as squamous intraepithelial lesions (SIL). Squamous dysplasia is significantly more common in women younger than 40 (15/18, 83%) and in patients with prior history of SIL (29/30, 97%). In addition, all nine patients diagnosed with endometrial lesions on subsequent histology were older than 40. Age, however, was not a discriminating factor in women proven to have endocervical glandular lesions. Additionally, certain tissue fragment cytomorphologic features were significantly more often observed on follow‐up in specific histologic diagnostic categories. The Pap smears of patients diagnosed with SIL were noted to contain tissue fragments composed of both dysplastic squamous and benign glandular cells in 29 of 30 (97%). The presence of two distinct populations of glandular tissue fragments (typical and atypical) was found in the Pap smears of all nine women with endometrial abnormalities and in the smears of most women subsequently diagnosed with endocervical glandular lesions (87%, 13/15). These observations suggest that a more specific and clinically useful Pap smear interpretation other than AGUS is often possible by consideration of the patient's age and prior history along with the correct identification of the type of atypical cells observed in abnormal tissue fragments. Diagn. Cytopathol. 2002;26:186–190; DOI 10.1002/dc.10070 © 2002 Wiley‐Liss, Inc.
Cytology of small‐cell carcinoma of the uterine cervix in serous effusion: A report on two cases
Authors: Khunamornpong Surapan , Siriaunkgul Sumalee , Suprasert Prapaporn
Published: August 2002

Cytologic features of 2 cases of small‐cell carcinoma of the uterine cervix in the body fluid are described. Case 1 was a 34‐yr‐old woman with a stage IIA cervical tumor. Pleural effusion developed 6 mo after initial diagnosis. Case 2 was a 38‐yr‐old woman with a stage IB tumor. Ascites was detected 11 mo after hysterectomy. Histologically, both cervical tumors were indistinguishable from small‐cell carcinoma of oat‐cell type in the lungs or other sites. Cytologically, the tumor cells in the pleural effusion of case 1 had characteristic features of small‐cell carcinoma, including nuclear molding. However, almost all tumor cells in the ascites of case 2 showed a single‐cell pattern mimicking malignant lymphoma. Mitotic figures and karyorrhetic bodies were occasionally seen. Nuclear molding was rarely identified. Small‐cell carcinoma should be included in the differential diagnosis of malignant effusions containing lymphoma‐like cells. Diagn. Cytopathol. 24:253–255, 2001. © 2001 Wiley‐Liss, Inc.
Interinstitutional review of thyroid fine‐needle aspirations: Impact on clinical management of thyroid nodules
Authors: Baloch Zubair W. , Hendreen Samantha , Gupta Prabodh K. , LiVolsi Virginia A. , Mandel Susan J. , Weber Randal , Fraker Douglas
Published: August 2002

Routine interinstitution pathology consultation can result in change in pathologic diagnosis in up to 10% of patients. In this study, we compared the outside cytopathologic diagnosis of thyroid fine‐needle aspiration (FNA) specimens with the in‐house diagnosis at the University of Pennsylvania Medical Center over an 18‐mo period and its effect on patient management. One hundred ten (60%) diagnostic disagreements were identified among 183 patients. In 16 cases, the diagnosis was changed from benign to malignant, and in 12, the diagnosis was reversed from neoplastic/malignant to benign. Histologic follow‐up was available in 109 cases; the overall accuracy of outside diagnosis was 73%, and that of inside diagnosis was 85%. In conclusion, we strongly recommend interinstitution cytology consultation on referred thyroid FNA cases, since our data showed a significant change in diagnosis, thus affecting patient management. Diagn. Cytopathol. 25:231–234, 2001. © 2001 Wiley‐Liss, Inc.