bluuebunny/crossref_metadata_2025 huggingface dataset:
Polymerase chain reaction‐based diagnosis of bone marrow involvement in 170 cases of non‐Hodgkin lymphoma
Authors: Kang Yoon Hee , Park Chan Jeoung , Seo Eul Joo , Huh Jooryung , Kim Sung Bae , Kang Yoon‐Koo , Chi Hyun Sook
Published: October 2002

BACKGROUND

Up to the current time, diagnosis of bone marrow (BM) involvement in non‐Hodgkin lymphoma (NHL) has been based on morphologic findings. Polymerase chain reaction (PCR) for antigen receptor gene rearrangements has the potential to increase the detection sensitivity of minimal degrees of BM involvement. The authors therefore assessed PCR‐based clonalities of BM concurrently with morphology from 170 cases with NHL and evaluated the usefulness of comparative analysis of clonalities between bilateral BMs and the lymph node and the clinical significance of PCR based clonalities of BM.

METHODS

Bilateral BM clot sections of 170 cases and 47 lymph nodes were tested for immunoglobulin heavy chain gene rearrangement or T‐cell receptor gamma gene rearrangement according to the B‐ or T‐lineage of the lymph node.

RESULTS

When compared with morphology, the results of PCR showed an unexpectedly low positive concordance rate of 61.0% for B‐cell NHL and 57.1% for T‐cell NHL. When the clonality of BM was compared with that of lymph nodes in B‐cell NHL, bilateral clonalities of BM showed high concordance with the clonality of the lymph nodes. PCR‐based clonality did not show significant impact on survival.

CONCLUSIONS

Morphology remains the gold standard in the evaluation of BM involvement by NHL. Although the comparative analysis of BM clonality and that of the lymph nodes is considered a valuable tool that increases the reliability of clonality, PCR‐based clonality of BM does not significantly add to the sensitivity of diagnosing BM involvement by NHL. Cancer 2002;94:3073–82. © 2002 American Cancer Society.

DOI 10.1002/cncr.10584
Prognostic impact of extensive parenchymal invasion pattern in pT3 renal pelvic transitional cell carcinoma
Authors: Yoshimura Koji , Arai Yoichi , Fujimoto Hiroyuki , Nishiyama Hiroyuki , Ogura Keiji , Okino Takeshi , Ogawa Osamu
Published: October 2002

BACKGROUND

Pathologic T3 renal pelvic transitional cell carcinoma exhibits various patterns of invasion. The authors investigated the prognostic impact of three patterns of invasion of pT3 renal pelvic transitional cell carcinoma.

METHODS

Of 212 patients who underwent surgery for renal pelvic transitional cell carcinoma, 70 with pT3 disease were eligible for the main analyses. The candidate predictors of prognosis included patient age, gender, lesion laterality, tumor grade, perioperative cisplatin‐based systemic chemotherapy, lymph node involvement, vascular involvement, and patterns of invasion. Invasion patterns were classified as fat invasion, ductal involvement, or parenchymal invasion.

RESULTS

Mean postoperative followup was 33.5 months (range, 1–136 months). On univariate analysis, gender, lymph node involvement, vascular involvement, and extensive parenchymal invasion each had a significant impact on the cause specific survival rate. A multivariate analysis using Cox stepwise regression revealed that extensive parenchymal involvement was the strongest prognostic predictor (P = 0.0004, hazard ratio = 5.59). Lymph node involvement (P = 0.0175, hazard ratio = 3.14) and gender (P = 0.0361, hazard ratio = 2.42) were other weaker predictors. Statistically, pT3 disease without extensive parenchymal invasion had a prognosis similar to that of lower stage disease, and pT3 disease with extensive parenchymal invasion had a prognosis similar to that of pT4 disease.

CONCLUSIONS

Extensive parenchymal invasion has a strong prognostic impact in renal pelvic transitional cell carcinoma. pT3 disease should be subclassified into two separate entities, that with and that without extensive parenchymal invasion, in view of prognosis. Cancer 2002;94:3150–6. © 2002 American Cancer Society.

DOI 10.1002/cncr.10609
Antifungal prophylaxis for severely neutropenic chemotherapy recipients
Authors: Bow Eric J. , Laverdière Michel , Lussier Nathalie , Rotstein Coleman , Cheang Mary S. , Ioannou Stratis
Published: October 2002

BACKGROUND

The overall clinical efficacy of the azoles antifungal agents and low‐dose intravenous amphotericin B for antifungal chemoprophylaxis in patients with malignant disease who have severe neutropenia remains unclear.

METHODS

Randomized‐controlled trials of azoles (fluconazole, itraconazole, ketoconazole, and miconazole) or intravenous amphotericin B formulations compared with placebo/no treatment or polyene‐based controls in severely neutropenic chemotherapy recipients were evaluated using meta‐analytical techniques.

RESULTS

Thirty‐eight trials that included 7014 patients (study agents, 3515 patients; control patients, 3499 patients) were analyzed. Overall, there were reductions in the use of parenteral antifungal therapy (prophylaxis success: odds ratio [OR], 0.57; 95% confidence interval [95% CI], 0.48–0.68; relative risk reduction [RRR], 19%; number requiring treatment for this outcome [NNT], 10 patients), superficial fungal infection (OR, 0.29; 95% CI, 0.20–0.43; RRR, 61%; NNT, 12 patients), invasive fungal infection (OR, 0.44; 95% CI, 0.35–0.55; RRR, 56%; NNT, 22 patients), and fungal infection‐related mortality (OR, 0.58; 95% CI, 0.41–0.82; RRR, 47%; NNT, 52 patients). Invasive aspergillosis was unaffected (OR, 1.03; 95% CI, 0.62–1.44). Although overall mortality was not reduced (OR, 0.87; 95% CI, 0.74–1.03), subgroup analyses showed reduced mortality in studies of patients who had prolonged neutropenia (OR, 0.72; 95% CI, 0.55–0.95) or who underwent hematopoietic stem cell transplantation (HSCT) (OR, 0.77; 95% CI, 0.59–0.99). The multivariate metaregression analyses identified HSCT, prolonged neutropenia, acute leukemia with prolonged neutropenia, and higher azole dose as predictors of treatment effect.

CONCLUSIONS

Antifungal prophylaxis reduced morbidity, as evidenced by reductions in the use of parenteral antifungal therapy, superficial fungal infection, and invasive fungal infection, as well as reducing fungal infection‐related mortality. These effects were most pronounced in patients with malignant disease who had prolonged neutropenia and HSCT recipients. Cancer 2002;94:3230–46. © 2002 American Cancer Society.

DOI 10.1002/cncr.10610
Expression and alteration of ras and p53 proteins in patients with lung carcinoma accompanied by idiopathic pulmonary fibrosis
Authors: Takahashi Toru , Munakata Mitsuru , Ohtsuka Yoshinori , Nisihara Hiroshi , Nasuhara Yasuyuki , Kamachi‐Satoh Atsuko , Dosaka‐Akita Hirotoshi , Homma Yukihiko , Kawakami Yoshikazu
Published: October 2002

BACKGROUND

The ras oncogene and the p53 tumor suppressor gene play important roles in the carcinogenic process of lung carcinoma. The authors evaluated whether alterations of the ras and p53 proteins may contribute to the development of lung carcinoma in patients with idiopathic pulmonary fibrosis (IPF) and whether such alterations may explain the high incidence of lung carcinoma among patients with IPF.

METHODS

Lung tissues were obtained from 35 patients who had IPF without complications of lung carcinoma and from 36 patients who had IPF with complications of lung carcinoma. Altered expression of ras and p53 proteins was evaluated by immunohistochemistry, and mutations of both genes were evaluated by polymerase chain reaction‐single strand conformation polymorphism and sequencing analyses.

RESULTS

The frequency of expression of ras protein in type II alveolar pneumocytes was significantly greater in lung tissues from patients with IPF who had lung carcinoma compared with lung tissues from patients with IPF who did not have lung carcinoma (75% vs. 40%, respectively; P < 0.01). K‐ras point mutation in codon 12 (GGT to GTT transversion) was detected in lung tissue with interstitial pneumonia, in which ras protein was overexpressed in type II alveolar pneumocytes obtained from 2 of 41 patients with IPF complicated by lung carcinoma, causing amino acid substitution (Gly to Val) in both patients. A p53 mutation was detected in three of six lung tissue samples from patients who had IPF lung with positive p53 immunoreactivity, and multiple mutations were detected in two samples.

CONCLUSIONS

Expression of ras protein in type II alveolar pneumocytes and mutation in the codon 12 of K‐ras gene in lung tissue may contribute to the induction of lung carcinoma in patients with IPF. Furthermore, the presence of multiple mutations in the p53 gene may explain the high incidence lung carcinoma in patients with IPF. Cancer 2002;95:624–33. © 2002 American Cancer Society.

DOI 10.1002/cncr.10708
Concurrent cyclophosphamide, methotrexate, and 5‐fluorouracil chemotherapy and radiotherapy for breast carcinoma
Authors: Isaac Neil , Panzarella Tony , Lau Anthea , Mayers Catherine , Kirkbride Peter , Tannock Ian F. , Vallis Katherine A.
Published: October 2002

BACKGROUND

The current study was conducted to assess the toxicity of concurrent adjuvant cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF) chemotherapy and radiotherapy (RT) for early breast carcinoma.

METHODS

In the current study, the authors reviewed the records of 680 consecutive breast carcinoma patients who received adjuvant CMF at the Princess Margaret Hospital between 1980–1990. Surgery was comprised of mastectomy in 64% of patients, breast conservation in 35% of patients, and was unknown in 1% of patients. Two hundred two patients received concurrent CMF/RT that was defined as an overlap in CMF and RT administration of at least 21 days. Forty‐seven patients received sequential CMF/RT (defined as no overlap or an overlap of < 7 days in CMF and RT administration). Other patients received CMF alone. Adverse effects of RT were graded retrospectively using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) system. Reasons for interruption or failure to complete RT were recorded. The magnitude of chemotherapy dose reductions and delays also were noted.

RESULTS

The median age of the patients was 44 years (range, 26–68 years) and 88% of the patients had lymph node‐positive disease. RT was interrupted or discontinued due to side effects in 4% of patients (95% confidence interval [95% CI], 1.7–7.7%) and 0% (95% CI, 0–7.6%), respectively, of the concurrent and sequential groups (P = 0.36). The incidence of Grade 3 or Grade 4 RT toxicity was 1.5% (95% CI, 0.3–4.3%) and 2.1% (95% CI, 0.1–11.3%), respectively, for the concurrent and sequential groups (P = 0.57). The median relative dose intensity of chemotherapy for patients receiving concurrent CMF/RT, sequential CMF/RT, and CMF alone was 0.87, 0.84, and 0.85, respectively (P = 0.22).

CONCLUSIONS

The results of the current study demonstrate that the concurrent administration of CMF and RT is associated with a low risk of serious toxicity and is an acceptable adjuvant regimen for patients with breast carcinoma. Cancer 2002;95:696–703. © 2002 American Cancer Society.

DOI 10.1002/cncr.10744
Treatment of micropapillary serous ovarian carcinoma (the aggressive variant of serous borderline tumors)
Authors: Seidman Jeffrey D. , Kurman Robert J.
Published: October 2002

Ovarian serous borderline tumors recently were categorized into benign and malignant types. A subset of these tumors, termed “micropapillary serous carcinoma (MPSC),” is reported to behave in a manner similar to low‐grade carcinoma. In this issue of Cancer, Bristow et al. report their experience with 26 patients with recurrent MPSC.

See also pages 677–80 and pages 791–800.
Expression of the transcription factors GATA3 and Pax2 during development of the mammalian inner ear
Authors: Lawoko‐Kerali Grace , Rivolta Marcelo N. , Holley Matthew
Published: October 2002

The transcription factors GATA3 and Pax2 are expressed throughout development of the mouse inner ear. We have used antibodies to study their temporal and spatial expression patterns from embryonic days E8–E16.5. The two factors show reciprocal relationships in the regional patterning of the early otocyst and cellular patterning within the sensory epithelia. GATA3 is expressed in the whole otic placode at E8. In the otocyst at E9.5–10.5, the distribution is lateral and complementary to the medial expression pattern of Pax2. Only Pax2 is expressed in the endolymphatic duct, but both factors are expressed in the cochlea. At E11.5–13.5, GATA3 is expressed strongly in the cochlea, but in the dorsal, vestibular region it is downregulated. In all sensory epithelia, downregulation coincides with sensory innervation. Pax2 is expressed in all sensory and some nonsensory epithelia, but within sensory epithelia at E16.5 it is restricted to hair cells. GATA3 is expressed throughout key periods of cell proliferation, fate determination, and differentiation and is not specifically associated with any of these processes. Expression persists most strongly in the main components of the developing auditory system. These include the auditory sensory epithelium, the afferent and efferent nerves, and the mesenchymal and ectodermal cells in regions that form key parts of the middle and outer ear. GATA3 is thus expressed in functionally distinct groups of cells that integrate to form a complete sensory system. The results suggest that both factors may be involved in tissue compartmentalisation, morphogenesis, and cell signalling. J. Comp. Neurol. 442:378–391, 2002. © 2002 Wiley‐Liss, Inc.
Glutamate transporters alterations in the reorganizing dentate gyrus are associated with progressive seizure activity in chronic epileptic rats
Authors: Gorter Jan A. , Van Vliet Erwin A. , Proper Evelien A. , De Graan Pierre N.E. , Ghijsen Wim E.J.M. , Lopes Da Silva Fernando H. , Aronica Eleonora
Published: October 2002

The expression of glial and neuronal glutamate transporter proteins was investigated in the hippocampal region at different time points after electrically induced status epilepticus (SE) in the rat. This experimental rat model for mesial temporal lobe epilepsy is characterized by cell loss, gliosis, synaptic reorganization, and chronic seizures after a latent period. Despite extensive gliosis, immunocytochemistry revealed only an up‐regulation of both glial transporters localized at the outer aspect of the inner molecular layer (iml) in chronic epileptic rats. The neuronal EAAC1 transporter was increased in many somata of individual CA1‐3 neurons and granule cells that had survived after SE; this up‐regulation was still present in the chronic epileptic phase. In contrast, a permanent decrease of EAAC1 immunoreactivity was observed in the iml of the dentate gyrus. This permanent decrease in EAAC1 expression, which was only observed in rats that experienced progressive spontaneous seizure activity, could lead to abnormal glutamate levels in the iml once new abnormal glutamatergic synaptic contacts are formed by means of sprouted mossy fibers. Considering the steady growth of reorganizing mossy fibers in the iml, the absence of a glutamate reuptake mechanism in this region could contribute to progression of spontaneous seizure activity, which occurs with a similar time course. J. Comp. Neurol. 442:365–377, 2002. © 2002 Wiley‐Liss, Inc.
Connections between the central posterior/prepacemaker nucleus and hypothalamic areas in the weakly electric fish Apteronotus leptorhynchus: Evidence for an indirect, but not a direct, link
Authors: Corrêa Sônia A.L. , Zupanc Günther K.H.
Published: October 2002

The central posterior/prepacemaker nucleus (CP/PPn) of the weakly electric fish Apteronotus leptorhynchus consists of a few thousands of neurons in the dorsal thalamus. Subpopulations of this complex play a crucial role in neural control of transient modulations of the otherwise extremely constant electric organ discharges. Because both the propensity to execute these modulations and the type of modulations produced may vary enormously with the behavioral situation, it has been hypothesized that this behavioral plasticity is, partially, mediated by peptidergic neuromodulators originating from hypothalamic areas. To define the structural basis of this proposed modulatory input, we have in the present study examined the connections between the CP/PPn proper and hypothalamic areas by employing an in vitro tract‐tracing technique. Neither anterograde nor retrograde tracing experiments could provide evidence for the existence of a direct link between the CP/PPn proper and hypothalamic areas. However, the results of our investigation suggest an indirect connection between the CP/PPn proper and two hypothalamic regions, the hypothalamus ventralis and the hypothalamus lateralis, with the preglomerular nucleus serving as a relay station. J. Comp. Neurol. 442:348–364, 2002. © 2002 Wiley‐Liss, Inc.
Patterns of expression of calcium binding proteins and neuronal nitric oxide synthase in different populations of hippocampal GABAergic neurons in mice
Authors: Jinno Shozo , Kosaka Toshio
Published: October 2002

We examined the expression of calcium binding proteins parvalbumin (PV), calretinin (CR), and calbindin D28K (CB), and neuronal nitric oxide synthase (nNOS) in γ‐aminobutyric acid (GABA)ergic neurons of the mouse hippocampus, with particular reference to areal and dorsoventral differences. First, we estimated the colocalization of the calcium binding proteins and nNOS. GABAergic neurons containing both PV and nNOS, i.e., PV‐immunoreactive (‐IR)/nNOS‐IR neurons, were rare in Ammon's horn but frequent in the dentate gyrus (DG). CR‐IR/nNOS‐IR neurons and CB‐IR/nNOS‐IR neurons were frequent in Ammon's horn but rare in the DG. In the entire hippocampus, the percentage of CR‐IR neurons containing nNOS was significantly higher at the ventral level (44.3%) than at the dorsal level (17.0%). The percentage of CB‐IR neurons containing nNOS was also significantly higher at the ventral level (42.3%) than at the dorsal level (29.3%). Next, we estimated the numerical densities (NDs) of calcium binding protein‐containing GABAergic neurons. The ND of PV‐IR neurons was comparable at the dorsal (1.16 × 103/mm3) and ventral levels (1.23 × 103/mm3), respectively. The ND of CR‐IR neurons was less at the dorsal level (0.52 × 103/mm3) than at the ventral level (0.64 × 103/mm3). The ND of CB‐IR neurons was also less at the dorsal level (0.91 × 103/mm3) than at the ventral level (1.57 × 103/mm3). Overall, approximately half of the GABAergic neurons contained one of the three calcium binding proteins (45% at the dorsal level and 47% at the ventral level). These data establish a baseline for examining potential roles of GABAergic neurons in hippocampal network activity in mice. J. Comp. Neurol. 449:1–25, 2002. © 2002 Wiley‐Liss, Inc.
Reduced postischemic apoptosis in the hippocampus of mice deficient in interleukin‐1
Authors: Mizushima Hidekatsu , Zhou Cheng J.i. , Dohi Kenji , Horai Reiko , Asano Masahide , Iwakura Yoichiro , Hirabayashi Takahiro , Arata Satoru , Nakajo Shigeo , Takaki Atsushi , Ohtaki Hirokazu , Shioda Seiji
Published: October 2002

The cytokine interleukin‐1 (IL‐1) has been implicated in ischemic brain damage, because the IL‐1 receptor antagonist markedly inhibits experimentally induced neuronal loss. However, to date, no studies have demonstrated the involvement of endogenous IL‐1α and IL‐ 1β in neurodegeneration. We report here, for the first time, that mice lacking IL‐1α/β (double knockout) exhibit markedly reduced neuronal loss and apoptotic cell death when exposed to transient cardiac arrest. Furthermore, we show that, despite the reduced neuronal loss, phosphorylation of JNK/SAPK (c‐Jun NH2‐ terminal protein kinase/stress activated protein kinase) and p38 enzymes remain elevated in IL‐1 knockout mice. In contrast, the inducible nitric oxide (iNOS) immunoreactivity after global ischemia was reduced in IL‐1 knockout mice as compared with wild‐type mice. The levels of nitrite (NO2−) and nitrate (NO3−) in the hippocampus of wild‐type mice were increased with time after ischemia‐reperfusion, whereas the increase was significantly inhibited in IL‐1 knockout mice. These observations strongly suggest that endogenous IL‐1 contributes to ischemic brain damage, and this influence may act through the release of nitric oxide by iNOS. J. Comp. Neurol. 448:203–216, 2002. © 2002 Wiley‐Liss, Inc.
WDR1 colocalizes with ADF and actin in the normal and noise‐damaged chick cochlea
Authors: Oh Seung‐Ha , Adler Henry J. , Raphael Yehoash , Lomax Margaret I.
Published: October 2002

Auditory hair cells of birds, unlike hair cells in the mammalian organ of Corti, can regenerate following sound‐induced loss. We have identified several genes that are upregulated following such an insult. One gene, WDR1, encodes the vertebrate homologue of actin‐interacting protein 1, which interacts with actin depolymerization factor (ADF) to enhance the rate of actin filament cleavage. We examined WDR1 expression in the developing, mature, and noise‐damaged chick cochlea by in situ hybridization and immunocytochemistry. In the mature cochlea, WDR1 mRNA was detected in hair cells, homogene cells, and cuboidal cells, all of which contain high levels of F‐actin. In the developing inner ear, WDR1 mRNA was detected in homogene cells and cuboidal cells by embryonic day 7, in the undifferentiated sensory epithelium by day 9, and in hair cells at embryonic day 16. We also demonstrated colocalization of WDR1, ADF, and F‐actin in all three cell types in the normal and noise‐damaged cochlea. Immediately after acoustic overstimulation, WDR1 mRNA was seen in supporting cells. These cells contribute to the structural integrity of the basilar papilla, the maintenance of the ionic barrier at the reticular lamina, and the generation of new hair cells. These results indicate that one of the immediate responses of the supporting cell after noise exposure is to induce WDR1 gene expression and thus to increase the rate of actin filament turnover. These results suggest that WDR1 may play a role either in restoring cytoskeletal integrity in supporting cells or in a cell signaling pathway required for regeneration. J. Comp. Neurol. 448:399–409, 2002. © 2002 Wiley‐Liss, Inc.
Up‐regulation of tyrosine kinase (Trka, Trkb) receptor expression and phosphorylation in lumbosacral dorsal root ganglia after chronic spinal cord (T8–T10) injury
Authors: Qiao Liya , Vizzard Margaret A.
Published: October 2002

Previous studies have demonstrated changes in urinary bladder neurotrophic factors after bladder dysfunction. We have hypothesized that retrograde transport of neurotrophin(s) from the bladder to lumbosacral dorsal root ganglia (DRG) may play a role in bladder reflex reorganization after spinal cord injury (SCI). In this study, we determined whether the expression of tyrosine kinase receptors (TrkA, TrkB) is altered in lumbosacral DRG after SCI through immunofluorescence techniques. Complete transection of the spinal cord (T8–T10) was performed in female Wistar rats (120–150 g), and animals were studied 5–6 weeks after SCI. One week before killing, Fast Blue (FB) was injected into the bladder to label bladder afferent cells in the L1, L2, L6, and S1 DRG. After SCI, a significant increase in the number of TrkA‐immunoreactive (IR) positive cells was detected in the L6‐S1 DRG (L6: 1.9‐fold, P ≤ 0.01; S1: 1.7‐fold, P ≤ 0.05) and in the L1 DRG (3.0‐fold; P ≤ 0.01) but not in the L4‐L5 DRG compared with spinal‐intact (control) rats. After SCI, a significant increase in the number of TrkB‐IR cells was also detected in the L6‐S1 DRG (L6: 2.2‐fold, P ≤ 0.01; S1: 1.5‐fold, P ≤ 0.05) and in the L1‐L2 DRG (L1: 1.5‐fold, P ≤ 0.01; L2: 1.3‐fold, P ≤ 0.05) but not in the L4‐L5 DRG compared with control rats. After SCI, the percentage of FB‐labeled cells expressing TrkA immunoreactivity (∼68%) or TrkB immunoreactivity (∼65%) in L1 and L6 DRG significantly (P ≤ 0.01) increased compared with control (20–30%) DRG. After SCI, the percentage of TrkA‐IR cells expressing phosphorylated (p)‐Trk immunoreactivity significantly increased (1.5‐ to 2.3‐fold increase) in the L1, L6, and S1 DRG. The percentage of TrkB‐IR cells expressing p‐Trk immunoreactivity after SCI also increased (1.3‐fold increase) in the L1 and L6 DRG. These results demonstrate that (1) TrkA and TrkB immunoreactivity is increased in bladder afferent cells after SCI and (2) TrkA and TrkB receptors are phosphorylated in DRG after SCI. Neuroplasticity of lower urinary tract reflexes after SCI may be mediated by both nerve growth factor and brain‐derived neurotrophic factor. J. Comp. Neurol. 449:217–230, 2002. © 2002 Wiley‐Liss, Inc.
Cellular localization and development of neuronal intranuclear inclusions in striatal and cortical neurons in R6/2 transgenic mice
Authors: Meade Christopher A. , Deng Yun‐Ping , Fusco Francesca R. , Del Mar Nobel , Hersch Steven , Goldowitz Dan , Reiner Anton
Published: October 2002

The cellular localization and development of neuronal intranuclear inclusions (NIIs) in cortex and striatum of R6/2 HD transgenic mice were studied to ascertain the relationship of NIIs to symptom formation in these mice and gain clues regarding the possible relationship of NII formation to neuropathology in Huntington's disease (HD). All NIIs observed in R6/2 mice were ubiquitinated, and no evidence was observed for a contribution to them from wild‐type huntingtin; they were first observed in cortex and striatum at 3.5 weeks of age. In cortex, NIIs increased rapidly in size and prevalence after their appearance. Generally, cortical projection neurons developed NIIs more rapidly than cortical interneurons containing calbindin or parvalbumin. Few cortical somatostatinergic interneurons, however, formed NIIs. In striatum, calbindinergic projection neurons and parvalbuminergic interneurons rapidly formed NIIs, but they formed more gradually in cholinergic interneurons, and few somatostatinergic interneurons developed NIIs. Striatal NIIs tended to be smaller than those in cortex. The early accumulation of NIIs in cortex and striatum in R6/2 mice is consistent with the early appearance of motor and learning abnormalities in these mice, and the eventual pervasiveness of NIIs at ages at which severe abnormalities are evident is consistent with their contribution to a neuronal dysfunction underlying the abnormalities. That cortex develops larger NIIs than striatum, however, is inconsistent with the preferential loss of striatal neurons in HD but is consistent with recent evidence of early morphological abnormalities in cortical neurons in HD. That calbindinergic and parvalbuminergic striatal neurons develop large NIIs is consistent with a contribution of nuclear aggregate formation to their high degree of vulnerability in HD. J. Comp. Neurol. 449:241–269, 2002. © 2002 Wiley‐Liss, Inc.
TRPC6 immunoreactivity is colocalized with neuronal nitric oxide synthase in extrinsic fibers innervating guinea pig intrinsic cardiac ganglia
Authors: Calupca Michelle A. , Locknar Sarah A. , Parsons Rodney L.
Published: October 2002

Tachykinins depolarize guinea pig intracardiac neurons by activating nonselective cationic channels. Recently, members of the transient receptor potential family of membrane channels (TRPC) have been implicated in the generation of G protein‐coupled receptor‐activated nonselective cationic currents. We have investigated whether guinea pig cardiac neurons exhibit immunoreactivity to TRPC. Our results showed that nerve fibers within guinea pig intrinsic cardiac ganglia exhibited immunoreactivity to TRPC6. After culture of cardiac ganglia whole‐mount explants for 72 hours, the TRPC6‐IR fiber networks were absent. Therefore, the TRPC6‐IR fibers were derived from sources extrinsic to the heart. A small percentage (∼3%) of intracardiac neurons also exhibited TRPC6 immunoreactivity in control preparations, and the percentage of cells exhibiting TRPC6 immunoreactivity was not changed following explant culture for 72 hours. The few intrinsic TRPC6‐IR neurons also exhibited nitric oxide synthase (NOS) immunoreactivity, indicating that they were nitrergic as well. We compared the immunohistochemical staining patterns of TRPC6‐IR fibers with the staining patterns of a number of other neurotransmitters or neurotransmitter synthetic enzymes that mark specific extrinsic inputs to the intrinsic cardiac ganglia. The TRPC6‐IR fibers were not immunoreactive for choline acetyltransferase, tyrosine hydroxylase, or substance P. However, the TRPC6‐IR fibers exhibited immunoreactivity to neuronal NOS. Therefore, we propose that the TRPC6‐IR fibers within the guinea pig intrinsic cardiac ganglia are vagal sensory fibers that also contain NOS. We found, in support of this conclusion, that TRPC6‐IR cells were also present in sections of nodose ganglia. J. Comp. Neurol. 450:283–291, 2002. © 2002 Wiley‐Liss, Inc.
Immunolocalization of PICK1 in the ascending auditory pathways of the adult rat
Authors: McInvale Andrew C. , Staudinger Jeff , Harlan Richard E. , Garcia Meredith M.
Published: October 2002

Protein that interacts with C‐kinase α (PICK1) is a PDZ domain protein that interacts with many binding partners in the central nervous system (CNS), including activated protein kinase Cα and subunits of the AMPA subtype of glutamate receptor. Almost nothing is known about the anatomic distribution of PICK1 in the intact adult CNS. By using PICK1 antisera and peroxidase immunocytochemistry, we report on the distribution of PICK1 in the ascending pathways of the central auditory system of the adult rat. PICK1‐immunoreactivity (ir) was observed in many component nuclei of the central auditory system, including the dorsal cochlear nucleus, anteroventral cochlear nucleus, posteroventral cochlear nucleus, some divisions of the superior olivary complex, inferior colliculus, medial geniculate body, and primary auditory cortex. The general staining pattern for PICK1‐immunoreactivity was somatodendritic with scattered puncta in neuropil and somatodendritic regions. The distribution of PICK1 partially overlaps with PKCα and glutamate receptor subunits such as GluR2. These data suggest that PICK1 may function in the regulation of PKCα and GluR2 localization in components of the rat auditory system, which may be a fundamental mechanism of synaptic transmission and/or plasticity. J. Comp. Neurol. 450:382–394, 2002. © 2002 Wiley‐Liss, Inc.
Groundwater parameter estimation via the unsteady adjoint variable formulation of discrete sensitivity analysis
Authors: Burg C. O. E.
Published: October 2002

Discrete sensitivity analysis (DSA) is a method that efficiently estimates the derivatives of a numerically approximated objective function with respect to a set of parameters at a fraction of the cost of using finite differences. Coupled with an optimization algorithm, this method can be used to locate the optimal set of parameters for the objective function. The time dependent adjoint variable formulation of discrete sensitivity analysis is derived and applied to a time‐dependent, two‐dimensional groundwater code. The derivatives agreed with finite difference derivatives to between 6 and 8 significant digits, at approximately ⅛ the computational cost. Using the BFGS optimization algorithm to update the parameters, the parameter estimation technique successfully identified the target values, for problems with small number of parameters. Copyright © 2002 John Wiley & Sons, Ltd.
A beam finite element for through‐cracked tubular node behaviour modelling
Authors: Rouhan A. , Wielgosz C.
Published: October 2002

This paper deals with the problem of a through‐cracked tubular joint behaviour modelling. A new beam finite element has been created, in order to take into account the loss of stiffness of the joint due to through‐thickness crack presence, and the coupling between axial force and bending momentum. This allows to study at a low computing time large damaged offshore structures, using beam elements. The mechanical model used to build the finite element is first described. An analytical identification of its internal parameters (eccentricity and stiffness) is then performed. Finally, some results are presented. Copyright © 2002 John Wiley & Sons, Ltd.
Time‐accurate solution of stabilized convection–diffusion–reaction equations: I—time and space discretization
Authors: Huerta Antonio , Donea Jean
Published: October 2002

The paper addresses the development of time‐accurate methods for solving transient convection–diffusion–reaction problems using finite elements. Multi‐stage time‐stepping schemes of high accuracy are used. They are first combined with a Galerkin formulation to briefly recall the time–space discretization. Then spatial stabilization techniques are combined with high‐order time‐stepping schemes. Moreover, a least‐squares formulation is also developed for these high‐order time schemes combined with C0 finite elements (in spite of the diffusion operator and without reducing the strong form into a system of first‐order differential equations). The weak forms induced by the SUPG, GLS, SGS and least‐squares formulations are presented and compared. In a companion paper (Part II of this work), the phase and damping properties of the developed schemes are analysed and numerical examples are included to confirm the effectiveness of the proposed methodology for solving time‐dependent convection–diffusion–reaction problems. Copyright © 2002 John Wiley & Sons, Ltd.
A note on the CVBEM for the two‐dimensional Helmholtz equation or its modified form
Authors: Ang Whye‐Teong
Published: October 2002

A complex variable boundary element method is outlined for the numerical solution of the two‐dimensional Helmholtz equation or its modified form in a simply connected region subject to suitable boundary conditions. It is applied to solve a specific test problem. Copyright © 2002 John Wiley & Sons, Ltd.
Color identification data obtained from photopic to mesopic illuminance levels
Authors: Ishida Taiichiro
Published: October 2002

To use colors properly as an aid in visual tasks, it is necessary to know how colors are identified under various illuminating environments. In this study color identification was examined under a wide range of illuminances, from photopic to mesopic levels. Fifteen subjects named a color chip using one of the preselected color terms: red, orange, yellow, yellow‐green, green, blue‐green, blue, purple, pink, brown, white, gray, and black. The 256 color chips were selected from value planes of 4, 6, and 8 of the Munsell color space. The illuminance levels tested were 1000, 10, 1, and 0.1 lx. At 1000 lx the color chips were identified consistently by each of the color terms. At 10 lx the pattern of color identification was very similar to that at 1000 lx, though the consistency of the identification evidently declined. At 1 lx great changes in color identification occurred. By 0.1 lx reliable color identification was completely lost, though blue and red responses remained. At the lower illuminances green was replaced with blue, and red, orange, and pink were frequently confused with each other. However, the border between blue and purple was almost constant. These results provide a scientific basis for the appropriate use of colors in various illuminating environments. Also, they are useful for studies in color appearance modeling. © 2002 Wiley Periodicals, Inc. Col Res Appl, 27, 252–259, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.10065
Nonlinear data analysis of experimental (EEG) data and comparison with theoretical (ANN) data
Authors: Das Atin , Das Pritha , Roy A. B.
Published: October 2002

In this article, nonlinear dynamical tools such as largest Lyapunov exponents (LE), fractal dimension, correlation dimension, pointwise correlation dimension will be used to analyze electroencephalogram (EEG) data obtained from healthy young subjects with eyes open and eyes closed condition with the view to compare brain complexity under this two condition. Results of similar calculations from some earlier works will be produced for comparison with present results. Also, a brief report on difference of opinion among coworkers regarding such tools will be reported; particularly applicability of LE will be reviewed. The issue of nonlinearity will be addressed by using surrogate data technique. We have extracted another data set that represented chaotic state of the system considered in our earlier work of mathematical modeling of artificial neural network. We further attempt to compare results to find nature of chaos arising from such theoretical models. © 2002 Wiley Periodicals, Inc.
Cognitions and their origins in women with anorexia nervosa, normal dieters and female controls
Authors: Turner Hannah , Cooper Myra
Published: October 2002

The objective of the study was to develop a semi‐structured interview with which to investigate cognitions and their origins in female patients with anorexia nervosa, normal female dieters and female non‐dieting controls and to explore group differences in cognitions and, where appropriate, the role of early experience in their development. Following piloting, all participants completed the semi‐structured interview and five self‐report questionnaires to assess reliability and validity of the interview. When discussing eating‐related concerns clinical participants reported more eating‐related thoughts than non‐clinical participants. These differences were also evident, although to a slightly lesser extent, when discussing concerns about weight and shape. Clinical participants reported more assumptions relating to eating, and weight and shape as a means to acceptance by self and others, and to control over‐eating than non‐clinical participants. A similar pattern of group difference was reported in degree of belief and associated distress. Clinical participants identified more negative self‐beliefs than non‐clinical participants. A similar pattern of group difference was reported in degree of rational and emotional belief, and associated distress. All clinical participants identified an association between negative early experiences and negative self‐beliefs, and all reported a link between negative self‐beliefs and dieting. There are clear differences in cognitive characteristics between women with anorexia nervosa, normal dieters and non‐dieting female controls. The meaning attached to dieting may also distinguish dieters from those with a clinical eating disorder. Copyright © 2002 John Wiley & Sons, Ltd.
Personality style, psychological adaptation and expectations of trainee clinical psychologists
Authors: Brooks Jeni , Holttum Sue , Lavender Anthony
Published: October 2002

The literature suggests that personality affects how individuals experience stress, cope, utilize social support and psychologically adapt. This study examined the personality style, psychological adaptation and expectations of 364 UK trainee clinical psychologists. Personality traits characterizing the sample were: enhancing, modifying, extraversing, outgoing, and agreeing. Mean overall personality adjustment was significantly better than the normal population. The sample scored significantly poorer on self‐esteem, anxiety and depression, but well outside the defined range for poor adaptation. A small percentage (8%, n = 31) had ‘poor’ personality adjustment scores, scored worse on indicators of psychological adaptation and reported greater shortfall of course aspects compared with expectations. However, 41% scored as having a significant problem on one or more of: anxiety, depression, low self‐esteem and work adjustment. About one‐third had a probable substance use problem. In regression analyses, poor personality adjustment, and different areas of expectation‐shortfall, especially impact of training on life variously predicted anxiety, depression, and poor work adjustment. Satisfaction with social support was not predictive of adaptation after personality adjustment was accounted for. Implications for clinical psychology training include the need for enhanced expectation‐management through pre‐course marketing, and better attention to trainees' personal and professional development throughout training. Copyright © 2002 John Wiley & Sons, Ltd.
Monitoring tumour cells in the peripheral blood of small cell lung cancer patients
Authors: Kularatne B.Y. , Lorigan P. , Browne S. , Suvarna S.K. , Smith M.O. , Lawry J.
Published: October 2002

BACKGROUND

Flow cytometry was used to enumerate tumour cells in longitudinal studies of peripheral blood from small cell lung cancer (SCLC) patients, together with magnetic bead selection to isolate and identify these cells. As part of a trial, 11 patients received either standard (four weekly) chemotherapy with ifosfamide, carboplatin, and etoposide (ICE) or accelerated (two weekly) ICE with filgrastim (granulocyte colony‐stimulating factor [G‐CSF]) and autologous stem cell support. Methods: Fresh venous blood was taken throughout treatment and follow‐up. Aliquots were stained with a “tumour‐specific” antibody against epithelial tissue (Ber EP4), verified as a good marker of SCLC cells by immunohistochemistry. Matched samples labelled with Ber EP4 were separated magnetically by adding a secondary bead‐antibody conjugate for confirmation of tumour cell identity. Results: Circulating tumour cells were detected and monitored throughout treatment periods. An initial rise in circulating cells after the first cycle was followed by a fall in both treatment arms to baseline levels set by normal controls. This was achieved by week 12 in the accelerated treatment arm and by week 24 in the standard arm. Conclusions: Flow cytometry and magnetic bead isolation can be used to identify changes in numbers of circulating tumour cells in patients undergoing chemotherapy for SCLC and thereafter during follow‐up periods. Absence of tumour cells may indicate a more favourable patient group who would benefit from a more intense course of treatment. Cytometry (Clin. Cytometry) 50:160–167, 2002. © 2002 Wiley‐Liss, Inc.
Price‐coupled scheduling for differentiated services: Gcµversus GPS
Authors: Van Mieghem Jan A. , Van Mieghem Piet
Published: October 2002

We present an integrated approach to pricing and scheduling for services that are differentiated in terms of throughput, delay and loss specifications. The key building block to the model are quality value curves that specify a user's value of higher quality levels. From the analysis emerges a pricing rule that charges based on rate and quality grade, and a dynamic scheduling rule, called the Gcµrule. The analysis also derives the economically optimal probabilistic quality of service (QoS) guarantee parameters.

We compare our model to the deterministic approach of QoS guarantees using burstiness constraints and fair scheduling rules. The scheduling that arises from such a deterministic approach is the well‐known Generalized Processor Sharing (GPS). A comparative analysis inspires the fair Gcµ‐PS rule as the scheduling rule that combines the unique strengths of GPS and Gcµ. This Gcµ‐PS rule is proposed as a tailored scheduling solution forboththe expedited forwarding class and the four assured forwarding classes in the IETF's differentiated services. Copyright © 2002 John Wiley & Sons, Ltd.
An innovative channel management strategy for highly reliable handoff in cellular networks
Authors: Hong Seung S. , Chung Tai M.
Published: October 2002

In this paper, we have resolved the problem of forced call termination that occurs when mobile traffic is concentrated on a hot‐spot cell in cellular networks. Enhanced Channel Management Scheme (ECMS) is an innovative way to increase the flexibility of channel usage over non‐uniform traffic distribution. ECMS exploits mobile hosts initiated or active in overlapping areas between cells. The scheme consists of three phases to monitor the status of channels on each base station and to make a channel reservation using the availability list maintained for the candidate‐MH selection. When the traffic load in a cell is intolerably high, ECMS invokes the load‐balancing procedure to distribute its traffic to adjacent cells. The reserved channels are used to support the safe and fast handoff. From the simulation, we observed that ECMS outperformed other compatible channel assignment schemes such as directed handoff schemes in blocking probability and channel utilization. Copyright © 2002 John Wiley & Sons, Ltd.
Diagnostic intraocular aspiration cytology of choroidal melanoma
Authors: Kashyap Seema , Sen Seema , Sharma M.C. , Sethi Anita
Published: October 2002

Fine‐needle aspiration cytology (FNAC) was performed on an intraocular mass in a 32‐yr‐old Indian woman and a cytologic diagnosis of malignant melanoma was made, supported by immunocytochemistry. The cytologic features included spindle‐shaped tumour cells with minimal pleomorphism and the presence of nuclear grooves. No intracellular pigment was identified; however, positivity for HMB‐45 allowed a rapid and reliable diagnosis. The utility of FNAC in an atypical presentation of choroidal melanoma is discussed. Diagn. Cytopathol. 2002;26:389–391. © 2002 Wiley‐Liss, Inc.
Rare atypical squamous cells of undetermined significance (ASCUS): A clinically significant diagnosis?
Authors: Hoerl H. Daniel , Roth‐Cline Michelle D. , Shalkham John E. , Pfister John , Stewart Jimmie , Guo Ziwen , De Las Casas Luis E. , Caya James G. , Kurtycz Daniel F.I.
Published: October 2002

To determine the clinical significance of rare atypical squamous cells of undetermined significance (ASCUS) in cervical screening, we studied 748 ASCUS cases prospectively noted to have rare abnormal cells. Comparing the rare ASCUS (RASC) group (defined as five or fewer abnormal cells) statistically to cases diagnosed as within normal limits (WNL), ASCUS unqualified as to number of cells low‐grade squamous intraepithelial lesion (LGSIL), and high‐grade SIL (HGSIL), we found that the probability of the RASC patients having an abnormal cytology (ASCUS/SIL) or biopsy (dysplasia) result within 1 yr was greater than that of the WNL group, but less than that for ASCUS unqualified, LGSIL, or HGSIL. When only ThinPrep® specimens or cases with subsequent definitive SIL/dysplasia were considered, the RASC group was not significantly different from the WNL group. We conclude that RASC increases the risk of a subsequent abnormal cytology/biopsy result in conventional smears, but only when the threshold for abnormality is a subsequent ASCUS. It did not predict dysplasia (SIL/CIN) in those conventional samples. RASC did not have the power to predict any subsequent abnormality and did not appear to be clinically significant in ThinPrep® samples. Diagn. Cytopathol. 2002;27:5–9. © 2002 Wiley‐Liss, Inc.
Nonneoplastic findings in loop electrical excision procedure specimens from patients with persistent atypical squamous cells of uncertain significance in two consecutive pap smears
Authors: Pinto Álvaro P. , Tuon Felipe F.B. , Tizzot Edson L.A. , Bleggi Torres Luiz Fernando , Collaço Luiz Martins
Published: October 2002

The present study aimed to determine the histopathological correspondence of the diagnosis of atypical squamous cells of uncertain significance (ASCUS) in the absence of squamous intraepithelial neoplasia (SIL) in loop electrical excision procedure (LEEP) products. Retrospective histopathological analysis of 70 LEEP products preceded by ASCUS was consistently detected by two consecutive Pap smears. The presence or absence of several histopathological findings in cases with (23/70) and without (47/70) histological diagnosis of SIL were compared. Immature squamous metaplasia, severe cervicitis, and tube‐endometrial metaplasia were found with similar frequency on positive and negative neoplastic disease specimens. Reactive squamous atypia, keratosis, atrophy, glandular reactive/inflammatory atypia, tunnel clusters, and microglandular hyperplasia were less frequently found in LEEP specimens presenting with SIL. Reactive squamous atypia and keratosis were consistently associated with SIL absence and appear to be responsible for the cytological diagnosis of ASCUS (P < 0.05). Diagn. Cytopathol. 2002;27:123–127. © 2002 Wiley‐Liss, Inc.