bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated expression of cyclooxygenase‐2 is a negative prognostic factor for disease free survival and overall survival in patients with breast carcinoma
Authors: Denkert Carsten , Winzer Klaus‐Jürgen , Müller Berit‐Maria , Weichert Wilko , Pest Sören , Köbel Martin , Kristiansen Glen , Reles Angela , Siegert Antje , Guski Hans , Hauptmann Steffen
Published: May 2003

BACKGROUND

Cyclooxygenases regulate the production of prostaglandins and play a role in tumor development and progression. The authors investigated the prognostic impact of expression of the cyclooxygenase (COX) isoforms, COX‐1 and COX‐2, on disease‐free survival and progression‐free survival in patients with primary breast carcinoma as well as the association between COX expression and other clinicopathologic parameters.

METHODS

In this study COX isoform expression was determined by immunohistochemistry in a cohort of 221 patients with primary breast carcinoma.

RESULTS

Expression of COX‐2 was detected in 36% of breast carcinoma samples and was associated significantly with several clinicopathologic parameters, including positive lymph node status (P < 0.0005), larger tumor size (P < 0.0005), poor differentiation (P < 0.0005), vascular invasion (P = 0.03), and negative estrogen receptor status (P = 0.04). In contrast, COX‐1 was expressed in 45% of tumors and was associated with smaller tumor size (P = 0.02) and with negative lymph node status (P = 0.01). In a univariate survival analysis, a significant association was observed between elevated COX‐2 expression and decreases in disease‐free survival (P = 0.0007) and overall survival (P = 0.02). In a multivariate analysis, expression of COX‐2 was of borderline significance for disease‐free survival (relative risk, 1.90; 95% confidence interval, 1.00–3.59), adjusting for tumor size, histologic grade, number of positive lymph nodes, and patient age. Elevated expression of COX‐1 in tumor tissue had no statistically significant influence on patient prognosis.

CONCLUSIONS

The current data suggest that increased expression of COX‐2 may play a role in the progression of primary breast carcinoma. It remains to be investigated whether treatment with selective inhibitors of COX‐2 may be an additional therapeutic option for patients with breast carcinoma. Cancer 2003;97:2978–87. © 2003 American Cancer Society.

DOI 10.1002/cncr.11437
Sentinel lymph nodes
Authors: Covens Allan
Published: May 2003

DOI 10.1002/cncr.11438
Seeking the solution to the problem of metastatic renal carcinoma
Authors: Russo Paul
Published: May 2003

DOI 10.1002/cncr.11439
Hepatic steatosis in patients with chronic hepatitis C virus infection
Authors: Zhu Andrew X. , Chung Raymond T.
Published: May 2003

DOI 10.1002/cncr.11440
Cancer in the Minnesota Hmong population
Authors: Ross Julie A. , Xie Yang , Kiffmeyer William R. , Bushhouse Sally , Robison Leslie L.
Published: May 2003

BACKGROUND

The Hmong are an isolated, agrarian people who settled in the mountainous regions of what today are Vietnam, Cambodia, and Laos. After the Vietnam War, many Hmong were relocated to the U.S. Minnesota has the second largest population (after California) of Hmong individuals. The objective of this study was to examine cancer incidence in this population, because it may indicate areas for targeted surveillance and intervention.

METHODS

The Minnesota Cancer Surveillance System database was screened for Hmong surnames, and proportional incidence ratios (PIRs) were calculated for the period 1988–1999.

RESULTS

Compared with all Minnesotans, the Hmong population had increased PIRs for nasopharyngeal cancer (PIR, 39.39; 95% confidence interval [95% CI], 21.01–66.86), gastric cancer (PIR, 8.70; 95% CI, 5.39–13.25), hepatic cancer (PIR, 8.08; 95% CI, 3.88–14.71), and cervical cancer (PIR, 3.72; 95% CI, 2.04–6.20) and had decreased PIRs for prostate cancer, breast cancer, Hodgkin disease, and melanoma.

CONCLUSIONS

The current observations have implications for cancer control interventions. In particular, an increased incidence of cervical cancer might be addressed in part by targeting culturally sensitive screening programs in the Hmong population. Cancer 2003;97:3076–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11443
Cancer incidence in the U.S. radiologic technologists health study, 1983–1998
Authors: Sigurdson Alice J. , Doody Michele Morin , Rao R. Sowmya , Freedman D. Michal , Alexander Bruce H. , Hauptmann Michael , Mohan Aparna K. , Yoshinaga Shinji , Hill Deirdre A. , Tarone Robert , Mabuchi Kiyohiko , Ron Elaine , Linet Martha S.
Published: May 2003

BACKGROUND

Workers exposed to low doses of radiation can provide information regarding cancer risks that are of public concern. However, characterizing risk at low doses requires large populations and ideally should include a large proportion of women, both of which rarely are available.

METHODS

Among 90,305 radiologic technologists in the U.S. (77% women) who were followed during 1983–1998, data concerning incident cancer occurrence was obtained from mailed questionnaires and from death records. Standardized incidence ratios (SIRs) were computed using age‐specific, gender‐specific, race‐specific, and calendar year‐specific cancer rates from the Surveillance, Epidemiology, and End Results Program.

RESULTS

The SIR for all cancers in both genders combined was 1.04 (95% confidence interval [95% CI], 1.00–1.07; n = 3292 technologists). Female technologists had an elevated risk for all solid tumors combined (SIR = 1.06; 95% CI, 1.02–1.10; n = 2168 women) and for breast cancers (SIR = 1.16; 95% CI, 1.09–1.23; n = 970 women), melanoma (SIR = 1.66; 95% CI, 1.43–1.89; n = 181 women), and thyroid cancers (SIR = 1.54; 95% CI, 1.24–1.83; n = 107 women). Male technologists experienced a decreased risk for solid tumors (SIR = 0.92; 95% CI, 0.85–0.98; n = 755 men); however, melanoma (SIR = 1.39; 95% CI, 1.00–1.79; n = 56 men) and thyroid cancers (SIR = 2.23; 95% CI, 1.29–3.59; n = 17 men) were increased. Among both genders, the risks were decreased for buccal cavity/pharyngeal cancers (SIR = 0.73; 95% CI, 0.55–0.90; n = 54 technologists), rectal cancers (SIR = 0.62; 95% CI 0.48–0.76; n = 53 technologists), and lung cancers (SIR = 0.77, 95% CI, 0.70–0.85; n = 307 technologists).

CONCLUSIONS

The elevated risk for breast cancer may have been related to occupational radiation exposure. The observed excesses of melanoma and thyroid cancers may reflect, at least in part, earlier detection among medical workers with easy access to health care. Cancer 2003;97:3080–9. © 2003 American Cancer Society.

DOI 10.1002/cncr.11444
Pharmacoeconomic analysis of oprelvekin (recombinant human interleukin‐11) for secondary prophylaxis of thrombocytopenia in solid tumor patients receiving chemotherapy
Authors: Cantor Scott B. , Elting Linda S. , Hudson David V. , Rubenstein Edward B
Published: May 2003

BACKGROUND

Previous research has shown oprelvekin (recombinant human interleukin‐11 [rhIL‐11]) to be effective in reducing the requirements for platelet transfusions after myelosuppressive chemotherapy in patients who have previously experienced thrombocytopenia. The economic consequences of the routine use of this platelet growth factor and the usual standard of platelet transfusions for prophylaxis of severe chemotherapy‐induced thrombocytopenia have not been compared.

METHODS

The authors constructed a decision‐analytic model to compare the alternatives of rhIL‐11 versus usual care using probability, outcome, and cost data from previously published clinical trials and their own institutional sources. They incorporated the costs of platelet transfusions and adverse events from rhIL‐11 into the analysis. Quality‐of‐life outcomes were not considered. The pharmacoeconomic analysis was based on the criterion of cost minimization from the payer's perspective.

RESULTS

The expected cost of the usual care strategy for prophylaxis of severe thrombocytopenia (transfusion when platelets < 20,000 μL−1) was $3495 for a 3‐week cycle of chemotherapy. The prophylactic rhIL‐11 strategy was more expensive, with an expected cost of $5328 over the same time period. Nonetheless, it was associated with fewer platelet transfusions, avoiding an average of 6.7 U compared with usual care. The savings from avoidance of platelet transfusion and adverse reactions to transfusion from the use of rhIL‐11 were not offset by the substantial cost of the pharmaceutical. The greater expected costs from the rhIL‐11 strategy were relatively insensitive to the unit price and efficacy of rhIL‐11 and the costs of platelet transfusions and monitoring.

CONCLUSIONS

From the payer's perspective, rhIL‐11 cannot be considered a cost‐saving clinical strategy compared with routine platelet transfusions for patients with severe chemotherapy‐induced thrombocytopenia. Cancer 2003;97:3099–106. © 2003 American Cancer Society.

DOI 10.1002/cncr.11447
Quality‐of‐life–adjusted survival comparison of sustained‐release cytosine arabinoside versus intrathecal methotrexate for treatment of solid tumor neoplastic meningitis
Authors: Cole Bernard F. , Glantz Michael J. , Jaeckle Kurt A. , Chamberlain Marc C. , Mackowiak John I.
Published: May 2003

BACKGROUND

The authors compared the quality of life of patients with solid tumor neoplastic meningitis treated in a controlled trial that compared conventional intrathecal methotrexate with a depot cytosine arabinoside liposomal injection (DepoCyt). The authors evaluated the trade‐off between toxicity and improved clinical outcome.

METHODS

Quality‐adjusted time without symptoms or toxicity (Q‐TWiST) analysis was used to evaluate data collected prospectively from a randomized clinical trial that compared DepoCyt with methotrexate. Sixty‐one patients with confirmed solid tumor neoplastic meningitis were randomized to receive either methotrexate or DepoCyt.

RESULTS

Within the 12‐month follow‐up, the average patient in the DepoCyt arm (compared with the methotrexate arm) achieved 71 more days of neurologic progression‐free survival and 52 more days of overall survival, but experienced slightly more days with toxicity. The DepoCyt regimen provided greater quality‐adjusted survival regardless of the quality‐of‐life valuations placed on time with toxicity and time following disease progression (range, 44–79 days). This gain was significant (P < 0.05) for all patients except for those who placed a high relative value on time following disease progression.

CONCLUSIONS

The clinical benefits of DepoCyt offset a trend toward additional toxicity among patients with sold tumor neoplastic meningitis. The magnitude of the benefit depends on how the patient values time spent in toxicity and disease progression. The results of this analysis can be used at the bedside to make evidence‐based individual treatment decisions. Cancer 2003;97:3053–60. © 2003 American Cancer Society.

DOI 10.1002/cncr.11449
Nuclear accumulation of basic fibroblast growth factor in human astrocytic tumors
Authors: Fukui Shinji , Nawashiro Hiroshi , Otani Naoki , Ooigawa Hidetoshi , Nomura Namiko , Yano Akiko , Miyazawa Takahito , Ohnuki Akira , Tsuzuki Nobusuke , Katoh Hiroshi , Ishihara Shoichiro , Shima Katsuji
Published: May 2003

BACKGROUND

The authors recently reported that nuclear accumulation of basic fibroblast growth factor (bFGF) demonstrated a significant correlation with recurrence of pituitary adenomas. The current study sought to determine whether nuclear bFGF accumulation was a predictor of survival in patients with astrocytic tumors.

METHODS

The authors examined 52 patients with primary astrocytic tumors. Immunohistochemical assays for bFGF, fibroblast growth factor receptor 1 (FGFR1), and proliferating cell nuclear antigen were performed. Immunoreactivity of bFGF in nuclei was recorded in terms of the bFGF nuclear index (NI), which was calculated as the percentage of tumor cells with nuclear immunoreactivity. Western blot analysis of bFGF in nuclear fractions was performed.

RESULTS

The bFGF NI had a mean value of 35.1% and was < 30% (low NI) in 27 patients and ≥ 30% (high NI) in 25 patients. In all cases, FGFR1 immunoreactivity was observed in the cytoplasm but not in the nucleus. Western blot analysis indicated that the nuclear fractions from tumor specimens with high NI contained high–molecular‐weight bFGF. Univariate analyses showed that age, tumor histology, gender, and bFGF NI were significantly correlated with patient survival. Multivariate analyses demonstrated that NI had the greatest influence (P = 0.0073) on survival rate, compared with age (P = 0.0083) and gender (P = 0.0492). Compared with low NI, high NI was associated with a relative risk of 3.292.

CONCLUSIONS

The findings of the current study suggest that bFGF NI may be a useful predictor of survival in patients with astrocytic tumors. Cancer 2003;97:3061–7. © 2003 American Cancer Society.

DOI 10.1002/cncr.11450
Measurement of serum squamous cell carcinoma antigen levels as a predictor of radiation response in patients with carcinoma of the uterine cervix
Authors: Ohno Tatsuya , Nakayama Yuko , Nakamoto Soken , Kato Shingo , Imai Reiko , Nonaka Tetsuo , Ishikawa Hitoshi , Harashima Koichi , Suzuki Yoshihiko
Published: May 2003

BACKGROUND

Optimal timing of the measurement of serum squamous cell carcinoma (SCC) antigen during radiation therapy (RT) and its significance for predicting the response of cervical carcinoma patients as early as possible remain unknown.

METHODS

Sixty‐three patients with SCC of the uterine cervix who received RT only were studied. Patients were treated with a combination of external beam irradiation and high‐dose rate intracavitary irradiation. The serum SCC antigen level was measured before, every 2 or 3 weeks during, and 1 or 2 months after RT. Clinical outcome was divided into complete response and incomplete response.

RESULTS

Forty‐seven patients (74.6%) had serum SCC antigen levels 1.5 ng/mL (the reference value) before RT. Normalization of serum SCC antigen levels at the end of RT were found to be significantly correlated with complete response in the SCC‐positive patients. It was especially noted that in patients with serum SCC levels between 5–30 ng/mL before RT, a > 70% decrease in the serum SCC antigen level at 4 weeks was correlated significantly with complete response. In this group, a significant correlation also was found between a > 70% decrease in serum SCC level at 4 weeks and the normalization of SCC at the end of RT.

CONCLUSIONS

The current study data suggest that the serum SCC antigen level not only before, but also during and at the end of RT can predict the response of patients with cervical carcinoma and help in identifying those patients who are at high risk of local recurrence and/or distant metastasis. Cancer 2003;97:3114–20. © 2003 American Cancer Society.

DOI 10.1002/cncr.11453
Author reply
Authors: Glaspy John
Published: May 2003

DOI 10.1002/cncr.11454
Author reply
Authors: Akechi Tatsuo , Okamura Hitoshi , Nishiwaki Yutaka , Uchitomi Yosuke
Published: May 2003

DOI 10.1002/cncr.11455
Neoadjuvant chemotherapy for high‐grade central osteosarcoma of the extremity
Authors: Bacci Gaetano , Bertoni Franco , Longhi Alessandra , Ferrari Stefano , Forni Cristiana , Biagini Roberto , Bacchini Patrizia , Donati Davide , Manfrini Marco , Bernini Gabriella , Lari Stefano
Published: May 2003

BACKGROUND

In primary central high‐grade osteosarcoma, a number of distinct subtypes have been identified, but little is known about the response to chemotherapy.

METHODS

The authors investigated whether the subtypes correlated with histologic response to chemotherapy in 1058 patients with osteosarcoma of the extremities who were treated with neoadjuvant chemotherapy over the last 20 years. The tumors were classified as osteoblastic (70%), chondroblastic (13%), fibroblastic (9%), and telangiectatic (6%). At diagnosis, 911 patients had localized disease and 147 had resectable lung metastases.

RESULTS

The response to preoperative chemotherapy was good (90% or more tumor necrosis) in 59% of patients and poor (< 90% tumor necrosis) in 41% of patients. The rate of good responses was significantly higher (P = 0.0001) in the fibroblastic (83%) and telangiectatic (80%) tumors and significantly lower in chondroblastic tumors (43%). Prognosis was significantly correlated with the histologic subtypes. The 5‐year overall survival rate was significantly higher (P = 0.0001) in fibroblastic (83%) and telangiectatic (75%) tumors than in osteoblastic (62%) and chondroblastic (60%) tumors. In all subtypes, except for the chondroblastic subtype, the 5‐year overall survival rate was significantly higher (P = 0.0001) in good responders P = 0.0001 (68%) than in poor responders (52%).

CONCLUSIONS

The authors concluded that the histologic subtype of primary central high‐grade osteosarcoma of the extremity was strictly correlated with histologic response to chemotherapy and probably, as a consequence, also with prognosis. Further studies are needed to establish whether these results justify a specific therapeutic approach based on the histologic subtype of the tumor. Cancer 2003;97:3068–75. © 2003 American Cancer Society.

DOI 10.1002/cncr.11456
A safe and effective method for converting patients from transdermal to intravenous fentanyl for the treatment of acute cancer‐related pain
Authors: Kornick Craig A. , Santiago‐Palma Juan , Schulman Glenn , O'Brien Peter C. , Weigand Stephen , Payne Richard , Manfredi Paolo L.
Published: May 2003

BACKGROUND

The delayed effects (12–16 hours) of transdermal fentanyl make dose titration difficult during acute exacerbations of cancer pain. Patients at the authors' institution routinely are switched from transdermal to intravenous (IV) fentanyl using a 1:1 (transdermal:IV) conversion during severe episodes of pain.

METHODS

The authors evaluated nine consecutive hospitalized patients with cancer who had severe pain for up to 6 days following the conversion from transdermal to IV fentanyl. Pain intensity was rated using an 11‐point (0–10) verbal numeric rating scale (NRS). All 9 patients initially reported their pain intensity with movement as ≥ 8 during treatment with transdermal fentanyl. Eight patients initially reported their pain at rest as ≥ 8. In each patient, all transdermal patches were removed, and a continuous infusion (CI) delivering IV fentanyl at the same hourly rate was initiated simultaneously. Demand boluses of IV fentanyl equivalent in dosage to 50–100% of the CI rate remained available by patient‐controlled analgesia (PCA). Pain intensity (0–10), sedation (0–3), and hourly fentanyl requirements (micrograms per hour) were assessed and recorded immediately prior to patch removal and at least once daily after the initiation of IV fentanyl. The CI and demand boluses were titrated whenever necessary on the basis of pain intensity and supplemental PCA use.

RESULTS

All 9 patients reported mild levels (≤ 4) of pain at rest within 5 days. The median time to achieve mild levels of pain at rest was 1.5 days. Six patients achieved mild levels of pain with movement within 3 days. Three patients never achieved mild levels of pain with movement while receiving IV fentanyl. No serious side effects were reported.

CONCLUSIONS

The conversion from transdermal to IV fentanyl can be accomplished safely and effectively using a 1:1 (transdermal:IV) conversion during acute exacerbations of cancer pain. Cancer 2003;97:3121–4. © 2003 American Cancer Society.

DOI 10.1002/cncr.11457
Role of neurosecretory cells in the photoperiodic induction of pupal diapause of the tobacco hornworm Manduca sexta
Authors: Shiga Sakiko , Davis Norman T. , Hildebrand John G.
Published: June 2003

In the tobacco hornworm, Manduca sexta, pupal diapause can be induced by exposure of fifth‐instar larvae to a short‐day photoperiod. We studied the effect of surgical ablation of tissues containing the neurosecretory cells of the brain of fifth‐instar larvae on the photoperiodic induction of pupal diapause. At the end of the experiments, we immunostained the neurosecretory cells to determine the success of the ablations. Under long‐day conditions (LD 16:8 at 22°C), all intact larvae, most of the sham‐operated larvae, and control‐operated larvae developed into nondiapausing pupae. Under short‐day conditions (LD 10:14 at 22°C), most intact, sham‐operated, and control‐operated larvae developed into diapausing pupae. Removal of type‐II cells did not interfere with the photoperiodic response. Under long‐day conditions, elimination of type‐Ia1 cells did not affect the incidence of nondiapausing pupae. When type‐Ia1 cells were removed under short‐day conditions, however, the incidence of nondiapausing pupae was higher (51%, n = 41) than that of the intact (16%, n = 75), sham‐operated (24%, n = 88), control‐operated larvae (5%, n = 40), and larvae with type‐II cells removed (11%, n = 27). Thus, removal of type‐Ia1 cells can impede induction of diapause. These results indicate that the type‐Ia1 neurosecretory cells have an important role in the induction of pupal diapause. J. Comp. Neurol. 462:275–285, 2003. © 2003 Wiley‐Liss, Inc.
Marked loss of myelinated nerve fibers in the human brain with age
Authors: Marner Lisbeth , Nyengaard Jens R. , Tang Yong , Pakkenberg Bente
Published: June 2003

The white matter is the structure of the brain that declines most with age—almost 30%, but little is known about the age‐effect on the fibers that constitute the white matter. In the present study, the total length of myelinated fibers was measured with a newly developed stereologic method. Specimens came from 36 normal Danes (18 males and 18 females) with an age ranging between 18 and 93 years. Samples were taken systematically and randomly from the white matter, and the biopsy specimens were randomly rotated before sectioning to avoid bias due to the anisotropic nature of nerve fibers. The fibers were counted at light microscopic level at approximately 10,000× magnification, and the diameter of each counted fiber was measured to get the diameter distribution. Males were found to have a total myelinated fiber length of 176,000 km at the age of 20 and 97,200 km at the age of 80, whereas the total length in females was 149,000 km at the age of 20 and 82,000 km at the age of 80. This finding corresponds to a 10% decrease per decade or a total decrease of 45% from the age of 20 to 80 years, and a sex difference of 16%. The fiber diameter distribution showed that primarily the thinner fibers were lost with a relative preservation of the thicker ones. The marked loss of myelinated nerve fibers with age could explain some of the cognitive decline seen in the elderly. J. Comp. Neurol. 462:144–152, 2003. © 2003 Wiley‐Liss, Inc.
Regeneration of myenteric plexus in the mouse colon after experimental denervation with benzalkonium chloride
Authors: Hanani Menachem , Ledder Oren , Yutkin Vladimir , Abu‐Dalu Ribhi , Huang Tian‐Ying , Härtig Wolfgang , Vannucchi Maria‐Giuliana , Faussone‐Pellegrini Maria‐Simonetta
Published: June 2003

Recent reports suggest a far greater plasticity in nerve tissue than previously believed. As the digestive tract is exposed to a variety of insults, this question is relevant to enteric nerves, but little is known about their ability to recover from damage. To address this problem, we ablated the myenteric plexus of the mouse colon with the detergent benzalkonium chloride (BAC) and followed the ensuing morphologic changes for up to 60 days by using light‐ and electron microscopy. We found that, 2 days after BAC application, the treated area was essentially devoid of intact nerve elements. From day 7, new nerve fibers were observed within the denervated region. This growth progressed until, at days 30–60, newly grown nerve fibers were present in most of this region, and the pattern of muscle innervation was similar to the normal one. At least part of these fibers originated at neurons within intact ganglia surrounding the denervated region. The cross‐sectional area of neurons near the denervated region at day 14 was 52% greater than controls. Glial cells were closely associated with the regenerating nerve fibers. From day 14 onward, we observed undifferentiated cells and differentiating neurons in ganglia surrounding the denervated region, and by day 30, new neurons were present in the myenteric region, along with regenerating nerve fibers. We conclude that the myenteric plexus is endowed with a considerable ability of regeneration and plasticity. The results provide evidence for the presence of stem cells and for an adult neurogenesis in this plexus. J. Comp. Neurol. 462:315–327, 2003. © 2003 Wiley‐Liss, Inc.
Abnormal thalamocortical pathfinding and terminal arbors lead to enlarged barrels in neonatal GAP‐43 heterozygous mice
Authors: McIlvain Vera A. , Robertson Douglas R. , Maimone Margaret M. , McCasland James S.
Published: June 2003

GAP‐43 has been implicated in axonal pathfinding and sprouting, synaptic plasticity, and neurotransmitter release. However, its effect on cortical development in vivo is poorly understood. We have previously shown that GAP‐43 knockout (−/−) mice fail to develop whisker‐related barrels or an ordered whisker map in the cortex. Here we used cytochrome oxidase (CO) histochemistry to demonstrate that GAP‐43 heterozygous (+/−) mice develop larger than normal barrels at postnatal day 7 (P7), despite normal body and brain weight. Using serotonin transporter (5HT‐T) histochemistry to label thalamocortical afferents (TCAs), we found no obvious abnormalities in other somatosensory areas or primary visual cortex of GAP‐43 (+/−) mice. However, TCA projections to (+/−) primary auditory cortex were not as clearly defined. To clarify the mechanism underlying the large‐barrel phenotype, we used lipophilic (DiI) axon labeling. We found evidence for multiple pathfinding abnormalities among GAP‐43 (+/−) TCAs. These axons show increased fasciculation within the internal capsule, as well as abnormal turning and branching in the subcortical white matter. These pathfinding errors most likely reflect failures of signal recognition and/or transduction by ingrowing TCAs. In addition, many DiI‐labeled (+/−) TCAs exhibit widespread, sparsely branched terminal arbors in layer IV, reflecting the large‐barrel phenotype. They also resemble those found in rat barrel cortex deprived of whisker inputs from birth, suggesting a failure of activity‐dependent synaptogenesis and/or synaptic stabilization in (+/−) cortex. Our findings suggest that reduced GAP‐43 expression can alter the fine‐tuning of a cortical map through a combination of pathfinding and synaptic plasticity mechanisms. J. Comp. Neurol. 462:252–264, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of aromatase mRNA and protein in the brain and pituitary of female rainbow trout: Comparison with estrogen receptor α
Authors: Menuet Arnaud , Anglade Isabelle , Le Guevel Remy , Pellegrini Elisabeth , Pakdel Farzad , Kah Olivier
Published: June 2003

Recent data indicate that estrogens locally produced in the brain by aromatization of androgens could be important for neurogenesis and brain repair. In this respect, fish are interesting because of the extremely high aromatase activity of their brain. In this study, the rainbow trout brain aromatase was cloned and riboprobes were used to map the distribution of cells expressing the corresponding mRNAs. A very strong hybridization signal was detected in the pituitary and in cells bordering the ventricles in the telencephalon and ventral diencephalon, with the highest expression in the preoptic area and hypothalamus. A weaker signal was detected in the ependymal layer bordering the torus semicircularis and optic tectum. This localization was fully confirmed by immunohistochemistry using antibodies against a teleost aromatase. In addition, this antibody showed that aromatase expression in fact corresponds to radial glial cells because immunoreactive cells had long cytoplasmic processes extending toward the pial surface. Because brain aromatase was shown to be upregulated by estradiol in fish, the distribution of aromatase mRNAs was compared with that of rainbow trout estrogen receptor α (rtERα) on adjacent sections. Although the highest aromatase expression was found in regions expressing rtERα, no obvious coexpression was found, as rtERα was never observed in radial cells. However, reverse transcriptase‐polymerase chain reaction experiments performed on brain cell cultures enriched in glial cells suggest that a weak expression of rtERα in glial cells cannot be excluded. The possible role of the high brain aromatase content in fish could be related to the continuous growth of their central nervous system during adulthood. J. Comp. Neurol. 462:180–193, 2003. © 2003 Wiley‐Liss, Inc.
Expression patterns of epidermal growth factor receptor and fibroblast growth factor receptor 1 mRNA in fetal human brain
Authors: Fu Lijuan , Abu‐Khalil Amir , Morrison Richard S. , Geschwind Daniel H. , Kornblum Harley I.
Published: June 2003

Factors that interact with the epidermal growth factor and fibroblast growth factor receptors have numerous effects in the central nervous system (CNS), inducing the proliferation of CNS stem cells and astrocytes and the survival and differentiation of neurons. Both receptors are expressed in the embryonic rodent brain in proliferative and nonproliferative regions, suggesting roles in numerous developmental processes. However, the roles of these factors in human brain development are not known. In the current study, we examined the expression of human epidermal growth factor receptor (HEGFR) and human fibroblast growth factor receptor 1 (HFGFR1) mRNAs in the human fetal brain. The expression of both receptors is strikingly conserved relative to previously reported patterns in the rodent. In the germinal zones, the sites of cellular proliferation, HFGFR1 was expressed primarily in the ventricular zone, whereas HEGFR was expressed in the subventricular zone, suggesting different roles in CNS progenitor proliferation. Differential expression was also observed in other brain areas examined, including the hippocampus and the cerebellum. The current study suggests that HEGFR and HFGFR1 are likely to play different roles during human brain development, but that these roles will be similar to those observed in the rodent brain. J. Comp. Neurol. 462:265–273, 2003. © 2003 Wiley‐Liss, Inc.
Examination of the relationship between astrocyte morphology and laminar boundaries in the molecular layer of adult dentate gyrus
Authors: Bushong Eric A. , Martone Maryann E. , Ellisman Mark H.
Published: June 2003

Astrocytes are known to play an integral role in the development of compartmental boundaries in the brain and in the creation of trauma‐induced boundaries. However, the physical relationship between astrocytes and such boundaries in the adult brain is less clear. If astrocytes do respect or play an ongoing role in maintaining such boundaries, a correlation between the position of such a boundary and the morphology of neighboring astrocytes might be observable. In this study, we examined the distribution of astrocytes with respect to the laminar boundaries compartmentalizing afferents to the dentate gyrus molecular layer. In addition, we attempted to determine whether astrocyte morphology is influenced by these laminar boundaries. To this end, protoplasmic astrocytes in the adult rat dentate gyrus were revealed with fluorescent tracer dyes and subsequently analyzed with respect to laminar boundaries demarcated by means of immunolabeling for the lamina‐specific molecules EphA4 and neural cell adhesion molecule (N‐CAM). We find that astrocyte distribution is influenced by the boundary separating the associational/commissural and perforant path afferents. In addition, we show that astrocytes in this region are polarized in their morphology, unlike typically stellate astrocytes, but that the laminar boundaries themselves do not appear to confer this morphology. This polarized morphology, however acquired, may have import for the functioning of astrocytes within the highly organized composition of the dentate gyrus molecular layer and for the overall microphysiology of this and other brain regions. J. Comp. Neurol. 462:241–251, 2003. © 2003 Wiley‐Liss, Inc.
Brain nitric oxide synthase expression in the developing ferret lateral geniculate nucleus: Analysis of time course, localization, and synaptic contacts
Authors: Mccauley Anita K. , Carden W. Breckinridge , Godwin Dwayne W.
Published: June 2003

Nitric oxide (NO) is a diffusible neurotransmitter that has been implicated in key developmental events, including the refinement of retinogeniculate axons into ON/OFF sublayers in the ferret lateral geniculate nucleus (LGN), and in the formation of eye‐specific laminae in other species. To understand the role of NO in the LGN, it is critical to fully characterize the pattern of brain nitric oxide synthase (bNOS) expression within the nucleus, including the phenotype of the neural elements that express it. We have examined the temporal and spatial pattern of bNOS expression in the ferret LGN during the first 6 weeks of postnatal development, and in the adult, by detecting bNOS with a monoclonal antibody as well as β‐nicotinamide adenine dinucleotide phosphate–diaphorase histochemistry. We have found that bNOS is expressed in neurons in the A laminae of the LGN as early as postnatal day 7 (P7), a time coincident with eye‐specific segregation of retinal axons. This expression continues through P35, with peak somatodendritic expression at P21. Fluorescent double labeling using antibodies to bNOS and glutamic acid decarboxylase indicate that bNOS is expressed in γ‐aminobutyric acid–ergic interneurons within the A laminae. Electron microscopic examination of bNOS‐labeled cells showed synaptic contacts from terminals with two distinct morphologic profiles. Expression of bNOS within interneurons that receive contacts from multiple sources indicates that the synaptic circuitry associated with bNOS activation and the potential targets of NO may be more complex than originally thought and supports a potential new role for interneurons as cellular intermediaries in the refinement of pathways in the LGN. Our findings broaden the window of time that bNOS may be active within the developing LGN, suggesting an expanded role for NO during early postnatal development. J. Comp. Neurol. 462:342–354, 2003. © 2003 Wiley‐Liss, Inc.
Primary cortical motor neurons undergo apoptosis after axotomizing spinal cord injury
Authors: Hains Bryan C. , Black Joel A. , Waxman Stephen G.
Published: June 2003

Spinal cord injury (SCI) results in loss of voluntary motor control followed by incomplete recovery, which is partly mediated by the descending corticospinal tract (CST). This system is an important target for therapeutic repair strategies after SCI; however, the question of whether apoptotic cell death occurs in these axotomized neurons remains unanswered. In this study, adult (150–175 g) male Sprague‐Dawley rats underwent T9 transection of the dorsal funiculus, which axotomizes the dorsal CST, and introduction of the retrograde tracer Fluoro‐Gold into the lesion site. Primary motor cortex (M1) was then examined for evidence of apoptosis weekly for 4 weeks after injury. Axotomized pyramidal cells, identified by retrograde transport of Fluoro‐Gold, were found in M1 (57.5 ± 9.6/median section, 6,127 ± 292 total), and a significant proportion were terminal deoxynucleotidyl transferase (TdT) ‐mediated deoxyuridine triphosphate (dUTP)‐rhodamine nick end labeling (TUNEL) ‐positive at 1 week after injury (39.3 ± 5.6%), compared with animals undergoing sham surgery (1.2 ± 1.4%). At 2–4 weeks, fewer cells were Fluoro‐Gold–positive (24.6 ± 65.06 to 25.3 ± 6.4/median section, 2,338 ± 233 to 2,393 ± 124 total), of which very few were TUNEL‐positive. In TUNEL‐positive cells, Hoechst 33342 staining revealed nuclear morphology consistent with apoptosis, chromatin condensation, and formation of apoptotic bodies. Fluoro‐Gold–positive cells showed increased caspase‐3 and Bax immunoreactivity. Hematoxylin and eosin staining revealed similar nuclear changes and dystrophic cells. Internucleosomal DNA fragmentation was detected by gel electrophoresis at the 1‐week time point. Lesioned animals not receiving Fluoro‐Gold exhibited the same markers of apoptosis. These results document, for the first time, features of apoptotic cell death in a proportion of axotomized cortical motor neurons after SCI, suggesting that protection from apoptosis may be a prerequisite for regenerative approaches to SCI. J. Comp. Neurol. 462:328–341, 2003. © 2003 Wiley‐Liss, Inc.
Trafficking of the muscarinic m2 autoreceptor in cholinergic basalocortical neurons in vivo: Differential regulation of plasma membrane receptor availability and intraneuronal localization in acetylcholinesterase‐deficient and ‐inhibited mice
Authors: Decossas Marion , Bloch Bertrand , Bernard Veronique
Published: June 2003

In vivo, the abundance of receptors at the neuronal plasma membrane may be critical in the mediation of pre‐ and postsynaptic responses. Thus, we have studied the membrane availability and intraneuronal distribution of the m2 muscarinic autoreceptor (m2R) in cholinergic neurons of the nucleus basalis magnocellularis (NBM) projecting to the frontal cortex (FC). We have studied the subcellular compartmentalization of m2R at somatodendritic postsynaptic and axonal presynaptic sites in control animals (AChE +/+) and in two animal models: mice displaying acute acetylcholinesterase (AChE) inhibition by treatment with metrifonate, and AChE‐deficient mice (AChE ‐/‐). In control animals, m2R was mainly located at the plasma membrane in the somatodendritic field of NBM and in cortical varicosities. Acute AChE inhibition and chronic AChE deficiency induced a dramatic decrease of cell surface m2R in the somatodendritic compartment. This finding was associated with two different intracytoplasmic events: (1) internalization of m2R in endosomes after acute AChE inhibition, (2) exaggerated storage of m2R in the endoplasmic reticulum and Golgi complex in AChE ‐/‐ mice. In contrast, the m2R density was higher at the membrane of cortical varicosities in AChE ‐/‐ mice but unchanged in acutely AChE‐inhibited mice. Our data demonstrate that acute and chronic stimulation provoke, in vivo, depletion of the membrane store of somatodendritic m2R through different intracellular mechanisms: endocytosis of receptors from the plasma membrane to the cytoplasm (acute) or regulation of their delivery from intracytoplasmic stores to the plasma membrane (chronic). The increase of m2R at the membrane of axonal varicosities after chronic stimulation suggest modulation of presynaptic cholinergic activity, including neurotransmitter release. J. Comp. Neurol. 462:302–314, 2003. © 2003 Wiley‐Liss, Inc.
Distribution of glutamate‐gated chloride channel subunits in the parasitic nematode Haemonchus contortus
Authors: Portillo Virginia , Jagannathan Suchitra , Wolstenholme Adrian J.
Published: June 2003

Glutamate‐gated chloride channels (GluCl) are related to γ‐aminobutyric acid‐A (GABAA) receptors and are the target sites for the avermectin/milbemycin (A/M) anthelmintics, drugs that cause paralysis of the somatic and pharyngeal muscles in nematodes. We have previously identified four GluCl subunits, HcGluClα, HcGluClβ, HcGluClα3A, and HcGluClα3B from the sheep parasite Haemonchus contortus. We raised specific antisera against all of these subunits and used them in immunofluorescence experiments on adult parasites. All of the subunits were expressed in the motor nervous system, especially motor neuron commissures. Double‐immunostaining experiments suggested that HcGluClα and HcGluClβ were expressed on the same commissures; these were also stained with an anti‐GABA antibody, suggesting that they may be inhibitory motor neurons. The HcGluClβ subunit was also detected in lateral and sublateral nerve cords. The HcGluClα3A and ‐B subunits, products of an alternatively spliced gene, were expressed in different neurons. We found HcGluClαA in a pair of sensory, possibly amphid, neurons in the head, in addition to the motor neuron commissures. HcGluClα3B was detected in three cell bodies, probably of pharyngeal neurons, and to ventral and lateral cords. These results indicate that the GluCl are widely distributed in the H. contortus nervous system and suggest that they have critical roles controlling locomotion, pharyngeal function, and possibly sensory processing in parasitic nematodes. They also provide an explanation for the observed effects of the A/M anthelmintics. J. Comp. Neurol. 462:213–222, 2003. © 2003 Wiley‐Liss, Inc.
Rats and mice exhibit distinct inflammatory reactions after spinal cord injury
Authors: Sroga Julie M. , Jones T. Bucky , Kigerl Kristina A. , McGaughy Violeta M. , Popovich Phillip G.
Published: June 2003

Spinal contusion pathology in rats and mice is distinct. Cystic cavities form at the impact site in rats while a dense connective tissue matrix occupies the injury site in mice. Because inflammatory cells coordinate mechanisms of tissue injury and repair, we evaluated whether the unique anatomical presentation in spinally injured rats and mice is associated with a species‐specific inflammatory response. Immunohistochemistry was used to compare the leukocytic infiltrate between rats and mice. Microglia/macrophage reactions were similar between species; however, the onset and magnitude of lymphocyte and dendritic cell (DC) infiltration were markedly different. In rats, T‐cell numbers were highest between 3 and 7 days postinjury and declined by 50% over the next 3 weeks. In mice, significant T‐cell entry was not evident until 14 days postinjury, with T‐cell numbers doubling between 2 and 6 weeks. Dendritic cell influx paralleled T‐cell infiltration in rats but was absent in mouse spinal cord. De novo expression of major histocompatability class II molecules was increased in both species but to a greater extent in mice. Unique to mice were cells that resembled lymphocytes but did not express lymphocyte‐specific markers. These cells extended from blood vessels within the fibrotic tissue matrix and expressed fibronectin, collagen I, CD11b, CD34, CD13, and CD45. This phenotype is characteristic of fibrocytes, specialized blood‐borne cells involved in wound healing and immunity. Thus, species‐specific neuroinflammation may contribute to the formation of distinct tissue environments at the site of spinal cord injury in mice and rats. J. Comp. Neurol. 462:223–240, 2003. © 2003 Wiley‐Liss, Inc.
Using a continuous index of laterality to determine how laterality is related to interhemispheric transfer and bimanual coordination in children
Authors: Fagard Jacqueline , Corroyer Denis
Published: June 2003

We sought to determine whether laterality is related to interhemispheric transfer and bimanual coordination during development. Children between 3 and 8 years of age were observed. In the first part of the experiment, we devised a continuous index to order the subjects according to their laterality. The laterality index included evaluation of hand and eye preference, and the right–left performance difference. In the second part of the experiment, we used this single index to determine whether laterality is related to interhemispheric transfer and bimanual coordination. Interhemispheric transfer was assessed by means of two tactile transfer tasks and one visuo–manual transfer task. We assessed bimanual coordination using the tapping task and the bimanual crank‐rotation task. Results showed that right‐ and left‐hand writers overlap on certain measures of laterality. They confirmed the improvement of interhemispheric transfer at around age 5 years, earlier progress in bimanual coordination with mirror than with parallel movements, and the existence of a relationship between visuo–manual interhemispheric transfer and bimanual coordination. The laterality index was not related to interhemispheric transfer, but it was related to the younger subjects' performance on the bimanual crank‐rotation task: the less right handed, the better the bimanual coordination. In addition, on the same bimanual task, crossed hand–eye laterality was associated with better performance. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 44–56, 2003.
Placentophagia in rabbits: Incidence across the reproductive cycle
Authors: Melo Angel I. , González‐Mariscal Gabriela
Published: June 2003

Rabbits show placentophagia at parturition, but the regulation of this behavior and its incidence across the reproductive cycle are unknown. By testing estrous, midpregnant, prepartum (day 1), and postpartum (days 1 and 5) food‐deprived rabbits with liver and placenta, we found an absence or infrequency (<%) of placentophagia in the former three groups, an invariable occurrence at parturition, and a persistence into postpartum days 1 and 5 (50 and 48%, respectively). Most placentophagic females also ate liver on postpartum day 1, but not on postpartum day 5. In different food‐deprived rabbits, tested every 2 hr with placenta and food pellets, placentophagia incidence was 20% at 8 hr prepartum, 100% at parturition, and 67 and 21% at 8 and 24 hr postpartum, respectively. Most placentophagic rabbits also ate food pellets in postpartum (but not in prepartum) tests. Results suggest that somatosensory, hormonal, or both factors of the peripartum period regulate placentophagia expression. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 37–43, 2003.
Effects of perinatal visual stimulation on preference, growth, and mortality in African clawed frogs (Xenopus Laevis)
Authors: Mann Katherine M. , Sleigh Merry J.
Published: June 2003

Two exploratory experiments examined the effects of flashing light stimulation on growth, mortality, and behavioral preferences of Xenopus laevis tadpoles. Experiment 1 showed that tadpoles exposed to continuous visual stimulation, from egg‐laying through postnatal day 40, had significantly higher mortality rates and weighed significantly less than controls. In contrast to controls, experimental tadpoles showed a preference for visual stimulation throughout early development. Results support the notion that augmented visual stimulation during early development affects species‐typical development and the creation of postnatal preferences. Experiment 2 exposed subjects to propranolol in their water to investigate a potential sympathetic nervous system (SNS) mechanism responsible for the previous results. Tadpoles exposed to propranolol and visual stimulation simultaneously did not show a preference for the visual stimulation. Although this preliminary finding suggests SNS involvement, this notion deserves further investigation. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 28–36, 2003.
The effects of isolation rearing on open‐field behavior in male rats depends on developmental stages
Authors: Arakawa Hiroyuki
Published: June 2003

The effects of the duration of isolation and age during isolation on open‐field behavior in rats were examined. An inner wall divided the floor of the field into two areas, a peripheral alley and the center square, and the subjects' behavior in each area was measured. An increase in the tendency to avoid the center square was found in rats isolated during their juvenile stage, which disappeared if they were reared in pairs for a long period after isolation. On the other hand, subjects isolated during their postmaturity stage displayed an increased tendency to approach the center square whereas isolation during sexual maturity had no effect. The duration of isolation showed no consistent effect; rather, the effect depended on the age of the subjects during isolation. These findings suggest that isolation affects the open‐field behavior of rats in various ways, depending on their age during isolation. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 11–19, 2003.