bluuebunny/crossref_metadata_2025 huggingface dataset:
Femoral head of the rectus femoris muscle
Authors: Tubbs R. Shane , Salter George , Oakes W. Jerry
Published: March 2004

Variability of the muscles of the anterior thigh is minimal. After review of the extant medical literature, we believe this to be the first reported case of a femoral head of the left and right rectus femoris muscles. In addition to this anomaly, our anatomic specimen demonstrated an accessory head of the right brachialis muscle and the quadratus plantae muscles inserted into the tendons of both the flexor hallucis longus and flexor digitorum longus. In clinical practice, knowledge of the possibility of an anomalous accessory femoral head of the rectus femoris muscle in clinical practice would be useful for those who might palpate this unusual muscle or encounter it surgically. Clin. Anat. 17:276–278, 2004. © 2004 Wiley‐Liss, Inc.
Restoration of motor function of the deep fibular (peroneal) nerve by direct nerve transfer of branches from the tibial nerve: An anatomical study
Authors: Bodily Kale D. , Spinner Robert J. , Bishop Allen T.
Published: March 2004

Traction injuries of the common fibular (peroneal) nerve frequently result in significant morbidity due to tibialis anterior muscle paralysis and the associated loss of ankle dorsiflexion. Because current treatment options are often unsuccessful or unsatisfactory, other treatment approaches need to be explored. In this investigation, the anatomical feasibility of an alternative option, consisting of nerve transfer of motor branches from the tibial nerve to the deep fibular nerve, was studied. In ten cadaveric limbs, the branching pattern, length, and diameter of motor branches of the tibial nerve in the proximal leg were characterized; nerve transfer of each of these motor branches was then simulated to the proximal deep fibular nerve. A consistent, reproducible pattern of tibial nerve innervation was seen with minor variability. Branches to the flexor hallucis longus and flexor digitorum longus muscles were determined to be adequate, based on their branch point, branch pattern, and length, for direct nerve transfer in all specimens. Other branches, including those to the tibialis posterior, popliteus, gastrocnemius, and soleus muscles were not consistently adequate for direct nerve transfer for injuries extending to the bifurcation of the common fibular nerve or distal to it. For neuromas of the common fibular nerve that do not extend as far distally, branches to the soleus and lateral head of the gastrocnemius may be adequate for direct transfer if the intramuscular portions of these nerves are dissected. This study confirms the anatomical feasibility of direct nerve transfer using nerves to toe‐flexor muscles as a treatment option to restore ankle dorsiflexion in cases of common fibular nerve injury. Clin. Anat. 17:201–205, 2004. © 2004 Wiley‐Liss, Inc.
Study on the anatomical dimensions of the human sigmoid colon
Authors: Bhatnagar B.N.S. , Sharma C.L.N. , Gupta S.N. , Mathur M.M. , Reddy D.C.S.
Published: March 2004

Although the sigmoid colon is commonly afflicted with disease, studies on its anatomical dimensions are scarce. It is suspected that dimensions of the sigmoid colon change with age. This study documents data on the anatomical measurements of the sigmoid colon in 70 Indian subjects (51 live and 19 cadavers). Seven parameters of sigmoid colon anatomy measured included length and width of the sigmoid colon and mesocolon at specific points. Three mesocolic indices (width to length ratios) were calculated. Comparisons of measurements in the live and cadaver subjects and in the two sexes were made. The relationship of change in parameters with age was assessed. Appropriate statistical methods were used and the differences were considered significant at P ⩽ 0.05. The study showed wide ranging variations in the values of various measured parameters of the sigmoid colon. Seven patterns of the shape of the sigmoid loop were identified. In the commonest pattern the sigmoid mesocolon was vertically longer than wide (dolichomesocolic), the sigmoid loop having its maximum convexity located just a little proximal to the apex. Patterns where the width of the mesocolon was greater than the vertical length (brachymesocolic) were also observed. The gender analysis showed that the sigmoid mesocolon of the female was brachymesocolic (wider than long), whereas that of the male was dolichomesocolic (longer than wide). This might explain the higher incidence of sigmoid volvulus in the male. This study also showed that the measurements of the sigmoid colon and its mesocolon do not change significantly within the age range of 16–60 years in the two sexes. Also noteworthy is the observation that in the cadaver the sigmoid colon shows considerable shrinkage, particularly of its mesocolon; consequently the data from cadaver subjects, though valuable for anthropometric use, have limitations when used for clinical applications. Clin. Anat. 17:236–243, 2004. © 2004 Wiley‐Liss, Inc.
Lateral costal artery: Accessory thoracic vessel of clinical interest
Authors: Barberini F. , Cavallini A. , Carpino G. , Correr S. , Brunone F.
Published: March 2004

The lateral costal artery (LCA), a supernumerary branch of the internal thoracic artery (ITA), occurs in several ethnic groups on one side of the thorax or on both, in 15–30% of cases. It has been considered responsible for the “steal‐syndrome” of the coronary blood after coronary artery bypass grafting and it used occasionally for myocardial revascularization. To clarify its functional significance, an interpretation based on our findings and human and comparative anatomy and embryology has been attempted. We report on a case where a right LCA of about 2 mm in caliber, rising from the ITA 2.5 cm below the subclavian, coursed as far as the 4th intercostal space for a distance of 13 cm after the anterior axillary line. Anastomosing with the intercostal arteries, it can act as a blood derivative circuit of the thoracic wall. Embryologically, this artery, like the normal parietal arteries of the trunk, might form a longitudinal channel connecting the intersegmental arteries. In mammals having a thoracic cage transversely restricted (quadrupeds), the ITA is more lateral than in primates having a circular thorax, and gives off a ventral branch toward the sternum. It might be hypothesized that the sternal branch occurring in quadrupeds, undergoing adaptation to the thoracic shape of primates, may become the main trunk of the ITA, whereas the LCA may be the remnant of the ITA of quadrupeds. Because the LCA ran partly along the “milk line” of humans, it might be regarded as a supernumerary mammary artery. Clin. Anat. 17:218–226, 2004. © 2004 Wiley‐Liss, Inc.
The use of complementary and alternative medical providers by insured cancer patients in Washington state
Authors: Lafferty William E. , Bellas Allen , Corage Baden Andrea , Tyree Patrick Timothy , Standish Leanna J. , Patterson Ruth
Published: March 2004

BACKGROUND

Insurance coverage of complementary and alternative medicine (CAM) is expanding. However, to the authors' knowledge, little is know concerning CAM utilization among cancer patients under the insurance model of financing. In this study, the authors evaluated CAM provider utilization by cancer patients in a state that requires the inclusion of alternative practitioners in private, commercial insurance products.

METHODS

An analysis was carried out of year 2000 claims data from two large Washington State insurance companies.

RESULTS

Of 357,709 claimants, 7915 claimants (2.3%) had a cancer diagnosis. Among cancer patients, 7.1% had a claim for naturopathy, acupuncture, or massage; and 11.6% had a claim for chiropractic during the study year. The use of naturopathy (odds ratio [OR], 2.0; P < 0.001) and acupuncture (OR, 1.4; P < 0.001) were more common, and the use of chiropractic was less common (OR, 0.9; P < 0.001) for cancer patients compared with those without cancer. No significant differences were noted in the use of massage between the two groups. Except in 2 individuals (0.03%), cancer patients also had at least 1 conventional provider claim during the year. Factors associated with nonchiropractic alternative provider use were female gender, the presence of metastatic cancer, hematologic malignancy, and the use of chemotherapy. Increased use of naturopathic physicians accounted for much of this trend. Musculoskeletal pain was the most common diagnosis at the CAM provider visit. Billed amounts for alternative services were < 2% of the overall medical bills for cancer patients.

CONCLUSIONS

A substantial number of insured cancer patients will use alternative providers if they are given the choice. The cost of this treatment is modest compared with conventional care charges. For individuals with cancer, CAM providers do not appear to be replacing conventional providers but instead are integrated into overall care. Cancer 2004;100:1522–30. © 2004 American Cancer Society.
Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole
Authors: Cheung Annie N. Y. , Khoo Ui Soon , Lai Caroline Y. L. , Chan Kelvin Y. K. , Xue Wei‐Cheng , Cheng Danny K. L. , Chiu Pui‐Man , Tsao Sai‐Wah , Ngan Hextan Y. S.
Published: March 2004

BACKGROUND

Hydatidiform mole (HM) is classified into partial (PHM) and complete (CHM) subtypes according to histopathologic and genetic criteria. Traditionally, it is believed that PHM carries a better prognosis and rarely develops metastasis. However, making a distinction between PHM and CHM using histologic criteria alone may be difficult.

METHODS

The authors used fluorescent microsatellite genotyping following laser‐capture microdissection and chromosome in situ hybridization (CISH) to perform a genetic analysis of six patients with histologically diagnosed PHM who subsequently developed metastatic gestational trophoblastic neoplasia.

RESULTS

Patients ranged in age from 25 years to 44 years (mean, 33.2 years). The gestational age of the molar pregnancies varied from 6 weeks to 20 weeks. All six patients had pulmonary metastases, with additional liver metastasis in two patients. Among the six patients with histologically diagnosed PHM, it was found that four patients had a diploid karyotype and no maternal alleles; thus, their neoplasms actually were CHM. Maternal genome was detected in the remaining two patients consistent with a biparental origin, and these patients had a triploid karyotype. CISH findings in all patients correlated with the genotyping findings. Triploid HM had maternally derived alleles, whereas diploid HMs were purely androgenetic.

CONCLUSIONS

In the current study, which may be the largest series of genetically analyzed metastatic PHMs to date, the difficulty of histologic distinction between PHM and CHM was confirmed. Molecular analysis may help to refine the classification of HM. Although the current findings support the belief that most aggressive trophoblastic diseases are derived from CHM, a small number of PHMs do progress to metastatic disease. Thus, the current study reaffirmed that all patients with HM should be followed closely irrespective of histologic subclassification. Cancer 2004;100:1411–7. © 2004 American Cancer Society.
Intracranial meningeal hemangiopericytoma: The role of radiotherapy
Authors: Soyuer Serdar , Chang Eric L. , Selek Ugur , McCutcheon Ian E. , Maor Moshe H.
Published: March 2004

BACKGROUND

The current retrospective study was undertaken to evaluate the treatment outcomes of patients with meningeal hemangiopericytoma (M‐HPC), to define the role of radiotherapy in the management of the disease, and to report on the patterns of failure.

METHODS

The medical records of 29 patients with nonmetastatic M‐HPC treated at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between August 1979 and March 1999 were reviewed. Fifteen patients (52%) underwent macroscopic total resection (‘gross total resection’ [GTR]), 10 (34%) underwent subtotal resection (STR), and 4 (14%) had unknown extent of surgery. Ten of 24 patients received adjuvant radiotherapy.

RESULTS

The 5, 10, and 15‐year overall survival rates were 85%, 68%, and 43%, respectively. The local control rates at 5 and 10 years were 68% and 22%, respectively. Two patients experienced disease recurrence at another intracranial site. Sixteen patients (55%) developed extraneural metastases. Four patients (14%) developed spinal metastases. The 5‐, 10‐, and 15‐year distant metastasis–free survival rates were 80%, 46%, and 21%, respectively. The 5‐year local control rates for patients treated with GTR and STR were 84% and 38%, respectively (P = 0.003). Of the 15 patients treated with GTR, 3 received adjuvant radiotherapy as part of their initial treatment. Malignant disease did not recur locally in these three patients. However, the effect of the adjuvant radiotherapy on local control was not statistically significant.

CONCLUSIONS

M‐HPCs can recur locally or distantly in the neural axis or as extraneural distant metastases. Based on literature review and the patterns of failure in the current series, attempting to perform GTR followed by limited‐field radiotherapy appeared to represent a reasonable approach for the initial management of M‐HPC. Cancer 2004;100:1491–7. © 2004 American Cancer Society.
Strongyloidiasis in patients at a comprehensive cancer center in the United States
Authors: Safdar Amar , Malathum Kumthorn , Rodriguez Saul J. , Husni Rola , Rolston Kenneth V. I.
Published: March 2004

BACKGROUND

The frequency of Strongyloides stercoralis infestation and complication in patients with cancer in the United States is unknown.

METHODS

The authors performed a retrospective analysis of S. stercoralis infection in patients who were undergoing cancer treatment at The University of Texas M. D. Anderson Cancer Center (Houston, TX).

RESULTS

The overall S. stercoralis infection frequency was approximately 1.0 per 10,000 new cancer cases between 1971 and 2003. Twenty‐two of 25 patients (88%) were U.S. residents (19 from Texas; 1 each from Mississippi, Tennessee, and Puerto Rico), and the remaining 3 (13%) were from Latin America. Thirteen (52%) had solid‐organ malignancies, whereas 12 (48%) had hematologic malignancies (lymphoma or multiple myeloma, n = 8; leukemia, n = 3; aplastic anemia, n = 1). Twelve patients (48%) received systemic corticosteroids, 9 (36%) received antineoplastic therapy, and 2 underwent hematopoietic stem cell transplantation (HSCT). Diarrhea was reported in 13 patients (57%), and eosinophilia was observed in 11 patients (48%); 4 patients (16%) had probable hyperinfection syndrome (in 3 cases of polymicrobial gram‐negative bacteremia, 1 patient had Klebsiella pneumoniae pneumonia, whereas 1 patient presented with K. pneumoniae lung infection alone). Evidence of definite pulmonary hyperinfection syndrome was observed in 2 HSCT recipients (8%). Fourteen (74%) of 19 patients responded to thiabendazole therapy. Two patients with definite pulmonary hyperinfection syndrome developed fatal S. stercoralis hemorrhagic alveolitis despite receiving high‐dose thiabendazole plus ivermectin therapy.

CONCLUSIONS

In the current study, strongyloidiasis was uncommon in patients with cancer and remained localized in individuals with solid‐organ malignancies. Definite pulmonary accelerated autoinfections were observed only in HSCT recipients. Therefore, pre‐HSCT S. stercoralis screening in individuals from endemic regions of the United States warrants further study. Cancer 2004;100:1531–6. © 2004 American Cancer Society.
Risk perception and concern among brothers of men with prostate carcinoma
Authors: Beebe‐Dimmer Jennifer L. , Wood David P. , Gruber Stephen B. , Chilson Doug M. , Zuhlke Kimberly A. , Claeys Gina B. , Cooney Kathleen A.
Published: March 2004

BACKGROUND

It is important for clinicians, researchers, and others who shape public health policy to understand the demographic correlates and psychologic factors that drive health behaviors, such as screening for early detection of cancer, particularly among individuals at high risk for developing the disease.

METHODS

One‐hundred eleven men whose brothers were diagnosed with prostate carcinoma completed a computer‐assisted telephone interview aimed to assess their perception of absolute risk and concern about developing prostate carcinoma over the next 10 years and across their lifetime. Comparisons were made between selected demographic, behavioral, family pedigree characteristics, and measures of perceived risk and concern.

RESULTS

The majority of men perceived their personal risk of developing prostate carcinoma to be ≥ 50%. Men who at the time of the interview were younger than their affected brother were significantly more concerned about prostate carcinoma and perceived their risk to be higher than men who were older than their brother. Estimates of personal risk and concern were also uniformly higher among men with more than one first‐degree relative affected with prostate carcinoma compared to men with only one affected first‐degree relative. Risk perception and concern about an impending prostate carcinoma diagnosis were associated with the use of supplements marketed for prostate health.

CONCLUSIONS

The findings indicated that birth order in relation to a brother diagnosed with prostate carcinoma is significantly associated with risk perception and concern in unaffected family members. These results highlight the need for further study of the familial dynamics and characteristics that drive health behaviors and stress importance of public health education to inform men of personal risk assessment as well as the risks and benefits of screening. These studies ultimately can contribute to the success of strategies for the primary prevention and early detection of cancer. Cancer 2004;100:1537–44. © 2004 American Cancer Society.
Phase I and pharmacokinetic study of a low‐clearance, unilamellar liposomal formulation of lurtotecan, a topoisomerase 1 inhibitor, in patients with advanced leukemia
Authors: Giles Francis J. , Tallman Martin S. , Garcia‐Manero Guillermo , Cortes Jorge E. , Thomas Deborah A. , Wierda William G. , Verstovsek Srdan , Hamilton Marta , Barrett Emma , Albitar Maher , Kantarjian Hagop M.
Published: March 2004

BACKGROUND

OSI‐211 is a low‐clearance, unilamellar liposomal formulation of a water‐soluble camptothecin analogue, lurtotecan. OSI‐211 has significant activity in severe combined immunodeficient mouse models of human leukemia.

METHODS

This study was conducted to define the dose‐limiting toxicities (DLT) and pharmacokinetics of OSI‐211 in patients with refractory myeloid leukemias. Patients with refractory acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelogenous leukemia in blastic phase (CML‐BP) were eligible. OSI‐211 was given as an intravenous infusion over 30 minutes daily for 3 days. The starting dose was 1.5 mg/m2 per day (4.5 mg/m2 per course). The dose was escalated by 50% until Grade 2 toxicity was observed and then by 30–35% until the DLT was defined. Serial plasma and urine samples were collected, and drug levels were determined by high‐performance liquid chromatography with fluorescence detection.

RESULTS

Twenty patients (18 patients [90%] with AML, and 1 patient each [5%] with MDS and CML‐BP) were treated. Mucositis and diarrhea were considered to be the DLTs. The maximum tolerated dose was 3.7 mg/m2 per day. Fourteen of 18 evaluable patients (78%) with AML or MDS achieved transient bone marrow aplasia. The mean systemic clearance of lurtotecan in plasma was 0.946 ± 1.53 L/hour/m2. Urinary recovery of lurtotecan was 6.66% ± 5.26% (range, 1.05–18.4%).

CONCLUSIONS

Liposomal encapsulation of lurtotecan altered its metabolism significantly. There was no evident correlation between exposure, as measured by plasma pharmacokinetics of lurtotecan, and clinical response or toxicities. OSI‐211 merits further study in hematologic malignancies. Cancer 2004;100:1449–58. © 2004 American Cancer Society.
A Ser49Cys variant in the ataxia telangiectasia, mutated, gene that is more common in patients with breast carcinoma compared with population controls
Authors: Buchholz Thomas A. , Weil Michael M. , Ashorn Cheryl L. , Strom Eric A. , Sigurdson Alice , Bondy Melissa , Chakraborty Ranajit , Cox James D. , McNeese Marsha D. , Story Michael D.
Published: March 2004

BACKGROUND

Mothers of children who have ataxia telangiectasia have been reported to be at increased risk for development of breast carcinoma. To test whether sequence variants in the ataxia telangiectasia, mutated, gene (ATM) are associated with breast carcinoma, the authors compared the frequency of ATM cDNA sequence changes in patients with breast carcinoma with the corresponding frequency in control patients.

METHODS

The authors sequenced ATM cDNA from 91 patients with breast carcinoma and compared the frequencies of sequence changes in these patients with the corresponding frequencies in a control sample of 940 individuals with no history of malignant disease.

RESULTS

Thirty‐five patients with breast carcinoma had one or more single‐base changes in ATM. Three genetic variants were found in at least two patients. These variants resulted in Asp1853Asn, Pro1054Arg, or Ser49Cys amino acid substitutions in the ATM protein. The Ser49Cys variant was more common in patients with breast carcinoma than in the control patients, with respective frequencies of 6.7% (5 of 75 patients) and 1.3% (12 of 940 patients; P = 0.006; Fisher two‐sided exact test). The subgroup of patients with bilateral breast carcinoma had a Ser49Cys frequency of 11.8% (2 of 17 patients), which again was significantly different from what was observed in the control group (P = 0.024; Fisher two‐sided exact test). The allele frequencies of the other two variants were not different between case patients and control patients.

CONCLUSIONS

Patients with breast carcinoma, particularly those with bilateral disease, were more likely to have a variant in the ATM gene that resulted in a Ser49Cys substitution in the gene product. Additional studies are needed to evaluate the potential functional consequences of the Ser49Cys substitution and confirm the relevance of this variant in the development of breast carcinoma. Cancer 2004;100:1345–51. © 2004 American Cancer Society.
Time‐dependent effects on survival in breast carcinoma
Authors: Warwick Jane , Tabàr Lazlo , Vitak Bedrich , Duffy Stephen W.
Published: March 2004

BACKGROUND

Tumor size, lymph node status, and histologic grade are reported to be important predictors of survival in the first 5 years after the diagnosis of invasive breast carcinoma. However, to the authors' knowledge, the effect of these factors in the longer term (> 10 years after diagnosis) is not yet clear.

METHODS

It is now > 20 years since the Swedish Two‐County Trial of breast carcinoma screening with mammography was instigated and long‐term follow‐up is now available to December 1998. In the current study, the authors analyzed the effects of tumor size, lymph node status, and tumor grade on survival to death from breast carcinoma using Cox regression and frailty models that allow the baseline hazard and/or effect of a covariate to vary with time.

RESULTS

The effects of tumor size, lymph node status, and tumor grade were shown to progressively diminish with time from diagnosis. The Cox regression model with time‐varying coefficients and a dampening parameter then was fitted to allow for the attenuation of prognostic effects; tumor size, lymph node status, and tumor grade were all found to be highly significant (P< 0.001).

CONCLUSIONS

The results of the current study suggest that long‐term survival in women with invasive breast carcinoma could be modelled satisfactorily using either frailty models or Cox regression models with time‐varying coefficients. The results also suggest that the value of tumor grade, lymph node status, and tumor size at the time of diagnosis have a lasting influence on subsequent survival, albeit attenuated in later years. The long‐term effects of these prognostic factors may explain the fact that the impact of mass screening programs on breast carcinoma mortality rates is still apparent many years later. Cancer 2004;100:1331–6. © 2004 American Cancer Society.
An assessment of World Health Organization criteria for severe acute respiratory syndrome in patients with cancer
Authors: Gu Jin , Wu Aiwen , Li Jiyou , Zhang Xiaopeng , Fang Jian , Li Ming , Yao Yunfeng , Ke Yang , Gu Jiang , Chen Mingzhe , You Weicheng
Published: March 2004

BACKGROUND

The differential diagnosis of severe acute respiratory syndrome (SARS) in patients with cancer can be challenging. Although diagnostic criteria for SARS have been issued by the World Health Organization (WHO), simple adoption of the established criteria may lead to overdiagnosis in patients with cancer or to an increase in the risk of spreading SARS within cancer hospitals.

METHODS

The authors report their experience with the exclusion and quarantine of patients with cancer during the peak of the SARS epidemic in Beijing, China. The patients included 4 males and 7 females with a median age of 66 years (range, 39–73 years).

RESULTS

All 11 patients met the WHO diagnostic criteria for probable SARS. Among those 11 patients with probable SARS, only 1 had confirmed SARS; for the other 10 patients, the possibility of SARS infection was ruled out.

CONCLUSIONS

Special attention must be paid to patients with cancer who have symptoms similar to those seen in SARS. Although the WHO diagnostic criteria for SARS should be widely accepted, they are not definite or practical in certain populations. Cancer 2004;100:1374–8. © 2004 American Cancer Society.
Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma
Authors: Rizzieri David A. , Johnson Jeffrey L. , Niedzwiecki Donna , Lee Edward J. , Vardiman James W. , Powell Bayard L. , Barcos Maurice , Bloomfield Clara D. , Schiffer Charles A. , Peterson Bruce A. , Canellos George P. , Larson Richard A.
Published: March 2004

BACKGROUND

The objective of the current study was to evaluate the efficacy of intensive chemotherapy with and without cranial radiation for central nervous system (CNS) prophylaxis in adults with Burkitt leukemia or lymphoma.

METHODS

Patients received 18 weeks of therapy. Prophylactic cranial radiation (2400 centigrays) and 12 doses of triple intrathecal chemotherapy were administered to the first cohort of patients. A subsequent cohort received the same therapy, with the exceptions that intrathecal therapy was reduced to six doses and radiotherapy was administered only to high‐risk individuals.

RESULTS

The median follow‐up durations were 6.8 years in Cohort 1 and 4.1 years in Cohort 2. Three occurrences of transverse myelitis, 2 severe neuropathies, 3 cases of aphasia, and 1 case of blindness were documented in the first cohort of 52 patients (Cohort 1). In the subsequent cohort of 40 patients (Cohort 2), none of these occurrences were observed, and patients experienced less neurologic toxicity overall (61% vs. 26%; P = 0.001). Responses were similar, and the 3‐year event‐free survival rate was 0.52 (95% confidence interval, 0.38–0.65) for Cohort 1 and 0.45 (0.29–0.60) for Cohort 2.

CONCLUSIONS

Intensive, short‐duration chemotherapy with less intensive CNS prophylaxis led to control at this sanctuary site with little neurotoxicity and may be curative for adults with Burkitt leukemia or lymphoma. Cancer 2004;100:1438–48. ©2004 by the American Cancer Society.
CVD of Epitaxial SnO2 Films by the SnI4/O2 Precursor Combination
Authors: Sundqvist J. , Ottosson M. , Hårsta A.
Published: March 2004

Thin films of SnO2 have been successfully deposited by CVD using the SnI4/O2 precursor combination. Depositions were carried out in the temperature range 350–700 °C on α‐Al2O3(012) substrates. The growth kinetics and conditions for epitaxial growth were investigated. From 350 °C to 475 °C, the growth rate was controlled by surface kinetics and increased exponentially from 5 nm h–1 to 735 nm h–1. Two different surface reactions are proposed, one at low temperatures involving SnI4, and one at high temperatures involving SnI2. Above 475 °C the growth rate was controlled by mass transport of the tin‐containing species. The epitaxial relationships were established to the in‐plane orientation relationships, [010]∥[100] and [10$\bar 1$]∥[$\bar 1$$\bar 2$1]. No iodine contamination was detected by X‐ray photoelectron spectroscopy (XPS).
Sonic hedgehog signaling plays an essential role during embryonic salivary gland epithelial branching morphogenesis
Authors: Jaskoll T. , Leo T. , Witcher D. , Ormestad M. , Astorga J. , Bringas Pablo , Carlsson P. , Melnick M.
Published: March 2004

Gene targeting studies indicate that sonic hedgehog (Shh) signaling plays an essential role during craniofacial development. Because numerous mandibular derivatives (e.g., teeth, tongue, Meckel's cartilage) are absent in Shh null mice and the embryonic submandibular salivary gland (SMG) develops from the mandibular arch, we postulated that Shh signaling is important for embryonic SMG development. To address this question, we first determined the spatiotemporal distribution of Shh; two transmembrane proteins, patched 1 (Ptc) and Smoothened (Smo), which act as a negative or a positive regulator of the Shh signal, respectively; and the Gli 3 transcription factor, which is downstream of the Shh signal. The epithelial localization of Shh, Ptc, Smo, and Gli 3 suggests that Shh signaling may act within the epithelium in a juxtacrine manner. The SMG phenotype in our embryonic day (E) 18.5 Shh null mice can be characterized as “paedomorphic,” that is, it fails to progress to ontogenic stages beyond the Early Pseudoglandular (∼E14). In a complementary set of experiments, we used organ culture to evaluate the effect of enhanced or abrogated Shh signaling on embryonic SMG development in vitro. Paired E13 (Late Initial Bud stage) or E14 (Pseudoglandular stage) SMGs were cultured in the presence or absence of exogenous Shh peptide supplementation; Shh‐supplemented explants exhibit a significant stage‐dependent increase in branching morphogenesis compared with control explants. Furthermore, by using cyclopamine, a steroidal alkaloid that specifically disrupts the Shh pathway, to abrogate endogenous Shh signaling in vitro, we found a significant decrease in branching in cyclopamine‐treated explants compared with controls, as well as a significant decrease in epithelial cell proliferation. Our results indicate that Shh signaling plays an essential role during embryonic SMG branching morphogenesis. Exogenous FGF8 peptide supplementation in vitro rescues the abnormal SMG phenotype seen in cyclopamine‐treated explants, demonstrating that overexpression of a parallel, but related, downstream signaling pathway can compensate for diminished Shh signaling and restore embryonic SMG branching morphogenesis. Developmental Dynamics 229:722–732, 2004. © 2004 Wiley‐Liss, Inc.
Developmental expression of the POU domain transcription factor Brn‐3b (Pou4f2) in the lateral line and visual system of zebrafish
Authors: DeCarvalho Ana C. , Cappendijk Susanne L.T. , Fadool James M.
Published: March 2004

Members of the class IV POU domain transcription factors are important regulators of neural development. In mouse, Brn‐3b (Pou4f2, Brn3.2) and Brn‐3c (Pou4f3, Brn3.1) are essential for the normal differentiation and maturation of retinal ganglion cells (RGCs) and hair cells of the auditory system, respectively. In this report, the cloning and expression profile of brn‐3b in the zebrafish (Danio rerio) were assessed as the first step for understanding its role in the development of sensory systems. Two brn‐3b alternative transcripts exhibited different onset of expression during development but shared overlapping expression domains in the adult visual system. The brn‐3b expression in the zebrafish retina was consistent with a conserved role in differentiation and maintenance of RGCs. Expression was also observed in the optic tectum. Unexpectedly, brn‐3b was prominently expressed in the migrating posterior lateral line primordium and larval neuromasts. For comparison, brn‐3c expression was limited to the otic vesicle and was not detected in the lateral line during embryonic development. The expression of brn‐3b in the mechanosensory lateral line of fish suggests a conserved function of a class IV POU domain transcription factor in sensory system development. Developmental Dynamics 229:869–876, 2004. © 2004 Wiley‐Liss, Inc.
Identification of a nonchordate‐type classic cadherin in vertebrates: Chicken Hz‐cadherin is expressed in horizontal cells of the neural retina and contains a nonchordate‐specific domain complex
Authors: Tanabe Koji , Takeichi Masatoshi , Nakagawa Shinichi
Published: March 2004

Classic cadherins mediate calcium‐dependent cell–cell adhesion in a variety of animals, but there are marked differences in their domain structures between chordate and nonchordate animals. The extracellular domain of chordate‐type classic cadherins (type I and type II classic cadherins) consists of five tandem repeats of conserved sequences called EC domains, whereas that of nonchordate‐type classic cadherins (designated as type III classic cadherin) contains a variable number of EC domains, followed by a characteristic domain complex made of laminin‐A globular domains and EGF‐like repeats. In the present study, we identified a novel vertebrate type III cadherin showing high sequence similarity to Drosophila N‐cadherin, and named this molecule chicken Hz‐cadherin (cHz‐cadherin), because of the distinct expression in horizontal cells of the neural retina. cHz‐cadherin functioned as an adhesion molecule when introduced into cultured cells. Database search revealed one cHz‐cadherin homologue in zebrafish and two in puffer fish, but none in other vertebrate species examined. These observations indicate that type III classic cadherins have been conserved in vertebrate species, being expressed by limited cells types, but lost in particular phylogenic groups of the vertebrates. Developmental Dynamics 229:899–906, 2004. © 2004 Wiley‐Liss, Inc.
Characterization of c‐Kit and nestin expression during islet cell development in the prenatal and postnatal rat pancreas
Authors: Yashpal Nina Kaur , Li Jinming , Wang Rennian
Published: March 2004

It has been well documented that there are abundant endocrine progenitor cells in the neonatal pancreas. However, little is known of their relative proportions or even their phenotypes. The aim of this study was to examine the normal distribution and characteristics of putative endocrine precursor cells, identified by c‐Kit or nestin expression, within the prenatal and postnatal rat pancreas during islet cell development. Here, we provide evidence of the existence of a subset of ductal, islet, and acinar cells with an immature morphology and high proliferative capacity that expressed c‐Kit or nestin. The proportion of islet cells expressing c‐Kit or nestin was highest at embryonic day 18 (25 ± 4% and 28 ± 6%) and decreased significantly by postnatal day 28 (P < 0.01), 1.3 ± 0.2% and 5.7 ± 1%, respectively. The expression of nestin mRNA decreased throughout development, while c‐Kit mRNA expression was found to slightly increase in the developing pancreas. Coexpression patterns indicated that c‐Kit and nestin form two distinct cell populations in the postnatal pancreas, and infrequently coexpress with other pancreatic cell‐specific markers. Furthermore, decreased c‐Kit and nestin expression in the islets in postnatal life correlated with an increase in cells immunopositive for Pdx‐1 compared with birth (36 ± 5% vs. 60 ± 3%, P < 0.01), which accompanied a doubling in the proportion of Glut‐2–positive cells (39.4 ± 4% vs. 68.8 ± 3%, P < 0.01), both of which are mature β‐cell markers. Taken together, these findings suggest that c‐Kit‐ and nestin‐expressing cells represent endocrine precursor cells that undergo marked changes in population dynamics during the transition from prenatal to postnatal pancreatic development in the rat. Characterization of the phenotype, relative abundance and location of these cells within the developing pancreas is an important step toward creating a strategy for isolating stem cell populations and modeling islet cell differentiation in vitro. Developmental Dynamics 229:813–825, 2004. © 2004 Wiley‐Liss, Inc.
Cellular growth and rearrangement during the development of the mammalian organ of Corti
Authors: McKenzie Erynn , Krupin Alison , Kelley Matthew W.
Published: March 2004

The sensory epithelium of the mammalian cochlea, the organ of Corti, is comprised of ordered rows of cells, including inner and outer hair cells. Recent results suggest that physical changes in the overall size and shape of the cochlear duct, including possible convergence and extension, could play a role in the development of this pattern. To examine this hypothesis, changes in cell size and distribution were determined for different regions of the cochlea duct during embryonic development. In addition, changes in the spatial distribution of sensory precursor cells were determined at different developmental time points based on expression of p27kip1. Unique changes in luminal surface area, cell density, and number of cell contacts were observed for each region of the duct. Moreover, the spatial distribution of p27kip1‐positive cells changed from short and broad early in development, to long and narrow. These results are consistent with the hypothesis that convergence and extension plays a role in cellular patterning within the organ of Corti. Developmental Dynamics 229:802–812, 2004. Published 2004 Wiley‐Liss, Inc.
Intestinal intraepithelial lymphocytes prevent pathogen‐driven inflammation and regulate the Smad/T‐bet pathway of lamina propria CD4+ T cells
Authors: Mennechet Franck J. D. , Kasper Lloyd H. , Rachinel Nicolas , Minns Laurie A. , Luangsay Souphalone , Vandewalle Alain , Buzoni‐Gatel Dominique
Published: March 2004

Intraepithelial lymphocytes (IEL) play a key role in gut homeostasis and are critical effector cells preventing the inflammatory intestinal lesions induced in mice following oral infection with Toxoplasma gondii. In this intestinal inflammatory model, CD4+ T lymphocytes from the lamina propria (LP) synergize with the infected enterocytes to secrete pro‐inflammatory chemokines and cytokines. In this study, we assessed the mechanisms accounting for the ability of IEL to modulate the inflammatory activity of these cells. Adoptive transfer of IEL purified from wild‐type mice, or CD154‐,CD95L‐ or IL‐10‐deficient mice infected with T. gondii completely impairs the development of the lethal ileitis in recipient mice orally infected with T. gondii.Compared with unprimed IEL isolated from naive mice, the CD8α β TCRα β subset of primed IEL, isolated from T. gondii‐infected mice, secretes increased amount of TGF‐β. IEL interact with the LP CD4+ T lymphocytes, down‐regulate their production of inflammatory cytokines such as IFN‐γ and reduce their proliferative activity. These effects are linked to the secretion of TGF‐β and are correlated with a shift in the balance between Smad7/T‐bet down‐regulation and Smad2/Smad3 up‐regulation in LP CD4+ T lymphocytes.
Mechanisms of tolerance induced by TGFβ‐treated APC: CD4 regulatory T cells prevent the induction of the immune response possibly through a mechanism involving TGFβ
Authors: Alard Pascale , Clark Sherry L. , Kosiewicz Michele M.
Published: March 2004

Transforming growth factor β (TGFβ)‐treated antigen‐presenting cells (APC) pulsed with antigen induce tolerance in mice, i.e. inhibition of IFN‐γ production and delayed type hypersensitivity response. Although evidence suggests that regulatory T cells are involved, their mechanism of action is currently unknown and is the subject of the present study. Both CD4 and CD8 splenic T cells from mice injected i.v. with adherent thioglycolate‐elicited peritoneal exudate cells cultured with TGFβ2 and antigen (TGFβ‐treated APC) transferred tolerance to naive recipients. Interestingly, TGFβ‐treated APC from class II knockout mice were unable to induce tolerance in wild‐type mice, whereas wild‐type TGFβ‐treated APC could induce tolerance in CD8 knockout mice. TGFβ was detected in cultures of lymphoid cells from mice injected with TGFβ‐treated APC, and treatment with anti‐TGFβ antibody in vivo impaired tolerance induction. TGFβ appeared to be involved in both the development of CD4 regulatory T cells and the effector function of the CD4 regulatory T cells. In summary, the important findings in this study are that CD4, and not CD8, regulatory T cells are required for tolerance induced by TGFβ‐treated APC in naive mice, and tolerance appears to be mediated by a mechanism involving TGFβ.
Anti‐Gal IgG potentiates natural killer cell migration across porcine endothelium via endothelial cell activation and increased natural killer cell motility triggered by CD16 cross‐linking
Authors: Hauzenberger Elenor , Klominek Julius , Holgersson Jan
Published: March 2004

Xenoreactive antibodies (Ab) are important for the development of acute vascular rejection (AVR) of xenografts characterized by monocytes, natural killer (NK) cells and neutrophils infiltrating the graft. The mechanisms by which anti‐galactoseα1,3galactose (α‐Gal) IgG influence NK cell migration across porcine aortic endothelium (PAEC) were investigated. NK cell migration across PAEC increased in the presence of anti‐α‐Gal IgG. Anti‐α‐Gal IgG exposure activated PAEC as shown by an increased expression of CD62E and CD106. NK cells adhered, spread and showed motile forms on plastic surfaces coated with human IgG, IgG Fc and on mAb against CD16, but not on mouse IgG or BSA, suggesting that CD16 cross‐linking can mediate increased adhesiveness. Increased NK cell motility was observed on Boyden filters coated with human IgG, IgG Fc, and mAb against CD16 and the α4, α5, αL, β1 and β2 integrin chains. No motile response was seen on mouse IgGor CD7, CD56 and α6 integrin mAb. NK cell migration on human IgG and anti‐CD16 Ab was blocked by anti‐CD16 or anti‐β2, but not anti‐β1 Ab, implying that the motile response triggered by CD16 cross‐linking is mediated via β2 integrins. Preformed or induced anti‐α‐Gal IgG may therefore contribute to AVR by stimulating innate immune cell infiltration of the graft.
Toll‐like receptor stimulation induces airway hyper‐responsiveness to bradykinin, an effect mediated by JNK and NF‐κB signaling pathways
Authors: Bachar Ofir , Adner Mikael , Uddman Rolf , Cardell Lars‐Olaf
Published: March 2004

Airway infections induce hyper‐responsiveness in asthmatic patients. Toll‐like receptors (TLR) mediate inflammatory responses to microbes. Occurrence and effects of TLR2, TLR3 and TLR4 were examined in a mouse organ culture model of asthma focusing on the smooth muscle responses to bradykinin. TLR2, TLR3 and TLR4 mRNA, and TLR2 and TLR4 immunoreactivity were detected in the tracheal muscle layer. Tracheal organ culture for 1 or 4 days with lipopolysaccharide (LPS; TLR2/4 agonist) or polyinosinic polycytidylic acid (poly‐I‐C; TLR3 agonist) enhanced bradykinin‐ and [des‐Arg9]‐bradykinin‐induced contractions. Simultaneous LPS and poly‐I‐C treatment resulted in synergistic enhancement of bradykinin‐induced contraction. In carbachol‐pre‐contracted segments TLR stimulationinduced less potent relaxations to bradykinin and [des‐Arg9]‐bradykinin. The LPS and poly‐I‐C enhancement of bradykinin‐induced contraction was inhibited by the transcriptional inhibitor actinomycin‐D, dexamethasone, the proteasome inhibitor MG‐132 and the c‐Jun N‐terminal kinase (JNK) inhibitor SP600125. LPS and poly‐I‐C induced translocation of NF‐κB p65 to the nucleus and up‐regulation of kinin B1 and B2 receptor mRNA. In summary, TLR2, TLR3 and TLR4 are expressed in the mouse tracheal smooth muscle. Costimulation of these receptors results in NF‐κB‐ and JNK‐mediated transcription of B1 and B2 receptor, inducing hyper‐responsiveness to bradykinin.
Aberrant expression of α‐Gal on primary human endothelium does not confer susceptibility to NK cell cytotoxicity or increased NK cell adhesion
Authors: He Zhong , Ehrnfelt Cecilia , Kumagai‐Braesch Makiko , Islam Khalid B. , Holgersson Jan
Published: March 2004

The contribution of Galα1,3Gal (α‐Gal) to cell‐mediated organ xenograft rejection is controversial. We have used recombinant lentiviruses encoding a porcine α1,3 galactosyltransferase (α1,3GalT) to obtain α‐Gal‐expressing primary human aortic endothelial cells (HAEC) at a frequency of 70–90%. These cells were compared to non‐transduced and mock‐transduced HAEC with regard to their susceptibility to human NK cell‐mediated lysis, ability to stimulate IFN‐γ production by NK cells, and support of NK cell adhesion under static and dynamic conditions. Using green fluorescent protein (GFP) as a reporter gene, it was shown that the frequency of green fluorescent HAEC increased until day 5 post‐transduction, and at a multiplicity of infection of 2.5, it reached98%. Lentiviral transduction did not result in activation of HAEC, and transduced HAEC responded as expected to TNF‐α and IFN‐γ stimulation. No differences were detected between non‐α‐Gal‐ and α‐Gal‐expressing HAEC in terms of their susceptibility to NK cell‐mediated lysis, ability to stimulate IFN‐γ production by NK cells, or ability to support NK cell adhesion under static and dynamic conditions. In conclusion, these data argue against an important role for the α‐Gal epitope in the direct interaction between endothelium and NK cells and prove that recombinant lentiviruses are efficient gene carriers for primary human endothelial cells.
NF‐κB synergizes with NF‐AT and NF‐IL6 in activation of the IL‐4 gene in T cells
Authors: Li‐Weber Min , Giaisi Marco , Baumann Sven , Pálfi Katalin , Krammer Peter H.
Published: March 2004

IL‐4 plays a pivotal role in the development of the Th2 cell mediated humoral immune response and causes IgE‐dependent allergic inflammatory diseases. Expression of IL‐4 in differentiated Th2 cells is regulated by transcription factors such as NF‐AT, AP‐1 and NF‐IL6. Recently, increasing evidence indicates that the pro‐inflammatory transcription factor NF‐κB may also participate inIL‐4 expression. In this study, we show that the IL‐4 promoter is synergistically activated by NF‐κB, NF‐AT and NF‐IL6 at the NF‐κB/NF‐AT/NF‐IL6 composite sites. In addition, we performed the chromatin immunoprecipitation technique to determine the functional relevance of NF‐κB in the activation of the IL‐4 gene in vivo. We demonstrate that NF‐κB binds to the IL‐4 promoter in vivo upon T cell activation. Inhibition of NF‐κB nuclear translocation in living cells blocked binding of NF‐κB to the IL‐4 promoter. The data provide first evidence that NF‐κB is directly involved in IL‐4 transcription.
Identification of naturally processed CD8 T cell epitopes from prostein, a prostate tissue‐specific vaccine candidate
Authors: Friedman Rachel S. , Spies A. Gregory , Kalos Michael
Published: March 2004

Prostein is a prostate tissue‐specific protein that is uniquely and abundantly expressed in normal and cancerous prostate tissues. Due to this expression profile, we examined the immunogenicity of prostein as a potential vaccine candidate for prostate cancer. To determine the presence of CD8 T cells specific for naturally processed prostein‐derived epitopes in healthy individuals, we developed and applied an in vitro stimulation protocol. Using this protocol, we identified CD8 T cells specific for prostein in the peripheral blood of a male and a female donor. Prostein‐specific CD8 T cell clones specifically recognized prostein‐expressing targets, including prostate tumor cell lines expressing the relevant HLA alleles. CD8 T cell clones isolated from the male donor were significantly less effective in recognizing target cells compared to cells isolated from the female donor and appeared to recognize subdominant epitopes. The identification of a prostein‐specificCD8 T cell repertoire supports the development of prostein in vaccination strategies against prostate cancer. Furthermore, the naturally processed peptide epitopes identified provide tools for the development of peptide‐based vaccination strategies against prostate cancer and for monitoring of prostein‐specific responses in vaccinated patients.