bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitogenic Effects of the Up-Regulation of Minichromosome Maintenance Proteins in Anaplastic Thyroid Carcinoma
Authors: Guida Teresa , Salvatore Giuliana , Faviana Pinuccia , Giannini Riccardo , Garcia-Rostan Ginesa , Provitera Livia , Basolo Fulvio , Fusco Alfredo , Carlomagno Francesca , Santoro Massimo 
Published: August 2005

Context: Anaplastic thyroid carcinomas (ATC) are among the most aggressive human malignancies and are characterized by high mitotic activity. Minichromosome maintenance proteins (MCM) 2–7 are required to initiate eukaryotic DNA replication, and their overexpression has been associated with dysplasia and malignancy.Objective: In an attempt to cast light on the mechanisms governing ATC, we evaluated MCM5 and MCM7 expression in human normal, papillary (PTC), and anaplastic thyroid samples, as well as in primary culture cells and transgenic mouse models.Results: MCM5 and MCM7 expression was high in 65% of ATC and negligible in normal thyroid tissue and papillary thyroid carcinomas. In ATC, high MCM5 and MCM7 expression was paralleled by high levels of MCM2 and MCM6. An analysis of human ATC primary cell cultures and of a transgenic mouse model of ATC confirmed these findings. An increased transcription rate accounted for MCM7 up-regulation, because the activity of the MCM7 promoter was more than 10-fold higher in ATC cells compared with normal thyroid cells. Adoptive overexpression of wild-type p53, but not of its inactive (R248W and R273H) mutants, strongly down-regulated transcription from the MCM7 promoter, suggesting that p53 knock-out contributes to MCM7 up-regulation in ATC. Treatment with small inhibitory duplex RNAs, which decrease MCM7 protein levels, reduced the rate of DNA synthesis in ATC cells.Conclusion: MCM proteins are overexpressed in ATC and sustain the high proliferative capacity of ATC cells.
Urocortin 1, Urocortin 3/Stresscopin, and Corticotropin-Releasing Factor Receptors in Human Adrenal and Its Disorders
Authors: Fukuda Tsuyoshi , Takahashi Kazuhiro , Suzuki Takashi , Saruta Masayuki , Watanabe Mika , Nakata Taisuke , Sasano Hironobu 
Published: August 2005

Abstract
Context: Urocortin 1 (Ucn1) and urocortin 3 (Ucn3)/stresscopin are new members of the corticotropin-releasing factor (CRF) neuropeptide family. Ucn1 binds to both CRF type 1 (CRF1) and type 2 receptors (CRF2), whereas Ucn3 is a specific agonist for CRF2. Recently, direct involvement of the locally synthesized CRF family in adrenocortical function has been proposed.
Objective, Design, and Setting: We examined in situ expression of Ucn and CRF receptors in nonpathological human adrenal gland and its disorders using immunohistochemistry and mRNA in situ hybridization.
Results: Ucn immunoreactivity was localized in the cortex and medulla of nonpathological adrenal glands. Ucn1 immunoreactivity was marked in the medulla, whereas Ucn3 was immunostained mostly in the cortex. Both CRF type 1 and CRF2 were expressed in the cortex, particularly in the zonae fasciculata and reticularis but very weakly or undetectably in the medulla. Immunohistochemistry in serial tissue sections with mirror images revealed that both Ucn3 and CRF2 were colocalized in more than 85% of the adrenocortical cells. mRNA in situ hybridization confirmed these findings above. In fetal adrenals, Ucn and CRF receptors were expressed in both fetal and definitive zones of the cortex. Ucn and CRF receptors were all expressed in the tumor cells of pheochromocytomas, adrenocortical adenomas, and carcinomas, but its positivity was less than that in nonpathological adrenal glands, suggesting that Ucn1, Ucn3, and CRF receptors were down-regulated in these adrenal neoplasms.
Conclusions: Ucn1, Ucn3, and CRF receptors are all expressed in human adrenal cortex and medulla and may play important roles in physiological adrenal functions.
Association of Cryptorchidism with a Specific Haplotype of the Estrogen Receptor α Gene: Implication for the Susceptibility to Estrogenic Environmental Endocrine Disruptors
Authors: Yoshida Rie , Fukami Maki , Sasagawa Isoji , Hasegawa Tomonobu , Kamatani Naoyuki , Ogata Tsutomu 
Published: August 2005

Context: The prevalence of cryptorchidism (CO) has increased during the past few decades in several countries, and this event has primarily been ascribed to the estrogenic effects of environmental endocrine disruptors (EEDs). Little is known, however, about the role of genetic susceptibility to EEDs in this phenomenon.Objective: The objective of this study was to determine whether CO is associated with a specific haplotype of the gene for estrogen receptor α (ESR1) that mediates the estrogenic effects of EEDs.Design: This was a case-control study.Setting: The study was performed at the National Research Institute and University Hospitals.Subjects: Sixty-three cryptorchid males, aged 1–13 yr, and 47 control males, aged 4–12 yr, were studied.Intervention: After genotyping 15 single nucleotide polymorphisms widely distributed in the greater than 300-kb genomic sequences of ESR1, haplotype analysis was performed.Main Outcome Measure: Identification of a specific ESR1 haplotype associated with CO was the main outcome measure.Results: A haplotype block was identified for an approximately 50-kb region encompassing single nucleotide polymorphisms 10–14 in the 3′ region of ESR1 in both groups. The frequency of the estimated AGATA haplotype within the block was higher in the patients than in the control males (34.0% vs. 21.3%; P = 0.037), and the association of this haplotype with CO phenotype was significant in a recessive mode (P = 0.0060). The homozygosity for this haplotype was identified only in the patients, and the frequency of the homozygotes was significantly different between the two groups (10 of 63 vs. zero of 47; P = 0.0042).Conclusions: The association of CO with homozygosity for the specific ESR1 haplotype suggests the relevance of genetic susceptibility to EEDs in the development of CO.
Occupational Exposure to Ionizing Radiation Is Associated with Autoimmune Thyroid Disease
Authors: Völzke Henry , Werner André , Wallaschofski Henri , Friedrich Nele , Robinson Daniel M. , Kindler Stefan , Kraft Matthias , John Ulrich , Hoffmann Wolfgang 
Published: August 2005

Context: The thyroid gland is a potential target organ for radiation-related damage.Objective: The aim of the analysis was to investigate the association between occupational exposure to ionizing radiation and autoimmune thyroid disease (AITD).Design: Our design was the cross-sectional Study of Health in Pomerania.Setting: The setting was the general community.Subjects: Analyses were performed in a population-based sample of 4299 subjects. Among them, 160 persons reported a history of occupational exposure to ionizing radiation.Main Outcome Measure: AITD was defined as the combined presence of hypoechogenicity in thyroid ultrasound and antithyroxiperoxidase antibodies greater than 200 IU/ml.Results: Females with occupational exposure to ionizing radiation had more often AITD than nonexposed females (10.0 vs. 3.4%; P &lt; 0.05). This association persisted after adjustment for relevant confounders (odds ratio, 3.46; 95% confidence interval, 1.16–10.31; P &lt; 0.05). In males, there were too few subjects who fulfilled the criteria of AITD, but the association between the exposure to radiation and hypoechogenicity of the thyroid gland barely missed statistical significance (odds ratio, 2.20; 95% confidence interval, 0.92–5.26; P = 0.08). In both females and males, subjects who reported a length of exposure of more than 5 yr exhibited the highest risk of the endpoints.Conclusions: We conclude that occupational exposure to ionizing radiation is related to the risk of AITD. The usage of thyroid protection shields by radiation workers is strongly recommended.
Novel Mutations within the POU1F1 Gene Associated with Variable Combined Pituitary Hormone Deficiency
Authors: Turton James P. G. , Reynaud Rachel , Mehta Ameeta , Torpiano John , Saveanu Alexandru , Woods Kathryn S. , Tiulpakov Anatoly , Zdravkovic Vera , Hamilton Jill , Attard-Montalto Simon , Parascandalo Ray , Vella Cecil , Clayton Peter E. , Shalet Stephen , Barton John , Brue Thierry , Dattani Mehul T. 
Published: August 2005

Context: Mutations within the gene encoding the pituitary-specific transcription factor POU1F1 are associated with combined pituitary hormone deficiency (CPHD). Most of the affected individuals manifest GH, prolactin, and TSH deficiency.Objective: We have now screened 129 individuals with CPHD and isolated GH deficiency for mutations within POU1F1.Results: Causative mutations were identified in 10 of 129 individuals (7.8%). Of these, five patients harbored the dominant negative R271W mutation, which is a well-recognized mutational hot spot. We have also identified a second frequently occurring mutation, E230K, which appears to be common in Maltese patients. Additionally, we describe two novel mutations within POU1F1, an insertion of a single base pair (ins778A) and a missense mutation (R172Q). Functional studies have revealed that POU1F1 (E230K) is associated with a reduction in transactivation, although DNA-binding affinity is similar to the wild-type protein. On the other hand, POU1F1 (R172Q) is associated with a reduction in DNA binding and transactivation, whereas POU1F1 (ins778A) is associated with loss of DNA binding and a reduction in transactivation.Conclusions: Our data suggest that the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion. Additionally, our data revealed POU1F1 mutations in three patients who were diagnosed as having ACTH deficiency but who, on further evaluation, were found to have normal cortisol secretion. Hence, elucidation of the genotype led to further evaluation of the phenotype, with the cessation of cortisol replacement that had been commenced unnecessarily. These data reflect the importance of mutational analysis in patients with CPHD.
Serial Single-photon Emission Computed Tomographic and Transcranial Doppler Measurements for Evaluation of Vasospasm after Aneurysmal Subarachnoid Hemorrhage
Authors: Egge Arild , Sjøholm Hans , Waterloo Knut , Solberg Tore , Ingebrigtsen Tor , Romner Bertil 
Published: August 2005

ABSTRACT

OBJECTIVE:
To assess the clinical value of serial single photon-emission computed tomographic (SPECT) measurements after aneurysmal subarachnoid hemorrhage (SAH).

METHODS:
Thirty-two patients were studied prospectively during the first 26 days after SAH with repeated SPECT measurements, clinical examinations, and transcranial Doppler recordings. Time trends were analyzed with a general linear model. A final SPECT measurement was performed after 1 year.

RESULTS:
A mean of 2.6 (range, 1–5) SPECT measurements revealed a significant (P = 0.001) quadratic curve consistent with initial hypoperfusion and then with hyperperfusion during the acute stage. SPECT findings were significantly associated with transcranial Doppler recordings (P = 0.016) and clinical assessments (P = 0.008). Patients fulfilling clinical and transcranial Doppler criteria for vasospasm demonstrated a more pronounced relative hypoperfusion-hyperperfusion time course. A multivariate logistic regression analysis identified SPECT measurements obtained during Days 7 to 14 after the SAH as the only independent predictor (β = 0.042, P = 0.02) for impaired perfusion after 1 year.

CONCLUSION:
Serial SPECT measurements after aneurysmal SAH demonstrate that regional changes in cerebral perfusion follow a nonlinear time trend, and repeated measurements are necessary. This observation, as well as the low feasibility of SPECT, restricts the clinical value of such measurements.
Stereotactic Radiosurgery for Vestibular Schwannomas: Analysis of 317 Patients Followed More Than 5 Years
Authors: Hasegawa Toshinori , Fujitani Shigeru , Katsumata Shun , Kida Yoshihisa , Yoshimoto Masayuki , Koike Joji 
Published: August 2005

ABSTRACT

OBJECTIVE:
Many investigators have reported successful treatment of vestibular schwannomas with gamma knife radiosurgery (GKRS). However, long-term outcomes should be evaluated before concluding that GKRS is truly safe and effective for the treatment of vestibular schwannomas.

METHODS:
Between May 1991 and December 1998, 346 consecutive patients (excluding those presenting with neurofibromatosis Type 2) were treated with GKRS. Of these, 317 patients were assessed. Twenty-nine patients were lost to follow-up within 5 years.

RESULTS:
The median follow-up period was 7.8 years. Of 301 patients who underwent serial follow-up imaging, two (1%) experienced complete remission, 184 (61%) experienced partial remission, 93 (31%) had stable tumors, and 22 (7%) experienced treatment failure. The actuarial 5- or 10-year progression-free survival (PFS) rate was 93 and 92%, respectively. Tumors less than 15 cm3 in volume (10-yr PFS, 96%; P &lt; 0.001) or which did not compress the brainstem and deviate the fourth ventricle (10-yr PFS, 97%; P = 0.008) resulted in significantly better PFS rates. Failure of treatment usually occurred within 3 years. When the tumor was treated with a marginal dose of 13 Gy or less, the hearing preservation rate was 68%, transient facial palsy developed at a rate of 1%, and facial numbness developed at a rate of 2%.

CONCLUSION:
GKRS proved to be a safe and effective treatment for patients followed longer than 5 years who presented with tumors with a volume of less than 15 cm3 and who did not have significant fourth ventricle deviation. Good functional outcomes were observed in this group of patients.
Cushing's Disease in Children and Adolescents: 20 Years of Experience in a Single Neurosurgical Center
Authors: Joshi Shabin M. , Hewitt Richard Jonathan David , Storr Helen L. , Rezajooi Kia , Ellamushi Habib , Grossman Ashley B. , Savage Martin O. , Afshar Fary 
Published: August 2005

ABSTRACT

OBJECTIVE:
This is a retrospective analysis of 25 consecutive pediatric patients with Cushing's disease who underwent transsphenoidal surgery performed by a single neurosurgeon in a specialist center during a 20-year period. This article discusses the presentation of Cushing's disease, the endocrinological investigation with particular reference to bilateral inferior petrosal sinus sampling (BIPSS), the operative management with reference to specific pediatric difficulties of the transsphenoidal approach and the use of intraoperative image guidance, and the analysis of these cases as regards postoperative complications and outcomes of this rare condition in young patients.

METHODS:
All patients underwent detailed endocrine investigation and imaging in the form of computed tomography and/or magnetic resonance imaging. BIPSS was performed in 19 patients (76%), with successful lateralization of the side of the microadenoma in 14 (74%) and prediction of a central tumor in four (94% total prediction rate). Surgical removal was via the sublabial, paraseptal, transsphenoidal route.

RESULTS:
There were 15 male and 10 female patients, with a mean age of 13.4 years (range, 6.6–17.8 yr). Weight gain was the most common presentation (100%), and then growth impairment (96%), fatigue and skin changes (64%), and hypertension (32%). Postoperative complications included growth hormone deficiency (36%), transient diabetes insipidus (12%), panhypopituitarism (4%), and transient cerebrospinal fluid rhinorrhea (4%). The median follow-up period was 59.5 months (range, 6–126 mo). Overall, 15 patients (60%) achieved surgical cure or remission, of which 14 outcomes were obtained using the results of BIPSS. Ten patients (40%) required postoperative radiotherapy to achieve “remission.” There were no cases of meningitis, no neurological deficits, no reoperations, and no mortality.

CONCLUSION:
Cushing's disease in children and adolescents is a rare illness. The accurate preoperative localization of the adenoma is essential for achieving good results. In this series, BIPSS was far more accurate in localizing the adenoma than computed tomography or magnetic resonance imaging. Imaging, however, is useful for the exclusion of other intracranial problems. Transsphenoidal surgery was safe and efficacious in achieving cure in the majority of cases. The challenge of transsphenoidal surgery in this age group is the small pituitary fossa and the absence of sphenoid sinus aeration in some cases. We found the use of intraoperative neuronavigation to be an excellent aid in overcoming such anatomic difficulties.
Herniation Secondary to Critical Postcraniotomy Cerebrospinal Fluid Hypovolemia
Authors: Komotar Ricardo J. , Mocco J , Ransom Evan R. , Mack William J. , Zacharia Brad E. , Wilson David A. , Naidech Andrew M. , McKhann Guy M. , Mayer Stephan A. , Fitzsimmons Brian-Fred M. , Connolly E Sander 
Published: August 2005

ABSTRACT

OBJECTIVE:
Cerebrospinal fluid hypovolemia resulting in postural headaches is a well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia with altered mental status and signs of transtentorial herniation (“brain sag”) have rarely been reported. This article describes the clinical features of brain sag after craniotomy in an attempt to increase recognition of this syndrome.

METHODS:
Between April 2001 and January 2003, 220 consecutive patients with subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping. Among these patients, the diagnosis of brain sag was made when all three of the following criteria were present: clinical signs of transtentorial herniation, head computed tomographic scans revealing effacement of the basal cisterns with an oblong brainstem, and improvement of symptoms after placement of the patient in the Trendelenburg position (–15 to –30 degrees). For each patient, the symptoms, clinical course, and subsequent response to treatment were characterized. In addition, brainstem dimensions were measured on computed tomographic scans taken before, during, and after resolution of brain sag. A “sag ratio” was generated for these time points by dividing the maximum anteroposterior distance by the maximum bipeduncular distance.

RESULTS:
Eleven (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy and an intraoperative spinal drain met the criteria for brain sag. Signs of transtentorial herniation developed most commonly between 2 and 4 days postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients, whereas the other patient demonstrated extensor posturing. The Trendelenburg position reversed the symptoms in all patients. The mean sag ratios before, during, and after resolution of brain sag were 0.91 ± 0.03 (mean ± standard error), 1.18 ± 0.03, and 0.91 ± 0.03, respectively. This represented a 30.9% elongation of the brainstem during sag (P &lt; 0.001) and a 23.6% change back to baseline after resolution of the syndrome (P &lt; 0.002). There was no significant difference between the presag and postsag ratios.

CONCLUSION:
Severe cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic herniation syndrome that is completely reversed by the Trendelenburg position. Brain sag should be included in the differential diagnosis for acute postoperative clinical deterioration in this patient population.
Cervical Spondylotic Myelopathy, Depression, and Anxiety: A Cohort Analysis of 89 Patients
Authors: Stoffman Michael R. , Roberts Mark S. , King Joseph T. 
Published: August 2005

ABSTRACTOBJECTIVE:To determine the prevalence of depressed and anxious mood states in patients with cervical spondylotic myelopathy (CSM), a degenerative spine condition with symptoms of neck pain, numb clumsy hands, gait difficulties, sphincter dysfunction, and impotence. To examine the relation between mood and functional deficits produced by CSM.METHODS:We surveyed a cohort of 89 patients with CSM recruited during 1 year from a neurosurgery clinic. Patients underwent a structured interview to collect information on demographics, personal habits, CSM symptoms, comorbid diseases, and symptoms of depression and anxiety. Patients self-completed the Hospital Anxiety and Depression scale and were scored on the Nurick, Cooper, Harsh, and modified Japanese Orthopaedic Association (mJOA) scales.RESULTS:According to the Hospital Anxiety and Depression scale threshold value of 11, 29% of the cohort had a depressed mood and 38% had an anxious mood. Higher depression scores were associated with worse myelopathy, as measured by the Nurick scale (P = 0.01), the Cooper leg subscale (P = 0.006), the Harsh scale (P = 0.02), the mJOA arm subscale (P = 0.006), and the mJOA leg subscale (P = 0.004). There was no relation between depression scores and the Cooper arm subscale, Harsh sphincter scale, mJOA sensory subscale, or mJOA bladder subscale. Similar patterns were seen in the relations between myelopathy and anxiety.CONCLUSION:More than one-third of patients with CSM have a depressed or anxious mood. In patients with CSM, depression and anxiety scores are strongly associated with decreased mobility, inconsistently associated with arm dysfunction, and not associated with sensory deficits or sphincter dysfunction, suggesting that ambulatory dysfunction may cause or exacerbate the symptoms of depression and anxiety in patients with CSM.
The Anteroinferior Cerebellar Artery Embedded in the Subarcuate Fossa: A Rare Anomaly and Its Clinical Significance
Authors: Tanriover Necmettin , Rhoton Albert L. 
Published: August 2005

ABSTRACT

OBJECTIVE:
The purpose of this study is to call attention to an anomaly in which a segment of the anteroinferior cerebellar artery (AICA) is embedded in the dura or bone surrounding the subarcuate fossa, a small depression in the bone posterior to the internal acoustic meatus (IAM), through which the subarcuate artery enters the bone. This anomaly places the artery at risk in removing the posterior wall of the IAM.

METHODS:
An anomalous AICA having a segment that was embedded in the dura covering on the bone surrounding the subarcuate fossa was found during a microsurgical dissection course. The senior author (ALR) has observed this anomaly in four patients during surgery for acoustic neuromas and in three specimens in microsurgery dissection courses. To define the microsurgical anatomy of the anomalous artery further, the latex-injected specimen was dissected in a stepwise manner using ×3 to ×40 magnification.

RESULTS:
The anomalous AICA described in this report bifurcated into a rostral trunk and a caudal trunk near the facial-vestibulocochlear nerve complex. The caudal trunk formed a sharp lateral loop that was embedded in the dura covering the subarcuate fossa. The involved trunk continued to supply the suboccipital area normally supplied by the posteroinferior cerebellar artery, which was hypoplastic. The dura surrounding the anomalous loop was opened, and the adjacent bone was removed to free the anomalous loop from the subarcuate fossa so that the artery could be displaced medially to remove the posterior wall of the IAM. Although it has been reported that the AICA may occasionally be adherent to the dura over the subarcuate fossa, this study is the first to demonstrate an AICA that is embedded in the dura and bone of the subarcuate fossa.

CONCLUSION:
Mobilizing the AICA loop that is embedded in the subarcuate fossa posterior to the IAM places the involved AICA at significant risk in exposing the contents of the IAM.