bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life in early Parkinson's disease: Impact of dyskinesias and motor fluctuations
Authors: Marras Connie , Lang Anthony , Krahn Murray , Tomlinson George , Naglie Gary ,   The Parkinson Study Group
Published: January 2004

AbstractThe impact of dyskinesias and motor fluctuations on quality of life (QOL) at various stages in the course of Parkinson's disease (PD) is not well understood. In 301 subjects with early PD enrolled in a clinical trial (CALM‐PD), we quantified the impact of motor complications on QOL and investigated how this changes over time. We also compared QOL related to demographic and treatment characteristics. The presence of dyskinesias was associated with visual analogue scale (VAS) scores 3.0 of 100 points higher (better) than those without dyskinesias in years 1 to 2, even when adjusting for Unified Parkinson's Disease Rating Scale (UPDRS) motor scores. The positive association between dyskinesias and QOL scores was more marked in older patients. In years 3 to 4, dyskinesias no longer had a significant relationship with QOL. Younger subjects had higher VAS scores. Gender, motor fluctuations, and treatment regimen had no significant association with QOL, although a trend was found toward a small negative effect of motor fluctuations on QOL. We conclude that motor complications that occur within the first 4 years of treatment of PD do not have a significant negative effect on quality of life as measured by a visual analogue scale for most patients. © 2003 Movement Disorder Society
Long‐term outcome of focal dystonia in string instrumentalists
Authors: Schuele Stephan , Lederman Richard J. 
Published: January 2004

AbstractThis study describes the clinical characteristics and long‐term outcome in string instrumentalists with focal task‐specific dystonia. We present the results of a follow‐up telephone survey of 21 violin and viola players with focal dystonia. Eighteen musicians responded to the questionnaire. Information on long‐term outcome was available on average 13.8 years after onset of symptoms. Main complaints were playing‐related loss of control and involuntary movements affecting the fingering hand in 16 and the bow arm in 5 patients. In 18 patients (86%), signs of abnormal posture could be detected by watching them play their instrument. Treatment attempts included nerve decompression, physical therapy, retraining, and anticholinergic medication. In selected patients, botulinum toxin injections or splint devices were offered. Only 38% of the performing artists were able to maintain their professional careers, among them none with bow arm dystonia. Focal dystonia may affect the fingering hand or bow arm in violin and viola instrumentalists. Treatment benefit is limited and in more than half of the patients, dystonia leads to the end of their musical career. © 2003 Movement Disorder Society
Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden‐Spatz syndrome) and pantothenate kinase‐associated neurodegeneration
Authors: Thomas Madhavi , Hayflick Susan J. , Jankovic Joseph 
Published: January 2004

AbstractHallervorden Spatz syndrome (HSS), also referred to as neurodegeneration with brain iron accumulation (NBIA), is a rare inherited neurodegenerative disorder with childhood, adolescent, or adult onset. Patients with HSS/NBIA have a combination of motor symptoms in the form of dystonia, parkinsonism, choreoathetosis, corticospinal tract involvement, optic atrophy, pigmentary retinopathy, and cognitive impairment. After the recent identification of mutations in the PANK2 gene on chromosome 20p12.3–p13 in some patients with the HSS/NBIA phenotype, the term pantothenate kinase‐associated neurodegeneration (PKAN) has been proposed for this group of disorders. To characterize clinically and genetically HSS/NBIA, we reviewed 34 affected individuals from 10 different families, who satisfied the inclusion criteria for NBIA. Relatives of patients who had clinical, magnetic resonance imaging (MRI), or pathological findings of NBIA were included in the study. Four patients were found to have mutations in the pantothenate kinase 2 (PANK2) gene. We compared the clinical features and MRI findings of those with and without PANK2 mutations. The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance. Parkinsonism is seen predominantly in adult‐onset patients whereas dystonia seems more frequent in the earlier‐onset cases. The phenotypic heterogeneity observed in our patients supports the notion of genetic heterogeneity in the HSS/NBIA syndrome. © 2003 Movement Disorder Society
A comparative study of mRNA and protein expression of the autoimmune regulator gene (Aire) in embryonic and adult murine tissues
Authors: Adamson KA , Pearce SHS , Lamb JR , Seckl JR , Howie SEM 
Published: January 2004

AbstractAutoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive human disorder caused by mutations in the autoimmune regulator gene (AIRE) and characterized by multiple autoimmune diseases. As reports of the tissue expression pattern of the murine Aire gene are discordant, a comprehensive survey of Aire expression was undertaken in adult and embryonic tissues at the mRNA and protein levels using real‐time RT‐PCR, in situ hybridization, and immunohistochemistry. In the adult, the highest Aire mRNA expression was in the thymus. All the other tissues investigated expressed Aire mRNA at low levels, but it was barely detectable in the adrenal gland. Aire protein expression was observed in the thymus, spleen, and lymph nodes. A common pattern was observed in other tissues, with staining in epithelial cells. An exception to this was the gut, where staining was seen in the mucin spaces. In embryonic tissue, Aire mRNA and protein expression was detected from E14.5 in the thymus. In the fetal liver, unlike the adult, staining was observed at E14.5 and decreased towards term. Thus, Aire is expressed in immunologically relevant tissues and in a restricted number of extra‐immunological tissues in the adult. Furthermore, the presence of Aire protein is reported in extra‐thymic tissues of the embryo. Copyright © 2004 John Wiley & Sons, Ltd.
Aberrant CpG island hypermethylation of multiple genes in prostate cancer and prostatic intraepithelial neoplasia
Authors: Kang Gyeong Hoon , Lee Sun , Lee Hyeon Joo , Hwang Kyu Sang 
Published: January 2004

AbstractTo date, several reports have been published about CpG island methylation of various genes in prostate cancer. However, most of these studies have focused on cancer tissue only or a single gene and data about concurrent methylation of multiple genes in prostate cancer or prostatic intraepithelial neoplasia (PIN) are limited. The aim of the present study was to determine the methylation profile of 11 tumour‐related genes in prostate cancer and PIN. Seventy‐one samples, including 37 prostate cancers, 14 PINs, and 20 normal prostates, were examined for the methylation status of 11 tumour‐related genes using methylation‐specific PCR. The mean number of genes methylated was significantly higher in prostate cancer and PIN than in non‐neoplastic prostate (4.4, 3, and 0.2, respectively; p < 0.001). In prostate cancer, APC, GSTP1, MGMT, and RASSF1A were frequently methylated at a frequency of 56.8%, 86.5%, 75.7%, and 83.8%, respectively. These genes were methylated in more than 30% of PINs. Prostate cancers with high serum prostate‐specific antigen (PSA) (more than 8 ng/ml) or a high Gleason score (GS) (3 + 4 or more) showed higher numbers of methylated genes than those with low serum PSA (8 or less) or low GS (3 + 3 or less) (5.4 versus 2.5 and 5.4 versus 3.1, respectively; p < 0.05). The methylation frequency of APC, RASSF1A, and RUNX3 was higher in prostate cancers with high serum PSA or with high GS than in those with low PSA or with low GS, respectively, the differences reaching statistical significance (p < 0.05). A strong association between MGMT methylation and loss of MGMT expression was demonstrated by immunohistochemistry. CpG island methylation is a frequent event, occurs early, and accumulates during multi‐step prostatic carcinogenesis. High levels of CpG island hypermethylation might serve as a potential biological marker for aggressive prostate cancer. Copyright © 2004 John Wiley & Sons, Ltd.
Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy‐type T‐cell lymphoma
Authors: Obermann EC , Diss TC , Hamoudi RA , Munson P , Wilkins BS , Camozzi MLP , Isaacson PG , Du MQ , Dogan A 
Published: January 2004

AbstractEnteropathy‐type T‐cell lymphoma (ETL) and ulcerative jejunitis (UJ) are rare disorders often occurring in patients with coeliac disease. The genetic events associated with the accumulation of intraepithelial lymphocytes in coeliac disease and tumour development are largely unknown. Deletions at chromosome 9p21, which harbours the tumour suppressor genes p14/ARF, p15/INK4b, and p16/INK4a, and 17p13, where p53 is located, are associated with the development and progression of lymphomas. To examine whether deletions at 9p21 and 17p13 play a role in ETL, 22 cases of ETL and seven cases of UJ were screened for loss of heterozygosity (LOH) by tissue microdissection and polymerase chain reaction (PCR) analysis for microsatellite markers. Furthermore, p53 and p16 protein expression was examined by immunohistochemistry. In addition, polymerase chain reaction–single strand conformational polymorphism (PCR–SSCP) analysis for detection of mutations in exons 5–8 of the p53 gene was performed in five cases of ETL and three cases of UJ. LOH was found in at least one microsatellite marker at the 9p21 locus in 8 of 22 (36%) ETLs, but not in UJ. Five of nine (56%) tumours composed of large cells showed LOH at 9p21, as opposed to two of eight (25%) tumours with small‐ or medium‐sized cell morphology. The region spanning the p14/p15/p16 gene locus was most frequently affected (five cases); LOH at these markers coincided with loss of p16 protein expression in all of these cases. p53 overexpression was demonstrated in all ETLs examined and in four of seven cases of UJ. However, no alterations of the p53 gene were detected by LOH or PCR–SSCP analysis. The results of this study show that LOH at chromosome 9p21 is frequent in ETL, especially in tumours with large cell morphology; this finding suggests that gene loss at this locus may play a role in the development of ETL. Copyright © 2004 John Wiley & Sons, Ltd.
Expression of BRCA1 protein in benign, borderline, and malignant epithelial ovarian neoplasms and its relationship to methylation and allelic loss of the BRCA1 gene
Authors: Wang Cuiju , Horiuchi Akiko , Imai Tsutomu , Ohira Satoshi , Itoh Kazuko , Nikaido Toshio , Katsuyama Yoshihiko , Konishi Ikuo 
Published: January 2004

AbstractBRCA1 is a putative tumour suppressor gene responsible for a hereditary ovarian cancer syndrome. To clarify the possible involvement of BRCA1 in the development of sporadic ovarian neoplasms, this study analysed the immunohistochemical expression of BRCA1 protein in normal ovarian surface epithelium and 119 epithelial ovarian tumours (19 benign, 24 borderline, and 76 malignant tumours). Loss of heterozygosity (LOH) of BRCA1 was examined using three microsatellite markers to analyse the relationship between BRCA1 expression and alterations of the BRCA1 gene. Methylation of the BRCA1 promoter was also analysed by methylation‐specific PCR. In ovarian carcinomas showing heterogeneous expression of BRCA1 protein in the same tumour, LOH and methylation status were analysed using microdissection techniques. Finally, the relationship of BRCA1 expression or its genetic alteration to clinicopathological parameters and patient survival was analysed. Ovarian surface epithelial cells expressed BRCA1 protein. Decreased expression of BRCA1 was found in 16% of benign tumours, 38% of borderline tumours, and 72% of carcinomas. LOH of BRCA1 was demonstrated in no benign tumours, 15% of borderline tumours, and 66% of carcinomas. Methylation of BRCA1 was not detected in benign or borderline tumours, but was present in 31% of carcinomas. Reduced expression of BRCA1 correlated with the presence of gene methylation. The frequency of BRCA1 methylation and LOH was higher in serous carcinomas than in other types. In one of the three serous carcinomas that showed heterogeneous expression of BRCA1, BRCA1‐positive borderline‐like tumour cells were LOH‐positive and methylation‐negative, whereas adjacent BRCA1‐negative carcinoma cells were LOH‐positive and methylation‐positive. The prognosis of carcinoma patients did not correlate with BRCA1 expression or genetic status. These findings suggest that reduced expression of BRCA1 protein along with genetic and epigenetic changes of the BRCA1 gene play an important role in the development of sporadic ovarian carcinomas, particularly those of serous histology. Copyright © 2004 John Wiley & Sons, Ltd.
Expression of IL‐27 in human Th1‐associated granulomatous diseases
Authors: Larousserie Frédérique , Pflanz Stefan , Coulomb‐L'Herminé Aurore , Brousse Nicole , Kastelein Rob , Devergne Odile 
Published: January 2004

AbstractInterleukin (IL)‐27 is a newly described member of the IL‐12 family. It is a heterodimeric cytokine composed of two subunits, p28 and Epstein–Barr virus‐induced gene 3 (EBI3). In vitro studies have shown that IL‐27 is mainly produced by activated monocytes and dendritic cells. It induces the proliferation of naïve CD4‐positive T cells and synergizes with IL‐12 for interferon‐γ (IFN‐γ) production. Knock‐out mice for the IL‐27 receptor (WSX‐1/TCCR) have impaired Th1 responses and form abnormal granulomas when injected with bacillus Calmette‐Guérin. However, the expression profile of IL‐27 in vivo is currently unknown. To investigate the potential role of IL‐27 in the development of a Th1 response in humans in vivo, this study has analysed the in situ expression of IL‐27 subunits in three types of granulomatous disease (tuberculosis, sarcoidosis, and Crohn's disease), each characterized by a Th1 response. Tissue sections from patients with tuberculosis (n = 9), sarcoidosis (n = 8), or Crohn's disease (n = 7) were analysed by immunohistochemistry with anti‐EBI3 and anti‐p28 antibodies, in parallel with control tissues (control reactive lymph nodes, n = 14, and control intestinal tissues, n = 11). In granulomatous tissues, EBI3 and p28 co‐expression was detected in epithelioid and multinucleate giant cells in granulomas. In addition, sinus or tissue macrophages, endothelial cells, and plasma cells were found to co‐express EBI3 and p28. These data support a possible role for IL‐27 in human Th1 responses. Copyright © 2004 John Wiley & Sons, Ltd.
Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases
Authors: To KF , Tong Joanna HM , Chan Paul KS , Au Florence WL , Chim Stephen SC , Allen Chan KC , Cheung Jo LK , Liu Esther YM , Tse Gary MK , Lo Anthony WI , Dennis Lo YM , Ng HK 
Published: January 2004

AbstractSevere acute respiratory syndrome (SARS) is a new human infectious disease with significant morbidity and mortality. The disease has been shown to be associated with a new coronavirus (SARS‐CoV). The clinical and epidemiological aspects of SARS have been described. Moreover, the viral genome of SARS‐CoV has been fully sequenced. However, much of the biological behaviour of the virus is not known and data on the tissue and cellular tropism of SARS‐CoV are limited. In this study, six fatal cases of SARS were investigated for the tissue and cellular tropism of SARS‐CoV using an in‐situ hybridization (ISH) technique. Among all the tissues studied, positive signals were seen in pneumocytes in the lungs and surface enterocytes in the small bowel. Infected pneumocytes were further confirmed by immunofluorescence–fluorescence in‐situ hybridization (FISH) analysis. These results provide important information concerning the tissue tropism of SARS‐CoV, which is distinct from previously identified human coronaviruses, and suggest the possible involvement of novel receptors in this infection. Whereas the lung pathology was dominated by diffuse alveolar damage, the gut was relatively intact. These findings indicated that tissue responses to SARS‐CoV infection are distinct in different organs. Copyright © 2004 John Wiley & Sons, Ltd.
Anti‐tumor effect of combination therapy with intratumoral controlled‐release paclitaxel (PACLIMER® microspheres) and radiation
Authors: Lapidus Rena G. , Dang Wenbin , Rosen David Marc , Gady Alyssa M. , Zabelinka Yelena , O'Meally Robert , DeWeese Theodore L. , Denmeade Samuel R. 
Published: January 2004

AbstractBACKGROUNDPaclitaxel is one of the few chemotherapeutics effective in patients with advanced protstate cancer. Paclitaxel has also been reported to have radiosensitizing effects in prostate cancer. Local delivery of a controlled‐release paclitaxel product may allow for increase local concentrations of paclitaxel at the tumor site and, in conjunction with radiation, may enhance cell kill by its radiosensitization mechanism.METHODSOrthotopic LNCaP tumors were injected with 40% PACLIMER® Microspheres (40% loading; w:w) when tumors were 100–200 mm3. Twenty‐eight days post cell injection, mice were sacrificed, tumors weighed, and serum measured for PSA. TSU–xenografts were injected with PACLIMER Microspheres (10% and 40% loaded; w:w) or placebo microspheres when the tumors were approximately 100 mm3. Half of xenograft tumors were irradiated with a single dose (10 Gy) of radiation. Tumor volume was followed over time.RESULTSForty percent PACLIMER Microspheres significantly reduced tumor growth in the LNCaP orthotopic model. PSA was a good indicator of response. Forty percent PACLIMER Microspheres had a significant effect on slowing TSU growth compared to placebo microspheres. Addition of a single acute dose of radiation significantly enhanced the effect of 10% PACLIMER Microspheres (P < 0.05), had minimal effect on 40% PACLIMER Microspheres, and no enhancing effect on tumors treated with placebo microspheres.CONCLUSIONSA controlled‐release formulation of paclitaxel can be very effective in the treatment of prostate cancer. Additionally, PACLIMER Microspheres may be effectively used as a radiosensitizer in genitourinary cancers. © 2003 Wiley‐Liss, Inc.
In situ shortening of CAG repeat length within the androgen receptor gene in prostatic cancer and its possible precursors
Authors: Tsujimoto Yuichi , Takakuwa Tetsuya , Takayama Hitoshi , Nishimura Kazuo , Okuyama Akihiko , Aozasa Katsuyuki , Nonomura Norio 
Published: January 2004

AbstractBACKGROUNDThe amino‐terminal transcriptional activation domain of the androgen receptor (AR) gene contains two polymorphic trinucleotide repeat segments that encode polyglutamine (CAG)n and polyglycine (GGC)n tracts. Shorter CAG repeat lengths are associated with higher transcriptional activity. The previous studies using peripheral blood leukocytes showed the relationship between shorter CAG repeat length and risk for prostate cancer (PCA).METHODSProstatic cancer (PCA), its possible precursors [high grade prostatic intraepithelial neoplasia (HGPIN) and postatrophic hyperplasia (PAH)], and non‐neoplastic epithelium were microdissected from a whole‐mount prostatectomy specimen from 34 cases with PCA. DNA extracted from each lesion was processed for PCR‐based electrophoresis on 6% denaturing polyacrylamide gels, followed by direct sequencing. To examine whether the in situ shortening of CAG repeat was confined to the CAG repeat or was a part of phenomenon induced by microsatelite instability (MSI), BAT‐25 and BAT‐26, effective markers for detection of MSI, were also examined.RESULTSAll non‐neoplastic epithelial lesions had identical numbers of CAG repeat in the same prostate. CAG repeat lengths were identical in lesions in 25 cases. Two distinct products were found in 9 of 34 cases (26.5%); one product identical to that of non‐neoplastic epithelium and another smaller one. In situ shortening of CAG repeat lengths in PCA, HGPIN, and PAH was found in 3 of 34 (8.8%), 6 of 34 (17.6%), and 3 of 10 (30%) cases, respectively. Frequency of CAG shortening was significantly higher in PAH than in PCA lesions (P < 0.05). The length of GGC repeats, BAT‐25 and ‐26 was identical among all lesions in the same case. There was no significant correlation between shortening of CAG repeat length and the clinicopathologic parameters.CONCLUSIONShortening of CAG repeat length was found in in situ lesions of PCA and its possible precursors. © 2003 Wiley‐Liss, Inc.
Membrane properties of single muscle cells of the rhabdosphincter of the male urethra
Authors: Berjukow Stanislav , Margreiter Eva , Marksteiner Rainer , Strasser Hannes , Bartsch Georg , Hering Steffen 
Published: January 2004

AbstractBACKGROUNDThe electrophysiological properties of myoblast cultures established from the human and porcine rhabdosphincter (RS) and porcine lower limb muscle (LLSKM) were studied to elucidate their potential for tissue engineering applications in the lower urinary tract.METHODSMuscle biopsies were collected from the prostatic part of the RS, the RS of male pigs, and the porcine LLSKM. Ion channels were studied by means of the patch‐clamp technique.RESULTSOnly one subtype each of voltage gated Na+ and Ca2+ channels was observed in porcine RS and LLSKM. Two types of voltage gated Ca2+ channels were identified in human RS cells. The porcine RS and LLSKM myoblasts displayed similar fusion competence.CONCLUSIONSPorcine RS and LLSKM myoblasts and human RS and human skeletal muscle cells show a high degree of similarity. Injection of autologous skeletal muscle myoboblasts in the lower urinary tract might, therefore, represent a promising approach to treat stress incontinence after radical prostatectomy. © 2004 Wiley‐Liss, Inc.
Long‐term morbidity and mortality of transurethral prostatectomy: A 10‐year follow‐up
Authors: Varkarakis John , Bartsch Georg , Horninger Wolfgang 
Published: January 2004

AbstractBACKGROUNDLong‐term complication and reoperation rates in 1,211 patients undergoing TURP for symptomatic BPH between 1988 and 1991 were evaluated after a follow‐up of at least 10 years.METHODSOf the 1,211 patients who underwent TURP, 577 (47.6%) were available for follow‐up. Long‐term complications as well as reoperation rates were evaluated on the basis of a patient questionnaire or a physician interview.RESULTSRepeat operation had to be performed in 35 patients (6%). TUR for bladder neck contracture had to be done in 14 patients (2.4%), while repeat TURP for BPH obstruction was required in 11 patients (1.9%). Finally, urethral strictures mandating surgical correction were present in 10 patients (1.7%).CONCLUSIONSTURP is associated with low reoperation rates and therefore remains the gold standard in BPH therapy. Nevertheless, follow‐up of these patients must be continued, as late complications requiring intervention may occur even after 10 years postoperatively. © 2003 Wiley‐Liss, Inc.