bluuebunny/crossref_metadata_2025 huggingface dataset:
Is a long‐term high‐intensity exercise program effective and safe in patients with rheumatoid arthritis?: Results of a randomized controlled trial
Authors: Zuzana de Jong  , Munneke Marten , Zwinderman Aeilko H. , Kroon Herman M. , Jansen Annemarie , Ronday Karel H. , van Schaardenburg Dirkjan , Dijkmans Ben A. C. , Van den Ende Cornelia H. M. , Breedveld Ferdinand C. , Vlieland Theodora P. M. Vliet , Hazes Johanna M. W.
Published: September 2003

Objective

There are insufficient data on the effects of long‐term intensive exercise in patients with rheumatoid arthritis (RA). We undertook this randomized, controlled, multicenter trial to compare the effectiveness and safety of a 2‐year intensive exercise program (Rheumatoid Arthritis Patients In Training [RAPIT]) with those of physical therapy (termed usual care [UC]).

Methods

Three hundred nine RA patients were assigned to either the RAPIT program or UC. The primary end points were functional ability (assessed by the McMaster Toronto Arthritis [MACTAR] Patient Preference Disability Questionnaire and the Health Assessment Questionnaire [HAQ]) and the effects on radiographic progression in large joints. Secondary end points concerned emotional status and disease activity.

Results

After 2 years, participants in the RAPIT program showed greater improvement in functional ability than participants in UC. The mean difference in change of the MACTAR Questionnaire score was 2.6 (95% confidence interval [95% CI] 0.1, 5.2) over the first year and 3.1 (95% CI 0.7, 5.5) over the second year. After 2 years, the mean difference in change of the HAQ score was −0.09 (95% CI −0.18, −0.01). The median radiographic damage of the large joints did not increase in either group. In both groups, participants with considerable baseline damage showed slightly more progression in damage, and this was more obvious in the RAPIT group. The RAPIT program proved to be effective in improving emotional status. No detrimental effects on disease activity were found.

Conclusion

A long‐term high‐intensity exercise program is more effective than UC in improving functional ability of RA patients. Intensive exercise does not increase radiographic damage of the large joints, except possibly in patients with considerable baseline damage of the large joints.
Genome‐wide association study for regions of systemic sclerosis susceptibility in a Choctaw Indian population with high disease prevalence
Authors: Zhou Xiaodong , Tan Filemon K. , Wang Ning , Xiong Momiao , Maghidman Samuel , Reveille John D. , Milewicz Dianna M. , Chakraborty Ranajit , Arnett Frank C.
Published: September 2003

Objective

Systemic sclerosis (SSc) is a complex, multisystem connective tissue disease in which genetic factors contribute to disease susceptibility. The aim of this study was to localize chromosome regions associated with susceptibility to SSc in a relatively isolated and homogenous population of Choctaw Indians with a high prevalence of SSc.

Methods

A genome‐wide microsatellite screen at 10 cM resolution (400 markers) was performed in 20 Choctaw patients with SSc and 76 ethnically matched controls. Based on the results of the initial screen, fine‐scale microsatellite mapping at ≤1 cM resolution was performed in 10 selected chromosome regions. Allele and marker haplotype frequencies were compared between SSc patients and controls.

Results

From the genome‐wide screen, 12 markers showed evidence of highly significant associations with SSc in this population (P < 0.01), while 5 other markers showed significant associations (0.01 < P < 0.05). Among these markers, loci D5S410, D6S422, D15S978, and D20S107 are near the SPARC, MHC, FBN1, and TOPOI genes, respectively, confirming the results of our previous studies, which used different markers. D1S2800 and D14S63 have been reported to show linkage to systemic lupus erythematosus (SLE) in family‐based studies, and D1S206, D6S422, and D6S264 are loci on 1p21.2, 6p22.3, and 6q23‐27, respectively, which are in regions reported as showing linkage to SLE and other autoimmune diseases. Other markers showing unique associations with SSc were D7S510 (7p12‐11), D7S661 (7q35), D8S514 (8q24.12), D19S221 (19p13.2), D19S220 (19q13.2), D22S423 (22q13.1), DXS1068 (Xp11.4), and DXS8055 (Xq21‐23). Further analysis with fine‐scale microsatellite mapping revealed at least 14 potential haplotypes associated with SSc.

Conclusion

Our findings indicate that a number of genetic loci may contribute to the high prevalence of SSc in the Choctaw and are consistent with the paradigm that some autoimmune rheumatic diseases are likely to share genetic determinants.
Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice
Authors: Hasegawa Hitoshi , Kohno Masashi , Sasaki Miho , Inoue Atsushi , Ito Mitsuko R. , Terada Miho , Hieshima Kunio , Maruyama Hiroki , Miyazaki Jun‐ichi , Yoshie Osamu , Nose Masato , Fujita Shigeru
Published: September 2003

Objective

To examine whether chemokine antagonists inhibit the initiation and progression of lupus nephritis in MRL/lpr mice.

Methods

NH2‐terminal–truncated monocyte chemoattractant protein 1 (MCP‐1)/CCL2 or thymus and activation–regulated chemokine (TARC)/CCL17 analogs were inserted into the pCXN2 expression vector and transfected into a nonmetastatic fibroblastoid cell line, MRL/N‐1, established from an MRL/gld mouse.

Results

MCP‐1 antagonist– or TARC antagonist–transfected MRL/N‐1 cells were injected subcutaneously into MRL/lpr mice ages 7 weeks (before the onset of lupus nephritis) and 12 weeks (at the early stage of the disease). After 8 weeks, mice bearing the MCP‐1 antagonist showed markedly diminished infiltration of macrophages and T cells, glomerular hypercellularity, glomerulosclerosis, crescent formation, and vasculitis compared with control mice. This seemed to be due to decreased production of interferon‐γ and interleukin‐2 in the kidney. In contrast, there was no significant difference in renal damage between mice bearing TARC antagonist and control mice.

Conclusion

We established a new system using MRL/N‐1 cells that allows long‐term observation of the effects of chemokine antagonists on lupus nephritis in MRL/lpr mice. We also showed that the MCP‐1 antagonist ameliorated the initiation and progression of lupus nephritis and of renal vasculitis, which might provide a new approach to the treatment of the disease.
Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen‐induced and collagen‐induced models of arthritis
Authors: Mould Arne W. , Tonks Ian D. , Cahill Marian M. , Pettit Allison R. , Thomas Ranjeny , Hayward Nicholas K. , Kay Graham F.
Published: September 2003

Objective

To determine the role of vascular endothelial growth factor B (VEGF‐B) in 2 mouse models of arthritis, antigen‐induced arthritis (AIA) and collagen‐induced arthritis (CIA).

Methods

For AIA studies, monarticular AIA was induced by methylated bovine serum albumin (mBSA) priming of Vegfb gene knockout (Vegfb−/−) and wild‐type (Vegfb+/+) mice, followed by intraarticular injection of mBSA or saline control 8 days later. CIA was induced in Vegfb−/− and Vegfb+/+ mice by intradermal injection of chick type II collagen in adjuvant. Arthritis was monitored in both models using defined criteria (clinical and histologic). Angiogenesis was measured by synovial vessel density in diseased and control joints.

Results

In AIA studies, Vegfb+/+ mice displayed significant knee joint swelling and synovial inflammation 7 days after intraarticular injection of antigen. Synovial inflammation was associated with angiogenesis, since vessel density in AIA synovium was significantly higher in arthritic than in control joints from the same animal. Knee joint swelling, synovial inflammation, and inflammation‐associated vessel density in arthritic joints were reduced in Vegfb−/− mice compared with arthritic joints from Vegfb+/+ mice. Similarly, in CIA, both disease incidence and mean clinical severity scores were significantly reduced in Vegfb−/− mice compared with Vegfb+/+ mice. Mean histologic severity scores and mean synovial vessel density were reduced in diseased joints from Vegfb−/− mice when compared with diseased joints from Vegfb+/+ mice.

Conclusion

The reduction in inflammation‐associated synovial angiogenesis in Vegfb−/− mice implicates VEGF‐B in pathologic vascular remodeling in inflammatory arthritis. VEGF‐B may be an attractive target in the design of anti‐angiogenic therapies for rheumatoid arthritis.
HLA–DQA1 is not an apparent risk factor for microchimerism in patients with various autoimmune diseases and in healthy individuals
Authors: Artlett Carol M. , O'Hanlon Terrence P. , Lopez Ana M. , Song Yeong Wook , Miller Frederick W. , Rider Lisa G.
Published: September 2003

Objective

Microchimeric cells have been identified in lesions and peripheral blood of patients with systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM), and HLA–DQA1*0501 is a risk factor for these diseases in some populations. Furthermore, DQA1*0501 has been associated with T lymphocyte microchimerism in SSc. To better define the strength of this association, we assessed the relationship among DQA1 alleles and microchimerism.

Methods

DNA from whole peripheral blood or magnetically sorted T cells was tested for microchimeric cells by polymerase chain reaction of the Y chromosome or of HLA–Cw in 87 SSc patients, 28 juvenile IIM patients, and 88 healthy controls. Thirty‐seven mother–son pairs were also analyzed for microchimerism and DQA1*0501.

Results

We were unable to demonstrate that DQA1*0501 is associated with microchimerism in T lymphocytes or in whole peripheral blood DNA in patients with SSc or juvenile IIM or in healthy individuals. In the 37 mother–son pairs, we were unable to demonstrate an association of DQA1*0501 with microchimerism in peripheral blood DNA or T lymphocytes, and compatibility between the donor's and recipient's HLA alleles did not influence microchimerism in the recipient.

Conclusion

These data suggest that HLA–DQA1 alleles do not appear to play a role in the persistence of microchimerism in the peripheral blood or T lymphocytes of patients with selected autoimmune diseases or in healthy individuals.
Doppler ultrasound and magnetic resonance imaging of synovial inflammation of the hand in rheumatoid arthritis: A comparative study
Authors: Terslev L. , Torp‐Pedersen S. , Savnik A. , von der Recke P. , Qvistgaard E. , Danneskiold‐Samsøe B. , Bliddal H.
Published: September 2003

Objective

To compare the quantitative and qualitative information obtained by Doppler ultrasound (US) measurements of the wrist joints and the small joints of the hand with the information obtained by postcontrast magnetic resonance imaging (MRI) and to correlate the imaging results with clinical observations in patients with rheumatoid arthritis (RA).

Methods

Twenty‐nine consecutive RA patients were studied; 196 joints (29 wrist and 167 finger joints) were examined by both US and MRI. Parameters of inflammation were the color fraction and the resistance index (RI) obtained with color Doppler US and the thickness of enhanced synovium (in mm) and the MRI score obtained with postcontrast MRI. Clinical examination and measurements of the erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP) level were performed on the same day as the imaging studies.

Results

There was a highly significant association between US indices of inflammation and postcontrast MRI scores. The mean values for both the color fraction and the RI were significantly different in the group without joint swelling compared with the other groups. The mean RI values were significantly different in the group without joint tenderness compared with the other groups. The mean thickness of enhanced synovium on postcontrast MRI was significantly different between the group without joint swelling and the other groups, but this difference was statistically significant only for the comparison of the group without joint tenderness versus the group with maximum tenderness. No association between the MRI or US estimates of inflammation and values on the visual analog scale for pain, Health Assessment Questionnaire, duration of morning stiffness, ESR, or CRP was found.

Conclusion

Estimates of synovial inflammatory activity by Doppler US and postcontrast MRI were comparable. Estimation of synovial inflammatory activity by the RI and color fraction parameters of US appears to be a promising method of detecting and monitoring inflammatory activity in patients with RA.
Expression of bone morphogenetic protein 6 in healthy and osteoarthritic human articular chondrocytes and stimulation of matrix synthesis in vitro
Authors: Bobacz K. , Gruber R. , Soleiman A. , Erlacher L. , Smolen J. S. , Graninger W. B.
Published: September 2003

Objective

To elucidate the role of bone morphogenetic protein 6 (BMP‐6) in human articular cartilage, we investigated whether BMP‐6 is expressed in adult human articular chondrocytes and analyzed the potential stimulatory effects of BMP‐6 on these cells. In addition, we investigated whether osteoarthritic (OA) and normal cartilage chondrocytes behave differently.

Methods

Endogenous expression of the BMP‐6 gene was examined by reverse transcription–polymerase chain reaction. BMP‐6 protein was detected by Western immunoblotting. Chondrocytes were grown as monolayer cultures for 7 days in a chemically defined serum‐free medium, in the absence or presence of recombinant BMP‐6. Proteoglycan (PG) synthesis was measured by 35S‐sulfate incorporation into newly synthesized macromolecules. Cell proliferation was assessed by 3H‐thymidine incorporation.

Results

BMP‐6 was expressed in both healthy and OA chondrocytes at the messenger RNA and protein levels. Total PG synthesis was significantly increased after BMP‐6 stimulation of healthy (mean ± SEM 191 ± 11%; P < 0.001) and OA (150 ± 25%; P < 0.03) chondrocyte cultures. A direct comparison between healthy and OA samples revealed no significant difference. The proliferation rates of normal and OA chondrocytes were not affected by BMP‐6 treatment.

Conclusion

BMP‐6 is endogenously expressed in chondrocytes obtained from OA and normal adult human articular cartilage. Furthermore, BMP‐6 has the potential to stimulate total PG synthesis in human articular chondrocytes derived from normal as well as OA joints. We conclude that the presence of BMP‐6 in adult human articular cartilage indicates a functional role for this growth factor in the maintenance of joint integrity.
Judgingmens rea: the tension between folk concepts and legal concepts of intentionality
Authors: Malle Bertram F. , Nelson Sarah E.
Published: September 2003

Concepts such asintention,motive, orforethoughthave generated a great deal of doubt, dispute, and confusion in legal decision making. Here we argue for an empirically based strategy of defining and using suchmens reaconcepts. Instead of the standard approach of settling these concepts by theoretical argument and the debaters' own intuitions, we rely on social psychological research to determine the meaning and significance of folk concepts concerningmens rea. We demonstrate the reliable and systematic use of people's concept of intentionality, contrast it with the bewildering variety of related legal concepts, and apply the folk model of intentionality to debated distinctions between intention and intentionality, desire and intention, and belief and intention. This folk‐conceptual approach promises clarity ofmens reaconcepts and a reconciliation of the legal and layperson's view of human behavior. Copyright © 2003 John Wiley & Sons, Ltd.
Cervical cytological studies in women inserted with Norplant‐I contraceptive
Authors: Misra Jata S. , Tandon Prabha , Srivastava Aarti , Das Kalyani , Chandrawati  , Saxena Nirakar C.
Published: September 2003

The study was carried out by the Human Reproduction Research Centre of the Indian Council of Medical Research at Lucknow and Kanpur, India as part of a multicenter study to ascertain the oncogenic potential of Norplant‐I, a progestational contraceptive, by periodic cytological evaluation of cervical smears. In total, 278 fertile healthy women were inserted with Norplant‐I at the Contraceptive Clinic of the Department of Obstetrics and Gynaecology of K.G.'s Medical College, Lucknow and G.S.V.M. Medical College, Kanpur, were and followed for periods ranging from 1–5 yr. It was reassuring to note that squamous intraepithelial lesion (SIL) incidence was found to be significantly higher only in the initial stages of contraception after 1 yr of Norplant insertion, after which it declined; no SIL was seen after 3 yr of contraception. The retrogression of SIL was also seen in all 11 pre‐ and 15 of 18 postinsertional cases. As SIL incidence showed a rise with increasing age and parity, the study also highlighted the need for constraint in offering Norplants to women of high age and parity. The percentage of inflammatory smears were also high till 4 yr of Norplant use, warranting a need for adequate treatment and early repeat cytology to exclude the persistence of inflammation. The accumulated data indicate the safety of long‐term use of Norplants upto 5 yr, as far as oncogenic potential is concerned. Diagn. Cytopathol. 2003;29:136–139. © 2003 Wiley‐Liss, Inc.
Loa loa presenting in a ThinPrep® Pap test™: Case report and review of parasites in cervicovaginal cytology specimens
Authors: Stelow Edward B. , Pambuccian Stefan E. , Bardales Ricardo H. , Cartwright Charles P. , Reif Christopher J. , Stanley Michael W.
Published: September 2003

Parasites other than Trichomonas vaginalis may occasionally present in Pap tests obtained during gynecologic examination. We present a case of Loa loa found on a Pap test from an apparently healthy 19‐yr‐old woman who had immigrated to the US at the age of 15 from Cameroon. We discuss the cytologic features from this case and then briefly review Loa loa and the presence of parasites in Pap tests and other cervicovaginal specimens. Diagn. Cytopathol. 2003;29:167–171. © 2003 Wiley‐Liss, Inc.
Role of HPV DNA testing in predicting cervical intraepithelial lesions: Comparison of HC HPV and ISH HPV
Authors: Qureshi M. Nasar , Rudelli Raoul D. , Tubbs Raymond R. , Biscotti Charles V. , Layfield Lester J.
Published: September 2003

Human papillomavirus (HPV) is widely accepted as the primary agent involved in the development of squamous intraepithelial neoplasia and cervical carcinoma. Several commercial tests are available for detecting HPV DNA. This study compares the efficacy of INFORM®HPV (in situ hybridization [ISH] HPV) and HCII (HC HPV) in predicting cervical lesions. A total of 762 sequential Papanicolaou (Pap) smears determined by cytologic examination to be either atypical squamous cells of undetermined significance (ASC‐US) or low‐grade squamous intraepithelial lesions (LSIL) were tested by both Hybrid Capture (HC) HPV and ISH HPV; 250 follow‐up biopsies were reviewed as the reference standard for presence or absence of a lesion. ISH HPV and HC HPV differed significantly in accurately predicting biopsy findings from ASC‐US and LSIL cases. The overall sensitivity and specificity of ISH HPV were 97% (28/29) and 86% (191/221); and HC HPV was 79% (23/29) and 56% (123/221). The positive predictive value (PPV) of ISH HPV was 48% (28/58) vs HC HPV value of 19% (23/121). Negative predictive value (NPV) was also better with ISH HPV at 99% (191/192) and HC HPV at 95% (123/129). Of equal importance, ISH HPV demonstrated a lower false‐positive rate compared to HC HPV, 12% (30/250) vs 39% (98/250), as well as having a slightly lower false‐negative rate 0.4% (1/250) vs 2.4% (6/250). ISH HPV is more predictive of biopsy histopathology in patients with detectable cervical lesions than is HC HPV. Effective triage of patients by HPV analysis using ISH HPV as compared to HC HPV has the potential of significant public health impact by reducing unnecessary colposcopies, as well as adverse medical, social, and psychological patient consequences. Diagn. Cytopathol. 2003;29:149–155. © 2003 Wiley‐Liss, Inc.
Leiomyosarcoma of the breast: A difficult diagnosis on fine‐needle aspiration biopsy
Authors: Jun Wei Xiao , Hiotis Karen , Garcia Roberto , Hummel Levine Pascale
Published: September 2003

Leiomyosarcoma of the breast is rarely encountered in fine‐needle aspiration (FNA) cytologic material. We report a case of primary leiomyosarcoma of the breast in a 52‐yr‐old female. Aspiration cytology showed large, dissociated round to spindle cells with abundant vacuolated cytoplasm, pleomorphic nuclei, prominent nucleoli, and occasional intranuclear cytoplasmic invaginations. Mitotic figures, osteoclast‐like giant cells, and stromal fragments were identified. A diagnosis of malignant neoplasm representing either a sarcoma, a poorly differentiated carcinoma, or a metaplastic carcinoma was made. The patient underwent a wide excision of the lesion after negative work‐up. Histologic examination and immunohistochemical studies established the diagnosis of leiomyosarcoma. This case is presented here because we feel that, although FNA cytology with eventual ancillary studies is a valuable diagnostic tool to evaluate any breast mass, malignant spindle cell neoplasms of the breast still represent a diagnostic challenge for the cytopathologist. Recognition of all cytologic features of leiomyosarcoma may help to formulate a correct diagnosis. Diagn. Cytopathol. 2003;29:172–178. © 2003 Wiley‐Liss, Inc.
Chemical composition variability of the essential oil of Conyza canadensis Cronq.
Authors: Lis Anna , Piggott John R. , Góra Józef
Published: September 2003

The essential oils from different botanical parts (herb, leaves, ﬂowers, stems, roots) of Conyza canadensis Cronq. were analysed at various ontogenesis phases. R‐(+)‐limonene and trans‐α‐bergamotene were the main constituents of the herb, leaf and ﬂower oil at all phases of vegetation. The early ﬂowering phases are the best time for harvesting C. canadensis herb, because the oil yield is the highest (0.7–0.8%) and its chemical composition is constant (limonene 80–81%, trans‐α‐bergamotene 6–8%). Limonene was the dominating compound of the oils of European origin (French, Italian, Spanish, Belgian, Bulgarian and Lithuanian). Copyright © 2003 John Wiley & Sons, Ltd.
Chemical composition of fruit and stem essential oils of Lantana camara from northern India
Authors: Khan M. , Srivastava S. K. , Jain Neetu , Syamasundar K. V. , Yadav Anju K.
Published: September 2003

The chemical composition of fruits and stem essential oils of Lantana camara from the northern plains of India were analysed by GC and GC–MS, which resulted in the identiﬁcation of 52 and 66 constituents, representing 98.1% and 96.6% of the oils, respectively. The major constituents in the fruits oil were palmitic acid (22.8%), stearic acid (12.8%) and germacrene‐D (7.1%), while the major constituents in the stem oil were palmitic acid (32.7%) and stearic acid (23.9%). Copyright © 2003 John Wiley & Sons, Ltd.
Antimicrobial activity of essential oils from Tunisian aromatic plants
Authors: Bouzouita Nabiha , Kachouri Faten , Hamdi Moktar , Chaabouni Mohamed Moncef
Published: September 2003

The essential oils from Thymus capitatus (L.) Hoffmgg. et Link, Ocimum basilicum (L.), Myrtus communis (M.) and Laurus nobilis (L.) have been characterized and tested against two bacteria (Lactobacillus plantarum and Escherichia coli) and a fungus (Geotrichum candidum), using a submerged broth culture method. The results obtained showed that T. capitatus and O. basilicum were the greatest inhibitors of all the strains tested, and that Escherichia coli was more inhibited than Lactobacillus plantarum by all the essential oils tested. Copyright ©2003 John Wiley & Sons, Ltd.
Chemical composition of the leaf volatile oils of Callitris intratropica R. T. Baker & H. G. Smith from Nigeria
Authors: Ogunwande Isiaka A. , Olawore Nureni O. , Kasali Adeleke A. , König Wilfried A.
Published: September 2003

The chemical composition of the leaf volatile oils of Callitris intratropica from two different regions in Nigeria were investigated by GC and GC–MS. The essential oils comprised mainly monoterpenoids (93.0–95.9%), while sesquiterpenoids constituted the minor components (1.4–4.4%). The quantitatively signiﬁcant constituents of the essential oils were α‐pinene (35.9–55.6%), limonene (21.6–50.5%) and myrcene (6.0–10.1%). Copyright © 2003 John Wiley & Sons, Ltd.
Volatile components from the roots of Scrophularia ningpoensis Hemsl.
Authors: Miyazawa Mitsuo , Okuno Yoshiharu
Published: September 2003

The composition of the volatile oil from the radix of Scrophularia ningpoensis has been investigated by capillary GC, GC–MS. The oil contained 103 volatile components, of which 3.49% were terpenoids. The main constituents were fatty acids, such as palmitic acid (25.40%), linoleic acid (10.04%), α‐linolenic acid (6.06%), γ‐linolenic acid (4.82%), cis‐palmitoleic acid (3.94%), trans‐oleic acid (3.52%), cis‐oleic acid (2.67%) and trans‐palmitoleic acid (1.20%). Copyright © 2003 John Wiley & Sons, Ltd.
Secretory elements of needles and berries of Juniperus communis L. ssp. communis and its volatile constituents
Authors: Shahmir F. , Ahmadi L. , Mirza M. , Korori S. A. A.
Published: September 2003

The structure of the secretory elements and the essential oils of the needles and berries of Juniperus communis L. ssp. communis growing in north Iran were studied. The needles, which contain ducts and transfusion tissue, act as conduction structures, and the berries containing elongate tubercles which act as reservoirs of volatile oils. The essential oils, isolated by hydrodistillation, were analysed by GC–MS. The oil contained 41 and 27 components in the needles and berries, respectively. The needle oil consisted mainly of sabinene (40.7%), α‐pinene (12.5%) and terpinen‐4‐ol (12.3%) and the berry oil included sabinene (36.8%), α‐pinene (20%), limonene (10.6%), germacrene D (8.2%) and myrcene (4.8%) as the main components. Copyright © 2003 John Wiley & Sons, Ltd.
Enones of (+)‐ and (−)‐3‐pinanone: inﬂuence of chirality on ﬂavour
Authors: Buchbauer G. , Shaﬁi‐Tabatabai A.
Published: September 2003

Starting with (+)‐ and (−)‐3‐pinanone [(+)‐ and (−)‐2], the enones 3–12 were prepared by aldol condensation with various aldehydes. Without isolating the corresponding β‐hydroxy ketones, the target compounds 3–12 could be obtained in good to moderate yields directly from the starting bicyclic ketone. The odour properties of the enones were evaluated and described. It could be shown that the structure of the aldehyde as well as the chirality is crucial for the ﬂavour impression of the enone. However, the (+)‐enantiomers generally possess more agreeable odours than their antipodes. Copyright © 2003 John Wiley & Sons, Ltd.
Essential oil composition of Aloysia polystachya (Griseb.) Moldenke under rust disease
Authors: Cabanillas Carmen M. , Lopez María L. , Daniele Graciela , Zygadlo Julio A.
Published: September 2003

Prospodium lippiae (Speg.) Arth.‐Berth (Basidiomycota, Heterobasidiomycetes, Uropyxidaceae) affects essential oil composition in Aloysia polystachya (Griseb.) Moldenke. Infected plants increased their content of carvone to 72.0%, while decreasing their percentage of α‐thujone to zero. Copyright © 2003 John Wiley & Sons, Ltd.
Characteristic odour components of Citrus inflata Hort. ex Tanaka (Mochiyu) cold‐pressed peel oil
Authors: Minh Tu N. T. , Onishi Y. , Son U. S. , Ogawa E. , Ukeda H. , Sawamura M.
Published: September 2003

Characteristic odour components of Citrus inflata Hort. ex Tanaka (Mochiyu) were studied by sensorial and instrumental techniques. Flavour dilution (FD) factor and relative flavour activity (RFA) of individual volatile components were evaluated by aroma extraction dilution analysis (AEDA) and gas chromatography–olfactometry (GC–O). The results indicated that hydrocarbons (98.1%) made up most of the oil: monoterpenes and sesquiterpenes were 97.6% and 0.5%, respectively. Among oxygenated compounds, linalool (0.2%) as an alcohol, perillaldehyde (0.1%) and tridecanal (0.1%) as aldehydes showed relatively high quantities, while the others were all less than 0.05%. AEDA and GC–O indicated that myrcene, (E)‐ocimene, cis‐linalool oxide, trans‐linalool oxide, β‐copaene, perillaldehyde and perillyl alcohol were the odour characteristic compounds, showing Mochiyulike odour. Careful sniff testing revealed that (E)‐ocimene could be an key odour compound of Mochiyu aroma. Copyright © 2003 John Wiley & Sons, Ltd.
Oct4 RNA interference induces trophectoderm differentiation in mouse embryonic stem cells
Authors: Velkey J. Matthew , O'Shea K. Sue
Published: September 2003

Summary: We examined whether suppression of Oct4 via RNA interference (RNAi) would affect embryonic stem (ES) cell lineage choice. Cells were transfected with plasmids containing an independently expressed reporter gene and an RNA polymerase type III promoter to constitutively express small stem‐loop RNA transcripts corresponding to Oct4 mRNA. Cells transfected with Oct4 RNAi constructs demonstrated reduced levels of Oct4 mRNA and exhibited characteristics of trophectodermal differentiation. These findings support the critical role of Oct4 in regulating stem cell identity and suggest that future experiments using RNAi in ES cells can elucidate the roles of other genes affecting lineage specification during differentiation. genesis 37:18–24, 2003. © 2003 Wiley‐Liss, Inc.
RNA inhibition of BMP‐4 gene expression in postimplantation mouse embryos
Authors: Gratsch Theresa E. , De Boer Lisa S. , O'Shea K. Sue
Published: September 2003

Short, hairpin RNA (shRNA) directed against bone morphogenetic protein 4 (Bmp‐4) was delivered to early postimplantation staged mouse embryos via tail vein injection of pregnant dams. As early as 24 h postinjection, embryos expressed a DsRed marker and later exhibited defects of neural fold elevation and closure and of cardiac morphogenesis. Immunohistochemical analysis of sectioned embryos indicated that Bmp‐4 protein was depleted and gene expression analysis indicated there was a reduction in Bmp‐4 mRNA and an upregulation of the Bmp‐4 antagonists, noggin and chordin, in embryos exposed to the shRNA, but not in control embryos. There was no change in the expression of Gata4, brachyury, or claudin6 in RNAi exposed embryos, indicating that RNA silencing was specific to Bmp‐4 rather than producing widespread gene inhibition. Delivery of shRNA to embryos has the potential to specifically knockdown the expression of developmentally essential genes and to rescue gene mutations, significantly decreasing the time required to analyze the function(s) of individual genes in development. genesis 37:12–17, 2003. © 2003 Wiley‐Liss, Inc.
α Complementation in the Cre recombinase enzyme
Authors: Casanova Emilio , Lemberger Thomas , Fehsenfeld Sandra , Mantamadiotis Theo , Schütz Günther
Published: September 2003

Summary: The Cre‐loxP system is increasingly exploited for spatial and temporal gene inactivation. Here we present a novel approach to achieve this goal of selective gene inactivation. Following the model of α complementation in the β‐galactosidase enzyme, where the enzyme is split into independent polypeptides which are able to associate and maintain the enzymatic activity, we divided the Cre recombinase into two independent polypeptides (one containing the NH2 terminus (α) and a second one containing the COOH‐terminus (β)). Individually, the two polypeptides have no detectable activity. However, when coexpressed the polypeptides are able to associate, giving rise to Cre enzymatic activity, which optimally is as high as 30% of that seen with wildtype Cre recombinase in vitro. We present this strategy as a modification of the traditional Cre‐loxP system, which could be used to obtain a highly specific recombination pattern by expressing the two halves under the control of separate promoters. genesis 37:25–29, 2003. © 2003 Wiley‐Liss, Inc.
Involvement of nuclear phosphatidylinositol‐dependent phospholipases c in cell cycle progression during rat liver regeneration
Authors: Albi Elisabetta , Rossi Graziella , Maraldi Nadir Mario , Magni Mariapia Viola , Cataldi Samuela , Solimando Liliana , Zini Nicoletta
Published: September 2003

Nuclear lipid metabolism is involved in the regulation of cell proliferation. Modulation of the expression and activity of nuclear PI‐phospholipase C (PI‐PLC) has been reported during liver regeneration after partial hepatectomy, although it has not been determined whether different PLC isoforms play specific roles in the regulation of cell cycle progression. Here, we report evidence that the increased activity of nuclear PLCs in regenerating rat liver occurs before the peak of DNA replication and involves the enzyme activity associated to the chromatin and not that associated to the nuclear membrane. Immunocytochemical analyses indicate that PI‐PLC β1 isoform is exclusively localized at the chromatin level, PI‐PLC β1 co‐localizes with DNA replication sites much more than PI‐PLC γ1, which is also present at the nuclear envelope. These findings and the increased amount of PI‐PLC γ1 occurring after the peak of DNA replication suggest that PI‐PLC β1 and γ1 play different roles in cell cycle progression during regenerating liver. The increased activity of PI‐PLC β1 constitutively present within the hepatocyte nucleus, should trigger DNA replication, whereas PI‐PLC γ1 should be involved in G2/M phase transition through lamin phosphorylation. J. Cell. Physiol. 197: 181–188, 2003. © 2003 Wiley‐Liss, Inc.
Synaptic vesicle morphology and recycling are altered in myenteric neurons of mice lacking dystrophin (mdx mice)
Authors: Vannucchi Maria Giuliana , Corsani Letizia , Faussone‐Pellegrini Maria‐Simonetta
Published: September 2003

Several dystrophin isoforms are known. The full‐length isoform is present in striated and smooth muscles and neurons and its lack causes Duchenne Muscular Dystrophy, a progressive myopathy accompanied by mild cognitive deficits and gastrointestinal dismotility. An ultrastructural study was undertaken in the colon of mice lacking full‐length dystrophin and maintaining shorter isoforms (mdx mice) to ascertain whether myenteric neurons have an altered morphology. Results showed a significant increase in the size of synaptic vesicle and in the number of recycling vesicles. An enlargement of endoplasmic reticulum cisternae in a subpopulation of neurons was also seen. Immunohistochemistry confirmed that the shorter isoforms were expressed in mdx mice myenteric neurons. These findings indicate the presence of a neuropathy at the myenteric plexus which might justify the defective neuronal control of gastrointestinal motility reported for these animals and which might be correlated with full‐length dystrophin loss, since the shorter isoforms are present. J. Cell. Physiol. 197: 232–242, 2003. © 2003 Wiley‐Liss, Inc.
NF1 modulates the effects of ras oncogenes: Evidence of other NF1 function besides its GAP activity
Authors: Corral Teresa , Jiménez María , Hernández‐Muñoz Inmaculada , Castro Ignacio Pérez de , Pellicer Angel
Published: September 2003

Neurofibromin (NF1) (the product of Nf1 gene) is a large cytosolic protein known as a negative regulator of Ras. A fragment of some 400 residues located at the center of the NF1 GAP‐Related Domain (NF1‐GRD) has strong identity with other molecules of the GAP family, which comprises, among others, the mammalian proteins NF1 and p120GAP, and the yeast proteins IRA1 and IRA2. GAP family members are known by their ability to promote the GTPase activity of Ras proteins, facilitating the transit of those proteins to their inactive state. Recent findings (Tong et al., 2002, Nat Neurosci 5:95–96) indicate that NF1 may be involved in the regulation of adenyl cyclase activity. Our results show that NF1‐GRD cooperates with Ras in the anchorage‐independent growth capacity of Ras‐expressing fibroblasts, without affecting: (i) their ability to grow in low serum, (ii) their cellular adhesion capability, or (iii) the expression of key proteins involved in cell–cell and cell–matrix interactions. On the other hand, NF1 overexpression induces an increase in the expression levels of the focal adhesion kinase (FAK), and specific changes in the activation status of the mitogen‐activated protein kinases (MAPKs). These results suggest the existence of a Ras‐independent NF1‐dependent pathway able to modify the levels of expression of FAK and the levels of activation of MAPKs. Because FAK and many proteins recently found to bind NF1 have a role in the cytoskeleton, this pathway may involve rearrangement of cytoskeletal components that facilitate anchorage independence. J. Cell. Physiol. 197: 214–224, 2003. © 2003 Wiley‐Liss, Inc.
Decapeptide with fibroblast growth factor (FGF)‐5 partial sequence inhibits hair growth suppressing activity of FGF‐5
Authors: Ito Chikako , Saitoh Yuko , Fujita Yasuko , Yamazaki Yoshimitsu , Imamura Toru , Oka Syuichi , Suzuki Satoshi
Published: September 2003

Earlier studies demonstrated that knock‐out of fibroblast growth factor‐5 gene (Fgf‐5) prolonged anagen VI phase of hair cycle, resulting long hairs in the mice. We showed the activities on hair growth of the two Fgf‐5 gene products, one of which, FGF‐5 suppressed hair growth by inhibiting anagen proceeding and inducing the transition from anagen to catagen, and FGF‐5S, a shorter polypeptide with FGF‐5‐antagonizing activity translated from alternatively spliced mRNA, suppressed this activity of FGF‐5. As the results suggested that FGF‐5 antagonist would increase hair growth, we synthesized various peptides having partial sequences of human FGF‐5 and FGF‐5S and determined their FGF‐5 antagonist activity. Among them, a decapeptide designated P3 (95‐VGIGFHLQIY‐104) that aligns with receptor binding sites of FGF‐1 and FGF‐2 suppressed FGF‐5‐induced proliferation of BALB/3T3 A31 and NIH/3T3 murine fibroblasts, and FGF receptor‐1c (FGFR‐1c)‐transfected Ba/F3 cell line (FR‐Ba/F3 cells). IC50s of this peptide on these cell proliferations were 64, 28, 146 μM, respectively. On the other hand, IC50 of this peptide on binding of FGF‐5 to the FGFR‐1(IIIc)/Fc chimera was 483 μM. Examination in dorsal depilated mice revealed that the P3 peptide reduced the activity of FGF‐5 to recover hair pigmentation and hair follicle lengths. The classification of histologically observed skin sections showed FGF‐5‐induced delations of anagen procedure had reduced by the P3 peptide. The anti‐Ki67 antibody staining of hair follicles was inhibited by administration of FGF‐5, and this inhibition by FGF‐5 was recovered by administration of the P3 peptide. The P3 peptide alone did not affect hair follicle length and hair cell proliferation. These results indicate that the decapeptide antagonized FGF‐5 activity in vivo, and reduced the inhibition of FGF‐5 in hair growth, confirming that FGF‐5 inhibitors are promising substances against hair loss and/or for promoting hair growth. J. Cell. Physiol. 197: 272–283, 2003. © 2003 Wiley‐Liss, Inc.
Hand tremor and orofacial dyskinesia: Clinical manifestations of glutaric aciduria type I in a young girl
Authors: Fernández‐Álvarez Emilio , García‐Cazorla Angeles , Sans Anna , Boix Cristina , Vilaseca María Antonia , Busquets Christianne , Ribes Antonia
Published: September 2003

A 16‐year‐old girl with a history of postural hand tremor was investigated. Magnetic resonance imaging, biochemical, enzymatic, and molecular studies demonstrated glutaric aciduria type I (GA1). Now, at 19 years of age, focal dystonia and oral dyskinesia are also present. This is the first reported case of GA1 with such clinical phenotype. © 2003 Movement Disorder Society
Fast micrographia and pallidal pathology
Authors: Quinn Niall , Kuoppamäki Mikko
Published: September 2003

Fast micrographia differs from the customary micrographia of Parkinson's disease and appears to be characteristic of patients with pallidal lesions. © 2003 Movement Disorder Society
Analysis of the ϵ‐sarcoglycan gene in familial and sporadic myoclonus‐dystonia: Evidence for genetic heterogeneity
Authors: Valente Enza‐Maria , Misbahuddin Anjum , Brancati Francesco , Placzek Mark R. , Garavaglia Barbara , Salvi Sergio , Nemeth Andrea , Shaw‐Smith Charles , Nardocci Nardo , Bentivoglio Anna‐Rita , Berardelli Alfredo , Eleopra Roberto , Dallapiccola Bruno , Warner Thomas T.
Published: September 2003

The ϵ‐sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus–dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus–dystonia. To evaluate the relevance of SGCE in myoclonus–dystonia, we sequenced the entire coding region of the ϵ‐sarcoglycan gene in 16 patients with either sporadic or familial myoclonus–dystonia. No mutations were found. This study suggests that ϵ‐sarcoglycan does not play an important role in sporadic myoclonus–dystonia and supports genetic heterogeneity in familial cases. © 2003 Movement Disorder Society
Patients', doctors', and caregivers' assessment of disability using the UPDRS‐ADL section: Are these ratings interchangeable?
Authors: Martínez‐Martín Pablo , Benito‐León Julian , Alonso Fernando , Catalán M. José , Pondal Margarita , Tobías Aurelio , Zamarbide Ivana
Published: September 2003

This multicenter study sought to analyze the validity and reliability of the Unified Parkinson's Disease Rating Scale (UPDRS)‐section 2 (Activities of Daily Living, ADL) as applied by patients and caregivers. Sixty pairs of PD patients–caregivers were enrolled for study purposes. Neurologists used a set of scales to determine disease severity and patients' functional state. Patients and caregivers used adapted versions of the UPDRS‐section 2 in tandem with other measures. Wilcoxon and Mann‐Whitney tests, weighted κ, intraclass and Spearman's correlation coefficients, as well as multivariate linear regression models were applied. On the whole, PD patient self‐assessment and caregiver evaluation of patients' disability showed close concordance with neurologists' ratings. Correlation between caregiver ratings and clinical evaluation tended to be slightly lower than that for patient‐based self‐assessment. Depression showed a positive correlation with disability and had a nonsystematic influence on UPDRS‐section 2 (ADL) scores. As expected, there was a significant correlation between perceived disability and health‐related quality of life measures. Caregiver burden did not reduce the level of agreement with neurologists as to the overall rating of any given patient's disability. In PD, UPDRS‐section 2–based assessment of disability by patients themselves and caregivers is a valid and reliable outcome. © 2003 Movement Disorder Society
Prospective study of presynaptic dopaminergic imaging in patients with mild parkinsonism and tremor disorders: Part 1. Baseline and 3‐month observations
Authors: Benamer Hani T.S. , Oertel Wolfgang H. , Patterson Jim , Hadley Donald M. , Pogarell Oliver , Höffken H. , Gerstner A. , Grosset Donald G.
Published: September 2003

To record prospectively, from early presentation, the clinical features of parkinsonism and tremor disorders, in relation to evidence of dopaminergic deficit shown with [123I]‐FP‐CIT (DaTSCAN, Amersham Health) single photon emission computerised tomography (SPECT). Clinical signs were recorded in 62 patients, of whom 24 failed standard Parkinson's disease (PD) and essential tremor criteria, and 38 fulfilled UK Brain Bank step 1 PD criteria. Striatal radioligand uptake was graded visually as normal or abnormal, and specific:nonspecific ratios were calculated. Bradykinesia and rigidity showed significant overall association with abnormal scans (P ≤ 0.003), but rest tremor did not (P = NS). In the 24 patients not fulfilling specific criteria (mean age 63 [SD 9] years, disease duration 3 [SD 4] years), 10 (42%) had abnormal visual SPECT assessment and 14 (58%) had normal scans. Of 38 patients with early PD by clinical criteria (mean age 60 [SD 9] years, disease duration 3 [SD 1.7] years), 33 (87%) were visually abnormal. Baseline clinical diagnosis corresponded with SPECT imaging results in 51 of 62 cases (82%), which increased to 56 of 62 cases (90%) with amendment of seven clinical diagnoses at 3 months (blind to SPECT results). Akinetic–rigid cardinal diagnostic features of parkinsonism associate well with dopaminergic deficit in patients with early and mild clinical features. When these clinical features are uncertain, or the patient fails clinical diagnostic criteria, testing for dopaminergic deficit with [123I]‐FP‐CIT SPECT may assist the diagnostic process. © 2003 Movement Disorder Society
Nigral glutathione deficiency is not specific for idiopathic Parkinson's disease
Authors: Fitzmaurice Paul S. , Ang Lee , Guttman Mark , Rajput Ali H. , Furukawa Yoshiaki , Kish Stephen J.
Published: September 2003

The consistent findings of decreased levels of the major antioxidant glutathione in substantia nigra of patients with idiopathic Parkinson's disease (PD) has provided most of the basis for the oxidative stress hypothesis of the etiology of PD. To establish whether a nigral glutathione deficiency is unique to PD, as is generally assumed, or is present in other Parkinsonian conditions associated with nigral damage, we compared levels of reduced glutathione (GSH) in postmortem brain of patients with PD to those with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). As compared with the controls, nigral GSH levels were decreased in the PD and PSP patient groups (P < 0.05 for PD [−30%], PSP [−21%]), whereas a similar decrease in the MSA patient group did not reach statistical significance (P = 0.078, MSA [−20%]). GSH levels were normal in all examined normal and degenerating extra‐nigral brain areas in PSP and MSA. A trend for decreased levels of uric acid (antioxidant and product of purine catabolism) also was observed in nigra of all patient groups (−19 to −30%). These data suggest that glutathione depletion, possibly consequent to overutilisation in oxidative stress reactions, could play a causal role in nigral degeneration in all nigrostriatal dopamine deficiency disorders, and that antioxidant therapeutic approaches should not be restricted to PD. © 2003 Movement Disorder Society
TorsinA immunoreactivity in inclusion bodies in trinucleotide repeat diseases
Authors: Walker Ruth H. , Good Paul F. , Shashidharan P.
Published: September 2003

A mutation of the DYT1 gene, which codes for torsinA, has been identified as a cause of autosomal dominantly inherited dystonia. The function of torsinA is not yet known, but it is found throughout the central nervous system and has been identified in Lewy bodies in Parkinson's disease. We examined cases of Huntington's disease, spinocerebellar ataxia type III, and Huntington's disease‐like 2 using antibodies to torsinA, and found that ubiquitinated, intranuclear neuronal inclusions were torsinA‐immunoreactive, possibly indicating a role for torsinA in protein degradation. © 2003 Movement Disorder Society