bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosynthesis and degradation of Rubisco during ovary senescence and fruit development induced by gibberellic acid in Pisum sativum
Authors: Cercós Manuel , Carrasco Pedro , Granell Antonio , Carbonell Juan
Published: April 2005

The concentration, biosynthesis and proteolytic degradation of ribulose‐1,5‐bisphosphate carboxylase/oxygenase (Rubisco; EC 4.1.1.39) and the level of the transcripts of the large and the small subunits were studied in unpollinated ovaries of Pisum sativum L. cv. Alaska during the early stages of ovary senescence and during early parthenocarpic fruit development induced by gibberellic acid (GA). De novo synthesis of Rubisco during fruit development is associated with both an activation of protein synthesis and an increase of the mRNA levels, especially of those for the small subunit of the protein. However, in senescent ovaries, senescence‐specific proteolysis seems to be the operating mechanism controlling Rubisco level as supported by the following observations: (1) Rubisco cleavage fragments of 52 and 30 kDa were detected in crude extracts from senescent ovaries, but these in‐vivo‐produced polypeptides were not present in extracts from either presenescent or GA‐treated ovaries; (2) a new proteolytic activity at neutral pH and an enhancement of acidic proteolytic activity were detected in an in vitro assay only in extracts of senescent ovaries.
Photosynthesis and photoinhibition in leaves of chlorophyll b‐less barley in relation to absorbed light
Authors: Leverenz Jerry W. , Öquist Gunnar , Wingsle Gunnar
Published: April 2005

The response of photosynthesis to absorbed light by intact leaves of wild‐type (Hordeum vulgare L. cv. Gunilla) and chlorophyll b‐less barley (H. vulgare L. cv. Dornaria, chlorina‐f22800) was measured in a light integrating sphere. Up to the section where the light response curve bends most sharply the responses of the b‐less and wild‐type barley were similar but not identical. Average quantum yield and convexity for the mutant light response curves were 0.89 and 0.90, respectively, times those of the wild‐type barley. The maximum quantum yield for PSII photochemistry was also 10% lower as indicated by fluorescence induction kinetics (Fv/Fm). Just above the region where the light curve bends most sharply, photosynthesis decreased with time in the mutant but not in the wild‐type barley. This decrease was associated with a decrease in Fv/Fm indicating photoinhibition of PSII. This photoinhibition occurred in the same region of the light response curve where zeaxanthin formation occurs. Zeaxanthin formation occurred in both the chlorophyll b‐less and wild‐type leaves. However, the epoxidation state was lower in the mutant than in the wild‐type barley. The results indicate that chlorophyll b‐less mutants will have reduced photosynthetic production as a result of an increased sensitivity to photoinhibition and possibly a lowered quantum yield and convexity in the absence of photoinhibition.
Induction of heat shock‐like proteins in Vigna sinensis seedlings growing under ultraviolet‐B (280‐320 nm) enhanced radiation
Authors: Nedunchezhian N. , Annamalainathan K. , Kulandaivelu G.
Published: April 2005

The effect of ultraviolet‐B (UV‐B) enhanced fluorescent radiation on protein profile and protein synthesis has been investigated in Vigna sinensis L. cv. Walp seedlings growing at various temperatures. In seedlings growing at 30°C, UV‐B radiation decreased the level of several proteins as seen in Coomassie brilliant blue stained gel. However, fluorography of the same gel indicates induction of three sets of proteins in the range of 70. 53 and 16 k Da. Such induction under UV‐B enhanced radiation resembled that found after heat shock treatments. In seedlings at 10 and 20°C, induction of such proteins varied both qualitatively and quantitatively. At 40°C. UV‐B enhanced radiation caused a cumulative effect with temperature. Strong induction of specific proteins by UV‐B radiation in seedlings growing under normal temperature indicates a possible protective role.
An extracellular β‐galactosidase secreted from cell suspension cultures of carrot. Its purification and involvement in cell wall‐polysaccharide hydrolysis
Authors: Konno Haruyoshi , Katoh Kenji
Published: April 2005

β‐Galactosidase (β‐Galase, EC 3.2.1.23) activity has been detected in a culture medium of cell suspension cultures of carrot (Daucus carota L. cv. Kintoki). The extracellular β‐Galase (β‐Galase‐II) was purified to electrophoretic homogeneity from the concentrated medium using ammonium sulfate precipitation, chromatography on CM‐Sephadex C‐50. DEAE‐Sepharose CL‐6B and Sephacryl S‐200HR, and preparative PAGE. The molecular mass of the purified enzyme was estimated to be 65 kDa by Sephacryl S‐200HR gel‐permeation, and 60 kDa by SDS‐PAGE after treatment with SDS and 2‐mercaptoethanol. The pI was 6.5. The Km and Vmax values for p‐nitrophenyl (PNP)‐β‐D‐galactopyranoside were 0.17 mM and 31.9 μmol (mg protein)‐1, h‐1, respectively. The optimal activity in McIlvaine's buffer occurred at pH 4.0–4.4. The enzyme activity was inhibited by Co24, Cu2+, Hg2‐, p‐chloromercuribenzoate (PCMB) and D‐galactono‐1,4‐lactone. The enzyme acted on citrus galactan and larchwood arabinogalactan in an exo‐fashion, and was slightly involved in the hydrolysis of an acidic pectic polymer containing arabinosyl and galactosyl residues and in the breakdown of cell walls isolated from carrot cell cultures.
Rhizobial siderophore as an iron source for clover
Authors: Derylo Mieczyslawa , Skorupska Anna
Published: April 2005

Iron uptake by clover plants (Trifoliuin pratense L. cv. Hruszowska) was studied using radioactive ferric iron (55FeCl2). As shown by autoradiography of non‐infected plants, purified rhizobial siderophore isolated from Rhizobium leguminosarum by, trifolii, stimulated the uptake and shoot transport of iron. Addition of rhizobial siderophore into the growth medium of nodulated clover did not affect the iron transport to the shoots. In the absence of the rhizobial siderophore, clover infected by either nitrogen‐fixing (Nod− Fix+) or nonfixing (Nod+ Fix−) R. L. trifolii strains took up and transported into the shoots more iron than the non‐infected control plants. Nodulated clover reduced Fe(III) more efficiently than the non‐infected control plants.
The effects of development at sub‐optimal growth temperatures on photosynthetic capacity and susceptibility to chilling‐dependent photoinhibition in Zea mays
Authors: Nie Gui‐Ying , Long Steve P. , Baker Neil R.
Published: April 2005

When plants of Zea mays L. cv. LG11 that have been grown at optimal temperatures are transferred to chilling temperatures (0–12°C) photoinhibition of photosynthetic CO2 assimilation can occur. This study examines how growth at sub‐optimal temperatures alters both photosynthetic capacity and resistance to chilling‐dependent photoinhibition. Plants of Z. mays cv. LG11 were grown in controlled environments at 14, 17, 20 and 25°C. As a measure of the capacity for photosynthesis under light limiting conditions, the maximum quantum yields of CO2 assimilation (φa.c) and O2 evolution (φa.o) were determined for the laminae of the second leaves at photon fluxes of 50–150 μmol m‐2s‐1. To determine photosynthetic capacity at photon fluxes approaching light saturation, rates of CO2 uptake (A1500) and O2 evolution (A1500) were determined in a photon flux of 1500 μmol m‐2s‐1. In leaves developed at 14°C, φ and φ were 26 and 43%, respectively, of the values for leaves grown at 25°C. Leaves grown at 17°C showed intermediate reductions in φ and φ, whilst leaves developed at 20°C showed no significant differences from those grown at 25°C. Similar patterns of decrease were observed for A1500 and A1500.0 with decreasing growth temperature. Leaves developed at 25°C showed higher rates of CO2 assimilation at all light levels and measurement temperatures in comparison to leaves developed at 17 and 14°C. A greater reduction in A1500 relative to A1500.0 with decreasing growth temperature was attributed to increased stomatal limitation. Exposure of leaves to 800–1000 μmol m‐2 s‐1 when plant temperature was depressed to ca 6.5°C produced a photoinhibition of photosynthetic CO2 assimilation in all leaves. However, in leaves developed at 17°C the decrease in A1500 following this chilling treatment was only 25% compared to 90% in leaves developed at 25°C. Recovery following chilling was completed earlier in leaves developed at 17°C. The results suggest that growth at sub‐optimal temperatures induces increased tolerance to exposure to high light at chilling temperatures. This is offset by the large loss in photosynthetic capacity imposed by leaf development at sub‐optimal temperatures.
Colorectal intervention as part of surgery for patients with gynaecological malignancy
Authors: Bedirli A. , Mentes B. B. , Onan A. , Kerem M. , Pala M. I. , Sakrak O. , Oguz M.
Published: April 2005

Objective  This study was conducted to determine the indications for and outcome of colorectal intervention in patients with advanced gynaecological malignancy.

Methods  Between January 1999 and June 2004, 27 gynaecological cancer patients underwent 36 colorectal intervention performed by general surgeons. The 36 operations were associated with 14 (39%) primary surgical procedures, 9 (25%) second‐look laparotomies, and 13 (36%) procedures for recurrence or palliation.

Results  The mean age was 56 years (range 32–83 years). The majority of operations were performed in patients with ovarian (67%), endometrial (18%) and cervical (15%) malignancy. The primary indications for colorectal resection was tumour cytoreduction in 56% of the 36 operations. Other indications included repair of iatrogenic bowel injuries (n = 9, 25%), resection for multiple iatrogenic enterotomies (n = 4, 11%), and bowel obstruction (n = 3, 8%). The most frequently performed bowel operation was rectosigmoid resection with end‐to‐end anastomosis (n = 19, 53%). Colostomy was performed in 14% of the rectosigmoid resections at primary surgery. Small‐bowel resection was required in 31% of the 36 operations. Postoperative complications included wound complications (14%), pulmonary infections (8%), cardiac complications (6%) and intra‐abdominal abscess (6%). There was a single surgical mortality (3%).

Conclusion  Colorectal intervention is frequently indicated during operations for advanced gynaecological malignancy, and they are associated with a significant rate of postoperative complications. Specialists operating on gynaecological malignancy should have the technical skills necessary to perform these procedures.
MRI assessment of the bony pelvis may help predict resectability of rectal cancer
Authors: Boyle K. M. , Petty D. , Chalmers A. G. , Quirke P. , Cairns A. , Finan P. J. , Sagar P. M. , Burke D.
Published: April 2005

Objective  The outcome after surgical treatment of rectal cancer may be influenced by the technical difficulty of the operation, which is thought to be affected by pelvic size. The aim of this study was to examine the association between bony pelvic dimensions and CRM involvement.

Patients and methods  All patients with primary rectal cancer between December 1999 and January 2002 were studied. Staging was performed by pelvic MRI. Nine pelvic dimensions were measured from the MR images on a workstation. Pathology reports were obtained for all patients and the mesorectal specimen was examined. Technical difficulty was assessed by circumferential resection margin (CRM) involvement.

Results  Of 126 patients with primary rectal cancer, 88 had staging MRI and rectal excision; there were significant differences between the sexes in all 9 pelvic dimensions (P < 0.05). In females, the interspinous diameter was significantly shorter in patients with CRM involvement compared with patients with a negative CRM. In female patients predicted to have a negative CRM, the anteroposterior diameter of the inlet, the anteroposterior diameter of the midplane and the transverse diameter of the midplane (interspinous distance) were significantly shorter in patients who actually had a positive CRM compared with those in whom the CRM was negative. In male patients, there was no correlation between pelvic dimensions and CRM status.

Conclusions  In certain patients with rectal cancer, CRM positivity may be predicted from pre‐operative MRI pelvic measurements. This may influence the choice of adjuvant therapy.
The mbuna cichlids of Lake Malawi: a model for rapid speciation and adaptive radiation
Authors: Genner Martin J. , Turner George F.
Published: April 2005

Mbuna, the dominant fishes on the rocky shores of Lake Malawi, have become a major ‘model system’ for the study of rapid speciation and adaptive radiation. At least 295 putative species are known, of which more than 200 remain undescribed. There is no good evidence for monophyly in the mbuna, rather mitochondrial DNA phylogenies indicate that they are polyphlyetic with respect to benthic feeding cichlids of the generaAulonocara,Alticorpusand some species ofLethrinops. Male mbuna hold territories for 18 months or more and breed year‐round. All species are maternal mouthbrooders, but females do not guard free‐swimming young. Mbuna are polygamous (both sexes). There is sexual dimorphism in size, colour and fin length, and many species show within‐population colour polymorphism. Mbuna genera are largely differentiated on the basis of head, jaw and tooth morphology, but congeneric species are generally distinguished by male colour. Many morphologically specialized forms have broad diets and often feed on common easily obtainable resources. While it is likely that dietary and habitat niche partitioning contributes to species coexistence, this has never clearly been demonstrated under experimental conditions. Populations on spatially separated habitat patches are often genetically differentiated, probably because most species are specialized for life on rocky shores, and lack a dispersal phase in their life histories. Males seem to disperse more than females, but are able to home several kilometres back to their territories. Some closely related ecologically equivalent allopatric populations are differentiated in male colour. Those tested have been shown to mate at least partially assortatively. Sexual selection acting on male colour seems the most plausible mechanism for initial species divergence. The same colour forms seem to have arisen several times, suggesting frequent parallel evolution. The main conservation threat to mbuna at present seems to be translocation of species within the lake as a result of the aquarium trade. However, deleterious effects on indigenous populations are not documented. In the long run, sedimentation, pollution, introduction of alien species and the development of targeted food fisheries could be more serious threats.
Perianal ulceration: a case of tuberculosis cutis orificialis
Authors: Leon‐Mateos A , Sánchez‐Aguilar D , Lado F , Toribio J
Published: April 2005

Background  Tuberculosis cutis orificialis is an extremely rare variant of cutaneous tuberculosis. Perianal location is a possible site of presentation.

Methods  We describe the management of a young male with a painless non‐specific perianal ulcer, who presented an asymptomatic disseminate pulmonary and intestinal tuberculosis. He had a history of pulmonary sarcoidosis and long‐term corticosteroid therapy.

Results  Healing of the ulcer was achieved after three‐drug antituberculous therapy, with an improvement of the radiographic pulmonary alterations.

Conclusions  Tuberculous origin should be considered in persistent perianal ulcers to avoid delays in the treatment of this rare form of tuberculosis.
Mucosal vulval lichen planus: outcome, clinical and laboratory features
Authors: Kirtschig G , Wakelin SH , Wojnarowska F
Published: April 2005

Background  Mucosal lichen planus of the vulva is a rare but increasingly recognized condition. It has potentially severe complications such as fusion of the labia and vagina; the risk of developing squamous cell carcinoma (SCC) may be increased. An association between hepatitis B and C infection and skin or oral lichen planus appears to exist in certain geographical areas.

Objective  To investigate the course of mucosal vulval lichen planus, its response to treatment and associated laboratory features.

Subjects and methods  Forty‐four women with mucosal vulval lichen planus were studied between 1997 and 2000 and laboratory data were collected.

Results  Thirty of 44 patients had additional oral lesions, only nine had cutaneous findings compatible with lichen planus. We did not find an association with antibodies to hepatitis B or C virus in this British study population. All women were treated with potent to very potent topical corticosteroids; however, in the majority of patients symptoms persisted. In seven (16%) patients vulval lichen planus was in remission after a disease duration between 2 and 18 years (mean 10.6 years). One patient developed a vulval SCC.

Conclusions  Screening for hepatitis B and C in women with mucosal vulval lichen planus in the UK seems unnecessary. We recommend long‐term follow‐up, and that all non‐healing ulcerative and papular lesions should be biopsied.
Clinico‐pathological analysis of the cutaneous lesions of a patient with type I pseudohypoaldosteronism
Authors: Martín JM , Calduch L , Monteagudo C , Alonso V , García L , Jordá E
Published: April 2005

The autosomal recessive form of type I pseudohypoaldosteronism (PHA‐I) is an unusual disorder characterized by aldosterone resistance at the target organs, which leads to an excessive loss of sodium chloride through urine, sweat and saliva, among other secretions. Such a high concentration of salt in the sweat during the depletive crises directly causes inflammation and damage in the eccrine structures, with cutaneous lesions similar to those appearing in miliaria rubra. We report an autosomal recessive PHA‐I in a 4‐year‐old girl, with cutaneous lesions mimicking miliaria rubra, that improved after treatment with astringent solutions and avoidance of profuse sweating.
Hyaluronic acid: a unique topical vehicle for the localized delivery of drugs to the skin
Authors: Brown MB , Jones SA
Published: April 2005

Hyaluronic acid (HA) is a naturally occurring polyanionic, polysaccharide that consists of N‐acetyl‐d‐glucosamine and β‐glucoronic acid. It is present in the intercellular matrix of most vertebrate connective tissues especially skin where it has a protective, structure stabilizing and shock‐absorbing role. The unique viscoelastic nature of HA along with its biocompatibility and non‐immunogenicity has led to its use in a number of clinical applications, which include: the supplementation of joint fluid in arthritis; as a surgical aid in eye surgery; and to facilitate the healing and regeneration of surgical wounds. More recently, HA has been investigated as a drug delivery agent for various routes of administration, including ophthalmic, nasal, pulmonary, parenteral and topical. In fact, regulatory approval in the USA, Canada and Europe was granted recently for 3% diclofenac in 2.5% HA gel, Solaraze®, for the topical treatment of actinic keratoses, which is the third most common skin complaint in the USA. The gel is well tolerated, safe and efficacious and provides an attractive, cost‐effective alternative to cryoablation, curettage or dermabrasion, or treatment with 5‐fluorouracil. The purpose of this review is to describe briefly the physical, chemical and biological properties of HA together with some details of its medical and pharmaceutical uses with emphasis on this more recent topical application.
Kaposi sarcoma associated with lipoedema
Authors: Ekmekci TR , Ayabakan O , Sakiz D , Koslu A
Published: April 2005

Lipoedema is a form of lipodistrophy, which consists of abnormal accumulation of fat in subcutaneous tissue of the lower limbs. It does not cause any disease and it has not been reported association with malignity. We describe a 63‐year‐old woman occuring of Kaposi sarcoma on the lipoedema base.
Case–control study to identify melanoma risk factors in the Belgian population: the significance of clinical examination
Authors: Nijsten T , Leys C , Verbruggen K , Verlinden V , Drieghe J , Stas M , Lambert J , DeGreef H , Garmyn M
Published: April 2005

Background  Although numerous studies have evaluated risk factors associated with cutaneous malignant melanoma (CMM), no such study has been carried out in Belgium.

Objectives  To identify individuals who are at high risk of developing malignant melanoma in Belgium, which could enhance the efficacy of screening interventions and avoid unnecessary skin inspections.

Study design/setting/subjects  We prospectively included patients who were diagnosed with invasive malignant melanoma between 1998 and 2001 at the Department of Dermatology in a case–control study. Controls were selected from the outpatient dermatology clinic. Participants were interviewed and clinically examined by a dermatologist. We asked questions concerning most known risk factors associated with malignant melanoma such as phenotypical and skin characteristics, and environmental and lifestyle exposures. To adjust for confounding variables and to estimate odds ratios (ORs) and 95% confidence intervals (CIs), a multivariate model was used.

Results  Although sunburn in childhood and substantial occupational solar exposure were modestly, but significantly, associated with malignant melanoma risk, clinical examination yielded several stronger risk factors. In a multivariate model, which adjusted for age, gender and skin phototype, phenotypical characteristics such as skin, hair and eye colour were significantly associated with the development of malignant melanoma. In the multivariate model, people with three or more atypical naevi were at more than 10‐fold risk of developing a malignant melanoma (≥ 3 atypical naevi; adjusted OR = 11.40, 95% CI = 4.79–17.53) compared to those without an atypical naevus. The presence of one or more palpable naevi on the upper extremities or having solar lentigines increased the odds of developing malignant melanoma at least twofold.

Conclusions  In Belgium, risk factors associated with malignant melanoma appear to be in accordance with previous studies. To assess peoples’ risk profile, clinical skin examination is likely to yield the most important sporadic malignant melanoma risk factors. Therefore, focusing screening campaigns on individuals with predefined findings on skin self‐examination may increase its efficacy.
Position paper on diagnosis and treatment of atopic dermatitis
Authors: Darsow U , Lübbe J , Taïeb A , Seidenari S , Wollenberg A , Calza AM , Giusti F , Ring J ,   for the European Task Force on Atopic Dermatitis
Published: April 2005

The diagnosis of atopic dermatitis (AD) is made using evaluated clinical criteria. Management of AD must consider the symptomatic variability of the disease. It is based on hydrating topical treatment, and avoidance of specific and unspecific provocation factors. Anti‐inflammatory treatment is used for exacerbation management. Topical corticosteroids remain the first choice. Systemic anti‐inflammatory treatment should be kept to a minimum, but may be necessary in rare refractory cases. The new topical calcineurin inhibitors (tacrolimus and pimecrolimus) expand the available choices of topical anti‐inflammatory treatment. Microbial colonization and superinfection (e.g. with Staphylococcus aureus, Malassezia furfur) can have a role in disease exacerbation and can justify the use of antimicrobials in addition to the anti‐inflammatory treatment. Evidence for the efficacy of systemic antihistamines in relieving pruritus is still insufficient, but some patients seem to benefit. Adjuvant therapy includes ultraviolet (UV) irradiation preferably of UVA wavelength; UVB 311 nm has also been used successfully. Dietary recommendations should be specific and only given in diagnosed individual food allergy. Stress‐induced exacerbations may make psychosomatic counselling recommendable. ‘Eczema school’ educational programmes have proved to be helpful.
Functional analysis of the foot and ankle myology of gibbons and bonobos
Authors: Vereecke Evie E. , D’Août Kristiaan , Payne Rachel , Aerts Peter
Published: April 2005

This study investigates the foot and ankle myology of gibbons and bonobos, and compares it with the human foot. Gibbons and bonobos are both highly arboreal species, yet they have a different locomotor behaviour. Gibbon locomotion is almost exclusively arboreal and is characterized by speed and mobility, whereas bonobo locomotion entails some terrestrial knuckle‐walking and both mobility and stability are important. We examine if these differences in locomotion are reflected in their foot myology. Therefore, we have executed detailed dissections of the lower hind limb of two bonobo and three gibbon cadavers. We took several measurements on the isolated muscles (mass, length, physiological cross sectional area, etc.) and calculated the relative muscle masses and belly lengths of the major muscle groups to make interspecific comparisons. An extensive description of all foot and ankle muscles is given and differences between gibbons, bonobos and humans are discussed. No major differences were found between the foot and ankle musculature of both apes; however, marked differences were found between the ape and human foot. The human foot is specialized for solely one type of locomotion, whereas ape feet are extremely adaptable to a wide variety of locomotor modes. Apart from providing interesting anatomical data, this study can also be helpful for the interpretation of fossil (pre)hominids.
Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease
Authors: Wang J. , Xiong S. , Xie C. , Markesbery W. R. , Lovell M. A.
Published: April 2005

Increasing evidence suggests that oxidative stress is associated with normal aging and several neurodegenerative diseases, including Alzheimer's disease (AD). Here we quantified multiple oxidized bases in nuclear and mitochondrial DNA of frontal, parietal, and temporal lobes and cerebellum from short postmortem interval AD brain and age‐matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring (GC/MS‐SIM) and stable labeled internal standards. Nuclear and mitochondrial DNA were extracted from eight AD and eight age‐matched control subjects. We found that levels of multiple oxidized bases in AD brain specimens were significantly (p < 0.05) higher in frontal, parietal, and temporal lobes compared to control subjects and that mitochondrial DNA had approximately 10‐fold higher levels of oxidized bases than nuclear DNA. These data are consistent with higher levels of oxidative stress in mitochondria. Eight‐hydroxyguanine, a widely studied biomarker of DNA damage, was approximately 10‐fold higher than other oxidized base adducts in both AD and control subjects. DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was only slightly affected in AD brains. These results suggest that oxidative damage to mitochondrial DNA may contribute to the neurodegeneration of AD.
Elevation of the Hsp70 chaperone does not effect toxicity in mouse models of familial amyotrophic lateral sclerosis
Authors: Liu Jian , Shinobu Leslie A. , Ward Christopher M. , Young Darren , Cleveland Don W.
Published: April 2005

Mutations in copper/zinc superoxide dismutase (SOD1) account for 10–20% of a familial form of amyotrophic lateral sclerosis (ALS). A common feature of SOD1 mutants is abnormal aggregation of the aberrant SOD1 in neurons and glia. We now report that in ALS transgenic mouse models the constitutively expressed heat shock protein 70 (Hsp70) is mislocalized into aggregates together with mutant SOD1 and ubiquitin. Forcing increased synthesis of Hsp70 ameliorates both aggregate formation and toxicity in primary motor neurons in culture. However, chronic increase in an inducible form of Hsp70 to about 10‐fold its normal level is shown here not to affect disease course or pathology developed in mice from accumulation of any of three familial ALS causing SOD1 mutants with different underlying biochemical characteristics. Therefore, increasing Hsp70 to a level that is protective in mouse models of acute ischemic insult and selected neurodegenerative disorders is not sufficient to ameliorate mutant SOD1‐mediated toxicity.
Modulatory effects of progesterone on inducible nitric oxide synthase expression in vivo and in vitro
Authors: Coughlan Teresa , Gibson Claire , Murphy Sean
Published: April 2005

Nitric oxide (NO) is produced in the CNS following injury‐induced expression of inducible nitric oxide synthase (iNOS), yet its role as protective or damaging is unclear. Previous studies investigating the therapeutic potential of female sex steroids in stroke and trauma suggest that NO from this source is harmful, since oestradiol and progesterone decreased the level of iNOS expression in vitro and improved neurological outcome. We investigated the effects of progesterone on stroke‐induced expression of iNOS in mice, as well as cytokine‐induced expression of iNOS and its transcriptional activators in cells relevant to injury. We observed a significant reduction in stroke‐induced iNOS transcript in progesterone‐treated mice and in cultured macrophages. In contrast, progesterone significantly amplifed cytokine‐induced iNOS mRNA in cultured primary astrocytes, although the expression of protein was decreased. We sequenced upstream of the 1.5 kb reported iNOS promoter region and identified a potential progesterone response element (PRE). Astrocytes transiently transfected with iNOS promoter/CAT reporter gene constructs containing the PRE displayed a significant increase in induction of CAT expression after progesterone treatment, and this was diminished in cells transfected with a construct containing a disrupted PRE. These observations suggest the involvement of iNOS in the neuroprotective effects of progesterone.
In vivo up‐regulation of brain‐derived neurotrophic factor in specific brain areas by chronic exposure to Δ9‐tetrahydrocannabinol
Authors: Butovsky Elena , Juknat Ana , Goncharov Igor , Elbaz Judith , Eilam Raya , Zangen Abraham , Vogel Zvi
Published: April 2005

Cannabinoids are widely abused drugs. Here we show that chronic administration of Δ9‐tetrahydrocannabinol (Δ9‐THC), the active psychotropic agent in marijuana and hashish, at 1.5 mg per kg per day intraperitoneally for 7 days, increases the expression, at both mRNA and protein levels, of brain‐derived neurotrophic factor (BDNF), in specific rat brain areas, notably in those involved in reward and addiction. Real‐time PCR revealed a 10‐fold up‐regulation of BDNF mRNA in the nucleus accumbens (NAc) upon chronic Δ9‐THC treatment, but there was no change at 3 or 24 h after a single injection. Smaller increases in mRNA levels were found in the ventral tegmental area (VTA), medial prefrontal cortex and paraventricular nucleus (PVN). Immunohistochemistry showed large increases in BDNF‐stained cells in the NAc (5.5‐fold), posterior VTA (4‐fold) and PVN (1.7‐fold), but no change was observed in the anterior VTA, hippocampus or dorsal striatum. Altogether, our study indicates that chronic exposure to Δ9‐THC up‐regulates BDNF in specific brain areas involved with reward, and provides evidence for different BDNF expression in the anterior and posterior VTA. Moreover, BDNF is known to modulate synaptic plasticity and adaptive processes underlying learning and memory, leading to long‐term functional and structural modification of synaptic connections. We suggest that Δ9‐THC up‐regulation of BDNF expression has an important role in inducing the neuroadaptive processes taking place upon exposure to cannabinoids.
Suberoylanilide hydroxamic acid (SAHA) has potent anti‐glioma properties in vitro, ex vivo and in vivo
Authors: Eyüpoglu Ilker Y. , Hahnen Eric , Buslei Rolf , Siebzehnrübl Florian A. , Savaskan Nicolai E. , Lüders Mike , Tränkle Christian , Wick Wolfgang , Weller Michael , Fahlbusch Rudolf , Blümcke Ingmar
Published: April 2005

Current treatment modalities for malignant gliomas do not allow long‐term survival. Here, we identify suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylases (HDAC), as an effective experimental anti‐glioma agent. Administration of SAHA to various glioma cell lines obtained from human, rat and mouse inhibited tumour cell growth in a range of 1–10 μm. This anti‐glioma property is associated with up‐regulation of the cell cycle control protein p21/WAF, as well as the induction of apoptosis. A novel tumour invasion model using slice cultures of rat brain corroborated the anti‐glioma properties of SAHA in the organotypic brain environment. In this model, glioma invasion compromised adjacent brain parenchyma, and this tumour‐associated cytotoxicity could be inhibited by SAHA. In addition, a 10‐fold dose escalation experiment did not challenge the viability of cultured brain slices. In vivo, a single intratumoural injection of SAHA 7 days after orthotopic implantation of glioma cells in syngeneic rats doubled their survival time. These observations identify chromatin‐modifying enzymes as possible and promising targets for the pharmacotherapy of malignant gliomas.
INNOVATIONS AND ECONOMIC DEVELOPMENT–THE CANADIAN CASE
Authors: Firestone O. J.
Published: April 2005

This paper assesses the role of inventive and innovational activity in the growth process of Canada, a country which relies overwhelmingly, some 90 per cent, on the importation of technological advances and operational know‐how from abroad. Canada has prospered under this arrangement but at a price. With technology came foreign capital, foreign management and substantial foreign control. To lessen Canada's dependence on foreign know‐how, this country has embarked on an expanded R & D programme. But the pay‐off from these efforts has been less than expected. To throw a light on the subject, the results of two new surveys are presented: one a sample survey of patents granted, the other an interview survey of large corporations. Questions examined include sources of know‐how and technological advances, utilization of inventions and abandonment of innovations, R & D and innovations, domestic and foreign innovations, and the profitability of innovations. Aggregative assessment is supplemented by disaggregative analysis using cross‐section and industry data.
Sm–Nd and U–Pb dating of high‐pressure granulites from the Złote and Rychleby Mts (Bohemian Massif, Poland and Czech Republic)
Authors: LANGE U. , BRÖCKER M. , ARMSTRONG R. , TRAPP E. , MEZGER K.
Published: April 2005

In the Orlica‐Śnieżnik complex at the NE margin of the Bohemian Massif, high‐pressure granulites occur as isolated lenses within partially migmatized orthogneisses. Sm–Nd (different grain‐size fractions of garnet, clinopyroxene and/or whole rock) and U–Pb [isotope dilution‐thermal ionization mass spectrometry (ID‐TIMS) single grain and sensitive high‐resolution ion microprobe (SHRIMP)] ages for granulites, collected in the surroundings of Červený Důl (Czech Republic) and at Stary Gierałtów (Poland), constrain the temporal evolution of these rocks during the Variscan orogeny. Most of the new ages cluster atc.350–340 Ma and are consistent with results previously reported for similar occurrences throughout the Bohemian Massif. This interval is generally interpreted to constrain the time of high‐pressure metamorphism. A more complex evolution is recorded for a mafic granulite from Stary Gierałtów and concerns the unknown duration of metamorphism (single, short‐lived metamorphic cycle or different episodes that are significantly separated in time?). The central grain parts of zircon from this sample yielded a large spread in apparent206Pb/238U SHRIMP ages (c.462–322 Ma) with a distinct cluster atc.365 Ma. This spread is interpreted to be indicative for variable Pb‐loss that affected magmatic protolith zircon during high‐grade metamorphism. The initiating mechanism and the time of Pb‐loss has yet to be resolved. A connection to high‐pressure metamorphism atc. 350–340 Ma is a reasonable explanation, but this relationship is far from straightforward. An alternative interpretation suggests that resetting is related to a high‐temperature event (not necessarily in the granulite facies and/or at high pressures) around 370–360 Ma, that has previously gone unnoticed. This study indicates that caution is warranted in interpreting U–Pb zircon data of HT rocks, because isotopic rejuvenation may lead to erroneous conclusions.
Timing and nature of fluid flow and alteration during Mesoproterozoic shear zone formation, Olary Domain, South Australia
Authors: CLARK C. , MUMM A. SCHMIDT , FAURE K.
Published: April 2005

The development of shear zones at mid‐crustal levels in the Proterozoic Willyama Supergroup was synchronous with widespread fluid flow resulting in albitization and calcsilicate alteration. Monazite dating of shear zone fabrics reveal that they formed at 1582 ± 22 Ma, at the end of the Olarian D3 deformational event and immediately prior to the emplacement of regional S‐type granites. Two stages of fluid flow are identified in the area: first an albitizing event which involved the addition of Na and loss of Si, K and Fe; and a second phase of calcsilicate alteration with additions of Ca, Fe, Mg and Si and removal of Na. Fluid fluxes calculated for albitization and calcsilicate alteration were 5.56 × 109 to 1.02 × 1010 mol m−2 and 2.57 × 108–5.20 × 109 mol m−2 respectively. These fluxes are consistent with estimates for fluid flow through mid‐crustal shear zones in other terranes. The fluids associated with shearing and alteration are calculated to have δ18O and δD values ranging between +8 and +11‰, and −33 and −42‰, respectively, and ɛNd values between −2.24 and −8.11. Our results indicate that fluids were derived from metamorphic dehydration of the Willyama Supergroup metasediments. Fluid generation occurred during prograde metamorphism of deeper crustal rocks at or near peak pressure conditions. Shear zones acted as conduits for major crustal fluid flow to shallow levels where peak metamorphic conditions had been attained earlier leading to the apparent ‘retrograde’ fluid‐flow event. Thus, the peak metamorphism conditions at upper and lower crustal levels were achieved at differing times, prior to regional granite formation, during the same orogenic cycle leading to the formation of retrograde mineral assemblages during shearing.
An investigation of the relationship between bulk composition, inferred reaction progress and fluid‐flow parameters for layered micaceous carbonates from Maine, USA
Authors: EVANS K. A. , BICKLE M. J.
Published: April 2005

Reaction progress exhibited by multivariant assemblages in micaceous limestones can provide an excellent record of metamorphic fluid flow. However, it is necessary to understand the sensitivity of these assemblages to bulk‐composition parameters. Here, analysis of bulk composition on different scales and pseudosection construction are used to draw conclusions on relationships between bulk composition, fluid flow and reaction progress. Issues addressed include the effects of bulk composition on the mineralogical evolution of micaceous carbonates, the sensitivity of bulk composition to bulk‐composition sampling methods, the magnitude of cross‐layer fluid‐composition gradients, the potential for metasomatism to drive reaction progress, and the relative timing of reaction in adjacent layers. Pseudosections successfully represent observed mineral assemblages, constrain the position of reactions in T–X(CO2) space, and allow assessment of the sensitivity of reaction position, inferred reaction progress and calculated fluid fluxes to uncertainties in bulk composition. The scale of bulk‐composition sampling affects bulk compositions, calculated modes, predicted mineral assemblages and calculated fluid compositions. Larger samples record an average of different lithological subdomains, while point‐count‐derived bulk compositions are subject to uncertainties related to the small number of sample points. The optimum bulk composition for pseudosection purposes probably lies between measured bulk compositions. Results suggest that reaction progress in some extensively reacted layers was driven by infiltration of H2O‐rich fluid which flowed or diffused parallel to layering, perpendicular to layering in response to fluid‐composition gradients, and out of veins. Small variations in fluid composition across layering (ΔX(CO2) < 0.02) were maintained by internal buffering by the mineral assemblages. Internal buffering must also have driven samples up a sequence of narrow low‐variance fields in T–X(CO2) space, and so reaction in adjacent layers must have close to simultaneous. Metasomatic effects on reaction progress are likely to have been small, so long as the porosity was low.
Inhibition of Persistent Sodium Current Fraction and Voltage‐gated L‐type Calcium Current by Propofol in Cortical Neurons: Implications for Its Antiepileptic Activity
Authors: Martella Giuseppina , De Persis Cristiano , Bonsi Paola , Natoli Silvia , Cuomo Dario , Bernardi Giorgio , Calabresi Paolo , Pisani Antonio
Published: April 2005

Summary:  Purpose: Although it is widely used in clinical practice, the mechanisms of action of 2,6‐di‐isopropylphenol (propofol) are not completely understood. We examined the electrophysiologic effects of propofol on an in vitro model of epileptic activity obtained from a slice preparation.

Methods: The effects of propofol were tested both on membrane properties and on epileptiform events consisting of long‐lasting, paroxysmal depolarization shifts (PDSs) induced by reducing the magnesium concentration from the solution and by adding bicuculline and 4‐aminopyridine.These results were integrated with a patch‐clamp analysis of Na+ and high‐voltage activated (HVA) calcium (Ca2+) currents from isolated cortical neurons.

Results: In bicuculline, to avoid any interference by γ‐aminobutyric acid (GABA)‐A receptors, propofol (3–100 μM) did not cause significant changes in the current‐evoked, sodium (Na+)‐dependent action‐potential discharge. However, propofol reduced both the duration and the number of spikes of PDSs recorded from cortical neurons. Interestingly, relatively low concentrations of propofol [half‐maximal inhibitory concentration (IC50), 3.9 μM) consistently inhibited the “persistent” fraction of Na+ currents, whereas even high doses (≤300 μM) had negligible effects on the “fast” component of Na+ currents. HVA Ca2+ currents were significantly reduced by propofol, and the pharmacologic analysis of this effect showed that propofol selectively reduced L‐type HVA Ca2+ currents, without affecting N or P/Q‐type channels.

Conclusions: These results suggest that propofol modulates neuronal excitability by selectively suppressing persistent Na+ currents and L‐type HVA Ca2+ conductances in cortical neurons. These effects might cooperate with the opening of GABA‐A–gated chloride channels, to achieve depression of cortical activity during both anesthesia and status epilepticus.
Hippocampal Sclerosis in Severe Myoclonic Epilepsy in Infancy: A Retrospective MRI Study
Authors: Siegler Zsuzsanna , Barsi Peter , Neuwirth Magdolna , Jerney Judit , Kassay Maria , Janszky Jozsef , Paraicz Eva , Hegyi Marta , Fogarasi Andras
Published: April 2005

Summary: Purpose:Severe myoclonic epilepsy in infancy (SMEI; Dravet's syndrome) is a malignant epilepsy syndrome characterized by early prolonged febrile convulsions (PFCs) with secondary psychomotor delay and a variety of therapy‐resistant seizures. Although the initial symptoms are repeated PFCs, the MRI performed at the onset of disease shows no hippocampal structural abnormalities. We aimed to assess clinical and serial MRI data of patients with SMEI with a special attention to the temporomedial structures. To our knowledge, this is the first systematic MRI study in this disease.

Methods:Clinical and MRI data of all SMEI patients treated in our hospitals between 1996 and 2004 were reviewed.

Results:Twenty‐eight MRIs from 14 children (one to four images/patient) were included. Age at disease onset was between 3 and 9 months; age at initial MRI was 5 months to 13 years. Ten of 14 patients showed hippocampal sclerosis (HS) during the course of the disease (nine unilateral, one bilateral). Six of these 10 had a normal initial MRI. Age at the first verified HS was between 14 months and 13 years. Neither complex partial seizures nor anterior temporal irritative zone was recorded in these children.

Conclusions:After initially normal structures, in most patients with SMEI, HS develops several months or years after the first PFC. These data support the hypothesis that PFC might be responsible for HS, but other factors and individual sensitivity should play a role in this process.
Entorhinal Cortex Involvement in Human Mesial Temporal Lobe Epilepsy: An Electrophysiologic and Volumetric Study
Authors: Bartolomei Fabrice , Khalil Mouhamad , Wendling Fabrice , Sontheimer Anna , Régis Jean , Ranjeva Jean‐Phillipe , Guye Maxime , Chauvel Patrick
Published: April 2005

Summary:  Purpose: Several studies have demonstrated diminution in the volume of entorhinal cortex (EC) ipsilateral to the pathologic side in patients with temporal lobe epilepsy (TLE). The relation between the degree of EC atrophy and the epileptogenicity of this structure has never been directly studied. The purpose of the study was to determine whether atrophy of the EC evaluated by the quantitative magnetic resonance imaging (MRI) method is correlated with the epileptogenicity of this structure in TLE.

Methods: Intracerebral recordings (SEEG method) of seizures from 11 patients with mesial TLE were analyzed. Seizures were classified according to patterns of onset: pattern 1 was the emergence of a low‐frequency, high‐amplitude rhythmic spiking followed by a tonic discharge, and pattern 2 was the emergence of a tonic discharge in the mesial structures. A nonlinear measure of SEEG signal interdependencies was used to evaluate the functional couplings occurring between hippocampus (Hip) and EC at seizure onset. MRI volumetric analysis was performed by using a T1‐weighted three‐dimensional gradient‐echo sequence in TLE patients and 12 healthy subjects.

Results: Significant interactions between Hip and Ec were quantified at seizure onset. The EC was found to be the leader structure in most of the pattern 2 seizures. Volumetric measurements of EC demonstrated an atrophy in 63% of patients ipsilateral to the epileptic side. A significant correlation between the strength of EC–Hip coupling and the degree of atrophy was found. In addition, in those patients that had a normal EC volume, the EC was never the leader structure in Ec–Hip coupling.

Conclusions: These results validate the potential role of volumetry to predict the epileptogenesis of the EC in patients with hippocampal sclerosis and MTLE.