bluuebunny/crossref_metadata_2025 huggingface dataset:
Element localization in ultrathin cryosections of high‐pressure frozen ectomycorrhizal spruce roots
Authors: FREY B. , BRUNNER I. , WALTHER P. , SCHEIDEGGER C. , ZIEROLD K.
Published: November 2003

We present, for the first time, elemental mapping of ultra‐thin cryosections from high‐pressure frozen ectomycorrhizal roots of Picea abies–Hebeloma crustuliniforme. The maps provide interpretable information on the relationship between elements and the structure of inhomogeneous objects. Cryoultramicrotomy together with energy dispersive X‐ray microanalysis (EDX) offers the potential to study the subcellular localization of specific ions and ecologically important tracers (Cs and Sr) in ectomycorrhizal roots under conditions resembling the natural slate as closely as possible. Structural changes of the ectomycorrhizal roots, in particular the absence of a Hartig net at high NH4+ levels in the nutrient solution, were accompanied by elemental modification of Ca in cortical cell walls, where markedly higher concentrations of Ca were found. Cs and Sr applied to the nutrient solution were localized in root and fungal cells of the Hartig net. Cs accumulated mainly in the vacuoles of the Hartig net hyphae and its distribution was very similar to the distribution of K. In contrast to Cs, Sr was found to occur mainly in electron‐opaque and P‐rich granules. From this study, (here is no indication that Ca is the only ion accompanying P in the P‐rich granules. Several elements including Ca, K, Cl, S, Cs and Sr, with highest concentrations for S, can occur together with P in these granules. The occurrence of the P‐rich electron‐opaque deposits in fungal cells might be the first evidence of polyphosphate granules in the native state, since our specimen preparation technique did not include chemical fixation.
Uptake and transport of zinc in the hyperaccumulator Thlaspi caerulescens and the non‐hyperaccumulator Thlaspi ochroleucum
Authors: SHEN Z. G. , ZHAO F. J. , McGRATH S. P.
Published: November 2003

Growth and zinc uptake of the hyperaccumulator species Thlaspi caerulescens J. & C. Presl and the non‐hyperaccumulator species Thlaspi ochroleucum Boiss. & Heldr. were compared in solution culture experiments. T. caerulescens was able to tolerate 500 mmol m−3 (32.5 g m−3) Zn in solution without growth reduction, and up to 1000 mmol m−3 (65 g m−3) Zn without showing visible toxic symptoms but with a 25% decrease in dry matter (DM) yield. Up to 28 g kg−1 of Zn in shoot DM was obtained in healthy plants of T. caerulescens. In contrast, T. ochroleucum suffered severe phytotoxicity at 500 mmol m−3 Zn. Marked differences were shown in Zn uptake, distribution and redistribution between the two species. T. caerulescens had much higher concentrations of Zn in the shoots, whereas T. ochroleucum accumulated higher concentrations of Zn in the roots. When an external supply of 500 mmol m−3 Zn was withheld, 89% of the Zn accumulated previously in the roots of T. caerulescens was transported to the shoots over a 33 d period, whereas in T. ochroleucum only 32% was transported. T. caerulescens was shown to have a greater internal requirement for Zn than other plants. Increasing the supply of Zn from 1 to 10 mmol m−3 gave a 19% increase in the total DM of this species. liven the shoots from the 1 mmol m−3 Zn treatment which showed Zn deficiency contained 10 times greater Zn concentrations than the widely reported critical value for Zn deficiency to occur in many other plant species. The results obtained suggest that strongly expressed constitutive sequestration mechanisms exist in the hyperaccumulator T. caerulescens, which detoxify the large amount of Zn present in shoot tissues and decrease its physiological availability in the cytosol. Both T. caerulescens and T. ochroleucum had constitutively high concentrations of malate in shoots, which were little affected by different Zn treatments. Although malate may play a role in Zn chelation because of the high concentrations present, it cannot explain the species specificity of Zn tolerance and hyperaccumulation.
Effects of nitrogen supply on the anatomy and chemical composition of leaves of four grass species belonging to the genus Poa, as determined by image‐processing analysis and pyrolysis–mass spectrometry
Authors: VAN ARENDONK J. J. C. M. , NIEMANN G. J. , BOON J. J. , LAMBERS H.
Published: November 2003

Previous experiments have shown that the anatomy and chemical composition of leaves of inherently fast‐ and slow‐growing grass species, grown at non‐limiting nitrogen supply, differ systematically. The present experiment was carried out to investigate whether these differences persist when the plants are grown at an intermediate or a very low nitrogen supply. To this end, the inherently fast‐growing Poa annua L. and Poa trivialis L., and the inherently slow‐growing Poa compressa L. and Poa pratensis (L.) Schreb. were grown hydroponically at three levels of nitrate supply: at optimum (RGRmax) and at relative addition rates of 100 and 50 mmol N (mol N)−1 d−1 (RAR100 and RAR50), respectively.

As expected, at the lowest N supply, the potentially fast‐growing species grew at the same rate as the inherently slow‐growing ones. Similarly, the differences in leaf area ratio (LAR, leaf area:total dry mass), specific leaf area (SLA, leaf arear:leaf dry mass) and leaf mass ratio (LMR, leaf dry mass:total dry mass) disappeared. Under optimal conditions, the fast‐growing species differed from the slow‐growing ones in that they had a higher N concentration. There were no significant differences in C concentration. With decreasing N supply, the total N concentration decreased and the differences between the species disappeared. The total C concentration increased for the fast‐growing species and decreased for the slow‐growing ones, i.e. the small, but insignificant, difference in C concentration between the species at RGRmax increased with decreasing N supply.

The chemical composition of the leaves at low N supply, analysed in more detail by pyrolysis–mass spectrometry, showed an increase in the relative amounts of guaiacyl lignin, cellulose and hemicellulose, whereas those of syringyl lignin and protein decreased.

The anatomy and morphology of the leaves of the four grass species differing in RGRmax were analysed by image‐processing analysis. The proportion of the total volume occupied by mesophyll plus intercellular spaces and epidermis did not correlate with the amount of leaf mass per unit leaf area (specific leaf mass, SLM) at different N supply. The higher SLM at low N supply was caused partly by a high proportion of non‐veinal sclerenchymatic cells per cross‐section and partly by the smaller volume of epidermal cells.

We conclude that the decrease in relative growth rate (and increase in SLM) at decreasing N supply is partly due to chemical and anatomical changes. The differences between the fast‐ and slow‐growing grass species at an optimum nutrient supply diminished when plants were growing at a limiting nitrogen supply.
The gradient between pre‐dawn rhizoplane and bulk soil matric potentials, and its relation to the pre‐dawn root and leaf water potentials of four species
Authors: SCHMIDHALTER U.
Published: November 2003

Uptake of soil water by plants may result in significant gradients between bulk soil and soil in the vicinity of roots. Few experimental studies of water potential gradients in close proximity to roots, and no studies on the relationship of water potential gradients to the root and leaf water potentials, have been conducted. The occurrence and importance of pre‐dawn gradients in the soil and their relation to the pre‐dawn root and leaf water potentials were investigated with seedlings of four species. Pre‐germinated seeds were grown without watering for 7 and lid in a silt loam soil with initial soil matric potentials of ‐0.02, ‐0.1 and ‐0.22 MPa. Significant gradients, independent of the species, were observed only at pre‐dawn soil matric potentials lower than ‐0.25 MPa; the initial soil matric potentials were ‐0.1 MPa. At an initial bulk soil matric potential of ‐0.22 MPa, a steep gradient between bulk and rhizoplane soil was observed after 7 d for maize (Zea mays L. cv. Issa) and sunflower (Helianthus annuus L. cv. Nanus), in contrast to barley (Hordeum vulgare L. cv. Athos) and wheat (Triticum aestivum L. cv. Kolibri). Pre‐dawn root water potentials were usually about the same as the bulk soil matric potential and were higher than the rhizoplane soil matric potential. Pre‐dawn root and leaf water potentials tended to be much higher than rhizoplane soil matric potentials when the latter were lower than ‐0.5 MPa. It is concluded that plants tend to become equilibrated overnight with the wetter bulk soil or with wetter zones in the bulk soil. Plants can thus circumvent negative effects of localized steep pre‐dawn soil matric potential gradients. This may be of considerable importance for water uptake and growth in drying soil.
MCA Sarcomas Induced in scid Mice are More Immunogenic than MCA Sarcomas Induced in Congenic, Immunocompetent Mice
Authors: ENGEL A.‐M. , SVANE I. M. , RYGAARD J. , WERDELIN O.
Published: November 2003

With the aim of studying possible T‐cell mediated selection of the cells in growing tumours, 108 mice of the C.B‐17 strain, either immunocompetent C.B‐17 mice or histocompatible immunodeficient C.B‐17 severe combined immune deficiency (scid) were treated with 3‐methylcholanthrene (MCA) in two different dosages. A total of 51 tumours were obtained, 44 of which were established as uncloned tumour cell lines, and used for further study. Tumour incidence correlated with carcinogen‐dosage in that more tumours developed in groups treated with a high MCA dose than in groups treated with a low MCA dose, but not with immune status of the tumour host. No significant difference in the level of MHC class I molecule expression was found between the two groups of tumours. The rate of rejection after transplantation to syngeneic immunocompetent hosts was significantly higher for the scid tumours than for the non‐scid tumours. The authors suggest that this reflects an immunoselection performed by T cells in the immunocompetent host in which the tumour originated, which has eliminated highly immunogenic tumour cells, leaving non‐immunogenic tumour cells to grow.
Analysis of the T‐Cell Receptor Vβ Usage in Monozygotic and Dizygotic Twins Living in a Plasmodium falciparum Endemic Area in West Africa
Authors: TROYE‐BLOMBERG M. , FOGDELL A. , EL‐GHAZALI G. , LARSSON Å. , HASSAN KING M. , SISAY‐JOOF F. , OLERUP O. , GRUNEWALD J. , JEPSON A.
Published: November 2003

To investigate the influence of genetic and/or environmental factors in the development and shaping of the human peripheral T cell repertoire the authors studied the T‐cell receptor (TCR) Vβ usage in 10 adult monozygous (Mz) and nine dizygous (Dz) twin pairs living in a Plasmodium falciparum endemic area in West Africa. The TCR repertoire was determined using a small panel of anti‐Vβ specific monoclonal antibodies (MoAbs) using conventional immunofluorescence assays. The results revealed that the Vβ repertoire was similar to that recently described for a Caucasian population using a similar panel of antibodies. The frequencies of particular Vβ genes tested were influenced neither by anti‐malarial antibody titres nor by parasite densities, indicating that the P. falciparum parasite is not a dominating factor in determining the peripheral T cell repertoire. All donors were human leucocyte antigen (HLA) class I and II typed; no association was found between the expression of any Vβ genes and MHC haplotype. The Vβ usage was more concordant within the Mz than within the Dz pairs. For a group comprising four HLA class II identical individuals, the average within‐pair difference was significantly greater than for the whole Mz group, but similar to that seen for the total Dz group. Thus, the data suggest that genetic, rather than environmental, factors have a profound effect on the shaping of the human circulating T cell repertoire and that the major genetic factors are encoded by non‐HLA class II genes.
The Effects of Cyclosporin A on V(D)J Recombination Activity
Authors: DÖBBELING U.
Published: November 2003

V(D)J recombination is up‐regulated by the protein kinase A (PKA) pathway and down‐regulated by the protein kinase C (PKC) and Ca2+ pathways. When activators of the PKA and PKC pathways or the PKA and Ca2+ pathways are given at the same time, a strong reduction of the PKA effect is observed. The V(D)J recombination suppressing effect of elevated intracellular Ca2+ levels, but not that of the PKC pathway, can be abrogated by the addition of the calcineurin inhibitor cyclosporin A (CsA), indicating that the effect of Ca2+ is mediated by calcineurin. This effect is observed in a pre B cell line as well as in the V(D)J recombination competent fibroblast cell line L4, indicating that the mechanisms of the cross talk between different signalling pathways are basically the same in both cell types. In the absence of Ca2+ mobilizer CsA increases the V(D)J recombination rate in pre B cells but not in L4 cells.
Changes in Arrangement and in Conformation of Molecular Components of Peripheral T‐Cell Antigen Receptor Complex After Ligand Binding: Analyses by Co‐Precipitation Profiles
Authors: Osono E. , Sato N. , Yokomuro K. , Saizawa M. K.
Published: November 2003

Amounts of co‐precipitating CD3 components by anti‐T‐cell receptor (TCR)Vβ or anti‐CD4/8 monoclonal antibodies were compared between non‐stimulated and stimulated splenic T cells. The amounts of co‐precipitating CD3δ, ε and γ chains with TCRαβ and with CD4/8 were not significantly changed after TCR ligation. The apparent amount of CD3ζ chain co‐precipitated with TCRαβ increased up to threefold, while the actual amount of co‐precipitating CD3ζ with TCRαβ and the total amount of specifically precipitated CD3ζ are not changed after cross linking of TCR. The apparent amount of CD3ζ chain co‐precipitated with CD4/8 also increased. Unlike co‐precipitation with TCRαβ, the actual amount of CD3ζ co‐precipitated with CD4/8 increased significantly. This observation suggests a conformational change as well as the relocation of CD3ζ molecules within the TCR complex after the signal delivery. After TCR ligation, CD3ζ chains relocate to the vicinity of either CD4 or CD8 molecules. In addition, when cross linking and binding signals are compared, CD3 chains undergo two distinct phases of conformational change. The early conformational change caused by ligand binding is positively related to the induction of proliferative responses, while the later conformational change caused by the cross linking of TCR does not induce but enhances the proliferative response.
Characterization of the Delayed Type Hypersensitivity‐Inducing Epitope of MPT64 from Mycobacterium tuberculosis
Authors: OETTINGER T. , HOLM A. , HASLØV K.
Published: November 2003

Mycobacterium tuberculosis secretes several proteins into the extracellular environment, some of which are restricted to the M. tuberculosis complex. One of these antigens is MPT64. Recently, the authors showed that native as well as recombinant MPT64 is able to distinguish between an M. tuberculosis infection and a BCG Danish 1331 vaccination. Improved distinction between tuberculin purified protein derivative (PPD) sensitivity conferred by an M. tuberculosis infection and that induced by a BCG vaccination or infection with environmental mycobacteria would be useful in the control of tuberculosis. In this study, the authors report the mapping and characterization of a Dth‐inducing epitope by the use of synthetic peptides in guinea‐pigs vaccinated with BCG Danish 1331 or Tokyo. Studies with overlapping synthetic peptides have pinpointed the biological activity to a single Dth‐inducing epitope at the carboxyterminal region of MPT64 consisting of 15 residues between amino acids Gly‐173 and Ala‐187, the core epitope (CE15). A fine mapping using truncated versions of CE15 indicates the epitope is restricted to 13 residues between amino acids Val‐174 to Glu‐186. However, the optimal Dth reactivity is obtained by CE15. Different modifications of CE15 revealed that a lysine tree construction improves the skin reactivity to a maximum level approaching that of the reactivity to tuberculin PPD.
Ex Vivo PKH26‐Labelling of Lymphocytes for Studies of Cell Migration In Vivo
Authors: JOHNSSON C. , FESTIN R. , TUFVESON G. , TÖTTERMAN T. H.
Published: November 2003

A prerequisite for studies of cell migration is that the cells of interest can be appropriately labelled and subsequently easily traced. The use of radioisotopes or fluorescent substances that bind covalently to the cell surface, e.g. fluorescein isothiocyanate (FITC) or rhodamine isothiocyanate (RITC), have limitations such as rapid loss of the labelling, toxicity and interference with cell surface molecules. In the present work the authors labelled rat spleen lymphocytes with the fluorescent labelling molecule PKH26, which is incorporated into the lipid bilayer of cytoplasmic membranes. The labelled lymphocytes were injected intravenously into syngeneic recipients and 2 or 6 days later the lymphocytes were detected in various organs by using flow cytometry and fluorescence microscopy. As could be expected, the lymphocytes homed to lymphoid tissues, preferably the spleen, and no labelled cells were found in non‐lymphoid organs such as the heart and the kidney. Membrane labelling proved to be intense, uniform and stable and PKH26 positive cells were easily detectable in fractions less than 0.2% in peripheral blood and the various tissues after 6 days of in vivo circulation. Thus, the PKH26 dye appears to be suitable for labelling cell populations used in the study of cell migration in vivo, both under normal conditions and when specific immunological processes are taking place, such as graft rejection and tumour growth.
The Amino Acid Sequence of the Glycosylated Amyloid Immunoglobulin Light Chain Protein AL MS
Authors: OMTVEDT L. A. , HUSBY G. , CORNWELL III G. G. , KYLE R. A. , SLETTEN K.
Published: November 2003

The authors report on the amino acid sequence of the glycosylated amyloid protein AL MS. The amyloid fibrils were extracted from the spleen of a patient (MS.) with amyloidosis. The protein AL MS was purified from the amyloid fibrils by gel filtration. SDS–PAGE performed on the purified protein material showed glycosylated protein bands in the range of 22 to 32 kDa, corresponding to polymerization of N‐terminal fragments. The protein was characterized by amino acid analysis and Edman degradation. Tryptic digest combined with Staphylococcal V8 protease, chymotrypsin and pyroglutamate aminopeptidase digestion, as well as cleavage with BNPS‐skatole, established the complete amino acid sequence of 168 residues. The protein was compared to other proteins in the SWISSPROT databank, showing homology with the immunoglobulin light chain variable subgroup λI. AL MS showed some unique amino acid substitutions. Highly conserved residues Gly(57) and Arg(61), were exchanged to arginine and glutamine, respectively, possibly altering the three‐ dimensional structure of the protein.
MHC Class I Presentation of Live and Heat‐Inactivated Sendai Virus Antigen in T2Kb Cells Depends on an Intracellular Compartment with Endosomal Characteristics
Authors: LIU T. , ZHOU X. , ABDEL‐MOTAL U. M. , LJUNGGREN H.‐G. , JONDAL M.
Published: November 2003

T2Kb cells, which do not express TAP1/2 peptide transporters or the low molecular weight protein 2/7 (LMP2/7) proteasomal subunits, can still process and present both live and heat‐inactivated Sendai virus (SV). As this operation may also reflect the existence of an alternative processing pathway in normal antigen‐presenting cells (APC), the authors have characterized it using intracelluular inhibitors and anti‐Kb monoclonal antibodies (MoAbs). From the results with lipophilic amines (ammonium chloride, methylamine and chloroquine), cytoskeletal inhibitors (cytochalasin B and vinblastine), and an endoprotease inhibitor (phenylmethylsulfonyl fluoride, PMSF), the authors conclude that the processing of SV antigen in T2Kb cells has endosomal characteristics depending on cellular activities such as uptake, vesicular transport and intracellular–vesicular proteolysis. In addition, internalized ‘empty’ Kb molecules derived from the T2Kb cell surface appeared to be involved in the presentation of SV antigen, as demonstrated by a protocol using a combination of the Golgi inhibitor brefeldin A(BFA) and anti‐Kb antibodies. The results thus indicate that T2Kb cells process SV antigen in an endosomal‐like compartment which contain recycling ‘empty’ Kb molecules.
Mood‐stabilizers: the archeology of the concept
Authors: Harris Margaret , Chandran Summit , Chakraborty Nabonita , Healy David
Published: November 2003

Objective:  To review the history of ‘mood‐stabilizing’ treatments.

Method:  We have reviewed primary source data on the origin of the use of current mood‐stabilizers.

Results:  This historical record on the origins of the mood‐stabilizers points to a more ambiguous picture as regards pharmacotherapeutic specificity to bipolar disorders than is commonly conceded.

Conclusions:  This review suggests a need for alternative formulations of the concept of a mood‐stabilizer. An alternative to the currently dominant paradigm is that these agents have treatment effects, which need to be matched more precisely with patients’ constitutional types in order to optimize outcomes.
Polymorphism of the brain‐derived neurotrophic factor gene and performance on a cognitive prefrontal test in bipolar patients
Authors: Rybakowski Janusz K , Borkowska Alina , Czerski Piotr M , Skibińska Maria , Hauser Joanna
Published: November 2003

Objectives:  The aim of the study was to test a possible association between the Val66Met polymorphism of the brain‐derived neurotrophic factor (BDNF) gene and performance on a neurocognitive test, the Wisconsin Card Sorting Test (WCST), in bipolar patients.

Methods:  Fifty‐four bipolar patients were studied, 18 male and 36 female, aged 18–72 (mean 46 years). The number of perseverative errors (WCST‐P), non‐perseverative errors (WCST‐NP), completed corrected categories (WCST‐CC), conceptual level responses (WCST‐%CONC) and set to the first category (WCST‐1st CAT) were measured in relation to the Val66Met genotypes of BDNF.

Results:  The percentages of subjects with Val/Val, Val/Met and Met/Met genotypes were respectively 81.5, 16.7 and 1.8%. Subjects with Val/Val and Val/Met genotypes did not differ on clinical factors except for the age of onset of the illness, which was earlier in Val/Val than Val/Met genotype (27 years versus 38 years). The performance in all domains of WCST was significantly better in subjects with Val/Val BDNF genotype compared with Val/Met genotype.

Conclusions:  The results suggest a role of BDNF in prefrontal cognitive function in bipolar illness. The tests of prefrontal cognition may be considered as endophenotypic markers in bipolar illness.
Antidepressants in bipolar disorder: the case for caution
Authors: Ghaemi S Nassir , Hsu Douglas J , Soldani Federico , Goodwin Frederick K
Published: November 2003

The 2002 American Psychiatric Association (APA) guidelines for the treatment of bipolar disorder recommended more conservative use of antidepressants. This change in comparison with previous APA guidelines has been criticized, especially from some groups in Europe. The Munich group in particular has published a critique of assumptions underlying the conservative recommendations of the recent APA treatment guidelines. In this paper, we re‐examine the argument put forward by the Munich group, and we demonstrate that indeed, conceptually and empirically, there is a strong rationale for a cautious approach to antidepressant use in bipolar disorder, consistent with, and perhaps even more strongly than, the APA guidelines. This rationale is based on support for the following four propositions: (i) The risk of antidepressant induced mood‐cycling is high, (ii) Antidepressants have not been shown to definitively prevent completed suicides and reduce mortality, whereas lithium has, (iii) Antidepressants have not been shown to be more effective than mood stabilizers in acute bipolar depression and have been shown to be less effective than mood stabilizers in preventing depressive relapse in bipolar disorder and (iv) Mood stabilizers, especially lithium and lamotrigine, have been shown to be effective in acute and prophylactic treatment of bipolar depressive episodes. We therefore draw three conclusions from this interpretation of the evidence: (i) There are significant risks of mania and long‐term worsening of bipolar illness with antidepressants, (ii) Antidepressants should generally be reserved for severe cases of acute bipolar depression and not routinely used in mild to moderate cases and (iii) Antidepressants should be discontinued after recovery from the depressive episode, and maintained only in those who repeatedly relapse after antidepressant discontinuation (a minority we judge to represent only about 15–20% of bipolar depressed patients).
Naive T cells are maintained by thymic output in early ages but by proliferation without phenotypic change after age twenty
Authors: Murray John M , Kaufmann Gilbert R , Hodgkin Philip D , Lewin Sharon R , Kelleher Anthony D , Davenport Miles P , Zaunders John J
Published: November 2003

Analysing T‐cell receptor excision circle numbers in healthy individuals we find a marked change in the source of naive T cells before and after 20 years of age. The bulk of the naive T cell pool is sustained primarily from thymic output for individuals younger than 20 years of age whereas proliferation within the naive phenotype is dominant for older individuals. Over 90% of phenotypically naive T cells in middle age are not of direct thymic origin. Moreover, this change in source of naive T cells is accompanied either by an increased death rate of T cells from the thymus or reduced thymic export. Modelling of these processes shows that new naive T cells of a thymic origin have a half‐life of approximately 50 days before this change occurs, and that either the life‐span of recent thymic emigrants (but not necessarily of all naive cells) decreases approximately threefold in middle age, or thymic production drops by this same amount. The decay rate of T‐cell receptor excision circle levels for individuals over 20 years of age is consistent with the decay rate of the productive thymus. Our modelling suggests that at age 25, thymic export is responsible for 20% of naive T‐cell production and that this percentage decreases with the 15.7 year half‐life of the productive thymus so that by age 55 only 5% of naive production arises from thymic export.
Depletion of cellular cholesterol interferes with intracellular trafficking of liposome‐encapsulated ovalbumin
Authors: Rao Mangala , Peachman Kristina K , Alving Carl R , Rothwell Stephen W
Published: November 2003

Cholesterol is a major constituent of plasma cell membranes and influences the functions of proteins residing in the membrane. To assess the role of cholesterol in phagocytosis and intracellular trafficking of liposomal antigen, macrophages were treated with inhibitors of cholesterol biosynthesis for various time periods and levels of cholesterol depletion were assessed by thin layer chromatography. In control macrophages, cholesterol was present in the plasma membrane and in intracellular stores, as visualised by staining with the cholesterol‐binding compound filipin, whereas macrophages treated with cholesterol inhibitors failed to stain with filipin. However, these macrophages were still capable of phagocytosis as evidenced by their internalisation of fluorescent‐labelled bacteria and liposome‐encapsulated Texas red labelled‐ovalbumin, L(TR‐OVA). While fluorescent ovalbumin (OVA) was consistently transported to the Golgi in macrophages incubated with L(TR‐OVA), in cells treated with cholesterol inhibitors, OVA remained spread diffusely throughout the cytoplasm. Even though the mean fluorescence intensity of MHC class I molecules on cholesterol inhibitor‐treated macrophages was equivalent to that of the control macrophages, the amount of MHC class I‐liposomal OVA‐peptide complex detected on the cell surface of cholesterol inhibitor‐treated macrophages, was only 45.6 ± 7.4% (n = 4, mean ± SEM) of control levels after intracellular processing of L(OVA). We conclude that cholesterol depletion does not eliminate phagocytosis or MHC class I surface expression, but does affect the trafficking and consequently the MHC class I antigen‐processing pathway.
Apoptosis of CD4+ and CD8+ T cells during experimental infection with Mycobacterium avium is controlled by Fas/FasL and Bcl‐2‐sensitive pathways, respectively
Authors: Zhong Jie , Gilbertson Brad , Cheers Christina
Published: November 2003

Both CD4+ and CD8+ T cells from mice infected with Mycobacterium avium suffered a high rate of apoptosis, beginning with the onset of the immune response and culminating in the loss of T cells from the tissues and loss of IFN‐γ production. Fas expression increased over the course of infection on both T cell populations, as did their susceptibility to the induction of apoptosis in vitro by anti‐Fas mAb. Nevertheless, although the rate of apoptosis among CD4+ T cells from infected mice was reduced to normal levels in lpr mice with a defective Fas, CD8+ T cells were unaffected, implying that Fas/FasL interaction was not important in these cells in vivo. Conversely, over‐expression of B‐cell lymphoma‐2 (Bcl‐2), which is known to protect T cells from apoptosis signalled through the TNF receptor or due to the withdrawal of cytokines, totally protected CD8+ T cells from infected mice but had no effect on CD4+. It is of interest that these two contrasting pathways of T‐cell apoptosis operate at the same time during a single infection.
Computed tomographic findings of environmental asbestos‐related malignant pleural mesothelioma
Authors: YILMAZ Ufuk , UTKANER Gülay , YALNIZ Enver , KUMCUOĞLU Ziya
Published: November 2003

Malignant pleural mesothelioma (MPM) is not an infrequent fatal neoplasm. It is endemically present in some regions of Turkey due to its aetiological relationship to exposure to environmental fibrous minerals. The aim of this study was to determine the thorax computed tomographic (CT) features of environmental asbestos‐related MPM. In this study, we examined retrospectively the CT scans of 46 untreated patients with pathological diagnosis of environmental asbestos‐related MPM among 151 patients with malignant pleural mesothelioma in the İzmir Chest Disease and Surgery Hospital. The CT scans were interpreted by consultation of four observers. Malignant pleural mesothelioma was unilateral in 45 (97.2%) of the patients. Pleural effusions were found in 42 (91%) of the patients, pleural calcifications in 12 (26%), contracted hemithorax in 14 (30%), interlobar fissure involvement in 25 (54%) and mediastinal pleural involvement in 26 (57%). A contracted hemithorax was significantly correlated with pleural rind configuration. Pleural thickenings were found in 45 (99%) of the patients. Pleural thickenings were in the form of nodularity in 10 (22%) cases, regular in 12 (27%) cases, as a focal mass in 3 (7%) cases and as a pleural rind in 20 (44%) cases. Pleural thickening was greater than 1 cm in 32 (71%) cases. The most common CT findings in our series were unilateral circumferential pleural thickening, nodular pleural thickening, pleural thickening greater than 1 cm and mediastinal pleural involvement. Generally, pleural effusion was accompanied by this. There was interlobar fissure involvement in half of the patients. There was no pathognomonic CT finding in environmental asbestos‐related MPM. But CT was useful in suggesting the diagnosis of malignant pleural disease in the cases with MPM.
Sarcoidosis induced by interferon therapy for chronic myelogenous leukaemia
Authors: KIKAWADA Masayuki , ICHINOSE Yuichi , KUNISAWA Akira , YANAGISAWA Naoshi , MINEMURA Kazushige , KASUGA Ikuma , YONEMARU Makoto , KAWANISHI Keiichi , TAKASAKI Masaru , TOYAMA Keisuke
Published: November 2003

A 31‐year‐old male was diagnosed as having chronic myelogenous leukaemia and has been treated with hydroxyurea and interferon‐α since February 1995. After 16 months, he complained of low‐grade fever and a cough. Bilateral hilar lymph node enlargement was detected on the chest X‐ray film and multiple subcutaneous erythematous nodules appeared. A skin biopsy revealed subcutaneous sarcoid granuloma. Two months after the cessation of interferon therapy, the subcutaneous nodules and the hilar lymph node enlargement resolved. It is possible that continuous interferon administration can promote granuloma formation in sarcoidosis by activating T cells and macrophages.
The effect of inhaled budesonide on the diurnal variation in airway mechanics, airway responsiveness and serum neutrophil chemotactic activity in Asian patients with predominant nocturnal asthma
Authors: TAN Wan , KOH TH , HAY CS , TAYLOR E
Published: November 2003

The effectiveness of inhaled corticosteroids in the control of daytime symptoms in asthma is well established, but the specific use against nocturnal asthma has not been systematically studied in Asian patients. This study examined the effect of treatment with inhaled budesonide on the nocturnal variation in measurements of airway calibre, bronchial hyperresponsiveness to inhaled histamine and circulating neutrophil chemotactic activity in Asian patients with nocturnal asthma. Thirty patients, with nocturnal asthma, were randomized into a 2‐month, double‐blind, parallel group study. Twice as many subjects were allocated to the group who received two consecutive months of inhaled budesonide 1600 μg daily as to the group who received placebo followed by budesonide. Spirometry, lung mechanics, bronchial hyperresponsiveness and serum neutrophil chemotactic factor (NCA) were measured at 16.00 h, 22.00 h and at 04.00 h on 3 days and nights, 4 weeks apart before and after either placebo or budesonide. The combined measurements for the two groups at 04.00 h before and after treatment with budesonide were: forced expiratory volume in 1 s (FEV1) mean (SEM) litres 1.34 (0.17) before, 2.00 (0.19) after; thoracic gas volume (TGV) litres 3.05 (0.32) before, 2.25 (0.14) after; specific airway conductance (sGaw) (cmH20.0 sec)−1 0.39 (0.07) before, 1.16 (0.17) after; PD20μg geometric mean 1.16 before, 44.74 after; neutrophil chemotactic activity (NCA) in units of graduations of migration 98.8 (4.2) before, 101 (14.2) after. The data showed that short and intermediate term high dose inhaled budesonide is an effective specific treatment for nocturnal asthma in Asian patients, resulting in marked improvements in symptoms and in lung mechanics, and reductions in the diurnal variations in bronchial hyperresponsiveness, before any change could be demonstrated in a circulating marker of airway inflammation.
Molecular studies of bronchial asthma, sarcoidosis and angiotensin converting enzyme inhibitor‐induced cough
Authors: KAWAKAMI Y , MUNAKATA M , YAMAGUCHI E , FURUYA K , MATSUDA T
Published: November 2003

The role of genetic factors was reviewed with respect to the pathophysiology of bronchial asthma, sarcoidosis and cough induced by angiotensin converting enzyme (ACE) inhibitor administration. The so‐called ‘atopy gene’ in 11q13 is not linked to atopy but is associated with serum IgE levels. The β 2‐adrenergic receptor gene on 5q32–33 was found to have polymorphism by Ban I and to be related to β 2‐receptor function; a defect of a 2.3 kb allele is related to lowered sensitivity to β 2‐agonists. This defect is also related to higher prevalence on non‐atopic bronchial asthma. The occurrence of amino acid mutation (Arg16 to Gly) of β 2‐receptors was lower and G1n27 to Glu mutation is extremely rare in the Japanese population compared with Caucasians. There is polymorphism of ACE genotypes among normal subjects and patients with sarcoidosis, II, ID and DD. The genotype is a significant determinant of serum ACE activity and may determine the prognosis of sarcoid patients. Genotype II has a higher incidence of coughing induced by ACE inhibitors.
Tumour‐infiltrating lymphocytes in non‐small cell lung cancer are activated T lymphocytes
Authors: KUO Sow‐Hsong , CHANG Dun‐Bing , LEE Yung‐Chie , LEE Ya‐Ting , LUH Kwen‐Tay
Published: November 2003

This study was carried out in order to investigate the local immune reaction of tumour‐infiltrating lymphocytes (TILs) in the primary tumours of non‐small cell lung carcinomas. Thirty non‐small cell lung cancer (NSCLC) patients were included. The tumour tissue was taken at thoracotomy and monocellular suspension of the tumour was obtained by mechanical disaggregation. Dual‐coloured flow cytometric analysis of TILs and their corresponding peripheral blood lymphocytes (PBLs) was performed. Tumour‐infiltrating lymphocytes contained significantly higher proportions of CD3(+) T lymphocytes and CD8(+) T lymphocytes than the corresponding PBLs (82.0%±13.9%vs 66.3%±10.6% for CD3, P<0.001; 39.0%±18.4%vs 26.4%±5.2% for CD8, P<0.001). Tumour‐infiltrating lymphocytes contained significantly higher proportions of activated memory lymphocytes than PBLs did (9.8%±8.6%vs 1.3%±1.5% for CD25, P<0.001; 40.5%±30.2%vs 10.2%±14.8% for CD71, P<0.001; 75.5%±11.9%vs 28.6%±9.8% for HLA‐DR, P<0.001). These findings were also found in both CD4(+) TILs and CD8(+) TILs. The TILs of NSCLC contained higher proportions of T lymphocytes and CD8(+) lymphocytes than their corresponding peripheral bloods. The proportions of activated memory lymphocytes were also significantly higher in the TILs, both in CD4(+) TILs and CD8(+) TILs, than the corresponding PBLs.
Recombinant human interferon beta in relapsing–remitting multiple sclerosis: a review of the major clinical trials
Authors: Chofflon M.
Published: November 2003

In this article the percentage increase in relapse‐free patients at 1 year as shown in Table 3 was presented incorrectly. The correct information is that the results reported for IFN‐β‐1a 66 mcg (59%) and 132 mcg (87%) are both statistically significant (P < 0.05) versus placebo, and should therefore have been marked with an asterisk (*), as this is the case for all other statistically significant results displayed in the table. The author apologizes for this error. The corrected version of the table appears below.
Juvenile Parkinsonism: a heterogeneous entity
Authors: Cardoso F. , Camargos S.
Published: November 2003

We studied the clinical features, laboratory investigation, management and natural history of a cohort of patients with Juvenile Parkinsonism (JP), seen at a tertiary referral centre. JP was defined as Parkinsonism with onset at age 20 years or less. Six patients (five male, one female) entered the study. The mean age at onset of Parkinsonism was 12.5 years (range 7–19) and the mean follow‐up time was 49.3 months (range 40–57). Bradykinesia, rigidity, and postural instability were observed in all patients and five subjects had tremor. Dystonia was present in four subjects. Other clinical features were dementia (five subjects), supranuclear ophthalmoparesis (five subjects), seizures (three subjects), multifocal myoclonus (one subject), decreased deep reflexes (one subject), pyramidal signs (one subject). Family history of Parkinson's disease (PD) was positive in one subject. Work‐up for Wilson's disease was negative in all patients. Neuroimaging studies showed cortical atrophy in two subjects and mild brainstem atrophy in two others. Sea‐blue histiocytes were found in one subject. L‐dopa improved the Parkinsonism in all subjects but four rapidly developed fluctuations and dyskinesias, requiring, in one, stereotaxic surgery. After a mean disease duration of 6.5 years, five subjects require assistance for performance of all daily activities. JP is a heterogeneous clinical entity. In the majority of patients, no underlying cause is identified. The unusual clinical features suggest most subjects have a CNS degenerative disease distinct from PD. There is, however, evidence suggesting that PD may rarely cause JP. Gangliosidosis is another cause of L‐dopa‐responsive JP. Regardless of the cause, in the present study JP displays an aggressive and rapidly progressive course in most patients.
Abnormal perception of the tonic vibration reflex in idiopathic focal dystonia
Authors: Yoneda Y. , Rome S. , Sagar H. J. , Grünewald R. A.
Published: November 2003

Although the pathophysiological basis of idiopathic focal dystonia (IFD) remains unclear, we recently reported abnormal perception of the tonic vibration reflex (TVR) in the biceps brachii in IFD. In this study we examined whether the abnormality affects muscles other than the biceps brachii. A 100‐Hz vibration stimulating predominantly the muscle spindle afferent was transcutaneously applied to one muscle tendon of the triceps brachii, the wrist extensor and flexor muscles in 29 subjects with IFD (18 with torticollis, 9 with writer's cramp, 2 with blepharospasm) and 15 control subjects. The blindfolded subjects were instructed to copy any perceived movement with the opposite tracking arm. The elbow or wrist angle changes were quantified electronically. The TVR and subjects’ perception of the TVR were evaluated by angle movements of the vibrated joint and of the tracking joint, respectively. Perception of the TVR was significantly reduced in dystonic subjects at both elbow and wrist joints, while magnitude of the TVR did not differ between the two groups. Abnormal central perception of the TVR is a feature of IFD, suggesting a widespread involvement of abnormal muscle spindle afferent processing in IFD.
Body packer: cocaine intoxication, causing death, masked by concomitant administration of major tranquilizers
Authors: Klein C. , Balash Y. , Pollak L. , Hiss J. , Rabey M. J.
Published: November 2003

Cocaine, derived from the leaves of the shrubErythroxylon coca, which grows on the slopes of the Andes, remains one of the most widely abused illicit drugs (Johnsonet al., 1993). Its abuse appears to be increasing and as a result, so is its trafficking across borders, with ever‐increasing sophistication of concealment (Rouse, 1992).

Over the past few years, cases of cocaine intoxication have been reported, resulting from ruptured packets of cocaine that have been swallowed, or inserted into the vagina or rectum by couriers (drug smugglers), so called ‘body packers’ or ‘mules’ (Westli and Mittleman, 1981;Ricaurte and Langston, 1995).

Cocaine is a powerful sympathomimetic and central nervous system stimulant, an overdose of which causes primarily cardiac, neurological and psychiatric effects (Ricaurte and Langston, 1995). Acute toxicity is dose‐related and is characterized in the first place by its sympathomimetic effects, which include tachycardia, hypertension and hyperthermia arrythmias, followed by seizures. Brainstem depression and cardio‐respiratory collapse, stroke, coma, intracranial vasculitis, myocardial infarction and sudden death have all been reported in cocaine abuse (Ricaurte and Langston, 1995).

We present a fatal case with neurological and psychiatric symptoms, but without the usual cardiac and systemic signs.
Evaluation of a German version of the Rivermead Mobility Index (RMI) in acute and chronic stroke patients
Authors: Schindl M. R. , Forstner C. , Kern H. , Zipko H. T. , Rupp M. , Zifko U. A.
Published: November 2003

The English Rivermead Mobility Index (RMI) has been proposed as a simple, valid and reliable measure in stroke rehabilitation. A German version was established and validated in two centres. In centre A 46 acute (median: 3.0 days after onset) and in centre B 151 chronic (median: 88.0 days after onset) stroke patients participated. Interrater reliability of the German RMI was tested in 12 subjects in the acute stage of stroke and was found to be statistically significant (r = 0.98, P < 0.0001). In centre A, a statistically significant correlation was found between the German RMI and the 10‐m walk time at baseline (r = 0.73, P < 0.0001) and after three weeks (r = 0.92, P < 0.0001). In centre B, the German RMI correlated significantly with the motor part of the Functional Independence Measure (motor‐FIM) on admission (r = 0.78, P < 0.0001) and after three weeks (r = 0.79, P < 0.0001), respectively. The change of the RMI correlated significantly with the change in 10‐m walk time in acute patients (r = 0.87, P < 0.0001) and with the change in motor‐FIM in chronic patients (r = 0.54, P < 0.0001). A moderate ceiling‐effect was detected in the chronic study population. The German RMI appears to be a reliable, valid and responsive measure for mobility disability in acute and chronic stroke patients.
Different phenotypes of Friedreich's ataxia within one ‘pseudo‐dominant’ genealogy: relationships between trinucleotide (GAA) repeat lengths and clinical features
Authors: Illarioshkin S. N. , Bagieva G. kH. , Klyushnikov S. A. , Ovchinnikov I. V. , Markova E. D. , Ivanova‐Smolenskaya I. A.
Published: November 2003

We examined a large Turkmen family with ‘pseudo‐dominant’ inheritance of Friedreich's ataxia resulting from consanguineous marriage of a Friedreich's ataxia patient to a heterozygote carrying an ancestral mutated allele. Two distinct phenotypes of the disease co‐segregated within this genealogy. Two brothers from the younger generation exhibited ‘classical’ Friedreich's ataxia with onset of symptoms before 10 years and a rapidly progressive course. In contrast, three patients (two sisters from the younger generation and their father) had a more benign phenotype of late‐onset Friedreich's ataxia with the onset at 26, 45 and 48 years and slow progression over decades. The patients with ‘classical’ Friedreich's ataxia were homozygous for a common ancestral expanded allele of the X25 gene containing 700–800 GAA repeats, while the patients with late‐onset Friedreich's ataxia had two different mutated alleles, the shorter 250‐repeat expansion of paternal origin and the longer 700‐repeat expansion of maternal origin. One may conclude that clinical variability of Friedreich's ataxia in our patients is accounted for predominantly by a modifying effect of one of the two (shorter or longer) expanded alleles inherited from their affected father. Our observation clearly demonstrates the significance of variable‐sized alleles for the phenotypic expression of the disease.
Elevation of serum soluble E‐selectin and antisulfoglucuronyl paragloboside antibodies in amyotrophic lateral sclerosis
Authors: Ikeda J. , Kohriyama T. , Nakamura S.
Published: November 2003

Immunological abnormality is often found in amyotrophic lateral sclerosis (ALS). Antibodies to sulfoglucuronyl paragloboside (SGPG) were reported in ALS, although the pathogenetic significance of the antibodies is still unknown. We have already demonstrated that SGPG, a unique glycolipid, is present in both peripheral nerve and vascular endothelial cells. To investigate whether serum anti‐SGPG antibodies would participate in activation and/or injury of endothelial cells in ALS, we examined serum anti‐SGPG antibodies in association with serum soluble E‐ and P‐selectins, which are markers of activated endothelial cells, in 25 patients with ALS and 14 age‐matched patients with other neurological diseases (ONDs) using the microtiter‐ELISA method. Seven out of 25 ALS patients had anti‐SGPG antibodies. Levels of sE‐selectin were significantly higher in patients with ALS (48.5 ± 23.4 ng/ml) compared with ONDs (24.0 ± 11.8 ng/ml) (P < 0.005). Four out of seven ALS patients with anti‐SGPG antibodies had concomitantly high sE‐selectin levels. The mean sE‐selectin levels were higher in patients with anti‐SGPG antibodies (61.9 ± 25.2 ng/ml) than in those without anti‐SGPG antibodies (43.3 ± 21.1 ng/ml). Anti‐SGPG antibodies may take part in the activation and/or injury of endothelial cells. The increased expression of E‐selectin may be related to an immunological process in some ALS patients.