The different types of limb apraxia errors made by patients with left vs. right hemisphere damage.
Limb apraxia errors were compared among normal controls and right- or left-hemisphere-damaged patients as they imitated gestures with the ipsilateral hand. Both brain-damaged groups made similar errors on nonrepresentative and representative/intransitive movements. In contrast for pretended object use movements (transitive), the left-hemisphere-damaged group made more arm position and classical body-part-as-object errors while the right hemisphere group made as many partial errors and more less-primitive, body-part-as-object errors than the left-hemisphere-damaged group. These results help explain why a certain percentage of right-hemisphere-damaged patients are labeled apraxic, but also suggest that the left hemisphere is more important for integrating intrapersonal space and the "representation" of extrapersonal space.


Identification of pirin, a novel highly conserved nuclear protein.
In this article we describe the molecular cloning of Pirin, a novel highly conserved 32-kDa protein consisting of 290 amino acids. Pirin was isolated by a yeast two-hybrid screen as an interactor of nuclear factor I/CCAAT box transcription factor (NFI/CTF1), which is known to stimulate adenovirus DNA replication and RNA polymerase II-driven transcription. Pirin mRNA is expressed weakly in all human tissues tested. About 15% of all Pirin cDNAs contain a short 34-base pair insertion in their 5'-untranslated regions, indicative of alternative splicing processes. Multiple Pirin transcripts are expressed in skeletal muscle and heart. Western blots and immunoprecipitations employing monoclonal anti-Pirin antibodies reveal that Pirin is a nuclear protein. Moreover, confocal immunofluorescence experiments demonstrate a predominant localization of Pirin within dot-like subnuclear structures. Homology searches using the BLAST algorithm indicate the existence of Pirin homologues in mouse and rat. The N-terminal half of Pirin is significantly conserved between mammals, plants, fungi, and even prokaryotic organisms. Genomic Southern and Western blots demonstrate the presence of Pirin genes and their expression, respectively, in all mammalian cell lines tested. The expression pattern, the concentrated localization in subnuclear structures, and its interaction with NFI/CTF1 in the two-hybrid system classify Pirin as a putative NFI/CTF1 cofactor, which might help to gain new insights in NFI/CTF1 functions.


Synthesis and antioxidant properties of enone core based dendrimers with carbazole as surface group.
Synthesis of enone core based dendrimers with carbazole as surface group has been achieved. All the synthesized dendrimers showed excellent antioxidant behavior with commercially available 1,1-diphenyl-2-picryl hydrazyl (DPPH).


Variations in the mechanical properties of cartilage from the canine scapulohumeral joint.
To measure the intrinsic material properties of scapulohumeral joint cartilage in adult dogs and determine whether regional differences exist within or between the humeral and glenoid cartilages. Paired shoulder joints from 7 clinically normal adult dogs. An automated indentation apparatus was used to obtain the intrinsic mechanical properties of the cartilage at 7 sites on each joint surface. Topographic variations in mechanical properties of the glenoid and humeral cartilages were observed. The largest aggregate modulus (HA) for the humerus was seen at the caudocentral site (0.92 MPa) and for the scapula was seen at the centrocenter site (0.84 MPa). The mean shear modulus (mu) of humeral cartilage (0.23 MPa) was significantly greater than that of the glenoid cartilage (0.19 MPa). The mean Poisson's ratio (v) of humeral cartilage (0.24) was significantly smaller than that for the glenoid cartilage (0.29). Mean humeral cartilage aggregate modulus (0.71 MPa) was larger than the value for glenoid cartilage (0.67 MPa), but these differences were not significant. There were no significant differences in the compressive stiffness of the opposing cartilage in the canine scapulohumeral joint. Differences in mechanical properties between opposing humeral and glenoid cartilages are not a cause of cartilage injury in the scapulohumeral joint of adult dogs. The mechanical properties of cartilage from young dogs with open physes and incomplete subchondral bone plates may be different from those of adult dogs.


Behçet's syndrome: ocular features in an Australian population.
Inflammatory eye disease (IED) is often the most severe manifestation of Behçet's syndrome (BS). This disease is a common cause of uveitis in Mediterranean countries, the Middle East and Japan. In order to ascertain the prevalence of this disease in Australia, we reviewed the aetiology of patients attending our uveitis clinic over a five-year period. Twelve of 426 patients with inflammatory eye disease had definite Behçet's syndrome. Four patients had anterior uveitis, four had posterior uveitis, four had retinal vasculitis and one also had optic neuritis. Although inflammatory eye disease was the initial clinical feature of Behçet's syndrome in only three of our patients, it was the feature that led to a definite diagnosis in all but one patient. The inflammatory eye disease of Behçet's syndrome was characteristically recurrent and severe with significantly decreased vision in 10 eyes, cataracts in six eyes, macula oedema in four eyes and glaucoma in two eyes. We conclude that Behçet's syndrome is a rare cause of inflammatory eye disease in Australia and is unlikely to be recognised as a distinct clinical entity prior to the onset of ocular involvement. The visual prognosis of ocular inflammation in Behçet's syndrome remains guarded despite the use of a variety of immunosuppressive agents.


Interaction of bilirubin and indocyanine green with the binding and conjugation of sulfobromophthalein by rat liver cytosol proteins.
The interaction of bilirubin and indocyanine green with sulfobromophthalein (BSP) binding and conjugation by rat liver cytosol proteins was studied. BSP bound to cytosol proteins X, ligandin and Z and the BSP-glutathione conjugate were isolated by sephadex gel chromatography. Neither bilirubin nor indocyanine green affected the binding of BSP to ligandin and Z protein. However, indocyanine green did significantly reduce BSP conjugation in both in vitro and in vivo experiments. Diethyl maleate significantly reduced liver glutathione levels and BSP conjugation. It is suggested that indocyanine gree competitively binds at the ligandin catalytic site whereas the primary binding site for bilirubin is probably a noncatalytic site.


Model-based analysis of dispersion curves using chirplets.
Time-frequency representations, like the spectrogram or the scalogram, are widely used to characterize dispersive waves. The resulting energy distributions, however, suffer from the uncertainty principle, which complicates the allocation of energy to individual propagation modes (especially when the dispersion curves of these modes are close to each other in the time-frequency domain). This research applies the chirplet as a tool to analyze dispersive wave signals based on a dispersion model. The chirplet transform, a generalization of both the wavelet and the short-time Fourier transform, enables the extraction of components of a signal with a particular instantaneous frequency and group delay. An adaptive algorithm identifies frequency regions for which quantitative statements can be made about an individual mode's energy, and employs chirplets (locally adapted to a dispersion curve model) to extract the (proportional) energy distribution of that single mode from a multimode dispersive wave signal. The effectiveness of this algorithm is demonstrated on a multimode synthetic Lamb wave signal for which the ground-truth energy distribution is known for each mode. Finally, the robustness of this algorithm is demonstrated on real, experimentally measured Lamb wave signals by an adaption of a correlation technique developed in previous research.


Cost of patient follow-up after potentially curative colorectal cancer treatment.
To estimate the cost of follow-up among colorectal cancer patients treated with curative intent based on the broad spectrum of surveillance strategies suggested in the literature. Economic analysis of the costs associated with 11 separate surveillance strategies. Charge data were obtained from the Part B Medicare Annual Data file and the Hospital Outpatient Bill file. Ambulatory care. Medicare-allowed charges and an actual-charge proxy for 5 years of follow-up after treatment for colorectal cancer patients on a nationwide basis. Medicare-allowed charges varied widely for the 5 years of posttreatment follow-up from a low of $561 to a high of $16,492. When Medicare-allowed charges were converted to a proxy for actual charges using a conversion ratio of 1.62, the range was $910 to $26,717, a 28-fold difference in charges. Charges vary extensively across follow-up strategies, with no indication that higher-cost strategies increase survival or quality of life.


Characterization of benzopyrene metabolism in rat pancreas.
The present studies characterized the pancreatic metabolic system which biodegrades benzo[a]pyrene (BP), in male Sprague-Dawley rats pretreated with 20 mg/kg 3-methylcholanthrene (3MC), 75 mg/kg phenobarbital (PB) or solvent as control. Type of cytochrome involved was examined by measuring the reaction in the presence of 7,8-benzoflavone (BF), an inhibitor of the cytochrome P-448-related enzyme activity. The data indicated that the enzyme activity was induced by pretreatment with PB but not with 3MC. These pretreatment protocols resulted in changes both in Km and Vmax. Studies with BF suggested that pancreatic tissue may not contain more than one class of hemoprotein. These studies pointed out species differences between the rat and guinea pig, and confirmed the pancreatic capability to metabolize procarcinogens and to further degrade carcinogenic metabolites.


PCR-based detection and genotyping of haematozoa (Protozoa) parasitizing eagle owls, Bubo bubo.
We genetically analysed haematozoa parasites (Protozoa) isolated from nestling eagle owls (Bubo bubo) in Toledo province, Central Spain. A total of 206 nestlings from 74 nests were screened for parasites of the genera Leucocytozoon, Plasmodium, and Haemoproteus using a very efficient polymerase chain reaction (PCR) approach that amplifies a partial segment of the mitochondrial cytochrome b gene of these parasites. PCR-based detection and sequence analyses revealed a unique lineage of Leucocytozoon (EO1) parasitizing nestling eagle owls. Ocular examination of blood smears identified these parasites as Leucocytozoon ziemanni, the only species deemed valid in owls based on morphology. Preliminary phylogenetic analyses using homologous published sequences isolated from other owl species suggest that L. ziemanni constitutes a monophyletic clade that may be composed by a complex of genetically differentiated cryptic species.


[Impact factor of Revista Iberoamericana de Micología].
The impact factor is a bibliometric indicator published annually in the Journal Citation Reports, and widely regarded as a quality ranking of the journals included in this database. The problem with this indicator is that the impact factor of several journals not listed in the Science Citation Index database is largely unknown. The aim of this study was to analyze the 2001 national and international impact factor of Revista Iberoamericana de Micología. The National impact factor of Revista Iberoamericana de Micología was obtained by adding the number of cites in 2001 from a total of 87 Spanish medical journals of greater scientific quality. Also, bibliographical references from Spanish journals indexed in the 2001 Journal Citation reports database have been included to determine the international impact factor of this analyzed journal. Revista Iberoamericana de Micología received a total of 62 cites from published articles in 1999 to 2001, coming from 20 different journals, being their self-citation index 10.1%. The journal with the highest number of cites to Revista Iberoamericana de Micología was Journal of Clinical Microbiology, with 12 cites (19.3%). According to this findings the national and international impact factor of Revista Iberoamericana de Micología was 0.266 and 0.606, respectively. The impact factor of Revista Iberoamericana de Micología, although not included in the Science Citation Index database, was higher than other Journal Citation Reports. Moreover, Revista Iberoamericana de Micología received most of its citations from high impact factor journals included in the Journal Citation Reports database. These data support the international recognition of the scientific level of the journal.


Proximal sacral deformity: a common element in lytic isthmic spondylolisthesis at L5 and in degenerative spondylolisthesis at L4-L5 segment. Two apparently very different etiopathogenic entities.
A radiographic study was carried out to investigate the relationship between proximal sacral sagittal anatomy (either kyphosis or lordosis) and either isthmic or degenerative spondylolisthesis. In addition, we studied whether there is a relationship between proximal sacral kyphosis and the degree of such listhesis in the case of L5 isthmic spondylolisthesis. Lateral standing x-rays were used from 173 patients, ninety of whom had degenerative spondylolisthesis L4-L5, and eighty-three an isthmic spondylolisthesis of L5 (67 low-grade and 16 high-grade) and compared with a control group of 100 patients adjusted by age and gender, without any type of spondylolisthesis. Listhesis was graded using Meyerding's classification and the proximal sacral kyphosis angle (CSP) was measured between S1 and S2 posterior walls, according to Harrison's method. In our series, there was a proximal sacral kyphosis in both types of spondylolisthesis, greater in the lytic type. By contrast, the control group had a proximal sacral lordosis. The differences were statistically significant. Therefore, we concluded that there was a proximal sacral kyphosis in patients with both degenerative and isthmic lytic spondylolisthesis, but with our results, we were not able to ascertain whether it is a cause or a consequence of this listhesis.


The discovery of stereoselectivity at biological receptors: Arnaldo Piutti and the taste of the asparagine enantiomers--history and analysis on the 125th anniversary.
In 1886, Italian chemist Arnaldo Piutti isolated, for the first time, d-asparagine, the enantiomer of the known l-asparagine. He obtained 100 g of D-asparagine from 6500 kg of vetches. Using an ingenious synthetic scheme, Piutti established the chemical structure of asparagine and demonstrated that his isolation of D-asparagine from plants was not the result of the racemization of L-asparagine during the extraction procedure. He found a striking difference in the taste of asparagine: L-asparagine was without taste, while D-asparagine was intensely sweet. This was the first example of enantioselectivity in a receptor-mediated biological activity. Receptors constitute one of the most important and most intensively studied phenomena in biology, and enantioselectivity in receptor-mediated activity, including at the sweetness receptor, is today an important and commonly seen aspect of receptor function. Therefore, Piutti's discovery, although made ca. 15 years before the emergence of the receptor concept, was a milestone. The publication of Piutti's asparagine work prompted several eminent scientists, including Louis Pasteur and Arthur Cushny, a leading pharmacologist of the time, to remark on the importance of the discovery. Piutti also carried out investigations in many other fields, e.g., other organic compounds and reactions, pharmaceuticals, alimentary products, radioactivity, noble gases, and spectroscopy. Considerable progress has been made in recent decades concerning the biology and chemistry of sweet taste, but the details of the interactions of chiral molecules with the sweetness receptor remain poorly understood. Piutti and his discovery are largely forgotten today; they deserve the attention of the chirality and receptor "communities."


P329G-CAR-J: a novel Jurkat-NFAT-based CAR-T reporter system recognizing the P329G Fc mutation.
Monoclonal antibody-based therapeutics are an integral part of treatment of different human diseases, and the selection of suitable antibody candidates during the discovery phase is essential. Here, we describe a novel, cellular screening approach for the identification and characterization of therapeutic antibodies suitable for conversion into T cell bispecific antibodies using chimeric antigen receptor (CAR) transduced Jurkat-NFAT-luciferase reporter cells (CAR-J). For that purpose, we equipped a Jurkat-NFAT reporter cell line with a universal CAR, based on a monoclonal antibody recognizing the P329G mutation in the Fc-part of effector-silenced human IgG1-antibodies. In addition to scFv-based second generation CARs, Fab-based CARs employing the P329G-binder were generated. Using these anti-P329G-CAR-J cells together with the respective P329G-mutated IgG1-antibodies, we established a system, which facilitates the rapid testing of therapeutic antibody candidates in a flexible, high throughput setting during early stage discovery. We show that both, scFv- and Fab-based anti-P329G-CAR-J cells elicit a robust and dose-dependent luciferase signal if the respective antibody acts as an adaptor between tumor target and P329G-CAR-J cells. Importantly, we could demonstrate that functional characteristics of the antibody candidates, derived from the anti-P329G-CAR-J screening assay, are predictive for the functionality of these antibodies in the T cell bispecific antibody format.


Dithiothreitol activation of the insulin receptor/kinase does not involve subunit dissociation of the native alpha 2 beta 2 insulin receptor subunit complex.
The subunit composition of the dithiothreitol- (DTT) activated insulin receptor/kinase was examined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and gel filtration chromatography under denaturing (0.1% SDS) or nondenaturing (0.1% Triton X-100) conditions. Pretreatment of 32P-labeled insulin receptors with 50 mM DTT followed by gel filtration chromatography in 0.1% SDS demonstrated the dissociation of the alpha 2 beta 2 insulin receptor complex (Mr 400,000) into the monomeric 95,000 beta subunit. In contrast, pretreatment of the insulin receptors with 1-50 mM DTT followed by gel filtration chromatography in 0.1% Triton X-100 resulted in no apparent alteration in mobility compared to the untreated insulin receptors. Resolution of this complex by nonreducing SDS-polyacrylamide gel electrophoresis and autoradiography demonstrated the existence of the alpha 2 beta 2 heterotetrameric complex with essentially no alpha beta heterodimeric or free monomeric beta subunit species present. This suggests that the insulin receptor can reoxidize into the Mr 400,000 complex after the removal of DTT by gel filtration chromatography. Surprisingly, these apparently reoxidized insulin receptors were also observed to be functional with respect to insulin binding, albeit with a 50% decrease in affinity for insulin and insulin stimulation of the beta subunit autophosphorylation. To prevent reoxidation, the insulin receptors were pretreated with 50 mM DTT followed by incubation with excess N-ethylmaleimide prior to gel filtration chromatography in 0.1% Triton X-100. Under these conditions the insulin receptors migrated as the Mr 400,000 alpha 2 beta 2 complex.(ABSTRACT TRUNCATED AT 250 WORDS)


Endoscopic surgery for lacrimal obstruction.
Intranasal access to the lacrimal drainage system has been greatly enhanced with the advent of endoscopic nasal surgery. This technique has been used for the treatment of recurrent lacrimal obstruction after failed external dacryocystorhinostomy (DCR) in 12 patients. Improved intranasal visualization with the endoscope allowed easy identification and opening of the lacrimal sac, with no need for a skin incision. Obstructing intranasal pathology, including adhesions from previous DCR, an enlarged middle turbinate, and ethmoid sinus disease, was readily identified and corrected. There were no intraoperative complications. Lacrimal obstruction was completely relieved in nine of 12 patients (75%), with a followup of 7 to 25 months. Endoscopic revision DCR should be considered in patients with recurrent epiphora after external DCR.


Oxidative stress responses of the yeast Saccharomyces cerevisiae.
All aerobically growing organisms suffer exposure to oxidative stress, caused by partially reduced forms of molecular oxygen, known as reactive oxygen species (ROS). These are highly reactive and capable of damaging cellular constituents such as DNA, lipids and proteins. Consequently, cells from many different organisms have evolved mechanisms to protect their components against ROS. This review concentrates on the oxidant defence systems of the budding yeast Saccharomyces cerevisiae, which appears to have a number of inducible adaptive stress responses to oxidants, such as H2O2, superoxide anion and lipid peroxidation products. The oxidative stress responses appear to be regulated, at least in part, at the level of transcription and there is considerable overlap between them and many diverse stress responses, allowing the yeast cell to integrate its response towards environmental stress.


Abundance and degree of dispersion of genomic d(GA)n.d(TC)n sequences.
The abundance of d(GA)n.d(TC)n tracts was determined in genomes of rodents and primates. Dot blot hybridization assays revealed that such tracts constitute 0.40%, 0.30%, and 0.40%, respectively, of the rat, hamster, and mouse genomes, but only 0.07% and 0.05% of the human and monkey genomes. A plaque hybridization assay of rat and human genomic libraries showed that 37% and 16%, respectively, of the recombinant phages in these libraries contain d(GA)n.d(TC)n tracts. A survey of sequences stored in the GenBank data bank showed that a significant fraction of the stored rodent genes (about 2.0%) contain long d(GA)n.d(TC)n tracts (n greater than 30) with greater than 10% mismatching. The primate genes contain only shorter tracts (n less than 15) with less than 10% mismatching. In addition, the rodent and the primate genes contain tracts with larger degrees of mismatching. The chicken, which represents an entirely different branch of the evolutionary tree, was found to be as low in d(GA)n.d(TC)n tracts as the primates. It is suggested that a common ancestor of the rodents has acquired the ability to amplify d(GA)n.d(TC)n tracts.


Caffeoylquinic acids from antiplasmodial active extract of Xanthium cavanillesii fruits and their molecular modelling studies.
The antiplasmodial active extract of Xanthium cavanillesii contains 3,4-dicaffeoyl quinic acid (3,4-DCQA), 3,5-dicaffeoyl quinic acid (3,5-DCQA) and 1,3,5-tricaffeoyl quinic acid (1,3,5-TCQA). These results inspired us to investigate the interaction of these molecules with a promising validated target of Plasmodium, PfATP6 orthologue of mammalian Ca+2-ATPase. Models of this receptor were obtained through comparative modelling. Afterwards, molecular docking studies were used to identify possible interaction modes of these caffeoyl quinic derivatives on the binding site. The 1,3,5-TCQA had the best energy, but all of these had better energy than thapsigargin, a non-competitive inhibitor of the sarco/endoplasmatic reticulum Ca+2-ATPase (SERCA).


Redox control of transcription: sensors, response regulators, activators and repressors.
In a growing number of cases, transcription of specific genes is known to be governed by oxidation or reduction of electron carriers with which the gene products interact. The biological function of such control is to activate synthesis of appropriate redox proteins, and to repress synthesis of inappropriate ones, in response to altered availability of specific electron sources and sinks. In prokaryotic systems this control appears to operate by two general classes of mechanism: by two-component regulation involving protein phosphorylation on histidine and aspartate; and by direct oxidation-reduction of gene repressors or activators. For the first class, termed 'two-component redox regulation', the term 'redox sensor' is proposed for any electron carrier that becomes phosphorylated upon oxidation or reduction and thereby controls phosphorylation of specific response regulators, while the term 'redox response regulator' is proposed for the corresponding sequence-specific DNA-binding protein that controls transcription as a result of its phosphorylation by one or more redox sensors. For the second class of redox regulatory mechanism, the terms 'redox activator protein' and 'redox repressor protein' are proposed for single proteins containing both electron transfer and sequence-specific DNA-binding domains. The structure, function and biological distribution of these components are discussed.


[Cutaneous congruence in vertical scar mammaplasty with preservation of mammary base. Geometrical bases and initial study].
After a geometrical analysis studying the principle of the "inverted T" scar in mammoplasties and particularly the significance of the horizontal limb of the "T", the authors have developed a mammoplasty technique without a horizontal scar, based on the concept of preservation of the mammary implantation basis. Application of this principle to a preliminary series of 92 breasts in 48 patients over a period of two years enabled the authors to perform cone resection of the mammary gland, while producing a congruent vertical scar not extending onto the inframammary sulcus. This technique, in contrast with other vertical scar mammoplasty techniques, does not generate any skin excess in the inframmary sulcus and avoids the need for skin resorption devices (cutaneous undermining, frowns), thereby decreasing the risk of morphological distortion and unsightly scars.


Comparative analysis of the applicability of the skeletal age determination methods of Greulich-Pyle and Thiemann-Nitz for forensic age estimation in living subjects.
Evaluation of hand ossification is a main pillar of radiological age diagnosis in living subjects. In the present study, we comparatively assessed the Greulich-Pyle and Thiemann-Nitz methods for accuracy of age estimation and degree of acceleration in the respective reference populations. For this, the skeletal age of 649 hand X-rays from German subjects aged 1-18 years was determined by both methods. Accuracy of the age estimates was determined based on regression and measures of certainty. In terms of accuracy, both methods seem to be equally well suited for forensic age diagnostics. The degree of acceleration in the reference populations for the two methods was calculated as the mean difference between the estimated skeletal age and the actual age of a test subject. Compared to the Greulich-Pyle population, the Thiemann-Nitz population was accelerated by 0.44 years in both male and female subjects. When an expert opinion is required and one cannot exclude the possibility that the investigated subject may come from a population with a high acceleration status, the Thiemann-Nitz method should preferably be used to prevent overestimation of age.


Structure of aldehyde reductase in ternary complex with a 5-arylidene-2,4-thiazolidinedione aldose reductase inhibitor.
The structure of aldehyde reductase (ALR1) in ternary complex with the coenzyme NADPH and [5-(3-carboxymethoxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid (CMD), a potent inhibitor of aldose reductase (ALR2), was determined at 1.99A resolution. The partially disordered inhibitor formed a tight network of hydrogen bonds with the active site residues (Tyr50 and His113) and coenzyme. Molecular modelling calculations and inhibitory activity measurements of CMD and [5-(3-hydroxy-4-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl]acetic acid (HMD) indicated that pi-stacking interactions with several conserved active site tryptophan residues and hydrogen-bonding interactions with the non-conserved C-terminal residue Leu300 in ALR2 (Pro301 in ALR1) contributed to inhibitor selectivity. In particular for the potent inhibitor CMD, the rotameric state of the conserved residue Trp219 (Trp220 in ALR1) is important in forming a pi-stacking interaction with the inhibitor in ALR2 and contributes to the difference in the binding of the inhibitor to the enzymes.


Usefulness of hemilaminectomy for microsurgical management of intraspinal lesions.
Hemilaminectomy is a limited, unilateral approach to the spinal cord that provides excellent exposure of the dorsolateral and ventral portions of the spinal canal. This approach is most suitable for microsurgical management of the majority of extramedullary tumors. Contrary to conventional laminectomy, the posterior supporting structures of the spine are completely preserved on the contralateral side with this access route. The procedure has been applied in 3 patients who harbored a cervical neurilemmoma, a cervical lipoma, and a thoracic neurilemmoma, respectively. Optimal exposure of the lesion was achieved in each case, and each patient's symptoms improved or completely resolved postoperatively. There were no surgical complications. It is concluded that hemilaminectomy combined with microsurgical techniques should be given priority over standard laminectomy in the surgical management of extramedullary lesions arising in the spinal canal.


Acquired thymic tolerance and experimental allergic encephalomyelitis in the rat. I. Parameters and analysis of possible mechanisms.
Intrathymic injection of guinea pig myelin basic protein (MBP) or the immunodominant, encephalitogenic fragment of MPB, 68-86, without otherwise compromising the peripheral lymphocyte pool in adult LEW rats, dramatically inhibits onset of experimental allergic encephalomyelitis (EAE) caused by the usual peripheral inoculation with MBP in complete Freund's adjuvant. This surprising finding demonstrates that interaction of antigen and one or more components of an intact thymus can down-regulate systemic responses by mature T cells already existing in the peripheral lymphocyte pool. How this happens is not known. In studies designed to explore possible mechanisms: (a) adult thymectomized animals remain susceptible to active EAE, thus EAE cannot be attributed solely to recent thymic emigrants that might be inactivated by antigen deposited in the thymus; (b) heterotopic isografts of injected thymic lobes transfer thymic tolerance to secondary recipients, thus the tolerance effect is dominant over an intact, non-treated thymus; (c) T cells from made thymic tolerant but not immunized donors are less effective in causing EAE following adoptive transfer into, and active immunization of, secondary, irradiated recipients; and (d) animals resistant to active EAE as a consequence of thymic tolerance are fully vulnerable to adoptive EAE caused by already activated MBP-specific T cell subpopulations. These results rule out a possible mechanism previously proposed for acquired thymic tolerance, i. e., that potentially pathogenic T cells traffic to the antigen-injected thymus where they are inactivated or eliminated.


The differential miscibility of lipids as the basis for the formation of functional membrane rafts.
The formation of sphingolipid-cholesterol microdomains in cellular membranes has been proposed to function in sorting and transport of lipids and proteins as well as in signal transduction. An increasing number of cell biological and biochemical studies now supports this concept. Here we discuss the structural properties of lipids in a cell biological context. The sphingolipid-cholesterol microdomains or rafts are described as dispersed liquid ordered phase domains. These domains are dynamic assemblies to which specific proteins are selectively sequestered while others are excluded. The proteins associated to rafts can act as organizers and can modulate raft size and function.


The child as the presenting symptom, and what happens when things go wrong?
In this paper I wish to draw attention to Balint's concept of 'the Child as the presenting symptom' and ask whether this concept is relevant to us as psychiatrists. What arises is whether this concept might illuminate situations where there is serious mental illness in the family, and whether the presentation of a child to a doctor might be indicative of mental illness in the family. If such an interpretation is possible, then there are important clinical implications, since at present, all UK government guidance, based on the analysis of many high-profile cases where children have been severely abused, is that the needs of the child are paramount, and thence it may be that, whilst quite dramatic intervention may well occur in order to protect the child, perhaps the mental health needs of the parents might be somewhat overlooked. Examples of the interplay between child and parents in the context of mental illness are given, and the present way in which children within families where there is mental illness are cared for is described, also considering the consequences for the parents.


The nuclear exporter, Crm1, is regulated by NFY and Sp1 in cancer cells and repressed by p53 in response to DNA damage.
The nuclear exporter protein, Crm1, plays a key role in normal cell functioning, mediating the nucleo-cytoplasmic transport of cargo proteins. Elevated Crm1 expression has recently been identified in various tumours; however, the mechanisms driving its expression have not been investigated to date. In this study we identified the Crm1 promoter and factors associated with its elevated expression and with its repression under conditions of DNA damage. The -1405 to +99 Crm1 promoter region was found to be significantly more active in cancer and transformed cells compared to normal, and the -175 to +99 region identified as responsible for the differential activity. Mutation of two CCAAT boxes and a GC box within this region significantly diminished Crm1 promoter activity and ChIP analysis revealed binding of NFY and Sp1 to these sites, with increased binding in transformed and cancer cells. In addition, p53 was found to repress Crm1 promoter activity, after induction with doxorubicin, with p53 siRNA blocking the effect. Crm1 promoter constructs with mutated CCAAT boxes were significantly less responsive to p53 repression, and in vivo binding of NFY to the CCAAT boxes was diminished upon p53 binding, suggesting that p53 mediates repression of the Crm1 promoter via interfering with NFY. This was confirmed using NFY knock-down cells, in which Crm1 promoter activity was significantly less responsive to p53. In vitro EMSAs revealed that NFY and p53 bind the CCAAT boxes as a single complex under conditions of DNA damage. In summary, this study is a first to analyse Crm1 promoter regulation and reveals NFY and Sp1 as contributors to Crm1 overexpression in cancer. In addition, this study reveals that Crm1 transcription is inhibited by DNA damage and that the mechanism of inhibition involves p53 interfering with NFY function.


Effects of high temperature and exposure to air on mussel (Mytilus galloprovincialis, Lmk 1819) hemocyte phagocytosis: modulation of spreading and oxidative response.
Hemocytes are a critical component of the mussel defense system and the present study aims at investigating their spreading and oxidative properties during phagocytosis under in vivo experimental stress conditions. The spreading ability was measured by an automated cell analyzer on the basis of the circularity, a parameter corresponding to the hemocyte roundness. The oxidative activity was investigated by micromethod assay, measuring the respiratory burst as expression of the fluorescence generated by the oxidation of specific probe. Following the application of high temperature and exposure to air, there was evidence of negative modulation of spreading and oxidative response, as revealed by a cell roundness increase and fluorescence generation decrease. Therefore, the fall of respiratory burst appeared as matched with the inhibition of hemocyte morphological activation, suggesting a potential depression of the phagocytosis process and confirming the application of the circularity parameter as potential stress marker, both in experimental and field studies.


Gram-positive cell wall structure of the A3 gamma type in heliobacteria.
The amino acid composition and structure of the peptidoglycan from Heliobacillus mobilis was determined by one- and two-dimensional thin-layer chromatography of completely and partially hydrolysed cell wall preparations. The structure was found to be of the A3 gamma type, with L,L-diaminopimelate in position 3, D-alanine in position 4 and a glycine interpeptide bridge, as found in certain groups of Gram-positive bacteria including Clostridium perfringens and Nocardioides simplex. The presence of a Gram-positive type of cell wall in heliobacteria is consistent with their phylogenetic relationship to the 'low G + C' Gram-positive bacteria, as previously demonstrated by 16S rRNA sequencing.


Determination of the functioning of autotransplanted parathyroid tissue in muscle.
Twenty dialysis and renal transplant patients with parathyroid hyperplasia underwent a total parathyroidectomy and an autotransplantation in forearm muscle. Twelve patients were available for investigation of the function of the transplanted parathyroid tissue. Differential studies of the two arms revealed functioning of the transplanted tissue in all cases. This was more readily demonstrated by determining the intact hormone in both arms.


Does cardiac transplantation prolong life and improve its quality? An updated report.
The current status of the human cardiac transplant experience at Stanford University Medical Center is presented in order to reassess its role in the treatment of end-stage cardiac disease. Of 109 patients undergoing transplantation at Stanford between January 1968 and August 1976, 44 were still alive as of August 1, 1976. The overall 1- and 2-year survival rates for the series are 52% and 43%, respectively. Sixty-nine patients have survived more than 3 months, and their overall 1- and 2-year survival rates are 80% and 66%, respectively. Of the 3-month survivors, 62 (90%) returned to functional Class I New York Heart Association cardiac status and most of these returned to their pre-illness activities. Of 40 patients selected for transplantation for whom a donor did not become available, 38 were dead in less than 6 months. Complications related to immunosuppression with steroids are currently the major barrier to longer survival and improved rehabilitation postransplantation. On the basis of these data we conclude that cardiac transplantation not only prolongs survival, but can return carefully selected recipients to an active life.


Determination of the minimal acid-inducible promoter region of the lipF gene from Mycobacterium tuberculosis.
The Mycobacterium tuberculosis gene lipF, Rv3487c, is transcriptionally upregulated by exposure to acidic growth media. We previously identified a 477 base pair (bp) region of DNA 147 bp upstream of lipF that is transcriptionally upregulated by exposure to growth media at pH 4.5 [Saviola, B., Woolwine, S., Bishai, W. R., 2003. Isolation of acid-inducible genes of Mycobacterium tuberculosis with the use of recombinase-based in vivo expression technology. Infect. Immun. 71, 1379-1388]. In this study we truncate the lipF promoter region first from the 3' DNA end and then from the 5' DNA end. The truncated promoter regions were placed upstream of the gene for the green fluorescent protein (gfp) and each promoter region was analyzed in Mycobacterium smegmatis for its ability to undergo transcriptional upregulation in response to acid stress. A minimal acid-inducible promoter region was identified and is located between -515 bp and -573 bp with respect to the start site of translation of lipF. The 59 bp minimal promoter region is a defined DNA sequence that confers full promoter activity that is transcriptionally upregulated in response to acid stress. Primer extension analysis was performed on acid-induced M. smegmatis bearing the minimal promoter region fused to gfp and revealed a start site of transcription specifically upregulated by acid stress corresponding to -511 bp upstream of lipF with respect to the start of translation.


Continuous and discrete stable processes.
The one-sided Lévy-stable probability densities and the discrete-stable distributions form a doubly stochastic Poisson transform pair. This relationship facilitates the formulation of a class of continuous-stable stochastic processes.


Accumulation of DC in lamina propria induced by FMS-like tyrosine kinase 3 ligand aggravates the intestinal inflammatory response during endotoxemia.
It is known that the loss of DC plays an important role for immune suppression during endotoxemia or sepsis. To verify our hypothesis that pre-enrichment of the lamina propria (LP) DC pool may improve protective immunity to bacterial translocation and outcome in endotoxemic mice, we pre-treated mice with Flt3L or normal saline, and then challenged them with or without LPS. Twelve hours later the population size and maturity of DC in the LP and circulation were analyzed by flow cytometry. Bacterial translocation to distant organs, inflammatory responses in the intestine and the survival rate of mice were evaluated. We observed that pretreatment of Flt3L significantly expanded DC in the LP and blood, but did not alter their maturation. However, exacerbation of DC growth induced by Flt3L-pretreatment aggravated intestinal inflammation and increased the mortality of endotoxemic mice rather than enhancing their resistance to bacterial translocation.


A report case of Cyclospora and Cryptosporidium mixed infection in a HIV-negative child in Thailand.
The first case of cyclosporosis in a non HIV-infected child in Thailand, co-infected with Cryptosporidium, was reported. The patient was a 3 year-old malnourished orphan who presented with fever, abdominal distension and relapsing diarrhea. There was no leukocyte in her stool, however, numerous Cyclospora and Cryptosporidium oocysts were identified by modified acid-fast staining. The illness was cured by co-trimoxazole and fluid therapy. More coccidial infections in Thailand may be detected if modified acid-fast staining is routinely performed.


In vitro and in vivo methodologies for studying the Sigma 54-dependent transcription.
Here we describe approaches and methods to assaying in vitro the major variant bacterial sigma factor, Sigma 54 (σ(54)), in a purified system. We include the complete transcription system, binding interactions between σ54 and its activators, as well as the self-assembly and the critical ATPase activity of the cognate activators which serve to remodel the closed promoter complexes. We also present in vivo methodologies that are used to study the impact of physiological processes, metabolic states, global signalling networks, and cellular architecture on the control of σ(54)-dependent gene expression.


T-tube or no T-tube in cadaveric orthotopic liver transplantation: the eternal dilemma: results of a prospective and randomized clinical trial.
To compare the incidence and severity of biliary complications due to liver transplantation after choledochocholedochostomy with or without a T-tube in a single-center, prospective, randomized trial. The usefulness of the T-tube for end-to-end biliary anastomosis to reduce the incidence of biliary complications in patients undergoing liver transplantation has been controversial. A per-protocol analysis was designed for liver recipients, who were randomly assigned to choledochocholedochostomy with (n = 95) or without (n = 92) a T-tube. The overall biliary complication rate was 22.5% (n = 42), with no difference between groups (P = 0.35). The majority (66.7%) of complications in the T-tube group were types I and II, whereas 50% were type IIIa and 44% were type IIIb in the non-T-tube group (P < 0.0001). Fewer anastomotic strictures were found in the T-tube group (n = 2, 2.1%) than in the non-T-tube group (n = 13, 14.1%; P = 0.002). No difference in anastomotic biliary leakage was observed between groups. Biliary complication-free survival rates showed that complications appeared earlier in the T-tube group. Graft and patient survival rates were similar in both groups. Complications in the T-tube group were less severe and required less aggressive treatment. The incidence of anastomotic strictures was higher in patients with no T-tube. We recommend conducting choledochocholedochostomy with a rubber T-tube during liver transplantation in risky anastomosis and when the bile duct diameter is less than 7 mm. This study is registered at http://www.clinicaltrials.gov: Clinical trial ID# NCT01546064.


Topographical differences in the trigeminal sensitivity of the human nasal mucosa.
The aim of the study was to investigate differences in the distribution of intranasal trigeminal receptors in humans using an electrophysiological measure of trigeminally induced activation, the negative mucosa potential. A total of 29 young, healthy volunteers participated, results were on the basis of data from 18 participants. The trigeminal irritant CO2 was presented using a computer-controlled olfactometer. Negative mucosa potential recording sites included the anterior olfactory cleft, the anterior septum, and the lower turbinate. Lowest amplitudes of the negative mucosa potential were found in the olfactory cleft, maximum amplitudes at the septum. Intranasal measurements of CO2 concentrations suggested that these differences were not due to the intranasal distribution of CO2. These results are compatible with the idea that the trigeminal system acts as a sentinel of the human airways.


Macrophage heterogeneity and differentiation: defined serum-free culture conditions induce different types of macrophages in vitro.
Macrophages (MAC) are important effector cells of the immune system. They arise from circulating blood monocytes (MO), which undergo further maturation upon leaving the vasculature and migrating into the various tissues and body cavities. A similar differentiation process can be followed in vitro when monocytes are cultured in the presence of serum. In this study, different factors and serum proteins, either alone or in combination, were tested for their ability to promote the survival and/or maturation of blood MO in the absence of serum. Elutriation-purified MO cultured for 8 days on hydrophobic teflon foils in the presence of 5% human serum differentiated into large, well-spread MAC, whereas in the absence of serum, MO rapidly died. The serum-induced maturation of MAC was accompanied by a strong expression of CD16, CD14 and MAX antigens. Secretion of TNF-alpha and neopterin increased about 10-fold as compared with freshly isolated MO. The replacement of serum by either M-CSF (100 ng/ml) or immunoglobulin (0.5-5 mg/ml) had a marked effect on MO survival (about 50% of serum-cultured MO), but cells were smaller, less spread out and had low expression of CD16, CD14 and MAX antigens. Their functional competence in terms of TNF-alpha and neopterin release was reduced to 10-20% as compared with MAC cultured in the presence of serum.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of gardenia yellow colorants in soft drink, pastry, instant noodles with ultrasound-assisted extraction by high performance liquid chromatography-electrospray ionization tandem mass spectrum.
A novel, rapid and simple analytical method was developed for the quantitative determination of crocin, crocetin and geniposide in soft drink, pastry and instant noodles. The solid samples were relatively homogenized into powders and fragments. The gardenia yellow colorants were successively extracted with methanol using ultrasound-assisted extraction. The analytes were quantitatively measured in the extracts by liquid chromatography coupled with electrospray ionization tandem mass spectrometry. High correlation coefficients (r(2)>0.995) of crocin, crocetin and geniposide were obtained within their linear ranges respectively (50-1000ng/mL, 50-1000ng/mL, 15-240ng/mL) by external standard method. The limits of detection (LODs) were 0.02μg/g for crocin, 0.01μg/g for crocetin and 0.002μg/g for geniposide. And the limits of quantitation (LOQs) were in the ranges of 0.05-0.45μg/g for crocin, and in the ranges of 0.042-0.32μg/g for crocetin, and in the ranges of 0.02-0.15μg/g for geniposide in soft drink, pastry and instant noodles samples. The average recoveries of crocin, crocetin and geniposide ranged from 81.3% to 117.6% in soft drink, pastry and instant noodles. The intra- and inter-day precisions were respectively in the range of 1.3-4.8% and 1.7-11.8% in soft drink, pastry and instant noodle. The developed methods were successfully validated and applied to the soft drink, pastry, and instant noodles collected from the located market in Beijing from China. Crocin, crocetin and geniposide were detected in the collected samples. The average concentrations ranged from 0.84 to 4.20mg/g for crocin, and from 0.62 to 3.11mg/g for crocetin, and from 0.18 to 0.79mg/g for gardenia in various food samples. The method can provide evidences for government to determine gardenia yellow pigments and geniposide in food.


External and internal reflection near field microscopy: experiments and results.
Two configurations of a scanning near field optical microscope working in reflection are presented. Results exhibiting nanometric resolution are given and discussed.


Large area UV casting using diverse polyacrylates of microchannels separated by high aspect ratio microwalls.
Large area molding of long and deep microchannels separated by high aspect ratio microwalls is important for high sensitivity and high throughput microfluidic devices. Ultraviolet (UV) casting is a feasible, economical and convenient method of replication of such microstructures in plastics. It is shown that a wide variety of polyacrylates with diverse properties such as those made from epoxy (EP), polyurethane (UR), polyester (ES), poly (ethylene glycol) (EG) and poly(propylene glycol) (PG) can be used for the high aspect ratio (7-9) UV casting of such linear microstructures over a 100 mm diameter, enlarging the range of applications of the replicated microstructures. Some challenges arise. With the EG formulation, wavy microstructures were observed; this can be overcome by stress relaxation. With non-polar PG formulation, poor adhesion between the polyester substrate and resin can lead to delamination of the casting from the substrate during demolding; this can be overcome by pre-coating a partially cured same resin on the polyester substrate. An optimum UV irradiation time was important for cure at the deepest end of the microstructure without excessive crosslinking leading to much increased demolding forces. The viscosity and wetting capability of the formulations were found to affect replication fidelity.


L-glycerol-3-phosphate dehydrogenase from the insect Ceratitis capitata. Purfication, physicochemical and enzymic properties.
Soluble L-glycerol-3-phosphate dehydrogenase (sn-glycerol-3-phosphate: NAD+ 2-oxidoreductase, EC 1.1.1.8) from the mediterranean fruit fly Ceratitis capitata has been purified 130-fold with an overall yield of about 40%. The final preparation had a specific activity of about 200 mumol NADH/min/mg protein. The enzyme preparation has been shown to be homogeneous throughout disc gel electrophoresis, dodecyl sulphate gel electrophoresis, isoelectric focusing and ultracentrifugation. The Km values for dihydroxyacetone phosphate, NADH, L-glycerol-3-phosphate and NAD+ were respectively 0.33, 0.018, 0.74 and 0.26 mM. L-glycerol-3-phosphate dehydrogenase from the insect had a maximal activity around pH 6.6 for the oxidation of NADH and pH 10.0 for the reduction of NAD+. It was stable from pH 6.0 to pH 9.0 at 20 degrees C for 1 h and remained active after incubating at 30 degrees C for 30 min at pH 6.6. The enzyme was completely inactivated by incubating at 60 degrees C for 5 min. Enzyme stability versus ionic strength as well as the dependence of the reaction velocity on temperature are also reported. The active enzyme was found to have a minimum molecular weight of approx. 63 000. Molecular weight determinations by sodium dodecyl sulphate gel electrophoresis gave subunit weights of 33 500. The isoelectric point of the protein was determined by electrofocusing and found to be 5.75 +/- 0.05. The extinction coefficient at 278 nm was calculated by dry weight measurements to be E1cm 1mg/ml = 0.42 +/- 0.1. Sedimentation velocity studies on ultracentrifuge indicated a dependence of the sedimentation coefficient on the enzyme concentration. The amino acid composition of the enzyme was determined. The protein has no free N-terminal residue and the digestion with carboxypeptidases gave the C-terminal sequence: -ala-gly-ser. All these data are discussed in relation to the properties of the enzyme from other sources.


Late noncardiac surgery in heart transplant patients.
Because of improved long-term survival of heart transplants (HT), patients often need noncardiac surgery (NCS). Immunosuppression may increase the infection rate. Inadequate management may increase the risk of dysfunction or acute rejection episodes (ARE). Long-term outcomes of NCS and optimal immunosuppressive management in the perioperative period are not well known. The objective of this study was to analyze the incidence, morbidity, and mortality of late NCS after HT. We retrospectively evaluated the incidence and type of late NCS as well as the risk factors for complications and the mortality among 207 HT patients. Immunosuppression and ARE rates were also analyzed. One hundred and sixteen late NCS (84.5% elective) were performed in 72 HT patients (34.8%). Interventions were: 35 urologic (30.2%), 29 abdominal (25%), 14 vascular (12.1%), 13 ENT (11.2%), 11 skin and soft tissue (9.5%), and 7 orthopedic (6%). Malignancy was the main indication for NCS (33.6%). Only 4 patients (5.6%) died preoperatively. Mortality was higher among emergent vs elective procedures (16.6% vs 1%; P = .012) and among patients with preoperative high vs middle/low risk (26.6% vs 0%). Postsurgical infection was the most frequent complication (6.9%). However, there were no relevant complications in 82.8% of HT patients. Hospitalization time was <15 days in two thirds of patients. Immunosuppression was modified in 33 patients (28.4%), especially when the surgical indication was neoplasia (P < .001). None of the patients with NCS displayed allograft dysfunction or an ARE. More than one-third of HT patients needed a late NCS. In our experience, elective surgical procedures with middle/low preoperative cardiovascular risk are safe. In this context, the risk of rejection was low when immunosuppression was carefully monitored to reduce the risk of infection.


A method to induce swapped binaural hearing.
This paper describes the application of a small hearing aid that precisely fits into a subject's ear canal (complete-in-canal, or CIC). The bandwidth of the device is about 7 kHz. The system allows for selective manipulation of the different acoustic cues used for sound localization. The potential of the system is illustrated by robustly interchanging the input of the left and right ear, and consequently changing the sign of the binaural difference cues (both interaural phase and intensity) that are used for horizontal sound localization. As a result, left-right perception is reversed, while high-frequency pinna cues are sufficiently preserved to maintain up-down localization. As the hearing condition is well-defined, the auditory system could in principle remap these cues into a new representation of sound azimuth by relating the modified cues to veridical sound locations. The hearing aids were applied in four human subjects. Swapped binaural hearing was tested in two of the subjects. Swapped localization experiments for an extended period indicated stable performance of both subjects. Interestingly, an adaptive response to the reversed interaural cues was not observed. The current system may prove useful for psychophysical studies that concern the independent processing of sound localization cues, as well as in long-term developmental and plasticity studies with animals.


Requirement of potassium for the action of anti-diuretic hormone (ADH) on frog skin.
The aim of the present study is to study whether the presence of K(+) in bathing media is required for the action of ADH to the ionic transport across the skin in the frog species Rana hexadactyla. lonic transport was measured as transepithelial potential difference (TEPD) and short circuit current (SCC) by using an indigenously developed computer based voltage-clamp technique. Addition of ADH (40 nM) on the serosal side significantly increased the TEPD and SCC with Normal Ringer (NR) on both sides. ADH had no effect subsequent to amiloride (100 µM) pre-treatment, which confirmed the ADH-induced Na(+) transport. Chloride also has a significant role in the development of TEPD. To determine the role of K(+), Potassium-free Ringer (KFR) was placed on both sides; addition of ADH had no effect consequently. Further experiments were carried out to find out which side of K(+) was required for the action of ADH. There was a lack of ADH effect with apical NR and serosal KFR, demonstrating that serosal K(+) is essential to activate Na(+), K(+)- ATPase. Similarly, the ADH effect was lacking with apical KFR and serosal NR that was the novel finding of this study. Due to the concentration gradient, the K(+) was secreted from serosal side to apical side through barium (1 mM) blockable K(+) channel. This study provides evidence that serosal as well as apical K(+) are necessary for the action of ADH.


Production of soluble, active acetyl serotonin methyl transferase in Leishmania tarentolae.
N-acetyl serotonin methyl transferase (ASMT) is the last enzyme in the melatonin synthesis pathway. Evidence linking autism-related disorders with disorders of melatonin metabolism, and, more specifically, with mutations of the gene encoding ASMT, prompted us to investigate the properties and localization of this enzyme. As a first step, we undertook to overproduce the protein in a recombinant host. Early attempts to produce ASMT in recombinant Escherichia coli yielded only insoluble and heavily degraded material. However, recombinant ASMT (rASMT) could be produced in soluble, active form and purified in milligram amounts when the gene was cloned and expressed in Leishmania tarentolae.


[Long-term results of treating acute erosion and ulcer of the digestive tract].
The authors studied results of treatment of acute erosions and ulcers of the digestive organs that developed in 43 patients after different operative interventions. Twenty-one patients developed uncomplicated erosions and ulcers, 20--complicated hemorrhages and 2--perforations. Follow-up terms--from 1 to 7 years. Approximately 50% of patients complained of stomach pain, some--of dyspeptic phenomena. Endoscopic findings indicate that these patients suffered of chronic diseases of the digestive organs (gastritis, gastroduodenitis). This evidences the necessity of prophylactic medical treatment of patients with a history of acute erosion and ulcers of the digestive organs.


Maintenance phase efficacy of sertraline for chronic depression: a randomized controlled trial.
The chronic form of major depression is associated with a high rate of prevalence and disability, but no controlled research has examined the impact of long-term treatment on the course and burden of illness. To determine if maintenance therapy with sertraline hydrochloride can effectively prevent recurrence of depression in the high-risk group of patients experiencing chronic major depression or major depression with antecedent dysthymic disorder ("double depression"). A 76-week randomized, double-blind, parallel-group study, conducted from September 1993 to November 1996. Outpatient psychiatric clinics at 10 academic medical centers and 2 clinical research centers. Maintenance treatment with either sertraline hydrochloride (n = 77) in flexible doses up to 200 mg or placebo (n = 84). A total of 161 outpatients with chronic major or double depression who responded to sertraline in a 12-week, double-blind, acute-phase treatment trial and continued to have a satisfactory therapeutic response during a subsequent 4-month continuation phase. Time to recurrence of major depression. Sertraline afforded significantly greater prophylaxis against recurrence than did placebo (5 [6%] of 77 in the sertraline group vs 19 [23%] of 84 in the placebo group; P = .002 for the log-rank test of time-to-recurrence distributions). Clinically significant depressive symptoms reemerged in 20 (26%) of 77 patients treated with sertraline vs 42 (50%) of 84 patients who received placebo (P = .001). With use of a Cox proportional hazards model, patients receiving placebo were 4.07 times more likely (95% CI, 1.51-10.95; P = .005) to experience a depression recurrence, after adjustment for study site, type of depression, and randomization strata. Maintenance therapy with sertraline is well tolerated and has significant efficacy in preventing recurrence or reemergence of depression in chronically depressed patients.


Yeast longevity and aging--the mitochondrial connection.
Studies of the yeast Saccharomyces cerevisiae reveal four processes determining life span: metabolism, stress resistance, chromatin-dependent gene regulation, and genome stability. The retrograde response, which signals mitochondrial dysfunction resulting in changes in nuclear gene expression, extends yeast life span and is induced during normal aging. This response involves extensive metabolic adaptations. The retrograde response links metabolism and genome stability during yeast aging. A reduction in the availability of nutrients also extends yeast life span. This metabolic mechanism operates by pathways distinct from the retrograde response, although it shares with the latter some longevity effectors. Life extension by calorie restriction entails re-modeling of mitochondrial function. The retrograde response appears to compensate for age changes, while calorie restriction may be a preventive mechanism. The maintenance of age asymmetry between the mother and daughter yeast cells also depends on mitochondrial function. Loss of this age asymmetry occurs during normal yeast aging and may be a paradigm for stem cell aging. The importance of mitochondrial integrity in yeast longevity is emphasized by the role of prohibition function in attenuating oxidative damage. Our studies point to the central role of mitochondria in yeast aging. They highlight the importance of the maintenance of mitochondrial membrane potential, which drives the transport of biosynthetic precursors derived from the Krebs cycle. Common threads weave their way through the studies of aging in yeast and in other model organisms. This suggests conserved features of aging across phyla.


Local application of gentamicin-containing collagen implant in the prophylaxis and treatment of surgical site infection following cardiac surgery.
For the cardiac surgeon and patient the development of sternal wound infection is a serious post-operative complication associated with increased risk of death and also considerable morbidity. Nine publications were identified using the PubMed online database and search terms 'gentamicin-containing collagen implant' plus 'surgical site infection', 'wound infection' and 'cardiac surgery'. Six out of eight studies demonstrated that prophylactic use of gentamicin-containing collagen implants (GCCI) significantly reduce the wound infection rate following cardiac surgery (via sternotomy) compared to standard treatment alone. The adjunctive use of GCCI is particularly beneficial in high-risk subjects e.g. diabetes and obese patients. GCCI significantly improve the morbidity associated with SSI following cardiac surgery by shortening the recovery phase and length of hospital stay; reducing the need for surgical revision and use of antibiotics. GCCI have been shown to be cost saving across a wide spectrum of patients. A further study has shown that GCCI may also have a therapeutic role to play in patients with deep sternal wounds. This review demonstrates that when used dry prior to insertion GCCI can be effective in reducing the rate of SSI following cardiac surgery. GCCI have also been shown to be cost saving as they reduce the substantial morbidity associated with deep SSI. The adjunctive use of GCCI is particularly beneficial in high-risk patients. GCCI may also have a role to play in the treatment of deep sternal wound infection.


Direct oxygen uptake from air by novel glycogen accumulating organism dominated biofilm minimizes excess sludge production.
The cost associated with treatment and disposal of excess sludge produced is one of the greatest operational expenses in wastewater treatment plants. In this study, we quantify and explain greatly reduced excess sludge production in the novel glycogen accumulating organism (GAO) dominated drained biofilm system previously shown to be capable of extremely energy efficient removal of organic carbon (biological oxygen demand or BOD) from wastewater. The average excess sludge production rate was 0.05 g VSS g-1 BOD (acetate) removed, which is about 9-times lower than that of comparative studies using the same acetate based synthetic wastewater. The substantially lower sludge yield was attributed to a number of features such as the high oxygen consumption facilitated by direct oxygen uptake from air, high biomass content (21.41 g VSS L-1 of reactor), the predominance of the GAO (Candidatus competibacter) with a low growth yield and the overwhelming presence of the predatory protozoa (Tetramitus) in the biofilm. Overall, the combination of low-energy requirement for air supply (no compressed air supply) and the low excess sludge production rate, could make this novel "GAO drained biofilm" process one of the most economical ways of biological organic carbon removal from wastewater.


Properties of whey protein isolates extruded under acidic and alkaline conditions.
Whey proteins have wide acceptance and use in many products due to their beneficial nutritional properties. To further increase the amount of whey protein isolates (WPI) that may be added to products such as extruded snacks and meats, texturization of WPI is necessary. Texturization changes the folding of globular proteins to improve interaction with other ingredients and create new functional ingredients. In this study, WPI pastes (60% solids) were extruded in a twin-screw extruder at 100 degrees C with 4 pH-adjusted water streams: acidic (pH 2.0 +/- 0.2) and alkaline (pH 12.4 +/- 0.4) streams from 2 N HCl and 2 N NaOH, respectively, and acidic (pH 2.5 +/- 0.2) and alkaline (pH 11.5 +/- 0.4) electrolyzed water streams; these were compared with WPI extruded with deionized water. The effects of water acidity on WPI solubility at pH 7, color, microstructure, Rapid Visco Analyzer pasting properties, and physical structure were determined. Alkaline conditions increased insolubility caused yellowing and increased pasting properties significantly. Acidic conditions increased solubility and decreased WPI pasting properties. Subtle structural changes occurred under acidic conditions, but were more pronounced under alkaline conditions. Overall, alkaline conditions increased denaturation in the extruded WPI resulting in stringy texturized WPI products, which could be used in meat applications.


Application of partial sliding mode in guidance problem.
In this paper, the problem of 3-dimensional guidance law design is considered and a new guidance law based on partial sliding mode technique is presented. The approach is based on the classification of the state variables within the guidance system dynamics with respect to their required stabilization properties. In the proposed law by using a partial sliding mode technique, only trajectories of a part of states variables are forced to reach the partial sliding surfaces and slide on them. The resulting guidance law enables the missile to intercept highly maneuvering targets within a finite interception time. Effectiveness of the proposed guidance law is demonstrated through analysis and simulations.


Lateral column symptomatology following plantar fascial release: a prospective study.
Plantar fasciitis or heel spur syndrome usually resolves with conservative management, but for patients with continued pain, surgical intervention is often pursued. In some cases, plantar fasciitis is relieved, but pain in the lateral column area appears postoperatively. This lateral column pain may be debilitating for the patient and often overlooked by the foot and ankle surgeon. The goal of the study was to identify the maximum amount of plantar fascia that can be surgically released to treat recalcitrant heel pain effectively while preventing the development of lateral column symptoms. All patients undergoing plantar fasciotomy after failing conservative treatment were eligible to participate. Patients rated their pain with an 11-point (0-10) visual analog scale (VAS) and described its location prior to and at monthly intervals after their surgery. Surgeons recorded whether 25, 50, or 66% of the plantar fascia was released during surgery. Open procedures were performed 72% of the time, and endoscopically in 28% of the patients. Key outcome variables included degree of fascial release and foot structure. Patients (n = 47) with lateral column pain after surgery (n = 15 feet) had a mean +/- S.E. of 60.6 +/- 3.0% of their plantar fascia released while those without pain (n = 35 feet) had only 48.7 +/- 1.9% of this fascia released during surgery (ANOVA, p = .019). Age, weight, body mass index, gender, smoking status, comorbidities, general health, surgical procedure, postoperative care, calcaneal inclination angle, and talar declination angle did not differ for these groups (p > .146). For this patient population, regardless of surgical technique (endoscopic or open release), lateral column symptoms were more likely to result when more than 50% of the plantar fascia was released. The report proposes that a maximum of 50% of the plantar fascia be released during surgery.


Low-dose paclitaxel elution by novel bioerodible sol-gel coating on stents inhibits neointima with low toxicity in porcine coronary arteries.
The present study was designed to evaluate a novel bioerodible sol-gel film coated paclitaxel-eluting stent (sol-gel-PES, 3 microg per stent) in a porcine coronary artery model. Although current polymer-based PES decrease restenosis, the permanent polymer and bound drug have raised concerns regarding delayed vessel healing and late stent thrombosis. Polymer-based PES (poly-PES, n = 8), sol-gel-PES (n = 15), bare metal (BMS, n = 14), and sol-gel film only (sham, n = 12), stents were implanted in 17 juvenile pigs. Animals were terminated 28 days post-implant for angiographic restudy and complete histopathologic and histomorphometric analyses. Angiographic late loss was equally reduced for both poly-PES and sol-gel-PES (0.51 +/- 0.64 and 0.61 +/- 0.52 mm, respectively) compared to both BMS and sham (0.98 +/- 0.74 and 1.25 +/- 0.72 mm, p < 0.05). Similarly beneficial results were observed for histomorphometric parameters of neointimal thickness and area, yielding reductions of in-stent stenosis by 43% and 48% for poly-PES, as well as 31% and 37% for sol-gel-PES, vs. BMS and sham, respectively (p < 0.05). Re-endothelialization was complete in all groups. Although the inflammatory cell infiltration and intramural thrombus scores were no different between poly- and sol-gel-PES, medial necrosis was increased for poly-PES (p < 0.05 vs. all others). A novel bioerodible sol-gel film coated with low-dose paclitaxel demonstrates less toxicity to the coronary tunica media, while retaining effective inhibition of neointimal formation at 28 days.


A human temporal bone study of stapes footplate movement.
This study was designed to determine whether stapes movement is pistonlike or complex. The literature provides conflicting information on whether stapes footplate motion is only pistonlike or has other types of movement, such as hingelike or rocking. Using 10 freshly harvested human cadaver temporal bones, 3 targets were placed on the stapes footplate through an extended facial recess approach. The targets were 0.5-mm pieces of reflective adhesive material positioned on the long axis of the footplate at the anterior crus, central footplate, and posterior crus. Displacement and phase of the three targets were measured from 0.2 to 10 kHz at a 90dB sound pressure level input at the tympanic membrane. The measuring system was a sophisticated laser Doppler vibrometer (LDV). A computer program (Tymptest) calculated footplate displacement and relative phase at the three sites and the ratio of anterior-posterior rocking movement of the footplate long axis to displacement at the center. Below 2.0 kHz, stapes vibration is predominately pistonlike. Above 2.0 kHz, anterior-posterior rocking motion increases logarithmically with frequency, and, near 4.0 kHz, rocking and pistonlike motion are approximately equal. Stapes footplate vibration is primarily pistonlike up to 2.0 kHz but becomes more complex at higher frequencies because of an increase in anterior-posterior rocking motion. Hingelike movements were not observed. This information may be helpful in the design of ossicular replacement prostheses that mimic or improve upon normal stapes vibration.


Influence of compaction properties and interfacial topography on the performance of bilayer tablets.
Bilayer tablets are generating great interest recently as they can achieve controlled delivery of different drugs with pre-defined release profiles. However, the production of such tablets has been facing great challenges as the layered tablets are prone to delaminate or fracture in the individual layers due to insufficient bonding strength of layers and adhesion at the interfaces. This paper will provide an insight into the role of interfacial topography on the performance of the bilayer tablets. In this study, two widely used pharmaceutical excipients: microcrystalline cellulose and lactose were investigated. Bilayer tablets were manufactured with a range of first and second layer compression forces. A crack of known dimensions was introduced at the interface to investigate the crack propagation mechanisms upon axially loading the bilayer tablet, and to determine the stress intensity factor (K(I)) of the interface (will be discussed in a separate paper). The results indicated that a strong dependency of the strength of bilayer tablets and mode of crack propagation on the material and compaction properties. The results showed that the strength of bilayer tablets increased with the increase of interfacial roughness, and the first layer and second layer forces determined the magnitude of interfacial roughness for both plastic and brittle materials. Further, the results also indicated that layer sequence and compaction forces played a key role in influencing the strength of the bilayer tablets. For the same (first and second layer) force combination, interfacial strength is higher for the tablets made of brittle material in the first layer. It was observed that interfacial strength decreased with the increase of lubricant concentration. The studies showed that the effect of lubricant (i.e. reduction in compact strength with the increase of lubricant concentration) on the strength of compacts is higher for tablets made of plastic material as compared to the tablets made of brittle material.


I. c. v. dopamine fails to alter adrenomedullary function in rats.
Intracerebroventricularly (i.c.v.) administered dopamine (50-400 micrograms/kg, 30 min; 400 micrograms/kg, 2 and 4 h) did not induce statistically significant changes in heart adrenaline (presumed to represent the adrenaline release from the adrenals). Only the highest dose (400 micrograms/kg, 30 min) brought about significant increase in adrenal dopamine (reflecting the catecholamine synthesis), accompanied by increase in heart dopamine, indicating leakage of dopamine into the peripheral circulation. The results did not support involvement of the central dopamine receptors in the short-term control of the adrenomedullary function in rats.


[Dental status in 42 chronically hemodialyzed patients].
Hemodialyzed patients often present with a deficient dental state. The objective of this study was to assess the oral state and dental hygiene of chronically hemodialyzed patients. Forty-two chronically hemodialyzed patients were followed at the dental consultation and treatment centre. Clinical and radiographic data was assessed (panoramic and retro alveolar x-ray). The patients' mean age was 41.7 years. The sex ratio was 16/26. 11.9% of patients were toothless. Dental hygiene was bad in 45.9% of the cases. 78.5% of patients brushed their teeth 35.1% of whom once a day. Periodontitis was noted in 73% of the cases and gingival bleeding in 48.6%. 89.2% of patients presented with caries and 78.4% were missing teeth. Nineteen percent of the patients used a prosthesis. Chewing was adequate for 47.6% of patients. The paleness of mucosal membranes and xerostomia was noted respectively in 40.5% and 21.4% of patients. The radiological exam findings were pathological for ten patients (23,6%). The mean plaque index was 1.9±0.84 and gingival index 1.8±0.87. 71.4% of patients consulted an odontologist in the year before the study. The dental status of chronically hemodialyzed patients is bad. They must be managed as early as possible.


Effect of High-salt Consumption on Rodent Gut Microbiome: A Meta-Analysis.
The global climate change brings about myriad of changes in the environment and ecosystem. The sea-level rise due to climate change results in salt-water intrusion into freshwater reservoirs of the coastal areas, increasing the salinity of the natural sources of potable water. People in the coastal areas consume saline water, exposing the intestinal tract to higher salt concentration on regular basis. This meta-analysis attempts to relate consumption of saline water to dysbiosis of rodent gut microbiome. Scientific reports were searched in PubMed/Medline, the Cochrane Library and Google Scholar. Original articles, abstracts and short communications were included depending on predetermined inclusion/exclusion criteria. A total of 8 original reports involving 124 rodents were included in this study. The pooled specificity and sensitivity of the reports were found to be 0.833 and 0.891 respectively by Meta Disc software v1.4. Pooled odds ratio and AUC were 20.056 and 0.896 respectively, implying a correlation between increased salt intake and gut microbiome dysbiosis (imbalance), measured from altered Firmicutes: Bacteroidetes ratio. Microbiome dysbiosis makes the intestine prone to enteric diseases. The outcomes of this meta-analysis indicates the dependence of mammalian gut microbiome on the amount of salt ingested, a condition aggravated by the global climate change and therefore necessitates similar studies on human populations living on coastal areas.


Oxidative/nitrative stress in the pathogenesis of systemic sclerosis: are antioxidants beneficial?
Systemic sclerosis (SSc) is a multisystem autoimmune disease: characterised from the clinical side by progressive vasculopathy and fibrosis of the skin and different organs and from the biochemical side by fibroblast deregulation with excessive production of collagen and increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4). The latter contributes to an overproduction of reactive oxygen species that through an autocrine loop maintains NOX4 in a state of activation. Reactive oxygen and nitrogen species are implicated in the origin and perpetuation of several clinical manifestations of SSc having vascular damage in common; attempts to dampen oxidative and nitrative stress through different agents with antioxidant properties have not translated into a sustained clinical benefit. Objective of this narrative review is to describe the origin and clinical implications of oxidative and nitrative stress in SSc, with particular focus on the central role of NOX4 and its interactions, to re-evaluate the antioxidant approaches so far used to limit disease progression, to appraise the complexity of antioxidant treatment and to touch on novel pathways elements of which may represent specific treatment targets in the not so distant future.


Can I play?
Physical activity and participation in sports are important for the well being of children and youth and should be encouraged by health care providers. Individuals with chronic diseases are often less active, which can have a negative impact on their health. This article will review the effects of exercise on a few chronic medical conditions including juvenile arthritis, cystic fibrosis, and hypertension. The clinician's role in providing advice about sport participation will also be addressed.


Lung transplantation on cardiopulmonary support: venoarterial extracorporeal membrane oxygenation outperformed cardiopulmonary bypass.
Patients requiring extracorporeal cardiorespiratory support during lung transplantation can be treated with conventional cardiopulmonary bypass (CPB) or venoarterial extracorporeal membrane oxygenation (ECMO). In a retrospective analysis, we compared the postoperative course and outcomes of patients treated using these approaches. Between August 2008 and September 2011, 92 consecutive patients underwent lung transplantation with extracorporeal support (CPB group, n = 46; and, since February 2010, ECMO group, n = 46) at our institution. We evaluated survival, secondary organ failure, bleeding complications, and the need for blood and platelet transfusions in these 2 patient populations. Intraoperatively, the CPB group required more packed red blood cell transfusions (12 ± 11 vs 7 ± 9 U; P = .01) and platelet concentrates (2.5 ± 1.6 vs 1.5 ± 1 U; P < .01) than the ECMO group. In-hospital mortality (39% vs 13%; P = .004), the need for hemodialysis (48% vs 13%; P < .01), and new postoperative ECMO support (26% vs 4%; P < .01) were greater in the CPB group than in the ECMO group, respectively. After propensity score analysis, multivariate analysis identified retransplantation (odds ratio, 7; 95% confidence interval, 1-43; P = .034) and transplantation with CPB support (odds ratio, 4.9; 95% confidence interval, 1.2-20; P = .026) as independent risk factors for in-hospital mortality. The survival rate at 3, 9, and 12 months was 70%, 59%, and 56% in the CPB group and 87%, 81%, and 81% in the ECMO group (P = .004). Intraoperative ECMO allows for better periprocedural management and reduced postoperative complications and confers a survival benefit compared with CPB, mainly because of lower in-hospital mortality. It is now the standard of care in our lung transplantation program.


New developments in 'any willing provider' laws.
As the debate over healthcare reform continues, the controversy concerning "any willing provider" laws also continues. "Any willing provider" laws require a healthcare insurer (or managed care organization) to establish criteria that a provider must meet in order to participate as a network provider. Such laws prohibit an insurer from denying any provider willing to meet those criteria from participating as a network provider. Proponents of any willing provider laws cite the recent decision by the U.S. Supreme Court not to review a lower court ruling finding in favor of a hospital as validation of such laws.


Identification of symbiotically defective mutants of Lotus japonicus affected in infection thread growth.
During the symbiotic interaction between legumes and rhizobia, the host cell plasma membrane and associated plant cell wall invaginate to form a tunnel-like infection thread, a structure in which bacteria divide to reach the plant root cortex. We isolated four Lotus japonicus mutants that make infection pockets in root hairs but form very few infection threads after inoculation with Mesorhizobium loti. The few infection threads that did initiate in the mutants usually did not progress further than the root hair cell. These infection-thread deficient (itd) mutants were unaffected for early symbiotic responses such as calcium spiking, root hair deformation, and curling, as well as for the induction of cortical cell division and the arbuscular mycorrhizal symbiosis. Complementation tests and genetic mapping indicate that itd2 is allelic to Ljsym7, whereas the itdl, itd3, and itd4 mutations identified novel loci. Bacterial release into host cells did occur occasionally in the itdl, itd2, and itd3 mutants suggesting that some infections may succeed after a long period and that infection of nodule cells could occur normally if the few abnormal infection threads that were formed reached the appropriate nodule cells.


Adrenal medullary transplants as a treatment for advanced Parkinson's disease.
Open autologous adrenal medullary to caudate nucleus transplantation was performed in 12 patients with advanced Parkinson's disease (PD). Ten of these patients had diurnal response fluctuations including "wearing off" and "on/off" phenomena. All of the patients were no longer satisfactorily responding to levodopa/carbidopa and dopamine agonists. The mean age of the patients was 55.1 years (range 37-65 yrs); mean duration of PD was 11.7 years (range 4-40 yrs); mean stage "on" was 3.3 (range 2-4); mean stage "off" was 4.8 (range 4-5). Mean duration of follow up from surgery was 10.4 months (range 2-17 months). Three patients improved dramatically with major changes in their lifestyle. The course of improvement in these 3 patients was different in each, implying that different mechanisms were responsible for the improvement. One of the patients died unexpectedly. In this patient, there were no surviving adrenal cells. Three patients improved moderately. Patients reported that they were "on" longer and had to take medication less often and were less dependent on individual doses of levodopa/carbidopa. The improvement has been sustained in two patients. However, in one of these patients there had to be frequent changes in scheduling to maintain the improvement. Two patients after technically successful implants did not improve. One of these patients subsequently died. In this patient there were a few surviving adrenal medullary cells. Four patients suffered major complications. One patient had a cerebral infarction and two had cerebral hemorrhages. One of these patients has shown a good recovery. One patient with autonomic insufficiency had a cardiac arrest with cerebral anoxia one week after surgery. This patient has shown a partial recovery.(ABSTRACT TRUNCATED AT 250 WORDS)


Fidaxomicin for treatment of clostridium difficile-associated diarrhea and its potential role for prophylaxis.
Clostridium difficile has become the most important healthcare-associated infection worldwide within the past decade. This is in part due to the emergence of a highly virulent epidemic strain of C. difficile as well as the relative ineffectiveness of current therapies at producing a sustained response. Fidaxomicin is a novel antibiotic that demonstrates a greater sustained response for C. difficile-associated diarrhea (CDAD) compared to existing drugs and its potential role as a prophylactic agent against C. difficile infection (CDI) is being intensely studied. In this article, we address the emergence of CDI and the current treatment options and identify the unmet needs of the marketplace. We also summarize the pharmacodynamic and pharmacokinetic properties of fidaxomicin, and review the current literature related to the use of fidaxomicin for both treatment and prophylaxis of CDI. Fidaxomicin is clearly as effective in the treatment of CDAD as oral vancomycin. It has also been shown to reduce recurrent CDAD, and we hypothesize that the same properties that confer reduced recurrence make it a promising agent for prophylaxis, particularly in high-risk patients.


Morphometric analysis of gastric dysplasia.
The grading of gastric epithelial dysplasia has been studied by means of computer aided morphometry. Measurements of histological features were made on segments of epithelium from 38 selected cases of dysplasia graded by subjective assessment. The measurements were statistically compared with the subjective scores using discriminant analysis. The measurements were found to provide significant discrimination between all groups. Nuclear size proved to be the main discriminating variable. Prediction of the likely group membership of individual cases was possible using classification equations derived from the discriminant analysis. Classification of the original data set revealed prediction errors which suggested a bias against diagnosis of dysplasia. As a result of this study reliable, repeatable and objective gradings of gastric epithelial dysplasia can be obtained by inexperienced persons with an accuracy approaching that of a skilled pathologist.


Lymphadenopathy and hepatosplenomegaly in the 1st year in children infected by HIV-1 in Zaire.
The children of 50 women positive for antibody to human immunodeficiency virus type 1 (HIV-1) and 42 children of antibody-negative mothers were examined for lymphadenopathy and hepatosplenomegaly at 3-month intervals during the 1st year of life. Lymphadenopathy was found to be significantly more frequent at 6 months (p less than 0.01), 9 months (p less than 0.001) and 12 months (p less than 0.01) in children who were subsequently shown to be infected with HIV-1. Hepatomegaly was seen more frequently (p less than 0.05) in the 1st year in HIV-1-infected children than in uninfected children. Splenomegaly was not more frequent in HIV-1-infected children in this area which is holoendemic for falciparum malaria.


Sleep apnea, sleep disorders, and hypothyroidism.
The symptoms of hypothyroidism are protean and include apathy, somnolence, lethargy, personality change, and intellectual deterioration. Many of these symptoms may be related to hypothyroid-induced sleep disorders. Hypothyroidism is associated with abnormal ventilatory drive, abnormal sleep architecture, and sleep apnea. Central, obstructive, and mixed patterns of sleep apnea are commonly observed in hypothyroidism. A case of severe sleep apnea in a grossly myxedematous patient who improved dramatically following thyroid replacement alone is presented. Myxedema is a reversible cause of sleep apnea, and thyroid function testing should be considered in its diagnostic work-up.


Coping with myocardial infarction: a model with clinical applications, a literature review.
Following a myocardial infarction any residual symptoms are likely to remind the patient of a possible fatal outcome and be detrimental to successful rehabilitation. Negative psychological attitudes need to be identified early. Intervention to improve the mental state should be introduced to restore self-confidence.


Regulation of mycothiol metabolism by sigma(R) and the thiol redox sensor anti-sigma factor RsrA.
Mycothiol (MSH) is the major thiol in Actinobacteria and plays a role analogous to that of glutathione. The biosynthetic pathway has been established in mycobacteria and is initiated by the glycosyltransferase MshA. A key mycothiol-dependent detoxification pathway utilizes the amidase (Mca) to cleave mycothiol S-conjugates to produce GlcN-Ins and a mercapturic acid excreted from the cell. How expression of mycothiol genes is regulated in mycobacteria has been unclear so the report in this issue by Park and Roe showing that in Streptomyces coelicolor the redox controlled anti-sigma factor RsrA that binds the regulator sigma(R) controls key elements of mycothiol metabolism is a major advance. Conditions that deplete thiols are shown to induce directly expression of sigR, rsrA, mshA and mca, as well as the thioredoxin reductase-thioredoxin system, generating an autoregulatory cycle that persists until the thiol-depleting condition is alleviated. Evidence for indirect induction of mshB-D to support mycothiol biosynthesis is also presented. It was shown in vitro that mycothiol, like reduced thioredoxin and dithiothreitol, can reduce oxidized RsrA to activate its binding to sigma(R). These studies establish for the first time how mycothiol metabolism is regulated to cope with stress from thiol reactive toxins.


Changes in dysferlin, proteins from dystrophin glycoprotein complex, costameres, and cytoskeleton in human soleus and vastus lateralis muscles after a long-term bedrest with or without exercise.
This study was designed to evaluate the effects of hypokinesia and hypodynamia on cytoskeletal and related protein contents in human skeletal muscles. Twelve proteins: dystrophin and its associated proteins (DGC), dysferlin, talin, vinculin and meta-vinculin, alpha-actinin, desmin, actin, and myosin, were quantitatively analyzed during an 84-day long-term bedrest (LTBR). The preventive or compensatory effects of maximal resistance exercise (MRE) as a countermeasure were evaluated. Most of these proteins are involved in several myopathies, and they play an important role in muscle structure, fiber cohesion, cell integrity maintenance, and force transmission. This is the first comparison of the cytoskeletal protein contents between slow postural soleus (SOL) and mixed poly-functional vastus lateralis (VL) human muscles. Protein contents were higher in VL than in SOL (from 12 to 94%). These differences could be mainly explained by the differential mechanical constraints imposed on the muscles, i.e., cytoskeletal protein contents increase with mechanical constraints. After LTBR, proteins belonging to the DGC, dysferlin, and proteins of the costamere exhibited large increases, higher in SOL (from 67 to 216%) than in VL (from 32 to 142%). Plasma membrane remodeling during muscle atrophy is probably one of the key points for interpreting these modifications, and mechanisms other than those involved in the resistance of the cytoskeleton to mechanical constraints may be implicated (membrane repair). MRE compensates the cytoskeletal changes induced by LTBR in SOL, except for gamma-sarcoglycan (+70%) and dysferlin (+108%). The exercise only partly compensated the DGC changes induced in VL, and, as for SOL, dysferlin remained largely increased (+132%). Moreover, vinculin and metavinculin, which exhibited no significant change in VL after LTBR, were increased with MRE during LTBR, reinforcing the pre-LTBR differences between SOL and VL. This knowledge will contribute to the development of efficient space flight countermeasures and rehabilitation methods in clinical situations where musculoskeletal unloading is a component.


Determination of mimosine by a sensitive indirect spectrophotometric method.
A simple and sensitive indirect spectrophotometric method is described for the determination of mimosine based on its reaction with diazotized sulfanilamide (DZSAM). DZSAM couples with N-(1-naphthyl)ethylenediamine (NEDA) forming a pink colored azodye, absorbing maximally at 540nm (epsilon(max)=27mM(-1)cm(-1)). In the present method, mimosine was first reacted with known excess of DZSAM and the unreacted DZSAM was determined by coupling with NEDA. The reaction of mimosine with DZSAM proceeded optimally at neutral pH. The decrease in absorbance of the DZSAM-NEDA-coupled product obeyed Beer's law in the concentration range of 0.005-0.15mugml(-1) of mimosine. The present method was applied to estimate mimosine in plant extracts containing lesser than 0.05mugml(-1) with recovery at 99+/-0.41%. The method described is superior to other reported methods in terms of ease of adaptability and sensitivity.


Expression of the carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD 15) in the adult guinea pig inner ear.
The expression of the CD 15 (3-fucosyl-N-acetyl-lactosamine) epitope was immunohistochemically studied on paraffin sections of adult guinea pig inner ears. Two regions of the inner ear expressed the epitope for CD 15: the tectorial membrane of the cochlea and the endolymphatic sac. The upper part of the main body of the tectorial membrane was deeply stained. In the rugosal and distal part of the endolymphatic sac several unevenly distributed cells showed strong intra- and extracellular localization of the CD15 epitope. The CD15 epitope is associated with a transduction structure (tectorial membrane) and with a "volume regulating" compartment (endolymphatic sac) and may be involved in the maintenance of the structural integrity of both.


Comparative Study of the Bush Dog (Speothos venaticus) Karyotype and Analysis of Satellite DNA Sequences and Their Chromosome Distribution in Six Species of Canidae.
The bush dog (Speothos venaticus, 2n = 74) is a near threatened species taxonomically classified among South American canids. We revised the bush dog karyotype and performed a comparative sequence analysis of satellite and satellite-like DNAs in 6 canids: the bush dog, domestic dog (Canis familiaris, 2n = 78), grey wolf (C. lupus, 2n = 78), Chinese raccoon dog (Nyctereutes procyonoides procyonoides, 2n = 54+B), red fox (Vulpes vulpes, 2n = 34+B), and arctic fox (V. lagopus, 2n = 48-50) to specify the species position among Canidae. Using FISH with painting and BAC probes, we found that the distribution of canid evolutionarily conserved chromosome segments in the bush dog karyotype is similar to that of the domestic dog and grey wolf. The bush dog karyotype differs by 2 acrocentric chromosome pairs formed by tandem fusions of the canine (29;34) and (26;35) orthologues. An interstitial signal of the telomeric probe was observed in the (26;35) fusion site in the bush dog indicating a recent evolutionary origin of this rearrangement. Sequences and hybridisation patterns of satellite DNAs were compared, and a phylogenetic tree of the 6 canid species was constructed which confirmed the bush dog position close to the wolf-like canids, and apart from the raccoon dog and foxes.