[Functional interaction between alpha- and beta-adrenoreceptors of the small intestine].
Effect of desensitization of alpha-adrenoreceptors on the functional state of beta-receptors and vice versa was studied in isolated sections of the rat small intestine. Neither blockade, nor desensitization of alpha-receptors produced any effect on the sensitivity of beta-receptors to isopropyl-noradrenaline (IPN) whereas desensitization of beta-receptors to IPN resulted in the increase of alpha-receptors sensitivity to phenylephrine with a decreased maximal reaction. In the presence of GTP (0.02 mM) and propranolol (2.00 x 10(-7) M) IPN acts as a competitive reversible auto-inhibitor, GTP fully removing the inhibitory effect of IPN on both alpha- and beta-adrenoreceptors. Existence of functional interrelationship between alpha- and beta-adrenoreceptors is suggested.


[The present status of tuberculosis in the Slovak Republic].
In 1988 the incidence of newly detected cases of TB in the Slovak Republic was 31.6/100,000 population. As compared with 1987, a decline of the disease by 9.8% was recorded. Its incidence in the SR shifts to higher age groups. The prevalence of active tuberculosis reached in 1988 34.4 and the mortality 0.4/100,000 population. Despite these relatively favourable indicators, TB remains in the SR a public health issue which will require also in future systematic attention and care.


Improved spinal cord perfusion during thoracoabdominal aortic repair.
The study's aim is to evaluate whether intraoperative neurophysiological monitoring with transcranial motor-evoked potentials (tcMEP) permits early recognition of neuronal lesions, thus making interventions to prevent irreversible spinal cord damage possible. TcMEP monitoring was carried out in twelve patients (mean age 60 years) during open surgical thoracoabdominal aortic replacement. Current approaches for corrective, spinal cord-protecting interventions consist of: raising distal perfusion by increasing cardiopulmonary bypass (CPB) flow, catecholamine application, reducing central venous pressure, reimplantation of segmental arteries, and cerebrospinal fluid (CSF) drainage. Nine patients exhibited loss of tcMEP after segmental aorta clamping. In five patients we observed a recovery of tcMEP through counteractive measures. Three patients died intraoperatively, one patient presented with postoperative paraplegia and loss of tcMEP. TcMEP loss is associated with spinal cord ischaemia, causing postoperative paraplegia. TcMEP monitoring is an excellent method to detect spinal cord ischaemia at an early stage.


Multifocal granulomatous hepatitis caused by Actinobacillus pleuropneumoniae serotype 2 in slaughter pigs.
In a survey of 66 894 slaughter pigs, 11 animals from three farms were found to have multifocal granulomatous lesions in the liver, caused by Actinobacillus pleuropneumoniae serotype 2. The lesions consisted of epithelioid cells and multinucleated giant cells, with asteroid bodies and discernible gram-negative bacteria. Lymph nodes and spleen were occasionally affected. The results suggested that haematogenous spread had occurred from pre-existing pulmonary infections.


Noxious peripheral stimulation produces antinociception mediated via substance P and opioid mechanisms in the rat tail-flick test.
Physiological experiments were run to examine the effects of noxious thermal stimulation of one hindpaw on the tail-flick reflex in the lightly anesthetized rat. Male Sprague-Dawley rats were anesthetized with an i.p. injection of a mixture of Na-pentobarbital (20 mg/kg) and chloral hydrate (120 mg/kg). After baseline readings were taken in the tail-flick test, either a non-noxious or a noxious stimulus was applied which consisted of immersion of one hindpaw in water at 40, 45, 50 or 55 degrees C for 1.5 min. After immersion, tail-flick readings were taken at 3-min intervals for at least 16 min. Paw immersion in water at 55 degrees C induced an antinociceptive response, consisting of an increase in the reaction time, at 0.5 min after immersion. Recovery to baseline levels occurred over the next 3-6 min. Immersion at lower temperatures provoked smaller antinociceptive responses, except at 40 degrees C, where readings remained around the baseline values. The increase in reaction time in response to immersion at 55 degrees C was attenuated or blocked by the novel, nonpeptide substance P (NK-1) receptor antagonist, CP-96,345, administered s.c. 30 or 60 min, respectively, prior to paw immersion. Similar injection of CP-96,344, the inactive stereoisomer, had no effect on the response, while another NK-1 receptor antagonist, CP-99,994, also attenuated the antinociceptive effect of the immersion. The increase in reaction time induced by immersion at 55 degrees C was absent in animals treated neonatally with capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)


The specificity of antibodies raised against a T cell peptide is influenced by peptide amidation.
Peptides used for immunization are designed on the basis of combination of B and T cell epitopes. They are sometimes acetylated and amidated in order to mimic the protein insertion of the B cell epitope, but to our knowledge the effect of modifying the N- and C-termini is not clearly identified. In this paper, we have investigated in detail the influence of amidation and acetylation on the immunogenic properties of the T cell epitope 24-36 which is derived from a snake neurotoxin. Acetylation enhanced the capacity of the peptides to bind to I-Ed and to stimulate specific T cells in vitro but both modifications did not influence in vivo the T cell priming ability of the peptides. However, amidation of the peptides 24-36 provoked a dramatic effect on the antibody specificity they elicited, whereas acetylation did not. Antibodies recruited by amidated peptides weakly recognized the non amidated ones, while the latter elicited antibodies which hardly bind to the former. These results show how a subtle chemical change of a peptide immunogen modifies the reactivity of the elicited antibodies in an unrelated manner from the peptide MHC II binding ability and T cell stimulating capacity. We thus amplify the previously described polarity of chimeric TB peptides that raise antibodies mainly against their C-terminal part. Finally, these results may also facilitate the choice of the status of N and C termini of the peptides designed for immunization which at present have their extremities indifferently free or modified by acetylation and/or amidation.


Protein l-isoaspartyl-O-methyltransferase of Vibrio cholerae: interaction with cofactors and effect of osmolytes on unfolding.
Protein l-isoaspartyl-O-methyltransferase (PIMT) is an ubiquitous enzyme widely distributed in cells and plays a role in the repair of deamidated and isomerized proteins. In this study, we show that this enzyme is present in cytosolic extract of Vibrio cholerae, an enteric pathogenic Gram-negative bacterium and is enzymatically active. Additionally, we focus on the detailed biophysical characterization of the recombinant PIMT from V. cholerae to gain insight into its structure, stability and the cofactor binding. The equilibrium denaturation of PIMT has been studied using tryptophan fluorescence and CD spectroscopy. The far- and near-UV CD, as well as fluorescence experiments reveal the presence of a non-native intermediate in the folding pathway. Binding of the hydrophobic fluorescent probe, bis-ANS, to the intermediate occurs with high affinity because of the exposure of the hydrophobic clusters during the unfolding process. The existence of the probable intermediate has also been confirmed from limited tryptic digestion and DLS experiments. The protein shows higher binding affinity for AdoHcy, in comparison to AdoMet, and the binding increases the midpoint of thermal unfolding by 6 and 5 °C, respectively. Modeling and molecular dynamics simulations also support the higher stability of the protein in presence of AdoHcy.


Common characteristics of upper and lower airways in rhinitis and asthma: ARIA update, in collaboration with GA(2)LEN.
This update aimed to review the new evidence available to support or refute prior Allergic Rhinitis and its Impact on Asthma (ARIA) statements. A Medline search of publications between 2000 and 2005 was conducted, with articles selected by experts. New evidence supports previous ARIA statements, such as: (i) allergic rhinitis (AR) is a risk factor for asthma; (ii) patients with persistent rhinitis should be evaluated for asthma; (iii) most patients with asthma have rhinitis; (iv) a combined strategy should be used to treat the airways and (v) in low- to middle-income countries, a different strategy may be needed. The increased risk of asthma has also been found among sufferers from non-AR. Recent reports show AR is a global problem. Many studies demonstrated parallel increasing prevalence of asthma and rhinitis, but in regions of highest prevalence, it may be reaching a plateau. Factors associated with a reduced risk of asthma and AR have been identified, confirming previous findings of protection related to exposure to infections. Treatment of rhinitis with intranasal glucocorticosteroids, antihistamines, leukotriene antagonists or immunotherapy may reduce morbidity because of asthma. To take advantage of the paradigm of unified airways, there is a need to rationalize diagnosis and treatment to optimize management.


A kinetic model for nanocrystal morphology evolution.
A kinetic model is developed with the goal of understanding and predicting the morphology evolution of nanocrystals in nonequilibrium growth conditions. The model is based on the assumption that under such conditions, different crystal planes have different kinetic parameters. This model focuses on the morphology-developing stage and is successfully related to the nucleation process and other crystal evolution mechanisms. It is believed to be a universal model and is applied to discuss the morphology evolution of CdSe nanocrystals, including the aspect ratio, injection schemes, ligands effect and morphology distribution.


Cutaneous and ungual phaeohyphomycosis caused by species of Chaetomium Kunze (1817) ex Fresenius, 1829.
Two cases of cutaneous and ungual phaeohyphomycosis caused by species of Chaetomium are reported. The patients showed no clinical signs of immunodeficiency. In Case 1 there was a small, ulcerated, crusted lesion on the right forearm. Direct microscopical examination of material from this lesion showed light-brown hyphae with thick-walled cells. The fungus isolated was identified as Chaetomium globosum. Case 2 had lesions of the fingernails. Direct microscopy showed dematiaceous septate hyphae in the nail. The isolate from the nails was identified as Chaetomium perpulchrum. Identification of the fungi was based on the classification of Ames (1963) as adapted by Cooke (1986). Such infections due to Chaetomium species are rare.


Alnespirone and buspirone have anxiolytic-like effects in a conflict procedure in rats by stimulating 5-HT(1A) receptors.
We studied the anxiolytic-like activity of alnespirone and buspirone, two 5-HT(1A) receptor agonists, in a modified Geller-Seifter conflict model, and examined the role of 5-HT(1A) receptors by studying whether WAY-100635, a selective antagonist at these receptors, blocked their effects. Administered s.c. 30 minutes before testing, 0.5 and 1mg/kg alnespirone significantly increased punished responding, whereas lower doses (0.125 and 0.25 mg/kg) had no effect. At 1mg/kg, alnespirone significantly reduced the rates of unpunished responding. One dose of buspirone (1mg/kg) significantly increased punished responding and reduced unpunished responding. Lower doses were ineffective. Administered s.c. 40 minutes before testing, WAY-100635 had no effect on any parameter but completely antagonized the effects of alnespirone (1mg/kg) and buspirone (1mg/kg) on punished responding. The ability of buspirone to reduce unpunished responding was not antagonized by WAY-100635, probably reflecting a sedative effect of buspirone due to dopamine D2 receptor blockade. The results suggest that alnespirone and buspirone have anxiolytic-like activity in a conflict procedure by stimulating 5-HT(1A) receptors, presumably at a presynaptic level. Like buspirone, alnespirone may have useful effects in the treatment of anxiety disorders.


The influence of maternal separation on humoral and cellular immunity in farmed deer.
The effect of maternal separation on in vivo and in vitro immune parameters was studied in young hybrid deer. Groups of fawns separated from their mothers either 2 days prior to or 7 days post immunization with keyhole limpet hemocyanin were compared with a control group of immunized, unseparated fawns. Animals separated prior to antigenic challenge had significantly higher concentrations of antigen-specific IgG in their serum than control animals. There was no influence on the humoral immune response in animals separated following immunization. In contrast, Con A transformations were transiently depressed in separated animals compared to the control group. The time separation was imposed relative to challenge and therefore influenced the subsequent immune response.


The alkylated thiohydantoin method for C-terminal sequence analysis.
The alkylated-thiohydantoin method for C-terminal sequencing makes a significant improvement to the thiohydantoin method first described by Schlack and Kumpf. Prior to cleavage from the protein, the C-terminal thiohydantoin is alkylated, making it a better leaving group than the unmodified thiohydantoin. The C-terminal alkylated-thiohydantoin can be cleaved from the protein under conditions that simultaneously form the next thiohydantoin. Combining cleavage and thiohydantoin formation in one step eliminates the need for activating the C-terminal carboxyl group before every sequencing cycle and prevents detection of C-termini formed by random cleavage of peptide bonds in the protein during the sequencing chemistry. The alkylated-thiohydantoin method includes the presequencing modification of cysteine and lysine and the automated modification of aspartic and glutamic acids, serine and threonine. Modifying the reactive side-chain groups improves the ability to sequence through and detect these amino acids. The alkylated-thiohydantoin method can sequence through and detect 19 of the 20 genetically coded amino acids. Sequencing stops at proline residues.


Formation characteristics of PCDD and PCDF during pyrolysis processes.
In recent years, pyrolysis processes have become technologies developed to industrial scale and discussed as alternatives to the existing waste combustion technology. However, little information is published regarding PCDD/F formation characteristics during pyrolysis processes. Two common shredder fractions--industrial light shredder (ILS) and refrigerators (REF)--both with high chlorine and copper content were pyrolysed for this pyrolysis study using a pilot plant with a capacity of 100 kg/h. At oxygen concentrations below 2% and temperatures between 430 degrees C and 470 degrees C, considerable amounts of PCDD/F were formed during the pyrolysis. More than 90% of total TEQ was found in the oil fraction (gas phase). The PCDD/PCDF ratio and the homologue pattern differed significantly from those formed during waste incineration. Considering mono- to octachlorinated congeners, up to 400 times more PCDF were formed compared to PCDD. For the investigated pyrolysis conditions, the formation of low chlorinated congeners was highly favoured. The distribution of TEQ within the individual congeners were very similar in all investigated runs. More than 80% of total TEQ stem from 2,3,7,8-substituted T4CDF and P5CDF. The isomer pattern, however, did not show significant differences compared to the common waste incineration pattern suggesting that the basic formation routes are similar.


Articular chondrocyte apoptosis in equine osteoarthritis.
Osteoarthritis (OA) is the most common joint disease in horses. Chondrocyte apoptosis has been implicated as a major pathological OA change in humans and experimental animals but no studies have been performed on equine OA. Articular cartilage was collected from three normal and five OA horses. Histopathological changes were scored by a modified Mankin grading system. A terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay was performed to identify chondrocyte apoptosis. Nitric oxide (NO) production from chondrocytes was indirectly evaluated by immunohistochemistry with polyclonal antibody to nitrotyrosine. The histopathological score and percentage of chondrocyte apoptosis from the OA cartilages were significantly higher than from normal cartilages. There was a significant correlation between histopathological grade and the percentage of chondrocyte apoptosis. OA cartilages exhibited stronger immunoreactivity to nitrotyrosine than normal cartilage. Topographical distributions of chondrocyte apoptosis, cartilage matrix degeneration, and NO production overlapped in equine OA cartilages, suggesting that these pathological phenomena are closely interrelated.


The cost-effectiveness of the use of clopidogrel in acute coronary syndromes in five countries based upon the CURE study.
The CURE study demonstrated that clopidogrel prevents a range of ischaemic cardiovascular events in patients with Acute Coronary Syndromes (unstable angina or non-ST-segment elevation MI). We undertook an economic analysis of the use of clopidogrel in the UK, USA, Sweden, France and Canada based on the CURE study. The costs of hospitalization, study drug and other medications were calculated, based on resource utilization for all patients in CURE. Unit costs were obtained for all resource items for each country, and are reported in local currencies in 2001 prices. While hospitalization costs were lower in the clopidogrel group, when the acquisition cost of clopidogrel for 9 months is included, the average cost per patient is higher in the clopidogrel group than the placebo group in all countries [difference in costs (with 95% CI) 208 pounds sterling (119, 297), 451 US dollars (58, 845), SKr 2571 (728, 4412), 325 euros (85, 565), 161 Canadian dollars (-185, 506)]. The absolute reduction in the number of total primary events was 2.0%, resulting in an incremental cost-effectiveness ratio (ICER) of 10,366 pounds sterling in the UK, 22,484 US dollars in the USA, SKr 127,951 in Sweden, 16,186 euros in France, and 7973 Canadian dollars in Canada per primary event avoided with clopidogrel. Clopidogrel in CURE reduced hospitalization costs but the acquisition cost of clopidogrel creates an overall increase in direct health care costs over 9 months. Nevertheless, the cost-effectiveness is in a range comparable to other therapies currently utilized for acute coronary syndromes.


Adjuvant endocrine therapy for postmenopausal women: Type and duration.
Postmenopausal women with ER positive breast cancers benefit from adjuvant endocrine therapy. Most such patients should consider aromatase inhibitor therapy at some point in their treatment course as there are modest additional risk reductions over tamoxifen therapy, alone. Longer durations of therapy - beyond five years of tamoxifen - with either ongoing tamoxifen or an AI also improve cancer outcomes. Markers of risk for early recurrence are the same as those for late recurrence. Decisions regarding the optimal type and duration of therapy reflect patient preferences in light of well described side effects of tamoxifen and AI therapy, tolerability of treatment, and established clinical, pathological and genomic markers of risk.


Lack of efficacy and potential aggravation of myoclonus with lamotrigine in Unverricht-Lundborg disease.
Unverricht-Lundborg disease (ULD) is a progressive myoclonus epilepsy with tonic-clonic seizures, action myoclonus, mild ataxia, without dementia. Persistence of invalidating action myoclonus is a major problem. Drugs like phenytoin can aggravate ULD. In this study, we retrospectively analyzed the effect of add-on lamotrigine (LTG) in the five patients under our care who received LTG. Three men and two women, aged 20-50 years who had ULD confirmed by molecular biology, followed in two epilepsy centers, received add-on LTG at 50-300 mg/d. All of them had valproate. The other drugs used in cotherapy were high-dose piracetam, benzodiazepines phenobarbital, topiramate, and primidone. The assessment of LTG was based on detailed interview and clinical examination. Aggravation was diagnosed when myoclonic jerks (MJ) increased without irregular intake of medication, inappropriate lifestyle, encephalopathic or metabolic complications, or overdosage. In two patients, LTG exacerbated MJ in a dose-dependent manner. In one patient, a delayed, severe exacerbation of myoclonus occurred that only ceased after LTG withdrawal and introduction of levetiracetam. These three patients had minor forms of ULD. In two patients with moderate to severe forms of ULD, LTG had no effect. Although symptoms may fluctuate in ULD, it was possible to pinpoint lack of improvement (2/5), dose-related exacerbation of myoclonus (2/5), and putative late-onset aggravation (1/5) in five patients treated with adjunctive LTG. LTG does not appear to be a sensible treatment option in ULD.


Novel self-sampling culture method to monitor excretion of live, oral Shigella flexneri 2a vaccine SC602 during a community-based phase 1 trial.
A culture technique for assessing the excretion of live enteric vaccines was developed and verified during an outpatient safety trial of the Shigella flexneri 2a SC602 vaccine. Preliminary studies showed that SC602 could be recovered on Hektoen enteric (HE) agar plates that had been inoculated with seeded stools in one quadrant, held for up to 48 hours, streaked for isolation, and incubated for 24 +/- 6 hours. Recovery results on HE plates held at 4 degrees C and 25 degrees C were comparable; however, 4 degrees C better inhibited overgrowth before streaking. To prepare for a community-based vaccine trial, volunteers were trained to self-sample fresh stool and to swab-inoculate a single quadrant of HE agar. The trial began with 36 volunteers ingesting 2.5 x 10(4) CFU of SC602 in bicarbonate buffer. During the study, volunteers inoculated HE plates with fresh stool, stored the plates at 4 degrees C, and delivered them to the laboratory within 48 hours. A microbiologist then streaked the HE for isolation, incubated the plates at 35 degrees C +/- 2 degrees C for 24 +/- 6 hours, and identified presumptive S. flexneri colonies by slide agglutination with poly-group B antiserum. The attenuating genetic signature of SC602 was confirmed on selected isolates with the polymerase chain reaction with two specific DNA primer sets. Vaccine was detected from 20% of volunteers on day 1, increasing to 86% by day 4, and all but one vaccinee had excreted SC602 at least once by day 7. The latest initial SC602 detection occurred on day 7, the longest excretion occurred in one vaccinee on day 33, and excretion throughout the trial was intermittent. The trial was terminated by ciprofloxacin treatment on day 35. Volunteer compliance with self-sampling and HE plating was excellent because of the convenience of the method, and the advantage of immediate "bedside" plating was evident in the high recovery rate of excreted vaccine. This method can be applied in other trials of live enteric vaccines that require accurate sampling of excreted organisms.


Preferential transposition of a Drosophila P element to the corresponding region of the homologous chromosome.
Genetic and physical analyses have demonstrated an intimate interaction or pairing of homologous chromosomes in the nuclei of many Drosophila cell types. Experiments were performed to determine whether P elements transposing from a given chromosome to its homolog would preferentially insert in the region corresponding to the donor site, perhaps due to such a proximity. A P [lacZ;ry+] element at the cactus locus (35F) on the second chromosome was mobilized and 96 insertions on the homolog were recovered. The distribution of these new insertions was determined by recombination mapping and molecular analysis, and compared with a control set of 93 second-chromosome insertions originating from the X chromosome. A nearly threefold preference was observed for re-insertion in a region of two to three number divisions around cactus on the homolog. However, none of these "local" insertions was actually within approximately 50 kb of the site at cactus corresponding to the starting site. This is in marked contrast to the previously described phenomenon of intrachromosomal local transposition, where the majority of local transpositions are within 10 kb. The data suggest that the mechanisms for intrachromosomal and interchromosomal local transposition are distinct, and are consistent with a model for interchromosomal local transposition involving proximity of homologous chromosomal regions in the nuclei of the germline cells.


Periodic planar disc packings.
Several conditions are given when a packing of equal discs in a torus is locally maximally dense, where the torus is defined as the quotient of the plane by a two-dimensional lattice. Conjectures are presented that claim that the density of any collectively jammed packing, whose graph does not consist of all triangles, and the torus lattice is the standard triangular lattice, is at most (n/(n + 1))π√12, where n is the number of packing discs in the torus. Several classes of collectively jammed packings are presented where the conjecture holds.


Effects of disruption of the peritrophic membrane on larval susceptibility to Bt toxin Cry1Ac in cabbage loopers.
The insect midgut peritrophic membrane (or peritrophic matrix) (PM) is an extracellular structure, lining the midgut epithelium. The PM facilitates the food digestion process and plays important roles in insect-microbe interactions as a barrier against microbial pathogens. The soil bacterium, Bacillus thuringiensis (Bt), and its proteinaceous toxins are widely used for insect control. To understand the protective role of PM in insects against Bt toxins, the effect of PM on larval susceptibility to Bt toxin Cry1Ac was examined in Cry1Ac-susceptible and -resistant strains of the cabbage looper, Trichoplusia ni. The PM in T. ni was disrupted, using a baculovirus enhancin (TnGV enhancin) to degrade the major PM mucin protein IIM and a chitin binding chemical, Calcofluor, to inhibit the binding of PM proteins to chitin. Bioassays of the susceptibility of T. ni larvae to Cry1Ac with treatment of TnGV enhancin showed significantly increased larval mortality in both the Cry1Ac susceptible and resistant strains, confirming that the PM is a protective barrier to the passage of Cry1Ac and plays a protective role against the toxin. However, treatment of T. ni larvae with Calcofluor significantly reduced the larval susceptibility to Cry1Ac. The level of mortality reduction by treatment with Calcofluor was more significant in the resistant T. ni strains than in the susceptible strain. The mechanism for the decrease of susceptibility to Cry1Ac in T. ni treated with Calcofluor needs to be understood. It may result from binding of the toxin to the over expressed PM proteins, preventing the Cry1Ac from reaching the midgut receptor for the toxin or from potential binding of Calcofluor to the midgut receptor for Cry1Ac, leading to inhibition of the toxicity of Cry1Ac in larvae.


The Csk homologous kinase, Chk, binds tyrosine phosphorylated paxillin in human blastic T cells.
In determining the role of Chk in T cell signaling, we have focused on its protein-protein interactions. We detected a tyrosine phosphoprotein that coimmunoprecipitated with Chk from pervanadate stimulated human blastic T cells. Subsequent Western blot analysis identified this tyrosine phosphoprotein as paxillin. Paxillin, a cytoskeletal protein involved in focal adhesions, was first identified as a v-Src substrate in transformed fibroblasts. Interestingly, Chk specifically bound tyrosine phosphorylated paxillin. Consistent with our in vivo data, Chk and paxillin were observed to localize in similar cellular regions prior to and following stimulation. Using GST fusion proteins, we determined that the Chk SH2 domain, not the SH3 domain, bound tyrosine phosphorylated paxillin. Specifically, paxillin bound to the FLVRES motif of the Chk SH2 domain. Using Far Western analysis, we revealed that the Chk SH2 domain directly associates with tyrosine phosphorylated paxillin. Finally, p52(Chk) expression in Csk-deficient mouse embryo fibroblasts decreased total phosphotyrosine levels of paxillin, implying a physiological role for Chk. These studies provide important insight into the role of Chk in tyrosine mediated signaling, as well as T cell physiology.


[DAHANCA (Danish Head and Neck Cancer)--20 years of cooperation].
A review of the DAHANCA-group's projects concerning cancer of the head and neck over 20 years is presented. Apart from the first, all projects were randomized trials. Two projects with neoadjuvant chemotherapy have not shown any notable tumour control or better survival. More than 1800 patients suffering from cancer of the head and neck treated in the five oncological centres of the country were included in the three projects concerning radiosensitizers and radiotherapy. The radiation has been accelerated during the years making it more effective. Each of the three projects has improved the local control rate by 11-15% and the survival is enhanced by 11-13% for each project. Cooperation between our five oncological centres has given good results and increased the survival for patients with head and neck cancer. It is now routine to give the radiosensitizer tablets Nimorazol 1 1/2 hours before radiation and to give six fractions weekly to patients with squamous cell cancer in the supraglottic region, pharynx and oral cavity.


[Nucleic acid content of skeletal muscles during hypokinesia and the recovery period].
The concentration of nucleic acids in the gastrocnemius muscle of Wistar rats was measured during 60-day hypokinesia and 30-day recovery periods. The data obtained indicate that this hypokinetic model leads to an arrest of muscle growth and inhibition of the age-related accumulation of nucleic acids in the gastrocnemius muscle. The content of DNA and RNA genetic matrixes largely depends on the muscle activity. Normalization of the motor function results in an activation of genetic mechanisms of biosynthesis regulation, acceleration of reparative processes and recovery of muscular activity.


The larval ontogeny of Coryphaeschna perrensi (McLachlan, 1887): Supporting monophyletic groups in Aeshnidae dragonflies (Insecta: Odonata: Anisoptera).
The development of the larval external morphology of Coryphaeschna perrensi is reported based primarily on a comparison of successive exuviae of reared specimens, with the second stadium larvae first described separately. Accentuated changes observable throughout successive moltings occur in some structures, such as the head capsule, labium, and anal appendages, allowing for the definition of characters with naturally ordered, polarized, and linear states (transformation series) by ontogenetic evidence. The terminal (less general) and nonterminal (more general) states of the described transformation series correspond by primary homology to the conditions found in larvae of other dragonfly species. Consequently, as the result of a parsimony analysis and subsequently ontogenetic rooting, the disposition of the states of 17 characters in a sample of final-stadium larvae of 23 species, representatives of the six Aeshnidae tribes (21) and Austropetaliidae (2), results in a hierarchical network comprising six distinct taxonomic levels of inclusion of C. perrensi. The levels correspond to Aeshnidae, Aeshninae, Aeshnini (part) + Gynacanthini, Coryphaeschna + Remartinia, Coryphaeschna, and Coryphaeschna except C. adnexa, which are groups previously recognized as monophyletic resulting from analyses considering adult morphology. Immature insect morphology coupled with ontogenetic observation presenting great potential to hypothesize phylogenetic relationships and investigate heterochronic events.


A novel endoproteolytic processing activity in mitochondria of erythroid cells and the role in heme synthesis.
The erythroid isoform of aminolevulinate synthase (eALAS) protein is a major control point in erythroid heme synthesis and hemoglobin formation. Erythroid cells were extracted from mouse blood and bone marrow and metabolically labeled with (35)S-methionine. This was followed by immunoprecipitation of eALAS protein products. The results show that the N-terminus of the expected full-length 59-kd form of the eALAS protein is truncated in bone marrow erythroid cells by approximately 7 kd. More differentiated erythroid cells in the peripheral blood exhibit very little of this protein truncation. Erythroid cells from the bone marrow were isolated using monoclonal antibody TER-119 and were shown to contain a unique endoprotease activity that could cleave the eALAS protein to the shorter form in vitro. With or without the mitochondrial signal sequence, the eALAS protein could serve as a substrate for the cleavage. This cleavage renders a functional eALAS protein and only removes a domain of unclear function, which has previously been reported to vary in size as a result of alternative RNA splicing. The protease activity was enriched from the membranes of mitochondria from bone marrow cells and was shown to be different from mitochondrial processing peptidase, medullasin, and other known proteases. Apart from the mitochondrial processing peptidase that cleaves the import signal sequence, this is the first description of a mitochondrially located site-specific processing protease activity. (Blood. 2000;96:740-746)


Arabitol dehydrogenase as a selectable marker for rice.
Arabitol dehydrogenase has been adapted for use as a plant selectable marker. Arabitol is a five-carbon sugar alcohol that can be used by E. coli strain C, but not by the laboratory K12 strains. The enzyme converts the non-plant-metabolizable sugar arabitol into xylulose, which is metabolized by plant cells. Rice was transformed with a plant-expression-optimized synthetic gene using Biolistic-mediated transformation. Selection on 2.75% arabitol and 0.25% sucrose yielded a transformation efficiency (9.3%) equal to that obtained with hygromycin (9.2%). Molecular analyses showed that the atlD gene was integrated into the rice genome of selected plants and was inherited in a Mendelian manner. This study indicates that arabitol could serve as an effective means of plant selection.


Reliability and validity of the family satisfaction instrument in families of children with pneumonia.
Family satisfaction has become an integral part of quality of care in hospitals. Thus, it is crucial to develop instruments that measure family satisfaction. The purpose of this study was to examine the validity and reliability of a family satisfaction questionnaire. This study used a survey questionnaire consisting of 26 items that identified nurses' constructs of behaviors and communication. The population surveyed were families whose children were hospitalized due to pneumonia. The results revealed that only 16 items of the instrument demonstrated evidence of acceptable constructs of reliability and validity. The study recommends further studies that add other potential constructs related to family satisfaction.


Foveal sparing. New anatomical evidence for bilateral representation of the central retina.
The pattern of retinal ganglion cell projections to the dorsal lateral geniculate nuclei has been demonstrated with horseradish peroxidase neuronography. A 1 degree-wide strip centered on the vertical meridian has been found in which ipsilaterally and contralaterally projecting ganglion cells intermingle. This strip expands to a width of 3 degrees at the fovea, since mixing of horseradish peroxidase-labeled and unlabeled ganglion cells was found in a band approximately 0.5 degrees wide along both the nasal and temporal rims of the foveola. These labeled ganglion cells rimming the foveal pit in its entirety represent a possible anatomical basis for "foveal sparing".


Histological and ultrastructural localization of antigen B in the metacestode of Taenia solium.
The morphological localization of antigen B (AgB) in the tissues of the Taenia solium metacestode was studied by immunological and biochemical methods. Indirect immunofluorescence carried out on vibratome sections showed that AgB is widely distributed throughout the tissue. A more intense fluorescence was observed in the tegumentary cytons of the bladder wall and in the lumen of the spiral canal of the invaginated scolex. Ultrastructural analysis of larvae washed in PBS after dissection from meat and then incubated with rabbit antibodies against AgB, followed by peroxidase-labeled goat anti-rabbit IgG, did not exhibit electron-dense material on the external surface. Larvae fixed in glutaraldehyde immediately after dissection and exposed to the immunoperoxidase reagents did exhibit electron-dense material on microtriches, indicating that AgB is only loosely bound to the external surface. Crude extracts of surface-radioiodinated cysticerci analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) contained no labeled proteins with the molecular weight of AgB. Autoradiography of the immunoelectrophoretograms in which the crude extract was confronted with antibodies to AgB demonstrated that this antigen was not labeled, and therefore is not exposed on the tegumentary surface. The results suggest that AgB is synthesized by the tegumentary cytons of the parasite and secreted through the tegumental membrane into the host tissues and the lumen of the spiral canal.


[A case report of heterosexual transmission of HIV infection between spouses with persistent condom use].
To report a case of heterosexual transmission of HIV infection between spouses with consistent condom use. The first case with HIV infection was detected in the contracted male workers returned from abroad in Qingdao in 1992 and both he and his spouse were given health education for AIDS/HIV prevention and instructions on condom use. And, his wife was followed-up every six months by detecting her serum anti-HIV. The wife of the index case was negative for anti-HIV in the first 12 blood tests before December 1996. But, she was found suspect of positive for anti-HIV an July 1997 and definitely positive for anti-HIV-1 in August 1997 during her 14th test. In the period of 1992 to 1997, they persisted in condom use during intercourse. Recall of the wife showed that she had low fever in May 1997, suggesting at the window phase of her acute HIV infection. It postulated that she infected with HIV curing March to April 1997. The case report indicated that incorrect use of condom could not prevent from HIV transmission between spouses.


Epsilon aminocaproic acid reduces transfusion requirements in patients with thrombocytopenic hemorrhage.
Epsilon aminocaproic acid (EACA) is an antifibrinolytic drug that has been used to control hemorrhage by stabilizing the thrombus. It has been used in thrombocytopenic patients largely on an empiric basis. Concerns regarding side effects have limited the use of this drug. The authors reviewed their experience with EACA at the Cleveland Clinic Foundation from 1997 to 2003. Of 77 patients with thrombocytopenic hemorrhage, 51 (66%) patients achieved a complete response and 13 (17%) patients achieved a partial response, resulting in a decrease in platelet and red blood cell transfusions. Adverse effects were manageable in this set of patients with severe underlying disease. Based on this experience, EACA may be a valuable adjunctive therapy in the treatment of patients with thrombocytopenic hemorrhage.


Knotless scleral fixation for implanting a posterior chamber intraocular lens.
I describe a technique for implanting an intraocular lens by scleral fixation sutures that has the advantages of knotless fixation of the haptics and an out-in approach for passing the needle through the sclera.


Assessment of pediatric residents' otoscopic interpretive skills by videotaped examinations.
Accurate diagnosis of otitis media is essential to facilitate appropriate management. Few residency programs assess formally their residents' competency in diagnosing middle ear disease. To evaluate the performance of pediatric residents' otoscopic interpretive skills by level of training, with a videotaped otoendoscopic examination (VOE). A VOE was used to assess and compare the performance of a cross-sectional sample of 141 residents with one another by level of training as well as with novice and expert groups. Total score, sensitivity, specificity, and kappa coefficients were calculated for each subject by comparing the subject's answers on the 50-ear test with the VOE's expert panel-derived answers, and averages were determined for each training level. Each pediatric resident training group had moderate agreement (mean kappa coefficient range: .45-.56) with the VOE answers, compared with the novice group (mean kappa: .31, fair) and expert group (mean kappa: .80, substantial). Twenty-eight residents (20%) had fair or less agreement (kappa<.41) with the VOE answers. The mean total scores of all pediatric resident training levels were significantly (P<.05) lower than the expert group and significantly (P<.05) higher than the novice group (with exception of the early postgraduate year-1 group). Subjects with more training had higher kappa levels (r=.33,<.001, Spearman) when results were compared among novice, residents, and experts. We found the VOE to be a feasible and reliable instrument to accurately distinguish novice, resident, and expert level skills in the determination of middle ear effusion status.


Comparative studies of interactions of hemoglobin with single-chain and with gemini surfactants.
The interactions of hemoglobin with glutamic acid-based gemini surfactants (L(2)G(2)C(n)) and with n-dodecylammonium alpha-glutamate (GDA) have been studied with isothermal titration microcalorimetry, fluorescence spectroscopy, UV-vis spectroscopy, and circular dichroism. The results indicate that GDA monomer can make the hemoglobin denatured, and that when the concentration of GDA is higher than cmc, heme monomer is released from the hydrophobic cavity of hemoglobin. On the other hand, L(2)G(2)C(n) surfactants can also interact with hemoglobin. Compared with GDA, L(2)G(2)C(n) have a much smaller binding ability with hemoglobin, and the circular dichroism spectra results show that the secondary structure of hemoglobin is possibly stabilized by a small amount of L(2)G(2)C(n), which may generate hydrophobic linkages between the nonpolar residues of hemoglobin. However, with further addition of L(2)G(2)C(n), the secondary structure of hemoglobin is unfolded, and the percentage of alpha helix in hemoglobin molecule is decreased. In addition, the L(2)G(2)C(n) surfactant with a longer spacer can reduce the denaturing degree of hemoglobin.


Fructose-6-phosphate modifies the pathway of the urea-induced dissociation of the allosteric phosphofructokinase from Escherichia coli.
Phosphofructokinase from Escherichia coli binds fructose-6-phosphate with the sugar moiety of the substrate interacting with one subunit and the phosphate group with another one, so that bound fructose-6-phosphate lies across the interface between the subunits [(1988) J. Mol. Biol. 204, 973-994]. When this interface is 'cross-linked' by fructose-6-phosphate, it becomes more stable because of the extra interactions between subunits: inactivation upon dissociation occurs only above 5 M urea, instead of 1 M urea for the free protein. At saturation in fructose-6-phosphate, this interface is no longer the first to dissociate as in the free protein [(1989) Biochemistry 28, 6836-6841]: instead, the addition of urea to phosphofructokinase in the presence of fructose-6-phosphate induces a conformational change within the tetramer which alters the environment of Trp-311 and distorts the regulatory site.


Reply to "Comment on 'Monte carlo study of structural ordering in charged colloids using a long-range attractive interaction' "
In the Comment by Grier and Crocker (preceding paper) the authors tried to refute our criticism [Phys. Rev. E 58, 2237 (1998)] on their work [J. C. Crocker and D. G. Grier, Phys. Rev. Lett. 77, 1897 (1996)] by simply fitting once again their old experimental data. Grier and Crocker claim that their pair-potential measurements on aqueous dilute suspension of charged colloidal particles confined between charged glass walls at gap of about 8 &mgr;m provide evidence for the failure of Sogami-Ise (SI) theory and demonstrate the applicability of the Dejaguin, Landau, Vervey, and Overbeek (DLVO) theory. Grier and Crocker do not provide additional experimental proof to counter our criticism. We continue to claim here based on our conductivity and conductometric titration measurements, which allow estimating the effective charge and determining the number and nature of the dissociable sites respectively, that their measurements using not well-characterized samples cannot provide clear evidence for the failure of SI theory. With the evidences available in literature, we refute all of the Grier and Crocker comments, including the effect of charged wall confinement on the measured colloidal interactions.


Calcium sequestration in the liver.
Hepatic parenchymal cells maintain intracellular total and cytosolic free Ca2+ levels by: entry of Ca2+ through channels, extrusion of Ca2+ by an outwardly directed Ca2+ pump, and controlled sequestration into intracellular pools. The mechanism of Ca2+ inflow is poorly characterized. The plasma membrane Ca2+ channels seem to share some of the characteristics of Ca2+ channels in excitable cells, but also differ from them. The outwardly directed plasma membrane Ca2(+)-ATPase is a calmodulin independent, P-type enzyme. Ca2+ uptake into the endoplasmic reticulum is due to the activity of a different Ca2(+)-ATPase, which is similar in molecular weight and shares antigenic determinants with the sarcoplasmic reticulum enzyme. In addition, mitochondria and nuclei also take up calcium. The exact mechanism by which Ca2+ is released from intracellular organelles is not well known. Several mechanisms for Ca2+ release from the endoplasmic reticulum were reported, including IP3 and GTP-induced. The most effective identified way of eliciting Ca2+ release from microsomal fraction is by the oxidation of critical -SH groups. This mechanism is likely to be involved in the rise of cytosolic Ca2+ observed in many situations of hepatocellular injury. In addition to being sequestered into subcellular organelles, some of the intracellular Ca2+ is bound to specific Ca2+ binding proteins. Both calmodulin and members of the annexin family were identified in the liver. Stimulation of the liver with gluconeogenic hormones results in increased Ca2+ entry into the cell, the release of Ca2+ from intracellular pools, and an oscillatory increase in free cytosolic Ca2+ levels. Extensive research is still needed for the elucidation of the exact mechanisms by which these events occur.


Migratory insertion and hydrogenation of a bridging azide in a thiolate-bridged dicobalt reaction platform.
A novel well-defined thiolate-bridged dicobalt azido complex is converted to a rare sulfilimide-bridged dicobalt complex via nitrogen atom migratory insertion into the Co-S bond upon thermolysis. Intriguingly, the homolytic cleavage of hydrogen is achieved by this azide under mild conditions to furnish a partially hydrogenated azido complex.


Effect of inhibiting prostaglandin synthesis in pregnant sheep with 4-aminoantipyrine under normothermic and hyperthermic conditions.
Infusion of the prostaglandin synthetase inhibitor 4-aminoantipyrine at a rate of 20 mg/min via the fetal tarsal vein during normothermic conditions (ambient temperatures = 24 degrees C) significantly decreased the concentrations of prostaglandins E2 and F2 alpha in maternal and fetal arterial plasma and in uterine and umbilical vein plasma. The infusion was associated with a small but significant rise in fetal temperature and a fall in fetal arterial pH. Respiratory alkalosis developed in fetuses during hyperthermia by raising the ambient temperature to 43 degrees C for 8 hours. In contrast, infusion of 4-aminoantipyrine during hyperthermia produced fetal metabolic acidosis as indicated by a fall in fetal pH and an increase in PaCO2, even though the ewe remained hypocapnic. Four of the 10 fetuses died during or shortly after the 4-aminoantipyrine infusion during hyperthermia. These results indicate that uteroplacental prostaglandin synthesis is essential to allow the fetus to adapt to an increase in body temperature and suggests that prostaglandin synthetase inhibitors should be used with caution during pregnancy.


Major amputation for irresectable extremity melanoma after failure of isolated limb infusion.
Isolated limb infusion (ILI) is an effective, minimally invasive treatment option that delivers high-dose regional chemotherapy to treat metastatic melanoma confined to a limb. In some patients, however, locoregional disease does not respond to the treatment or extensive recurrence occurs so that an amputation may become inevitable. In this study we analyzed indications for and results of amputation in these cases. 14 patients were identified in whom amputation of the affected limb had to be carried out after failure of ILI. Following ILI, three patients had a complete response, seven had a partial response, two had stable disease and two patients had progressive disease. The median duration of response after ILI was 7 months (range 2-30). The median interval between ILI and amputation was 10 months. Amputation was performed in six of 20 patients who had been treated with an upper limb ILI, compared to eight amputations that were performed in 215 patients who had been treated with a lower limb ILI (P = .001). The indications for amputation were severe pain due to progression of tumor (n = 3), uncontrollable and troublesome tumor progression (n = 6) and bleeding from ulcerated lesions (n = 5). Five patients developed stump recurrence after amputation; these were treated by excision or radiation. Six of the eight patients who had a lower limb amputation became ambulant with the aid of prosthesis. Median survival after amputation was 13 months: three patients survived more than 5 years. Amputation following upper extremity ILI is more common compared to lower extremity ILI. Amputation may provide effective long-term palliation in selected patients when there is extensive inoperable progressive or recurrent disease after ILI.


beta-Lactam resistance and beta-lactamase isoforms of Moraxella catarrhalis isolates in Taiwan.
Moraxella catarrhalis is an important pathogen in both upper and lower respiratory tract infections. More than 90% of isolates worldwide produce beta-lactamase. The beta-lactamases produced by M. catarrhalis can be differentiated by isoelectric focusing (IEF) into BRO-1 and BRO-2 patterns. In this study, we investigated the prevalence of various beta-lactamase isoforms in clinical isolates of M. catarrhalis in Taiwan, as well as the relationships of these isoforms with antibiotic resistance. A total of 271 clinical isolates of M. catarrhalis were collected from 12 large medical laboratories in Taiwan from 1 August 1993 to 31 July 1995. The overall prevalence of beta-lactamase production was 98.2% (266 of 271 isolates). Analytical IEF revealed BRO-1 was the most common beta-lactamase pattern among the isolates (238 isolates, 88%); BRO-2 was the only other pattern found, with 32 (12%) isolates. The geometric mean minimum inhibitory concentration of ampicillin for BRO-1 producers was 63-fold higher than that for beta-lactamase-negative isolates, and 6.5-fold higher than that for BRO-2 producers. beta-Lactam antibiotics, such as amoxicillin + clavulanate and the cephalosporins, tested were very active against this species, regardless of whether the isolate produced beta-lactamase or not. In conclusion, beta-lactamase is common among clinical isolates of M. catarrhalis in Taiwan, with BRO-1 being the most common isoform. However, because most isolates tested were still sensitive to amoxicillin + clavulanate and cephalosporins, these agents appear to be reliable alternatives to first-line therapy when M. catarrhalis is contributing to a clinical infection.


[Effect of combination chemotherapy of low-dose CDDP. Continuous infusion of 5-FU, and intermittent CPT-11 administration for 2 advanced pancreatic cancer cases with liver metastasis].
For advanced pancreatic cancer, there is no typical chemotherapy regimen non single chemotherapeutic agent. For example, 5-FU, Doxorubicin, MMC and Epirubicin obtained only 15-24% efficacy, and general combination chemotherapy was FAM, 5-FU+CDDP and 5-FU+Leucovorin for pancreatic cancer. Generally, in pancreatic cancer cases the performance status was poor, and most could not endure the chemotherapy regimen. 5-FU continuous infusion and low-dose CDDP regimen were effective and showed fewer side effects for pancreatic cancer. Then, for 2 cases of advanced pancreatic cancer with liver metastasis, 5-FU continuous infusion + low-dose CDDP + intermittent CPT-11 administration (5-FU 500 mg/body/24 hr + CDDP 5mg x 5 days-6 courses + CPT-11 100 mg-125 mg-150 mg, bolus i.v. intermittently) was effective. Thus, this regimen could well be effective for advanced pancreatic carcinoma.


Borderline personality disorder and chronic pain: a practical approach to evaluation and treatment.
Patients with chronic pain present a spectrum of complexity that can be overwhelming for the individual practitioner. These patients require thoughtful care and a comprehensive treatment plan. This complexity should be acknowledged, not avoided, and the patient should be engaged, not shunned. A practical approach will assist in developing expertise and proceeding empathically. The presence of a superimposed personality disorder significantly increases the difficulty of caring for these patients. Studies investigating the prevalence of borderline personality disorder in patients with chronic pain averaged 30 %, highlighting the importance of being able to effectively treat this patient population. Appropriate management of these patients should focus on a collaboration to practice productive behaviors despite intense emotional distress. Longitudinal research provides a foundation for an optimistic prognosis that can be enhanced with this rehabilitative approach.


A Tissue-Culture Derived Salt-Tolerant Line of Flax (Linum usitatissimum).
Flax seedlings (Linum usitatissimum) were used to initiate callus cultures. After a month of growth, the healthy callus was transferred to a similar medium supplemented with salts to meet or exceed those concentrations found in a saline soil of Saskatchewan. This salt medium also lacked growth hormones. After one month in the salt medium, most of the cells had died, but a few green cell aggregates remained. On non-salt-stress but otherwise similar medium, most cells remained healthy over the same period. The green pockets from the high salt medium were excised and transferred to a different medium that caused shoots to form from the callus. These shoots were later transferred to a medium that caused root formation from the base of the shoots. Plants taken through to maturity in soil have set seed and the progeny of these have been tested for salt-tolerance. Preliminary observations suggest that a salt-tolerant ability is present in the progeny. Some of the advantages and disadvantages of using this method to select for salt-tolerant lines are discussed.


cDNA cloning and regulation of two sex-hormone-repressed hamster tear lipocalins having homology with odorant/pheromone-binding proteins.
A major 20-kDa protein is female-specifically expressed in exorbital lacrimal gland (LG) of hamsters and secreted in tears. Here, we identify this female-specific LG protein (FLP) as a lipocalin, having 85% protein sequence identity with male-specific submandibular salivary gland proteins (MSP) secreted in saliva and urine of male hamsters. MSP is also female-specifically expressed in LG and secreted in tears but FLP was undetectable in submandibular gland (SMG). FLP and MSP have similar sex-hormonal regulation in LG, which is different from regulation of MSP in SMG. Female-specific expression of FLP and MSP in LG is due to their incomplete repression by endogenous estrogens and gonadectomy in both sexes and lactation in females resulted in their marked induction, which was prevented by estrogen or androgen treatment. FLP and MSP show best sequence identity with odorant/pheromone-binding lipocalins (58-29%). Maximum identity (58%) is with rat odorant-binding protein (OBP) expressed in lateral nasal glands, followed by aphrodisin of hamster vaginal discharge (39%). Cognate transcript and a cross-reacting 20-kDa protein were detected in nasal glands of rat in both sexes but not in hamsters. Results suggest that two closely related lipocalin genes encode FLP and MSP, which are evolutionarily closer to rat OBP than to hamster aphrodisin and these have evolved different tissue-specificity and sex-hormonal regulation. Possible functions for FLP and MSP are suggested, considering their homology to odorant/pheromone-binding lipocalins, their presence in tears, saliva and urine as well as their sex-specific and lactation-induced expression.


Surnames in Sardinia. II. Computation of migration matrices from surname distributions in different periods.
A method is described for obtaining migration matrices from data on frequency distributions of transmissible traits in at least two different periods. In the present case, surname frequency distributions were used. In this way migration matrices describing rates of movement among nine areas of Sardinia were found for the period 1850-1970. Data were kinship matrices from surname distributions over two or three time periods. Population growth was included in the model under the assumption that expected family size in all areas was constant, or that outside estimates of the relative family sizes exist. Use of variable vs. constant growth rates did not drastically affect the estimated matrices. The matrices estimated for different time periods are similar. Estimates of net migration into the different areas were relatively insensitive to different methods of summarizing statistics. The elements of the matrices indicate strong effects on migration rates of distance between areas, and somewhat weaker effects of economic differences. The diagonal elements of the matrices show a high negative correlation with independent estimates of rates of immigration into the same areas.


Towards establishing indicative values for metabolites of organophosphate ester contaminants in human urine.
In 2015, nine laboratories from Belgium, USA, Canada, China, and Australia participated in an interlaboratory exercise to quantify metabolites of organophosphate ester (OPE) contaminants in pooled human urine. Pooled human urine available as SRM 3673 (Organic contaminants in non-smokers' urine) was obtained from the U.S. National Institute of Standards and Technology and was analyzed for its content of OPE metabolites. Each participating laboratory received 10 mL sample and used its own validated method and standards to report the concentrations of the OPE metabolites of its choice. Four OPE metabolites were consistently measured by most laboratories and they were the following diesters: bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), bis(2-chloroethyl) phosphate (BCEP), and bis(1-chloro-2-propyl) phosphate (BCIPP). Concentrations of other OPE metabolites in SRM 3673 were also reported but are only considered as informative values since they were measured by three laboratories at most. All laboratories used liquid chromatography with tandem mass spectrometry (LC-MS/MS) with or without solid-phase extraction (SPE). This is the first study to report indicative values for OPE metabolites in a human urine Standard Reference Material. It is expected that these indicative values obtained for these four metabolites will be used as quality control to ensure compatibility of results in biomonitoring studies and by other researchers who validate their own methods for the quantification of OPE metabolites in human urine.


Transbronchoscopic needle aspiration in the diagnosis and staging of lung cancer.
We examined the safety and yield of transbronchial needle aspiration (TBNA) in 28 patients who were subsequently proven to have lung cancer. TBNA in 48 sites produced no complications. TBNA was positive for carcinoma in the two patients whose tracheal carinae appeared abnormal on computerized tomography. When the carinae were normal, only one of 13 aspirations was positive for cancer. None of eight paratracheal aspirations was positive. Aspiration of visibly abnormal bronchial bifurcations revealed carcinoma in four of 15 cases. We conclude that TBNA is a safe procedure for the diagnosis and staging of lung cancer, and that the likelihood of positive results is increased by the presence of radiologic and endoscopic abnormalities.


The Opportunity for Medical Systems to Reduce Health Disparities Among Lesbian, Gay, Bisexual, Transgender and Intersex Patients.
Lesbian, gay, bisexual, transgender, and intersex (LGBTI) people experience a variety of health care disparities, including higher rates of certain chronic illnesses, substance abuse, and HIV. The growing adoption of electronic health records (EHRs) presents an important opportunity to optimize care for LGBTI individuals by routinely capturing in structured form patient sexual orientation and gender identity (SO/GI), as well as a patient's preferred name and pronoun. In addition to improving care provided to LGBTI patients, collection of structured SO/GI information will facilitate important public health data collection efforts that can be used to further reduce health care disparities in this underserved population.


Structure, photoluminescent properties and photocatalytic activities of a new Cd(II) metal-organic framework.
A new metal-organic framework, [Cd(TDC)(bix)(H2O)]n (H2TDC = thiophene-2,5-dicarboxylic acid; bix = 1,4-bis(imidazol-1-ylmethyl)benzene), has been synthesized under hydrothermal conditions and structurally characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis, UV-vis and single X-ray diffraction. Cd-MOF is a 2D infinite layer framework, which is further interconnected by hydrogen-bond interactions leading to a 3D supramolecular architecture. The photoluminescent properties of the Cd-MOF were investigated and this compound shows intense fluorescent emissions in the solid state. In addition, it exhibits good photocatalytic activities for the degradation of methyl organic under UV light irradiation.


Intra-operative uterine artery embolization with caesarean delivery in an adjoining operating theatre and catheter lab (OT/CL) complex vs. conventional management in patients with abnormally invasive placenta: a retrospective case control study.
Patients of abnormally invasive placenta (AIP) undergoing caesarean delivery are at increased risk of haemorrhage. Conventional management includes piecemeal removal of placenta or placenta left in situ. However, they often require hysterectomy after delivery. Post-delivery prophylactic uterine artery embolisation (UAE) can help reduce morbidity and preserve fertility. We created an adjoining operating theatre and catheter lab (OT/CL complex). This is a retrospective case control study in which 37 patients of AIP were evaluated. Sixteen subjects (cases) had UAE immediately after caesarean delivery, and 21 subjects (controls) had usual care with traditional methods of controlling postpartum haemorrhage and hysterectomy where required. The hysterectomy rate (18.7% vs. 85.7%), mean duration of hospital stay (6.8 ± 2.6 vs. 13.9 ± 8.1) and number of units of blood transfusion required were significantly less in the case group as compared with controls. UAE is an effective conservative treatment along with caesarean delivery in patients with AIP. Impact statement What is already known? AIP is associated with high rates of PPH, maternal morbidity and mortality and need for hysterectomy after delivery. UAE has been advocated to preserve fertility and reduce PPH in these patients along with caesarean delivery. What does the study add? We created an adjoining operating theatre and catheter lab (OT/CL complex) in a tertiary care centre and managed these patients with prompt UAE after caesarean delivery with team approach. We have shown significant reduction in morbidity and hospital stay with this coordinated management. What are the implications for clinical practice and/or further research? UAE with caesarean delivery is a preferred mode of delivery for patients of AIP. These patients should be diagnosed and referred to tertiary care centres with such facilities electively so as to provide optimal care to these patients. Cooperation between interventionist and obstetrician and adjoining availability of OT and catheter lab can further help in reducing the time to embolisation after delivery. A hybrid operating theatre with digital subtraction angiography (DSA) facilities would be ideal for the management of such patients.


Guidelines for diagnosis, therapy and follow up of Anderson-Fabry disease.
Fabry disease (Anderson-Fabry disease) is one of the most common lysosomal storage diseases (after Gaucher disease) caused by deficient activity of the alpha-galactosidase A (alpha-Gal A) enzyme, which leads to progressive accumulation of globotriaosylceramide in various cells, predominantly in endothelium and vascular smooth muscles, with multisystem clinical manifestations. Estimates of the incidence range from one per 40,000 to 60,000 in males, and 1:117,000 in the general population. Pain is usually the first symptom and is present in 60%-80% of affected children, as well as gastrointestinal disturbances, ophthalmologic abnormalities and hearing loss. Renal failure, hypertrophic cardiomyopathy, or stroke as the presenting symptom may also be found even as isolated symptoms of the disease. Life expectancy is reduced by approximately 20 years in males and 10-15 years in females, therefore enzyme replacement therapy should be introduced in patients of any age and either sex, who meet treatment criteria for Anderson-Fabry disease.


Hepatoprotective role of neutrosecR on hepatic damage induced by combination of zidovudine and combined anti-tuberculous agents in rats.
Advent of the HIV/AIDS pandemic has led to a dramatic increase in the number of TB cases worldwide. Availability of highly active antiretroviral therapy (HAART) has significantly improved the outcome of HIV/AIDS, in terms of prevention of opportunistic infections (OIs) as well as mortality however; liver toxicity is one of the most relevant adverse effects of antiretroviral therapy (ART). In view of the inevitable use of zidovudine (a common ART) and antituberculous fixed-dose combination therapy (FDCs) in the management of HIV-TB co-infection and the resultant hepatotoxicity, this study was aimed to investigate the hepatoprotective role of neutrosec (a combination of aminoacid and vitamins) on the hepatotoxicity induced by co-administration of zidovudine and combined fixed dose antituberculous agents. Twenty four rats were randomly allotted to four groups, consisting of the control, zidovudine plus fixed dose combined anti TB agents treated group, zidovudine plus fixed dose combined anti TB agents plus neutrosec treated group and neutrosec alone treated group. Therapeutic doses of zidovudine (8.5 mg/kg/day), fixed dose combined anti TB agents (25 mg/kg/day) and neutrosec (0.4 ml/kg/day) were administered to the animals via oral gavage, daily over 60 days. After 60 days, rats were sacrificed for internal macroscopic and histological examination of the liver. The liver enzyme parameters (AST, ALP, Total bilirubin, Total protein, Albumin) were determined using fully automated clinical chemistry analyzer (Hitachi 912, Boehringer Mannheim, Germany). Antioxidant enzymes activity and lipid peroxidation were determined according to standard procedures. The AST results showed a significant (p ≤ 0.05) decreased in the zidovudine plus anti-TB plus neutrosec treated group (125.50 ± 22.71) compared with zidovudine plus anti-TB treated group (399. 10 ± 0.45). It further showed non-significant decreased (p ≥ 0.05) in the ALP levels between the zidovudine plus anti TB treated group (317.10 ± 73.48) and the zidovudine plus anti TB plus neutrosec treated group (203.20 ± 35.97). There was a non-significant (p ≤ 0.05) decrease in the MDA level of the zidovudine plus anti-TB plus neutrosec treated group compared with the zidovudine plus anti-TB treated group. The hepatotoxic effect of zidovudine plus combined anti TB drugs which may be due to free radical generation was modulated by neutrosec.


Guarding the guardians: Bioethics curricula for psychiatrists-in-training in developing countries.
A good physician must be both clinically and ethically competent. High ethical standards are especially important in psychiatry in which several unique challenges present due to a vulnerable patient population, intimate physician-patient relationships, diagnoses made on signs and symptoms rather than irrefutable laboratory investigations, and therapeutic options directed at altering thinking and behaviour. It is critical that psychiatric training equip practitioners with the ability to identify ethical dilemmas in clinical practice and research and respond appropriately. Despite a call to action and the development of guidelines for ethical practice by several regulatory bodies, formal ethics teaching in psychiatry training programmes is still in embryonic stages in the developed world and virtually non-existent in the developing world. Here we highlight the current status of bioethics teaching in psychiatry residency programmes in Pakistan, an example of a developing country where such training is vital, as unethical practices abound in resource-poor settings where clinical and research practices are non-transparent and there are no effective regulatory, legal and accountability bodies. It is critical and urgent that needs-responsive bioethics curricula are developed, institutionalized and implemented in medical schools and post-graduate training programs across the developing world. [Box: see text] [Box: see text].


Resveratrol as anti-aging therapy for age-related bone loss.
Previous studies have indicated that resveratrol, a natural phytoestrogen, can act as an anti-aging therapy to resist age-related changes of several body tissues. However, the anti-aging effects of resveratrol on bone have been poorly investigated in this natural aging population. Accordingly, this study was design to evaluate the effects of resveratrol on bone mass and biomechanical properties in old rat femora. Twenty 22-month-old male Wistar rats were divided into two randomly assigned groups (n=10). The first group was treated for 10 weeks with resveratrol (10 mg/kg per day) and the second group was left untreated (control). Rat femora were collected. Bone mass and bone microestructure were investigated by microcomputed tomography and histomorphometry. Biomechanical properties were determined by a three-point bending test. Plasma levels of CTX (carboxy-terminal telopeptide of type I collagen) and osteocalcin were also determined. Statistical analyses were performed by a Student two-tailed unpaired t-test. In all experiments, a value of p<0.05 was considered significant. Microcomputed tomography analyses demonstrated that resveratrol-treated rats had significant higher bone volume, bone trabecular number, and cortical thickness and lower spacing between trabeculae in comparison to the control group. Histomorphometric analyses confirmed the increase of bone volume in resveratrol-treated rats compared to controls. Resveratrol-treated rats had significant higher bone flexural modulus, stiffness, and ultimate load compared to control group. Treatment was not associated with changes in plasma CTX or osteocalcin. These findings demonstrate that resveratrol increases bone microstructure and bone mechanical properties in old male rats, suggesting that resveratrol might be used as anti-aging therapy to resist age-induced bone loss.


Identification of key genes involved in catechin metabolism in tea seedlings based on transcriptomic and HPLC analysis.
Tea is a non-alcoholic beverage with many benefits to human health and thereby widely consumed in the world. It contains plenty of secondary metabolites and tea catechins are the characteristic compounds. To further elucidate the biosynthetic and regulatory mechanisms of catechins in tea, high performance liquid chromatography (HPLC) and transcriptome analysis were performed in tea seedlings of different growth stages. A combined method of differential expression and correlation analysis was then conducted. The results showed that the order of total catechin (TC) contents was leaves > stems > roots, irrespective of growth stages. For transcriptome analysis, a total of 355.81 million clean reads were generated and mapped to the referencing tea genome. Further real time PCR analysis of 18 selected genes confirmed RNA-Seq results. A total of 7 structural genes and 35 transcription factors (TFs) were identified to be significantly correlated with TC changes. Among them, three TFs homologous to ANL2, WRKY44 and AtMYB113 might play key roles in catechin regulation. The de novo transcriptome data of different organs in tea seedlings provided new insights into the biosynthetic and metabolic pathways of catechins.


Cost-effectiveness of strategies to market and train primary health care physicians in brief intervention techniques for hazardous alcohol use.
The cost-effectiveness of strategies to market and train primary care physicians in brief intervention for hazardous alcohol consumption was examined. Physicians were randomly assigned to one of three marketing strategies designed to promote the "uptake" of a brief intervention package for hazardous and harmful alcohol consumption. The strategies were direct mail, tele-marketing, or academic detailing. One hundred and twenty-seven of those physicians who requested the package during the marketing phase (phase 1) and who also agreed to participate in the training and support phase of the project (phase 2) were matched into one of three training and support conditions: training and no support, training and minimal support, training and maximal support. An additional 34 physicians were randomly selected and assigned to a control condition. The ultimate aim of training and support was to maximise physician screening and counselling rates. Tele-marketing was found to be more cost-effective than academic detailing and direct mail in promoting the uptake of the package. For the training and support phase costs and effects increased with the level of support, hence the issue to be considered is whether the additional cost incurred in moving from one strategy to another is warranted given the increase in the level of outcome.


Criticality and mechanical enhancement in composite fiber networks.
Many biological materials consist of sparse networks of disordered fibers, embedded in a soft elastic matrix. The interplay between rigid and soft elements in such composite networks leads to mechanical properties that can go far beyond the sum of those of the constituents. Here we present lattice-based simulations to unravel the microscopic origins of this mechanical synergy. We show that the competition between fiber stretching and bending and elastic deformations of the matrix gives rise to distinct mechanical regimes, with phase transitions between them that are characterized by critical behavior and diverging strain fluctuations and with different mechanisms leading to mechanical enhancement.


Analysis of genome-wide DNA arrays reveals the genomic population structure and diversity in autochthonous Greek goat breeds.
Goats play an important role in the livestock sector in Greece. The national herd consists mainly of two indigenous breeds, the Eghoria and Skopelos. Here, we report the population structure and genomic profiles of these two native goat breeds using Illumina's Goat SNP50 BeadChip. Moreover, we present a panel of candidate markers acquired using different genetic models for breed discrimination. Quality control on the initial dataset resulted in 48,841 SNPs kept for downstream analysis. Principal component and admixture analyses were applied to assess population structure. The rate of inbreeding within breed was evaluated based on the distribution of runs of homozygosity in the genome and respective coefficients, the genomic relationship matrix, the patterns of linkage disequilibrium, and the historic effective population size. Results showed that both breeds exhibit high levels of genetic diversity. Level of inbreeding between the two breeds estimated by the Wright's fixation index FST was low (Fst = 0.04362), indicating the existence of a weak genetic differentiation between them. In addition, grouping of farms according to their geographical locations was observed. This study presents for the first time a genome-based analysis on the genetic structure of the two indigenous Greek goat breeds and identifies markers that can be potentially exploited in future selective breeding programs for traceability purposes, targeted genetic improvement schemes and conservation strategies.


Ghrelin's Orexigenic Effect Is Modulated via a Serotonin 2C Receptor Interaction.
Understanding the intricate pathways that modulate appetite and subsequent food intake is of particular importance considering the rise in the incidence of obesity across the globe. The serotonergic system, specifically the 5-HT2C receptor, has been shown to be of critical importance in the regulation of appetite and satiety. The GHS-R1a receptor is another key receptor that is well-known for its role in the homeostatic control of food intake and energy balance. We recently showed compelling evidence for an interaction between the GHS-R1a receptor and the 5-HT2C receptor in an in vitro cell line system heterologously expressing both receptors. Here, we investigated this interaction further. First, we show that the GHS-R1a/5-HT2C dimer-induced attenuation of calcium signaling is not due to coupling to GαS, as no increase in cAMP signaling is observed. Next, flow cytometry fluorescence resonance energy transfer (fcFRET) is used to further demonstrate the direct interaction between the GHS-R1a receptor and 5-HT2C receptor. In addition, we demonstrate colocalized expression of the 5-HT2C and GHS-R1a receptor in cultured primary hypothalamic and hippocampal rat neurons, supporting the biological relevance of a physiological interaction. Furthermore, we demonstrate that when 5-HT2C receptor signaling is blocked ghrelin's orexigenic effect is potentiated in vivo. In contrast, the specific 5-HT2C receptor agonist lorcaserin, recently approved for the treatment of obesity, attenuates ghrelin-induced food intake. This underscores the biological significance of our in vitro findings of 5-HT2C receptor-mediated attenuation of GHS-R1a receptor activity. Together, this study demonstrates, for the first time, that the GHS-R1a/5-HT2C receptor interaction translates into a biologically significant modulation of ghrelin's orexigenic effect. This data highlights the potential development of a combined GHS-R1a and 5-HT2C receptor treatment strategy in weight management.


Systems biology as a foundation for genome-scale synthetic biology.
As the ambitions of synthetic biology approach genome-scale engineering, comprehensive characterization of cellular systems is required, as well as a means to accurately model cell-scale molecular interactions. These requirements are coincident with the goals of systems biology and, thus, systems biology will become the foundation for genome-scale synthetic biology. Systems biology will form this foundation through its efforts to reconstruct and integrate cellular systems, develop the mathematics, theory and software tools for the accurate modeling of these integrated systems, and through evolutionary mechanisms. As genome-scale synthetic biology is so enabled, it will prove to be a positive feedback driver of systems biology by exposing and forcing researchers to confront those aspects of systems biology which are inadequately understood.


Pneumothorax as a complication of tumour response to chemotherapy.
A patient with extensive pulmonary involvement by disseminated adenocarcinoma is presented. Response to chemotherapy resulted in the direct rupture of necrotic tumour tissue into the pleural cavity leading to a pneumothorax. The condition failed to improve with chest drainage and suction, necessitating surgical intervention. The development of the pneumothorax proved to be a fatal complication of treatment.


Development and validation of Trivandrum Development Screening Chart for children aged 0-6 years [TDSC (0-6)].
To develop and validate a simple screening tool for identifying developmental delay among children of 0-6 y of age in the community. The 51-items of Trivandrum Development Screening Chart for children of 0-6 y [TDSC (0-6 y)], were carefully prepared from the norms in various existing developmental charts/scales, by experts keeping in mind the face validity and content validity. The criterion validity was assessed in a community sample of 1,183 children of 0-6 y with a mean age of 35.38 mo (SD of 19.25) including 597 (50.46%) boys and 586 (49.54%) girls. TDSC (0-6 y) was validated against Denver Developmental Screening Test (DDST) as the 'Reference Standard'. When one item delay in TDSC (0-6 y) was considered as 'TDSC delay' (test positive), the sensitivity and specificity of TDSC (0-6 y) was found to be 84.62% (95% CI: 71.92-93.12) and 90.8% (95% CI: 88.97-92.43) respectively with a Negative Predictive Value of 99.23% (95% CI: 98.48-99.67) and LR (negative) of 0.17(95% CI: 0.09-0.32). The test-retest and inter-rater reliability [an interclass correlation (ICC) of 0.77 for test-retest and ICC of 0.97 for inter-rater] were good and acceptable. TDSC (0-6 y) is a simple, reliable and valid screening tool for use in the community to identify children between 0 and 6 y with developmental delay, enabling early intervention practices.


Lengthening of below-the-knee amputation stumps using the Ilizarov technique.
Patients with short, traumatic, below-the-knee amputations (BKAs) frequently function as if they have knee disarticulations. The goal of this study was to evaluate the results in patients who had lengthening of their BKA stumps to improved prosthesis fit and increase ambulation. Three patients with traumatic BKAs, who were left with insufficient stumps for proper prosthesis wear, have had their stumps lengthened by Ilizarov's technique of distraction osteogenesis. The lengthening process produced a moderate degree of pain, and all patients had a temporary decrease in their range of motion. Two patients lost a substantial amount of gained length secondary to early full weight-bearing. Despite these difficulties, the procedure produced longer, more durable stumps in all patients with no final loss of knee range of motion.


Cross-category structure in semantic memory.
In Experiment I, subjects made similarity judgments about all 56 category terms listed in the Battig and Montague (1969) norms. These judgments were then subjected to a hierarchical clustering analysis. Experiment II demonstrated that the relations among the category labels are very similar to the relations among the high dominance exemplars of these categories. Experiment III showed that the distances between the category terms in the hierarchical clustering analysis could predict RTs in a same-different paradigm.


Microbial ecosystems in compost and granular activated carbon biofilters.
Compost and granular activated carbon biofilters operated at a wastewater treatment plant simultaneously removed low concentrations of hydrogen sulfide and volatile organic compounds. Through the use of phospholipid fatty acid analyses, the effects of declining pH caused by sulfide oxidation were established for microbial growth, microorganism stress, and microbial community structure. Microorganisms on both media demonstrated increases in microbial densities, varying degrees of environmental stress, and domination by gram-negative bacteria. However, the declining pH had little effect on compound removal, which was greater than 99% for the hydrogen sulfide and greater than 70% for the oxygenated and aromatic hydrocarbons. The microbial communities adjusted to difficult environmental conditions through acclimation of the species present or by growth of low-pH-tolerant species.


Health promotion for urban middle school students: a survey of learning needs.
Community based education programs and community partnerships are crucial for attaining the objectives of Healthy People 2010. The purpose of this descriptive study was to determine the health promotion needs of urban middle school students from the perspective of the participants in a health promotion partnership project. A convenience sample of 161 urban middle school students participated in the study. A Likert scale of health promotion topics was used for data collection. Findings from the study indicated that urban middle school students have a major interest in finding out more about hair care, safety issues, and prevention of infection. Students expressed a need for more information about issues related to why people use drugs, feelings about self, feelings of sadness and worry, and feelings about death. Important variations were found in the priority of interest in topics among the three grades. The researchers concluded that the psychosocial health promotion needs of urban middle school students should be explored further.


Entrainment to light of circadian activity rhythms in tench (Tinca tinca).
The present article analyzes locomotor activity rhythms in Tinca tinca. To that end, three different experiments were conducted on 24 animals (20 g body weight) kept in pairs in 60-liter aquaria fitted with infrared sensors connected to a computer to continuously record fish movements. The first experiment was designed to study the endogenous circadian clock under free-running conditions [ultradian 40:40 min LD pulses and constant dark (DD)] and after shifting the LD cycle. Our results demonstrate that tench has a strictly nocturnal activity pattern, an endogenous rhythm being evident in 45.8% of the fish analyzed. The second experiment was conducted to test the influence of different photoperiods (LD 6:18, 12:12, 18:6, and 22:2) on locomotor activity, the results showing that even under an extremely long photoperiod, tench activity is restricted to dark hours. The third experiment examined the effect of light intensity on locomotor activity rhythms. When fish were exposed to decreasing light intensities (from 300:0 lux to 30:0, 3:0, and 0.3:0 lux) while maintaining a constant photoperiod (LD 12:12), the highest percentage of locomotor activity was in all cases associated with the hours of complete darkness (0 lux). In short, our results clearly show that (a) tench is a species with a strictly nocturnal behavior, and (b) daily activity rhythms gradually entrain after shifting the LD cycle and persist under free-running conditions, pointing to their circadian nature. However, light strongly influences activity rhythms, since (c) the length of the active phase is directly controlled by the photophase, and (d) strictly nocturnal behavior persists even under very dim light conditions (0.3 lux). The above findings deepen our knowledge of tench behavior, which may help to optimize the aquacultural management of this species, for example, by adjusting feeding strategies to their nocturnal behavior.


Evidence for Cd101 but not Fcgr1 as candidate for type 1 diabetes locus, Idd10.
Among polygenes conferring susceptibility to type 1 diabetes in the NOD mouse, Idd10 on distal chromosome 3 has been shown to be important for disease susceptibility. In this study, we investigated the candidacy of Fcgr1 and Cd101 for Idd10, by congenic mapping and candidate gene sequencing. Among seven NOD-related strains studied, the IIS mouse was found to possess a recombinant Idd10 interval with the same sequence at Fcgr1 as the NOD mouse, but a different sequence at Cd101 from that in the NOD mouse with 10 amino acid substitutions. The frequency of type 1 diabetes in NOD mice congenic for IIS Idd10 (NOD.IISIdd10) was significantly reduced as compared to that in the NOD mouse, despite the presence of the identical Fcgr1 sequence. These data indicate that IIS mice possess a resistant allele at Idd10, and suggest that Cd101, but not Fcgr1, is responsible for the Idd10 effect.


Agricultural waste from the tequila industry as substrate for the production of commercially important enzymes.
Approximately 1 million tons of Agave tequilana plants are processed annually by the Mexican Tequila industry generating vast amounts of agricultural waste. The aim of this study was to investigate the potential use of Agave tequilana waste as substrate for the production of commercially important enzymes. Two strains of Aspergillus niger (CH-A-2010 and CH-A-2016), isolated from agave fields, were found to grow and propagate in submerged cultures using Agave tequilana waste as substrate. Isolates showed simultaneous extracellular inulinase, xylanase, pectinase, and cellulase activities. Aspergillus CH-A-2010 showed the highest production of inulinase activity (1.48 U/ml), whereas Aspergillus niger CH-A-2016 produced the highest xylanase (1.52 U/ml) and endo-pectinase (2.7U/ml) activities. In both cases production of enzyme activities was significantly higher on Agave tequilana waste than that observed on lemon peel and specific polymeric carbohydrates. Enzymatic hydrolysis of raw A. tequilana stems and leaves, by enzymes secreted by the isolates yielded maximum concentrations of reducing sugars of 28.2 g/l, and 9.9 g/l respectively. In conclusion, Agave tequilana waste can be utilized as substrate for the production of important biotechnological enzymes.


Validity of skinfold equations for estimating body density in youth wrestlers.
The present investigation examined the validity of 16 skinfold equations for predicting body density (BD) in youth wrestlers (mean age +/- SD = 11.0 +/- 1.3 yr) by comparing the values to those obtained from underwater weighing. Forty-eight members of youth wrestling clubs (mean BD +/- SD = 1.0634 +/- 0.0125 g.cm-3) volunteered to serve as subjects. The statistical analyses included examination of the constant error (CE), standard error of estimate (SEE), correlation coefficient (r), and total error (TE). The results of this investigation indicated that all of the equations resulted in TE values that were > or = 0.0106 g.cm-3 (range = 0.0106-0.0229 g.cm-3) which corresponded to > or = 4.9% body fat. The TE values were too large to provide accurate estimates of body composition in the present sample of youth wrestlers. Future studies should use the CE values from the present investigation to adjust the intercepts of the skinfold equations in the present study and cross-validate the modified equations on young male athletes.


[Hemolytic reaction resulting from propafenone administration].
Although adverse reactions of many kinds caused by propafenone have been observed, yet there has been no documented report of hemolytic reaction. Four episodes of hemolytic reaction in three patients receiving intravenous propafenone were reported. These reactions took place a few hours after the administration and one of the episodes was complicated with acute left ventricular heart failure and shock. Cessation of propafenone administration together with relevant therapeutic measures tide the patients over and hemolysis disappeared in several hours. Toxicological examination revealed no physical or chemical deterioration and biological contamination of the remaining medication and no such reaction was noted when the drug of the same batch was given to other patients. It is considered that the hemolytic episodes were related to allergic constitution of the patients. Judging from the clinical manifestations, these episodes were hemolytic reactions of immune complex type.


Early expression of MCS2 (CD13) in the cytoplasm of blast cells from acute myeloid leukaemia.
The expression of two myeloid antigens identified by the monoclonal antibodies (McAb) MCS2 (CD13) and MY9 (CD33) was investigated in 136 cases of leukaemia. MCS2 was positive in blast cells of 78 of 88 (88.5%) and MY9 in 51 of 81 (64%) cases of acute myeloid leukaemia (AML) and chronic granulocytic leukaemia in myeloid blast crisis. One or other McAb, or both, were positive in all but 2 (2.3%) of these cases. MCS2 was more sensitive than MY9 to detect blasts of the myeloid lineage due to its most frequent reactivity in the cytoplasm of fixed cells by the immunoperoxidase (IP) technique compared with its membrane expression on cell suspensions by immunofluorescence (IF). MY9 was not suitable for tests on fixed cells. MCS2 was positive by IP but not by IF in 24% of AML, but the reverse was not observed. This suggests that the antigen detected by MCS2 is expressed in myeloblasts first in the cytoplasm and later on the cell membrane, pattern which is similar to that of the early antigens CD3 and CD22 in T and B lineage lymphoblasts, respectively. MCS2 was always positive in FAB types of AML-involving myeloblasts (M1-M4), including cases of undifferentiated morphology (M0), whilst MY9 was more frequently positive in monocytic leukaemia (M5). On the other hand, MCS2 was positive in 4 of 33 cases of acute lymphoblastic leukaemia and MY9 in 1. We conclude that both McAb, particularly MCS2, contribute to the better characterisation of myeloid leukaemias but that other tests are required to clarify the nature of the blasts when unexpected reactivities are observed.


The induction of aryl hydrocarbon receptor (AHR) in immune organs of developing chicks by polycyclic aromatic hydrocarbons.
Polycyclic aromatic hydrocarbons are pollutants which are persistent in nature. The aryl hydrocarbon receptor is a ligand-activated cytosolic transcription factor activated by xenobiotics. The objective was to isolate and identify AHR mRNA transcript in immune organs of developing chicks and to interpret the correlation between AHR induction and dose of PAHs. Specific pathogen free embryonated eggs on day nine were inoculated with solutions of pyrene, phenanthrene, and fluoranthene dissolved in tricaprylin (vehicle) through the allantoic route at three dose levels: 0.2 mg/kg, 2 mg/kg, and 20 mg/kg. A 650 base pair product was observed by RNA extraction and reverse transcription PCR from thymus, bursa of Fabricius and spleen on 21st day. When AHR concentration was analyzed by ELISA in these organs, pyrene showed maximum potency in inducing AHR in thymus. Fluoranthene made highest concentration of AHR in bursa of Fabricius. None of these chemicals caused an increase in AHR concentration in spleen.


Utilization of LPG and gasoline engine exhaust emissions by microalgae.
The effect of engine exhaust emissions on air pollution is one of the greatest problems that the world is facing today. The study focused on the effects of realistic levels of engine exhaust emissions of liquid petroleum gas (LPG) and gasoline (GSN) on Phormidium sp. and Chlorella sp. Multi parameters including pH, different medial compositions, fuel types, flow rates and biomass concentrations were described in detail. Effects of some growth factors such as triacontanol (TRIA) and salicylic acid (SA) have also been tested. The maximum biomass concentration of Phormidium sp. reached after 15 days at 0.36 and 0.15 g/L initial biomass concentrations were found as 1.160 g/L for LPG emission treated cultures and 1.331 g/L for GSN emission treated cultures, respectively. The corresponding figures were 1.478 g/L for LPG emission treated cultures and 1.636 g/L for GSN emission treated cultures at 0.65 and 0.36 g/L initial Chlorella sp. biomass concentrations. This study highlights the significance of using Phormidium sp. and Chlorella sp. for utilization of LPG and GSN engine exhaust emissions by the help of growth factors.


New insights into the pathogenesis of adenosine deaminase-severe combined immunodeficiency and progress in gene therapy.
Adenosine deaminase (ADA)- deficient severe combined immunodeficiency (SCID) is a complex metabolic and immunological disorder, characterized by a severe immunodeficiency due to the accumulation of purine metabolites in plasma and cells. This review summarizes recent findings on the pathogenesis of immunological and nonimmunological defects in ADA deficiency and the successful outcome of gene therapy trials for this condition. Recent reports show that ADA-SCID is associated with an increased frequency of autoimmune manifestations and high risk of central nervous system (CNS) complications even after bone marrow transplantation. It remains unclear to what extent infection-related or disease-specific factors correlate with this divergent outcome.Recent trials represented the first demonstration of long-term clinical efficacy of HSC gene therapy for ADA-SCID, underlining that gene therapy has a favorable safety profile and is effective in restoring normal purine metabolism and immune functions. Molecular studies showed that the retroviral integration profile after successful gene therapy did not cause selection or expansion of malignant cell clones in vivo. Gene therapy for ADA-deficient SCID is an effective treatment, providing long-term clinical benefit for affected patients. Future research will be needed to address the occurrence of autoimmune manifestations and nonimmunological defects in order to improve patients' long-term prospects.


[Acute Idiopathic Scrotal Oedema - Differential Diagnosis of the Acute Scrotum].
Acute idiopathic scrotal edema (AISE) is regarded as a rare cause of scrotal pain, swelling and erythema. Testicular torsion, torsion of the appendage, epididymitis, hernia and hydrocele are the most common causes of acute scrotum. The clinical symptoms of AISE are usually mild and the characteristic Doppler sonography findings make it a valuable differential diagnosis, which can help to avoid unnecessary exploration.